Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

Tinnitus is a common phantom auditory percept, believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in absence of any clinical hearing loss. Then, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise, normal hearing, but the results are not consistent across studies. Here, we aim to investigate those differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis, which was associated with tinnitus found in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

The study of notable people as agents for increasing cancer awareness started just in the last decades of the 20th century. This study aimed to identify Pan-American notable people with head and neck cancer (HNC) and to assess HNC’s professional perspective on communicating stories of notable patients with HNC to promote prevention. Methods: This cross-sectional study was conducted by applying a RedCap questionnaire to oral medicinists, oral pathologists, head and neck surgeons, and clinical oncologists with experience in HNC research, education, or treatment in Pan-American countries. Additionally, a structured search was performed on PubMed, Scopus, EMBASE, Web of Science, LILACS, and gray literature Results: We identified 42 notable people from the United States, Brazil, Argentina, Mexico, El Salvador, Chile, Colombia, and Peru who were mainly actors, athletes, and musicians. Participants agreed that stories of notable patients with HNC can positively impact the population and promote prevention if communicated by the internet, social media, and television. Conclusion: In the Pan-American region, notable individuals who have suffered from HNC may be powerful advocates for increasing cancer awareness and promoting prevention strategies. The professionals involved in the study expressed a positive inclination towards using the stories of these notable HNC survivors as an effective prevention strategy.

Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.

Most head and neck cancers are diagnosed in advanced stages, when the curative interventions are no longer possible. The assessment and the multidisciplinary therapeutic approach of the locally advanced cases are difficult since the onset of the disease becomes a significant challenge for the whole attending team (including both the patient and his family) because they have to deal with to an extensive symptomatology (abundant secretions, refractory pain, mutilations predominantly in the cephalic area), with the cure of stomas (tracheostomy, gastrostomy) and with various post-therapeutic sequelae. The present paper reflects the impact of late diagnosis, the complexity of the multimodal specific oncological treatment (chemotherapy, radiotherapy, immunotherapy, pal-liative and terminal treatment), the adaptation of medical care to the psycho-emotional structure, having as an example the case of 54-year old patient (with his consent) diagnosed with pharyn-golaryngeal neoplasm who presented himself to “St. Luca” Chronic Disease Hospital, the Oncol-ogy-Palliative Care Department, in September 2021. In patients with locally advanced head and neck cancers, besides the specifically oncological therapeutic decisions, the empathic-emotional connection between the medical team with the patient and his family plays a key role in the ther-apeutic conduct.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

Head and neck cancers arise from mucosa lining the oral cavity, oropharynx, hypopharynx, larynx, sinonasal tract, and nasopharynx and the etiology of head and neck cancers is complex and involves many factors, among which oncogenic viruses are also enumerated. Nevertheless, this type of cancers are among the most common cancers around the world. The thorough knowledge of the pathogenesis of viral infection is needed to fully understand its impact on cancer development.

Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4 and c-MYC in all samples while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n=6) and reverse-transcription quantitative polymerase chain reaction (n=5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of four primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Because of their expression pattern, they have historically been attractive targets for immunotherapies. The investigation of mechanistic roles of CT antigens in promoting oncogenesis has historically been a prominent research question, and a growing number of studies implicate CT antigens in promoting almost all the hallmarks of cancer. This suggests that CT antigens may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas, although their role in the pathogenesis, prognostication, and treatment for this family of cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and therapeutic response and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.

Oral mucositis (OM) is inflammation of the mouth caused by damage to the mucous membranes that line the mouth and throat. It is a side effect of cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy, chemotherapy, and/or immunotherapy with immune checkpoint inhibitors. The etiology and pathogenic mechanisms of OM is complex and multifaceted, involving cytotoxicity (cell death), inflammation, infection, change in microbiome, and immune-mediated cytotoxicity. We summarize the literature about attempts to use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) to elucidate the biological pathways associated with the development or the severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and local environment (microbiomics).

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

EZH2 overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We previously analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (P < 0.001) and the methylation index of tumor suppressor genes (P < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (P = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, P < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; P < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.

Cancers of the head and ne¬ck and their treatment can cause disfigurement and loss of functioning, with a profound negative impact on the person’s self-image and psychosocial wellbeing. This can lead to experiences of shame and stigma, which are important targets for psychosocial interventions. Accurate measurement and identification of these problems enables clinicians to offer appropriate interventions and monitor patients’ progress. This study aimed to validate the Canadian version of the Shame and Stigma Scale (SSS) among French and English speaking head and neck cancer patients. Data from 258 patients from two major Canadian hospitals was analysed. The existing 4-factor structure of the SSS was supported, with the following subscales: Shame with Appearance, Sense of Stigma, Regret, and Social/Speech Concerns. The Canadian SSS showed adequate convergent and divergent validity and test-retest reliability. Rasch analysis suggested scale improvement by removing two misfitting item and two items with differential functioning between French and English speaking patients. The final 16-item scale version had adequate fit to the Rasch model. The SSS provides more accurate measures for people with high levels of shame and stigma, and thus has utility in identifying patients with more severe symptoms who may be in need of psychosocial interventions.

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor with sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as alternative to brachytherapy boost after external beam RT. It also used as a primary treatment option for elderly or medically unfit patients. More recently, SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

.Purpose: This paper presents a comparative analysis of state-of-the-art DIR algorithms in the context of head and neck squamous cell carcinoma (HNSCC) radiation therapy. Materials and Methods: We used a dataset of head and neck cancer patients within the Cancer Image Archive, which includes 31 patients with 3D CT image data from pre-treatment, mid-treatment, and post-treatment stages of radiotherapy. We applied DIR algorithms to two datasets, one for pre-treatment to mid-treatment registration and another for mid-treatment to post-treatment registration, by aligning one CT image to another CT image. To quantitatively analyze the patient data, we focused on the spinal cord, optic nerve, brain stem, cochlea, and PTV as the OAR datasets. To verify the DIR algorithm, we used two non-learning-based methods, SyN and NiftyReg, as well as three deep learning-based methods, Voxelmorph, Cyclemorph, and Transmorph. We trained a deep learning model by adjusting the ratio of the training dataset, validation dataset, and test dataset to 7:1:2. Results: The average DSCs of SyN and NiftyReg, the non-learning-based methods, were 0.74±0.06 and 0.70±0.12, respectively. The deep learning-based methods, Voxelmorph, Cyclemorph, and Transmorph, had average DSCs of 0.72±0.08, 0.68±0.11, and 0.69±0.13, respectively. The deep learning DIR algorithm produced transformed outputs of OAR/PTV in a shorter time than other models, including commercial and conventional mathematical algorithms (At Inference(sec/images), Voxelmorph: 0.36, Cyclemorph: 0.3, Transmorph: 5.1, SyN: 140, NiftyReg: 40.2). Conclusions: In conclusion, our study provides a comprehensive comparison of commercial DIR algorithms with traditional and deep learning-based DIR methods. Our results demonstrate that commercial DIR algorithms outperform traditional DIR methods in terms of accuracy and efficiency. However, we also show that deep learning-based DIR methods have the potential to achieve similar performance to commercial algorithms with proper training and optimization. Our findings suggest that both commercial and deep learning-based DIR methods have their respective advantages and limitations, and the choice of method should depend on the specific requirements of the clinical application. Overall, our study contributes to ongoing efforts to improve the accuracy and efficiency of DIR methods for better patient outcomes.

Chondrosarcoma, represents approximately 0.1% of all neoplasms of the head and neck, being considered a rare disease, but with a relatively good prognosis. The 5-year overall survival (OS) rate is estimated at 70-80%, being considered a disease with a low growth rate. About 13% of all cases of chondrosarcoma, are located in the region of the head and neck. We present the case of a young patient treated multimodally, lost from the oncological records less than two years after the diagnosis, without evidence of disease progression. The early loss from the oncological follow-up programs of patients with a lower risk of early repalpse, without evidence of a recurrence or metastasis could be the consequence of a major complication among which we could assume an aspiration pneumonia secondary to a dysphagia, associated with an aggressive multidisciplinary treatment. Large tumor size and positive resection margins (R1 resection) are risk factors that support an intensive adjuvant approach in order to reduce the risk of recurrence, but the low grade of tumor, associating a lower risk of recurrence as well as the adverse events (AE) of adjuvant radiotherapy and chemotherapy justifies a more reserved therapeutic approach. Taking into account the longer life expectancy of these patients, it is recommended to use a more conformal irradiation technique in order to reduce doses to radiosensitive structures as well as to omit elective neck irradiation, taking into account the lower risk of lymph node involvement. The lack of guidelines that include very rare tumors including low grade chondrosarcoma of head and neck make a unified approach difficult, but the data presented even in case reports could contribute to choosing the regimen that offers the best therapeutic ratio.

Head and neck cancer is the sixth most frequent cancer type. Drug resistance and toxicity are common challenges of the existing therapies, making the development of reliable preclinical models essential for the study of the involved molecular mechanisms as well as for eventual intervention approaches that improve the clinical outcome. Preclinical models of head and neck squamous cell carcinoma have been traditionally based in cell lines and murine models. In this review, we will go over the most frequently used preclinical models, from immortalized-cell and primary tumour cultures in monolayer or 3D, to the currently available animal models. We will scrutinize their efficiency in mimicking the molecular and cellular complexity of head and neck squamous cell carcinoma. Finally, the challenges and opportunities of other envisaged putative approaches, as well as the potential of the preclinical models to further develop customized therapies will be discussed.

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that contributes to the progression of several cancers. MIF overexpression has been reported in head and neck squamous cell carcinoma (HNSCC) patients. However, the exact role of MIF in HNSCC is not fully understood. Our aim was to evaluate the amount of secreted MIF and the role of MIF in the proliferation, cell cycle, and apoptosis in HNSCC cell lines. The MIF levels in conditioned media from human primary (HN18 and HN30) and metastatic (HN17 and HN31) HNSCC cell lines were evaluated using ELISA. The HNSCC cell lines were treated with recombinant MIF and its effect on proliferation, cell cycle, and apoptotic status was determined by MTT and flow cytometry, respectively. The HNSCC-secreted MIF concentration ranged from 49.33‒860 pg/ml. Exogenous MIF (25 ng/ml) significantly increased HN18, HN30, and HN31 cell proliferation. Moreover, MIF induced cell cycle progression and inhibited apoptosis in these cells. However, MIF did not affect growth or apoptosis in HN17 cell. In conclusion, the HNSCC cell lines were evaluated secrete MIF. Exogenous MIF promotes various effects on proliferation, cell cycle, and apoptosis in HNSCC cells.

Chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer; however, CRT may cause post-treatment dysphagia. Transcutaneous electrical sensory stimulation (TESS), developed in recent years for swallowing rehabilitation, has been used at many medical facilities. Although TESS has been used for dysphagia in several fields, its safety and efficacy in patients with head and neck cancer remain to be clarified. Therefore, this study evaluated the safety of TESS in ten patients with head and neck cancers undergoing CRT. Swallowing rehabilitation intervention and TESS implementation were performed for all patients during CRT. Non-blood toxicity adverse events (AEs), such as dermatitis and mucositis, occurred during CRT; however, the severity was less than Grade 3. No patient experienced pain due to TESS. As survival time analysis using the Kaplan–Meier method for interferential current device implementation rates revealed a feasibility of 100% for up to 60 Gy and a feasibility of 78% for up to 70 Gy, it concludes that TESS was feasible until 70 Gy. This study confirmed the feasibility and safety of TESS in the head and neck region, even during CRT. Although the precise mechanism of TESS on dysphagia is not yet clear, its continued use has great potential for improving sensory disturbance.

Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in chemical, but not bacterial, constituents of these products. In this study, we explore the composition and function of the bacteriome in ST products from 4 countries using q-PCR and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4E+6) and highest in Yemeni shammah (6.6E+11). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus, Paenibacillus, and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas, Massilia, Propionibacterium, Puniceispirillum and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia, Desemzia, Atopostipes and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. PICRUSt functional prediction showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively “high carcinogenicity” products. The bacteriome of ST products thus differed qualitatively, quantitatively and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.

We performed electronic research for articles published in PubMed, MEDLINE, and ScienceDirect databases from January 2004 to January 2023. The systematic review of twenty (20) peer-reviewed articles about dosimetric parameters and eight (8) articles about clinical outcomes confirmed the dosimetric advantages of ART through better target coverage and Organs at Risk (OARs) sparing, with subsequent benefits on decreased toxicity and improved clinical outcome, specifically local control of the disease. ART replanning is a sustainable strategy for minimizing toxicity by improving normal tissue sparing. Furthermore, it enhances target volume coverage by correctly determining the specific amount of dose to be delivered to the tumor. In conclusion, this review confirms that ART benefits dosimetric, clinical/therapeutic, and toxicity outcomes.

Cytoglobin has been implicated in a range of pathological conditions including fibrosis and cancer, where cytoglobin expression is linked to hypoxia- and drug-resistance. One disease where there is evidence of a role for cytoglobin is head and neck squamous cell carcinoma, a disease with a poor prognosis and where clinical resistance to platinum-based drugs is common. In the current study, we demonstrate that 3D-culture of head and neck cancer cells (PE/CA-PJ41, Liv-22K) and normal oral keratinocyte cells (NOK-hTERT) results in changes in sensitivity to cisplatin cytotoxicity compared to 2D-cultures. Relative to 2D-cultures, 3D-cultures of PE/CA-PJ41 and NOK-hTERT cells demonstrated increased cisplatin resistance. In contrast, 3D-cultures of Liv-22K cells were more sensitive to cisplatin. Evidence for cisplatin genotoxicity was observed in the form of GADD45A activation in PE/CA-PJ41 cells but not the other two cell types investigated. Furthermore, DNA-strand breaks were also detected by the alkaline comet assay in PE/CA-PJ41 cells although levels were not significantly affected by 3D-culture. Cytoglobin expression levels were elevated by 3D-culture in all three cell lines investigated and there were also changes in expression of genes related to cell division (MKI57, GJB6), cell adhesion (CDH1), stress response (NFkB, NQO1) and apoptosis (Casp3) but these changes were cell line specific. We also observed consistent transcriptional activation of HIF1a in 3D-cultures of all three cell lines, suggestive of hypoxic conditions in spheroids. In support of a direct role of hypoxia in cytoglobin induction, the HIF1a stabiliser cobalt chloride also induced cytoglobin expression in spheroids. Transcriptomic profiling of PE/CA-PJ41 cells over-expressing cytoglobin identified 121 differentially regulated genes, when cells were cultured under hypoxic conditions. Major changes identified included, upregulation of G1/S cell cycle regulation as well as wnt- and RhoGTPase-signalling pathways. In conclusion, 3D-cultures are a useful model to further study the biological function of cytoglobin in head and neck cancer and we provide evidence that further supports a role for cytoglobin in hypoxia-dependent cellular proliferation and phenotypic changes that could contribute to cisplatin resistance in vivo.

While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)—a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present virus (with about 7% of the population having oral HPV infection at any one time), only 1% of those infected develop OPSCC— suggesting that additional cofactors or coinfections may be required. Epstein-Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions—leading to tumor growth.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Radiotherapy and cisplatin-based chemotherapy belong to the main treatment modalities for head and neck squamous cell carcinoma (HNSCC), and induce cancer cell death by generating DNA damage, including the most severe double strand breaks (DSBs). Alterations in DSB response and repair genes may affect individual DNA repair capacity and treatment sensitivity, contributing to therapy resistance and poor prognosis often observed in HNSCC. In this study, we investigated the association of a panel of single nucleotide polymorphisms (SNPs) in 20 DSB signaling and repair genes with therapy results and prognosis in 505 HNSCC patients treated non-surgically with DNA damage-inducing therapies. In the multivariate analysis, there were a total of 14 variants associated with overall, locoregional recurrence-free or metastasis-free survival. Moreover, we identified 10 of these SNPs as independent predictors of therapy failure and unfavorable prognosis in the whole group or in two treatment subgroups. They were MRE11A rs2155209, XRCC5 rs828907, RAD51 rs1801321, rs12593359, LIG4 rs1805388, CHEK1 rs558351, TP53 rs1042522, ATM rs1801516, XRCC6 rs2267437 and NBS1 rs2735383. Only CHEK1 rs558351 remained statistically significant after correction for multiple testing. These results suggest that specific germline variants related to DSB response and repair may be potential genetic modifiers of therapy effects and disease progression in HNSCC treated with radiotherapy and cisplatin-based chemoradiation.

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

Background: Infantile hemangiomas (IHs) are the most common benign vascular tumors of infancy. Methods: We report our experience of 248 patients with head and neck IHs. Results: The median age on admission was 4 months, and female/male ratio was 2.17. Among the cases, 45% were followed without treatment. No local complications were observed in any of these patients. Propranolol was given to all patients who received medical treatment. The median duration of treatment was 12 months (1-30 months), and the median follow-up period of all patients was 14 months (0-118 months). The treatment response was 98%. Complication rate was 17% and children aged between 3 and 9 months accounted for 60% of patients who developed complications. Most of the complications were local complications such as bleeding, ulcer, and infection. Conclusion: Although most of them regress spontaneously, complications may occur. Propranolol alone is an effective treatment option, and early treatment initiation increases success rates.

Taxanes, particularly docetaxel (DTX), has been widely used for combination therapy of head and neck squamous cell carcinoma (HNSCC). For locally advanced unresectable HNSCC, DTX combined with cisplatin and 5-fluorouracil as a revolutionary treatment revealed an advantage in improvement of patient outcome. In addition. DTX plus immune check inhibitors (ICIs) showed low toxicity and increased response of patients with recurrent or metastatic HNSCC (R/M HNSCC). Accumulating data indicate that taxanes not only function as antimitotics but also impair diverse oncogenic signalings including angiogenesis, inflammatory response, ROS production, and apoptosis induction. However, despite an initial response, development of resistance remains a major obstacle to treatment response. Taxane resistance could result from intrinsic mechanisms such as enhanced DNA/RNA damage repair, increased drug efflux, and apoptosis inhibition, and extrinsic effects such as angiogenesis and interactions between tumor cells and immune cells. This review provides an overview of taxanes therapy applied in different stages of HNSCC and describe the mechanisms of taxane resistance in HNSCC. Through a detailed understanding the mechanisms of resistance may help developing the potential therapeutic methods and the effective combination strategies to overcome drug resistance.

1) Background: When women receive a diagnosis of a gynecologic malignancy, they can have questions about their diagnosis or treatment that can result in voice queries to virtual assistants. Recent advancement in artificial intelligence (AI) has transformed the landscape of medical information accessibility. The Google virtual assistant (VA) outperformed Siri, Alexa, and Cortana in voice queries presented prior to the explosive implementation of AI in early 2023. The efforts presented here focus on determining if advances in AI in the last 12 months improved the accuracy of Google VA responses related to gynecologic oncology. (2) Methods: Previous questions were utilized to form a common basis for queries prior to 2023 and responses in 2024. Correct answers were obtained from the UpToDate medical resource. Responses related to gynecologic oncology were obtained using Google VA, as well as the generative AI chatbots Google Bard/Gemini and Microsoft Bing-Copilot. (3) Results: The AI narrative responses varied in length and positioning of answers within the response. Google Bard/Gemini achieved an 87.5% accuracy rate, while Microsoft Bing-Copilot reached 83.3%. In contrast, the Google VA’s accuracy in audible responses improved from 18% prior to 2023 to 63% in 2024. (4) Conclusion: While the accuracy of the Google VA has improved in the last year, it underperformed Google Bard/Gemini and Microsoft Bing-Copilot so that there is considerable room for further improved accuracy.

In the past decade, it has been discovered that intestinal flora can influence various organ-specific cancers by altering the body's energy balance, increasing obesity, synthesizing genetic toxins and small signaling molecules, initiating and modulating immune responses, and metabolizing indigestible dietary components, exogenous substances, and drugs. In this review, we will focus on elucidating the role of gut flora based on its molecular mechanisms and its potential therapeutic implications in head and neck tumors in the near future.

The metastatic disease is a complex and sequential process that involves the migration of tumor cells from the primary site to distant areas. This metastatic pathway is not always predictable. Therefore, this paper presents three rare cases of unusual metastases, due to their primary site: two metastases of a clear cell renal cell carcinoma, one gingival and one nasal, as well as a mandibular metastasis of a hepatocellular carcinoma. In all cases, an incisional biopsy was performed in order to sign out the diagnosis. After microscopical examination of morphological Hematoxylin and Eosin stained slides, for all cases, immunohistochemical reactions were performed to support the primary tumor site. Two cases had a previous histopathological diagnosis of a primary tumor, while for the third case, the metastatic lesion represented the first manifestation of the neoplastic disease, with an unfavorable prognosis.

The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for the patients' dichotomization in the continuous gene expression. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the median or quantiles of gene expression value to perform the analyses. There are also few clinicopathological features available on their pre-processed data sets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustment with confounders, the clinical tumor stage and the surgical margin involvement are independent risk factors for patients' prognosis. According to the resulting tables with Bonferroni-adjusted P value under the optimal cutoff and the hazard ratio, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with the patients' overall survival. We validated this discovery by using the other independent HNSCC dataset (GSE65858). Thus, we suggest the transcriptomic analysis could help for biomarker discovery.

Introduction: Cleft lip with or without cleft palate (CL/P) is the most common congenital face anomaly in the world of multifactorial etiology. Objective: To determine the prevalence and characteristics of cleft palate. To identify associated risk factors to guide prevention and/or prenatal detection for early intervention and better health outcomes. To assess the rehabilitation protocols after operations in cleft palate. Design: Retrospective descriptive and clinical study. Patients: One hundred and three children with cleft palate treated in the Department of Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, University of Warmia and Mazury, were included in the study. Methods: Records evaluation was conducted regarding sex, cleft type, mother occupation, parents education, histories of cleft in any of parents. The data were analyzed using R (R core team 2021) and the ordinal logistic regression analyses. Results: Children of stressed mothers during pregnancy had 9.4 times higher odds of having bilateral cleft. While there was no evidence that children sex, order of birth, and body mass as well as risk of maternal toxicity at work or reporting infections or drugs toxicity had a significant effect on the dependent variable. Conclusions: Children of parents with cleft history and having low educated mothers had higher probability of bilateral cleft palate. Children of stressed mothers during pregnancy had higher odds of having bilateral cleft. In literature, there is a lack of reports about rehabilitation in different operations methods in children with cleft palates.

Single Nucleotide Polymorphisms (SNPs) are the most common type of genetic variation found in individual’s DNA sequences. SNPs can occur in both coding and non-coding regions of the genome and can affect gene expression, protein function, and disease susceptibility. In this systematic review we evaluate the influence of SNPs as a biomarker in the assessment of oral mucositis (OM) in head and neck cancer (HNC) patients. The study selection process involved screening 66 articles from different platforms, and after removing duplicates and excluding irrelevant articles, 23 articles were included for full-text evaluation. The main characteristics and findings of the selected articles are presented and discussed. We conclude that SNPs can be used as a reliable biomarker for the assessment of OM in HNC patients, and further research is needed to explore the potential of SNPs in personalized medicine for HNC treatment.

BACKGROUND: Head and Neck Sarcomas (HNSs) are rare malignant tumors derived from mesenchymal cells characterized by rapid growth, local aggressive behavior, and multiple re-lapses. The Rhabdomyosarcoma (RMS) and the Osteosarcoma (OS) are the more frequent HNS. The present study aims to evaluate the clinical impact of multimodal treatment in patients diagnosed with HNS. METHODS: A retrospective analysis of medical records from patients diagnosed with HNS multimodal treated, four groups were formed: a) surgery and chemotherapy (CTX); b) surgery, CTX, and RT; c) surgery and RT; d) CTX and RT exclusively. The overall survival (OSS), disease-free survival (DFS) and progression-free survival (PFS) rates were calculated using the Kaplan-Meier test. RESULTS: Among 39 patients, 23.1% were diagnosed with RMS , 66.7% with OS and 10.3% with other subtypes of HNS. Moreover, 59% showed initial clinical staging (T1/T2) and of those 35.9% were T1. Surgery was performed in 87.2% patients, RT in 35.9% and CTX in 84.7%. RT performed showed not statistically significant clinical role regarding OSS (p=0.74), DFS (p=0.09) and PFS (p=0.90) rates independent of histological subtype. Finally, OSS (p=0.89), DFS (p=0.13) and PFS (p=0.50) rates were not statistically different for patients treated with monotherapy or multimodal therapy. CONCLUSION: RT has not showed a clinically important role referred to improve OSS, DFS and PFS rates in patients with HNS, regardless of the histological subtype of the primary tumor. Multimodal treatment could influence in survival rates and locoregional control of the disease; however, longitudinal studies such as randomized clinical trials must be conducted.

The problem of drug resistance in terms of antifungal therapy, unknown until a few years ago, is assuming increasing importance. Particularly in immunosuppressed patients and subject to chemotherapy and radiotherapy. In the last years the use of essential oils as approach to improving the effectiveness of antifungal agents and reducing the antibiotic resistant has been proposed. Our research aimed to evaluate the antifungal activity of Colombian essential oil of Ruta graveolens (REO) against clinical strains of Candida albicans, Candida parapsilopsis, C. glabrata and Candida tropicalis. The data obtained showed that Candida tropicalis and Candida albicans were most sensible strains showing minimum inhibitory concentrations (MIC) of 0.5 and 1.0 µg/ml of REO. The Time Kill Kinetics assay demonstrated that REO showed fungicide effect against C. tropicalis and fungistatic effect against C. albicans. In addition, the 40% of the biofilm formed by C. albicans was eradicated using 1% of REO after 1 hour of exposure.

β₂-m, β₂-microglobulin; CAF, cancer associated fibroblast; CSC, cancer stem cell; CTL, cytotoxic T lymphocyte; DC, dendritic cell; ECM, extracellular matrix; EGF-R, epidermal growth factor receptor; ER, endoplasmic reticulum; FDA, Food and Drug Administration; HLA, human leukocyte antigen; HNSCC, head and neck squamous cell carcinoma; HPV, human papilloma virus; ICP immune checkpoint; ICPi, immune checkpoint inhibitor; IFN, interferon; LMP, low molecular weight protein; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; mTOR, mammalian target of rapamycin; MSI, multispectral imaging; NK, natural killer; OS, overall survival; PBL, peripheral blood lymphocytes; PBMNC, peripheral blood mononuclear cells; PD1, programmed death receptor 1; PD-L1, programmed death ligand 1; PFS, progression-free survival; PI3K, phosphatidyl-linositol-3-kinase; R/M, recurrence and or metastatic; STAT, signal transducer and activator of transcription; TAA, tumor-associated antigen; TAM, tumor associated macrophages; TAP, transporter associated with antigen processing; TCR, T cell receptor; TIL, tumor-infiltrating lymphocyte; TLS, tertiary lymphoid structure; TME, tumor microenvironment; Treg, regulatory T cell; TSA, tumor-specific antigen; VEGF, vascular endothelial growth factor; VEGF-R, vascular endothelial growth factor receptor.

(1) Background: Sleep disordered breathing represent a growing public health concern, especially among children and adolescents. Full-night polysomnography is considered the gold standard for diagnosing obstructive sleep apnea. Our goals are to identify personal and environmental risk factors for the onset and persistence of sleep respiratory disorders. We also want to investigate the differences in neuropsychological profiles; (2) Methods: This is an observational, retrospective cohort study. We collected information on adenoidectomy or adenotonsillectomy. We reviewed the clinical history and preoperative visits and collected data through a telephone questionnaire. Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory (PedsQL) are questionnaires used for screening sleep respiratory disorders in children. The data were statistically analyzed it using SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL); (3) Results: The study involved 138 patients, but only 100 parents participated. A higher percentage of patients with sleep disordered breathing were observed to have mothers who smoked during pregnancy. A smaller proportion of patients with sleep disordered breathing had a habit of using a pacifier. A rise in physical results is associated with a reduction in the PSQ at follow-up (p=0.051). An increase of overall academic achievement is associated with an average decrease in the PSQ at follow-up (p&lt;0.0001). A more significant proportion of patients undergoing adenotonsillectomy were observed to have a history of prematurity and cesarean birth (4) Conclusions: These results provide essential information on the effectiveness and effects of adenotonsillectomy intervention compared to adenoidectomy intervention and the factors associated with SDB in children undergoing these interventions.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

Being forced to live in an area following a catastrophic landslide may adversely impact people's mental well-being. Unprivileged communities such as Adivasis, Dalits, plantation workers, and people with low incomes in Kerala's hilly districts are forced to live in landslide-affected areas despite their fear. This paper examines the fears and concerns of landslide survivors from the marginalized sections of society from a broader framework of the political economy of mental health. This approach aligns with the assertion made by the World Health Organisation that individual factors do not solely determine mental health but are intricately linked to broader social, political, and economic circumstances. Data were collected through in-depth interviews with fatal landslide survivors and key informants [ ]. The study employed thematic data analysis from in-depth interviews of various fatal landslide survivors since 2018. The three major themes unveiled in the analysis are: 1. post-disaster fears, 2. The factors that triggered fear and concern and 3. Socio-economic marginality and mental health. The study asserts that individuals who are poor and unprivileged are highly susceptible to mental health issues associated with landslides.

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second Near-Infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting efficiency of anti-epidermal growth factor receptor (EGFR) antibody functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro. Four cell lines, KYSE-30, CAL-27, Hep-G2 and MCF-7 that either over or under expressed EGFR were used. This expression was confirmed by flow cytometry and immunofluorescence. Cytotoxicity assays showed no AuNRs toxicity to both EGFR positive and EGFR negative cell lines up to a concentrations of 19 µg/ml. Optical microscopy demonstrated a significant difference (p&lt;0.0001) between targeted AuNRs (tAuNRs) and untargeted AuNRs (uAuNRs) in all four cancer cell lines. This study demonstrates that anti-EGFR functionalisation significantly increased the number of tAuNRs associated with each EGFR positive cancer cell. This successful targeting highlights the use of tAuNRs for molecular photoacoustic imaging or tumour treatment through plasmonic photothermal therapy.

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1&gt;49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p&lt;0.05). In addition, patients diagnosed with adenocarcinoma, PDL1&lt;49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p&lt;0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Passive dynamics is an aspect of locomotion which is entirely dependent on the mechanical configuration and linkages of adjacent body segments. Tension distribution along mechanical linkages enables execution of movement patterns with reduced need for complex neurological pathways and may play a role in reestablishing postural stability following external disturbances. Here we demonstrate a uni-directional mechanical relationship between the equine forelimb, head and neck, which may have implications for balance and forelimb loading in the horse. These observations suggest that forelimb, head and neck movement coordination (observed in the horse during unrestrained locomotion) is largely controlled by the mechanical linkages between body segments, rather than being entirely dependent on neurological input as previously thought. This highlights the potential significance of research directed at investigating passively induced movements in understanding common locomotory patterns. Additionally, it suggests a mode of postural control which may provide instantaneous adjustments to postural disturbances, thus promoting rapid and efficient locomotion.

Importance: The rapidly expanding 2019 novel coronavirus pandemic (COVID-19, caused by the SARS-CoV-2 virus) has challenged the medical community to an unprecedented degree. Physicians and healthcare workers are at added risk of exposure and infection during the course of the patient care. Due to the rapid spread of this disease through respiratory droplets, healthcare providers such as otolaryngologists-head & neck surgeons who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures are particularly at risk. Here we present a set of safety recommendations based on our review of literature and communications with physicians with first-hand knowledge of safety procedures during the 2019 COVID-19 pandemic.Observations: A high number of healthcare providers were infected during the first phase of the pandemic in Wuhan province. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for healthcare providers without jeopardizing the care of patients. We reviewed the most common procedures related to the examination and treatment of upper aerodigestive tract diseases. Each category was reviewed based on the potential risk imposed to healthcare workers. Specific recommendations were made, based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in COVID-19 patients. Conclusions and Relevance: Preserving highly skilled healthcare work force is a top priority for any community and healthcare system. Based on the experience of healthcare systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of healthcare providers could be significantly reduced, while providing high levels of care. The provided recommendations could be used as broad guidance for all healthcare workers who are involved with the care of COVID-19 patients.

From the existing millions of fungal species only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck over a 19-year period (2005 to 2024) at a large academic healthcare system. Among 413 cases, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.

Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metastases-free survival; overall survival; toxicity.

The study delves into the multifaceted landscape of human-macaque conflict within temple ecosystems, with a specific focus on Bonnet Macaques. In the context of intertwined religious, cultural, and social values, understanding public attitudes towards these commensal species becomes pivotal. The research aims to decipher the socio-economic factors that shape perceptions of human-monkey conflict within temples and to explore public attitudes within sacred groves. To achieve these objectives, a comprehensive questionnaire was administered through household interviews to 100 residents living within both a 1 sq. km and a 2 sq. km radius of the study area, ensuring direct participant interaction. The survey, taking approximately 40 minutes per participant, examined six variables, including occupation, religion, and annual income. The data collected was analysed using SPSS ver. 24 software, employing the chi-square test of independence to explore associations between categorical variables. The findings revealed that occupation and religion emerged as influential factors in shaping perceptions of Bonnet Macaques as problematic. While annual income hinted at significance, age, education, and knowledge of Kysannur Forest Disease (KFD) did not significantly impact Bonnet Macaque perception. Interestingly, age emerged as a significant factor influencing the perception of the monkeys' religious significance, whereas only education and religious affiliation impacted feeding practices towards the monkeys. Surprisingly, other demographic variables such as age, gender, occupation, and income showed no significant influence on monkey feeding practices. These results underscore the intricate interplay of socioeconomic, cultural, and religious factors in shaping public attitudes and behaviours towards Bonnet Macaques. The study further sheds light on the impact of education and religious affiliation on feeding practices, emphasizing the need for nuanced conservation strategies. Recognizing these complexities is crucial for developing culturally sensitive conservation efforts. By acknowledging the influential factors identified in this research, conservation strategies can be tailored to specific communities, fostering harmonious coexistence between humans and Bonnet Macaques in temple ecosystems. This nuanced approach ensures that conservation efforts are not only effective but also respectful of the diverse socio-cultural contexts within which they are implemented.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

Until recently, research on the molecular signatures of HPV-associated head and neck cancers mainly focused on their differences with respect to HPV-negative HNSCCs. However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells, and oxidoreductive processes all play important roles.

Currently, data regarding optimal treatment modality, response, and outcome specifically for N3 head and neck cancer are lacking. This study aimed to compare the treatment outcomes between definitive concurrent chemoradiotherapy (CCRT) to the neck and upfront neck dissection followed by adjuvant CCRT. 93 N3 squamous cell carcinoma head and neck cancer patients were included. Primary tumor treatment was divided to definitive CCRT (CCRT group) or curative surgery followed by adjuvant CCRT (surgery group). Neck treatment was also classified into two treatment modalities: definitive CCRT to the neck (CCRT group) or curative neck dissection followed by adjuvant CCRT (neck dissection group). Overall, the 2-year overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 51.8%, 47.3%, 45.6%, and 43.6%, respectively. In both oropharyngeal cancer and nonoropharyngeal cancer patients, in terms of OS, LRFS, RRFS or DMFS no difference was noted regarding primary tumor treatment (CCRT vs. surgery) or neck treatment (CCRT vs. neck dissection). In summary, N3 neck patients treated with definitive CCRT can achieve similar outcomes to those treated with upfront neck dissection followed by adjuvant CCRT. Cautions should be made to avoid overtreatment for this group of patients.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Background: The accurate diagnosis of regional lymph node metastasis is critical for guiding treatment decisions in head and neck cancer patients. Despite advances in imaging techniques, detecting nodal metastasis remains challenging, leading to potential undertreatment or overtreatment. This systematic review aims to identify molecular markers associated with occult metastasis in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. Methods: The present research was conducted following PRISMA guidelines. Prospero registration nr. CRD42024522985. Results: Through a comprehensive literature search and review process, 634 articles were considered, 103 of them were finally included. Conclusions: Several promising markers were identified, including miR-205, DSG3, pan-CK AE1/AE3, HPV-16, Activin-A, Cyclin D1, and NPL that demonstrated effectiveness across multiple studies. Future research should focus on exploring combination scoring systems to improve diagnostic precision and optimize treatment selection in HNSCC patients.

Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitates the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK). Despite intensive multimodal treatment, survival rates remain below 40% for children with HR-NB. The aim of this work was to investigate the combined effect of the SSTA 177Lu-octreotide with the ALK inhibitor lorlatinib. Mice bearing human HR-NB CLB-BAR tumors were treated with lorlatinib, 177Lu-octreotide, combination of these pharmaceuticals or saline (control). Tumor volume was monitored and tumor samples were evaluated for cleaved caspase-3 and expression of 84 human genes involved in apoptosis. Combination treatment with 177Lu-octreotide and lorlatinib demonstrated synergistic antitumor effects. Increased number of cleaved caspase 3-positive cells was observed in tumors from mice treated with 177Lu-octreotide alone and in combination with lorlatinib. Modulation of Bcl-2 family gene expression was observed only in the presence of both 177Lu-octreotide and lorlatinib, with BID downregulated and HRK upregulated on days 2 and 7, respectively. The data suggests that ALK signaling pathway inhibition may contribute to radiosensitization in radionuclide therapy with 177Lu-octreotide.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

The ErbB/HER family of protein-tyrosine kinases (ErbB) and the phosphatidylinositol 3-kinase (PI3K) represent crucial targets in the treatment of head and neck squamous cell carcinoma (HNSCC). We previously reported that a combination therapy using Afatinib (ErbB inhibitor) and Copanlisib (PI3K inhibitor), both FDA-approved kinase inhibitors, suppressed the growth of HPV-positive HNSCC. In our current study, we further evaluated the efficacy and clinical potential of this combination therapy for treating HPV-negative HNSCC in vitro and in animal model. We found that the combination treatment of Afatinib and Copanlisib dramatically enhanced inhibition of cell proliferation and reduced cell survival when compared to treatment with either inhibitor in two HPV negative HNSCC cell lines. Notably, this combination led to significant inhibition of xenograft tumor growth in mice, without any apparent effects on body weight. Copanlisib alone effectively blocked PI3K/Akt signaling, but caused up-regulation of HER2 and HER3 phosphorylation as previously reported in other types of cancer. However, the combination treatment with Copanlisib and Afatinib completely blocked phosphorylation of the ErbB family (including HER3) and Akt, while also remarkedly increasing apoptosis. These results suggest that co-targeting the ErbB family and PI3K kinases by a combination treatment of Afatinib and Copanlisib can have clinical potential for patients.

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. One of the undisputed values of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make any conclusion on this topic hard. Current guidelines suggest considering micrometastasis (MIC) as a node-positive disease, while isolated tumor cells (ITC) as a node-negative disease, with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, prognostic and therapeutic role of LVM and underline the present and future challenges we are facing. We hope this review will guide further research, giving robust evidence on LVM and their impact on clinical practice.

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2 and neuroendocrine carcinoma: NEC) on the basis of Ki-67 proliferation index and mitotic count according to the 2010 WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic backround together with preclinical studies to develop new agents, including those already under investigation for SCLC, will be needed to improve the prognosis.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcome in high-risk patients. This retrospective case-control study involved two cohorts of 14 patients (“discovery cohort”) and 12 patients (“validation cohort”) with cSCC located in head-neck anatomical district and diagnosed at pT2 stage. Overall, cases developed early local relapse of the disease whereas controls never re-lapsed during the entire follow-up period. Next generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutation was identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating the recognition by the immune system. This could enhance and sustain immunological response, potentially preventing future recurrences.

Abstract Purpose Despite a considerable amount of literature on dual-energy-CT(DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. Material and Methods: Consecutive venous DECT scans of head and neck were reviewed, and unremarkable exams were included (n=617). 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male [n=403] vs female [n=214]; young [n=207] vs middle-aged [n=206] vs old [n=204]; normal weight [n=314] vs overweight [n=196] vs obese [n=107]]). Results: Overall mean iodine uptake values ranged between 0.5 and 9.4mg/ml. Women showed higher iodine concentration in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for tongue and palatine tonsils were lower compared to younger subjects (p0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with higher BMI (p0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with higher BMI (p0.04). Conclusion: Physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in clinical routine of head and neck DECT.

Previously, pseudomyogenic hemangioendothelioma (PMHE) is regarded as epithelioid sarcoma-like hemangioendothelioma due to significant histologic overlapping and diffuse cytokeratin expression since the first description in 1992. After considerable controversy and long-term debating, it is currently defined as a distinct intermediate malignant, rarely metastasizing neoplasm with vascular/endothelial differentiation in nature. PMHE is characterized by young age (typically < 40 years old) and extremity location (approximately ~80%) with t(7:19) SERPINE1-FOSB fusion as the most common molecular alteration. Here we reported a 59-year-old male presenting with multifocal lesions, including right temporalis muscle, right frontoparietal calvarium, right pterygoid muscles, and right mandibular condyle. Histologic examination of the lesion from right temporal mass revealed a multinodular biphasic lesion composed of sheets and fascicles of elongated spindle cells, and epithelioid small round to ovoid cells infiltrating into the adjacent skeletal muscle admixed with abundant neutrophilic infiltration. No rhabdomyoblast-like cells, prominent nuclear pleomorphism and mitosis were identified. IHC staining showed that the tumor cells were diffusely and strongly positive for FOSB, pan-cytokerain (AE1/AE3), CD31, ERG, and molecular testing further demonstrated a t(9:19) EGFL7::FOSB fusion mRNA. This constellation of morphological, IHC and molecular findings was consistent with the diagnosis of PMHE. This is the first reported case of multiple PMHEs with EGFL7::FOSB fusion in a patient aged more than 50 years old in the head and neck area. Since the vast majority of the differential diagnoses of PMHE are high-grade malignancies with aggressive clinical behavior and PMHE is rarely reported in the head and neck region, awareness of this tumor will avoid misdiagnosis and over-treatments of this entity.

Background: Recent researches have investigated the biological importance of RNA N1-methyladenosine (m1A) modifications in oncogenesis and progression of head and neck squamous cell carcinoma (HNSCC). However, whether m1A modifications also have latent effect in tumor microenvironment (TME) generation and immune regulation in HNSCC is unknown. Methods: We evaluated the m1A modification patterns and related to these modification patterns with TME cell infiltration features in 1041 HNSCC samples by bioinformatics approach. Results: The m1A score is an independent prognostic indicator. HNSCC patients with low m1A score group with poor overall survival (OS) was mainly characterized by stroma activation, lack of sufficient immune infiltration, and exhibited an immune- desert TME phenotype. Low m1A scores were also correlated with increased tumor mutation burden (TMB), and HNSCC patients with high TMB and low m1A scores had the worst OS. In addition, anti-CTLA-4 combined with anti-PD1 treatment was more effective in the high m1A score subgroup than in the low m1A score subgroup. Conclusions: This study revealed that m1A modifications play a non-negligible role in developing the TME versatility and complexity of HNSCC. Assessing m1A modification patterns in HNSCC helps improve our comprehension of its TME infiltration profile and guides more effective immunotherapeutic approaches.

Cervical cancer is one of the ailments that endangers the health of women all over the world and causes infertility. Fortunately, this disease can be avoided. Both the results and participation rates of the current preventative strategy remain poor. Hence, preventative or early detection methods remain challenging and open. In gynecology and computer science fields, few studies on identifying cervical cancer are based on behavior risk factor and machine learning. Moreover, various social and behavioral aspects might often make it more difficult to detect cervical cancer especially in low‑ and middle‑income countries (LMICs). Accordingly, focus on predicting the presence of cervical cancer through behavioral risk factors is the basic structure of this research. We proposed an approach to classify cervical cancer from a social-behavioral perspective using logistic regression to predict cervical cancer. We got significantly improved outcomes than the existing methods. Moreover, we used feature engineering to formulate less dimensionality as a pre-processing step and optimized parameters to be prepared for classification phase. The results proved that using the logistic regression with regularization type L1 had a promising performance. The accuracy of Logistic Regression (LR) L1 was 97.2%. Such results support the proposed work as a reliable classification predictive tool.

Background: Here, we investigated the inflammaging and physical performance in older adults before and after the COVID-19 pandemic. Methods: Women(n=18) and men(n=7) older were evaluated before the COVID-19 pandemic(PRE), 12 months after the lockdown(POST), and 10 months after resuming exercise training(POS-TR). Physical tests [gait speed(GS) and timed-up-and-go(TUG)]; muscle strength (handgrip-HG), and serum cytokine levels were assessed. Results: The older women showed higher GS and TUG at POST than PRE and POST-TR, besides lower HG at POST-TR than PRE, whereas older men exhibited lower HG at POST and POST-TR than PRE. Both groups presented (1)lower IL-10 and IL-12p70 values in contrast to higher IL-6/IL-10 and IL-8/IL-10 ratios at POST than PRE; (2)higher IL-10 values and lower IL-8/IL-10 ratio at POST-TR than POST; (3)higher IL-12p70/IL-10 ratio at POST-TR than PRE and POST. Particularly older women showed: (4)lower IL-6 values at POST and POST-TR than PRE; (5)lower IL-8 and IL-10 values at POST-TR than POST; (6)and higher TNF-α/IL-10 and IFN-γ/IL-10 ratios at POST than PRE and POST-TR. Significant correlations between the variables were found in both groups. Conclusion: During the COVID-19 pandemic, detraining and resumption of exercise training promoted distinct alterations in physical capacity and inflammaging among older women and older men population.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite advancement of the current treatment to HNSCC, such as surgery, chemotherapy, and radiotherapy, the overall survival rate of HNSCC remains poor due to late diagnosis and acquired resistance to treatment. Natural products have been extensively explored as a safer and more acceptable alternative to current treatments, with numerous studies displaying their potential against HNSCC. This review highlights preclinical studies in the past 5 years involving natural products against HNSCC and explores the signalling pathways altered by these products. This review also addresses challenges and future directions of the use of natural products as chemotherapeutic and chemoprevention agents against HNSCC.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ at risk (OAR) avoidance structure, provider and patient reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p=0.0082) and hospitalization (p=0.0356) during and within 30 days of completing RT. Conclusion: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

The most common type of head and neck cancer (HNC) is head and neck squamous cell carcinoma (HNSCC). It describes a heterogenous neoplastic disease that arises from the mucosal epithelium of the of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being is the eighth most common cancer worldwide, with 931,931 newly diagnosed cases and 467,125 deaths according to the latest Global Cancer Statistics (GLOBOCAN) data. Despite the use of modern low-invasive surgical techniques and application of promising new chemoradiotherapies or combination treatment, the frequency of recurrences and the five-year survival of these patients remains unsatisfactory. The microenvironment of head and neck cancer comprises various cells that regulate neoplastic expansion. It is believed that the mesenchymal stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and progression, in the regulation of cancer treatment response, survival rates, patient outcomes and long-term prognosis; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNSCC. MSCs, are multipotent, heterogeneous, mobile cells, which meet specific stemness criteria defined by the International Society for Cellular Therapy (ISCT). Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties, they may play a key role in the process of acquiring drug resistance, and thus treatment failure. MSCs must also demonstrate plastic adherence in vitro and be able to differentiate into specific mesodermal cell types after stimulation i.e., adipocytes, chondrocytes, and osteoblasts when cultured under well-defined conditions. The present narrative review examines the links between mesenchymal stromal/stem cells and HNC, as well as the different mechanisms involved in the development of resistance to current chemo- and radiotherapies in HNSCC. It provides an overview of the current literature, including key opinion-forming systematic reviews, as well as cross-sectional, longitudinal, prospective and interventional studies based on cell culture models in vitro, animal or in vivo models of HNSCC; it also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. The data concerning tumour-associated MSCs is arranged according to increasing clinical credibility.

Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on day -7, 5, 35, 80 and 105 with following cytokine analysis. The harvested submandibular salivary gland was assessed for presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC and MIP-1α showed increased levels in saliva in irradiated mice and strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.

Background: Cell proliferation and the cell cycle are fundamental to tumor development, with mitosis playing a crucial role in cell division. Understanding the complexities of the cell cycle and mitosis is critical for cancer research, especially in the context of developing therapeutic strategies. Objective: This review highlights mitotic poisons as potential anti-cancer pharmacotherapeutics, particularly their structural and functional group diversity presenting opportunity for semi-synthesis of new derivatives with multi-target mechanisms relevant for cancer pharmacotherapeutics. Also, the review explores naturally occurring mitotic poisons and inhibitors of microtubule-dependent molecular motors as promising cancer pharmacotherapeutics. Methods: A comprehensive review of literature from 2004 to 2023 was conducted, covering studies on cell proliferation, mechanism of cell cycle regulation, mitosis, cytokinesis, and anti-cancer drug development. The published literature was collected primarily from PubMed, Scopus, Medline, Web of Science Core Collections, Google Scholar and other relevant scientific databases using keywords including but not limited to mitotic poisons and cancer, sources of mitotic poisons, mechanism of mitotic poisons, targets of mitotic poisons and structural diversity of mitotic poisons. The efficacy and limitations of various mitotic poisons and their impact on different cancer types were examined. Recent advancements in targeted therapeutic interventions for various cancers were also explored. Results: The effectiveness and limitations of mitotic poisons, including Taxanes, Epothilones, Colchicine, Vinca alkaloids, Berberine, Laulimalide, and Pseudolaric acid B, were highlighted. Drugs targeting mitotic kinases such as CDKs, Aurora kinases, PLK1, and WEE1 inhibitors were reported. Inhibiting kinesin motor proteins such as Eg5 and KIF15 to interfere with spindle formation and cell division were discussed, along with specific genomic alterations in KIF genes and the discovery of KIFC1 as potential for future research and drug development. Conclusion: Targeting microtubules and mitotic kinases, along with inhibiting kinesin motor proteins, show promise for cancer pharmacotherapeutics. The combination of targeted therapies, patient stratification based on biomarkers (such as low alpha-1 acid glycoprotein and high p63 expression), and exploration of alternative natural sources of mitotic poisons and analogues can significantly advance cancer pharmacotherapy to improve patient outcomes.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The delineation of the clinical target volumes (CTVs) for radiation therapy is time-consuming, requires intensive training and shows high inter-observer variability. Supervised deep learning methods depend heavily on consistent training data, thus state-of-the-art research focuses on making CTV labels more homogeneous and strictly bounding them to current standards. International consensus expert guidelines standardize CTV delineation by conditioning the extension of the clinical target volume on surrounding anatomical structures. Training strategies that directly following the construction rules given in the expert guidelines or the possibility to quantify the conformance of manually drawn contours with the guidelines are still missing. 71 anatomical structures that are relevant for CTV delineation in head and neck cancer patients according to the expert guidelines were segmented on 104 CT scans to assess the possibility to automate their segmentation by state-of-the-art deep learning methods. nnU-Net models were trained to automatically segment those 71 structures on planning CT scans. We report the DICE, HD and sDICE for 71 + 5 anatomical structures for most of which no previous segmentation accuracies have been reported. For those structures, for that prediction values have been reported, our segmentation accuracy matched or exceeded the reported values. The predictions from our models were always better than those predicted by the TotalSegmentator. The sDICE with 2mm margin was larger than 80% for almost all structures. Individual structures with decreased segmentation accuracy are analyzed and discussed with respect to their impact on the CTV delineation following the expert guidelines. No deviation is expected to affect the rule-based automation of the CTV delineation.

Head and neck squamous cell carcinoma (HNSCC) takes the sixth place among the most common cancers in the world. Abnormal methylation can be one of the reasons for this cancer. The aim of this study was to investigate the DNA promotor methylation status of cancer-associated genes (ATM, APC, CDO1, RB1, TP53, WIF1) in patients with HNSCC. Bisulfite Conversion and Methylation-Sensitive High-Resolution Melting was used for analysis of the DNA methylation level of normal and tumor tissues in 44 patients. There were significant differences in DNA methylation level between patient’s tumor and normal tissues for CDO1 and WIF1 genes in all subjects and subgroups (p<0.05). In T3 subgroup there was significant correlation between CDO1 gene methylation and age in the normal tissue. The same correlation was detected also for the WIF1 gene methylation in tumor tissue samples in the subgroup with T3 and in normal tissue samples in the subgroup with T4 (p<0,05). In all genes no significant differences were found between the subgroups (T2, T3, T4 stage, primary/recurrent lesion, non-keratinizing/keratinizing SCC, age before/ after 50, smokers/non-smokers) of the patients. Thus, changes in the expression of the CDO1 and WIF1 genes can affect mechanisms of the occurrence and development of HNSCC.

The high prevalence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) is well-established, with p16 expression being a strong predictor. HPV-related tumors exhibit unique mechanisms targeting p16 and p53 proteins. However, re-search on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous squamous cell carcinomas (HNCSCC), especially in Asian populations, is limited. This retrospective study surveyed 62 HNCSCC patients (2011–2020), excluding those with facial warts or other skin cancers. All patients underwent wide excision and biopsy. Immuno-histochemical staining for HPV, p16, and p53 yielded both positive and negative results. The relevance of each marker was investigated by categorizing the tumor locations into high-risk (Area H) and mid-risk (Area M) zones based on recurrence frequency. Of the 62 patients, 20 (32.26%) were male, with an average age of 82.27 years (26–103). Area H included 19 cases (30.65%), with the eyelid and lip being the most common sites (five cases, 8.06%). Area M in-cluded 43 cases (69.35%), with the cheek being the most common site (29 cases, 46.77%). p16 ex-pression was positive in 24 patients (38.71%), p53 expression in 42 patients (72.58%), and HPV in five patients (8.06%). No significant association was found between p16 expression and HPV presence (p > 0.99), with a positive predictive value of 8.33%. This indicates that p16, a surrogate marker of HPV in OPSCC, is not a reliable marker for HPV in HNCSCC. This study enhances our understanding of the relationship between HPV, p53, and p16 in HNCSCC in Asian populations and offers valuable insights for further research.

Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

We developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. Near-infrared laser irradiation stimulated the generation of reactive oxygen species, causing short-term reactive molecular species and spatial-temporal restricted photodamage to the biological targets. The reactive molecular species and spatial-temporal restricted photodamage enhanced the release and uptake of chemotherapy drugs and increased the sensitivity to chemotherapy drugs in ovarian cancer cells. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and −27.8 ± 0.42 mV, respectively. SN38/IR820-Lipo@FSH exhibited good drug-loading properties and the in vitro release was slow. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited good tumor-targeting ability and anti-ovarian cancer activity in vivo. The SN38/IR820-Lipo@FSH exhibited specific targeting to A2780 ovarian cancer cells. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

The application of artificial intelligence to point-of-care testing (POCT) disease detection has become a hot research field, in which breath detection which detects the patient's exhaled VOCs combined with sensor arrays of Convolutional Neural Network (CNN) algorithms as a new lung cancer detection is attracting more researchers' attention. However, due to low accuracy, high complexity computation and large number of parameters make the CNN algorithms difficult transplant to the embedded system of POCT devices. A lightweight neural network (LTNet) in this work is proposed to deal with this problem, and meanwhile, achieve high-precision classification of acetone and ethanol gases, which are respiratory markers for lung cancer patients. Compared to currently popular lightweight CNN models such as EfficientNet, LTNet has fewer parameters (32K) and its training weight size is only 0.155 MB. LTNet achieved an overall classification accuracy of 99.06% and 99.14% in the own mixed gas dataset and the University of California (UCI) dataset, which are both higher than that of the five existing models’, and it also offers the shortest training (844.38s and 584.67s) and inference time (23s and 14s) in the same validation set. Compared to the existing CNN models, LTNet is more suitable for resource-limited POCT devices.

Background: this interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low-intermediate risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). Methods: forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low to intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a Day Hospital setting under local anesthesia. Patients underwent regular clinical assessments, PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. Statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. Results: forty patients were initially included, with 15 lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. Biopsies at 36 months revealed no malignant findings in 20 patients. No deterioration in sexual function or urinary symptoms was recorded. Conclusions: FLA appears to be safe, feasible and effective in the index lesion treatment of low-intermediate risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

Objectives: Non-adhesive gel-like embolic materials (NAGLEMs) are becoming increasingly dominant in the endovascular treatment of hypervascularised formations in the head and neck due to a combination of their key properties. The main advantages include their lack of adhesion, effective distribution and penetration through pathological vessels, and crucially, their controlla-bility during the process. Our assigned duty was to scrutinise the literature and assess the efficacy and outcomes of administering NAGLEMs, in comparison to other embolizing substances (name-ly, coils, glue, and particles), among patients treated at our clinic. The procedures involved ana-lyzing the technical aspects, efficiency, and safety of endovascular therapy applied to two catego-ries of hypervascular pathological anomalies, surgically managed from 2015 to 2023. Arteriove-nous malformations (AVMs) located in the head, neck, and paragangliomas with jugular/carotid body localization are combined by intense shunting blood flow and shared requirements for em-bolizates used in endovascular treatment (such as penetration, distribution, delayed polymeriza-tion and controllability). An analysis of the literature was also conducted. Results showed 18 pa-tients diagnosed with neck paragangliomas of the carotid body and jugular type. Five patients with arteriovenous malformation (AVM) of the face and neck were included, consisting of 16 fe-males and 7 males with an average age of 55 ± 13 years. Endovascular procedures were conduct-ed using NAGLEMs (ONYX (Medtronic), SQUID (Balt), and PHIL (Microvention)) and dimethyl sulfoxide (DMSO)-compatible balloon catheters. All patients achieved complete or partial embo-lization of hypervascularized formations using one or more stages of endovascular treatment. Additionally, three AVMs of the face and two paragangliomas of the neck were surgically ex-cised following embolization. In other instances, formations were not deemed necessary to be re-moved. The patients' condition upon discharge was assessed by the modified Rankin Scale (mRs) and rated between 0 and 2. Conclusion: Currently, NAGLEMs are predominantly used to treat hypervascularized formations in the neck and head due to their fundamental properties. These properties include a lack of adhesion and a delay in predictable polymerization (after 30-40 minutes). NAGLEMs also exhibit excellent distribution and penetration throughout the vascular bed of the formation. Adequate controllability of the process is largely achieved through the pres-ence of embolism forms of different viscosity, as well as excellent X-ray visualization.

The prognosis of patients with recurrent or metastatic of the head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is severe and, consequently, the identification of therapeutic options for this category of patients is a priority. Nivolumab, an anti- programmed cell death protein 1 (anti-PD-1) monoclonal antibody, has been approved for the treatment of recurrent or metastatic HNSCC after platinum-based therapy progressing. We present the early experience of two academic center including diagnostic, clinical, biological, therapeutic and outcomes characteristics of head and neck cancer (HNC) patients treated with Nivolumab. The purpose of the study is to identify certain peculiarities and to report them compared to the data from the literature in order to generate some hypotheses that coud constitute criteria for the selection of cases with maximum benefit to immunotherapy. Analyzing the data obtained from 18 patients treated in Emergency County Hospital Craiova, "Saint Nectarie" Oncological Hospital Craiova and Euroclinic Oncological Center Iasi January 2020 and March 2023 it could be hypothesized that lower nadir values of neutrophil to lymphocyte ratio (<3.5) and the adition of intensive regimens of chemotherapy and radiotherapy could justify a favorable response in terms of progression free survival (PFS) during immunotherapy with Nivolumab. To our knowledge, the study included the first two cases of second primary malignancy (SPM) in the head neck region treated with Nivolumab. The reported data support a possible benefit of the sequential administration of radiotherapy, immunotherapy for SPM cases. Higher positive dynamic of neutrophil to lymphocyt ratio (NLR) could be associated with worst outcome during immunotherapy. All study observations including the role of infections and antibiotic treatment as well as the possible biomarker value of NLR variation during immunotherapy should be investigated in multicenter clinical trials.

This article describes the history of research and development of surface-penetrating radar, starting from the 60s in the USSR, and ending today in Russia and neighboring states formed after the collapse of the USSR. The outstanding role played in the initial period of this technology development by Prof. M.I. Finkelstein and his colleagues is highlighted. Their research had a significant impact on subsequent developments in modern Russia and the neighboring countries.