Gastrointestinal cancers are a specific group of oncological processes in which the location and nature of growth are of key importance for clinical symptoms and prognosis. At the same time, as research shows, they can pose a very serious threat to the patient's life, especially at an advanced stage of development. The type of therapy used depends on the anatomical location of the cancer, its type and degree of progression. One of the modern forms of therapy used to treat gastrointestinal cancers is photodynamic therapy, which, as already mentioned, has been approved for the treatment of esophageal cancer in the United States. Despite the increasingly rapidly developing clinical use of this treatment method, the exact immunological mechanism it induces on cancer cells has not yet been known. This article presents the current findings on the mode of action of dynamic phototherapy on cells of various gastrointestinal cancers. There are most of them about the impact on colorectal cancer. The types of cell death induced by PDT include apoptosis, necrosis, and pyroptosis. The anticancer effect also results from the induction of destruction of tumor vessels and activation of the immune system. Most reports exist on the mechanism of apoptosis induction, in which the mitochondrial pathway is most often emphasized. Photodynamic therapy may also have a beneficial effect on such aspects of cancer as the ability to develop metastases, or contribute to reducing resistance to known pharmacological agents.

Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about the overall epidemiology and prognostic factors of the pathology. The purpose of this study is to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with GIST in the past decade. Methods: A total of 2,374 patients diagnosed with GIST, between 2010 and 2017, were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of GIST. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and GIST related mortality among US patients between 2010 and 2017 revealed higher overall mortality in Non-Hispanic Blacks (HR= 1.516, 95% CI 1.172-1.961, p= 0.002), age 80+ (HR= 9.783, 95% CI4.185-22.868, p= 0), followed by age 60-79 (HR= 3.408, 95% CI 1.488-7.807, p=0.004); male patients (HR= 1.795 , 95% CI 1.461-2.206, p=0); advanced disease with distant metastasis (HR= 3.865 , 95% CI 2.977-5.019, p=0), followed by regional involvement by both direct extension and lymph node involvement (HR= 3.853, 95% CI 1.551-9.57, p=0.004); and widowed patients (HR= 1.975, 95% CI 1.494-2.61, p= 0), followed by single patients (HR= 1.53, 95% CI 1.154-2.028, p=0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR= 1.687, 95% CI 1.19-2.392, p= 0.003). Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that non-Hispanic blacks, male patients, and patients older than 60 years have a higher mortality with GIST. Furthermore, patients who received chemotherapy have a higher GIST specific mortality and married patients had a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing those interactions. The results of this study may help treating clinicians to identify patient populations associated with dismal prognosis as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival, we hope to encourage clinicians to involve family members of the affected patients early in the disease course as the social support might impact the prognosis.

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.

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding 8 patients with pre-ESD levels of D-dimer >1.5 μg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but because the sedative effect of midazolam shows marked inter-individual variability, a “corrected midazolam dose” was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in subgroup analysis of the 103 patients who received midazolam. In subgroup analysis using the corrected midazolam dose as an explanatory variable, only corrected midazolam dose correlated with a change in D-dimer ≥ 1.0 μg/mL in multivariate analysis (odds ratio [OR]=1.5, 95% confidence interval [CI] 0.43–0.95; P=0.030). Corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT.

Imatinib 400 mg is the standard of care for medical treatment of advanced GISTs. In the majority of cases, however, GISTs eventually develop resistance to imatinib. The optimal second line treatment has not been established yet and imatinib dose escalation (800 mg) or sunitinib represent two feasible options. The objective of this retrospective, multi-institutional, study is to analyze the validity of several parameters as possible predictive factors of response to sunitinib after imatinib failure. We reviewed 128 metastatic GISTs treated with sunitinib between January 2007 to June 2017. Primary tumour site, metastatic site, c-KIT/PDGFR-α mutational status, PET-FDG status and type of disease progression to sunitinib were assessed as possible predictive factors of response. This study identifies the gastric site of primary tumor as a predictive factor to sunitinib efficacy in second line setting. The mutational status (GIST WT), the site of metastasis (peritoneum) and the FDG-PET status (negative), although not statistically significant, seem to be elements of increased activity for sunitinib treatment. These results provide the rationale to drive physician for sunitinib choice in second line setting for metastatic GISTs, to improve patients selection and to maximize the benefit from the treatment, on the basis of possible predictive factors of response.

Background: Pancreatic neuroendocrine tumors (pNETs) represents a rare subset of pancreatic cancer. Functional tumors caused hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management need a multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preserving, cen-tral pancreatectomy, pancreaticoduodectomy or total pancreatectomy. Minimally invasive ap-proach increased in the last decade compared to the open technique. The aim of this study is to analyze current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to PRISMA guidelines, conducting a systematic review of literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords was used ("NET", "pancreatic", "surgery", "laparoscopic", "minimally invasive", "robotic”, “enuclea-tion”,“parenchima sparing”) and relevant article references was manually checked. Manuscript quality was evaluated. Results: The study screened 3867 manuscripts, twelve studies were selected, primarily from Ita-ly, the United States, and China. A total of 7767 surgical treated patients was collected from 160 included centers. The mean age was 56,3 y.o. Enucleations (EN) and distal pancreatectomy (DP) was the most common performed surgery and represents 43.4% and 38.6% of the total interven-tions, respectively. Pancreatic fistula, post operative bleeding, re-operation and follow up was recorded and analyzed. Conclusions: Enucleation show better postoperative outcomes and lower mortality rates com-pared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite similar risks of postoperative pancreatic fistula (POPF). DP was preferred over enucleation for pancreas body-tail, while laparoscopic enucleation is better for head pNETs.

Modern gastroenterology, which occupies the pages of scientific journals without alternative, began as an initiative of manufacturers of diagnostic equipment. For widespread advertising, they selected practical doctors who were not familiar with the methodology of science and superficial knowledge of physiology. This is how a group led by DeMeester arose, which in 1976 published the DeMeester score, i.e., the normal limit for esophageal pH monitoring. pH <4, less than 4% of the time per day was considered normal, i.e., it was unreasonably claimed that such reflux is physiological. This article proves that this study was carried out with numerous methodological errors, which led to an erroneous conclusion. For a long time, pH monitoring was considered the gold standard and with its help hypotheses were proposed that form the basis of modern gastroenterology. The article proves the fallacy of 13 hypotheses, which are presented as theories. Numerous articles using pH monitoring have publicized this method. Practitioners became "great scientists", equipment manufacturers became successful businessmen. Over time, they found other groups of practitioners to promote devices for impedance ph monitoring, high-resolution manometry, and many others. At the same time, a network of reviewers who believe in the infallibility of the luminaries do not allow studies that contradict their faith to be published. Thus, fundamental science was destroyed, which alone could assess the harm of false research both for science and for patients. Conclusion This study provides a list of hypotheses, that were previously considered theories, but since scientific evidence has proven these assumptions to be false, they should be excluded from subsequent use and citation.

The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated. In the case of the urinary tract, the urine produced by the kidneys must flow to the bladder, where it is stored until its elimination from the body. Finally, in the case of the vagina, it must allow the evacuation of blood during menstruation, accommodate the male sexual organ during coitus, and is the natural way to birth a child. The present review describes the anatomy, pathologies and treatments of such organs, emphasizing tissue engineering strategies.

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.

Glioma tumors are one of the most devastating cancer types. Of the different glioma tumors, glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advantages in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OV) in cancer treatment is one of those immune-therapeutic alternatives. OV have a double oncolytic action by both, directly destroying the cancer cells, sparing the patient’s life, and stimulating a tumor specific immune response to revert the ability of tumors to escape the control of the immune system. OV are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility to use some viruses to specifically infect tumors eluding undesired toxic effects in the patient. Here we have revisited the literature in order to describe the main OV proposed so far as therapeutic alternatives to destroy glioma cells in vitro and trigger tumor destruction in vivo. Some clinical trials are exploring the use of this therapy as an alternative were other approaches provide limited hope.

The hypothalamus is the site of synthesis and secretion of a number of endocrine peptides that are involved in the regulation of hormonal activity of the pituitary and other endocrine targets. Tumors of the hypothalamus have been recognized to have both structural and functional effects including hormone hypersecretion. The classification of these tumors had advanced over the last few years and biomarkers are now available to classify these tumors and provide accurate structure-function correlations. This review provides an overview of tumors in this region that is critical to metabolic homeostasis with a focus on advances in the diagnosis of gangliocytomas, neurocytomas and pituicytomas that are unique to this region.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in treatment of PNETs at advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events which are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNET and commonly occurring, and therefore more extensively studied, malignancies. Finally, we will offer perspective on the future research direction of PNET epigenome and its potential applications in patient care.

The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. Maintaining homeostasis at the gastrointestinal tract requires stringent regulation of the immune responses against various environmental conditions. Diet can be converted into gut metabolites which have unique functional activities through host as well as microbial enzymatic activities. Accumulating evidences demonstrate that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and further integrate immune response of distal mucosal tissue. Metabolites, especially derived from microbiota, regulate immune cell functions by various ways including recognition and activation of cell surface receptors, controlling of gene expression by epigenetic regulation and integration of cellular metabolism. These mucosal immune regulations are key to understand underlying mechanism for the development of gastrointestinal disorders. Here, we review the recent advancement of our understanding on the role of gut metabolites in the regulation of gastrointestinal immunity with highlighting the cellular and molecular regulatory mechanisms by macronutrients-derived metabolites.

Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system. This rare tumor in duodenum is seen 5%. The diagnosis and treatment is hard because of its rarity and location. Case: A 63-year-old man with a solid mass at the third part of the duodenum, and local segmental resection of the tumor was performed. The histopathology was reported as gastrointestinal stromal tumor of the duodenum with negative surgical margins. Discussion: Gastrointestinal stromal tumors at the duodenum are seen rarely. They can be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumors less than 2 cm can be followed by endoscopic ultrasound. Local segmental resection with 1cm clear margin is the treatment choice.

Worldwide, the demand for natural and synthetic sweeteners in the food industry as an alternative to refined sugar is increasing. This prompted more research to estimate its safety and effect on health. The gut microbiome is critical in metabolizing selected sweeteners, which might affect overall health. Recently, more studies evaluated the relationship between sweeteners and the gut microbiome. This review summarizes the current knowledge addressing the role played by the gut microbiome in metabolizing selected sweeteners. It also addresses the influence of the five selected sweeteners or their metabolites on GI cancer-related pathways. Overall, the observed positive effect of sweetener consumption on GI cancer pathways, such as apoptosis and cell cycle arrest, requires further investigation to understand the underlying mechanism. Furthermore, more research is needed to address the main challenges of studying the field, thus advancing it further.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

Brain tumors still remain a deadly cancer that, in most cases, is difficult to diagnose at an earlier stage. Therefore, it is necessary to develop rapid, sensitive methods for detecting cancer biomarkers. Such a biomarker may be a microRNA which expression level in body fluids is strongly correlated with cancer. Numerous studies have demonstrated changes in the expression of microRNAs in cerebrospinal fluid and blood samples collected from patients with brain tumors. These new biomarkers have the potential to help diagnose brain cancers at an early stage, avoiding the most invasive procedures. This review discusses the functional role of microRNAs and the prospects for their use as diagnostic biomarkers in patients with brain tumors.

Canine mammary tumors (CMTs) are among the most common disease in female dogs and share similarities with human breast cancer, which have placed these animals as a model of study in comparative oncology. Metabolic reprogramming is one of them and is known as a hallmark of carcinogenesis whereby cells undergo adjustments to supply the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as therapeutic strategies which have been tested mostly in human clinical trials, but poorly explored in CMTs. In this dedicated review, we compilated the metabolic changes described for CMTs emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial function. We observed here key factors associated with the presence and aggressiveness of CMTs, such as the increase in glucose uptake followed by enhanced anaerobic glycolysis via upregulation of glycolytic enzymes, changes in glutamine catabolism due to overexpression of glutaminases, raise in fatty acid oxidation and distinct effects depending on the lipid saturation, in addition to mitochondrial DNA which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs.

Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) to the liver. Although there are established criteria for LT in HCC, the evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system and mostly seen at the stomach. We report a case of giant gastrointestinal stromal tumor of the stomach in a 71-year-old woman. The physical examination and radiological findings revealed that a giant mass occupied most of the abdominal cavity. The patient underwent an en-block resection of this giant mass with partial resection of the distal stomach and transverse colon and, reconstruction with gastro-jejunostomy and end-to end colo-colic anatomoses. The histopathologic diagnosis was revealed as gastrointestinal stromal tumor of the stomach. We suggest that complete surgical resection is the only effective radical treatment approach for giant gastrointestinal stromal tumors of the stomach.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

Metastasis is the main cause of anti-cancer therapies failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses, relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial to mesenchymal transition (ETM) thus promoting the colonization of distant sites that in turn sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short reviews we will give an overview of the most recent advances related to three main large families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, integrin antagonists and small interfering (siRNAs). Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Pediatric brain tumors are the most common solid tumors in children, causing the highest number of cancer-related deaths at young ages. Although existing therapies have improved the 5-year overall survival rate of PBT patients, some high-risk brain tumors continue to resist current treatments. Additionally, the survivors endure devastating long-term side effects, including cognitive defects and sensory and endocrinal dysfunctions. In the past two decades, immunotherapies have evolved significantly, with great success in many cancers. Immunotherapies developed specifically for PBTs also show promising results. Currently, scores of clinical trials are underway to evaluate the safety and feasibility of a wide-range of immunotherapeutics for PBTs, and this review overviews the most recent advances, including the exciting progress made toward treating medulloblastoma, pediatric glioma, and ependymoma. We summarized the cutting-edge immunotherapies under development, including immune checkpoint blockade, chimeric antigen receptor (CAR)-T cell therapy, natural killer (NK)-cell therapy, cancer vaccines, and oncolytic virus therapy. We find that the results from the recently concluded or ongoing clinical trials on safety and feasibility are very encouraging; however, non-responsiveness and tumor recurrence still haunt them. While this review judges the scope of the current immunotherapies, it also lays out strategies to find alternate solutions for persisting issues.

The DNA methylation profile of breast cancer differs from that in healthy tissue and can be used as a diagnostic and prognostic biomarker. Aim of the study: to compare gene methylation in small malignant breast tumors less than 2 cm and in healthy tissue and fibroadenoma. Methylation of the following 15 genes was studied: MAST1, PRDM14, ZNF177, DNM2, SSH1, AP2M1, CACNA1E, CPEB4, DLGAP2, CCDC181, GCM2, ITPRIPL1, POM121L2, KCNQ1, TIMP3. Methods: analysis was made by our modified MS-HRM method followed confirmation of the results by pyrosequencing. The genes were selected from publications that studied DNA methylation in breast cancer with high genome coverage. The study group included 48 samples of breast cancer, the control group included 24 samples of fibroadenoma and 24 samples of healthy tissue. Results: significant differences were found in methylation of 8 genes: CCDC181, GSM2, ITPRIPL1, ZNF177, CACNA1E, DLGAP2, TIMP3 (all р<0.001), and PRDM14 (р=0.002). The most accurate diagnostic value, based on logistic regression, was shown with the compound of two genes – CCDC181 and ZNF177 (AUC=0.99) in pyrosequencing analysis. Conclusion: small breast cancer tumors have a specific DNA methylation profile that distinguishes them from healthy tissue and benign proliferative lesions.

Ovarian cancer is the third most common female genital cancer. Therefore, the timely diagnosis and comprehensive treatment of postmenopausal patients with benign ovarian tumors remains crucial in the field of gynecology. The significance of ovarian tumors depends on their frequency and their effects on the quality of life of a woman, as well as the possible development of ovarian cancer. Most ovarian cancers are diagnosed late and as a result are difficult to treat and often carry a poor prognosis. Currently there is no clear algorithm available for examining and accurately diagnosing patients with postmenopausal ovarian tumors; moreover, reliable criteria allowing dynamic observation and determining surgical access and optimal surgical intervention measures in postmenopausal patients is lacking.

GI endoscopy forms an important part in a daily practice of a gastroenterologist. Musculoskeletal injuries related to GI endoscopy are on the rise. Observational studies and surveys depict the importance of proper ergonomical environment when performing GI endoscopy. Our aim is to outline preventive measures in gastrointestinal (GI) endoscopy in reducing possibility for occupational injury. We review most relevant studies that outline the gravity of the problem. A detailed analysis of proposed ergonomical recommendations is performed, outlining crucial steps in injury prevention. Proper ergonomical education is a key-step in preventing occupational injury. Robotics and other mechanical solutions offer a variety of approaches tackling the ergonomical challenge. Implementing proper ergonomical education and mechanical solutions lowers the possibility if occupational injury. Strategies and appliances presented are beneficial to all GI endoscopy practitioners.

Identifying the correct dosage and time are key factors to successful implementation of anthelmintic. Comparing differential evolution of infection between anthelmintic treated animals against untreated ones, we present a mathematical model that first calibrates data collected and analyzed over an extended period of 10 years (2011-2019), and then predicts the dynamical evolution of gastrointestinal parasites in livestock, focusing specifically on Stronglye \& Coccidia oocysts, the two prime negative contributors to cattle health, measured using the standard Eggs-Per-Gram (EPG) index. The model incorporates information about all three critical regimes of infection - low infection regime ($< 50$ EPG), medium infection regime ($50-100$ EPG) and high infection regime ($>100$ EPG), including fatally large doses of infection ($> 500$), and probabilistically estimates the variation in animal weight due to infection propagation. A key success of our model is its ability to accurately predict the appropriate anthelmintic treatment times for cattle from a numerical solution of the model presented. The generic model can be applied to other agroclimatic conditions and can serve as a major diagnostic tool for anthelmintic strategizing.

We present the case of a 35-year-old male with first degree family history of gastric cancer (father diagnosed at the age of 45), that was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Despite the extensive research conducted on ruminal methanogens and anti-methanogenic intervention strategies over the last 50 years, most of the currently researched enteric CH4 abatement approaches have shown limited efficacy. This is largely because of the complex nature of animal production and the ruminal environment, host genetic variability of CH4 production, and an incomplete understanding of the role of the ruminal microbiome in enteric CH4 emissions. Recent sequencing-based studies suggest the presence of methanogenic archaea in extra-gastrointestinal tract tissues, including respiratory and reproductive tracts of cattle. While these sequencing data require further verification by culture-dependent methods, the consistent identification of methanogens with relatively greater frequency in the airway and urogenital tract of cattle plus increasing appreciation of the microbiome-gut-organ axis highlight the potential interactions between ruminal and extra-gastrointestinal methanogenic communities. Thus, a traditional singular focus on ruminal methanogens may not be sufficient, and a holistic approach which takes into consideration of the transfer of methanogens between ruminal, extra-gastrointestinal, and environmental microbial communities is of necessity to develop more efficient and long-term ruminal CH4 mitigation strategies. In the present review, we provide a holistic survey of the methanogenic archaea present in different anatomical sites of cattle and discuss potential seeding sources of the ruminal methanogens.

The incidence of gastrointestinal cancers has seen a significant increase in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, among others. These issues have necessitated the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria, a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies.

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.

Fibroepithelial lesions (FL) of the breast, in particular Phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT, and FA. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions and EGFR amplifications may inform therapeutic decision-making.

Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.

The classification of kidney tumors has undergone a remarkable evolution since the early 19th century, reflecting advances in medical science and technology. This historical overview traces the development of renal tumor classification, beginning with early clinical observations and macroscopic descriptions to the integration of molecular diagnostics in contemporary classifications. The establishment of international organizations like the World Health Organization (WHO) facilitated collaboration and standardization in tumor classification, leading to refined classifications and standardized nomenclature. Advancements in histological and molecular studies, particularly genetic analyses, revolutionized the understanding of renal cell carcinomas, enabling precise categorization based on molecular characteristics. The journey from rudimentary classifications to sophisticated systems based on detailed histological, immunohistochemical, and molecular criteria underscores the continuous evolution of kidney tumor classification. This article provides a comprehensive overview of this evolution, highlighting the contributions of scholars and the impact of technological advancements on our understanding and management of kidney tumors.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. Germ cell tumors (GCTs) are relatively rare. However, they are the most diagnosed malignancies occurring in the testis (TGCT) among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified few significantly mutated somatic genes, primarily KIT and K-RAS, so affecting, at various levels, the KIT–RAS–RAF–MEK–ERK cascade. This review focuses on the most recent investigations about this signaling pathway in TGCTs concerning their development, natural history, response to standard chemotherapy protocols (i.e., cisplatin-based), and on the efforts being made to identify targetable markers for possible precision medicine approaches.

Borderline ovarian tumors (BOTs) show intriguing characteristics distinguishing them from other ovarian tumors. This unique type of non-invasive neoplasms is characterized by atypical growth of epithelial cells, nuclear atypia, and a moderate-level mitotic activity that places BOTs between benign tumors and invasive cancers. Similar to invasive carcinomas, BOTs can be categorized into six histological subtypes based on the type of epithelial cells present. The most prevalent subtypes are serous and mucinous BOTs, whereas endometrioid, clear cell, seromucinous, and borderline Brenner tumors are diagnosed less often. Noticeably, molecular changes found in BOTs can vary on a case-by-case basis, which warrants further research on the molecular landscape of these tumors. Identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. A growing body of evidence indicates that BOTs often remain clinically dormant for extended periods before a molecular trigger initiates increased cell replication, potentially leading to carcinoma development or recurrence. Continued research in this area is crucial for improving risk assessment and developing personalized treatment approaches. While molecular studies have contributed significantly to our understanding of BOT pathogenesis, substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches. The aim of the present systematic review was to analyze the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach.

Neither tumor growth nor regression is truly spontaneous, but both may under special circumstances be driven by similar events. We describe a sequence of processes that typically leads to tumor progression but may on occasion inadvertently result in regression. A possible procedure for reducing tumor mass through a controlled intervention is also outlined.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Collision tumors, even uncommon, characterized by two distinctive (morphological, as well immunohistochemical) and spatially independent tumor components in the same location, are always puzzling for clinicians, pathologists and patients because they don’t fit in usual approaching schemes, neither diagnostic, nor therapeutic. Reviewing the specialized literature, until now, collision tumors have been reported in multiple locations such as the skin, esophagus, stomach, liver, kidney, bladder, adrenal gland or thyroid. We report a case of coexistence on the same site of a malignant tumor of ascending colon and a benign one emerging from peritoneal lining, thought initially by the surgeon to be right sided serosal carcinomatosis. But the histopatological examination reveals that those multiple serosal nodules were benign granular cell tumors collided with highly aggressive transparietal signet-ring colon carcinoma. These results put the patient's prognosis and therapeutic strategy in a different light than the clinical-imaging and intraoperative assessment.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age &gt;18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p&lt;0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p&gt;0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of &gt;99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

This is growing recognition of early onset gastrointestinal (GI) malignancies in young adults

The gastrointestinal (GI) tract is a continuous channel through the body that consists of the esophagus, the stomach, the small intestine, the large intestine, and the rectum. Its primary functions are to move the intake of food for digestion before storing and ultimately expulsion of feces from the rectum through the anal sphincter. The mechanical behavior of GI tissues thus plays a crucial role for GI function in health and disease. The mechanical properties are typically characterized by a constitutive biomechanical model, which is a mathematical representation of the relation between load and deformation in a tissue. Hence, validated biomechanical constitutive models are essential to characterize and simulate the mechanical behavior of the GI tract under physiological and pathological conditions. Numerous constitutive models have consequently been proposed over the past three decades, mainly inspired by work done in cardiovascular tissues. Here, a comprehensive review of these constitutive models is provided. This review is limited to studies where a model of the strain energy function is proposed to characterize the stress-strain relation of a GI tissue. Several needs are identified for more advanced modeling of GI biomechanics including: 1) Microstructural models that provide actual structure-function relations; 2) Validation of coupled electro-mechanical models accounting for active muscle contractions; 3) Human data under physiological and pathological conditions to develop and validate models. The findings from this review provide guidelines for using existing constitutive models as well as perspective and directions for future studies aimed at establishing new constitutive models for GI tissues.

The incidence of gastrointestinal diseases (cancer in particular) has increased progressively with considerable morbidity, mortality, and a high economic impact on the healthcare system. Dietary intake of natural bioactive phytochemicals showed to have cancer-preventing and therapeutic effects. This includes the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC), a bioactive compound from watercress. PEITC antioxidant, anti-inflammatory and anti-cancer properties are of particular importance. This review summarizes the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discuss the safe and recommended dose of PEITC. Besides, we establish a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural nutraceutical for industrial use. This is a topic that still needs more scientific development, but with the potential to lead to a viable strategy in the prevention of cancer and other associated diseases of the gastrointestinal tract.

Here we explore the emerging role of NKG2D CAR-T cell therapy in the realm of solid tumor treatment. Unique capabilities of NKG2D CAR-T cells to recognize stress-induced ligands on cancer cells are discussed, highlighting the therapy's potential for targeted and precise antitumor responses. We also examine the challenges and opportunities associated with NKG2D CAR-T cell therapy, emphasizing the ongoing advancements and clinical trial progress shaping its future. Ultimately, the discussion underscores the transformative promise of NKG2D CAR-T cell therapy in revolutionizing the landscape of solid tumor treatment and enhancing the prospects for improved patient outcomes.

Background and Objectives: Intramedullary spinal cord tumors (IMSCT) are rare entities. Especially, a location in the upper cervical spine as a highly eloquent region carries the risk of postoperative neurological deficits, such as tetraparesis or respiratory dysfunction. Evidence for respiratory dysfunction is scarce. The aim of this study was to describe the early and late postoperative clinical course of this highly eloquent tumours. Patients and Methods: This is a single-centre retrospective cohort study. We included 35 patients with IMSCT at levels of craniocervical junction to C4 who underwent surgical treatment between January 2008 and December 2022. The authors analysed the patients' preoperative status, tumour- and surgery-specific characteristics, and follow-up functional status. Results: The study cohort included 22 patients with grade II ependymoma (62.9%), 2 low-grade astrocytomas (5.7%), 2 glioblastomas (5.7%), 6 hemangioblastomas (17.1%), 2 metastases (5.7%), and 1 patient with partially intramedullary schwannoma (2.9%). Gross total resection was achieved in 76% of patients. Early dorsal column related symptoms and motor deterioration occurred in 64% and 44% of patients, respectively. At a follow-up of 3.27 ± 3.83 years, 43% and 33% of patients preserved postoperative sensory and motor deterioration, respectively. The median McCormick Scale grade was 2 in the preoperative and late postoperative periods, respectively (p=0.0897, α=0.05). Only two out of 35 patients (5.7%) developed new intermittent respiratory dysfunction, of whom two were transient. There were no surgery-related deaths. Conclusions: The surgery of IMSCT of the upper cervical spine could be performed without major procedure-related risk. Roughly a half of the patients develop new neurological deficit in the immediate postoperative period. However, most of the patients still maintain functional independence. The rate of respiratory insufficiency is low and is strongly influenced by the rapid neurological deterioration in high-grade tumours.

Trophoblast cell-surface antigen 2 (Trop 2) is a transmembrane glycoprotein that is highly expressed in various cancer types with relatively low or no baseline expression in most of normal tissues. Its overexpression is associated with tumor growth and poor prognosis; Trop 2 is therefore, an ideal therapeutic target for epithelial cancers. Several Trop 2 targeted therapeutics have recently been developed for the treatment of cancers, such as anti-Trop 2 antibodies and antibody-drug conjugates (ADCs), as well as Trop 2-specific cell therapy. In particular, the safety and clinical benefit of Trop 2-based ADCs have been demonstrated in clinical trials across multiple tumor types, including those with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and heavily pretreated non-small cell lung cancer. In this review, we elaborate on recent advances in Trop 2 targeted modalities and provide an overview of novel insights for future developments in this field.

Granular cell tumors (GCTs), known also as Abrikossoff tumors, are rare tumors that originates from Schwann cells that primarily localize in the tongue, skin, and submucosal tissues and involve the gastrointestinal tract in 11% of cases. We present a case of a young woman who first presented to our centre in 2018, for an EGDS to assess a thickening of the esophageal wall, seen on a CT. In that occasion, a diagnosis of Abrikossoff tumor was made. She underwent endoscopic resection with subsequent yearly follow-up without evidence of recurrence. 5 Years later, on a routine colonoscopy, we found numerous white submucosal formations in all of the explored tracts, with a histological examination compatible with GCT. Her daughter presented with a white nodule on her tongue, also diagnosed as GCT. Her daughter was also diagnosed with GCT of the tongue a few months later.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system and their interplay and therefore potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.

Glioblastoma (GBM) is the most common primary brain tumor. Due to high resistance to treatment, local invasion, and high risk of recurrence, GBM patient prognoses are often dismal, with median survival around 15 months. The current standard of care is threefold: surgery, radiation therapy and chemotherapy with temozolomide (TMZ). However, patient survival has only marginally improved. Radioimmunotherapy (RIT) is a fourth modality under clinical trials and aims at combining immunotherapeutic agents with radiotherapy. Here, we develop in vitro assays for rapid evaluation of RIT strategies. Using a standard cell irradiator and an Electric Cell Impedance Sensor, we quantify cell migration following the combination of radiotherapy and chemotherapy with TMZ and RIT with durvalumab, a PD-L1 immune checkpoint inhibitor. We measure cell survival using a cloud-based clonogenic assay. Irradiated T98G and U87 GBM cells migrate significantly (p < 0.05) more than untreated cells in the first 20-40 hours post-treatment. Addition of TMZ increased migration rates for T98G at the 20 Gy (p < 0.01). Neither TMZ nor durvalumab significantly changed cell survival in 21 days post-treatment. Interestingly, durvalumab abolished the enhanced migration effect, indicating possible potency against local invasion. These results provide parameters for rapid supplementary evaluation of RIT against brain tumors.

With the progress of immunotherapy in cancer, oncolytic viruses (OVs) are getting more and more attention during the past decade. Due to their cancer-selective and immunogenic property, OVs are considered ideal candidates to be combined with immunotherapy to increase both specificity and efficacy in cancer treatment. OVs preferentially replicate in and lyse cancer cells, generating pathogen-associated molecular patterns (PAMPs) and danger (damage)-associated molecular patterns (DAMPs). These signals trigger innate immune response to modulate the solid tumor microenvironment, resulting in in situ autovaccination leading to adaptive anti-virus and anti-tumor immunity. Here, we summarize the conceptual updates of oncolytic virotherapy, immunotherapy, and the strategies to enhance the virus-mediated anti-tumor immune response, including: 1. Arm OVs with cytokines to modulated innate and adaptive immunity; 2. Combine OVs with immune checkpoint inhibitors to release T cell inhibition; 3. Combine OVs with immune co-stimulators to enhance T cell activation.

The impact of a non-anticholinergic spasmolytic drug (drotaverine hydrochloride) on 23 heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) motility in the normal, resting 24 horses was determined. Ten adult riding horses had ECG recordings for 180 minutes after treat-25 ment with drotaverine (180 mg) or saline. Horses from the drotaverine group presented a de-26 creased of GIT contraction for two hours after treatment, but also showed drowsiness. Drotaverine 27 caused a reduction in cardiac vagal modulation of HR at T30 (P=0.050) and T60 (P=0.008) compared 28 to those receiving saline. RMSSD and high frequency (HF) recorded significantly low values after 29 drotaverine treatment by the end of the study, suggesting a decrease in parasympathetic activity. 30 HRV analysis indicated that drotaverine decreased both the low frequency (LF) and Lf/HF ratio 31 reflecting a decrease in sympathetic system. Non linear parameters registered low values after 32 drotaverine administration pointing a diminished in parasympathetic (for SD1) and sympathetic 33 (for SD2) activity. Decreased HRV was suggestive for a pervasive state of sympathetic hypervigi-34 lance of horses. The marked effect of drotaverine on HRV and GIT function in horses should be 35 taken into consideration when evaluating a clinical response to this drug in diseases associated 36 with smooth muscle spasm.

Background: The prevalence of obesity, defined as body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. Methods: This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) track both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Results: Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC|>0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in 6 patients (2 obese and 4 normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Conclusions: Overall, obesity is associated with differential transcriptional and metabolic program in various disease sites. Further, these alterations, like kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

The discovery of more bioactive compounds for non-invasive administration has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals, but it is challenging to determine which components show high biomedical activity. However, based on the chemical structure of these active compounds, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski's, Veber's, Ghose's, and Muegge's rules) to attain these predictions for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we provide a detailed methodology using web-based platforms to determine the physicochemical properties of five phytochemicals in the phytonutrients ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the combination and integration of these rules, plus other extended parameter ranges, to reliably predict the GI absorption of natural compounds. The presented data and methodology can be beneficial for evaluating bioactive natural compounds as potential drug candidates and predicting their oral bioavailability in patients.

Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro- and neurotoxicity, then for effects on the gastrointestinal tract and the associated lymphoid tissue. The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies. studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies.

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.

OBJECTIVE: Although 3D-printed anatomic models are not new to medicine, the high costs and lengthy production times entailed have limited their application. Our goal was developing a new and less costly 3D modeling method to depict organ-tumor relations at faster printing speeds. METHODS: We have devised a method of 3D modeling using DICOM images. Coordinates are extracted at a specified interval, connecting them to create mesh-work replicas. Adjacent constructs are depicted by density variations, showing anatomic targets (ie, tumors) in contrasting color. RESULTS: An array of organ solid-tumor models were printed via Fused Deposition Modeling 3D printer at significantly less cost ($0.05/cm3) and time expenditure (1.73 min/cm3; both, p<.001). Printed models helped promote visual appreciation of organ-tumor anatomy and adjacent tissues. Our mesh-work 3D thyroidal prototype reproduced glangular size/contour and tumor location, readily approximating the surgical specimen. CONCLUSIONS: This newly devised mesh-type 3D printing method may facilitate anatomic modeling for personalized care and improve patient awareness during informed surgical consent.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

A developed six-port reflectometry (SPR) system was integrated to measure the relative permittivity of tumor and normal breast tissue for medical diagnostic purpose. In order to obtain an accurate and precise measurement, the calibration process was done to the SPR using the well-known three-standard technique. Next, the studied dielectric probe was connected to the calibrated measurement-port of the SPR. The open end of the probe aperture was dibbed into the normal and tumor synthetic breast tissue samples to measure the synthetic breast tissues dielectric constant, ɛrʹ, and loss factor, ɛrʺ in the frequency range of 1.5 GHz to 3.3 GHz. Finally, the comparative studies were conducted between commercial VNA with Keysight 85070E dielectric probe and the studied SPR-probe system based on the measured magnitude of the reflection coefficient, phase shift, dielectric constant, and loss factor of the synthetic breast samples. The maximum absolute errors of the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor were found to be 0.01, 1.07°, 1.12, and 0.75, respectively. It was ascertained that the predicted dielectric constant, ɛrʹ, is able to differentiate between normal, (ɛrʹ &lt; 50) and tumor, (ɛrʹ &gt; 50) breast tissues.

The oncological outcomes are improving in gastrointestinal cancer with advancement in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT)to allow for further improvements in outcomes. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. Consolidative nivolumab in esophageal cancer after neoadjuvant chemoradiation (CRT) and complete resection has recently been approved as standard treatment after improved disease free survival in phase III study. Immunotherapy has shown promising results in hepatocellular carcinoma and colorectal cancer as well. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Different kinds of freshwater fish soups show a diverse range of health functions, due to their different nutritional substances and corresponding bioactivities. Crucian carp soup and snakehead soup have different dietotherapy functions, crucian carp soup is suitable for lactating women and snakehead soup is suitable for postoperative patients. In the current study, the changes of nutrient profiles in the different fish soups, such as chemical composition, free amino acids, mineral and fatty acid contents, were investigated. The antioxidant activities of the fish soups were evaluated by using the DPPH radical scavenging activity, the ferrous ion chelating activity, the hydroxyl radical-scavenging activity and the reducing power effect. In order to learn the theoretical basis of the potential role fish soup plays in diet therapy functions after being digested by the human body, the nutrient profiling and bioactivities of the fish soup samples after simulated gastrointestinal digestion were also explored. The intensive profiles of nutritional composition and antioxidant activities of these two kinds of fish soups were expected to partly provide the theoretical basis of therapeutic effects.

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic and phenotypic data. This methodology converts GEBVs into SNP effects. Analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2), and 1,700 50K SNP genotypes. Comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21 and 25, and for FEC2 on OAR 5, 6 and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs.

Background: Patients undergoing dual antiplatelet therapy (DAPT) may experience recurrent gastrointestinal bleeding (GIB). We investigated the clinical characteristics and risk factors for recurrent non-variceal upper gastrointestinal bleeding (NVUGIB) in patients who had experienced NVUGIB during receiving DAPT. Methods: We enrolled patients diagnosed with NVUGIB during receiving DAPT between 2006 and 2020. Definite bleeding was confirmed by esophagogastroduodenoscopy in all NVUGIB patients. Results: A total of 124 patients were diagnosed with NVUGIB during receiving DAPT. Male was predominant (n = 103, 83.1%), bleeding mostly from the stomach (n = 94, 75.8%) and peptic ulcers (n = 72, 58.1%). After successful hemostasis of NVUGIB, 36 patients (29.0%) experienced at least one episode of recurrent upper GIB, 19 patients (15.3%) died, and 7 (5.6%) patients had a bleeding-related death. Multivariate analysis showed that age was a significant factor for re-bleeding (odds ratio [OR],1.050; 95% confidence interval [CI]:1.001-1.102, P-value:0.047), all-cause mortality (OR,1.096; 95% CI:1.020-1.178, P=0.013), and re-bleeding related mortality (OR,1.187; 95% CI:1.032-1.364, P-value:0.016). In Kaplan-Meier analysis, the cumulative probabilities of re-bleeding, death, and bleeding-related death were significantly higher in patients aged 70 and older (P=0.008, &lt;0.001, and 0.009, respectively). Conclusion: Clinicians should be cautious about re-bleeding and mortality when elderly patients who experienced NVUGIB during receiving DAPT.Keywords: dual antiplatelet therapy; upper gastrointestinal tract; bleeding; mortality

SARS-CoV-2 infects a range of host species. However, the susceptibility of companion animals to SARS-CoV-2 and their potential ability to transmit the virus to humans remains unclear. Here, we present a detailed clinical description of an immunosuppressed dog that was infected with SARS-CoV-2. The dog had severe gastrointestinal (GI) clinical signs, coagulopathy, elevated hepatic transaminases, and met canine systemic inflammatory response syndrome criteria, without respiratory clinical signs, mirroring a subset of humans with GI-restricted COVID-19. Viral sequencing demonstrated divergence from other reported sequences, based on phylogenetic analysis. The dog shed high levels of virus for a prolonged time period with positive virus isolation. The dog’s immunosuppressed state may have increased both susceptibility to infection and disease progression. Together, our findings suggest that certain individual companion animals may be at higher risk for severe SARS-CoV-2 infection, COVID-19-like disease, and high viral shedding, which may pose a transmission risk to humans.

This study aimed to introduce a novel machine learning (ML) model designed to predict the need of interventions during endoscopy in patients with upper gastrointestinal bleeding (UGIB). The risk stratification tools in current use, such as the Glasgow Blatchford Score (GBS) and pre-endoscopic Rockall score, have limitations in accurately predicting the need for endoscopic interventions. All patients diagnosed with UGIB from January 2013 to October 2023 who underwent endoscopy were included in the study. Variables extracted included demographics, social history ,clinical history, clinical presentation and symptoms, drug history, management prior to endoscopy, findings during endoscopy, laboratory variables and vitals, and post-endoscopic results. Three machine learning models including Random Forest Classifier (RFC), Gradient Boosting Classifier (GBC), and AdaBoost Classifier were used to evaluate the need for intervention during endoscopy in our study. A total of 1372 patients were included from three major hospitals in Jordan, of whom 242 underwent endoscopic intervention. The GBC outperformed all other models and pre-endoscopic scores in predicting the need for endoscopic intervention with an area under the curve of 0.861. Findings during endoscopy, platelet count, pulse rate and systolic blood pressure during admission were the most contributing features in predicting the need for the need of endoscopic intervention. This study highlights the potential of machine learning models in enhancing decision making for UGIB management.

This research explores a novel encapsulating agent for establishing a synbiotic relationship with Bacillus (B.) coagulans by combining different ratios of wall materials, including skim milk powder (S), maltodextrin (M), and cellulose acetate phthalate (C). The ratio options are represented as SMC1 (1:2:1), SMC3 (3:2:1), SMC5 (5:2:1), and SMC7 (7:2:1). These wall materials are incorporated with 5% inulin (a prebiotic). The results show that these agents effectively protect B. coagulans spores during spray-drying, resulting in spore vitality exceeding 6 log cfu/g; SMC5 and SMC7 yielded the highest spore viability values. Furthermore, SMC5 demonstrated the highest levels of antioxidant activity, encompassing the scavenging of DPPH, hydroxy radicals, and superoxide radicals. Additionally, it displayed notable antidiabetic effects, including inhibitions of α-amylase and α-glucosidase. In comparison, SMC7 exhibited the most potent antidiabetic activity by inhibiting DPP-IV. Subsequently, after simulated gastrointestinal digestion, SMC5 and SMC7 showed a slight decrease in spore viability during the 6-hour simulation. Therefore, the most suitable condition for synbiotic production was found to be SMC5, which can potentially protect B. coagulans spores and exhibit bioactive activities after microencapsulation and passage through gastrointestinal digestion. This innovative product can be utilized as an advanced food delivery system and as a functional ingredient in functional food products.

Modulating the gut microbiota with probiotics has been identified as a promising therapeutic method for the management of gastrointestinal illnesses. The effectiveness of probiotics in the treatment of gastrointestinal disorders can only be determined by delving into their underlying mechanisms of action. Through an analysis of the underlying processes, this study hopes to provide light on the potential benefits of probiotics for treating a variety of gastrointestinal conditions. The study covers a wide variety of gastrointestinal conditions, such as IBS, IBD, and antibiotic-associated diarrhea. Modifying the gut microbiota composition, strengthening the gut barrier function, modulating the immune system, and producing beneficial metabolites are among mechanisms of action that have been investigated. The strain- and dose-specific variables essential to getting the best treatment results are also highlighted. This review, which synthesizes the current information, gives a thorough overview of the effectiveness of probiotics in treating a variety of gastrointestinal illnesses and illuminates potential avenues for further study and therapeutic use.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

Cancer remains as a worldwide cause of death. Investigational research efforts have included the administration of tumors-derived extracts to healthy animals. Having previously demonstrated that administration of non-transmissible, human cancers-derived homogenates induced malignant tumors in mice; we examined here the consequences of administering 50 or 100 µg of protein of crude homogenates from samples of mammary carcinoma, pancreatic adenocarcinoma, and melanoma. The protocol conceived six inoculations per week during three months. Concurrent control group received homogenates of healthy donor skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke animals’ deterioration or mortality. Multiple foci of lung adenocarcinomas with broad expression of malignity histomarkers, coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers were detected in lymphoid nodes. Pancreas tumor and melanoma homogenates administrations severely deteriorated animals’ health. Pancreas tumor induced lung poorly-differentiated adenocarcinomas, as a remarkable pancreatic islets hyperplasia. Melanoma affected lungs with atypical adenomatous hyperplasia and solid pseudopapillary adenocarcinoma. Giant atypical hepatocytes with variegated nuclei were also observed. Kidney parenchyma exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. A noticeable nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in any mouse of the control groups. This study confirms and extends our hypothesis that tumor homogenates contain and may act as a vector for “malignancy drivers”, which ultimately implement a carcinogenesis process in otherwise healthy mice.

(1) Background: Bronchial artery embolization has been shown to be effective in the management of neoplastic hemoptysis. However, knowledge of pulmonary artery embolization is lacking. To evaluate safety and efficacy of pulmonary artery embolization in patients presenting with hemoptysis related to lung tumors. (2) Methods: This retrospective study reviewed all consecutive patients with cancer and at least one episode of hemoptysis that required pulmonary artery embolization from December 2008 to December 2020. The endpoints of the study were technical success, clinical success, recurrence of hemoptysis and complications. (3) Results: A total of 92 patients were treated with pulmonary artery embolization (63.1 years ± 9.9; 70 men). Most patients had stage III or IV advanced disease. Pulmonary artery embolization was technically successful in 82 (89%) patients and clinically successful in 77 (84%) patients. Recurrence occurred in 49% of patients. Infectious complications occurred in 15 patients (16%). The 30-days mortality rate was 31%. At 3 years, survival rate was 3.6%. Tumor size, tumor cavitation and necrosis and pulmonary artery pseudo-aneurysm were significantly associated with recurrence and higher mortality. (4) Conclusions: Pulmonary artery embolization is an effective treatment to initially control hemoptysis in patient with lung carcinoma but recurrence rate remains high and overall survival remains poor.

Clinical management in neuro-oncology has changed to an integrative approach that incorporates molecular profile alongside histopathology and imaging findings. While the WHO guideline recommends genotyping of informative alterations as a routine clinical practice for central nervous system (CNS) tumors, acquisition of tumor tissue in the CNS is invasive and not always possible. Liquid biopsy is a non-invasive approach that provides the opportunity to capture the complex molecular heterogeneity of the whole tumor through detection of circulating tumor biomarkers in body fluids, such as blood or cerebrospinal fluid. Despite all the advantages, the low abundance of tumor-derived biomarkers, particularly in CNS tumors, as well as their short half-life has limited the application of liquid biopsy in clinical practice. Thus, it is crucial to identify factors that are associated with the presence of these biomarkers and explore possible strategies that can increase the shedding of these tumoral components into biological fluids. In this review, we first describe the clinical applications of liquid biopsy in CNS tumors including its roles in early detection of recurrence and monitoring of treatment response. We then discuss the utilization of imaging in identifying factors that affect the detection of circulating biomarkers as well as how image-guided interventions such as focused ultrasound can help enhance the presence of tumor biomarkers through blood-brain barrier disruption.

The ubiquitin proteasome system (UPS) utilizes an orchestrated enzymatic cascade of E1, E2, and E3 ligases to add single or multiple ubiquitin-like molecules as post-translational modification (PTM) to proteins. Ubiquitination can alter protein functions and/ or marks ubiquitinated proteins for proteasomal degradation but deubiquitinases (DUBs) can reverse protein ubiquitination. While the importance of DUBs as regulatory factors in the UPS is undisputed, many questions remain on DUB selectivity for protein targeting, their mechanism of action, and the impact of DUBs on the regulation of diverse biological processes. Furthermore, little is known about the expression and role of DUBs in tumors of the human central nervous system (CNS). In this comprehensive review, we have used publicly available transcriptional datasets to determine the gene expression profiles of 99 deubiquitinases (DUBs) from five major DUB families in seven primary pediatric and adult CNS tumor entities. Our analysis identified selected DUBs as potential new functional players and biomarkers with prognostic value in specific subtypes of primary CNS tumors. Collectively, our analysis highlights an emerging role for DUBs in regulating CNS tumor cell biology and offers a rationale for future therapeutic targeting of DUBs in CNS tumors.

Hypoxia, associated with abnormal vessel growth, is a characteristic feature of many solid tumors that increases their metastatic potential and resistance to radiotherapy. Carbon ion radiation therapy, alone or in combination with other treatments, is one of the most promising treatments for hypoxic tumors because the oxygen enhancement ratio decreases with increasing particle LET. Nevertheless, the current clinical practice does not yet fully benefit from using carbon ions for tackling hypoxia. Here we give an overview of the existing experimental and clinical evidence supporting the efficacy of C-ion radiotherapy in overcoming hypoxia-induced radioresistance, followed by a discussion of the strategies proposed to enhance it, including different approaches to maximize the LET in the tumors.

“Gray zone” category tumors in thyroid follicular tumors are difficult to diagnose, especially to distinguish between follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC). This study aimed to assess the diagnostic performance of metabolite enzymes using imaging mass spectrometry to distinguish FTA from FTC and determine the association between metabolite enzyme expression with thyroid follicular borderline tumor diagnosis. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFAIDESI-MSI) was used to develop a classification model for the characteristics of thyroid follicular tumors among 24 samples. We analyzed the expression of metabolic enzyme markers in an independent validation set of 133 cases and evaluated the potential biological behavior of 19 borderline thyroid lesions. Phospholipids and fatty acids (FAs) were more abundant in FTA than in FTC (P<0.001). The metabolic enzyme panel—including FA synthase and Ca²⁺-independent PLA2, which are closely associated with altered metabolic pathways—was further identified in follicular thyroid tumors. The marker combination showed optimal performance in the validation group (area under the receiver operating characteristic curve, sensitivity, and specificity: 73.6%, 82.1%, 60.6%, respectively). The diagnostic strategy suggested considering a putative role of AFAIDESI-MSI in routine clinical triage for strict follow-up, with low metabolic enzyme expression combined with diagnostic in patients with a thyroid follicular borderline tumor diagnosis.

Tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes, B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and childhood. Here we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination each other or administered with standard therapies.

Human visual system (HVM) can quickly localize the most salient object in scenes, which has been widely applied on natural image segmentation [15]-[19]. In ultrasound (US) breast images, compared with background areas, tumor is more salient because of its higher contrast. In this paper, we develop a novel automatic localization method based on HVM for automatic segmentation of ultrasound (US) breast tumors. First, the input image is smoothed by convolution with a linearly separable Gaussian filter and then subsampled into a 9-layer Gaussian pyramid. Then intensity, blackness ratio, and superpixel contrast features are combined to compute saliency map, in which Winner Take All algorithm is used to localize the most salient region, presenting with a circle on the localized target. Finally the circle is taken as the initial contour of CV level set to finish the extraction of breast tumor. The localization method has been tested on 400 US beast images, among which 378 images have higher saliency than background areas and succeed in localization, with high accuracy 92.00%. The HVM localization method can be used to localize the tumors, combined with this method, CV level set can achieve the fully automatic segmentation of US breast tumors. By combing intensity, blackness ratio and superpixel contrast features, the proposed localization method can successfully avoid the interference caused by background areas with low echo and high intensity. Moreover, multi-object localization of US breast images can be considered in future employment.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like te-mozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glio-blastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. 3D glioblastoma organoids (GB-EXPs) obtained from 18 patients’ resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NR). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n=9) and 77% (n=20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp be-ing REGO-NR. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO com-pared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal ex-ploration of the molecular changes induced by treatment, unveiling promising biomarkers in-dicative of drug response.

Pediatric brain tumors are the leading cause of cancer-related death in children. Diagnosis cur-rently relies on surgical biopsy to obtain tumor tissue for histological analysis. There is a great need for less invasive approaches to molecularly profile tumors and monitor therapeutic response. Liquid biopsy analysis of circulating tumor biomarkers in biofluids like cerebrospinal fluid (CSF) and blood offers a promising minimally invasive strategy. This review discusses recent advances in developing liquid biopsy assays using next-generation sequencing, digital PCR, and emerging techniques to detect circulating tumor DNA (ctDNA), cells (CTCs), and exosomes in pediatric brain tumors. The ability to use these circulating biomarkers for non-invasive diagnosis, thera-peutic targeting, tracking response to therapy, and understanding resistance mechanisms is ex-amined. Technical and clinical validation challenges to translate liquid biopsies into routine clin-ical practice are also discussed.

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasm present in gastrointestinal tract (GI) (67.5%), bronchopulmonary tree (25.3-30%), and in 15% of cases, the primary sites cannot be identified. Although endoscopic screening, improvement in pathological techniques, and early detection have shown improvement in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of Gastrointestinal and pancreatic (GEPs) NETs grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011 -May 2021 following PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. Meta-analysis was performed, and pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. The forest plots were created using random-effects models and sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis grade 3 GEP NET were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with 92% heterogeneity between studies (p < 0.0001). To account for heterogeneity, sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after sensitivity analysis did not change and still showed significant association of grade 3 with poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%). Conclusion: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve mortality.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells were grown subcutaneously in mice up to ~0.5 cm3. Mice were anesthetized with isoflurane and IV infused in the MR magnet for ~20 sec with ~0.2 ml solutions containing either [2H9]choline (0.05g/kg) alone or together with [6,6’ 2H2]glucose (1.3g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 900 excitation pulse and 400ms repetition time. 3D DMI was recorded at high resolution (2x2x2mm) in 37 min or at low resolution (3.7x3.7x3.7mm) in 2:24 min. Absolute tissue concentrations were calculate assuming initial [HOD]=13.7mM. Within 5 minutes after [2H9]choline infusion its signal appeared in tumor spectra representing concentration increasing up to 0.3–1.2 mM and then slowly decreased or remained constant over 100 minutes. In plasma [2H9]choline disappeared within 15 minutes post-infusion implying that its tumor signal arises from tissue and not blood. After infusing a mixture of [2H9]choline and [6,6’ 2H2]glucose their signals were observed separately in tumor 2H spectra. Over time the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6’ 2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of all 2H compounds were reconstructed from high resolution DMIs. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

Vitamin D3 deficiency is a global phenomenon, which can be coped with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors, such as matrix composition and interactions throughout the gastrointestinal tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, and the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the vitamin D3 initial content in supplements and foods, as well as after each digestion stage. Results indicated that foods exhibited higher bioaccessibility indices compared to supplements, and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e. gastric pH=1) enhances vitamin’s bioaccessibility.

Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at a histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach in addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th) was published. The importance of understanding the molecular genetics of thyroid tumors as revealed by large-scale genomic analyses such as The Cancer Genome Atlas (TCGA). Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on tumor cell-of-origin and clinical risk. This paper outlines following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDN) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The Framework for benign lesions have revised. The WHO 5th introduces new categories such as "developmental abnormalities" and "thyroid follicular nodular disease" in benign FDN. 3. Low-Risk Tumors include NIFTP, TT-UMP, and HTT. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to shared genetic and prognostic features. 7. Hürthle cell adenoma/carcinoma is renamed oncocytic thyroid adenoma/carcinoma. 8. Other miscellaneous tumors are classified into salivary gland-type carcinomas of the thyroid, thyroid tumours of uncertain histogenesis, thymic tumours within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on genetic abnormalities together with histomorphology, aiding in accurate pathological diagnosis and treatment selection, including molecular-targeted therapies.

Right heart masses are usually suspected during a routine examination by transthoracic echocardiography or due to cardiac symptoms. Although very important, sometimes it may be a challenge to differentiate between normal structures (variants) and aberrant or pathologic masses regarding the right heart cardiac tumors. In the last entity, the majority of primary cardiac tumors in adults and children are benign; however, they may have a malignant counterpart. Right heart tumors might involve not only the walls (myocardium, endocardium and pericardium), but also valves and cardiac chambers. Cardiac tumors exhibit altered signal intensity and enhancement characteristics, requiring the use of several imaging methods following a multimodality-imaging algorithm that culminates in the excision or biopsy of the tumor formation. Therefore, various imaging modalities, including echocardiography, computer tomography, positron emission tomography, cardiac magnetic resonance imaging, scintigraphy or, even, invasive angiography, can be useful during their diagnosis. Echocardiography is the first-line non-invasive imaging modality used in the evaluation of the right heart tumors. Before the other diagnosis imaging modalities it is essential for defining morphology, assessing size, observing dynamic appearance, and evaluating functional abnormalities and hemodynamic consequences,. However, all imaging methods have frequently a complementary role; therefore, an integrated imaging approach is recommended.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, spectral CT has emerged in the field of computed tomographies, utilizing detailed information from extracted spectral parameters of the specimen. Metal nanoparticle platforms enable effective payload delivery for this technique. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 functionalized gold nanoparticles (AuNPs) for tumor specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities, but not on corresponding normal tissue cells, predestining this target epitope for tumor-selective in vivo targeting. In vitro microscopical analysis revealed the presence of cmHsp70.1-AuNP in the cytosol of tumor cell lines, being internalized via the endosomal-lysosomal pathway. In tumor bearing mice the biodistribution as well as the intratumorally enrichment of AuNP were examined 24h after i.v. application, in vivo. In parallel to spectral CT analysis, histological analysis confirmed the presence of tumor cells. In contrast to control NP, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively in tumors of different preclinical mouse models. Furthermore, the biodistribution of AuNP, following i.v. injection, was analyzed by a machine-learning approach on digitalized slides. In summary, utilizing mHsp70 on tumor cells for guidance of cmHsp70.1 antibody functionalized nanoparticles enables sufficient enrichment and uniform distribution of AuNPs in mHsp70-expressing tumor cells, adequate for various microscopical imaging techniques and spectral-CT-based tumor delineation, in vivo.

Background and objectives: Primary brain tumors include any tumors arising in the brain whose prognosis is poor due to their histologic characteristics. The aim of this research was to evaluate the frequency of HER2 tumor marker in primary malignant brain tumors. Materials and Methods: This descriptive study was conducted on the samples admitted to the pathology laboratory with diagnosis of primary brain tumor during 2008–2015. Results: From among 107 patients (61.7% males and the rest females) with mean age of 40.4 years, the highest frequency of tumor location was in supratentorial region of the brain (including lobes and ventricles) (63.85% cases). High-grade astrocytoma had the highest prevalence at diagnosis (43.9%), followed by low-grade astrocytoma (37.4%). As for HER2 score, 42.1% of patients were HER2-positive (scores 2 & 3). On the other hand, 5.6% of patients were HER2-negative (-), 40.2% were positive (+), and 54.2% were positive (++). The patients with high-grade astrocytoma had older age (P < 0.001), higher HER2 positivity (P = 0.024) and percentage (P < 0.001) compared to the patients with low-grade astrocytoma. Conclusions: HER2 expression is dependent on the type of brain tumors. High expression of HER2 in high-grade astrocytoma may be useful for therapeutic purposes. The future research is needed to confirm these results with a large number of patients in different areas.

This research evaluated the role and feasibility of the granular nanocellulose particles (GNC) from sugarcane bagasse obtained from enzymatic hydrolysis in reducing lipid digestibility and permeability in the in vitro simulated gastrointestinal (GI) system. GNC concentration (0.02%, w/v) had significantly affected the released free fatty acid (FFA) reduction of approximately 20%. The Pick-ring emulsion of the GNC and olive oil simulation mixture revealed higher oil droplet size distribution and stability in the initial stage than the vortexed mixture formation. The difference in particle size distribution and zeta potential of the ingested GNC suspension and GNC-olive oil emulsion were displayed during the in vitro gastrointestinal simulation. GNC particles interacted and distributed surrounding the oil droplet leading to the interfacial emulsion. The GNC concentration (0.01-0.10%, w/v) showed low toxicity on the HIEC-6 cell, ranging from 80.0 to 99% of cell viability. The release of FFA containing the ingested GNC suspension and GNC-olive oil emulsion was about 30% reduction compared to without GNC digest solution. The FFA and triglyceride permeability through the HIEC-6 intestinal epithelium monolayer were deceased in the digesta containing the ingested GNC and emulsion. This work indicated that GNC represented a significantly critical role and properties in the GI tract and reduced lipid digestion and absorption. This GNC could be utilized as an alternative food additive or supplement in fatty food for weight control due to their inhibiting lipid digestibility and assimilation.

A prospective, observational, multicenter, and exploratory study was conducted in 469 gastrointestinal cancer patients undergoing elective surgery. The Malnutrition Universal Screening Tool (MUST) and the Global Leadership Initiative on Malnutrition (GLIM) criteria were used to assess nutritional risk. On admission, 17.9% and 21.1% of patients were at moderate (MUST score 1) and severe (MUST score ≥ 2) nutritional risk, respectively. GLIM criteria used in patients with MUST score ≥ 2 showed moderate malnutrition in 35.3% of patients and severe in 64.6%. Forty-seven percent of patients with MUST score ≥ 2 on admission had the same score at discharge, and 20.7% with MUST score 0 had moderate/severe risk at discharge. Small bowel, esophageal and gastric cancer, and diabetes were predictors of malnutrition on admission. Complications were significantly higher among patients with MUST score 1 or ≥ 2 either on admission (p = 0.001) or at discharge (p &lt; 0.0001). In patients who received nutritional therapy (n = 231), 43% continued to have moderate/severe nutritional risk on discharge, and 54% of those with MUST ≥ 2 on admission maintained this score at discharge. In gastrointestinal cancer patients undergoing elective surgery, there is an urgent need for improving nutritional risk screening before and after surgery, as well as improving nutritional therapy during hospitalization