Search Results (27,839)

(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody–drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients. Full article

Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, ‘self-resistance’ to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor’s genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment. Full article

There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment. Full article

Background: Awake craniotomy (AC) is recommended for the resection of tumors in eloquent areas. It is traditionally performed under monitored anesthesia care (MAC), which relies on hypnotics and opioids. Hypnosis-assisted AC (HAAC) is an emerging technique that aims to provide psychological support while reducing the need for pharmacological sedation and analgesia. We aimed to compare the characteristics and outcomes of patients who underwent AC under HAAC or MAC. Methods: We retrospectively analyzed the clinical, anesthetic, surgical, and neuropsychological data of patients who underwent awake surgical resection of eloquent brain tumors under HAAC or MAC. We used Mann–Whitney U tests, Wilcoxon signed-rank tests, and repeated-measures analyses of variance to identify statistically significant differences at the 0.05 level. Results: A total of 22 patients were analyzed, 14 in the HAAC group and 8 in the MAC group. Demographic, radiological, and surgical characteristics as well as postoperative outcomes were similar. Patients in the HAAC group received less remifentanil (p = 0.047) and propofol (p = 0.002), but more dexmedetomidine (p = 0.025). None of them received ketamine as a rescue analgesic. Although patients in the HAAC group experienced higher levels of perioperative pain (p < 0.05), they reported decreasing stress levels (p = 0.04) and greater levels of satisfaction (p = 0.02). Conclusion: HAAC is a safe alternative to MAC as it reduces perioperative stress and increases overall satisfaction. Further research is necessary to assess whether hypnosis is clinically beneficial. Full article

There is limited information on whether the COVID-19 pandemic was associated with decreased breast cancer screening uptake and if COVID-19 vaccination was associated with an increase in screening uptake. Our study explored the uptake of breast cancer screening in Japan after the COVID-19 pandemic and assessed its association with the COVID-19 vaccination. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based prospective cohort survey, and we included 6100 women without cancer history who were aged 40 to 74 years that participated in the 2012 and 2022 surveys. We examined the regular breast cancer screening uptake before and after the pandemic and employed a multivariable Poisson regression model to seek any association between COVID-19 vaccination and screening uptake. Of 6110, 38.2% regularly participated in screening before the pandemic and 46.9% did so after the pandemic. Individuals unvaccinated due to health reasons (incidence rate ratio (IRR) = 0.47, 95% CI: 0.29–0.77, p = 0.003) and for other reasons (IRR = 0.73, 95% CI: 0.62–0.86, p < 0.001) were less likely to undergo screening compared to fully vaccinated individuals. There was no long-term decrease in breast cancer screening uptake after the pandemic in Japan. Vaccination was linked to increased uptake, but there was no dose relationship. Full article

Introduction: Spinal intradural tumors account for 15% of all CNS tumors. Typical tumor entities include ependymomas, astrocytomas, meningiomas, and neurinomas. In cases of multiple affected segments, extensive approaches may be necessary to achieve the gold standard of complete tumor resection. Methods: We performed a bicentric, retrospective cohort study of all patients equal to or older than 14 years who underwent multi-segment surgical treatment for spinal intradural tumors between 2007 and 2023 with approaches longer than four segments without instrumentation. We assessed the surgical technique and the clinical outcome regarding signs of symptomatic spinal instability. Children were excluded from our cohort. Results: In total, we analyzed 33 patients with a median age of 44 years and interquartile range IQR of 30–56 years, including the following tumors: 21 ependymomas, one subependymoma–ependymoma mixed tumor, two meningiomas, two astrocytomas, and seven patients with other entities. The median length of the approach was five spinal segments with a range of 4–14 and with the foremost localization in the cervical or thoracic spine. Laminoplasty was the most chosen approach (72.2%). The median time to follow-up was 13 months IQR (4–56 months). Comparing pre- and post-surgery outcomes, 72.2% of the patients (n = 24) reported pain improvement after surgery. The median modified McCormick scores pre- and post surgery were equal to II IQR (I–II) and II IQR (I–III), respectively. Discussion: We achieved satisfying results with long-segment approaches. In general, patients reported pain improvement after surgery and received similar low modified McCormick scores pre- and post surgery and did not undergo secondary dorsal fixation. Thus, we conclude that intradural tumor resection via extensive approaches does not seem to impair long-term spinal stability in our cohort. Full article

Among women, ovarian cancer ranks as the fifth most common cause of cancer-related deaths. This study examined the impact of Hippo signaling pathway on ovarian carcinogenesis. Therefore, the signatures related to Hippo signaling pathway were derived from the molecular signatures database (MSigDB) and were used for further analysis. The Z score-based pathway activation scoring method was employed to investigate the expression patterns of these signatures in the mRNA expression profiles of ovarian cancer cohorts. Compared to other subtype tumors, the results of this study show that the Hippo signaling pathway signatures are dysregulated prominently in serous subtype-specific ovarian carcinogenesis. A receiver operating characteristic (ROC) curve-based results of the Hippo gene set, yes-associated protein 1 (YAP1), and mammalian sterile 20-like kinases 1 (MST1) genes can predict the serous subtype tumors by higher specificity and sensitivity with significant areas under the curve values also further reconfirmed these signaling dysregulations. Moreover, these gene sets were studied further for mutation analysis in the profile of high-grade serous ovarian adenocarcinoma in the cBioPortal database. The OncoPrint results reveal that these Hippo signaling pathway genes are amplified highly during the grade three and stage third or fourth of serous type ovarian tumors. In addition, the results of the Dependency Map (DepMap) plot also clearly show that these genes are amplified significantly across the ovarian cancer cell lines. Finally, overall survival (OS) curve plot investigations also revealed that these gene expressions show poor survival patterns linked to highly expressed conditions in serous subtypes of ovarian cancer patients with significant p-values (p < 0.05). Thus, the current finding would help to develop the targeted therapies treatment for serous subtype ovarian carcinogenesis. Full article

In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody–drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed. Full article

Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting the synthesis of sphingosine 1-phosphate (S1P) by sphingosine kinase-2 and elevating dihydroceramides by inhibition of dihydroceramide desaturase. The present studies sought to determine the potential therapeutic activity of opaganib in cell culture and xenograft models of NB. Cytotoxicity assays demonstrated that NB cells, including cells with amplified MYCN, are effectively killed by opaganib concentrations well below those that accumulate in tumors in vivo. Opaganib was shown to cause dose-dependent decreases in S1P and hexosylceramide levels in Neuro-2a cells, while concurrently elevating levels of dihydroceramides. As with other tumor cells, opaganib reduced c-Myc and Mcl-1 protein levels in Neuro-2a cells, and also reduced the expression of the N-Myc protein. The in vivo growth of xenografts of human SK-N-(BE)2 cells with amplified MYCN was suppressed by oral administration of opaganib at doses that are well tolerated in mice. Combining opaganib with temozolomide plus irinotecan, considered the backbone for therapy of relapsed or refractory NB, resulted in increased antitumor activity in vivo compared with temozolomide plus irinotecan or opaganib alone. Mice did not lose additional weight when opaganib was combined with temozolomide plus irinotecan, indicating that the combination is well tolerated. Opaganib has additive antitumor activity toward Neuro-2a tumors when combined with the checkpoint inhibitor anti-CTLA-4 antibody; however, the combination of opaganib with anti-PD-1 or anti-PD-L1 antibodies did not provide increased antitumor activity over that seen with opaganib alone. Overall, the data demonstrate that opaganib modulates sphingolipid metabolism and intracellular signaling in NB cells and inhibits NB tumor growth alone and in combination with other anticancer drugs. Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody. Full article

Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[¹⁸F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[¹⁸F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUV_max was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUV_max = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence. Full article

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. ⁶⁸Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, ⁶⁸Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of ⁶⁸Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. ⁶⁸Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4–5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, ⁶⁸Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4–5 lesions, ⁶⁸Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of ⁶⁸Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and ⁶⁸Ga-PSMA-11 PET/CT. Full article

Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors. Full article

With the rapid increase in computer processing capacity over the past two decades, machine learning techniques have been applied in many sectors of daily life. Machine learning in therapeutic settings is also gaining popularity. We analysed current studies on machine learning in robotic urologic surgery. We searched PubMed/Medline and Google Scholar up to December 2023. Search terms included “urologic surgery”, “artificial intelligence”, “machine learning”, “neural network”, “automation”, and “robotic surgery”. Automatic preoperative imaging, intraoperative anatomy matching, and bleeding prediction has been a major focus. Early artificial intelligence (AI) therapeutic outcomes are promising. Robot-assisted surgery provides precise telemetry data and a cutting-edge viewing console to analyse and improve AI integration in surgery. Machine learning enhances surgical skill feedback, procedure effectiveness, surgical guidance, and postoperative prediction. Tension-sensors on robotic arms and augmented reality can improve surgery. This provides real-time organ motion monitoring, improving precision and accuracy. As datasets develop and electronic health records are used more and more, these technologies will become more effective and useful. AI in robotic surgery is intended to improve surgical training and experience. Both seek precision to improve surgical care. AI in ‘’master–slave’’ robotic surgery offers the detailed, step-by-step examination of autonomous robotic treatments. Full article

Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway. Full article

Immune checkpoint blockade (ICB) therapy is used to treat a wide range of cancers; however, some patients are at risk of developing treatment resistance and/or immune-related adverse events (irAEs). Thus, there is a great need for the identification of reliable predictive biomarkers for response and toxicity. The cytokine MIF (macrophage migration inhibitory factor) and its cognate receptor CD74 are intimately connected with cancer progression and have previously been proposed as prognostic biomarkers for patient outcome in various cancers, including solid tumors such as malignant melanoma. Here, we assess their potential as predictive biomarkers for response to ICB therapy and irAE development. We provide a brief overview of their function and roles in the context of cancer and autoimmune disease. We also review the evidence showing that MIF and CD74 may be of use as predictive biomarkers of patient response to ICB therapy and irAE development. We also highlight that careful consideration is required when assessing the potential of serum MIF levels as a biomarker due to its reported circadian expression in human plasma. Finally, we suggest future directions for the establishment of MIF and CD74 as predictive biomarkers for ICB therapy and irAE development to guide further research in this field. Full article