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Background: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB‐positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. Methods: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG‐ALL‐2015 and CCCG‐ALL‐2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Results: Pediatric PDGFRB‐positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B‐ALL and 4 T‐ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31‐33 abnormalities, and one suffered from a complex karyotype. The 3‐year event‐free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow‐up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine‐kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p <.05). Conclusions: Pediatric PDGFRB‐positive ALL has a poor outcome associated with high‐risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Plain Language Summary: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high‐risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse.Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive acute lymphoblastic leukemia (ALL) patients.The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. Pediatric acute lymphoblastic leukemia (ALL) patients with PDGFRB fusions are associated with high‐risk clinical features. Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive ALL patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone‐sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow‐up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan–Meier methods estimated overall survival (OS) and castration‐resistant prostate cancer (CRPC)‐free survival from mHSPC diagnosis date and a log‐rank test compared these outcomes by oligometastatic status. Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non‐omHSPC had higher median prostate‐specific antigen at diagnosis (151.7) than omHSPC (44.1). First‐line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non‐omHSPC (14%). More omHSPC patients received metastasis‐directed therapy/prostate radiation therapy (14%) versus non‐omHSPC (2%). Median OS and CRPC‐free survival (in months) were higher in omHSPC versus non‐omHSPC (44.4; 95% confidence interval [CI], 33.9–not estimated vs. 26.2; 95% CI, 20.5–32.5, p =.0089 and 27.6; 95% CI, 22.1–37.2 vs. 15.3; 95% CI, 12.8–17.9, p =.0049), respectively. Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non‐omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non‐omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies. In this observational retrospective Veterans Affairs cohort study, 20% of men had de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC). Although first‐line (1L) novel hormonal therapy was similar between groups, 1L chemotherapy use was lower in omHSPC, more omHSPC patients received metastasis‐directed therapy/prostate radiation therapy, and median overall survival and time to castration resistance was longer in men with omHSPC than non‐omHSPC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Comprehensive analysis of novel treatment modalities for Glioblastoma (GBM). • Role of nanocarriers in addressing limitations with conventional GBM therapeutics. • Updates of clinical landscape of novel GBM therapeutics. • Limitations with novel nanoparticles approach in GBM therapeutics. Glioblastoma multiforme (GBM) represents one of the most prevailing and aggressive primary brain tumors among adults. Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood–brain barrier (BBB). Nanotechnology has emerged as a promising avenue for GBM treatment, offering biosafety, sustained drug release, enhanced solubility, and improved BBB penetrability. In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. The conventional and novel treatment modalities for GBM and the potential of nanocarriers to overcome existing limitations are comprehensively covered. Furthermore, the updates in the clinical landscape of GBM therapeutics are presented in addition to the current status of drugs and patents in the same context. Through a critical evaluation of existing literature, the therapeutic prospect and limitations of nanocarrier-based drug delivery strategies are highlighted offering insights into future research directions and clinical translation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lung cancer is one of the most common malignant tumors with the worst prognosis worldwide. Its incidence rate and mortality rate have long been among the top of malignant tumors. The heterogeneity and drug resistance are among the reasons contributing to its poor prognosis. Lung cancer organoid, which is a 3D in vitro model cultured from patient-derived tumor cells recapitulating the biological characteristics of the primary tumor, can be used for various researches of lung cancer. OBJECTIVE: To review the application and research progress of lung cancer organoids in chemotherapy, targeted therapy, and immunotherapy drug sensitivity screening, analyze its limitations, aiming to provide new strategies for personalized and precision medicine of lung cancer. METHODS: The first author searched relevant articles published from 2013 to 2023 in CNKI and PubMed in July 2023. The search terms were “organoid, lung cancer organoid, lung cancer experimental model, precision medicine, drug sensitivity test, chemotherapy, targeted therapy, immunotherapy” in Chinese and English. Finally, a total of 84 articles were incorporated. RESULTS AND CONCLUSION: (1) Compared with traditional lung cancer research models, which can only demonstrate two-dimensional cell activities, lack cell-to-cell interactions, and suffer from species differences, lung cancer organoids offer a diverse cell source and continuously optimized culture conditions. They can simulate cellular interactions in a three-dimensional context while retaining the biological characteristics of the original tumor. These organoids represent a promising research model with significant potential, providing a solid foundation for their use in cancer drug screening. (2) Lung cancer organoids have shown preliminary significance in guiding anticancer drug selection. Their predictive outcomes align closely with actual clinical outcomes, marking a pivotal step towards precision in lung cancer treatment. By assessing the efficacy of common chemotherapy, targeted therapy, and immunotherapy drugs, these organoids enable the customization of individualized treatment strategies, reducing unnecessary drug trials and toxic and side reaction while exploring possible alternative drugs or combination regimens for drug resistance issues so as to guide the precision treatment of rare mutated lung cancer and fill the clinical gap. A more comprehensive drug evaluation is provided by comparing the activity of different drugs. Additionally, it is essential to consider the internal heterogeneity of organoids, emphasizing the importance of multiple sampling to enhance result accuracy. (3) Lung cancer organoids have limitations in practical applications such as inconsistent success rates and purity in cultivation and the lack of vascular tissue. To address these shortcomings, improvements are needed in cultivation conditions, expedited testing processes, and the development of multi-organ systems to simulate the overall effects of drugs in multiple organs. These enhancements will contribute to a more accurate assessment of drug efficacy and toxicity, thereby enhancing the precision of lung cancer treatment. [ABSTRACT FROM AUTHOR]

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p‐glycoprotein (P‐gp) mediated drug efflux is one of the primary causes, the development of P‐gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P‐gp exists in many tissues, the non‐selective P‐gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P‐gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P‐gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post‐modification, various benzofuran‐fused‐piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P‐gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA‐MB‐231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy. [ABSTRACT FROM AUTHOR]

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p‐glycoprotein (P‐gp) mediated drug efflux is one of the primary causes, the development of P‐gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P‐gp exists in many tissues, the non‐selective P‐gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P‐gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P‐gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post‐modification, various benzofuran‐fused‐piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P‐gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA‐MB‐231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy. [ABSTRACT FROM AUTHOR]

Background: Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited. Methods: ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur–gimeracil–oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints—centrally assessed progression-free survival (PFS) and overall survival (OS)—and landmark analyses of OS among patients alive using 3-year follow-up data. Results: At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55–0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75–1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy. Conclusion: This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer. Trial registration: NCT02746796 [ABSTRACT FROM AUTHOR]

Background: Olanzapine is prescribed as prophylaxis for chemotherapy-induced nausea and vomiting at a dose of 2.5 or 5 mg in Asian countries. We compared the effectiveness of olanzapine 2.5 mg and 5 mg in preventing chemotherapy-induced nausea and vomiting among patients receiving high-emetogenic chemotherapy for lung cancer. Methods: Using a Japanese national inpatient database, we identified patients who received olanzapine doses of 2.5 or 5 mg during high-emetogenic chemotherapy for lung cancer between January 2016 and March 2021. We conducted a 1:1 propensity score-matched analysis with adjustment for various factors, including those affecting olanzapine metabolism. The outcomes were additional antiemetic drug administration (within 2–5 days after chemotherapy initiation), length of hospital stay, and total hospitalization costs. Results: Olanzapine 2.5 and 5.0 mg were used in 2905 and 4287 patients, respectively. The propensity score-matched analysis showed that olanzapine 2.5 mg administration was significantly associated with a higher proportion of additional antiemetic drug administration (36% vs. 31%, p < 0.001) than olanzapine 5 mg. The median length of hospital stay was 8 days in both groups. Total hospitalization cost did not differ significantly between the two doses of olanzapine (5061 vs. 5160 USD, p = 0.07). The instrumental variable analysis demonstrated compatible results. Conclusion: Prophylactic use of olanzapine 2.5 mg during chemotherapy for lung cancer was associated with a higher rate of additional antiemetic drugs than olanzapine 5 mg. [ABSTRACT FROM AUTHOR]

Objective: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). Method: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. Results: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. Conclusion: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence. [ABSTRACT FROM AUTHOR]

Background: AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS. Setting: People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries. Methods: We estimated mortality rates over the trial period. Cox proportional hazards regressions were used to identify baseline characteristics associated with mortality and compared mortality rates between participants who had KS progression within 12 weeks of treatment initiation (early progression of KS [KS-PD]) and those who did not. Results: Of the 329 and 189 eligible participants in A5263/ AMC066 and A5264/AMC067, 71 (21.6%) and 24 (12.7%) died, respectively. In both trials, hypoalbuminemia was associated with increased hazards of death compared with normal albumin; A5263/ AMC066: mild hypoalbuminemia (adjusted hazard ratio [aHR] = 3.01; 95% CI: 1.42 to 6.29), moderate hypoalbuminemia (aHR = 5.11; 95% CI: 2.54 to 10.29), and severe hypoalbuminemia (aHR = 14.58; 95% CI: 6.32 to 35.60), and A5264/AMC067: mild hypoalbuminemia (aHR = 5.66; 95% CI: 1.90 to 16.93) and moderate hypoalbuminemia (aHR = 7.02; 95% CI: 2.57 to 19.15). The rate of death was higher among participants who had early KSPD than those without early KS-PD in A5263/AMC066 (HR = 5.09; 95% CI: 1.71 to 15.19) but not in A5264/AMC067 (HR = 1.74; 95% CI: 0.66 to 4.62). Conclusions: Albumin measurements may be used to identify individuals at higher risk of death after initiating KS treatment and for evaluation of interventions that can reduce AIDS-KS mortality. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with overt or occult hepatitis B virus (HBV) infection receiving immunosuppressive treatments have a wide risk of HBV reactivation (HBVr). We performed meta‐analysis with decision curve analyses (DCA) to estimate the risk of HBVr in HBsAg‐negative anti‐HBc‐positive patients naïve to nucleos(t)ide analogues (NAs) receiving immunosuppressive treatments. Approach and Results: Studies were identified through literature search until October 2022. Pooled estimates were obtained using random‐effects model. Subgroup analyses were performed according to underlying disease and immunosuppressive treatments. DCA was used to identify the threshold probability associated with the net benefit of antiviral prophylaxis in HBsAg‐negative anti‐HBc‐positive patients. We selected 68 studies (40 retrospective and 28 prospective), including 8034 patients with HBsAg negative anti‐HBc positive. HBVr was 4% (95% CI 3%–6%) in HBsAg‐negative anti‐HBc‐positive patients, with a significantly high heterogeneity (I2 69%; p <.01). The number‐needed‐to‐treat (NNT) by DCA ranged from 8 to 24 for chemotherapy plus rituximab, from 12 to 24 for targeted therapies in cancer patients and from 13 to 39 for immune‐mediated diseases. Net benefit was small for monoclonal antibodies. Conclusions: Our DCA in HBsAg‐negative anti‐HBc‐positive patients provided evidence that NA prophylaxis is strongly recommended in patients treated with chemotherapy combined with rituximab and could be appropriate in patients with cancer treated with targeted therapies and in patients with immune‐mediated diseases. Finally, in patients with cancer treated with monoclonal antibodies or with chemotherapy without rituximab, the net benefit is even lower. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) of the liver represent a rare entity. Amongst this group of uncommon diseases primary hepatic neuroendocrine neoplasm (PH‐NEN) represent only 0.3% of all NENs. Moreover, PH‐NEN has very rarely been reported in pregnancy. We report a 28‐year‐old young patient with metastatic small cell neuroendocrine carcinoma of the liver complicated with pregnancy. She was evaluated and managed through a multidisciplinary team approach and received two cycles of chemotherapy with a cisplatin/etoposide regimen during the antenatal period and delivered at 37 weeks period of gestation (POG). This case highlights the importance of major challenges faced during the diagnosis and management of this very rare disease in pregnancy and the successful fetomaternal outcome. Synopsis: Primary hepatic neuroendocrine neoplasms (PH‐NENs) constitute 0.3% of all NENs, and are rarely reported in pregnancy. A 28‐year‐old pregnant woman was managed successfully, emphasizing diagnostic and management challenges. [ABSTRACT FROM AUTHOR]

Thymic carcinoma (TC) is a rare form of highly invasive tumors. Currently, the standard first-line therapy involves paclitaxel plus carboplatin treatment, while the recommended regimen for second-line therapy remains uncertain. The purpose of this study is to explore the second-line mode of TC patients. We evaluated the outcome of subjects with advanced TC between 2009 and 2023 in three medical centers, retrospectively. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Kaplan-Meier was used for calculating Progression-free survival (PFS) and overall survival (OS). The factors affecting survival in the real world were evaluated by Cox analysis. Totally 136 patients were included in this study, the median PFS (mPFS) for all subjects was 5.97 months, and the median OS (mOS) was 25.03 months. According to patient's treatment modes, they are divided into monotherapy (n = 95) and combination therapy (n = 41), PFS manifested the difference between two groups (5.17 vs. 9.00 months, P = 0.043). OS also indicated a significant distinction (22.50 vs. 38.00 months, P = 0.017). Furthermore, there was a significant difference in PFS between patients using immunotherapy combined with chemotherapy and those with antivascular therapy (8.57 vs. 13.10 months, P = 0.047). In the second-line therapy for advanced TC, the efficacy of combination therapy was better than monotherapy, especially for immunotherapy combined with antivascular therapy. • One hundred and thirty-six patients were enrolled, including 95 patients with monotherapy and 41 with combination therapy. • The efficacy of combination therapy was better than that of monotherapy. • Immunotherapy combined with anti-angiogenesis therapy showed better efficacy in second-line TC patients. [ABSTRACT FROM AUTHOR]

introduction: This study aimed to study the potential effects of oxaliplatin-based chemotherapy on cardiorespiratory fitness, handgrip strength (HGS), body composition, and quality of life (QoL) of stages III–IV colorectal cancer (CRC) patients before the first cycle (T0) and after the last cycle of systemic adjuvant/neoadjuvant chemotherapy (T1). Methods: Cardiorespiratory fitness, HGS, body composition, and QoL were evaluated with the six-minute walk test (6MWT), hydraulic hand dynamometer, body composition analyzer, and Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire in both T0 and T1, respectively. Results: Twenty-eight CRC patients were included in this study. The total walked distance (TWD) was found to be decreased from T0 to T1 (499.72 m vs. 488.56 m); however, this change was not significant (z = -.706, p = 0.48). Type of chemotherapy whether adjuvant or neoadjuvant also showed no significant effect on TWD (z = -.1.372, p =.17 vs z = -1.180, p =.238, respectively). The QoL was significantly decreased (T0 = 118.35 vs T1 = 110.77, t = 2.176,p = 0.05). The TWD was significantly correlated with the physical well-being (PWB) subscale of FACT-C (r =.64, p = 0.001) as well as with HGS (r =.46, p =.018) in T0. After controlling for age, type of chemotherapy, and type of regimen, the HGS did not show a significant difference from T0 to T1 (F(1,23) = 1.557, p =.22, ηp2 =.06). However, the effect of time x gender showed significant difference from T0 to T1 (F(1,23) = 4.906, p =.037, ηp2 =.17). Conclusion: This study showed the decreased QoL and physical well-being of CRC patients who underwent oxaliplatin-based treatment. In addition, the gender effect of decreased HGS should be considered further when planning an oncological rehabilitation program. [ABSTRACT FROM AUTHOR]

Background: There is interest in using bladder-preserving therapy as an alternative definitive therapy for muscle invasive bladder cancer in certain high-risk groups such as the elderly. Objective: To determine if bladder-preserving therapy represents a safer alternative to surgical intervention in elderly patients with muscle invasive bladder cancer. Methods: We surveyed the Surveillance, Epidemiology and End Results database (SEER) for cases of non-metastasized malignant bladder cancer in patients aged 80+. Survival outcomes with radical cystectomy (RC) with or without chemotherapy were compared to those after chemotherapy and radiation without cystectomy. We performed log-rank tests and Kaplan-Meier and cox regression and hazard analyses before and after propensity score matching. Results: A total of 2995 patients were identified, with 49.98% treated with RC only, 8.65% treated with RC/chemotherapy, and 41.37% treated with chemotherapy and radiation without RC. Median overall survival for the RC only, RC/chemotherapy and chemotherapy/radiation groups were 31.4, 44.1, and 24.6 months, respectively. On multivariate analysis, hazard ratios (reference: RC/chemotherapy group) were RC Only (HR = 1.408 (95% CI 1.188–1.669), p < 0.0001) and chemotherapy/radiation (HR = 1.650 (95% CI 1.390–1.959), p < 0.0001). After matching the chemotherapy/radiation and RC/chemotherapy groups, the former continued to show survival hazard (HR = 1.744 (95% CI 1.414–2.155), p < 0.0001). Conclusions: Octogenarians should be offered definitive local therapy for their localized bladder cancer including RC and chemotherapy. Bladder-sparing alternatives should be reserved for patients unfit for surgery. [ABSTRACT FROM AUTHOR]

Objectives: Bladder-Sparing Approach was presented in patients who are not willing or not suitable for Radical Cystectomy (RC). There have been inconsistencies in the literature regarding the comparison of survival rates of these two methods. Our objective is to evaluate the survival rate of patients with muscle-invasive bladder cancer (MIBC) undergoing different treatment methods. Design: Retrospective cross-sectional study. Setting: A secondary care, multicenter study in Kerman, Iran 2008 to 2016. Participants: All 200 patients who were diagnosed with Muscle Invasive Bladder Cancer and were admitted to our hospitals. Patients with inaccessible medical files and patients with pathologies other than TCC were excluded. Main outcome measures: Radical cystectomy and different methods of bladder preservation were compared based on their survival rate. Interventions: Radical cystectomy or bladder preservation Results: Overall survival of the patients was 2 years [95% CI: 1.37–2.63]. The overall 5-year survival rate of patients with MIBC was 32%. Having a 6.4 years overall survival, the RC group showed the highest survival compared with others (p = 0.01); the overall survival of patients undergoing TMT, TURT, chemotherapy, or radiotherapy monotherapy was 3.15 years [95% CI: 2.242–4.061], 4.06 [95% CI: 3.207–4.931], 2.58 [95% CI: 1.767–3.399], and 3.14 [95% CI: 1.614–4.672] years, respectively. Patients younger than 65 undergoing RC had an overall survival of 7 years, compared with 2 years for the TMT group. (p = 0.0001). Conclusions: The Bladder-Preservation method, as a replacement for RC, showed a lower overall survival rate in our study. A prospective randomized clinical trial may declare the best treatment. [ABSTRACT FROM AUTHOR]

This study explores the critical role of inhibitors targeting the mammalian target of rapamycin (mTOR) signaling pathway in breast cancer research and treatment. The mTOR pathway, a central regulator of cellular processes, has been identified as a crucial factor in the development and progression of breast cancer. The essay explains the complex molecular mechanisms through which mTOR inhibitors, such as rapamycin and its analogs, exert their anticancer effects. These inhibitors can stop cell growth, proliferation, and survival in breast cancer cells by blocking critical signaling pathways within the mTOR pathway. Furthermore, the essay discusses the implications of using mTOR inhibitors as a comprehensive therapeutic strategy. It emphasizes the potential benefits of combining mTOR inhibitors with other treatment approaches to enhance the effectiveness of breast cancer treatment. The evolving landscape of breast cancer research underscores the significance of mTOR as a therapeutic target and highlights ongoing efforts to improve and optimize mTOR inhibitors for clinical use. In conclusion, the essay asserts that inhibitors of the mTOR signaling pathway offer a promising approach in the fight against breast cancer. These inhibitors provide a focused and effective intervention targeting specific dysregulations within the mTOR pathway. As research advances, the integration of mTOR inhibitors into customized combination therapies holds excellent potential for shaping a more effective and personalized approach to breast cancer treatment, ultimately leading to improved outcomes for individuals affected by this complex and diverse disease. [ABSTRACT FROM AUTHOR]

Cancer drug resistance poses a significant obstacle to successful chemotherapy, primarily driven by the activity of ATP‐binding cassette (ABC) transporters, which actively efflux chemotherapeutic agents from cancer cells, reducing their intracellular concentrations and therapeutic efficacy. Recent studies have highlighted the pivotal role of long noncoding RNAs (lncRNAs) in regulating this resistance, positioning them as crucial modulators of ABC transporter function. lncRNAs, once considered transcriptional noise, are now recognized for their complex regulatory capabilities at various cellular levels, including chromatin modification, transcription, and post‐transcriptional processing. This review synthesizes current research demonstrating how lncRNAs influence cancer drug resistance by modulating the expression and activity of ABC transporters. lncRNAs can act as molecular sponges, sequestering microRNAs that would otherwise downregulate ABC transporter genes. Additionally, they can alter the epigenetic landscape of these genes, affecting their transcriptional activity. Mechanistic insights reveal that lncRNAs contribute to the activity of ABC transporters, thereby altering the efflux of chemotherapeutic drugs and promoting drug resistance. Understanding these interactions provides a new perspective on the molecular basis of chemoresistance, emphasizing the regulatory network of lncRNAs and ABC transporters. This knowledge not only deepens our understanding of the biological mechanisms underlying drug resistance but also suggests novel therapeutic strategies. In conclusion, the intricate interplay between lncRNAs and ABC transporters is crucial for developing innovative solutions to combat cancer drug resistance, underscoring the importance of continued research in this field. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early life exposure to cisplatin induces TRPV1 and nociceptor sensitisation. • Cisplatin alters the developmental trajectory of nociceptors to be TrkA dependent. • Cisplatin induced survivorship pain is dependent upon TrkA signalling. Cisplatin-based chemotherapy is a common treatment for paediatric cancer. Unfortunately, cisplatin treatment causes neuropathic pain, a highly prevalent adverse health related complication in adult childhood cancer survivors. Due to minimal understanding of this condition, there are currently no condition tailored analgesics available. Here we investigated an alteration in nociceptor maturation that results in neuronal sensitisation and manifestation of cisplatin induced survivorship pain in a TrkA dependent manner. Cisplatin was administered (i.p. 0.1 mg/kg Postnatal day 14 and 16) to neonatal male and female Wistar rats and nociceptive behavioural assays were performed. In vitro studies utilised isolated neonatal dorsal root ganglia sensory neurons treated with cisplatin (5 μg/ml) to elucidate impact upon nociceptor activation and neurite growth, in combination with TrkA inhibition (GW441756 10 nM and 100 nM). Cisplatin treated male and female neonatal Wistar rats developed a delayed but lasting mechanical and heat hypersensitivity. Cisplatin administration led to increased TrkA expression in dorsal root ganglia sensory neurons. Nerve growth factor (NGF) induced TrkA activation led to sensory neuritogenesis and nociceptor sensitisation, which could be prevented through pharmacological TrkA inhibition (GW441756 either s.c. 100 nM or i.p. 2 mg/kg). Administration of TrkA antagonist suppressed cisplatin induced TRPV1 mediated nociceptor sensitisation and prevented cisplatin induced neuropathic pain. These studies provide greater understanding of the underlying mechanisms that cause cisplatin induced childhood cancer survivorship pain and allowing identification of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival. [ABSTRACT FROM AUTHOR]

Enfortumab vedotin (EV), a nectin‐4‐binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV‐induced cutaneous eruption. A 58‐year‐old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and "starburst" forms. The findings supported a diagnosis of EV‐induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV‐induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV‐induced eruption, which may inform dermatologic and oncologic management. [ABSTRACT FROM AUTHOR]

Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment. [ABSTRACT FROM AUTHOR]

Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). In vitro, Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are rarely used to treat advanced pancreatic ductal adenocarcinoma (PDAC) due to marginal efficacy. Patients and methods: This study included 92 consecutive patients diagnosed with advanced or recurrent PDAC who received nivolumab-based treatment. Univariate and multivariate analyses were used to identify prognostic factors. A control group of 301 patients with PDAC who achieved disease control with palliative chemotherapy but without ICIs was selected for comparison using propensity score matching (PSM). Results: The median overall survival (OS) since nivolumab treatment was 15.8 (95% confidence interval [CI], 12.5–19.0), 2.4 (95% CI 1.2–3.6), and 1.1 (95% CI 1.0–1.2) months in patients who received add-on nivolumab after achieving disease control with chemotherapy, in those who received concomitant nivolumab and chemotherapy without prerequisite confirmation of disease control, and in those who received nivolumab without concomitant chemotherapy, respectively (P < 0.001). After PSM, the median overall survival (OS) since initiation of the concomitant chemotherapy that achieved disease control was significantly longer (P = 0.026) in patients who received add-on nivolumab (19.8 months; 95% CI 14.5–25.1) than in those who received chemotherapy alone (13.8 months; 95% CI 10.8–16.9). The immune profiling of the tumors in resected patients revealed higher scores of CD8+ T cells to Tregs in patients with add-on nivolumab comparing to those who received chemotherapy alone. Conclusion: Adding-on nivolumab was associated with improved OS in patients with advanced PDAC who achieved disease control following chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract:ObjectivesMethodsResultsConclusionsPolyethylene glycol recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are used to prevent or treat chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). This study aimed to compare the efficacy and safety of same-day versus next-day PEG-rhG-CSF administration following chemotherapy and the effects of 3 mg versus 6 mg dosages.We retrospectively analyzed cohort data of patients with breast cancer who underwent chemotherapy and received PEG-rhG-CSF either within 24 h (same-day group) or 24 h (next-day group) after chemotherapy. The incidences of CIN and FN were assessed in each chemotherapy cycle between the two groups. The primary endpoint was the incidence of FN in the first cycle and throughout all cycles. The secondary endpoints included the incidences of various grades of CIN (CIN1–CIN4), antibiotic use, chemotherapy regimen modifications, and overall safety.Among the 2385 chemotherapy cycles with prophylactic PEG-rhG-CSF in 620 patients, 798 and 1587 cycleswere in the same-day and next-day group, respectively. No statistically significant differences were observed in the incidence of FN in the first cycle or across all cycles, CIN1-4, or adverse reactions between the two groups. However, the same-day group exhibited significantly higher rates of antibiotic use (2.88% vs. 0.42%, P = 0.03) and chemotherapy regimen modification (4.68% vs. 1.45%, P < 0.001). Subgroup analysis indicated no differences in outcomes for the 6 mg dosage, but a significantly lower incidence of CIN was observed in the same-day group receiving 3 mg (P = 0.025).These findings suggest that same-day administration of PEG-rhG-CSF is as effective and safe as next-day administration in preventing FN and CIN during chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: Chemotherapy during pregnancy has a certain risk of causing a series of complications, such as miscarriage, premature birth, or fetal growth restriction, although the relationship between these complications and chemotherapy is currently unclear. This experiment focuses on the possible damage mechanism of the chemotherapeutic drug paclitaxel on placental trophoblast cells, and explores whether chemotherapy can affect pregnancy outcomes by directly damaging placental tissue. Methods: This study explored the mechanism of paclitaxel induced damage on placental trophoblast cell lines JEG-3 and BEWO through immunofluorescence staining, Western blot experiments, cell flow cytometry, Seahorese cell metabolism experiments, and mouse modeling verification. Results: The experiment found that paclitaxel could induce JEG-3 and BEWO cells to produce reactive oxygen species (ROS), and elevate the ratio of Bax/Bcl-2 expression. Besides, paclitaxel mediated the reduction of mitochondrial membrane potential in JEG-3 and BEWO cells, causing damage and leading to mitochondrial autophagy and the occurrence of unfolded protein response. Paclitaxel inhibited the glycolysis rate of JEG-3 and BEWO cells, and leaded to impaired mitochondrial function, including decreased basal respiratory values, decreased respiratory reserve capacity, and proton leakage. In pregnant mice with tumor modeling, paclitaxel could cause DNA damage in placental tissue cells, and might lead to apoptosis of chemotherapy mice placental tissue cells and impairment of normal physiological functions. Conclusion: Paclitaxel may directly or indirectly affect the normal physiological functions of placental trophoblast cells, including energy metabolism and protein synthesis dysfunction, which may be related to the adverse pregnancy outcomes caused by paclitaxel chemotherapy. [ABSTRACT FROM AUTHOR]

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA‐based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy‐induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF‐1 in response to chemotherapy. Genetic inhibition of HIF‐1‐controlled polyamine anabolism blocks chemotherapy‐induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF‐1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy‐induced HIF‐1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT CCNU (1‐[2‐chloroethyl]‐3‐cyclohexyl‐1‐nitrosurea), lomustine, is an oral alkylating agent in the nitrosourea subgroup. The dose‐limiting toxicity of CCNU is neutropenia most frequently documented 7 days after its administration. Use of prophylactic antimicrobials to prevent chemotherapy‐related febrile neutropenia (FN) and its associated morbidity and mortality has been well‐documented in human oncology, but this information is limited in the veterinary literature. The purpose of this multi‐institutional retrospective study was to assess whether antimicrobial prophylaxis reduced the risk of FN approximately 7 days after CCNU administration in tumour‐bearing dogs. A secondary goal was to identify risk factors for fever development in neutropenic dogs. Two hundred dogs were included in the study. One hundred and fifty‐three dogs (76.5%) were neutropenic at the first post‐CCNU recheck. One hundred and six (69.3%) dogs received prophylactic antimicrobials and 47 (30.7%) did not. Of the 106 dogs on prophylactic antimicrobials, 8 (7.5%) developed FN. Of the 47 dogs in the no‐prophylactic antimicrobials group, 4 (8.5%) developed FN. Use of prophylactic antimicrobials did not reduce the risk of development of FN (p = 0.84). Older age (> 9 y), lower weight and body surface area, and pre‐treatment with chemotherapy or radiation therapy were significantly associated with development of FN (p = 0.009, p = 0.023, p = 0.015 and p = 0.01). Patients with a lower absolute neutrophil count, and a higher VCOG‐CTCAE v2 neutropenia grade were also at an increased risk of developing FN (p = 0.01, p < 0.001). Additional studies may help establish guidelines for antimicrobial prophylaxis in dogs treated with CCNU, especially for those at high‐risk for FN. [ABSTRACT FROM AUTHOR]

Drug resistance poses a significant obstacle to the success of anti-cancer therapy in head and neck cancers (HNCs). We aim to develop a platform for visualizing and analyzing molecular expression alterations associated with HNC drug resistance. Through data mining, we convened differentially expressed molecules and context-specific signaling events involved in drug resistance. The driver genes, interaction networks and transcriptional regulations were explored using bioinformatics approaches. A total of 2364 differentially expressed molecules were identified in 78 distinct drug-resistant cells against 14 anti-cancer drugs, comprising 1131 mRNAs, 746 proteins, 62 lncRNAs, 257 miRNAs, 1 circRNA, and 166 post-translational modifications. Among these, 255 molecules were considerably, the signature driver genes of HNC drug resistance. Further, we also developed a landscape of signaling pathways and their cross-talk with diverse signaling modules involved in drug resistance. Additionally, a publicly-accessible database named "HNCDrugResDb" was designed with browse, query, and pathway explorer options to fetch and enrich molecular alterations and signaling pathways altered in drug resistance. HNCDrugResDb is also enabled with a Drug Resistance Analysis tool as an initial platform to infer the likelihood of resistance based on the expression pattern of driver genes. HNCDrugResDb is anticipated to have substantial implications for future advancements in drug discovery and optimization of personalized medicine approaches. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the bladder (SCCB) is a rare, highly malignant neuroendocrine tumor. This study attempted to analyze tumor characteristics, treatments and clinical outcomes in China. We conducted a retrospective analysis of patients diagnosed with non-metastatic SCCB at multi-institutions between January 2007 and January 2022. The Kaplan-Meier method was used to calculate survival. A total of 20 patients were included. 10 had localized disease (T1-2N0), and 10 had locally advanced disease (≥ T3 or N+). 13 received local treatment (partial cystectomy or transurethral resection of the bladder tumor) and 7 received radical treatment (radical cystectomy or radiotherapy). A total of 18 patients (90%) received chemotherapy (CT), either neoadjuvant CT (n = 5) or adjuvant CT (n = 13). The median OS for the receiving local treatment was 65.3 months (95% CI 0 to 138 months) and the corresponding 1-year, 2-year, and 3-year OS was 77%, 54%, and 54%, respectively. The median OS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year OS was 100%, 100%, and 75%, respectively. The median PFS for receiving local treatment was 13.8 months (95% CI 9.3 to 18.3 months) and the corresponding 1-year, 2-year, and 3-year PFS was 46%, 31%, and 31%, respectively. The median PFS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year PFS was 83%, 56%, and 56%, respectively. This study reported the largest cohort of non-metastatic SCCB among Chinese population. Given its metastatic potential, CT remained an essential part of the treatment. The survival outcomes of radical cystectomy and RT in non-metastatic SCCB were encouraging. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Interpretations Chemotherapy‐induced peripheral neurotoxicity (CIPN), with paraesthesia, numbness, dysesthesia and neuropathic pain ranks among the most common dose‐limiting toxicity of several widely used anticancer drugs. Recent studies revealed the microvascular angiogenesis as a new important actor, beside peripheral neurons, in the neurotoxicity and neuropathic pain development and chronicisation. The aim of this work is to elucidate the role of vascular alterations in CIPN.We evaluated the severity of CIPN with neurophysiological, behavioural and neuropathological analysis together with the microvascular network in central and peripheral nervous systems of rats in order to correlate the features of the CIPN and the vascular abnormalities. The vascular network was quantitatively evaluated through synchrotron radiation‐based X‐ray phase‐contrast micro‐tomography imaging, measuring four specific parameters: vascular density, vessel diameter, vessel tortuosity and branching.Rats exposed to paclitaxel and affected by a severe painful sensory axonopathy showed an increased vascular density (putative sprouting angiogenesis) in the crucial districts of the central (somatosensory cortex and lumbar spinal cord) and peripheral nervous system (lumbar dorsal root ganglia). In addition, the complexity of the vascular network and the size of neo‐formed vessels were significantly decreased in specific regions. On the other hand, less significant changes were observed in rats exposed to cisplatin, affected by a painless peripheral neuropathy, suggesting a specific involvement of neo‐angiogenesis in the development of severe neurotoxicity and neuropathic pain.These new ground‐breaking results can shed light on new pathogenetic mechanisms and potential novel therapeutic approaches for painful‐CIPN. [ABSTRACT FROM AUTHOR]

Background: Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore, D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types. Objectives: This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients. Design: This was a prospective study. Methods: This study included two groups, 76 patients diagnosed with metastatic breast carcinoma and 25 patients with primary breast carcinoma. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. D-dimer levels before chemotherapy (D0) were analyzed using Receiver Operating Characteristic (ROC) curves to determine the optimal cut-off baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy. Results: In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 0.65 μg/ml in patients with partial response patterns, and by 0.5 μg/ml in patients with stable disease. In the disease progression group, a marked increase was seen in D-dimer levels by 1.2 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas progressive disease rate correlated with higher levels of D-dimer. Conclusion: D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Pericardial disease is a common and severe complication in patients with cancer, often presenting as acute pericarditis, pericardial effusion, or constrictive pericarditis. Causes include direct tumor invasion, metastasis, and cancer treatments like chemotherapy and radiotherapy. Lung cancer is the most frequent etiology, followed by breast cancer and lymphomas. Early detection and multidisciplinary management are crucial. Acute pericarditis requires careful diagnosis and treatment with NSAIDs and colchicine. Pericardial effusion is commonly incidental but can lead to cardiac tamponade, necessitating pericardiocentesis or a pericardial window. Immunotherapy-related effusions typically respond to treatment cessation and steroids. Constrictive pericarditis, although rare, requires prompt diagnosis and may necessitate surgical intervention. Multidisciplinary care and early intervention are vital for improving patient outcomes and quality of life. Pericardial disease is increasingly recognized in cancer patients, including acute pericarditis, pericardial effusion, and constrictive pericarditis, often indicating a poor prognosis. Acute pericarditis arises from direct tumor involvement, cancer therapies, and radiotherapy. Immune checkpoint inhibitor (ICI)-related pericarditis, though rare, entails significant mortality risk. Treatment includes NSAIDs, colchicine, and corticosteroids or anti-IL1 drugs in refractory cases. Pericardial effusion is the most frequent manifestation, primarily caused by lung cancer, followed by breast cancer, lymphoma, leukemia, gastrointestinal tumors, and melanoma. Chemotherapy, immunotherapy, and radiotherapy may also cause fluid accumulation in the pericardial space. Symptomatic relief for pericardial effusion may require pericardiocentesis, prolonged catheter drainage, or a pericardial window. Instillation of intrapericardial cytostatic agents may reduce recurrence. Constrictive pericarditis, though less common, often develops from radiotherapy and requires multimodality imaging for diagnosis, with pericardiectomy as the definitive treatment. Primary pericardial tumors are rare, with metastases being more frequent. Patients with cancer and pericardial disease generally have poor survival, emphasizing the need for early detection. A multidisciplinary approach involving hematologists, oncologists, and cardiologists is crucial to tailoring pericardial disease treatment to a patient's clinical status, thereby improving the quality of life and prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Inhibition of the DNA repair protein PARP-1 is a promising concept in cancer therapy. More recently, PARP-1 has been revealed as a possible target in colorectal cancer, which is the second leading cause of cancer-related death worldwide. In this work, we screened a compound library to identify novel PARP inhibitors with low cytotoxicity and tested their efficacy in colorectal cancer cell models with and without defects in the DNA damage response. Furthermore, we evaluated whether the putative PARP inhibitors synergize with chemotherapeutic drugs used in the clinics to treat colorectal cancer patients. Using various experimental approaches, we were able to identify two promising molecules with potent PARP inhibition in colorectal cancer cells without causing cytotoxicity on their own. Moreover, the novel PARP inhibitors sensitized colorectal cancer cells to the anticancer drug irinotecan dependent on homologous recombination deficiency. Remarkably, the clinically approved PARP inhibitor olaparib displayed the strongest synergistic effects, but it was also cytotoxic as a single agent in wildtype colorectal cancer cells. The novel PARP inhibitors might, therefore, be useful for a combination therapy with irinotecan to avoid overlapping toxicity on healthy tissue such as bone marrow, which warrants further preclinical studies. The DNA repair protein PARP-1 emerged as a valuable target in the treatment of tumor entities with deficiencies of BRCA1/2, such as breast cancer. More recently, the application of PARP inhibitors (PARPi) such as olaparib has been expanded to other cancer entities including colorectal cancer (CRC). We previously demonstrated that PARP-1 is overexpressed in human CRC and promotes CRC progression in a mouse model. However, acquired resistance to PARPi and cytotoxicity-mediated adverse effects limit their clinical applicability. Here, we detailed the role of PARP-1 as a therapeutic target in CRC and studied the efficacy of novel PARPi compounds in wildtype (WT) and DNA repair-deficient CRC cell lines together with the chemotherapeutics irinotecan (IT), 5-fluorouracil (5-FU), and oxaliplatin (OXA). Based on the ComPlat molecule archive, we identified novel PARPi candidates by molecular docking experiments in silico, which were then confirmed by in vitro PARP activity measurements. Two promising candidates (X17613 and X17618) also showed potent PARP-1 inhibition in a CRC cell-based assay. In contrast to olaparib, the PARPi candidates caused no PARP-1 trapping and, consistently, were not or only weakly cytotoxic in WT CRC cells and their BRCA2- or ATR-deficient counterparts. Importantly, both PARPi candidates did not affect the viability of nonmalignant human colonic epithelial cells. While both olaparib and veliparib increased the sensitivity of WT CRC cells towards IT, no synergism was observed for X17613 and X17618. Finally, we provided evidence that all PARPi (olaparib > veliparib > X17613 > X17618) synergize with chemotherapeutic drugs (IT > OXA) in a BRCA2-dependent manner in CRC cells, whereas ATR deficiency had only a minor impact. Collectively, our study identified novel lead structures with potent PARP-1 inhibitory activity in CRC cells but low cytotoxicity due to the lack of PARP-1 trapping, which synergized with IT in homologous recombination deficiency. [ABSTRACT FROM AUTHOR]

Simple Summary: Incidence of brain metastases from genito-urinary cancers has increased over the last years due to improved imaging techniques and better survival outcomes for patients even at an advanced metastatic stage thanks to therapeutic advances. However, no clear consensus exists on their management, and every case ought to be discussed in a multidisciplinary panel. We perform a single-centre retrospective study to report on incidence, patient demographics, clinicopathological characteristics, and treatment modalities. We also manage to identify predictive factors of outcome. Background: Incidence of brain metastases is precisely unknown and there is no clear consensus on their management. We aimed to determine the incidence of brain metastases among patients with genito-urinary primaries, present patients' characteristics and identify prognostic factors. Method: We identified 51 patients treated in Geneva University Hospitals between January 1992 and December 2019. We retrospectively correlated their overall survival with 23 variables. We repeated a multivariate analysis with significant variables. Results: Overall incidence of Brain Metastases (BMs) among Genito-Urinary (GU) patients is estimated to be 1.76% (range per primary GU tumour type: 0.00–6.65%). BMs originate from germ cell tumours in two cases (3.92%), from urothelial cell carcinoma in 15 cases (29.41%), from prostate cancer in 13 cases (25.49%), and from renal cell carcinoma in 21 cases (41.18%); there are no BMs from penile cancer in our cohort. The median age at BM diagnosis is 67 years old (range: 25–92). Most patients (54%) have a stage IV disease at initial diagnosis and 11 patients (22%) have BM at initial diagnosis. Only six patients (12%) are asymptomatic at BM diagnosis. The median Overall Survival (OS) from BM diagnosis is 3 months (range: 0–127). Five patients (10%) are long survivors (OS > 24 months). OS is significantly influenced by patient performance status and administration of systemic treatment. In the absence of meningeal carcinomatosis, OS is influenced by systemic treatment and stereotactic radiosurgery. We also apply the Graded Prognostic Assessment (GPA) score to our cohort and note significant differences between groups. Conclusion: Brain metastases from solid tumours is not a uniform disease, with a prognosis varying a lot among patients. The optimal management for patients with genito-urinary malignancies with brain metastases remain unclear and further research is needed. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, primarily due to the overexpression of transmembrane drug transporters, with P-glycoprotein (P-gp) being a central focus. Consequently, the development of P-gp inhibitors has emerged as a promising strategy to combat MDR. Given the P-gp targeting potential of soloxolone amides previously predicted by us by an absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, the aim of the current study was to experimentally verify their P-gp inhibitory and MDR reversing activities in vitro. Screening of soloxolone amides as modulators of P-gp using molecular docking and cellular P-gp substrate efflux assays revealed the ability of compound 4 bearing a N-3-(dimethylamino)propylamide group to interact with the active site of P-gp and inhibit its transport function. Blind and site-specific molecular docking accompanied by a kinetic assay showed that 4 directly binds to the P-gp transmembrane domain with a binding energy similar to that of zosuquidar, a third-generation P-gp inhibitor (ΔG = −10.3 kcal/mol). In vitro assays confirmed that compound 4 enhanced the uptake of Rhodamine 123 (Rho123) and doxorubicin (DOX) by the P-gp-overexpressing human cervical carcinoma KB-8-5 (by 10.2- and 1.5-fold, respectively (p < 0.05, unpaired t-test)) and murine lymphosarcoma RLS40 (by 15.6- and 1.75-fold, respectively (p < 0.05, unpaired t-test)) cells at non-toxic concentrations. In these cell models, 4 showed comparable or slightly higher activity than the reference inhibitor verapamil (VPM), with the most pronounced effect of the hit compound in Rho123-loaded RLS40 cells, where 4 was 2-fold more effective than VPM. Moreover, 4 synergistically restored the sensitivity of KB-8-5 cells to the cytotoxic effect of DOX, demonstrating MDR reversal activity. Based on the data obtained, 4 can be considered as a drug candidate to combat the P-gp-mediated MDR of tumor cells and semisynthetic triterpenoids, with amide moieties in general representing a promising scaffold for the development of novel therapeutics for tumors with low susceptibility to antineoplastic agents. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) has earned a notorious reputation as one of the most formidable and deadliest malignant tumors. Within the tumor microenvironment, cancer cells have acquired the capability to maintain incessant expansion and increased proliferation in response to hypoxia via metabolic reconfiguration, leading to elevated levels of lactate within the tumor surroundings. However, there have been limited studies specifically investigating the association between hypoxia and lactic acid metabolism-related lactylation in PDAC. In this study, multiple machine learning approaches, including LASSO regression analysis, XGBoost, and Random Forest, were employed to identify hub genes and construct a prognostic risk signature. The implementation of the CERES score and single-cell analysis was used to discern a prospective therapeutic target for the management of PDAC. CCK8 assay, colony formation assays, transwell, and wound-healing assays were used to explore both the proliferation and migration of PDAC cells affected by CENPA. In conclusion, we discovered two distinct subtypes characterized by their unique hypoxia and lactylation profiles and developed a risk score to evaluate prognosis, as well as response to immunotherapy and chemotherapy, in PDAC patients. Furthermore, we indicated that CENPA may serve as a promising therapeutic target for PDAC. [ABSTRACT FROM AUTHOR]

Chemotherapy‐based combination regimens are recommended as first‐line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD‐OxPt (IV) nanoparticles (NPs) via host‐guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD‐OxPt (IV) NPs exhibit prolonged circulation in the blood and intra‐tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD‐OxPt (IV) NPs exhibited proton‐driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD‐OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53‐mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino‐like cell death and enhanced immunogenicity. Furthermore, DAS@CD‐OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis. [ABSTRACT FROM AUTHOR]

In this study, a bovine serum albumin-decorated zeolitic imidazolate framework (ZIF-8@BSA) was used to enhance the anticancer and antimetastatic properties of methotrexate. SEM, DLS, FT-IR, and XRD confirmed the physicochemical suitability of the developed nanoparticles. According to the SEM analysis, the mean size of ZIF-8 nanoparticles was 68.5 ± 13.31 nm. The loading capacity and encapsulation efficiency of MTX@ZIF-8@BSA were 28.77 ± 2.54% and 96.3 ± 0.67%, respectively. According to the in vitro hemolysis test, MTX@ZIF-8@BSA showed excellent blood compatibility. MTX@ZIF-8@BSA exhibited pH sensitivity, releasing more MTX at pH 5.4 (1.73 times) than at pH 7.4. The IC50 value of MTX@ZIF-8@BSA on 4T1 cells was 32.7 ± 7.3 µg/mL after 48 h of treatment, outperforming compared to free MTX with an IC50 value of 53.3 ± 3.7 µg/mL. Treatment with MTX@ZIF-8@BSA resulted in superior tumor growth suppression in tumor-bearing mice than free MTX. Furthermore, based on histopathology tests, MTX@ZIF-8@BSA reduced the metastasis in lung and liver tissues. While there was not any noticeable toxicity in the vital organs of MTX@ZIF-8@BSA-receiving mice, free methotrexate resulted in severe toxicity in the kidneys and liver. According to the preliminary in vitro and in vivo findings, MTX@ZIF-8@BSA presents an attractive drug delivery system candidate for breast cancer due to its enhanced antitumor efficacy and lower toxicity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact that adjuvant therapies like radiotherapy, chemotherapy, and immunotherapy have on osteobiologic properties and bony regeneration in patients with metastatic spine disease (MSD) undergoing spinal fusion surgery. Methods: PubMed and ClinicalTrials.gov searches were performed. MSD patients undergoing fusion surgery with an osteobiologic and radiotherapy, chemotherapy and/or immunotherapy were included. Demographics, primary tumor, surgery, adjuvant treatments, osteobiologic type, fusion rates with scoring criteria, hardware failure, reoperation rates, follow-up, and survival were extracted. 1487 studies were screened, 20 included. Results: 585 patients (464 with MSD) had fusion rates ranging from 17.9 to 100%. In the setting of radiotherapy, fusion rates of 10 studies using autologous bone graft (autograft), 5 studies using allogenic bone graft (allograft), 5 studies using combination autograft/allograft, 4 studies using biomaterial scaffolds (BMS), 3 studies using demineralized bone matrices (DBM), and 1 study using growth factors (GF), were 50–100%, 17.9–100%, 57.8–100%, 52.9–100%, 20–100%, and 100%, respectively. A higher incidence of fusion in patients with autograft or allograft receiving stereotactic body radiotherapy (SBRT) at lower biologically effective doses (BED) and at least 1-month postoperatively was noted. Chemotherapy had no impact on fusion. No studies evaluated the impact of immunotherapy on fusion. Conclusions: SBRT at lower doses given greater than 1-month postoperatively may enhance bony fusion in patients receiving autograft, allograft, or autograft/allograft. Chemotherapy may delay bony fusion without affecting overall fusion rates. Preclinical studies suggest immunotherapy may prevent osteolysis and promote osteogenesis, but no studies have yet evaluated the clinical impact of these findings on spinal fusion. Further research is needed on osteobiologics in bony regeneration in the MSD population. [ABSTRACT FROM AUTHOR]

Purpose: The survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database. Methods: Patients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined. Results: A total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis. Conclusions: Based on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite the improvement of multi-modality treatment strategies, the prognosis of pancreatic cancer was not improved dramatically. For resectable or borderline resectable patients, the surgical strategy centered on improving R0 resection rate is consensus; however, the role of neoadjuvant therapy in resectable patients and the optimal neoadjuvant therapy of chemotherapy with or without radiotherapy in borderline resectable patients were debated. Postoperative adjuvant chemotherapy of gemcitabine/capecitabine or mFOLFIRINOX is recommended regardless of the margin status. Chemotherapy as the first-line treatment strategy for advanced or metastatic patients included FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan was the only standard of care second-line therapy. Immunotherapy is an innovative therapy although anti-PD-1 antibody is currently the only agent approved by for MSI-H, dMMR, or TMB-high solid tumors, which represent a very small subset of pancreatic cancers. Combination strategies to increase the immunogenicity and to overcome the immunosuppressive tumor microenvironment may sensitize pancreatic cancer to immunotherapy. Targeted therapies represented by PARP and KRAS inhibitors are also under investigation, showing benefits in improving progression-free survival and objective response rate. This review discusses the current treatment modalities and highlights innovative therapies for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite the improvement of multi-modality treatment strategies, the prognosis of pancreatic cancer was not improved dramatically. For resectable or borderline resectable patients, the surgical strategy centered on improving R0 resection rate is consensus; however, the role of neoadjuvant therapy in resectable patients and the optimal neoadjuvant therapy of chemotherapy with or without radiotherapy in borderline resectable patients were debated. Postoperative adjuvant chemotherapy of gemcitabine/capecitabine or mFOLFIRINOX is recommended regardless of the margin status. Chemotherapy as the first-line treatment strategy for advanced or metastatic patients included FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan was the only standard of care second-line therapy. Immunotherapy is an innovative therapy although anti-PD-1 antibody is currently the only agent approved by for MSI-H, dMMR, or TMB-high solid tumors, which represent a very small subset of pancreatic cancers. Combination strategies to increase the immunogenicity and to overcome the immunosuppressive tumor microenvironment may sensitize pancreatic cancer to immunotherapy. Targeted therapies represented by PARP and KRAS inhibitors are also under investigation, showing benefits in improving progression-free survival and objective response rate. This review discusses the current treatment modalities and highlights innovative therapies for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration: This study was registered at . Trial registration number: NCT05972655. Date of registration: 31 July 2023. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Design Data Sources Methods Results Conclusions Impact Reporting Methods Patient or Public Contribution Breast cancer patients experience various adverse symptoms during adjuvant chemotherapy. These adverse symptoms often form symptom clusters and have a negative impact on patients.To summarise common symptom clusters in different dimensions and their longitudinal changes among breast cancer patients receiving adjuvant chemotherapy.A systematic review.Ten electronic databases were searched from 2001 to January 2024, and the search was last updated on 16 August 2024.Two reviewers independently assessed the eligibility of each study and extracted data. The Standard Quality Assessment Criteria for Evaluating Primary Research Papers was used to evaluate the quality of included studies. The findings were synthesised narratively. This systematic review has been registered (CRD42022370210).Nine studies with a total of 1454 participants were included. The common symptom clusters in breast cancer patients receiving adjuvant chemotherapy were the gastrointestinal symptom cluster (nausea‐lack of appetite), the fatigue‐pain‐sleep disturbance symptom cluster and the psychological symptom cluster (worry‐sadness‐nervousness‐distress‐feeling irritable‐difficult concentrating). The severity dimension was the most frequently utilised in identifying symptom clusters, with the number and concurrence of symptom clusters showing variation over time.This study summarised common symptom clusters in breast cancer patients receiving adjuvant chemotherapy and revealed their changes from symptom dimensions and the chemotherapy process. These findings support further exploration of symptom cluster changes and underlying mechanisms, facilitating the design of targeted management strategies, including appropriate interventions and measurement dimensions in clinical nursing, to ultimately reduce patients' symptom burden.Common symptom clusters have been identified in breast cancer patients receiving adjuvant chemotherapy. Clinical nursing in oncology can prioritise these symptom clusters and provide patients with targeted management strategies.PRISMA guidelines and SWiM guidelines.No patient or public contribution. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance remains a significant obstacle that limits the long-term efficacy of cancer therapy, necessitating further investigations into the underlying mechanisms. Here, we find that DNA fragments induced by chemotherapeutic agents trigger the degradation of cGAS, a potent double-strand DNA (dsDNA) sensor, by lysosomes. Mechanically, the lysosome-localized protein LAMTOR1 is up-regulated, and the interaction between LAMTOR1 and cGAS is enhanced upon exposure to DNA fragments, boosting the accumulation and digestion of cGAS in lysosomes through the receptor protein p62. LAMTOR1 deficiency increases cGAS abundance and promotes activation of the cGAS-STING pathway, leading to subsequent production of type I interferons induced by cytosolic DNA stimulation. Loss of LAMTOR1 synergizes with immunotherapy and chemotherapy to inhibit tumor growth and prolong the survival time of tumor-bearing mice by promoting the infiltration of effective T lymphocytes. Thus, our study reveals a regulation of cGAS abundance and provides a potential strategy to overcome chemotherapy resistance by targeting LAMTOR1. [ABSTRACT FROM AUTHOR]

Background: Embryonal rhabdomyosarcoma (ERMS) is a highly aggressive form of soft-tissue sarcoma that predominantly affects children. Due to limited benefits and resistance to therapy, there is an unmet need to explore alternative therapeutic strategies. Case presentation: In this report, we present a rare case of pediatric ERMS located on the right side of the maxillary gingiva. A composite reference guide integrating clinical, radiographic, and histopathologic findings was used for a definitive diagnosis. Targeted next-generation sequencing of tumor biopsy was performed to identify genetic alterations. A 12-year-old female was admitted to the Pediatric Intensive Care Unit (PICU) and underwent a tracheotomy to relieve asphyxiation caused by a 5.5 cm diameter mass compressing the tongue root and pharyngeal cavity. Hematoxylin and eosin staining revealed a hybrid morphology characterized by clusters of round and spindle cells. Further immunohistochemistry assays indicated positive immunoreactivity for desmin, myogenin, and MyoD1. Various genetic alterations were identified, including mutations in GNAS, HRAS, LRP1B, amplification of MDM2 and IGF1R, and two novel IGF1R fusions. Negative PAX-FOXO1 fusion status supported the clinical diagnosis of ERMS. Initial treatment involved standard chemotherapy; however, the tumor persisted in its growth, reaching a maximum volume of 12 cm × 6 cm × 4 cm by the completion of treatment. Subsequent oral administration of anlotinib yielded a significant antitumor response, characterized by substantial tumor necrosis and size reduction. Following the ligation of the tumor pedicle and its removal, the patient developed a stabilized condition and was successfully discharged from PICU. Conclusions: Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most commonly diagnosed cancer worldwide. Although major treatments represented by chemotherapy have shown effectiveness at the initial period, recurrence and metastasis still occur later after treatments. The alternation of the tumor microenvironment by chemotherapy is confirmed as a trigger of the elevated proliferation and migration of the remaining tumor cells. Methods: Using bioinformatic methods, differential gene expression analysis was used to determine DEGs between post-chemotherapy and pre-chemotherapy samples of breast cancer patients, followed by survival analysis and ELISA analysis of the potential key genes. An in vitro model of 2 breast cancer cells lines was used to demonstrate the role of VWF in the evasion and migration of breast cancer cells, using cell migration, evasion and wound healing assays, PCR and molecular docking analysis. Results: 19 hub genes were further identified using GO and KEGG pathway analyses and WGCNA. The 5 secreted protein-coding genes with reported carcinogenesis effects (VWF, SVEP1, DPT, ADIPOQ, and LPL) were further analyzed in breast cancer patients and VWF was identified as a potential key regulator in the anthracycline-based chemotherapy-exacerbated metastasis. It was further confirmed that anthracycline-based chemotherapeutics doxorubicin exacerbated VWF upregulation and the evasion and migration of breast cancer cells. Based on molecular docking analysis and previous study, berberine was used as an inhibitor of VWF, and showed an effective inhibition of the doxorubicin-exacerbated VWF upregulation, migration and evasion in breast cancer. Conclusions: Doxorubicin-exacerbated evasion and migration through VWF upregulation. Berberine as an inhibitor of VWF was able to reversed the doxorubicin-exacerbated VWF upregulation and evasion and migration in breast cancer cells. [ABSTRACT FROM AUTHOR]

The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy. [ABSTRACT FROM AUTHOR]