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1261. N-acetyl-L-cysteine promoted hematopoietic recovery in patients with acute myeloid leukemia after complete remission--A pilot study.

作者: Li-Juan Hu.;Chen-Yuan Li.;Tong Xing.;Yu Wang.;Qian Jiang.;Hao Jiang.;Jing Wang.;Fei-Fei Tang.;Ying-Jun Chang.;Xiao-Hui Zhang.;Yuan Kong.;Xiao-Jun Huang.
来源: Cancer Lett. 2025年625卷217812页
Chemotherapy is a cornerstone treatment for acute leukemia (AL), but it often results in bone marrow (BM) failure, leading to infections, anemia, and bleeding, which significantly impact patient survival. Endothelial progenitor cells (EPCs) are critical elements of the BM microenvironment and are essential for hematopoiesis. Our previous research using in vitro and AML mouse models indicated that BM EPC dysfunction, characterized by impaired angiogenesis and elevated reactive oxygen species (ROS) levels in AML patients, could be partially reversed after complete remission (CR) and further improved with N-acetyl-L-cysteine (NAC) treatment. This pilot cohort study (NCT06024031, www.clinicaltrials.gov) evaluated the effects of NAC on hematopoietic recovery in 30 newly diagnosed AML patients after induction chemotherapy, compared to a propensity-matched control group of 60 patients. Patients received oral NAC (400 mg, three times daily) for 28 days post-chemotherapy alongside standard supportive care. NAC treatment did not affect CR rates (90 % vs. 80 %, P = 0.23), but significantly shortened platelet recovery time (19 vs. 22 days, P = 0.0001) among CR patients. NAC improved EPC percentages, reduced ROS, and enhanced EPC hematopoiesis-supporting functions in patients who achieved CR. NAC was safe and effective in promoting normal hematopoiesis recovery in AML patients in CR following chemotherapy.

1262. Elucidating the anticancer properties of posaconazole in triple-negative breast cancer through in-silico and in-vitro analysis.

作者: Lakshi Sharma.;Sujisha S Nambiar.;Arman Mohanty.;Arupam Patra.;Shivani Kumari.;Gurvinder Kaur Saini.
来源: Biochem Biophys Res Commun. 2025年771卷152001页
The present study focused on repurposing antifungal drugs for cancer treatment. Repurposing refers to the evaluation of an existing drug that has been used to treat a specific disease and to identify its potential to be used for other therapeutic purposes due to similarities in targets. Posaconazole is a second-generation lipophilic antifungal agent that exhibits broad-spectrum activity against various fungal infections associated with several fungal species. Posaconazole was chosen as the target drug for proteins screened through Swiss Pred to inhibit triple-negative breast cancer. The selected targets were allowed to develop a PPI network using a string database to identify bottleneck proteins. These target proteins were used for molecular docking and molecular dynamics simulations. In-silico analysis was further validated by cell viability assay in which posaconazole exhibited notable decrease in cell viability with an IC50 value of 7.2 μM in MDA-MB-231 triple negative breast cancer cell lines (TNBC). Furthermore, the migration potential of MDA-MB-231 cells following posaconazole treatment was investigated using a wound healing assay. Additionally, Posaconazole caused a notable decrease in sphere and colony formation ability. The mechanism of cell death was further analyzed using intracellular reactive oxygen species generation, mitochondrial depolarization, and cell cycle analysis. The results demonstrated that all tested variables including cell viability, migration colony formation, cell cycle analysis, ROS generation, mitochondrial depolarization and apoptosis showed statistically significant changes (p < 0.01) against the untreated control groups. The potent anticancer potential of posaconazole has opened new avenues for repurposing antifungal drugs to treat cancer.

1263. Repurposing HIV protease inhibitors as senotherapeutic agents in cervical cancer: Dual targeting of CDK1/6-cell cycle arrest and p53/p21/p16 signaling axis.

作者: Lan Yu.;Weiqiang Han.;Jing Zhang.;Guoxin Liu.;Hongjuan Li.;Yongqian Xu.;Fengyu Liu.;Shiguo Sun.
来源: Biochem Biophys Res Commun. 2025年771卷152040页
The clinical management of cervical cancer remains constrained by limited therapeutic options and a paucity of targeted pharmacological interventions. Drug repurposing emerges as a promising strategy to expedite oncological therapeutics development. This study systematically investigates the antineoplastic potential of HIV protease inhibitors saquinavir (SQV) and tipranavir (TPV) through multimodal mechanistic validation. In vitro analyses demonstrated dose-dependent inhibition of cervical cancer cell proliferation accompanied by significant upregulation of senescence-associated β-galactosidase (SA-β-Gal) activity. Molecular characterization revealed concomitant activation of senescence-regulatory proteins p53, p21, and p16, suggesting induction of tumor-suppressive senescence pathways. Transcriptomic profiling of inhibitor-treated SiHa cells identified critical cell cycle regulators CDK1 and CDK6, findings corroborated by molecular docking simulations revealing high-affinity binding to cyclin-dependent kinases (-32.0607 to -47.6820 kJ/mol). In vivo validation using xenograft models demonstrated comparable tumor growth inhibition to doxorubicin with preserved host viability and negligible systemic toxicity. Mechanistic integration revealed dual pathway modulation: G1-phase cell cycle arrest mediated through CDK1/6 suppression and coordinated activation of the p53/p21/p16 senescence signaling axis. These findings establish SQV and TPV as multi-targeted senotherapeutic agents, providing preclinical rationale for repurposing HIV antivirals as novel therapeutic strategy against cervical malignancies.

1264. Adiponectin: its role in diabetic and pancreatic cancer.

作者: Seema Kumari.;Sujatha Peela.;Mundla Srilatha.;Bala Prabhakar Girish.;Ganji Purnachandra Nagaraju.
来源: Mol Aspects Med. 2025年103卷101370页
Adiponectin (ApN) is an antidiabetic and anti-inflammatory protein synthesized by adipose tissue. It is essential in regulating insulin sensitivity, glucose, and lipid metabolism by controlling AMPK, PPARα, and MAPK signals. It is an anti-inflammatory property that protects pancreatic β-cells. Often, low levels of ApN are linked to obesity, type II diabetes and the development of PDAC. However, changes in lifestyle and the use of certain drugs can improve ApN function and insulin sensitivity. PDAC is a highly aggressive cancer linked to obesity, type II diabetes, and insulin resistance. ApN plays a complex role in PDAC progression and can suppress PDAC development by weakening β-catenin signaling. Decreases in ApN levels are associated with increased PDAC risk in diabetic patients. PDAC and diabetes are interconnected through the development of insulin resistance, islet dysfunction, change in immunological response, inflammation, oxidative stress, and altered hormone secretion. Genetic studies highlight specific genes like HNF4G and PDX1 that influence both conditions and miRNAs such as miR-19a promote tumor progression through the PI3K/AKT pathway. This review discusses the role of ApN in diabetes and PDAC and the interrelation between diabetes and PDAC.

1265. Rare Primary ALK-Positive Anaplastic Large Cell Lymphoma of the Central Nervous System.

作者: Nathalie Soler.;Kelly Paz Amador.;Alexandra Perez.;Camila Solis.;Alexander Reyes.;Jorge Garcia.;Maria Paula Gonzalez Zambrano.;Edgar Fabián Manrique Hernández.
来源: Oncology (Williston Park). 2025年39卷4期154-157页
Anaplastic large cell lymphoma (ALCL) is a rapidly growing and aggressive hematological malignancy. We present the case of a 12-year-old adolescent boy with a 2-week history of left iliac fossa and presacral pain radiating to the lower limbs associated with emesis and constipation. Subsequently, the patient developed poorly controlled hypertension and progressive lower limb weakness. Imaging revealed an intradural extramedullary mass at the L1 level, and pathology reported large, atypical cells consistent with ALK -positive ALCL. This case highlights the rarity of isolated intradural extramedullary manifestations in the pediatric population. Keywords : Anaplastic large-cell lymphoma; human central nervous system neoplasms; pediatric oncology; intradural neoplasms; treatment outcome; ALK protein, human.

1266. A design-based framework for optimal stratification using super-population models with application on real data set of breast cancer.

作者: Faizan Danish.
来源: PLoS One. 2025年20卷5期e0323619页
This study investigates the determination of stratification points for two study variables within the framework of simple random sampling, with a focus on estimating the population mean using a closely related auxiliary variable. Employing a superpopulation model, the research aims to minimize overall variance by deriving simplified equations that enhance the precision of parameter estimates. Instead of categorizing variables, the study emphasizes continuous variables to establish optimal strata boundaries (OSB), which are essential for creating homogeneous groups within each stratum. This stratification leads to more efficient sample sizes (SS) and improved accuracy in parameter estimation. However, achieving optimal OSB and SS poses challenges in scenarios with a fixed total sample size, such as survey designs constrained by limited budgets. To address this, the study proposes a robust methodology for calculating OSB and SS, leveraging knowledge of the survey's per-unit stratum measurement costs or its probability density function. An empirical application of the method is demonstrated using breast cancer data, where the mean perimeter is estimated based on mean radius and mean texture. Additionally, hypothetical examples using Cauchy and standard power distributions are provided to illustrate the versatility of the proposed approach. The newly developed method has been integrated into the updated stratifyR package and implemented in LINGO software, facilitating its practical application. Comparative analysis reveals that this approach consistently outperforms or matches existing methods in enhancing the precision of population parameter estimation. Furthermore, simulation studies confirm its higher relative efficiency, making it a valuable contribution to the field of stratified sampling.

1267. Molecular Landscape of Endometrial Stromal Tumors.

作者: Marta Brunetti.;Valeria Vitelli.;Anca Mihaela Naas.;Ane Gerda Zahl Eriksson.;Hans Kristian Haugland.;Camilla Krakstad.;Francesca Micci.
来源: JCO Precis Oncol. 2025年9卷e2400779页
The molecular heterogeneity of endometrial stromal tumors (ESTs) is demonstrated by the presence of the same fusion gene in distinct pathologic entities, such as endometrial nodules and low-grade endometrial stromal sarcoma, both exhibiting the JAZ1::SUZ12 chimeric transcript. Given the limited knowledge on these tumors, which is based on a small number of cases studied with a restricted range of techniques, we analyzed 47 ESTs to explore their methylation and transcriptomic landscapes.

1268. TP53 Mutations and Phosphatidylinositol 3-Kinase/AKT Pathway Alterations Are Key Determinants of Breast Cancer Outcome Independent of Subtype and Stage.

作者: Tibor A Zwimpfer.;Martin Heidinger.;Ricardo Coelho.;Nadja Stiegeler.;Fabienne D Schwab.;Céline Montavon.;Ruth S Eller.;Nadia Maggi.;Julie M Loesch.;Marcus Vetter.;Matteo Lambertini.;Walter P Weber.;Christian Kurzeder.;Viola Heinzelmann-Schwarz.
来源: JCO Precis Oncol. 2025年9卷e2400767页
Breast cancer (BC) is a heterogeneous disease with genetic alterations influencing prognosis and treatment response. TP53 mutations (TP53muts) are present in approximately 30% of BC, but their prognostic impact remains controversial. In addition, the phosphatidylinositol 3-kinase (PI3K)/Ak strain transforming (AKT) pathway is frequently altered and represents a promising therapeutic target for BC. Understanding the combined prognostic impact of TP53mut and PI3K/AKT pathway alterations across BC subtypes remains underexplored.

1269. Palbociclib, a Selective CDK4/6 Inhibitor, Administered Before and After Chemoradiotherapy for Human Papillomavirus-Negative, Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm, Phase II Trial.

作者: Peter J Oppelt.;Jessica C Ley.;Sidharth V Puram.;Ryan S Jackson.;Randall C Paniello.;Jason T Rich.;Patrik Pipkorn.;Jingxia Liu.;Wade L Thorstad.;Douglas R Adkins.
来源: JCO Precis Oncol. 2025年9卷e2500069页
The primary aim of this single-arm, phase II trial was to determine the objective response rate (ORR) with palbociclib, a selective CDK4/6 inhibitor, administered before chemoradiotherapy (CRT) in patients with human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC).

1270. Low-Dose Anti-PD1 Immune Checkpoint Inhibitors in Relapsed/Refractory Hodgkin Lymphoma: A Systematic Review.

作者: Héctor A Vaquera-Alfaro.;José Emiliano Montelongo-Cepeda.;Antonio Vega-Mateos.;Anahí Morales-Pedraza.;Haydeé Verduzco-Aguirre.;David Gómez Almaguer.;Luis Villela.;Perla R Colunga-Pedraza.
来源: JCO Glob Oncol. 2025年11卷e2400538页
Blockage of PD-1 with drugs such as nivolumab (Nivo) and pembrolizumab (Pembro) has been successfully implemented in the treatment of Hodgkin lymphoma among other types of tumors. Exorbitant costs hinder access for many patients living in low- and middle-income countries (LMICs). Dose reductions on the basis of pharmacodynamic studies have been used to allow access to these drugs to patients with no further options because of economic constraints. In this study, we aimed to systematically review and assess evidence regarding the efficacy and safety of this adapted intervention.

1271. Triple Oral Metronomic Chemotherapy Versus Chemotherapy of Physician Discretion After Failure of Platinum-Based Therapy in Advanced Head and Neck Cancer: A Phase III Randomized Study (METRO-CHASE Study).

作者: Akhil Kapoor.;Anuj Gupta.;Bipinesh Sansar.;Bal Krishna Mishra.;Pooja Gupta.;Arpita Singh.;Arvind Upadhyay.;Lakhan Kashyap.;Ankita Pal.;Amit Kumar.;Sambit S Nanda.;Ashutosh Mukherji.;Ankita Rungta Kapoor.;Satyajit Pradhan.;Aseem Mishra.;Zachariah Chowdhury.;Shashikant Patne.;Ipsita Dhal.;Neha Singh.;Shreya Shukla.;Satyendra Narayan Singh.;Varun Shukla.;M V Manikandan.;Arvind Suresh.;Shripad Banavali.;Somnath Dey.;Kunal Ranjan Vinayak.;Praveen Lakshman.;Lokendra Gupta.;Pratibha Gavel.;Bhavesh P Bandekar.;Vijay Patil.;Vanita Noronha.;Kumar Prabhash.
来源: JCO Glob Oncol. 2025年11卷e2500032页
Platinum-refractory advanced head and neck squamous cell carcinoma (HNSCC) has poor outcomes and limited treatment options, especially in resource-constrained settings. Triple oral metronomic chemotherapy (OMCT), involving low-dose continuous administration of chemotherapeutic agents, has shown promise in phase II studies but lacks evidence from randomized controlled trials. This study evaluated whether triple OMCT improves overall survival (OS) compared with chemotherapy of physician discretion (CPD).

1272. Insights Into Heart-Tumor Interactions in Heart Failure.

作者: Tal Caller.;Kathryn J Moore.;Lorenz H Lehmann.;Sean M Wu.;Jonathan Leor.
来源: Circ Res. 2025年136卷11期1262-1285页
Heart failure (HF) often coexists with cancer. Beyond the known cardiotoxicity of some cancer treatments, HF itself has been associated with increased cancer incidence. The 2 conditions share common risk factors, mechanisms, and interactions that can worsen patient outcomes. The bidirectional relationship between HF and cancer presents a complex interplay of factors that are not fully understood. Recent preclinical evidence suggests that HF may promote tumor growth via the release of protumorigenic factors from the injured heart, revealing HF as a potentially protumorigenic condition. Our review discusses the biological crosstalk between HF and cancer, emphasizing the impact of HF on tumor growth, with inflammation, and modulating the immune system as central mechanisms. We further explore the clinical implications of this connection and propose future research directions. Understanding the mechanistic overlap and interactions between HF and cancer could lead to new biomarkers and therapies, addressing the growing prevalence of both conditions and enhancing approaches to diagnosis, prevention, and treatment.

1273. Boosting immune response against cervical cancer: A combined approach using oncolytic virus and targeted therapies.

作者: Hedieh Zargaran.;Amir Ghaemi.;Mohammad Shenagari.;Mehdi Samadi.
来源: PLoS One. 2025年20卷5期e0312979页
Cervical cancer remains a primary reason for cancer malignancy among women worldwide, primarily due to human papillomavirus (HPV) strains HPV16 and HPV18. Despite having access to vaccines, there are few treatment options for advanced or recurring cases. This research investigates the possibility of using Newcastle disease virus (NDV) along with Everolimus (EVE) and Beclin-1 (BEC) to improve immune reactions and decrease tumor development in an experimental model of HPV-related cervical cancer.

1274. Exploring the mechanism of action of aspirin in improving endometrial receptivity in PCOS rats based on uterine lavage fluid metabolomics.

作者: Ying Zhang.;Xi Wang.;Yiqing He.;Quan Liu.;Shuo Yang.
来源: PLoS One. 2025年20卷5期e0324432页
Aspirin has been shown to enhance endometrial receptivity (ER) during the window of implantation in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms by which aspirin improves ER through metabolic analysis of uterine lavage fluid.

1275. Silencing NRF2 enhances arsenic trioxide-induced ferroptosis in hepatocellular carcinoma cells.

作者: Mi Huang.;Duanzhuo Li.;Zhengzhen Xia.;Shengjie Liao.;Wenxia Si.;Chao Yuan.;Yanli Liao.;Weibin Wu.;Minshu Jiang.;Xin Yu.;Yi Quan.
来源: PLoS One. 2025年20卷5期e0322746页
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with high mortality rates partially due to limited therapeutic options and drug resistance. Arsenic trioxide (ATO), a compound clinically proven for acute promyelocytic leukemia (APL), has garnered attention for its emerging efficacy in solid tumors, including HCC. However, the molecular mechanisms driving ATO's antitumor activity in HCC remain incompletely understood. In this study, we aimed to elucidate the ferroptosis-dependent effects of ATO on HCC and and propose a potential therapeutic strategy.

1276. Factors associated with switching from active surveillance to treatment in men with low-risk prostate cancer: A population-based study.

作者: Kevin B Ginsburg.;Michael S Sessine.;Cathryn H Bock.;Michael Goodman.;Rami Yacoub.;Justin Woo.;James Janisse.;Jinping Xu.
来源: Cancer. 2025年131卷11期e35909页
The authors sought to identify modifiable and nonmodifiable factors associated with switching from active surveillance to treatment among men with low-risk prostate cancer (LRPC).

1277. Musculoskeletal Lymphoma: Imaging Features, Diagnosis, and Assessment of Treatment Response.

作者: Connor D Sleeth.;Alexander R Moeller.;Cree M Gaskin.;John S Symanski.;Kirkland W Davis.;Maxine E Kresse.
来源: Radiographics. 2025年45卷6期e240175页
Lymphoma, a diverse group of neoplasms, has been frequently refined in classification, with over 100 types identified by the World Health Organization in 2022. Lymphoma represents 5% of new malignancies in the United States, the risk factors of which include genetic predisposition, infections, and inflammatory conditions. Extranodal lymphoma, constituting 25%-40% of cases, uncommonly involves the musculoskeletal system, with diffuse large B-cell lymphoma being the primary type. Bone lymphoma, classified as primary, primary multifocal, or secondary, predominantly affects the appendicular skeleton. Radiography and CT aid osseous evaluation and may reveal a lytic, sclerotic, mixed lytic and sclerotic, or near-normal appearance. MRI excels in soft-tissue and bone marrow assessment, and PET/CT plays a pivotal role in staging. Soft-tissue lymphoma, which involves various compartments, is best characterized with MRI, whereas US may be the modality first used for evaluation. Staging involves fluorodeoxyglucose (FDG) PET/CT, and treatment response is assessed through various imaging modalities. Skin involvement, commonly associated with primary cutaneous T-cell lymphoma, is described through stages, with FDG PET aiding diagnosis. Transspatial lymphoma involves multiple contiguous spaces and is known in the head and neck but not well documented in the musculoskeletal system. The authors provide comprehensive insight into musculoskeletal lymphoma by highlighting imaging findings crucial for diagnosis, classification, staging, and assessment of treatment response. ©RSNA, 2025.

1278. Predictors and risk model for positive circumferential resection margin after robot-assisted total mesorectal excision: retrospective cohort study.

作者: Ritch T J Geitenbeek.;Thijs A Burghgraef.;Rauand Duhoky.;Christina A Fleming.;Aurore Moussion.;Nabila Bouazza.;Eddy Cotte.;Anne Dubois.;Eric Rullier.;Quentin Denost.;Philippe Rouanet.;Jim Khan.;Roel Hompes.;Esther C J Consten.; .
来源: BJS Open. 2025年9卷3期
Positive circumferential resection margin (CRM) after total mesorectal excision (TME) is associated with higher local and systemic recurrence rates, affecting overall survival in patients with rectal cancer. Although risk factors for positive CRM have been identified for open, laparoscopic, and transanal TME, these may differ for robot-assisted total mesorectal excision (R-TME). This study aimed to assess the incidence of positive CRM following R-TME and identify the associated preoperative risk factors.

1279. SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma.

作者: Jiahe Nie.;Junjie Tang.;Zhihui Zhang.;Hetian Sun.;Xinyue Wang.;Longxiang Wang.;Meng Wang.;Weifeng Huang.;Yang Gao.;Jinmiao Li.;Chao Cheng.;Shicai Su.;Shuxia Chen.;Siming Ai.;Yuxiang Mao.;Ping Zhang.;Yaoming Liu.;Rong Lu.
来源: Invest Ophthalmol Vis Sci. 2025年66卷5期24页
This study aims to explore the role of SRY-related HMG box transcription factor 4 (SOX4) in promoting invasion in retinoblastoma (RB) and to elucidate the underlying oncogenic pathways.

1280. Microbiota Transplantation in Tumor Immunology Studies.

作者: Lingxi Li.;Muni Hu.;Xiaoqiang Zhu.;Xiaowen Huang.;Haoyan Chen.
来源: Methods Mol Biol. 2025年2930卷295-306页
This protocol outlines the standardized procedures for utilizing fecal microbiota transplantation (FMT) in tumor immunology studies. FMT, the process of transferring gut microbiota from a healthy donor to a recipient, has shown potential in modulating the immune response against tumors. This protocol details the selection criteria for donors and recipients, preparation and processing of fecal material, and the administration routes for transplantation. Additionally, it describes the pre- and posttransplantation monitoring of microbiota composition, immune parameters, and tumor progression. By following this protocol, researchers can systematically investigate the impact of microbiota on tumor growth and immune modulation, contributing to the development of microbiota-based therapeutic strategies in oncology.
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