Cancers最新文献

Endometrial hyperplasia (EH) comprises a spectrum of abnormal proliferative changes in the endometrium, ranging from benign glandular overgrowth to lesions with substantial malignant potential. The importance of risk stratification and early identification is highlighted by the growing recognition of EH as a precursor to endometrial cancer. The main causes of EH, according to epidemiological research, include obesity, polycystic ovarian syndrome (PCOS), metabolic dysfunction, and extended exposure to unopposed estrogen. Emerging molecular markers, histological analysis, and imaging are all necessary for a proper diagnosis of EH because it might appear with vague clinical symptoms such as irregular uterine bleeding. Surgical intervention or progestin therapy are two possible management techniques for EH, depending on the lesion's intricacy and the patient's medical history, including fertility issues. Personalized therapy techniques and recent developments in molecular profiling have the potential to enhance patient outcomes by matching treatment to tumor biology and individual risk profiles. This review highlights the translational potential of molecular insights while synthesizing the most recent data on the epidemiology, risk factors, diagnostic techniques, and therapy of EH. A deeper comprehension of these elements is necessary to maximize treatment results and stop the development of endometrial cancer.

Adverse effects of chemotherapeutic agents remain a significant clinical challenge in the management of gastric cancer. Across the literature, discussions of chemotherapy consistently document a range of toxicities, underscoring that even when treatment halts disease progression, it can leave substantial clinical sequelae. Chemotherapy can impact virtually every organ system, producing multiorgan toxicity with meaningful implications for patient quality of life and treatment feasibility. When initiating a new chemotherapy regimen, prior lack of therapeutic benefit is often associated with difficult recovery or inability to tolerate subsequent chemotherapy, thereby constraining future therapeutic options. Given these considerations and the current absence of universally personalized treatment, a multidisciplinary team-comprising a medical oncologist, gastroenterologist, and internist-is essential to the planning and execution of chemotherapy regimens. We recommend that these chemotherapy regimens be administered within internal medicine departments, in collaboration with the medical oncologist and gastroenterologist, because in many cases the adverse effects outweigh the potential benefits of chemotherapy.

GATA transcription factors, defined by their zinc finger DNA-binding domains, are central regulators of tissue development. They modulate gene expression by activating or repressing transcription, thereby coordinating cellular differentiation and cell cycle exit to maintain homeostasis. In progenitor cells, GATA factors promote proliferation, whereas in differentiating cells, they drive maturation and induce cell cycle arrest. Dysregulation of GATA factors has been linked to tumorigenesis and contributes significantly to cancer progression and metastasis. Mutations in GATA factor genes correlate with poor prognosis in multiple cancers, where they influence key oncogenic processes, including sustained proliferative signaling, activation of epithelial-mesenchymal transition, angiogenesis, resistance to cell death, and immune escape. Importantly, their context-dependent roles across tumor types highlight the complexity of their functions in malignancies. Meanwhile, non-coding RNAs have emerged as critical regulators of gene expression, acting as either tumor suppressors or oncogenes by modulating chromatin dynamics, transcription factor activity, and mRNA stability. Despite this, the regulation of GATA transcriptional activity by non-coding RNAs remains largely unexplored. This review highlights the role of GATA factors in regulating EMT and metastasis and focuses on the interplay between non-coding RNAs and GATA transcription factors in cancer progression, proposing a novel regulatory axis with potential implications for biomarker discovery and therapeutic targeting.

Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor-stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially ineffective or even harmful. This review summarizes recent progress in fibroblast origins, functional subtypes, and fibroblast-driven mechanisms that promote tumor progression and therapy resistance, as well as emerging therapeutic opportunities in prostate cancer. We conducted a structured literature search of PubMed, ScienceDirect, and major publisher platforms (including Nature and SpringerLink) from database inception to 15 February 2025, supplemented by targeted manual screening of reference lists. Evidence from single-cell/spatial-omics and mechanistic studies indicates that prostate tumors contain multiple fibroblast programs that occupy distinct niches yet can interconvert. Across these studies, it was found that these fibroblasts contribute to immune suppression, extracellular matrix remodeling and stromal barrier formation, angiogenesis, and metabolic support, collectively limiting drug penetration and reinforcing immune evasion; therapeutic pressure can further rewire fibroblast states and resistance-associated signaling. Overall, the literature supports a shift toward function- and subtype-directed intervention rather than "one-size-fits-all" targeting, with promising directions including precision targeting and reversible reprogramming, rational combination strategies, and localized delivery approaches that reduce stromal barriers while preserving tissue homeostasis in high-risk and treatment-refractory prostate cancer.

Objectives: To determine the incidence of delayed methotrexate elimination (DME) and acute kidney injury (AKI) and their associations with clinical outcomes in patients receiving high-dose methotrexate (HDMTX) for cancer treatment. Methods: The HDMTX European Registry collected medical records data from 12 institutions in 5 European countries to investigate the clinical practice patterns of healthcare providers utilizing HDMTX for cancer treatment. Cancer types included were acute lymphoblastic leukemia (ALL), primary central nervous system lymphoma (PCNSL), non-Hodgkin lymphoma (NHL), osteosarcoma, and other CNS cancers. Primary endpoints were the incidence of DME and AKI; secondary endpoints were clinical outcomes, including hospital length of stay (LOS), delay in the subsequent course of treatment, methotrexate dose reduction, and omission of next course of treatment. Associations between the primary and secondary endpoints were analyzed with Chi-square and Wilcoxon rank-sum tests. Results: Among the 2501 total HDMTX courses analyzed, DME occurred in 302 courses (12.1%), and AKI in 384 courses (15.4%). DME incidence was highest in courses for PCNSL (18.2%) and NHL (17.2%); AKI incidence was highest in ALL courses (21.0%). Incidence of DME and AKI varied by age and methotrexate infusion duration among the different cancer types. Occurrence of DME was associated with longer delays prior to the next course of treatment, longer hospital LOS, and more frequent methotrexate dose reductions and dose omissions. Conclusions: While HDMTX is a very effective and safe treatment, administration of efficacious doses of methotrexate can lead to AKI and DME, and no single or combination of patient or treatment factors was found to reliably predict their occurrence. Thus, diligent monitoring of methotrexate levels is imperative for early detection and prompt management of nephrotoxicity in all settings where HDMTX treatment is administered.

In the original publication, the annotation for equal authorship was not included due to editorial error [...].

Background: Electrochemotherapy (ECT) enhances the intracellular delivery of chemotherapeutic agents, most notably bleomycin, through electroporation. Despite high response rates, tumor sensitivity to ECT varies, highlighting the need for predictive biomarkers. Bleomycin hydrolase (BLMH), an enzyme that metabolically inactivates bleomycin, may influence treatment outcomes. This study investigated the relationship between BLMH expression and bleomycin-based ECT effectiveness. Methods: BLMH expression was evaluated at the mRNA and protein levels in six murine tumor cell lines and their corresponding syngeneic tumors using qPCR, immunofluorescence, and immunohistochemistry. Correlations between BLMH expression and tumor response to ECT were assessed both in vitro and in vivo. Results: BLMH expression varied significantly among tumor models, without consistent patterns across cancer types. In vitro, BLMH mRNA levels strongly correlated with IC30 values for bleomycin (R = 0.74), while the correlation weakened at IC50 doses, suggesting enzyme saturation. In vivo, BLMH expression levels moderately correlated with complete tumor response rates following ECT (R = 0.50). Differences between in vitro and in vivo expression highlighted the role of the tumor microenvironment. Conclusions: High BLMH expression reduces tumor sensitivity to bleomycin-based ECT, supporting its role as a predictive biomarker. Measuring BLMH levels may help stratify patients and personalize ECT application; however, it is not the sole factor for response prediction. Future studies in clinical tumor samples are warranted to evaluate its predictive value and to develop integrated biomarker models.

The development of safer, more effective, and tumor-specific therapeutic strategies remains a major challenge in oncology. Conventional treatments such as chemotherapy and radiotherapy often cause severe side effects and are limited in their ability to target deep-seated or resistant tumors. In this context, sonodynamic therapy (SDT) has emerged as a promising, non-invasive option, harnessing low-intensity ultrasound to activate sonosensitizers deep within tissues and generate cytotoxic reactive oxygen species (ROS) that selectively induce cancer cell death. Interestingly, SDT can also be combined with other therapies to achieve synergistic effects. However, despite encouraging preclinical results, SDT clinical translation is hindered by the poor aqueous solubility, instability, and low tumor specificity of traditional sonosensitizers. To overcome these limitations, recent studies have focused on employing extracellular vesicles (EVs), especially exosomes, as natural, biomimetic nanocarriers for sonosensitizer delivery. EVs offer unique advantages, including high biocompatibility, low immunogenicity, and intrinsic tumor-targeting ability, which make them ideal platforms for improving the therapeutic precision of SDT. Although several delivery strategies have been proposed, a comprehensive and focused overview of approaches specifically designed to enhance SDT performance using EVs is currently lacking. This review summarizes recent advances in integrating EVs with SDT for cancer treatment. It discusses the mechanisms underlying SDT, the engineering strategies developed to enhance exosome functionality, and the synergistic effects achieved through this combination. Furthermore, this review emphasizes that EV-based SDT not only enhances tumor accumulation of the therapeutic nanoplatforms, but also actively remodels the tumor microenvironment by improving oxygen availability, reversing immunosuppressive conditions, and triggering durable antitumor responses. Finally, the review addresses the translational challenges and outlines the critical future directions required to advance this promising therapeutic approach toward clinical application.

Background: Ewing sarcoma (ES) is a rare, aggressive small round cell sarcoma (SRCS) that peaks in adolescence. Given its rarity, atypical age or site presentations increase the risk of misclassification. This study examines age-related clinicopathological patterns in molecularly confirmed canonical ES (FET::ETS-fused). Methods: Between 2016 and 2025, 90 tumors diagnosed as ES or Ewing-like SRCSs underwent targeted RNA sequencing and/or EWSR1 break-apart fluorescence in situ hybridization. Patients were stratified into three age groups: 0-18, 19-39, and ≥40 years. Clinical, anatomical, pathological, molecular, and treatment/outcome variables were compared across strata. Results: Canonical ES accounted for 84% (76/90) of SRCSs, dominated by EWSR1::FLI1 (89%). ES comprised 91% of SRCSs in children but declined to 75% in older adults. Tumors arose mainly in bone (63%), with a significant age association (p = 0.016): children and young adults were primarily skeletal (73% and 62%), whereas older adults were predominantly extraskeletal (78%). Renal ES clustered in adults ≥40 years (p = 0.003). Classic histology predominated; atypical patterns were more common in extraskeletal tumors but lacked age specificity. Ewing-like SRCSs (n = 14), with heterogeneous or absent fusions, displayed a broader age distribution-including infants and older adults-and a marked extraskeletal predominance (86%, p = 0.001). Metastatic presentation strongly predicted inferior survival (p = 0.025). Treatment was multimodal, with neoadjuvant chemotherapy more frequent in children (90%, p = 0.029). Conclusions: Age significantly influences anatomic presentation and certain treatment choices in ES, whereas histology and survival remain broadly similar across groups. Age-linked extraskeletal trends reinforce the importance of routine molecular testing, particularly in underreported Middle Eastern populations.