-
[The role of the tumor microenvironment and BAP1 protein expression in the prognosis of uveal melanoma].3 days agoUveal melanoma is the most common primary malignant tumor of the eye. It is characterized by a low mutational burden and a limited response to immunotherapy, which is largely attributable to the immune-privileged status of the eye. Decreased expression of the BAP1 protein and specific features of the tumor microenvironment may influence disease prognosis, but its prognostic significance remains insufficiently investigated.
This study aimed to assess the impact of tumor microenvironment characteristics and BAP1 expression levels on survival in patients with uveal melanoma.
Retrospective analysis included 58 patients (58 eyes) with stage IIIA-IIIC uveal melanoma who underwent eye enucleation between 2014 and 2023 at the Moscow Regional Research and Clinical Institute (MONIKI). All specimens were subjected to morphological examination and immunohistochemical analysis using antibodies against BAP1, CD4, CD8, CD20, and CD68. Survival was evaluated using the Kaplan-Meier method, and the influence of prognostic factors was assessed using the Cox proportional hazards model.
Uniform or heterogeneous loss of BAP1 expression was detected in 55.2% of tumors and was associated with poorer survival compared with tumors retaining BAP1 expression (p=0.009). Presence of at least one immune marker (CD4+, CD8+, or CD68+) also correlated with worse prognosis (p=0.036). The most unfavorable outcomes were observed in cases combining BAP1 loss with the presence of these immune cells (p=0.01; HR=4.49; 95% CI: 1.63-12.37). No deaths were recorded in the subgroup of patients with preserved BAP1 expression and absence of CD4+, CD8+, and CD68+ cells.
Loss of BAP1 expression in combination with immune cell infiltration in the tumor microenvironment is associated with an increased risk of mortality in uveal melanoma. Combined assessment of BAP1 and immune markers enables more accurate patient stratification and refinement of prognostic evaluation.CancerAccessCare/ManagementAdvocacy -
OVCA2 acts as an oncogene in pediatric AML by negatively regulating CDKN1A to drive cell cycle progression.3 days agoPediatric acute myeloid leukemia (AML) is biologically distinct from adult AML and carries a poor prognosis. OVCA2, a serine hydrolase with context-dependent roles, has unknown function in AML. We aimed to investigate its role, regulation, and clinical significance in pediatric AML.
OVCA2 was identified as a downstream target of a pediatric AML-specific core transcriptional regulatory circuit using CUT&Tag integrative analysis. Expression and prognostic associations were assessed in TARGET (pediatric) and TCGA (adult) datasets. Functional validation via lentiviral shRNA knockdown was performed in MV4-11 and Kasumi-1 cells using CCK-8, colony formation, and cell cycle assays. RNA-seq and GSEA elucidated mechanisms. Co-knockdown of CDKN1A tested functional rescue.
OVCA2 was significantly upregulated in AML and correlated with worse overall survival exclusively in the pediatric cohort. Knockdown impaired proliferation, colony formation, and induced G1 arrest, with reduced C-MYC and CDK2 levels. Transcriptomic analysis revealed activation of 'Negative Regulation of Cell Population Proliferation' pathway, with CDKN1A as a top upregulated gene. Co-knockdown of CDKN1A partially rescued the anti-proliferative effect.
OVCA2 acts as a novel oncogene in pediatric AML by transcriptionally repressing CDKN1A to drive cell cycle progression. Its age-specific prognostic association and origin from a pediatric AML core regulatory circuit highlight its role in age-related regulatory networks.
OVCA2 represents a promising therapeutic target in pediatric AML, with its effects mediated through CDKN1A repression.CancerCare/ManagementPolicy -
Plasticity, signaling, and metabolic rewiring in melanoma persister cells.3 days agoDespite advances in therapy, survival rates for metastatic melanoma remain low. Drug-tolerant persister cells (persisters) can facilitate cancer recurrence, yet their characteristics and vulnerabilities differ across cancers and even within melanoma, depending on mutational context and treatment strategy. Both preexisting phenotypic traits and drug-induced adaptations contribute to persister formation, linked by "primed" persisters that exhibit intermediate states observed in multiple studies. Compared with parental melanoma cells and other phenotypic variants such as melanoma stem cells or senescent cells, persisters show altered and reversible differentiation programs, distinct metabolic adaptations, and rewired signaling networks, all affected by the tumor microenvironment, but remain poorly understood. This review focuses on melanoma persisters, highlighting advances in understanding their origins, signaling plasticity, metabolic rewiring, and therapeutic vulnerabilities. By identifying gaps, this review further provides much-needed recommendations for future research and outlines priorities for advancing persister-directed interventions toward clinical translation.CancerCare/Management
-
Placental mesenchymal dysplasia: diagnostic and management insights from a case report and literature review.3 days agoLimited awareness of placental mesenchymal dysplasia (PMD) and the diagnostic challenges in differentiating it from partial hydatidiform moles on imaging often lead to inappropriate management. This study presents a case report and literature review to elucidate the etiology, clinical features, and management of PMD.
The patient was admitted with a history of amenorrhea lasting over two months and experiencing vaginal bleeding for four days. Ultrasonography at 12 weeks of gestation revealed extensive cystic changes within the placenta, and was subsequently corroborated by magnetic resonance imaging. The differential diagnosis comprised placental structural abnormalities indicative of PMD or a hydatidiform mole. The patient opted to terminate the pregnancy citing concerns regarding an unfavorable prognosis. Placental pathology confirmed PMD. Fetal short tandem repeat analysis revealed a biparental diploid, whereas the placenta demonstrated androgenetic and biparental chimerism. Postoperative serial monitoring indicated a progressive decrease in serum β-hCG level, and no signs of gestational trophoblastic disease or other maternal complications were observed.
PMD should be considered when prenatal ultrasonography reveals cystic placental lesions, typically manifested as cystic or hypoechoic regions within an enlarged placenta and often accompanied by mildly elevated maternal serum β-hCG levels. The fetal karyotype is typically normal, with a predominance of females. Pathological examination demonstrates a considerably enlarged placenta characterized by vesicular, grape-like structures on its surface. Some mothers may develop complications such as hypertensive disorders of pregnancy, while adverse perinatal outcomes-such as preterm delivery or stillbirth due to fetal distress or malformations-may also occur. However, a considerable proportion of maternal and fetal outcomes remains favorable. Enhanced maternal and fetal monitoring in PMD pregnancies has the potential to enhance perinatal outcomes.CancerCare/Management -
Berberine enhances cisplatin efficacy in ehrlich ascites carcinoma via modulation of apoptotic pathway and efferocytosis.3 days agoBerberine, a bio-alkaloid from medicinal plants, shows therapeutic potential against various ailments, including cancer. This study evaluated berberine's effects on the PI3K/Akt pathway and efferocytosis in an adenocarcinoma model to reduce cisplatin chemotherapy side effects and Ehrlich ascites carcinoma (EAC) proliferation. Eighty Swiss albino mice were divided into eight groups: control, berberine, cisplatin, cisplatin & berberine, EAC, EAC & berberine, EAC & cisplatin, and EAC & cisplatin & berberine. Tumor response, weight change, cell count, survival analysis, biochemical analysis, molecular studies, and histopathological assessment were performed. Results showed berberine enhanced cisplatin's antitumor efficacy in EAC-bearing mice by reducing tumor volume and cell counts. Berberine ameliorated cisplatin's hepato-renal toxicity and downregulated Akt1, Axl, Mertk, and Gas6 gene expression. Histopathological analysis showed berberine's ability to recover cisplatin's lethal effects on liver tissue. In conclusion, berberine showed promising effects on the PI3K/Akt pathway and efferocytosis, reducing cisplatin's side effects and EAC proliferation.CancerCare/Management
-
MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumor growth.3 days agoCholangiocarcinoma (CCA) comprises a heterogeneous group of biliary malignant tumors with poor prognosis and limited therapeutic options. Recent studies have highlighted the role of the immune system in the development and progression of intrahepatic CCA (iCCA). In this study, we investigated the role of the scavenger receptor MARCO in iCCA. Employing transcriptomic, spatial proteomic and histological analyses of human samples, MARCO was found on a specific subtype of tumor-associated macrophages linked to immunosuppression and extracellular matrix remodeling within the tumor microenvironment. High MARCO expression in human iCCA tumors correlated with worse overall survival, T cell dysfunction and increased collagen deposition. In line with this, MARCO expression was associated with a TH2-skewed immune response and was increased in macrophages exposed to IL-4 and IL-13. Marco-/- mice were protected against iCCA development, exhibiting reduced tumor burden, fewer innate immune cells related to TH2 responses and attenuated fibrosis. Moreover, Marco-/- mice exhibited lower levels of immunosuppressive markers on macrophages and cytotoxic T cells, resulting in improved overall survival and reduced lung metastases in an orthotopic tumor model. The use of an anti-MARCO antibody further reduced tumor volume in wild-type mice. This study identifies MARCO as a key regulator of immunosuppression, fibrosis and tumor progression in iCCA, and supports its potential as a novel therapeutic target for macrophage-directed immunotherapy.CancerCare/Management
-
Impact of line-field optical coherence tomography in preoperative margin assessment of head and neck basal cell carcinoma: a cohort study.3 days agoIn head-and-neck basal cell carcinoma (BCC), accurate preoperative delineation of lateral tumour margins remains challenging. Line-field confocal-optical coherence tomography (LC-OCT) offers real-time, high-resolution imaging that may improve surgical planning. This study evaluated the impact of preoperative LC-OCT on oncologic and procedural outcomes, focusing on lateral positive margins.A mixed prospective-retrospective cohort study was conducted, comparing BCC cases treated after LC-OCT implementation (2023-2024) with historical controls (2018-2021). Lesions with unclear clinical or dermoscopic margins underwent LC-OCT-guided mapping. Primary outcomes were positive histological margins and recurrence; secondary outcomes included time to surgery, operative time, frozen section use, reconstruction, and minimum lateral margin distance. Multivariable logistic regression adjusted for group, age, tumour size, H-zone location, presentation, histologic subtype, and pT stage.A total of 102 patients were included (LC-OCT n = 23; controls n = 79). H-zone distribution was comparable between groups (69.5% vs 53.2%, P = 0.50). Positive margins occurred in 19.0% vs 24.6% (P = 0.772), and recurrence in 0% vs 5.2% (P = 0.573). Median time to surgery was longer with LC-OCT (48 vs 34 days, P = 0.016), while operative time was shorter (55 vs 95 minutes, P = 0.013).In multivariable analysis, H-zone location (aOR 3.96, P = 0.041) and aggressive histology (aOR 6.39, P = 0.015) predicted lateral positivity, whereas LC-OCT did not (aOR 1.61, P = 0.565; AUC 0.774).LC-OCT did not independently reduce lateral positive margins but may support precision mapping, at the cost of longer treatment timelines. Prospective studies with standardized workflows are warranted.CancerCare/Management
-
[Current status of artificial intelligence applications in cervical cancer screening: a systematic review].3 days agoObjective: To systematically summarize and evaluate the current application status and research progress of artificial intelligence (AI) in cervical cancer screening in China. Methods: Literature related to the application of AI in cervical cancer screening in China was searched in PubMed, Embase, Cochrane Library, IEEE, China National Knowledge Infrastructure (CNKI), and Wanfang Database using the keywords"cervical cancer","artificial intelligence","screening","machine learning","deep learning","neural network","uterine cervical neoplasms,"uterine cervical tumor","diagnosis", and"China". The search was limited to studies published in Chinese and English. As of July 2025, a total of 35 eligible articles were included. Basic information from the included studies was extracted and summarized. In addition, the National Medical Products Administration (NMPA) official website was searched using the term"cervix"to identify approved AI-assisted cervical cancer screening products. Results: A total of 21 AI-assisted cervical cancer screening technologies were identified, including 17 technologies for primary screening, mainly AI-assisted cytology, and 4 technologies for colposcopic diagnosis. For AI-assisted cytology, the sensitivity ranged from 67.5% to 100.0% and the specificity ranged from 9.9% to 99.8% in hospital-based populations, with the overall accuracy of some technologies exceeding 90%. In community-based screening populations, the sensitivity ranged from 83.0% to 100.0% and the specificity ranged from 74.2% to 99.9%. Most studies suggested that AI could improve the diagnostic performance of pathologists to some extent, shorten the average slide-reading time, and enhance overall screening efficiency. A total of 24 AI-assisted cervical cancer screening products have been approved by the NMPA, all of which are AI-assisted cytology technologies, and corresponding studies were identified for 8 of these products. For AI-assisted colposcopic diagnosis used as a standalone screening modality, the sensitivity and specificity for identifying cervical intraepithelial neoplasia grade 2 (CIN2) or worse ranged from 43.6% to 95.5% and from 51.8% to 93.9%, respectively; for cervical intraepithelial neoplasia grade 3 (CIN3) or worse, the sensitivity ranged from 35.1% to 97.5% and the specificity ranged from 56.6% to 87.2%. In the physician-assisting mode, the sensitivity increased to 95.1%-97.5%, with improvements in interobserver consistency and diagnostic accuracy among less experienced colposcopists. Conclusions: AI has shown promising potential in cervical cancer screening in China. However, more scientific evidence is needed to determine whether it can be effectively integrated into the existing cervical cancer prevention and control system in China.CancerCare/Management
-
Clinical Presentation, Misdiagnosis, and Imaging Findings of Anterior Disc Herniations.3 days agoAnterior and anterolateral lumbar disc herniations are uncommon and usually do not present with classic radicular symptoms. This contributes to a broader and sometimes misleading differential diagnosis based on the initial presentation. When identified on cross-sectional imaging performed for nonspinal indications, displaced disc material can be mistaken for a retroperitoneal mass, potentially prompting additional imaging or invasive evaluation. We report six cases of anterior and anterolateral disc herniations identified on CT and MRI, including some patients presenting with abdominal or flank pain. Imaging demonstrated anterior disc extrusion, some with marked inflammatory changes. In some cases, the initial diagnosis included retroperitoneal neoplasm or an inflammatory process. Recognizing this imaging pattern and its clinical context may help accurate diagnosis, avoid unnecessary procedures, and guide appropriate management.CancerCare/Management
-
Clinical Utility of Body Weight Monitoring During Cisplatin-based Chemotherapy.3 days agoAcute kidney injury (AKI) is one of the most frequent adverse effects induced by cisplatin (CDDP). One clinical indicator of CDDP-induced AKI is urine output, which reflects water balance; however, urine collection can expose healthcare workers to anticancer drugs. An alternative monitoring approach for CDDP-induced AKI is weight-based assessment of fluid balance. Although previous studies have evaluated the relationship between body weight change and CDDP-induced AKI, few have evaluated the amount of water ingested. Therefore, we evaluated water intake, urine output, and body weight changes in patients treated with CDDP to determine the utility of weight monitoring as an indicator of fluid balance during CDDP-based chemotherapy.
We evaluated 15 patients who received CDDP-vinorelbine as postoperative adjuvant chemotherapy for non-small cell lung cancer from March to December 2019. Patients recorded their oral fluid intake, and body weight changes were evaluated on days 2-4 relative to baseline on day 1.
No cases of CDDP-induced AKI occurred. Compared with day 1, urine output decreased on day 2 but recovered on day 3. Body weight fluctuations were highest (+3.6 kg) on day 3 and started decreasing on day 4. Serum creatinine and estimated glomerular filtration rate did not differ significantly pre- and post-chemotherapy. A positive correlation was observed between water balance and next-morning weight change (r=0.68).
Weight monitoring may reduce healthcare workers' exposure to anticancer agents while serving as a practical indicator of fluid balance during CDDP-based chemotherapy.CancerChronic respiratory diseaseCare/Management