Discover. Oncology最新文献

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor prognosis, where radiotherapy is a key treatment modality. However, radioresistance significantly limits its efficacy, leading to treatment failure. Septin9 (SEPT9), a cytoskeletal regulatory protein, has been implicated in various cancers, with its methylation status serving as a biomarker for diagnosis and prognosis. While extensively studied in colorectal cancer, the role of SEPT9 and its methylation in ESCC remains unclear. This study aimed to investigate the role of SEPT9 in ESCC and its potential as a predictive biomarker. SEPT9 expression and methylation levels were analyzed in 80 ESCC patients undergoing radiotherapy using qMS-PCR and immunohistochemistry (IHC). Functional experiments using SEPT9-knockout (KO) and overexpressing (Sep) ESCC cell lines were conducted in in vitro and in vivo models. The results demonstrated that SEPT9 overexpression enhances radiosensitivity, while SEPT9-knockout promotes radioresistance. Additionally, higher SEPT9 methylation correlated with radioresistance and poor survival. These findings indicate a potential association between SEPT9 methylation and radiotherapy response in ESCC. While promising, further validation is needed before SEPT9 methylation can be established as a reliable clinical biomarker or therapeutic target.

Background: Mesenchymal stem cell (MSC)-derived exosomes revealed therapeutic ability, particularly in cancer treatment, by transferring bioactive molecules like miRNAs. Hypoxia, a common tumor condition, influences both tumor progression and MSC behavior. This review explores how hypoxic conditions affect MSC-derived exosomes and their impact on cancer-related pathways and genes.

Method: The current systematic review study was conducted by searching four different databases, including PubMed, Scopus, Embase, and Web of Science, using keywords such as mesenchymal stem cells, exosomes, hypoxia, cancer, and related terms. All original pre-clinical studies that focused on the role and effect of hypoxia in MSC-derived extracellular vesicles in different cancers were included. Data were collected qualitatively.

Result: Overall, 264 articles were identified from searching in databases, and eight of them met the eligibility criteria and were included in the current study. Among the articles, four focused on lung cancer, two on breast cancer, one on hepatocellular carcinoma, and one on Multiple Myeloma. The results indicated that MSC-derived exosomes have an enhanced effect on cell viability, migration, proliferation, and invasion of cancerous cells both in vitro and in vivo settings, and also cause a reduction in apoptosis in these cells. Besides, hypo MSC-exosomes can change the expression of some miRNAs in cancer cells, which affect different signaling pathways.

Conclusion: In general, the current study suggests that hypoxia-preconditioning of MSC-derived exosomes can influence specific genes, miRNAs, and signaling pathways in cancer cells, leading to increased proliferation, migration, and invasion, as well as decreased apoptosis. Besides, the biological effects of hypoxia-modulated exosomes seem to be significantly context-dependent. Although they may exacerbate malignancy in cancer microenvironments, analogous pathways can also facilitate tissue repair and regeneration in non-cancerous situations.

Introduction: Breast cancer is the most prevalent malignancy among women worldwide. A significant portion of patients possess homologous recombination deficiency (HRD), often caused by BRCA1/2 mutations, which may sensitize tumors to PARP inhibitors and platinum-based chemotherapy through synthetic lethality. Since mutations in BRCA genes have been previously suggested in association with impaired biology of telomeres, in the present study we investigated leukocyte telomere length (LTL) to evaluate its potential utility as a biomarker for BRCA1 mutations and HRD.

Methodology: LTL was measured using multiplex monochrome real-time qPCR in four groups: breast cancer patients with pathogenic hereditary BRCA1 mutations (n = 99), age-matched non-cancerous controls carrying the same BRCA1 mutations (n = 99), breast cancer patients with wild-type BRCA1 (n = 105), and age-matched non-cancerous controls with wild-type BRCA1 (n = 107). BRCA1 mutations were tested by the DNA sequencing approach.

Results: A significant negative correlation between age and LTL was observed across all studied groups, except in breast cancer patients carrying pathogenic hereditary BRCA1 mutations. Interestingly, after adjusting for age, BRCA1 mutation carriers had shorter LTL compared to non-carriers, regardless of the presence of cancer (P = 0.024).

Conclusion: LTL shortening is associated with BRCA1 mutations, regardless of cancer status. Further validation studies are needed.