Discover. Oncology最新文献

Background: Helicobacter pylori (H. pylori) infection is a major pathogen associated with gastric cancer. However, the causal relationship between H. pylori infection and extra-gastric tumors has not been fully elucidated.

Methods: A two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) data on serum H. pylori IgG levels as the exposure variable and GWAS data on 268 benign and malignant tumors as the outcome variable. Single nucleotide polymorphisms (SNPs) associated with the exposure were identified from the OpenGWAS and GWAS Catalog databases, while those linked to the outcome were sourced from the FinnGen database. Independent MR analyses were performed on the discovery and validation cohorts. Sensitivity analyses, including heterogeneity and pleiotropy assessments, were conducted to ensure the robustness of the results. Meta-analysis was used to integrate significant findings from both cohorts.

Results: Our findings demonstrated negative causal effects of H. pylori infection on benign neoplasms of cranial nerves and extrahepatic bile ducts in both discovery and validation cohorts. Moreover, we found a potentially positive causal link between H. pylori infection and certain malignancies of the hypopharynx, kidney, lip, brain, pancreas, and neuroendocrine system, as well as malignant immunoproliferative diseases and leukemia, although these results were only observed in a single cohort. Sensitivity analyses showed no significant heterogeneity or horizontal pleiotropy in the significant MR directions, supporting the reliability of the results. Meta-analysis further confirmed the protective effect of H. pylori infection on benign cranial nerve and extrahepatic bile duct tumors.

Conclusion: This study revealed that H. pylori infection is causally associated with extra-gastric tumors, suggesting a potential protective role of H. pylori infection in certain benign tumors.

Bladder cancer ranks as the 11th most frequent form of cancer and is the most common malignancy of urinary tract cells. A major contributor to bladder cancer development is oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and is found to regulate oxidative stress in cancer cells. This study aimed to investigate the relationship between oxidative stress and the NRF2/TAZ pathway in bladder cancer. In this study, a total of 35 bladder cancer patients and 35 healthy subjects were recruited. The expression of NRF2 and TAZ genes was evaluated using real-time PCR. Total Oxidant Status (TOS) and total antioxidant capacity (TAC) of the samples were measured. Our findings revealed a higher expression of NRF2 (p < 0.001) and TAZ (p < 0.001) mRNA in cancerous tissue as compared to healthy subjects. We also found that there is a positive correlation between tumor grading and NRF2 (r = 0.522, p = 0.001) as well as TAZ (r = 0.462, p = 0.02) genes mRNA expression. Also, our results revealed that there is a significant correlation between TAZ and NRF2 genes mRNA expression in bladder cancer patients. Furthermore TAC level was considerably lower in bladder cancer patients (p < 0.01), while the TOS level was significantly higher compared to the control group(p < 0.05). Finally, our findings suggested that NRF2 and TAZ, as transcriptional factors, are associated with higher grades of bladder cancer as well as oxidative stress in patients with bladder cancer.

Hodgkin lymphoma is a rare lymph node malignancy that has the presence of Reed-Sternberg cells. We describe a case of a 72-year-old male with progressive bilateral cervical and inguinal lymphadenopathy with the absence of constitutional symptoms. Primary clinical and radiographic assessment was in favor of an infectious or metastatic etiology. Classical Hodgkin lymphoma was confirmed by excisional biopsy of the lymph nodes that demonstrated classic Reed-Sternberg cells in a polymorphous inflammatory background. Additional support to the diagnosis was provided by immunohistochemistry. The patient was staged at Ann Arbor stage IIIB disease and sent to oncologic care, where he was placed on systemic chemotherapy. The case demonstrates that persistent lymphadenopathy can be a hard-to-detect disease, particularly in tuberculosis-endemic regions, and that a timely biopsy and comprehensive evaluation are necessary to avoid diagnostic lag time and offer treatment before it is too late.

Estrogen receptor α (ERα) is a key therapeutic target in ER-positive breast cancer. Structurally, ERα contains activation function (AF) domains that drives breast cancer proliferation, metastasis, and drug resistance through classical genomic, non-genomic, and ligand-independent signaling pathways. Clinically approved and investigational drugs targeting Erα include selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators/degraders (SERDs), and novel strategies such as proteolysis-targeting chimeras (PROTACs). Current research focuses on overcoming endocrine resistance via combination therapies targeting mutations in ESR1, the gene encoding ERα, non-genomic signaling pathways, and the tumor microenvironment, which may advance precision medicine in breast cancer. This article summarizes recent advances in ERα-targeting inhibitors and their therapeutic implications, to provide potential precision therapeutic strategies for breast cancer patients with ER positive.