Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies

Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103205 - 103205

Published: May 21, 2024

Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In endometrium, local conditions induced by hormonal fluctuations and endometrial vascular remodeling contribute to production HIF-1α, which plays an indispensable role in series physiological activities, such as menstruation metamorphosis. The sensitive regulation HIF-1α maintains cellular viability regenerative capacity endometrium against stresses hypoxia excess reactive oxygen species. contrast, abnormal levels exacerbate development various pathologies. This knowledge opens important possibilities for promising HIF-1α-centered strategies ameliorate disease. Nonetheless, additional efforts are required elucidate regulatory network promote applications human endometrium. Here, we summarize HIF-1α-mediated pathway physiology pathology, highlight latest treating diseases, improve receptivity.

Language: Английский

The Role of YY1 in the Regulation of LAG-3 Expression in CD8 T Cells and Immune Evasion in Cancer: Therapeutic Implications

Cancers, Journal Year: 2024, Volume and Issue: 17(1), P. 19 - 19

Published: Dec. 25, 2024

The treatment of cancers with immunotherapies has yielded significant milestones in recent years. Amongst these immunotherapeutic strategies, the FDA approved several checkpoint inhibitors (CPIs), primarily Anti-Programmed Death-1 (PD-1) and Programmed Death Ligand-1/2 (PDL-1/2) monoclonal antibodies, various unresponsive to immune therapeutics. Such treatments resulted clinical responses prolongation survival a subset patients. However, not all patients responded CPIs, due mechanisms resistance. One such mechanism is that, addition PD-1 expression on CD8 T cells, other inhibitory receptors exist, as Lymphocyte Activation Gene 3 (LAG-3), cell Immunoglobulin Mucin (TIM3), immunoreceptor Ig ITIM domains (TIGIT). These might be active presence above CPIs. Clearly, it clinically challenging block simultaneously using conventional antibodies. To circumvent this difficulty, we sought target potential transcription factor that may involved molecular regulation more than one receptor. Yin Yang1 (YY1) was found regulate PD-1, LAG-3, TIM3. Therefore, hypothesized targeting YY1 cells should inhibit and, thus, prevent inactivation anti-tumor by receptors, corresponding ligands tumor cells. This strategy result prevention evasion, leading inhibition growth. In addition, will particularly effective cancer who were review, discuss LAG-3 proof principle for use an alternative therapeutic approach preventing evasion cancer. We present findings regulations both expressions, direct YY1, approaches evade their challenges. also bioinformatic analyses demonstrating overexpression PD-L1 cancers, associations infiltrates, fact when hypermethylated its promoter region correlates better overall survival. Hence, restoring response regression. Notably, beneficial effects suggest overexpressed which YY1-associated pro-tumorigenic activities.

Language: Английский

Perspective review: lessons from successful clinical trials and real-world studies of systemic therapy for metastatic pheochromocytomas and paragangliomas

Therapeutic Advances in Medical Oncology, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 1, 2024

Pheochromocytomas and paragangliomas (PPGLs) are orphan tumors with the potential to spread distant organs such as lymph nodes, skeleton, lungs, liver. These metastatic exhibit high rates of morbidity mortality due their frequently large tumor burden, progression disease, excessive secretion catecholamines that lead cardiovascular disease gastrointestinal dysmotility. Several molecular drivers responsible for development PPGLs have been described over last 30 years. Although therapeutic options limited, substantial progress has made in recognition effective systemic therapies these tumors. Successful clinical trials radiopharmaceuticals high-specific-activity meta-iodobenzylguanidine tyrosine kinase inhibitors cabozantinib sunitinib recently published. This review will discuss results studies impact on current practices. In addition, this provide valuable information how design treat patients novel medications.

Language: Английский