Int. J. Transl. Med., Volume 4, Issue 3 (September 2024) – 3 articles

Background: Tissue factor pathway inhibitors (TFPI1 and TFPI2) are ubiquitously distributed in humans and exhibit inhibitory activity against serine proteinases. TFPI1 inhibits the tissue factor (TF)-dependent extrinsic coagulation pathway, while TFPI2 modulates extracellular matrix remodeling. TFPI2 has been reported to be an epigenetically silenced tumor suppressor and independent prognostic factor in various human cancers. However, elevated serum levels of TFPI2 have been observed in ovarian and endometrial cancers compared to healthy controls, with increased levels correlating with poor prognosis in endometrial cancer. This raises the question of why the tumor suppressor TFPI2 is elevated in the blood of patients with gynecological cancers and is associated with adverse outcomes. Methods: A comprehensive literature search was performed in PubMed and Google Scholar without time restriction. Results: TFPI2 gene expression may be influenced by both cancer cell-specific gene expression profiles (e.g., oncogenic signaling pathways) and epigenetic modifications (e.g., DNA methylation, histone modifications, and non-coding RNAs). Although TFPI2 generally exhibits an anti-invasion effect in most human cancers, it has been reported to have a paradoxical pro-invasive effect in certain cancers. TFPI2 facilitates cancer invasion through aberrant alternative splicing or through a pathophysiological process known as angiotropism or vasculogenic mimicry. The overproduction of TFPI2 in the tumor microenvironment may reinforce the extracellular matrix, thereby enhancing tumor cell adhesion and invasion. Conclusion: This review summarizes the current understanding of the seemingly contradictory functions of TFPI2 in human malignancies, primarily focusing on the mechanisms regulating its expression and function, and discusses future prospects for translational research. Full article

While existing local therapies partially restore vision loss from diabetic retinopathy (DR), there is currently no reliable treatment to prevent the onset or stop the progression of the disease. This review seeks to explore the inflammatory molecular mechanisms underpinning DR pathogenesis, which have not been targeted by current interventions. Specifically, this review explores the role of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) inflammasome in DR onset and progression. Evidence through clinical trials has begun to note that specific drugs (fenofibrate, metformin) appear effective in slowing DR progression independent of lipid or glucose-lowering, respectively, suggesting that other mechanisms are at play. Novel therapeutics that inhibit the activation of the NLRP3 inflammasome pathway may provide a novel treatment for halting DR progression. Full article

Gastric gastrointestinal stromal tumors (GIST) are rare, neuroectodermal tumors primarily residing in the stomach with characteristic genetic mutations. They are often identified using ultrasound and cross-sectional imaging, or they are noted during endoscopy. Localized gastric GISTs are commonly treated with surgical resection, with the possible use of neoadjuvant or adjuvant medical therapies as they are considered to have malignant potential. The use of tyrosine kinase inhibitors (TKI) such as imatinib has been shown to successfully reduce pre-operative tumor burden, recurrence, and disease progression. Surgical resection considerations vary depending on tumor size, location, and malignant potential. Neoadjuvant and adjuvant TKI therapy dosing varies in response to the type of GIST mutation present and greatly influences prognosis. Novel cooperative minimally invasive surgical techniques and targeted therapies are currently in development to address challenges in GIST treatment for tumors in challenging locations or with significant potential for progression. The management of localized gastric GISTs continues to rapidly evolve; each case should be managed individually, where care is taken in considering details, including tumor location, tumor size, and the molecular genetic profile, before embarking on a course of treatment. Full article