Angiogenic systemic response to the hypoxic microenvironment in prostate tumorigenesis: A pilot study

Abstract

The present paper aimed to investigate the altered angiogenetic mechanisms in hypoxic conditions in patients with prostate tumours, in correlation with common clinicopathologic variables. A case-control study was developed and included 87 patients with prostate tumours [40 diagnosed with benign prostatic hyperplasia (BPH) and 47 diagnosed with prostate cancer (PCa), using prostate transrectal biopsy] and 40 healthy subjects. The following parameters were evaluated in the serum of volunteers: Hypoxia-inducible factor (HIF)-1α, fibroblast growth factor (FGF)-2, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and -9, thrombospondin (TSP)-1 and soluble VEGF-1 receptor. Experimental data analysis demonstrated increasing amounts of inflammation in patients with PCa (IL-6, 18.1±4.7 ng/ml) and BPH (IL-6, 16.3±5.1 ng/ml) vs. control (IL-6, 4.1±1.2 ng/ml); overregulation of HIF1α in patients with PCa (129.3±21.8 ng/ml) compared with patients with BPH (65.6±18.2 ng/ml) and control (61.3±12.7 ng/ml); angiogenesis abnormalities in patients with PCa (upregulation of FGF-2, VEGF, MMP-2 and -9, suppression of TSP-1 and soluble VEGR-1) and BPH (upregulation FGF-2 and VEGF) compared with the control group. In conclusion, a greater understanding of the biological mechanism, the pathological roles and the clinical significance of various proangiogenic parameters and angiogenic-suppressor proteins seem useful in clinical practice for establishing an early diagnosis of prostate pathology and finding an individualized therapeutic approach.

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas—A Narrative Review

“…An increase in ROS results in the activation of the NLRP3 inflammasome and the release of pro-inflammatory cytokines, which suppress immune surveillance, allowing tumor progression. Persistent stress increases susceptibility to cancer and enhances RCC's capacity to develop secondary manifestations through a variety of mechanisms: tumor signaling, TME reorganization, immune evasion, invasion and metastasis, DNA mutations, angiogenesis, treatment response, and induction of cellular ferroptosis/apoptosis [13,[25][26][27]. Potential inducers of cellular stress from within and outside cells are excessive amounts of oxidants [15].…”

“…Recently, a transcription factor for the oxidative stress response, broad complex-tramtrack-bric-a-brac and cap 'n' collar homology 1 (BACH1), has been labeled an essential factor involved in RCC progression in vivo [32]. BACH1-mediated RCC evolution contributes to increased invasion and migration abilities, activation of epithelial-mesenchymal transition, dysregulation of inflammatory responses, immunomodulation, cytoprotection, the anti-inflammatory response, angiogenesis, mTOR, increased tumor metabolism, and the metastatic potential [23][24][25]32,33].…”