ARTICLE | doi:10.20944/preprints202103.0273.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: testicular germ cell tumors (TGCTs); human seminoma; p75 neurotrophin receptor (p75NTR); p75NTR -signaling.
Online: 9 March 2021 (14:52:34 CET)
Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr=40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in tumor tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway, and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK, and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker of differentiation in TGCTs.
REVIEW | doi:10.20944/preprints201709.0069.v1
Subject: Life Sciences, Biochemistry Keywords: Glyoxalases; urological malignancies; prostate cancer; kidney cancer; bladder cancer testicular cancer
Online: 15 September 2017 (14:28:24 CEST)
Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide and although advances have been made toward understanding the molecular basis of these diseases, a complete insight of the pathogenic mechanisms is still a research challenge for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these neoplasms for which no effective therapies exist. Glyoxalases are enzymes that catalyzes the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggest that glyoxalases, especially Glo1, would act as oncogenes in urological malignancies and be central to their initiation, growth and progression. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-PCa therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.
REVIEW | doi:10.20944/preprints202208.0163.v1
Subject: Medicine & Pharmacology, Urology Keywords: STAT3; prostate cancer; bladder cancer; upper tract urothelial carcinoma; renal cell carcinoma; penile cancer; testicular cancer
Online: 8 August 2022 (15:09:21 CEST)
Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.