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Low hypoxia inducible factor-1? (HIF-1?) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

ABSTRACT: The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-1? (HIF-1?) expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.

SUBMITTER: Shenoy N

PROVIDER: S-EPMC5592826 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

Shenoy Niraj N Dronca Roxana R Quevedo Fernando F Boorjian Stephen A SA Cheville John J Costello Brian B Kohli Manish M Witzig Thomas T Pagliaro Lance L

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20170801 4

The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology le ...[more]

PMID: 28947870

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Project description:IntroductionSystemic sclerosis is an autoimmune disease characterized by tissue fibrosis and microangiopathy. Vascular changes such as a decrease in capillary density diminish blood flow and impair tissue oxygenation. Reliable ways to monitor disease activity and predict disease progression are desired in the process of patient selection for clinical trials and to optimize individual patient outcomes. Hypoxia-inducible factor-1 (HIF-1) is a dimeric protein complex that plays an integral role in the body's response to hypoxia. Our study aimed to investigate the potential abnormalities of HIF-1α plasma concentration and its possible association with disease activity and vascular abnormalities in patients with systemic sclerosis.MethodsBlood plasma levels of HIF-1α were measured in patients with systemic sclerosis (n = 50) and in healthy individuals (n = 30) using commercially available ELISA test kits.ResultsThe results showed a marked increase in HIF-1α levels in patients with systemic sclerosis (3.042 ng/ml [2.295-7.749]) compared to the control group (1.969 ng/ml [1.531-2.903] p < 0.01). Patients with diffuse cutaneous SSc (2.803 ng/ml, IQR 2.221-8.799) and limited cutaneous SSc (3.231 ng/ml, IQR 2.566-5.502) exhibited elevated serum HIF-1α levels compared to the control group (p < 0.01). We found a notable increase in HIF-1α plasma concentration in patients with an "active" pattern (6.625 ng/ml, IQR 2.488-11.480) compared to those with either an "early" pattern (2.739, IQR 2.165-3.282, p < 0.05) or a "late" pattern (2.983 ng/ml, IQR 2.229-3.386, p < 0.05). Patients with no history of digital ulcers had significantly higher levels of HIF-1α (4.367 ng/ml, IQR 2.488-9.462) compared to patients with either active digital ulcers (2.832 ng/ml, IQR 2.630-3.094, p < 0.05) or healed digital ulcers (2.668 ng/ml, IQR 2.074-2.983, p < 0.05).ConclusionsOur results indicate that HIF-1α may serve as a biomarker in assessing microcirculatory changes in individuals with systemic sclerosis.

Dataset Information

Low hypoxia inducible factor-1? (HIF-1?) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

Publications

Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

Similar Datasets

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