Dataset Information

Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

ABSTRACT:

Context

Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass.

Objective

To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients.

Methods

Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry.

Results

Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 μm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 μm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (-12% ± 12% and -20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 μm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 μm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05).

Conclusion

The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.

SUBMITTER: Overkamp M

PROVIDER: S-EPMC10505531 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

Overkamp Maarten M Houben Lisanne H P LHP Aussieker Thorben T van Kranenburg Janneau M X JMX Pinckaers Philippe J M PJM Mikkelsen Ulla R UR Beelen Milou M Beijer Sandra S van Loon Luc J C LJC Snijders Tim T

The Journal of clinical endocrinology and metabolism 20230901 10

<h4>Context</h4>Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass.<h4>Objective</h4>To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients.<h4>Methods</h4>Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or r ...[more]

PMID: 37161470

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Project description:BACKGROUND:Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS:Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP. RNA microarray, mass spectrometry, integrative transcriptomic and proteomic differential analysis coupled with GeneOntology and multivariate analyses were applied to identify deregulated genes and proteins involved in CRPC evolution. RESULTS:Treating the androgen-responsive LNCaP cell line for over a year with 10 ?M bicalutamide both in the presence and absence of 0.1 nM 5-?-dihydrotestosterone (DHT) we obtained two cell sublines, designated PDB and MDB respectively, presenting several analogies with CRPC. Molecular and functional analyses of PDB and MDB, compared to the parental cell line, showed that both resistant cell lines were PSA low/negative with comparable levels of nuclear androgen receptor devoid of activity due to altered phosphorylation; cell growth and survival were dependent on AKT and p38MAPK activation and PARP-1 overexpression; their malignant phenotype increased both in vitro and in vivo. Performing bioinformatic analyses we highlighted biological processes related to environmental and stress adaptation supporting cell survival and growth. We identified 15 proteins that could direct androgen-resistance acquisition. Eleven out of these 15 proteins were closely related to biological processes involved in PCa progression. CONCLUSIONS:Our models suggest that environmental factors and epigenetic modulation can activate processes of phenotypic adaptation driving drug-resistance. The identified key proteins of these adaptive phenotypes could be eligible targets for innovative therapies as well as molecules of prognostic and predictive value.

Project description:BackgroundAndrogen deprivation therapy (ADT) in patients with prostate cancer can have several debilitating side effects. Supervised exercise is recommended to ameliorate these negative effects.ObjectiveTo systematically evaluate the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer undergoing ADT, primarily according to the patient critical outcomes, 'disease-specific quality of life' and 'walking performance' measured at end of treatment.MethodsWe searched PubMed/Medline, Embase, Cochrane Library, Cinahl and Pedro, to identify randomised controlled trials (RCTs), which investigated the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer receiving ADT, last search: June 2021. Two independent reviewers extracted data, and assessed risk of bias using Cochrane Risk of Bias Tool and evaluated the certainty of evidence using the GRADE-method.ResultsEigthteen RCTs (n = 1477) comprised patients with prostate cancer stages T1-T4 were included in the meta-analyses. Compared to no exercise therapy, supervised exercise therapy showed clinically relevant improvements in 'disease-specific quality of life' and 'walking performance'. The standardised mean differences were 0.43 (95% confidence interval (CI): 0.29, 0.58) and -0.41 (95% CI: -0.60, -0.22), respectively. The overall certainty of evidence was moderate due to serious risk of bias.ConclusionsEvidence of moderate quality shows that supervised exercise therapy probably is superior to no exercise therapy in improving 'disease-specific quality of life' and 'walking performance' in patients with prostate cancer undergoing ADT. The results apply to all patients receiving androgen deprivation therapy regardless of cancer stage. The results support a strong recommendation for supervised exercise therapy for managing side effects in this population.Protocol registrationNKR-38-Focused-questions-PICOs-for-updating1.ashx (sst.dk).

Dataset Information

Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

Context

Objective

Methods

Results

Conclusion

Publications

Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

Similar Datasets

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