Growth Hormone Action as a Target in Cancer: Significance, Mechanisms and Possible Therapies DOI Creative Commons
Reetobrata Basu, César Luiz Boguszewski, John J. Kopchick

et al.

Endocrine Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Growth hormone (GH) is a pituitary derived endocrine required for normal post-natal growth and development. Hypo or hypersecretion of GH results in two pathologic conditions, namely deficiency (GHD) acromegaly. Additionally, also produced non-pituitary tumoral tissues where it acts rather as cellular factor with an autocrine/paracrine mode action. An increasingly persuasive large body evidence over the last 70 years concur that action implicit escalating several cancer-associated events, locally systemically. This pleiotropy GH's effects puzzling, but association cancer-risk automatically raises concern patients acromegaly individuals treated GH. By careful assessment available knowledge on fundamental concepts cancer, suggestions from epidemiological clinical studies, specific reports, this review we aimed to help clarify distinction vs. promoting cancer reconcile discrepancies between experimental data. Along discourse, critically weigh targetability - firstly by detailing molecular mechanisms which posit critical node tumor circuitry, secondly, enumerating currently therapeutic options targeting On basis our discussion, infer targeted intervention appropriate patient population can benefit sizeable subset current prognoses.

Language: Английский

Growth hormone signaling and clinical implications: from molecular to therapeutic perspectives DOI
Zahra Aghili,

Golnoosh Khoshnevisan,

Rezvan Mostoli

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 4, 2025

Language: Английский

Citations

0
Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer DOI Open Access
Reetobrata Basu, Prateek Kulkarni,

Deborah Swegan

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7438 - 7438

Published: July 6, 2024

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)-GH receptor (GHR) pair a covert driver multimodal in cancer and overexpressed PDAC tumors, yet the therapeutic potential targeting same has not been explored. Here, we report that GHR expression negative prognostic factor patients with PDAC. Combinations gemcitabine different antagonists (GHRAs) markedly improve outcomes nude mice xenografts. Employing cultured cells, mouse xenografts, analyses human transcriptome, identified attenuation multidrug transporter epithelial-to-mesenchymal transition programs tumors underlie observed augmentation chemotherapy efficacy GHRAs. Moreover, patients, strongly correlates gene signature tumor promotion immune evasion, which corroborate syngeneic wild-type vs. GH transgenic mice. Overall, found action promoted therapy-refractory vivo, can be effectively attenuated antagonism. Our results collectively present proof concept toward considering to chemotherapeutic highly chemoresistant

Language: Английский

Citations

2
Transition Period and Young Adulthood in Patients with Childhood Onset Growth Hormone Deficiency (COGHD): Impact of Growth Hormone Replacement on Bone Mass and Body Composition DOI Open Access
Mirjana Doknić, Marko Stojanović, Aleksandra Marković

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10313 - 10313

Published: Sept. 25, 2024

The aim of this review article is to highlight the consequences COGHD after end linear growth on bone mass and body composition opposing beneficial effects continuing GH replacement in transition period young adults. role hormone late adolescence adulthood well established, mainly achieving peak a favorable composition, characterized by muscle increase fat reduction. Patients with childhood onset deficiency (COGHD), reaching adult height, have reduced mineral density increased compared healthy controls. Inadequate predictor for cardiovascular risk, while low early youth hallmarks risk osteoporosis fractures later life. Cessation (GHr) completion will lead delayed unbalanced abdominal deposits. According numerous clinical studies monitoring treatment physical psychological status patients persistent GHD growth, we suggest between 16 25 years age. It advised that GHr be administered intermediate doses those pediatric population population. Usual daily are 0.3 0.5 mg but need individually optimized, maintaining IGF-I age-specific normal range.

Language: Английский

Citations

0
Growth Hormone Action as a Target in Cancer: Significance, Mechanisms and Possible Therapies DOI Creative Commons
Reetobrata Basu, César Luiz Boguszewski, John J. Kopchick

et al.

Endocrine Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Growth hormone (GH) is a pituitary derived endocrine required for normal post-natal growth and development. Hypo or hypersecretion of GH results in two pathologic conditions, namely deficiency (GHD) acromegaly. Additionally, also produced non-pituitary tumoral tissues where it acts rather as cellular factor with an autocrine/paracrine mode action. An increasingly persuasive large body evidence over the last 70 years concur that action implicit escalating several cancer-associated events, locally systemically. This pleiotropy GH's effects puzzling, but association cancer-risk automatically raises concern patients acromegaly individuals treated GH. By careful assessment available knowledge on fundamental concepts cancer, suggestions from epidemiological clinical studies, specific reports, this review we aimed to help clarify distinction vs. promoting cancer reconcile discrepancies between experimental data. Along discourse, critically weigh targetability - firstly by detailing molecular mechanisms which posit critical node tumor circuitry, secondly, enumerating currently therapeutic options targeting On basis our discussion, infer targeted intervention appropriate patient population can benefit sizeable subset current prognoses.

Language: Английский

Citations

0