Study on the function of intestinal flora in castration treatment of prostate cancer complicated with metabolic syndrome
Ontology highlight
ABSTRACT:
DISEASE(S): Prostate Cancer
PROVIDER: 2692103 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Prostate cancer development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Androgen deprivation therapy (ADT) provides short-term efficacy for patient treatment, but inevitably promotes a castration-resistant phenotype with poor prognosis. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for prostate cancer patients who have poor expected outcomes and/or receive ADT. Here we show that there is a dynamic balance between sortilin and syndecan-1 that reports on different metabolic phenotypes. Sortilin, enhances glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, syndecan-1 interacts with LPL and β3 integrin, to promote lipid metabolism and this process is upregulated in androgen-insensitive cells. We report a hitherto unappreciated molecular mechanism for prostate cancer, which has significance for disease progression and how ADT may promote castration-resistant prostate cancer.
2023-08-21 | GSE220618 | GEO
Project description:Hypoxia is associated with poor prognosis in solid tumours and hypoxia has been associated with prostate cancer progression. The investigation of how chronic (CH) hypoxia affected prostate cancer show a loss in sensitivity to androgen deprivation and increased dependancy on glucose uptake in cells.
2023-04-06 | GSE227811 | GEO
Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration. We compare the gene expression of 5 LuCaP35 xenografts from non-treated mice (Control), and 5 androgen-deprived LuCaP35 xenografts from castrated mice (Castration).
2011-12-06 | E-GEOD-33316 | biostudies-arrayexpress
Project description:Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and use of a vertebrate 'insulin-free' model to identify insulin-independent modulators of glucose metabolism. insulin knockout zebrafish recapitulate core characteristics of diabetes and survive only up to larval stages. Utilizing a highly efficient endoderm transplant technique, we generated viable chimeric adults that provide the large numbers of insulin mutant larvae required for our screening platform. Using glucose as a disease-relevant readout, we screened 2233 molecules and identified 3 that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels. Our study proposes therapeutic roles for androgen signaling in diabetes and, more broadly, offers a novel in vivo model for rapid screening and decoupling of insulin-dependent and -independent mechanisms.
2018-12-13 | PXD012027 | Pride
Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration.
2011-12-06 | GSE33316 | GEO
Project description:A subpopulation of prostate luminal epithelial cells has been previously reported to be sufficient to regenerate prostatic architecture following consecutive rounds of androgen deprivation/repletion. This functional characteristic suggest prostate luminal epithelial cells as the putative cell-of-origin for castration-resistant prostate cancer - which more notizable fenotype is the lack of response to androgen deprivation thereapy. We used microarrays to profile the androgen-induced transcripts in luminal prostate epithelial cells involved in a cycle of prostate regression/regeneration in Hoxb13-rtTA|TetO-H2BGFP transgenic mice.
2021-04-06 | GSE171490 | GEO
Project description:To assess the effect of sleep deprivation on glucose metabolism and elucidate the mechanism, we established the mouse model wth C57BL/6J that is useful for the intervention on sleep deprivation associated diabetes and evaluate the liver metabolism and gene expression. Single six hours sleep deprivation induced increased hepatic glucose production assessed by pyruvate tolerance test and the hepatic triglyceride content was significantly higher in the sleep deprivation group than freely sleeping control group. Liver metabolites such as ketone bodies were increased in sleep deprivation group. Some gene expressions which associated with lipogenesis were increased.
2016-12-27 | GSE92913 | GEO
Project description:Following androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics. Experiment Overall Design: To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI).
2008-04-07 | E-GEOD-8702 | biostudies-arrayexpress
Project description:Prostate tumor cells growth is interconected to androgen signaling. Indeed, the main line of treatment for advanced prostate cancer is focused on inhibiting androgen signaling by either surgical or pharmacological castration (or androgen-ablation, e.g. degarelix). We used microarrays to detail the global programme of gene expression following androgen-deprivation therapy (ADT) and identified distinct classes of up-regulated genes during this process that could contribute to the development of castration resistance.
2021-04-06 | GSE171491 | GEO
Project description:In order to understand the mechanism associated with SIRT1-mediated development of prostate cancer progression, we conducted RNA-sequencing analysis in SIRT1 suppressed hormone sensitive prostate cancer cells (LNCaP) under conditions of androgen sufficiency, deprivation, androgen stimulation or AR suppression.
2021-05-22 | GSE152820 | GEO