A prospective observational study evaluating intestinal microbiome as a biomarker to predict the efficacy and toxicity of BRCA1/2 mutant metastatic castration resistant prostate cancer patietns receiveing PARP inhibitors
Ontology highlight
ABSTRACT:
DISEASE(S): Prostate Cancer
PROVIDER: 2695487 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: case series:None
Primary outcome(s): side effects
Study Design: Sequential
| 2707329 | ecrin-mdr-crc
Project description:The majority of prostate cancer (PCa) cases are diagnosed as a localized disease. Definitive treatment, active surveillance or watchful waiting are employed as therapeutic paradigms. The current standard of care for the treatment of metastatic PCa is either medical or surgical castration. Once PCa progresses in spite of castrate androgen levels it is termed 'castration-resistant prostate cancer' (CRPC). Patients may even exhibit rising PSA levels with possible bone, lymph node or solid organ metastases. In 2010, the only agent approved for the treatment of CRPC was docetaxel, a chemotherapeutic agent. It is now known that cells from patients with CRPC express androgen receptors (AR) and remain continuously influenced by androgens. As such, treatments with novel hormonal agents that specifically target the biochemical conversion of cholesterol to testosterone have come to the forefront. The use of cytochrome P450c17 (CYP17A1) inhibitor underlies one of the most recent advances in the treatment of CRPC. Abiraterone acetate (AA) was the first CYP17A1 inhibitor approved in the United States. This review will discuss CRPC in general with a specific focus on AA and novel CYP17A1 inhibitors. AA clinical trials will be reviewed along with other novel adjunct treatments that may enhance the effectiveness of abiraterone therapy. Furthermore, the most recently identified CYP17A1 inhibitors Orteronel, Galeterone, VT-464, and CFG920 will also be explored.
| S-EPMC4323677 | biostudies-literature
Project description:Prostate cancer (PCa) metastasis is considered the leading cause of cancer death in males. Therapeutic strategies and diagnosis for stage-specific PCa have not been well understood. Rho guanine nucleotide exchange factor 38 (ARHGEF38) is related to tumor cell polarization and is frequently expressed in PCa. Microarray data of PCa were downloaded from GEO and TCGA databases. A total of 243 DEGs were screened, of which, 32 genes were upregulated. The results of enrichment analysis showed the participation of these DEGs in the tumor cell metastasis pathway. ARHGEF38 was significantly up-regulated in the four most prevalent cancers worldwide (p < 0.05), and its expression was higher in the tumor samples with higher Gleason score (GS). IHC, qRT-PCR, and western-blot analyses showed the higher expression of ARHGEF38 in PCa than benign prostatic hyperplasia (BPH). In addition, IHC results demonstrated a higher expression of ARHGEF38 in high-grade PCa than the low-grade PCa.
| S-EPMC7083745 | biostudies-literature
Project description:affy_molecularmechanism_medicago - affy_molecularmechanism_medicago - -Aphanomyces euteiches (Ae), a soilborne oomycete, is the causal agent of pea root rot, a major disease on various cultivated legume species. To gain insight into the mechanism underlying partial resistance to this pathogen, a pathosystem has been developed using the model legume Medicago truncatula (Mt). Two Mt accessions A17 and F83005.5 have been shown to display differential responses upon infection with Ae (partially resistance and susceptibility, respectively). Genetic analyses using a RIL population derived from a cross between those two lines lead to the identification of, prAe1, a major QTL involved in the observed partial resistance. Near isogenic lines (NIL) NR2 and NS2 whose genomes are identical except at the prAe1 locus (resistant alleles for NR2, susceptible alleles for NS2) have been generated, and the same differential response toward Ae has been found. The aim of this experiment is to analyse and compare NR2 and NS2 transcriptomes at 1 and 6 days after Ae inoculation to identify gene networks that are regulated in a prAe1 dependent manner.--Fifteen-day-old NR2 or NS2 plants were grown in vitro on M medium. The entire roots were then inoculated (or not = 0dpi) with a A. euteiches zoospores (75000zsp/ml) and harvested one or six days after inoculation. Three independent repeats were performed.
2014-02-28 | GSE31198 | GEO
Project description:Protein profiles of insecticide resistance Ae. aegypti in Penang island, Malaysia
2022-04-14 | MSV000089259 | MassIVE
Project description:affy_molecularmechanism_medicago - affy_molecularmechanism_medicago - -Aphanomyces euteiches (Ae), a soilborne oomycete, is the causal agent of pea root rot, a major disease on various cultivated legume species. To gain insight into the mechanism underlying partial resistance to this pathogen, a pathosystem has been developed using the model legume Medicago truncatula (Mt). Two Mt accessions A17 and F83005.5 have been shown to display differential responses upon infection with Ae (partially resistance and susceptibility, respectively). Genetic analyses using a RIL population derived from a cross between those two lines lead to the identification of, prAe1, a major QTL involved in the observed partial resistance. Near isogenic lines (NIL) 5B2 and 5D2 whose genomes are identical except at the prAe1 locus (resistant alleles for 5B2, susceptible alleles for 5D2) have been generated, and the same differential response toward Ae has been found. The aim of this experiment is to analyse and compare 5B2 and 5D2 transcriptomes at 1 and 6 days after Ae inoculation to identify gene networks that are regulated in a prAe1 dependent manner.--Fifteen-day-old 5B2 or 5D2 plants were grown in vitro on M medium. The entire roots were then inoculated (or not = 0dpi) with a A. euteiches zoospores (75000zsp/ml) and harvested one or six days after inoculation. Three independent repeats were performed. 18 arrays - Medicago; resistance vs susceptibility comparison,time course,treated vs untreated comparison
2014-02-28 | E-GEOD-31198 | biostudies-arrayexpress
Project description:BACKGROUND:Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, or the combination) enhance anti-tumor immune responses, yielding durable clinical benefit in several cancer types, including melanoma. However, a subset of patients experience immune-related adverse events (irAEs), which can be severe and result in treatment termination. To date, no biomarker exists that can predict development of irAEs. METHODS:We hypothesized that pre-treatment antibody profiles identify a subset of patients who possess a sub-clinical autoimmune phenotype that predisposes them to develop severe irAEs following immune system disinhibition. Using a HuProt human proteome array, we profiled baseline antibody levels in sera from melanoma patients treated with anti-CTLA-4, anti-PD-1, or the combination, and used support vector machine models to identify pre-treatment antibody signatures that predict irAE development. RESULTS:We identified distinct pre-treatment serum antibody profiles associated with severe irAEs for each therapy group. Support vector machine classifier models identified antibody signatures that could effectively discriminate between toxicity groups with >?90% accuracy, sensitivity, and specificity. Pathway analyses revealed significant enrichment of antibody targets associated with immunity/autoimmunity, including TNF? signaling, toll-like receptor signaling and microRNA biogenesis. CONCLUSIONS:Our results provide the first evidence supporting a predisposition to develop severe irAEs upon immune system disinhibition, which requires further independent validation in a clinical trial setting.
| S-EPMC5880088 | biostudies-literature
Project description:Lung adenocarcinomas with mutant epidermal growth factor receptor (EGFR) respond to EGFR-targeted tyrosine kinase inhibitors (TKIs), but resistance invariably occurs. We found that the Janus kinase (JAK)/signal transduction and activator of transcription 3 (STAT3) signaling pathway was aberrantly increased in TKI-resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells. JAK2 inhibition restored sensitivity to the EGFR inhibitor erlotinib in TKI-resistant cell lines and xenograft models of EGFR-mutant TKI-resistant lung cancer. JAK2 inhibition uncoupled EGFR from its negative regulator, suppressor of cytokine signaling 5 (SOCS5), consequently increasing EGFR abundance and restoring the tumor cells' dependence on EGFR signaling. Furthermore, JAK2 inhibition led to heterodimerization of mutant and wild-type EGFR subunits, the activity of which was then blocked by TKIs. Our results reveal a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC.
| S-EPMC4950506 | biostudies-literature
Project description:Purpose: This study gives insight into transcriptomic dynamics and the set of important candidate acting as modules to regulate the changes in resistant NIL upon M.oryzae infection. Methods: Rice leaves were collected after M. Oryza (Mo-nwi-53) infection from resistant NILs and suceptible line were frozen in liquid nitrogen. RNA was extracted using Spectrum™ Plant Total RNA Kit (Sigma). Standard Illumina protocols was used for preparing RNA sequencing libraries. Results: Around 30 million pairs of filtered 101 base paired reads were obtained for each biological replicate. Conclusions: Pathway, gene set enrichment and co-expression analysis of SDEL unique to each resistant NIL respectively decipher the common broad spectrum resistance mechanism found in resistant NIL and provide important candidate genes.
2019-12-04 | GSE117030 | GEO
Project description:Cell toxicity may result in organ dysfunction and cause severe health problem. Recent studies revealed many toxicants may induced the over production of Nitric oxide, reactive oxygen species and the subsequent oxidative stress, cause cell toxicity. Mitochondrion dysfunction maybe the subsequent consequence of oxidative stress and has been recognized as another contributing factor in cell toxicity. Besides, oxidative products induced by some toxicants may also produce the compounds that damage cell DNA, leading to toxicity. Especially, the significance of nanoparticle induced cell toxicity was disclosed recently and attract more concern. The mechanism mainly includes inflammation, oxidative stress and DNA damage. On the other side, some biomarkers of cell toxicity including autophagy, cytokines, miRNA has been identified. The understanding of these phenomenon may enable us to clarify the cell toxicity mechanism then contribute to cell toxicity protection, disease treatment and drug side effect prevention.
| S-EPMC6206310 | biostudies-other