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Transcriptional CDK inhibitors as potential treatment option for testicular germ cell tumors

ABSTRACT: Transcriptional CDK inhibitors as potential treatment option for testicular germ cell tumors

PROVIDER: PRJNA814284 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18280500.fastq.gz	Fastqsanger.gz
	SRR18280501.fastq.gz	Fastqsanger.gz
	SRR18280502.fastq.gz	Fastqsanger.gz
	SRR18280503.fastq.gz	Fastqsanger.gz
	SRR18280504.fastq.gz	Fastqsanger.gz

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Transcriptional CDK inhibitors as potential treatment option for testicular germ cell tumors

Project description:Type II testicular germ cell tumors (TGCT) are the most frequently diagnosed solid malignancy in young men. Up to 15 % of patients with metastatic non-seminomas show cisplatin resistance having a very poor survival rate due to lacking treatment options. Transcriptional cyclin-dependent kinases (CDK) have been shown to be effective targets in treatment of different types of cancer. Here, we investigated the effects of the CDK inhibitors dinaciclib, flavopiridol, YKL-5-124, THZ1, NVP2, SY0351 and THZ531. XTT viability assay revealed strong cytotoxic impact of CDK7/ 12/ 13 inhibitor SY0351 and CDK9 inhibitor NVP2 on the TGCT wild type cell lines (2102EP, NCCIT, TCam2) and the cisplatin resistant cell lines (2102EP-R, NCCIT-R). The CDK7 inhibitor YKL-5-124 showed strong impact on 2102EP, 2102EP-R, NCCIT and NCCIT-R cell lines leaving the MPAF control cell line mostly unaffected. FACS based analysis revealed mild effects on the cell cycle of 2102EP and TCam2 cells after SY0351, YKL-5-124 or NVP2 treatment. Molecular analysis showed a cell line specific response for SY0351 and NVP2 inhibition while YKL-5-124 induced similar molecular changes in 2102EP, TCam2 and MPAF cells. Thus, after TGCT subtype determination CDK inhibitors might be a potential alternative for optimized and individualized therapy independent of chemotherapy sensitivity.

2022-03-26 | GSE198248 | GEO

Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors.

Project description:Type II testicular germ cell tumors (TGCT) are the most frequently diagnosed solid malignancy in young men. Up to 15% of patients with metastatic non-seminomas show cisplatin resistance and a very poor survival rate due to lacking treatment options. Transcriptional cyclin-dependent kinases (CDK) have been shown to be effective targets in the treatment of different types of cancer. Here, we investigated the effects of the CDK inhibitors dinaciclib, flavopiridol, YKL-5-124, THZ1, NVP2, SY0351 and THZ531. An XTT viability assay revealed a strong cytotoxic impact of CDK7/12/13 inhibitor SY0351 and CDK9 inhibitor NVP2 on the TGCT wild-type cell lines (2102EP, NCCIT, TCam2) and the cisplatin-resistant cell lines (2102EP-R, NCCIT-R). The CDK7 inhibitor YKL-5-124 showed a strong impact on 2102EP, 2102EP-R, NCCIT and NCCIT-R cell lines, leaving the MPAF control cell line mostly unaffected. FACS-based analysis revealed mild effects on the cell cycle of 2102EP and TCam2 cells after SY0351, YKL-5-124 or NVP2 treatment. Molecular analysis showed a cell-line-specific response for SY0351 and NVP2 inhibition while YKL-5-124 induced similar molecular changes in 2102EP, TCam2 and MPAF cells. Thus, after TGCT subtype determination, CDK inhibitors might be a potential alternative for optimized and individualized therapy independent of chemotherapy sensitivity.

| S-EPMC8997165 | biostudies-literature

CDK inhibitors and flavopiridol profiling on A2780 and MCF7 cells

Project description:This SuperSeries is composed of the following subset Series: GSE18486: CDK inhibitors PHA-848125 and PHA-690509 profiling on A2780 GSE18498: CDK inhibitor PHA-793887 profiling on A2780 GSE18501: CDK inhibitor PHA-848125 gene expression profiling on MCF7 cell line GSE18504: Flavopiridol profiling on A2780 GSE19638: Compounds profiling on MCF7 Refer to individual Series

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CDK inhibitors PHA-848125 and PHA-690509 profiling on A2780

Project description:The effects of the CDK inhibitors PHA-848125 and PHA-690509 on the A2780 cell line were analysed by gene expression profiling. The A2780 cell line was treated with PHA-848125 (CDk-125) or PHA-690509 (CDk-509) for 6 hours at a dose equal to 5 times the IC50. Untreated A2780 cells were used as a control. Three replicates per treatment.

2010-07-14 | E-GEOD-18486 | biostudies-arrayexpress

CDK inhibitors PHA-848125 and PHA-690509 profiling on A2780

Project description:The effects of the CDK inhibitors PHA-848125 and PHA-690509 on the A2780 cell line were analysed by gene expression profiling.

2010-07-14 | GSE18486 | GEO

Digital gene expression (DGE) based transcript profiling of CDK inhibitors

Project description:We compare differences in gene expression induced after 6 hours of exposure to one of three CDK4/6 inhibitors or a pan-CDK inhibitor

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Testicular germ cell tumors and their histological subgroups

Project description:Normal, premalignant and various histological subtypes of testicular germ cell tumor (TGCT) tissues were hybridized against Universal Human Reference RNA (Stratagene) onto Agilent 60mer oligo microarrays (GEO accession no GPL885). In vitro time series of two TGCT cell lines, NTERA2 and 2102Ep, treated with retinoic acid for 0, 3, and 7 days were also included. The data set (30 hybridizations) is particularly useful for comparisons between various histological subtypes of TGCT versus each other or versus normal testis. Keywords = 2102Ep Keywords = Agilent oligo microarrays Keywords = carcinoma in situ Keywords = choriocarcinoma Keywords = development Keywords = developmental biology Keywords = differenciation Keywords = embryogenesis Keywords = embryonal carcinoma Keywords = homo sapiens Keywords = human Keywords = human development Keywords = intratubular germ cell tumor Keywords = nonseminoma Keywords = NTera2 Keywords = pluripotency Keywords = pluripotent Keywords = retinoic acid Keywords = seminoma Keywords = teratocarcinoma Keywords = teratoma Keywords = testis Keywords = testicular germ cell tumor Keywords = testicular neoplasm Keywords = totipotency Keywords = totipotent Keywords = undifferentiated Keywords = universal human reference RNA (Stratagene) Keywords = yolk sac tumor Keywords: other

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Role of MIR9-2 in testicular germ cell tumours

Project description:The testicular germ cell tumour cell lines were transfected with MIR9-2-5p mimic to study the effect on gene expression by RNA sequencing.

2024-04-15 | GSE232791 | GEO

Genomic Screening of Testicular Germ Cell Tumors from Monozygotic Twins

Project description:Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development.

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Identification of 22 novel susceptibility loci associated with testicular germ cell tumors [ATAC-seq]

Project description:To investigate the role of the testicular germ cell tumor cells in complex traits, we generated ATAC-seq and Promoter Focused Capture C to gain insight into the gene regulatory arcitecture contacting promoters in an testicular cell line NT2-D1 model of testicular cancer

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