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Single-cell RNA sequencing of murine tumor-susceptible germ cells

ABSTRACT: Single-cell RNA sequencing of murine tumor-susceptible germ cells

PROVIDER: PRJNA661059 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12572805.fastq.gz	Fastqsanger.gz
	SRR12572806.fastq.gz	Fastqsanger.gz
	SRR12572807.fastq.gz	Fastqsanger.gz
	SRR12572808.fastq.gz	Fastqsanger.gz
	SRR12572809.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing of murine tumor-susceptible germ cells

Project description:In response to signals from the embryonic testis, germ cell intrinsic factor NANOS2 coordinates a sex-specific transcriptional program necessary for differentiation of pluripotent-like primordial germ cells toward a unipotent spermatogonial stem cell fate. Emerging evidence indicates that genetic risk factors contribute to testicular germ cell tumor initiation by disrupting sex-specific differentiation. Here, using a mouse model of spontaneous testicular teratomas, we report that a subpopulation of germ cells failing to express NANOS2 is enriched for developmental phenotypes required for tumorigenesis. We demonstrate that only in the absence of NANOS2 do germ cells have a transcriptional profile enriched for Myc signaling and primed pluripotency and transform into embryonal carcinoma cells. We conclude that NANOS2 is the nexus through which many genetic risk factors exert their influence on tumor susceptibility. We propose that NODAL signaling, which is present in the developing testis, drives germ cell transformation in the absence of sex specification.

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The Immune Effects of Fermented Wheat Germ Nutritional Supplementation in Patients With Advanced Solid Tumor Cancers Being Treated With Standard of Care Checkpoint Inhibitors

Project description:This phase I clinical trial tests the immune effects of fermented wheat germ in patients with advanced solid tumor cancers who are being treated with standard of care checkpoint inhibitors. Fermented wheat germ is a nutritional supplement that some claim is a "dietary food for special medical purposes for cancer patients" to support them in treatment. There have also been claims that fermented wheat germ is "clinically proven" and "recognized by medical experts" to "enhance oncological treatment" and boost immune response to cancer; however, there are currently no documented therapeutic effects of fermented wheat germ as a nutritional supplement. Checkpoint inhibitors, given as part of standard of care for advanced solid tumors, are a type of immunotherapy that may help the body’s immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. The information gained from this trial may allow researchers to determine if there is any value of giving fermented wheat germ with standard of care checkpoint inhibitors for patients with advanced solid tumor malignancies.

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Identification of factors secreted by testicular germ cell tumor cell lines and microenvironmental cells.

Project description:Type II germ cell tumors (GCTs) are the most common neoplasia in young men of age 14-45 years. It is generally accepted that GCTs arise from a common precursor lesion, called germ cell neoplasia in situ (GCNIS), eventually developing into seminomas or non-seminomas, such as (embryonal carcinomas, ECs). The latter stem-cell like EC can further differentiate into teratomas (TE), yolk-sac tumors (YST), or choriocarcinomas (CC). Even though cisplatin-based chemotherapy is an efficacious standard of care during the management of GCT patients, the development of cisplatin resistance remains a major obstacle. As such, the surrounding tumor microenvironment and its secreted factors could endorse the development of drug resistance. These stromal cells, including immune cells (e.g. macrophages, T-lymphocytes), endothelial cells, and fibroblasts, can influence tumor cells by promoting proliferative and anti-apoptotic signaling pathways. Vice versa, microenvironmental cells can be influenced by tumor cells as well. For the identification of secreted proteins, cell lysates and supernatants from seven human germ cell tumor cell lines (seminoma: TCam-2; embryonal carcinoma (EC): 2102EP, NCCIT; choriocarcinoma (CC): JAR, JEG-3), yolk-sac tumor (YST): GCT72; 1411H) and five human cell types from the microenvironment (fibroblasts: MPAF, HVHF2; M2 macrophages: THP-1-M2; T-lymphocytes: JURKAT; endothelial cells: HUVEC) have been evaluated using liquid chromatography coupled with mass spectrometry (LC-MS).

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Expression data from testicular germ cell tumor cells

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