Project description:The fetal ovarian grafts under the kidney capsule of adult male mice undergo a partial sex-reversal showing ectopic SOX9-positive Sertoli cell-like cells around 15-20 days post-transplantation. However, the molecular bases of such masculinization of fetal ovaries in the paternal environment were unclear. We examined the temporal changes of the gene expression profiles of the grafted fetal ovaries during the partial masculinizing process in the male nude mice.
Project description:<p>Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from mutations or duplications in the BRAF kinase in specific subclasses, few genetic driver events are known. Diffuse PLGGs compose a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. These tumors are particularly poorly understood. We performed high-resolution copy-number analysis of 44 diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gains, was observed in 28% of diffuse astrocytoma WHO grade II (DA2) and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene MYB on 6q23.3. Whole genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Two truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth when expressed in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. "Reprinted from www.pnas.org/cgi/doi/10.1073/pnas.1300252110 with permission from PNAS." </p>
Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts Tumor fragments derived from 7 patients with MIBC were grafted under the renal capsule of NOD-SCID mice and subsequently transplanted to further mice over multiple generations. Patient tumor and xenograft tissue were processed for analysis of , gene expression by microarray, and expression of select potential target pathways by immunohistochemistry (IHC).
Project description:There has been growing interest in the relationship between maternal undernutrition and reproductive disorders in male offspring. In the present study, we determined the effects of maternal calorie restriction throughout the critical period for in utero development of the male reproductive system, termed the “masculinization programming window” on the reproductive system of mice. The intratesticular testosterone concentration of the fetuses of calorie-restricted (R) dams was lower than in control fetuses at 17.5 days post coitum. In addition, there was global down-regulation of genes encoding steroidogenic enzymes and a low sperm count in the offspring of R dams (R-offspring) at 6 weeks of age. Microarray analysis of the testes of the offspring identified dysregulation of several genes that might explain the derangement in spermatogenesis in the R-offspring. Thus, the present study provides insights into the impact of maternal undernutrition on the male reproductive system in mice. The deleterious effects probably originate in lower androgen exposure during the “masculinization programming window.”
Project description:Vanin1, a regulator of vitamin B5 metabolism, is expressed by sarcoma tumors. We evaluated its impact on sarcoma growth by using sarcoma cell lines derived from p16p19Vnn1-deficient mice and further transduced with an oncogenic RasV12 oncogene (R tumors) in the presence or not of a catalytically active (VR tumors) or mutated (VdR tumors) Vnn1 isoform. We used microarrays to detail the global programme of gene expression associated with the growth potential of various tumor cell lines grafted in Nude mice
Project description:This batch of data is for three independent projects. Since in this three projects, the mouse strains are all CD1/ICR, the sex are both female, and the mouse ages are all two-month-old, three projects shared control data to save expenditure legitimately. But in our hand we couldn't segregate the raw data into two parts corresponding to two projects, so we uploads all raw data. However, we also provided researcher-analyzable excel files including the expression of all phosphorylated proteins. The concise description of these three projects are as follow: Project 1: We found that in Chronic Resistant Stress (CRS)-treated mice, the fertility and oocyte quality significantly decreased, and plenty of biochemical indexes significantly changed, so we guessed that the overall physical health of CRS mice was severely impacted. As one major strategy to investigate the mechanism how CRS impact the physical health, We chose TMT-labeled quantitative ovarian phosphoproteomics service from Hangzhou PTM Bio Co. We sent two repeats of two-month-old CRS CD1/ICR mouse ovaries and two repeats of control ovaries for characterization of differentially phosphorylated proteins. Each repeat contained about 60 ovaries from 30 female mice, about 300 mg. Project 2: We found that in High Salt (HS)-treated mice, the fertility and oocyte quality significantly decreased, and plenty of biochemical indexes significantly changed, so we guessed that the overall physical health of HS mice was severely impacted. As one major strategy to investigate the mechanism how HS impact the physical health, We chose TMT-labeled Quantitative ovarian phosphoproteomics service from Hangzhou PTM Bio Co. We sent two repeats of two-month-old HS CD1/ICR mouse ovaries and two repeats of control ovaries for characterization of differentially phosphorylated proteins. Each repeat contained about 60 ovaries from 30 female mice, about 300 mg. Project 3: We found that in arecoline (Are)-treated mice, the fertility and oocyte quality significantly decreased, and plenty of biochemical indexes significantly changed, so we guessed that the overall physical health of Are mice was severely impacted. As one major strategy to investigate the mechanism how Are impact the physical health, We chose TMT-labeled Quantitative ovarian phosphoproteomics service from Hangzhou PTM Bio Co. We sent two repeats of two-month-old Are CD1/ICR mouse ovaries and two repeats of control ovaries for characterization of differentially phosphorylated proteins. Each repeat contained about 60 ovaries from 30 female mice, about 300 mg. Two repeats of control samples and data were shared among project 1, 2 and 3. Gross protein levels were also examined and used to normalize the protein phosphorylation level.
Project description:To identify biomarkers regulated by traditional Chinese medicine Astragalus membranaceus Fischer Bge. var. mongolicus Bge. Hsiao in colorectal cancer. We have identified several differentially expressed genes including microRNAs using Affymetrix HTA-2.0 array. In this dataset, we include the expression data obtained from colon cancer cell line HCT116 grafted into nude mice. The mice was treated either water or traditional Chinese medicine Astragalus membranaceus for 28 days. These data are used to obtain 1425 genes that are differentially expressed in response to Astragalus membranaceus treatment.
Project description:We found that in Chronic Resistant Stress (CRS)-treated mice, the fertility and oocyte quality significantly decreased, and plenty of biochemical indexes significantly changed, so we guessed that the overall physical health of CRS mice was severely impacted. As one major strategy to investigate the mechanism how CRS impact the physical health, We chose label-free quantitative ovarian crotonylproteomics service from Hangzhou PTM Bio Co. We sent two repeats of two-month-old CRS CD1/ICR mouse ovaries and two repeats of control ovaries for characterization of differentially crotonylated proteins. Each repeat contained about 60 ovaries from 30 female mice, about 300 mg. Gross protein levels were also examined and used to normalize the protein crotonylation level.
Project description:We investigated the molecular mechanisms for osteolytic bone metastasis by selecting human lung cancer cell line subpopulations with elevated metastatic activity and validating genes that are overexpressed in these cells. A bone-seeking squamous lung cancer cell line (HARA-B4) was established by sequentially injecting parental HARA cells into the left ventricle of male 5-week-old nude mice 4 times.
Project description:We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in various vertebrate species. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. To understand the function of Runx1 during fetal development of the ovary, we ablated Runx1 specifically in the somatic cell lineage of the fetal ovaries using Sf1-Cre . We compared ovarian differentiation in wild type, Runx1 and Foxl2 single knockouts, and Runx1/Foxl2 double knockout ovaries. Transcriptome comparisons of newborn ovaries revealed that loss of Runx1 or Foxl2 affected a similar set of genes: 41% of the genes affected by the loss of Runx1 were also changed by the loss of Foxl2. Despite these transcriptomic changes, granulosa cell identity was maintained during fetal life in both Runx1 or Foxl2 single knockout ovaries. However, the combined loss of Runx1/Foxl2 resulted in masculinization of the ovaries during fetal life. To further characterize the impacts of the combined loss of Runx1 and Foxl2 on ovarian differentiation, we compared the transcriptome of Runx1/Foxl2 DKO newborn ovaries with the transcriptomes of control, Runx1, or Foxl2 single KO ovaries.