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Next Generation Sequencing Facilitates Quantitative Analysis of Vehicle Control and Vismodegib Treated Tumor Transcriptomes II

ABSTRACT: Purpose: The goal of this study is to compare transcriptome profiling (RNA-seq) between tumors of mammary tumor bearing mice treated with a vehicle control or FDA approved Hedgehog signaling inhibitor, Vismodegib.

ORGANISM(S): Mus musculus

PROVIDER: GSE171168 | GEO | 2021/11/10

REPOSITORIES: GEO

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Next Generation Sequencing Facilitates Quantitative Analysis of Vehicle Control and Vismodegib Treated Tumor Transcriptomes

Project description:Purpose: The goal of this study is to compare transcriptome profiling (RNA-seq) between tumors of mammary tumor bearing mice treated with a vehicle control or FDA approved Hedgehog signaling inhibitor, Vismodegib.

2023-02-01 | GSE146222 | GEO

Transcriptomic analysis of early-stage basal cell carcinomas in murine skin following ablative fractional laser and vismodegib treatment

Project description:Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration, and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterize the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of the FDA approved hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation. Both AFL and vismodegib treatments were able to reverse this upregulation with vismodegib demonstrating superior performance by reversing the most genes (AFL: 59/277; vismodegib 180/277). Surprisingly, Ingenuity Pathway Analysis revealed that both treatments also caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages, and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment highlight key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining AFL’s effects on the immune system with other topical treatments.

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Next Generation Sequencing Facilitates Quantitative Analysis of Vehicle Control and Vismodegib Treated Tumor Transcriptomes

Project description:Next Generation Sequencing Facilitates Quantitative Analysis of Vehicle Control and Vismodegib Treated Tumor Transcriptomes

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Next Generation Sequencing Facilitates Quantitative Analysis of Vehicle Control and Vismodegib Treated Tumor Transcriptomes II

Project description:Next Generation Sequencing Facilitates Quantitative Analysis of Vehicle Control and Vismodegib Treated Tumor Transcriptomes II

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Expression profile of Rhabdomyosarcoma (RMS) cells after Vismodegib treatment

Project description:A cDNA microarray was performed to identify pathways differentially regulated between untreated and Vismodegib-treated cells.

2017-09-01 | GSE77996 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of Hedgehog Signaling Blockade on Macrophage Transcriptomes

Project description:Purpose: The goal of this study is to compare transcriptome profiling (RNA-seq) between macrophages inhibited for Hedgehog signaling and vehicle control.

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ATAC sequencing of sorted BCC cells after vismodegib treatment

Project description:K14Cre-ER; Ptch1fl/fl; p53fl/fl;Lgr5GFP mice were aged until the appropriate tumor density was achieved. Skin samples were taken from control mice (untreated) or mice treated for 6 days or 14 days at twice a day dosing with vismodegib (75mg/kg body weight). RNA was extracted from freshly FACS sorted tumor cells based on GFP intensity. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.

2018-08-08 | GSE116965 | GEO

Identification of anaplastic lymphoma kinase as a candidate of new therapeutic target for BCC

Project description:Background; Basal cell carcinoma (BCC) is the most common cancer in humans. The pathogenesis of BCC is associated with the sonic hedgehog (SHH) signaling pathway. Vismodegib, a smoothened inhibitor, that targets this pathway is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. Methods; We studied gene expression profiling of BCC tumour tissue coupled with laser capture microdissection to identify tumor specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. The expression of selected molecules was confirmed by quantitative RT-PCR (qRT-PCR) and by immunohistochemistry. The action of kinase inhibitors was examined on primary normal human epidermal keratinocytes. Results; We found a >250 fold change increase (false discovery rate <10-4) of the oncogene, anaplastic lymphoma kinase (ALK) as well as its ligands, pleiotrophin and midkine in BCC compared to microdissected normal epidermis. qRT-PCR confirmed increased expression of ALK (p<0.05). Stronger staining of phosphorylated ALK in BCC tumour nests than normal skin was observed by immunohistochemistry. Additionally, Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met, another receptor tyrosine kinase, inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 mRNA by approximately 60% and 20%, respectively (p<0.05). Conclusions; Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promotes keratinocyte proliferation. Furthermore, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients. Laser capture microdissection was performed on 5 cases of nodular/superficial BCC, 5 cases of infiltrative BCC.

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A Study of Vismodegib (GDC-0449) in Patients Treated With Vismodegib in a Previous Genentech-sponsored Phase I or II Cancer Study

Project description:This was a multicenter, open-label extension study. Patients who received vismodegib (GDC-0449) in a Genentech-sponsored study and who had completed the parent study or who continued to receive vismodegib at the time the parent study closed were eligible for continued treatment in this protocol.

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ATAC sequencing of sorted BCC cells after vismodegib treatment

Project description:ATAC sequencing of sorted BCC cells after vismodegib treatment

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