5-FU and SN-38 impact on colon microbiota
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ABSTRACT:
PROVIDER: PRJEB19934 | ENA |
REPOSITORIES: ENA
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Project description:Anti-programmed cell death 1 (PD-1) therapy shows definite but modest activity in patients with advanced/metastatic HNSCC. Preliminary evidence suggests that SN-38, an activated form of irinotecan that activates the transcription factor FoxO3a, may suppress the expression of PD-L1 in breast and ovarian tumor models. Here, we explore the efficacy of SN-38 in combination with anti-PD1 for HNSCC treatment. In vitro, SN-38 enhances FoxO3a expression and reduces the expression of PD-L1 dose-dependently in HNSCC cells. Low dose SN-38 increases interferon- excretion by natural killer (NK) cells and promotes NK cell-mediated cytotoxicity of tumor cells. In vivo studies reveal that, at non-cytotoxic drug concentrations, SN-38 significantly enhances anti-PD-1 activity in suppressing murine tumor growth. An increased infiltration of CD8+ T cells and NK cells was found in the post-treatment tumors. RNA-seq analysis confirms that SN-38 promotes the enrichment of immune cells and biological function genes related to the immune response became abundant in SN-38 and anti-PD1 treated tumors. Thus, SN-38 is a potentially beneficial adjunct to checkpoint inhibitor therapy in HNSCC. Further studies to explore its mechanism of action and possible application are mandatory.
2023-01-11 | GSE222450 | GEO
Project description:SN-38 resistant breast cancer cell lies (MCF-7 and MDA-MB-231) were established by stepwise increasing the concentration of SN-38. Gene expression profiling was performed on parental (sensitive) MCF-7 and parental (sensitive) MDA-MB-231 cell lines and their respective SN-38 resistant cell lines. For each cell line we harvested RNA from three independent passages and conducted 3 arrays.
2016-01-05 | E-MTAB-3224 | biostudies-arrayexpress
Project description:RATIONALE: Drugs used in chemotherapy, such as liposomal SN-38, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase II trial is studying how well liposomal SN-38 works in treating patients with metastatic colorectal cancer.
| 2027849 | ecrin-mdr-crc
Project description:SNB-101 is a novel nano-particle formulation of SN-38, the active metabolite of irinotecan(CPT-11). Study SNB101P01 is a multicenter, open-label, dose escalation, phase 1 study of SNB 101 with its active ingredient SN-38, in participants with advanced solid tumors. Dose escalation will occur using a modified accelerated titration design (ATD).
All participants will receive SNB 101 in different cohorts. SNB 101 will be administered intravenously to participants on day 1 and day 15 of each 28 day treatment cycle until progressive disease, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
A Safety Review Committee will determine dose escalation, de-escalation, and modification and the MTD/RP2D based on DLTs and other safety information.
| 2358597 | ecrin-mdr-crc
Project description:The aim of this study was to identify biomarkers of drug response and investigate mechanisms of drug resistance to the two chemotherapeutic drugs oxaliplatin and irinotecan (active metabolite SN-38) in colorectal cancer, using a cell-based model system of drug-sensitive parental colon cancer cell lines and sub-cell lines with acquired drug resistance.
2015-03-15 | GSE42387 | GEO
Project description:SN-38, an active metabolite of irinotecan, enhances anti-PD1 treatment efficacy in head and neck squamous cell carcinoma
| PRJNA922128 | ENA
Project description:Gut bacterial β-glucuronidases (GUS) promote the toxic side effects of therapeutics by reactivating drugs from their inactive glucuronide conjugates. It is increasingly clear that the interindividual variability of bacterial GUS-producing species in the gut microbiota contributes to differential drug responses. Indeed, the anticancer drug irinotecan exhibits variable clinical toxicity outcomes that have been linked to interindividual differences in the composition of the gut microbiota. However, identification of the specific GUS enzymes responsible for drug metabolism in the context of the complexity of the human fecal microbiota has not been achieved. Here we pinpoint the specific bacterial GUS enzymes that reactivate SN-38, the active metabolite of irinotecan, from complex human fecal microbiota samples with activity-based protein profiling (ABPP). We identify and quantify gut bacterial GUS enzymes from human feces with ABPP-enabled proteomics and then integrate this information with ex vivo kinetics to reveal the specific GUS enzymes responsible for the reactivation of SN-38. The same ABPP approach also reveals the molecular basis for differential gut bacterial GUS inhibition between human fecal samples. Taken together, this work provides an unprecedented pipeline to identify the specific bacterial GUS enzymes responsible for drug-induced GI toxicity from the complexity of human feces, which may serve as highly precise biomarkers of clinical outcomes for irinotecan and other therapeutics.
2019-12-03 | PXD014864 | Pride
Project description:Hydrogenobaculum sp. SN genome sequencing
| PRJNA39709 | ENA
Project description:The molecular properties of benign melanocytic lesions are poorly understood. Only few studies have been performed on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expression of 25 SN and 15 NCN were analyzed. Molecular profiling was done using the RNA NanoString nCounter Gene Expression Platform (No. of genes = 770). Marker discovery was performed with a training set consisting of 7 SN and 7 NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and 8 NCN samples. Using the training set, 197 differentially expressed genes were identified in SN versus NCN. Of these, 74 genes validated in the validation set (FDR Q value ≤ 0.13). In addition, using Random Forest and LASSO feature selection a molecular signature of SN versus NCN was identified including 15 top-ranked genes. Gene set analysis showed upregulation of gene pathways with increased expression of transcripts related to immunomodulatory, inflammatory and extracellular matrix interactions as well as angiogenesis associated processes in SN. Although the molecular characteristics of malignant melanoma have been studied in detail, the molecular properties of benign melanocytic lesions such as common nevocellular nevi (NCN) and Spitz nevi (SN) remain poorly understood. This limited knowledge hinders a better understanding of atypical and malignant transformation of melanocytes. The present study identified a distinct molecular expression profile in SN compared to NCN, even when lesions were obtained from the same patients. These findings strongly indicate that SN represent a distinct group of melanocytic neoplasms and evolve differentially and not sequentially from NCN.
2018-02-15 | GSE110589 | GEO
Project description:We analyzed the differentially regulated genes in 5-fluorouracil-resnstant human colon cancer cells to discover novel biomarkers involved in 5-FU resistance in colorectal cancer.
2017-03-27 | GSE56322 | GEO