Project description:Actinic keratoses were treated with either calcipotriol plus 5-FU or vaseline plus 5-FU in the randomized clinical trial. We have Day 0 before treatment samples and Day 5 after treatment samples in two groups.
Project description:In this study, we validated 992 previously identified differentially methylated regions (DMRs) in colorectal precancerous lesions compared to adjacent normal mucosa in a new series of 59 prospectively collected lesions and matched normal tissue using targeted bisulfite sequencing. Strong differences in methylation level were observed across the full set of validated DMRs. Based on the mean methylation levels of a panel of 30 selected DMRs tumors could be accurately classified. We thus provide a large list of validated DNA markers to be exploited in the development of noninvasive, colorectal tumor screening assays.
Project description:Oral squamous cell carcinomas are neoplasms that are mostly preceded by precancerous lesions such as leukoplakia and erythroplakia. It is important for the clinician to know about the predilection and possibility of these precancerous conditions transforming to cancer. This will inturn help to efficiently treat and manage patients. It is therefore important to understand the molecular events that explain the biology of predilection and transformation of precancerous lesions such as erythroplakia and leukoplakia to cancer. Our study aims to identify potential biomarker proteins in precancerous lesions of leukoplakia and erythroplakia that can flag its transformation to oral cancer. Four biological replicate clinical phenotypes of healthy control, leukoplakia, erythroplakia, and oral carcinoma were recruited based on clinical screening and histopathological evaluation of buccal mucosa tissue. Differentially expressed proteins were delineated using Label-free quantitative proteomics experiment done on Orbitrap fusion Tribrid mass spectrometer in three technical replicate sets of samples. Raw files were processed using Maxquant version 2.0.1.0. and down stream analysis was done by Perseus version 1.6.15.0. Validation included functional annotation based on biological process and KEGG pathways using ClueGO plug-in of cytoscape. Hierarchical clustering, and principal component analysis were performed using ClustVis tool. Across control, leukoplakia, and cancer, l- lactate dehydrogenase A chain, plectin, and WD repeat-containing protein 1 were upregulated, whereas thioredoxin 1 and spectrin alpha chain non-erythrocytic 1 were downregulated. Across control, erythroplakia, and cancer, l- lactate dehydrogenase A chain was upregulated whereas aldehyde dehydrogenase 2, peroxiredoxin 1, Heat shock 70 kDa protein 1B, and spectrin alpha chain non-erythrocytic 1 were downregulated. We found proteins involved in leukoplakia were associated with alteration in cytoskeletal reorganization and glycolysis, while in erythroplakia they were associated with alteration in response to oxidative stress and glycolysis across phenotypes. Hierarchical clustering sub-grouped half of precancerous samples under the main branch of control and the remaining half under carcinoma. Similarly, principal component analysis identified segregated clusters of control, precancerous lesions, and cancer but erythroplakia phenotypes particularly overlapped more with cancer cluster. Label-free proteomics offers a good platform for identification of protein biomarkers that can flag premalignant conditions that could become malignant. Qualitative and quantitative protein signatures across control, precancer and cancer phenotypes explain the possible functional outcomes that dictate malignant transformation to oral carcinoma. The observations place the previously observed clinical findings of erythroplakia having more predilection for cancer, in the right perspective.
Project description:Modern pharmacology has proved that Codonopsis Radix and its active ingredients can treat stomach diseases by ameliorating gastrointestinal motility and regulating oxidase levels. However, the detailed molecular mechanism is still unclear. In this study, we systematically evaluated the pharmacodynamic effects of Codonopsis Radix in Gastric Precancerous Lesions animal models. Considering the combination of proteomics and metabolomics, we found that CR could significantly reversed the biological pathways related to energy metabolism which were disturbed by GPL model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix contained serum could ameliorate gastritis injury, and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in above cells.
Project description:Epidemiological data have linked vitamin D deficiency to the onset of various cancers, including prostate cancer, and although in-vitro studies have demonstrated anti-cancer activities for the vitamin, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically-engineered mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analogue with reported anti-cancer activities, and comprehensively analyzed its effects on various cell types in such lesions. We show that this analogue induces apoptosis in senescent PINs and normalizes extracellular matrix remodeling by stromal fibroblasts in an epithelial VDR-dependent manner. Furthermore, it reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells in an epithelial VDR-independent manner. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal epithelial cells, expressing Krt4 and Tacstd2 (termed luminal-C) with enhanced interferon signature, is lost by such a treatment, anti-apoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of prostatic precancerous lesions and the microenvironment to the vitamin D analogue, and shed light on mechanisms that limit treatment’s efficacy.
Project description:To investigate the changes in molecular expression, biological processes, stemness, immune microenvironment, tumor hallmark activities and co-expression relationships during intestinal-type gastric cancer carcinogenesis and to excavate the prognostic information contained in the carcinogenesis process. RNA expression profiles of ninety-four gastroscope biopsy samples with different stages of precancerous lesions or early gastric cancers and their paired controls were detected by Agilent Microarray.
Project description:Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Recent studies have shown that DMBT1 expression is up-regulated in areas of intestinal metaplasia and in gastric tumors. Here, we examined the role of DMBT1 in the development of inflammatory response and gastric precancerous lesions in Caucasian, African American and Hispanic populations as well as in a mouse model. We found that mucosal DMBT1 expression is significantly increased in individuals with more advanced gastric precancerous lesions. We also show that H. pylori infection of Dmbt1-/- mice results in enhanced gastric inflammation and the development of mucous metaplasia that is accompanied by increased cell proliferative rates and reduced IL-33 expression levels in the inflamed mucosa. Taken together, our data suggest that DMBT1 may be mediating mucosal protection that may reduce the risk of developing gastric precancerous lesions in response to H. pylori infection