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Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

ABSTRACT: Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

PROVIDER: PRJNA731942 | ENA |

REPOSITORIES: ENA

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Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

Project description:Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

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Profiling long non-coding RNA expression in oral premalignant lesions.

Project description:Oral epithelial dysplasias are believed to progress through a series of histopathological stages; from mild to severe dysplasia, to carcinoma in situ, and finally to invasive OSCC. Underlying this change in histopathological grade are gross chromosome alterations and changes in gene expression of both protein-coding genes and non-coding RNAs. Recent papers have described associations of aberrant expression of microRNAs, one class of non-coding RNAs, with oral cancer. However, expression profiling of long non-coding RNAs (lncRNAs) has not been reported. Long non-coding RNAs are a novel class of mRNA-like transcripts with no protein coding capacity, but with a variety of functions including roles in epigenetics and gene regulation. In recent reports, the aberrant expression of lncRNAs has been associated with human cancers, suggesting a critical role in tumorigenesis. Here, we present the first long non-coding RNA expression map for the human oral mucosa. We describe the expression of 325 long non-coding RNAs, suggesting lncRNA expression contributes significantly to the oral transcriptome. Intriguingly, 60% of the detected lncRNAs show aberrant expression in oral premalignant lesions. A number of these lncRNAs have been previously associated with other human cancers. A total of six normal oral samples and ten oral premalignant lesions were used to construct SAGE libraries which were then queried for long non-coding RNA expression profiles. The six normal oral samples were previously deposited as GSE8127.

2011-08-14 | E-GEOD-31021 | biostudies-arrayexpress

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Palonosetron Hydrochloride in Preventing Nausea and Vomiting Caused by Radiation Therapy in Patients With Primary Abdominal Cancer

Project description:RATIONALE: Palonosetron hydrochloride may prevent nausea and vomiting caused by radiation therapy. It is not yet known whether palonosetron hydrochloride is more effective than a placebo in preventing nausea and vomiting. PURPOSE: This randomized phase II trial is studying the side effects of palonosetron hydrochloride and to see how well it works in preventing nausea and vomiting caused by radiation therapy in patients with primary abdominal cancer.

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Transcription profiling of human oral lesions treated with bioadhesive black rasberry gel to determine the effect on gene expression and proinflammatory proteins

Project description:This portion of the study evaluated the effects of topical 10% black raspberry gel application on gene expression profiles of premalignant oral lesions. Topical application of the bioadhesive black rasberry gel was observed to modulate gene expression and reduce proinflammatory proteins in human premalignant oral lesions. Experiment Overall Design: Each patient served as their own internal control. A pretreatment specimen of the premalignant lesion was obtained for baseline parameters. Following six weeks of treatment, the treated lesional tissue was removed. All tissue samples were immediately placed in RNA later and placed in a -80 degree freezer until sample preparation.

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Project description:BACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.

| S-EPMC8492350 | biostudies-literature

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