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The Laboratory of Human Carcinogenesis' Mission and Uniqueness:
LHC utilizes an integrative biology and translational research strategy to investigate: molecular mechanisms of carcinogenesis including human liver, lung and colon carcinogenesis, hypoxia-driven carcinogenesis and tumor progression; and molecular epidemiology of human cancer including breast, prostate, lung, and colon.

LHC has pioneered studies in molecular epidemiology of cancer and continues to focus on the investigation of Genes and the Environment, Signatures of the Cancer Cell and its Microenvironments, and Research on Tobacco and Tobacco-Related Cancer, which are highlighted as NCI Broad Research Priorities in "The Nation's Investment in Cancer Research. A Plan and Budget Proposal for Fiscal year 2005." LHC research also has a strong translational component, e.g., development of diagnostic and prognostic biomarkers, and therapeutic targets of liver and lung cancer.



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RECENT DEVELOPMENTS & TECHNOLOGIES

Micro RNAs Linked to Cancer


Basics of StemCell Research

Chronic Inflammation & Cancer





Recent Publications

MicroRNAsÑnoncoding RNA molecules that regulate the translation of genesÑmay function as diagnostic biomarkers and therapeutic targets in cancer. Schetter and colleagues examined microRNA expression patterns in colon tumors and paired nontumorous tissue from 2 independent cohorts of patients with sporadic colon adenocarcinoma. The authors identified expression patterns that were associated with colon tumor formation, response to chemotherapy, and cancer-specific survival. In particular, tumors with a high expression of microRNA miR-21 were associated with a poor response to adjuvant chemotherapy and poor patient survival.

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Infection and chronic inflammation contribute to about 1 in 4 of all cancer cases. Mediators of the inflammatory response, e.g., cytokines, free radicals, prostaglandins and growth factors, can induce genetic and epigenetic changes including point mutations in tumor suppressor genes, DNA methylation and post-translational modifications, causing alterations in critical pathways responsible for maintaining the normal cellular homeostasis and leading to the development and progression of cancer. Recent discovery of an interaction between microRNAs and innate immunity during inflammation has further strengthened the association between inflammation and cancer.

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To investigate our hypothesis, 14 polymorphisms in TP53, including haplotype tagging and coding single nucleotide polymorphisms, were genotyped in two studies from the greater Baltimore, Maryland area. One study is a case-control study and the second is a case-only study for which TP53 mutational spectra data are available. African Americans with Pro-T-A-G-G haplotypes of the combined TP53 polymorphisms TP53_01 (rs1042522), TP53_65 (rs9895829), TP53_66 (rs2909430), TP53_16 (rs1625895), and TP53_11 (rs12951053) had both an increased risk for lung cancer (odds ratio, 2.32; 95% confidence interval, 1.18-4.57) and a worsened lung cancer prognosis (hazards ratio, 2.38; 95% confidence interval, 1.38-4.10) compared with those with Arg-T-A-G-T haplotypes.

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DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line.


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CANCER Website NIH Website

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