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Medical Sciences

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Colorectal cancer

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Full-Text Articles in Medicine and Health Sciences

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell Jan 2013

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

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Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …


Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li Jan 2013

Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li

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Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …


Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac, Jason Derek Whitt Jan 2012

Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac, Jason Derek Whitt

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ABSTRACT The nonsteroidal anti-inflammatory drug (NSAID) sulindac has displayed the ability to inhibit the proliferation of colorectal cancer (CRC) cells and to increase the sensitivity of multidrug resistant (MDR) cancer cells to a wide variety of chemotherapeutic agents. The antineoplastic activity of sulindac has been attributed to inhibition of the prostaglandin producing enzyme COX-2, but the exact mechanism remains elusive and the inhibition of prostaglandin synthesis can result in gastrointestinal, hepatic, and cardiovascular toxicities. Enzymatic, cellular, and imaging assays were used to identify mechanisms that could contribute to the antiproliferative and apoptotic activity of sulindac. Screening of more than 500 …