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      Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management

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          Abstract

          The toxicity of cancer chemotherapy is among the most important factors limiting its use. Clear delineation and communication of benefits and risks is an essential component of treatment decisions. Gastrointestinal toxicity during chemotherapy is frequent and contributes to dose reductions, delays and cessation of cancer treatment. The development of intervention strategies that could eliminate an expected side effect of chemotherapy is vital. Physiologic changes that can increase the toxicity of chemotherapy are decreased stem cell reserves, decreased ability to repair cell damage, progressive loss of body protein, and accumulation of body fat. Symptoms only arise when physiological functions are altered. The gastrointestinal symptoms arising during cancer chemotherapy can often be cured if newly acquired, and if gastrointestinal physiological deficits are identified. Developing new chemotherapy regimens with similar efficacy but less toxicity should be a priority for future research.

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          Most cited references111

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          Structure, Recognition, and Processing of Cisplatin-DNA Adducts.

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            Drug-induced hepatotoxicity.

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              Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas.

              PTEN is a tumor suppressor gene mutated in many human cancers, and its expression is reduced or absent in almost half of hepatoma patients. We used the Cre-loxP system to generate a hepatocyte-specific null mutation of Pten in mice (AlbCrePten(flox/flox) mice). AlbCrePten(flox/flox) mice showed massive hepatomegaly and steatohepatitis with triglyceride accumulation, a phenotype similar to human nonalcoholic steatohepatitis. Adipocyte-specific genes were induced in mutant hepatocytes, implying adipogenic-like transformation of these cells. Genes involved in lipogenesis and beta-oxidation were also induced, possibly as a result of elevated levels of the transactivating factors PPARgamma and SREBP1c. Importantly, the loss of Pten function in the liver led to tumorigenesis, with 47% of AlbCrePten(flox/flox) livers developing liver cell adenomas by 44 weeks of age. By 74-78 weeks of age, 100% of AlbCrePten(flox/flox) livers showed adenomas and 66% had hepatocellular carcinomas. AlbCrePten(flox/flox) mice also showed insulin hypersensitivity. In vitro, AlbCrePten(flox/flox) hepatocytes were hyperproliferative and showed increased hyperoxidation with abnormal activation of protein kinase B and MAPK. Pten is thus an important regulator of lipogenesis, glucose metabolism, hepatocyte homeostasis, and tumorigenesis in the liver.
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                Author and article information

                Journal
                Ann Gastroenterol
                Ann Gastroenterol
                AnnGastroenterol
                Annals of Gastroenterology
                Hellenic Society of Gastroenterology (Greece )
                1108-7471
                1792-7463
                2012
                : 25
                : 2
                : 106-118
                Affiliations
                [a ]Department of Medical Oncology (Stergios Boussios, George Pentheroudakis, Nicholas Pavlidis)
                [b ]First Department of Internal Medicine & Hepato-Gastroenterology Unit (Konstantinos Katsanos), Ioannina University Hospital, Ioannina, Greece
                Author notes
                Correspondence to: Nicholas Pavlidis, Department of Medical Oncology, Ioannina University Hospital, Niarhou Avenue, Ioannina, Greece, Tel. – Fax: +30 26510 99394, e-mail: npavlid@ 123456uoi.gr
                Article
                AnnGastroenterol-25-106
                3959393
                24713845
                dea798f1-b565-465f-abfd-94e26efbee4d
                Copyright: © Hellenic Society of Gastroenterology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 December 2011
                : 16 January 2012
                Categories
                Invited Review

                chemotherapy,gastrointestinal toxicity,cancer
                chemotherapy, gastrointestinal toxicity, cancer

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