Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 56-year-old man was diagnosed to have a huge gastric cancer extending from the lesser curvature of the stomach to the pancreas with multiple hepatic and peritoneal metastases. Two days after completing chemotherapy with cisplatin plus high dose leucovorin and fluorouracil, drastic necrotising tumour lysis led to gastric perforation and septic shock most likely due to bacterial peritonitis. The image of tumour lysis looked like an emphysematous pancreatitis. Afterwards, immunohistochemical study of the tumour specimen confirmed moderate positivity of dihydropyrimidine dehydrogenase and absence of Bcl-2 expression. The incomplete expression of dihydropyrimidine dehydrogenase and total deficiency of Bcl-2 are considered to be the main underlying causes of such extraordinary chemosensitivity and so severe a tumour lysis phenomenon. Pre-emptive intensive survey of possible biomarkers of chemosensitivity is thus highly recommended upon treating a massive gastric cancer.
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PMID:Chemotherapy-induced necrotising tumour lysis and perforation of a huge gastric cancer simulating emphysematous pancreatitis. 3258 69

To date, 5-Fluorouracil (5FU) is a major component of several chemotherapy regimens, thus its study is of fundamental importance to better understand all the causes that may lead to chemoresistance and treatment failure. Given the evident differences between prognosis in Asian and Caucasian populations, triggered by clear genetic discordances and given the extreme genetic heterogeneity of gastric cancer (GC), the evaluation of the most frequent mutations in every single member of the 5FU conversion and activation pathway might reveal several important results. Here, we exploited the cBioPortal analysis software to query a large databank of clinical and wide-genome studies to evaluate the components of the three major 5FU transformation pathways. We demonstrated that mutations in such ways were associated with a poor prognosis and reduced overall survival, often caused by a deletion in the TYMP gene and amplification in TYMS. The use of prodrugs and dihydropyrimidine dehydrogenase (DPD) inhibitors, which normally catabolizes 5FU into inactive metabolites, improved such chemotherapies, but several steps forward still need to be taken to select better therapies to target the chemoresistant pools of cells with high anaplastic features and genomic instability.
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PMID:5-Fluorouracil Conversion Pathway Mutations in Gastric Cancer. 3288 17


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