Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of a single oral dose of 320 mg/kg body wt. N-nitrosomorpholine (NNM) to 62 Sprague-dawley rats resulted in neoplastic and preneoplastic changes in different organs, especially in liver and kidney. After a lag period of 4 weeks, nearly all experimental animals developed preneoplastic (clear cell, acidophilic, basophilic, mixed cell) foci of the liver parenchyma. Sporadically, small neoplastic nodules were found in the liver as early as 4 weeks after the beginning of the experiment. After a lag period of 1--2 years, 4 of 13 rats showed multiple neoplastic hepatic nodules and one animal a hepatocellular carcinoma. The bile ductules of some animals responded to the carcinogen by forming mucous cholangiofibroses and cystic cholangiomas. After long lag periods, large cholangiofibromas were found in two experimental animals. One or two years after application of the carcinogen, many animals developed epithelial (clear cell, acidophilic, chromophobic, basophilic, oncocytic) kidney tumors, often cystic. Pathologically changed (clear cell, chromophobic, basophilic, oncocytic) tubules are regarded as precursors of the epithelial tumors. The latered tubules appear for the first time at about half a year after application of the carcinogen. Apart from multiple cysts of the liver and kidneys some pancreatic cysts developed in two animals. In addition, two mesenchymal kidney tumors, one malignant neurinoma, two subcutaneous fibromas, one fibroadenoma, and one squamous cell carcinoma of the skin were observed.
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PMID:[Neoplastic and preneoplastic lesions in rats after oral administration of a single dose of N-nitrosomorpholine (author's transl)]. 47 63

The Grainyhead-like (GRHL) family of transcription factors has three mammalian members, which are currently termed Grainyhead-like 1 (GRHL1), Grainyhead-like 2 (GRHL2), and Grainyhead-like 3 (GRHL3). These factors adopt a DNA-binding immunoglobulin fold homologous to the DNA-binding domain of key tumor suppressor p53. Their patterns of expression are tissue and developmentally specific. Earlier studies of the GRHL proteins focused on their functions in mammalian development. In recent years, these factors have been linked to many different types of cancer: squamous cell carcinoma of the skin, breast cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, clear cell renal cell carcinoma, neuroblastoma, prostate cancer, and cervical cancer. The roles of GRHL proteins in these various types of cancer are complex, and in some cases appear to be contradictory: they can serve to promote cancer development, or they may act as tumor suppressors, depending on the particular GRHL protein involved and on the cancer type. The reasons for obvious discrepancies in results from different studies remain unclear. At the molecular level, the GRHL transcription factors regulate the expression of genes whose products are involved in cellular proliferation, differentiation, adhesion, and polarity. We herein review the roles of GRHL proteins in cancer development, and we critically examine relevant molecular mechanisms, which were proposed by different authors. We also discuss the significance of recent discoveries implicating the involvement of GRHL transcription factors in cancer and highlight potential future applications of this knowledge in cancer treatment.
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PMID:Recent discoveries concerning the involvement of transcription factors from the Grainyhead-like family in cancer. 2606 69