Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia of malignancy. We present the case of a patient with recurrent adenosquamous carcinoma of the ascending colon found to have hypercalcemia. The patient is a 76-year-old white woman who initially presented with colon cancer in the cecum and underwent a right hemicolectomy. All lymph nodes and surgical margins were free of tumor. Pathological examination at that time revealed adenosquamous carcinoma of the colon. Eight months later she complained of dizziness, anorexia, and constipation and was found to have a calcium level of 13.6 mg/dL. CT scan revealed a mass measuring 10.5 to 12.7 cm in the right hepatic lobe, and a bone scan was normal. Her intact parathyroid hormone (PTH) level was 6 pg/mL (normal 12-72) and her PTH-related protein (PTHrP) level was 25.7 pmol/L (normal <1.3). She then underwent a hepatic resection. The serum PTH, calcium, and PTHrP levels normalized after resection. Hypercalcemia of malignancy in colon cancer is rare and has an association with adenosquamous histology. The hypercalcemia is attributed to PTHrP, and here we demonstrate this in the serum and tumor specimens. The effects of PTHrP are shown to be short-lived postoperatively. We find only 14 other cases in the literature of hypercalcemia related to a colonic neoplasm, and this is the only patient reported to be surviving. The diagnosis of a paraneoplastic syndrome mediated via PTHrP should be considered when hypercalcemia is encountered in the setting of metastatic colon carcinoma.
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PMID:Paraneoplastic hypercalcemia in a patient with adenosquamous cancer of the colon. 1140 9

Deletions and/or loss of heterozygosity (LOH) on chromosome 15 (15q15 and 15q21) have been found in several human tumors, including carcinomas of the colorectum, breast, lung, prostate, and bladder, suggesting the presence of potential tumor suppressor gene(s) in this particular region of chromosome 15. GCIP also called CCNDBP1, DIP1, or HHM, localized at chromosome 15q15, is a recently identified helix-loop-helix leucine zipper (HLH-ZIP) protein without a basic region like the Id family of proteins. In this study, we reported that the expression of GCIP was significantly downregulated in several different human tumors, including breast tumor, prostate tumor, and colon tumors. In human colon tumors, both mRNA and protein expression levels of GCIP were decreased significantly compared to the normal tissues. Treatment of colon cancer cells SW480 with sodium butyrate (NaB), which induces colon cancer cell differentiation, can induce the upregulation of GCIP expression, suggesting that the protein functions as a negative regulator in cell proliferation. Overexpression of GCIP in SW480 colon cancer cell line resulted in a significant inhibition on tumor cell colony formation, while silencing of GCIP expression by siRNA can promote cell colony formation. Furthermore, overexpression of GCIP inhibited the transcriptional activity of cyclin D1 promoter and the expression of cyclin D1 protein in the cell. Finally, we demonstrate that GCIP specifically interacts with one of the class III HDAC proteins, SirT6, which is important for maintaining genome stability. Together, our data suggest a possible function of GCIP in tumor suppression.
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PMID:GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. 1713 81

The extracellular calcium-sensing receptor (CaR) is a versatile 'sensor' for di- and polycationic molecules in the body. CaR plays a key role in the defense against hypercalcemia by "sensing" extracellular calcium levels in the parathyroid and kidney, the key organs maintaining systemic calcium homeostasis. Although mutation of CaR gene has so far not been associated with any malignancy, aberrant functions of CaR have implications in malignant progression. One situation is loss of CaR expression, resulting in loss of growth suppressing effects of elevated extracellular Ca(2+) by CaR, reported in parathyroid adenoma and in colon carcinoma. Another situation is activation of CaR, resulting in increased production of parathyroid hormone-related peptide (PTHrP), a primary causal factor in hypercalcemia of malignancy and a contributor to metastatic processes involving bone. CaR signaling and effects have been studied in several cancers including ovarian cancers, gastrinomas, and gliomas in addition to comparatively detailed studies in breast, prostate, and colon cancers. Studies on H-500 rat Leydig cells, a xenotransplantable model of humoral hypercalcemia of malignancy has shed much light on the mechanisms of CaR-induced cancer cell growth and survival. Pharmacological agonists and antagonists of CaR hold therapeutic promise depending on whether activation of CaR is required such as in case of colon cancer or inactivating the receptor is required as in the case of breast- and prostate tumors.
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PMID:Calcium-sensing receptor in cancer: good cop or bad cop? 1901 96