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)

In 82 patients, a preoperative diagnosis of primary hyperparathyroidism has been established by means of transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients have had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and four were members of families with multiple endocrine adenomatosis (MEA, Types I and II). In six other hypercalcemic patients, high levels of iPTH were found also in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. In addition, a high serum level of iPTH was found in the superior vena cava of a seventh patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastasis with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in either the neck or the mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; three were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease had metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver; the liver contained a large amount of iPTH. The results of these investigations suggest that (1) venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production; (2) primary benign hyperparathyroidism is not uncommon in patients with cancer, and its co-existence must be recognized; (3) high serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity; and (4) hyperparathyroidism may be the first hint of a familial multiple endocrine syndrome.
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PMID:Hypercalcemia in patients with known malignent disease. 96 5

Tumor neovascularization is considered to be a critical step in the development of a malignant tumor. Endothelin (ET)-1 is a powerful vasoconstrictor and mitogenic peptide that is produced by many cancer cell lines. The cellular distribution of the ET components was evaluated in human colon tumors and compared to normal colon. There was more of the ET components (preproET-1, endothelin-converting enzyme-1, and ETA and ETB receptors) in adenomas and adenocarcinomas than in the normal colon. There was overproduction of preproET-1 and endothelin-converting enzyme-1 in carcinoma cells and stromal vessels, suggesting that they are a local source of ET-1. ETA receptors were present in stromal myofibroblasts of neoplastic tissue, and there were large amounts of ETB receptors in the endothelium and myofibroblasts. There was also a redistribution of alpha-smooth muscle actin-positive cells in the vascular structures of tumors. An experimental rat model of induced colon cancer treated for 30 days with bosentan, a mixed antagonist of both ET receptors, confirmed the morphological changes observed during the tumor vascularization. Our data suggest that ET-1 and its receptor play a role in colon cancer progression, with ET-1 functioning as a negative modulator of the stromal response.
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PMID:Modulation of human colon tumor-stromal interactions by the endothelin system. 1110 59

Autocrine activation of c-kit (KIT receptor tyrosine kinase) has been postulated to be a potent oncogenic driver in small cell lung cancer, neuroblastoma (NB), and poorly differentiated colorectal carcinoma (CRC). Although targeted therapy involving tyrosine kinase inhibitors (TKIs) such as imatinib mesylate is highly effective for gastrointestinal stromal tumor carrying V560G c-kit mutation, it does not show much potential for targeting wild-type KIT (WT-KIT). Our study demonstrates the role of stem cell factor (SCF)-based toxin conjugates for targeting WT-KIT-overexpressing malignancies such as NBs and CRCs. We constructed SCF-based recombinant bacterial toxins by genetically fusing mutated form of natural ligand SCF to receptor binding deficient forms of Diphtheria toxin (DT) or Pseudomonas exotoxin A (ETA') and evaluated their efficacy in vitro. Efficient targeting was achieved in all receptor-positive neuroblastoma (IMR-32 and SHSY5Y) and colon cancer cell lines (COLO 320DM, HCT 116, and DLD-1) but not in receptor-negative breast carcinoma cell line (MCF-7) thereby proving specificity. While dose- and time-dependent cytotoxicity was observed in both neuroblastoma cell lines, COLO 320DM and HCT 116 cells, only an anti-proliferative effect was observed in DLD-1 cells. We prove that these novel targeting agents have promising potential as KIT receptor tyrosine kinase targeting system.
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PMID:Targeting c-kit receptor in neuroblastomas and colorectal cancers using stem cell factor (SCF)-based recombinant bacterial toxins. 2642 35