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)

Sixteen tumor markers are reviewed, and measured to the ideal: produced by the tumor cell alone absent in health and in benign disease present in all patients with a given malignancy level in the blood representative of tumor mass detectable in occult disease. The only marker that approaches the ideal is human chorionic gonadotropin (HCG) in gestational trophoblastic tumors. In this malignancy, the HCG level suggests the diagnosis and stage, confirms response to therapy, and predicts relapse. The three most widely used and intensely studied tumor markers are carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and HCG. CEA cannot be used in screening for cancer, but in carcinoma of the colon its elevation preoperatively increases the likelihood of advanced disease and postoperative recurrence. Postoperatively, elevated titers are often but not invariably associated with recurrent disease. AFP and HCG are useful in the management of nonseminomatous germ cell testicular tumors. Like CEA, they cannot be used for screening. They are more likely to be increased with advancing stage, and after therapy rising levels almost always mean recurrent disease. Some markers are valuable in specific circumstances, such as calcitonin in screening for familial medullary carcinoma of the thyroid. In multiple myeloma, immunoglobulins are useful in determining the tumor mass and response to therapy. In neuroblastoma, catecholamine metabolites are useful primarily in making the diagnosis. In some malignancies, the absence of effective therapy lowers the value of the marker, as for AFP in hepatoma. The remaining markers are too unreliable or too little studied to be useful in the management of an individual patient with cancer. The purpose of this paper is to provide the clinician with an understanding of the limitations of the present tumor markers that will lead to wiser use of the tests, and to provide standards to which future tumor markers should be measured.
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PMID:Tumor markers: value and limitations in the management of cancer patients. 241 41

We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.
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PMID:111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection. 281 44

Uptake of 131iodine-metaiodobenzylguanidine (131I-MIBG) by 6-23 rat medullary thyroid carcinoma (MTC), was studied in vitro and in vivo. In vitro, there was an 8-fold increase in 131I uptake by 6-23 cells when labeled with 131I-MIBG (131I 24 +/- 15 cpm/10(6) cells, 131I-MIBG 196 +/- 9 cpm/10(6) cells). MIBG uptake in vitro was the same at 4 degrees C and 37 degrees C. In contrast, 131I-MIBG uptake by PC-12 rat pheochromocytoma cells were 200 times greater (131I-MIBG 42,412 +/- 6,755 cpm/10(6) cells). 131I-MIBG uptake by rat MTC cells in vitro were of a comparable magnitude to the uptake of 131I-MIBG by rat ileal enterochromaffin cells (RIE-1) and mouse colon cancer cells (MC-26). In vivo, uptake of 131I-MIBG by 6-23 MTC tumor was considerably less than in the normal tissues (muscle, liver, spleen, kidney, adrenal and thyroid). Gamma camera studies of 131I-MIBG uptake by 6-23 MTC tumors growing in Wag-Rij rats were only transiently positive in 1 out of 4 rats studied. We conclude that 131I-MIBG is poorly taken up by rat medullary thyroid carcinoma and is an unpredictable marker for localization of rat MTC.
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PMID:Uptake of 131I-metaiodobenzylguanidine by 6-23 rat medullary thyroid carcinoma. 278

Pancreas cancer-associated antigen (PCAA), primarily isolated from the ascites of pancreatic cancer (PC) patients, is strongly positive in PC, colon cancer and normal colonic mucosa. In immunohistochemical staining of tumor tissues with antibodies, medullary thyroid carcinoma (MTC) was no less strongly positive for PCAA than PC, and we studied its details. Antibodies to PCAA, calcitonin and CEA were used in the immunostaining of normal thyroid tissues and thyroid tissues from patients with adenomas, MTC, papillary carcinomas, and follicular carcinomas. The PCAA from the liver metastases of MTC was studied for molecular weight and antigenicity in comparison with the PCAA from the ascites of PC patients. Serum levels of PCAA were determined in MTC patients. Of 11 patients with MTC, PCAA, calcitonin and CEA were studied immunohistologically and positive in 10, 11 and 10 patients, respectively. The PCAA from the metastases had a molecular weight of about 700,000, and was immunochemically identical to that from the ascites of PC patients. Serum levels of PCAA were elevated in 4 of 6 MTC patients. The thyroid tissues from the MTC patients, familial or non-familial, were as strongly positive for PCAA as for calcitonin and CEA. It was antigenically identical to that of PC origin, and positive in the serum of MTC patients.
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PMID:Pancreas cancer-associated antigen (PCAA) in medullary thyroid carcinoma. 760 6

The science of cancer is being revolutionized by the collaboration of cancer-afflicted families and determined scientists. The result has been an explosion of knowledge about inherited susceptibilities to particular types of cancer and the possibilities of testing for those susceptibilities. Susceptibility tests are becoming available for breast cancer, ovarian cancer, prostate cancer, colon cancer, retinoblastoma, and hereditary medullary thyroid cancer--cancers both common and rare. Now, cancer patients, cancer families, and cancer physicians face the challenge of determining how--and whether--such tests can be put to good use.
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PMID:Genetic testing for cancer susceptibility: challenges for creators of practice guidelines. 968 74

Sunitinib (SU011248) is an oral small molecular tyrosine kinase inhibitor that exhibits potent antiangiogenic and antitumor activity. Tyrosine kinase inhibitors such as SU6668 and SU5416 (semaxanib) demonstrated poor pharmacologic properties and limited efficacy; therefore, sunitinib was rationally designed and chosen for its high bioavailability and its nanomolar-range potency against the antiangiogenic receptor tyrosine kinases (RTKs)--vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). Sunitinib inhibits other tyrosine kinases including, KIT, FLT3, colony-stimulating factor 1 (CSF-1), and RET, which are involved in a number of malignancies including small-cell lung cancer, GI stromal tumors (GISTs), breast cancer, acute myelogenous leukemia, multiple endocrine neoplasia types 2A and 2B, and familial medullary thyroid carcinoma. Sunitinib demonstrated robust antitumor activity in preclinical studies resulting not only in tumor growth inhibition, but tumor regression in models of colon cancer, non-small-cell lung cancer, melanoma, renal carcinoma, and squamous cell carcinoma, which were associated with inhibition of VEGFR and PDGFR phosphorylation. Clinical activity was demonstrated in neuroendocrine, colon, and breast cancers in phase II studies, whereas definitive efficacy has been demonstrated in advanced renal cell carcinoma and in imatinib-refractory GISTs, leading to US Food and Drug Administration approval of sunitinib for treatment of these two diseases. Studies investigating sunitinib alone in various tumor types and in combination with chemotherapy are ongoing. The clinical benchmarking of this small-molecule inhibitor of members of the split-kinase domain family of RTKs will lead to additional insights regarding the biology, potential biomarkers, and clinical utility of agents that target multiple signaling pathways in tumor, stromal, and endothelial compartments.
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PMID:Sunitinib: from rational design to clinical efficacy. 1760 94

Obesity, accompanying or independent of type 2 diabetes mellitus (T2DM), is associated with higher rates of malignancy. Hence, there is considerable interest in understanding whether therapies used to treat obese patients with T2DM impact cancer cell growth. Glucagon-like peptide-1 (GLP-1) is produced in enteroendocrine cells and secreted after meal ingestion. GLP-1 regulates blood glucose through multiple mechanisms, principally inhibition of glucagon and stimulation of insulin secretion. GLP-1 also exerts independent effects promoting cell growth and survival, and sustained activation of GLP-1 receptor (GLP-1R) signaling in rodent thyroid glands leads to C-cell hyperplasia and medullary thyroid cancer. Hence, whether therapies based on GLP-1R activation modify growth or survival of cancer cells is of ongoing interest. We studied the biological actions of GLP-1 in mouse CT26 colon cancer cells that express a functional GLP-1R. The GLP-1R agonist exendin (Ex)-4 (exenatide) increased intracellular cAMP levels and inhibited the activity of signaling kinases glycogen synthase kinase 3 and ERK1/2 in CT26 cells. The Ex-4-induced inactivation of glycogen synthase kinase 3, but not ERK1/2, was dependent on protein kinase A and blocked by the GLP-1R antagonist Ex(9-39). Furthermore, Ex-4 altered cell morphology, induced apoptosis, and inhibited proliferation of CT26 cells in vitro. Moreover Ex-4 decreased CT26 colony formation in soft agar and augmented apoptosis induced by irinotecan. Twice-daily treatment of CT26 tumor-bearing BALB/c mice with Ex-4 for 2 wk increased tumor apoptosis. Hence, GLP-1R activation reduces growth and survival in CT26 colon cancer cells that express the endogenous classical GLP-1R.
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PMID:Glucagon-like peptide-1 receptor activation inhibits growth and augments apoptosis in murine CT26 colon cancer cells. 2177 84

RET kinase is aberrantly activated in thyroid cancers and in rare cases of lung and colon cancer, and has been validated as a molecular target in these tumors. Vandetanib was recently approved for the treatment of medullary thyroid cancer. However, vandetanib is ineffective in vitro against RET mutants carrying bulky aminoacids at position 804, the gatekeeper residue, similarly to drug-resistant BCR-ABL mutants in chronic myeloid leukemia. Ponatinib is a multi-target kinase inhibitor that was recently approved for treatment-refractory Philadelphia-positive leukemia. We show here potent inhibition of oncogenic RET by ponatinib, including the drug-insensitive V804M/L mutants. Ponatinib inhibited the growth of RET+ and BCR-ABL+ cells with similar potency, while not affecting RET-negative cells. Both in biochemical and in cellular assays ponatinib compared favorably with known RET inhibitors, such as vandetanib, cabozantinib, sorafenib, sunitinib and motesanib, used as reference compounds. We suggest that ponatinib should be considered for the treatment of RET+ tumors, in particular those expressing vandetanib-resistant V804M/L mutations.
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PMID:Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase. 2381 Dec 35

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.
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PMID:Metastasis of colon cancer to medullary thyroid carcinoma: a case report. 2536 99

Carcinoembryonic antigen (CEA) is still the most widely used tumour marker for gastrointestinal cancer. CEA was originally thought to be a specific marker for colorectal cancer, but it turned out to be a non-specific marker for further studies. CEA levels can be elevated in breast, lung and liver cancers, among others, including medullary thyroid cancer. The authors report a case of a 73-year-old woman who had a right hemicolectomy for an ascending colon adenocarcinoma and showed a persistent elevation in the CEA marker during follow-up. After several imaging tests, recurrence of the colon cancer was not found, but the presence of thyroid nodules had been detected. The diagnosis of a medullary thyroid carcinoma was made after the finding of a high value of calcitonin. The patient had a total thyroidectomy with resection of the central and lateral lymph nodes.
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PMID:Persistent elevation of carcinoembryonic antigen as first presentation of a medullary thyroid carcinoma. 2989 42


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