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)

We report a case of a 23-year-old Turcot female patient who was first diagnosed as having a pinealoblastoma. Thyroid papillary carcinoma was diagnosed a few months later, and multiple colonic polyps were detected three years after that. A genetic workup revealed an APC gene mutation in her family. Long-term survival (i.e., >5 years) of pinealoblastoma is considered to be 20 percent. A review of 25 documented Turcot cases determined that the average age at death is 20.3 years, raising the difficult question of whether she should undergo restorative proctocolectomy. Restorative proctocolectomy may itself cause major morbidity but is currently the only way to prevent colon cancer.
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PMID:Pinealoblastoma in a patient with familial adenomatous polyposis: variant of Turcot syndrome type 2? Report of a case and review of the literature. 1640 May 11

Six octapeptide bombesin (BN) analogs were synthesized by substituting alpha-aminoisobutyric acid (Aib), in place of Ala9 or Gly11, or both, in the [D-Phe6, desMet14]-BN (6-14) sequence: D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-NH2 (P0). Additionally, Leu13 was replaced with isoleucine in two analogs and one of the analogs was butanoylated at the N-terminus. The antiproliferative activity of the analogs was tested in vitro on human pancreatic (MiaPaCa-2) and colon cancer (SW620, HT29 and PTC) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer activity in the above cell lines at concentrations ranging from 0.01 nM to 1 microM. One of the analogs, P6, was evaluated for in vivo tumor regression in a xenograft model of human primary colon cancer in athymic nude mice and was found to cause significant reduction in tumor volume. NMR and molecular dynamics (MD) simulation studies for this analog revealed the presence of a mixed 3(10)/alpha-helical structure. This study demonstrates that the designed BN analogs retain their anticancer activity after the incorporation of the constrained amino acid, Aib, and are potential molecules for future use in cancer therapy and drug targeting.
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PMID:Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer activity. 1703 71

Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm of the thyroid originating from the thyroid follicular cell (TFC). Although the formation of PTC is believed to result from rearrangements of RET or TRK oncogenes or MET point mutations, these structural aberrations or point mutations do not correlate with the clinicopathological features of PTC and do not seem to be a useful prognostic marker of the disease. Therefore, further experiments should be carried out in order to find new practical clinical markers. Recently, oncogene BRAF has become a subject of great interest. The mutation of BRAF gene is characteristic for PTC and poorly differentiated and/or undifferentiated cancers derived from PTC. The occurrence of BRAF mutation has often been observed in various human tumours. The presence of mutation was confirmed in melanoma, colon cancer, gliomas and lung cancer. In the majority of cases, there is only one type of point mutation - V600E. The RAS/RAF/MEK/MAPK kinase pathway mediates the cellular response to mitogenic signals. BRAF gene mutation results in increased kinase activity, leading to excessive activation of the above mitogenic pathway and to uncontrolled proliferation of cancer cells. Some correlation was noticed between BRAF gene mutation and the clinical stage of the neoplastic disease in question. Preliminary investigations indicate that the presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. Further investigations could also bring further improvements into the therapeutic management of thyroid cancer. There are reports emphasizing the possibility of using the inhibitors of BRAF proteins in the treatment of PTC. Certainly, in order to confirm the diagnostic usefulness of this marker, further studies should be carried out.
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PMID:BRAF mutations in papillary thyroid carcinoma. 1720 87

Constitutive ERK activation is a common finding in human cancer and is often the result of activating mutations of BRAF and RAS. BRAF missense mutations occur in approximately 8% of human tumors, most frequently in melanoma, papillary thyroid cancer and colon cancer. Mutations in BRAF have been found predominantly in tumors in which RAS is commonly mutated but concurrent mutations of both BRAF and RAS are extremely rare. Though over 40 different kinase domain mutations in BRAF have been identified, a single base-pair substitution in exon 15 at codon 600 (V600E) is found in over 80% of cases. These mutations cluster in the glycine-rich loop and activation segments of the kinase and are predicted to induce kinase activation by disrupting the inhibitory glycine-rich loop/activation segment interaction which characterizes the inactive conformation. The majority of mutations identified cause constitutive kinase activation with the V600E mutation demonstrating approximately 500-fold greater kinase activity than wild-type BRAF. Supporting its classification as an oncogene, V600E BRAF stimulates ERK signaling, induces proliferation and is capable in model systems of promoting transformation. However, BRAF mutations are common in nevi and colon polyps suggesting that BRAF mutation alone is insufficient for tumorigenesis and additional mutations are required for cancer development. Though such data suggest that BRAF mutation is likely an early initiating event in tumors such as melanoma and colon cancer, preclinical studies suggest that tumors with V600E BRAF mutation remain dependent upon BRAF for proliferation and survival. Given its frequent occurrence in human cancer and the continued requirement for BRAF activity in tumors with BRAF mutation, efforts are underway to develop targeted inhibitors of BRAF and its downstream effectors. The first generation of RAF inhibitors, including sorafenib, were notable for their lack of specificity and potency for RAF and these agents have shown limited efficacy in tumors with a high incidence of BRAF mutation such as melanoma. Novel inhibitors of the pathway with greater selectivity for BRAF and MEK are now in Phase 1 and 2 clinical trials with promising early results. To maximize the likelihood of success with these agents, clinical trials enriched with patients whose tumors possess BRAF and RAS mutations have been proposed.
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PMID:Therapeutic strategies for targeting BRAF in human cancer. 1847 97

A 75-year-old woman with a history of extrapulmonary malignancies (ie, thyroid cancer and colon cancer) underwent a lobectomy for a solitary nodule in the left lung. Pathologic examination showed a lung metastasis from papillary thyroid cancer treated 30 years earlier. Solitary metastasis to the lung from thyroid cancer is unusual, and our case presented the long interval from initial treatment to the identification of metastasis. A careful follow-up is mandatory, and one should keep in mind the delayed metastasis in the patient with differentiated thyroid cancer.
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PMID:Solitary lung metastasis diagnosed 30 years after surgery for thyroid cancer. 1993 83

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein involved in several cellular processes, including proliferation, senescence and apoptosis. Loss of IGFBP7 expression is a critical step in the development of human tumors, including melanoma and colon cancer. By microarray gene expression studies, we have detected downregulation of IGFBP7 gene expression in follicular and papillary thyroid tumors in comparison with normal thyroid tissue. Evaluation of publicly available PTC microarray gene expression data sets confirmed, in a consistent fraction of tumors, the downregulation of IGFBP7 transcript levels. The functional consequence of IGFBP7 downregulation was addressed in the PTC-derived NIM1 cell line in which IGFBP7 expression is repressed by promoter hypermethylation. Exposure to soluble IGFBP7 protein or restoration of IGFBP7 expression by complementary DNA transfection reduced growth rate, migration, anchorage-independent growth and tumorigenicity of NIM1 cells. We show that the effects of IGFBP7 are related to apoptosis. Our data suggest that loss of IGFBP7 expression has a functional role in thyroid carcinogenesis, and it may represent a possible basis for therapeutic strategies.
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PMID:IGFBP7: an oncosuppressor gene in thyroid carcinogenesis. 2044 Feb 62

We describe a patient with MUTYH-associated polyposis diagnosed with colon cancer at 33 years of age, as well as gastric polyps at a later age. She was also diagnosed with papillary thyroid cancer at age 35. MUTYH-associated polyposis is an autosomal recessively inherited disease which has clinical overlap with Familial adenomatous polyposis and its attenuated form, in that it is associated with risk of colon cancer at a young age. Extra-intestinal cancers have also been reported in patients with MUTYH-associated polyposis; however the tumor spectrum is still evolving. National Comprehensive Cancer Network guidelines recommend screening for colon, duodenal and gastric polyps in individuals with MUTYH-associated polyposis. Screening for extra-intestinal cancers i.e. thyroid cancer is presently not part of these recommendations. These will likely continue to evolve as the MUTYH-associated polyposis tumor spectrum is better understood as a result of future case reports and research.
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PMID:Papillary thyroid cancer in a patient with MUTYH-associated polyposis (MAP). 2062 37

A 70-year-old man with a history of surgery for colon cancer was found to have multiple enlarging pulmonary nodules( 2 in the left lower lobe and 1 in the right upper lobe), and was suspected of having pulmonary metastases from colon cancer. He underwent left lower lobectomy, and subsequent histopathological examination revealed that one was a pulmonary metastasis from colon cancer, and the other was a pulmonary metastasis from papillary thyroid cancer. There were no abnormalities in the thyroid gland according to computed tomography and ultrasonography findings. Therefore, the patient was diagnosed with synchronous pulmonary metastases of both colon cancer and occult thyroid cancer in the same lobe. This is an exceedingly rare case;to the best of our knowledge, there has been no report thus far regarding multiple pulmonary metastases from different primary sites.
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PMID:[Pulmonary metastases from colon cancer and occult thyroid cancer in the same lobe]. 2491 98

The human retinoblastoma binding protein 6 (RBBP6) is implicated in esophageal, lung, hepatocellular and colon cancers. Furthermore, RBBP6 was identified as a strong marker for colon cancer prognosis and as a predisposing factor in familial myeloproliferative neoplasms. Functionally, the mammalian protein interacts with p53 and enhances the activity of Mdm2, the prototypical negative regulator of p53. However, since RBBP6 (known as PACT in mice) exists in multiple isoforms and pact-/- mice exhibit a more severe phenotype than mdm2-/- mutants, it must possess some Mdm2-independent functions. The function of the invertebrate homologue is poorly understood. This is complicated by the absence of the Mdm2 gene in both Drosophila and Caenorhabditis elegans. We have experimentally identified the promoter region of Snama, the Drosophila homologue, analyzed potential transcription factor binding sites and confirmed the existence of an additional isoform. Using band shift and co-immunoprecipitation assays combined with mass spectrometry, we found evidence that this gene may be regulated by, amongst others, DREF, which regulates hundreds of genes related to cell proliferation. The potential transcription factors for Snama fall into distinct functional groups, including anteroposterior embryonic patterning and nucleic acid metabolism. Significantly, previous work in mice shows that pact-/- induces an anteroposterior phenotype in embryos when rescued by simultaneous deletion of p53. Taken together, these observations indicate the significance of RBBP6 proteins in carcinogenesis and in developmental defects.
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PMID:The Drosophila retinoblastoma binding protein 6 family member has two isoforms and is potentially involved in embryonic patterning. 2595 46

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.
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PMID:Risk factors for malignancy in systemic sclerosis patients. 2711 99


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