Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer is an important problem in the United States. It results in more deaths (over 10,000 annually) than rectal cancer. Furthermore, the incidence of esophageal adenocarcinoma is increasing at a rate faster than that of nearly any other cancer and the reasons for the increase are not well understood. A variety of tumor-suppressor genes (including p53, APC, DCC and Rb) and proto-oncogenes (including prad1, EGFR, c-erb-2 and TGF alpha) may be involved in the development and progression of esophageal cancer. Clinical prognostic factors include stage, Karnofsky performance status, sex, age, anatomic location of the tumor, and degree of weight loss. A new staging system based on depth of wall penetration and lymph node involvement correlates well with prognosis for patients undergoing esophagectomy. Newer staging procedures including endoscopic ultrasound as well as the use of minimally invasive surgery, such as thoracoscopy and laparoscopy, may allow accurate staging without esophagectomy. Surgical resection provides excellent palliation; however, the chance for cure with esophagectomy alone is only 10% to 20%. Adjuvant treatment with pre- or postesophagectomy radiation may improve local-regional control but does not improve survival. Nor has preoperative chemotherapy been shown to improve survival; however, it remains an active area of investigation. Multimodality therapy, namely, chemotherapy and radiation (chemoradiation), given concurrently prior to surgical resection shows promise, with one study indicating a 5-year survival of 34%. A complete pathologic response to chemoradiation correlates with improved survival. Chemoradiation has been shown to be superior to radiation as primary management of esophageal cancer. There has been no successfully completed randomized trial of surgery versus definitive radiation or chemoradiation. However, chemoradiation represents a reasonable alternative to esophagectomy in the primary management of squamous cell carcinoma of the esophagus and chemoradiation also appears to be effective in the treatment of patients with adenocarcinoma of the esophagus, offering significant palliation and a chance for long-term survival as well. Randomized studies of preoperative chemoradiation versus surgery or versus chemoradiation alone are needed. The treatment of advanced esophageal cancer must be directed toward palliation of symptoms. Newer endoscopic techniques, including the use of expansile metal stents, laser ablation, intraluminal high-dose rate brachytherapy, BICAP tumor probe, or photodynamic therapy, offer selected patients short-term palliation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Esophageal cancer. 753 69

EphB2, a member of the Eph receptor protein-tyrosine kinase family, is overexpressed in several human gastrointestinal tumors. Furthermore, the EphB2 gene is localized at 1p35-p36.1, a frequently deleted region in colon and other cancers. So, despite its overexpression in some kind of tumors, we decided to study the possibility of involvement in the EphB2 gene (EPHB2) mutation in colon cancers, because some of the well known tumor suppressor genes (e.g. p53) is overexpressed (really accumulated) in tumors. Fifty colon tumor samples of matched with their respective normal tissues, were studied for mutation of the EPHB2. Analysis of the genomic structure of EphB2 and survey of all 16 exons revealed an infrequent polymorphism (intron 2) and mutation (intron 8). Another polymorphism in exon 6, localized at nucleotide 1359 (A-->G) was found to be rather frequent in Japanese and Chinese subjects, but very rare in Caucasians. Taking advantage of this polymorphism within EPHB2, we surveyed the loss of heterozygosity (LOH) status of this gene in Japanese colorectal tumors. Among the 50 samples analyzed, 24 were informative, and LOH was found in five of the15 (33.3%) informative rectal cancer cases. Mutation analysis covering all 16 exons in the remaining allele did not reveal any mutations. Thus, EPHB2 is not a classical tumor suppressor gene.
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PMID:Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer. 1116 21

Folate is crucial for normal DNA methylation, synthesis and repair, and deficiency of this nutrient is hypothesized to lead to cancer through disruption of these processes. There is some evidence to suggest that relatively high dietary folate intake might be associated with reduced colorectal cancer risk, especially among individuals with low methionine intake. A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993, a total of 389 women were diagnosed with colorectal cancer, identified by linkage to the Canadian Cancer Database. For comparative purposes, a subcohort of 5,681 women was randomly selected from the full dietary cohort at baseline. After exclusions for various reasons, the analyses were based on 295 cases and 5,334 non-cases. Folate intake was inversely associated with colorectal cancer risk (IRR = 0.6, 95% CI = 0.4-1.1, p for trend = 0.25). The inverse association was essentially similar among individuals with low and high methionine intake, and was similar for colon and rectal cancers when those endpoints were analyzed separately. Among individuals with low methionine intake, folate intake did not appear to lower the risk of rectal cancer, a finding that may be due, in part, to the low number of cases in the subgroup analysis. Overall, our data lend some support to the hypothesis that high folate intake is associated with a reduced risk of colorectal cancer.
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PMID:Dietary intake of folic acid and colorectal cancer risk in a cohort of women. 1185 69

We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, E-cadherin, beta-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Immunostaining revealed frequent upregulation and/or aberrant staining patterns for several of the markers, but Ki-67, p53, Bcl-2 and EGFR did not show any correlation to prognosis. However, reduced membranous staining for beta-catenin (p = 0.04), lack of cytoplasmic staining for beta-catenin (p = 0.04), reduced membranous staining for E-cadherin (p = 0.02) and lack of cytoplasmic staining for E-cadherin (p = 0.02) correlated with metastatic disease. Multivariate analysis including the factors Dukes' stage and tumor differentiation grade demonstrated increased risk of metastatic disease in tumors with lack of cytoplasmic staining for beta-catenin (HR = 3.1, p = 0.02), reduced membranous staining for beta-catenin (HR = 1.7, p = 0.06) and reduced membranous staining for E-cadherin (HR = 2.1, p = 0.06). Loss of MMR protein expression was confirmed to be a rare event in rectal cancer with loss of MLH1 staining in 3% and MSH2 in 1% of the tumors. The lack of prognostic information contributed by most of these markers suggests that single markers for prognosis may be of limited value in rectal cancer. However, altered expression of beta-catenin and E-cadherin correlated with metastatic disease, and these markers may have prognostic importance in rectal cancer.
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PMID:Immunohistochemical patterns in rectal cancer: application of tissue microarray with prognostic correlations. 1530 Aug 4

Much information has been reported on the genetic and genomic alterations in colorectal cancer (CRC) in literature; however, nonrandom chromosomal alterations in Chinese CRC patients have only one report in Hong Kong. To further identify genomic alteration in primary sporadic colorectal carcinomas (SCRC) in Chinese patients and understand the molecular mechanisms in CRC development, progress, and metastasis, we used comparative genomic hybridization to screen for losses and/or gains of DNA copies along chromosomes in 24 SCRC tissues from 24 patients. Comparative genomic hybridization was applied to investigate the genomic imbalance in 24 cases of primary SCRC and compared the differences between tumors in different loci and between tumors with and without metastasis. The common chromosomal alterations in the SCRC included gains of chromosomes 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q and also losses of chromosomes 9p, 16q, 17p, 18q. Among them, gains of 1q, 7q, 20q and losses of 17p, 18q were related with lymph node metastasis of SCRC (P<0.05). The gains of 4q, 7q, 20q and losses of 9p, 18q were related with the sites (P<0.05), colon and rectum, respectively; gain of 20q and loss of 9p were commonly found in the colon cancer; gain of 4q, 7q and loss of 18q were easily seen in the rectal cancer. There are multiple regions of chromosomes with copy-number changes in SCRC. The tumor suppressor genes and oncogenes on these regions may be involved in the development and progress of SCRC. The chromosome 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q regions may have oncogenes such as epidermal growth factor, MET, platelet-derived growth factor receptor A, and 9p, 16q, 17p, 18q regions may have tumor suppressor genes such as p53,DCC, IGFR1 associated with occurrence of SCRC. The chromosome 1q, 7q, 20q, 17p, 18q regions may have genes related with metastasis of SCRC. The development mechanisms of colon cancer and rectal cancer may not be completely similar. Additionally, gain of chromosome 1q was verified by the second technique-Real-time reverse transcription PCR.
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PMID:Chromosomal alteration in Chinese sporadic colorectal carcinomas detected by comparative genomic hybridization. 1752 79

We report on a patient with rectal malignant melanoma. The patient was a 40-year-old man who complained of anal bleeding. His grandmother had died of pancreatic cancer and his mother had been operated for rectal cancer. Physical examination revealed a hard mass at the 12 o'clock position, 2 cm from the anal verge. A colonoscopic examination revealed an irregular surface mass, approximately 4.0 cm in size, located on the anterior wall of the lower rectum. A biopsy of the rectal tumor showed the proliferation of epithelioid cells with pleomorphic features. Immunohistochemical analysis was performed. S-100 protein, CD-56, and KIT expression were positive, but HMB-45 expression was negative. Abdominopelvic computed tomography (CT) revealed multiple liver and lymph node metastases. With the diagnosis of neuroendocrine carcinoma of the rectum, abdominoperineal resection was performed. After the operation, the serum lactate dehydrogenase level had rapidly increased. An abdominal CT showed progressive liver metastases. Thirteen days after the surgery, abdominal angiography was performed, which showed multiple hypervascular tumor stains in the liver. The reservoir was implanted transcutaneously with the aid of angiography and the catheter was fixed to the proper hepatic artery. Neoadjuvant chemotherapy using cisplatin and irinotecan via the subcutaneous reservoir port was performed and a partial response was obtained. However, the final pathological diagnosis of the surgically resected specimen was malignant amelanotic melanoma of the rectum. Immunohistochemical expression differed between rectal biopsy specimens and surgically resected specimens. HMB-45 expression was positive and KIT expression was negative in the resected specimen. As preoperative pathological diagnosis showed rare rectal tumor, we measured the chemosensitivity of the rectal tumor using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to determine the most appropriate chemotherapy regimen for the patient. However, there were no anticancer drugs tested by CD-DST for malignant melanoma. With informed consent, the patient received two cycles of immunochemotherapy consisting of dacabazine, nimustine hydrochloride, vincristine sulfate, and interferon -beta. Although the patient was treated with immunochemotherapy for metastatic liver tumor, he died because of progression of metastases.
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PMID:Case of rectal malignant melanoma showing immunohistochemical variability in a tumor. 1796 34

Neoadjuvant chemoradiotherapy is considered at the present time as the standard treatment of most T3-4 rectal cancer. In France a combination of radiotherapy (45 Gy/5 weeks) with concurrent capecitabine (1,600 mg/m2) is the most popular protocol. Randomized trials try to optimize this approach using new cytotoxic drugs and/or radiation dose-escalation. The introduction of biotargeted therapies (anti-EGFR or antiangiogenic) is an attractive field especially selecting the treatment according to K-ras mutation. For T2 and 'early T3' present studies are using neoadjuvant chemoradiation followed by transanal local excision in case of good tumor response. In frail elderly patients, a new trend is to use mainly exclusive irradiation to control the tumor and avoid the excessive toxicity of open surgery in this group of patients. As rectal cancer is presenting many different clinical situations, an individualised treatment appears justified.
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PMID:[Neoadjuvant approach for non-metastatic rectal cancer combining radiotherapy and chemotherapy. Biotargeted drugs]. 1931 10

This case-cohort study examined the association between plasma enterolactone concentration and incidence of colon and rectal cancer in the Diet, Cancer and Health cohort, which enrolled 57,053 participants aged 50-64. Information about diet and lifestyle was obtained by questionnaire, and data on prescriptions of antibiotics were obtained from the Danish Prescription Registry. Cases diagnosed during 5.9 years of follow-up and a randomly selected sample of the cohort had a plasma sample analyzed for enterolactone by time-resolved fluoro-immuno assay. Associations were analyzed by Cox proportional hazards model. A total of 244 colon cancer cases, 137 rectal cancer cases, and 370 sub-cohort members were included in the statistical analyses. For each doubling in enterolactone concentration, we found lower risk of colon cancer among women [IRR (95% CI) = 0.76 (0.60-0.96)] and a tendency toward lower risk of rectal cancer [IRR (95% CI) = 0.83 (0.60-1.14)]. Among men, a doubling in enterolactone tended to be associated with higher risk of colon cancer [IRR (95% CI) = 1.09 (0.89-1.34)] and was associated with statistically significantly higher risk of rectal cancer [IRR (95% CI) = 1.74 (1.25-2.44)]. Exclusion of antibiotics users strengthened the results slightly. In conclusion, with higher enterolactone levels, we found lower risk of colon cancer among women and higher risk of rectal cancer among men.
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PMID:Plasma enterolactone and risk of colon and rectal cancer in a case-cohort study of Danish men and women. 1984 97

Previously, significant increase in survival in locally-advanced rectal cancer as a result of heated intraoperative intraperitoneal chemotherapy was reported. Our study used cisplatin 0.5 mg/ml (0.05 per cent solution) in the culture of pharyngeal epidermoid carcinoma (PEC) cells (HEP-2) and A-549 culture of lung carcinoma cells. The number of viable cells was estimated colorimetrically after 24 and 48 hr incubation. 50%-rise in inhibition of culture growth was assumed to be biologically significant. Forty-eight hours after inoculation, single dose of cisplatin 8 mg/kg was injected in mice bearing transplanted lung carcinoma of Lewis (LLC). That was followed by death of tumor cells. Preheating (45 deg. C, 1 hr) did not influence either the cytostatic or therapeutic effect of cisplatin in vivo.That procedure inhibited tumor growth by 7-8% and the effect did not wear off until day 11 or longer. Survival in LLC-bearing mice rose by 26% which pointed to the advantages offered by heated cytostatic chemotherapy.
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PMID:[Experimental foundation of using intraoperative endopelvic cisplatin with hyperthermia for rectal cancer]. 2055 96

Anti-EGFR monoclonal antibodies, cetuximab, and panitumumab, are administrated under the condition that advanced colo-rectal cancer (CRC) carries a wild-type KRAS gene. Thus, clinicians request pathologists to genotype KRAS before treatment. In the near future routine mutation testing at the same time of the surgery may be implemented. The reliability of a rapid KRAS testing on ex vivo cytological samples obtained by direct scraping of the colon tumour tissue is here evaluated. A consecutive series of 20 surgically resected, primary CRC specimens was analysed. Fresh tissue from CRC was scraped with a scalpel blade, smeared on uncoated glass slides, air-dried and Diff-Quik stained to ensure malignant cell presence. The same tissue area was also histologically processed. Exon 2 KRAS gene mutations were evaluated on both cytological and histological specimens by dideoxy sequencing and by the DxS KRAS Mutation Test Kit (DxS, Manchester, England). Data obtained on on imprint cytology and matched histological samples showed full concordance; however, the mutation frequency was slightly higher (35%) by the DxS KRAS Mutation Test Kit than by the dideoxy sequencing (30%). Thus, colon cancer imprint cytology sample is a reliable biospecimen for both dideoxy-sequencing and DxS KRAS Mutation Test Kit analysis and it may be useful to abbreviate the KRAS assay turnaround time.
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PMID:KRAS testing on colo-rectal carcinoma cytological imprints. 2060 79


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