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)

Nine platinum analogs are currently in clinical development, including three that contain the diaminocyclohexane substituent and five that contain the cyclobutanedicarboxylato leaving group. Many of them have shown activity in at least one cisplatin (CDDP)-resistant cell line, most commonly L1210 murine leukemia. In addition, most were less nephrotoxic than CDDP in preclinical evaluations. While these agents share certain key structural similarities, there are important differences in their toxicity profiles that may be exploitable in future combination therapies. Though neuropathy has been a troubling toxicity with two of the three diaminocyclohexane (DACH) compounds, it differs in that it appears to be less chronic and cumulative with oxaliplatin (I-OHP), which is also associated with much less myelosuppression. Of the cyclobutanedicarboxylato compounds that are structurally related to carboplatin (CBDCA), there are several notable differences. For several compounds, isolated neutropenia has been dose-limiting and thrombocytopenia, which is common with CBDCA, has been uncommon. Like CBDCA, neurotoxicity has not been an issue with this group. Therefore, the potential for dose escalation with a colony stimulating factor (CSF) appears enhanced. Furthermore, promising early clinical leads, such as the substantial response rates in cervix and head and neck cancers with 254-S and in patients with colon cancer using circadian modulation of I-OHP, require careful evaluation. Preclinical synergy data are also cited that suggest other potential clinical leads. The development of a number of these agents has been complicated by unanticipated issues, including unexpected chronic dose-limiting neurotoxicity with ormaplatin (OP), formulation and stability problems with liposomal-neodecanoato-diaminocyclohexane platinum (II) (L-NDDP), and problematic nephrotoxicity with zeniplatin (ZP). However, several of these new compounds are likely to enter broader phase II and III development and should provide important information not only about the utility of the agents themselves but also about the predictive value of some of these preclinical models of CDDP resistance.
Semin Oncol 1992 Dec
PMID:The current status of new platinum analogs. 146 69

Gastrin has been postulated to stimulate proliferation in colorectal neoplasms. Although gastrin mRNA has been demonstrated to be present in colon cancer cell lines, the intact peptide had not been recovered from human colorectal neoplasms. We demonstrate that gastrin and its precursors are present in both colorectal neoplasia and adjacent normal-appearing colonic mucosa. In colonic tissue, the glycine-extended precursor form of the peptide is over 10-fold more abundant than the amidated gastrin, and progastrin is more than 700-fold more abundant. In contrast, amidated gastrin in the human antrum is the predominant form of gastrin by a factor of 10. Furthermore, the ratio of gastrin precursors to gastrin is significantly increased in neoplastic colonic mucosa when compared with normal colonic tissue. These data suggest that the processing of gastrin is unique in the human colon and that further differences in processing occur in neoplastic colonic tissue.
Biochem Biophys Res Commun 1992 Dec 15
PMID:Post-translational processing of gastrin in neoplastic human colonic tissues. 147 26

We have produced a high-affinity chimeric anti-colorectal carcinoma antibody, ccM4, chimerized in both heavy and light chains by the construction of two expression vectors, the chimeric heavy-chain expression vector mpSV2neo-EP1-Vm4Cr1 and chimeric light-chain vector mpSV2gpt-EP1-VKCK. These vectors contained the neo or gpt gene as a selection marker, the murine immunoglobulin promoter and enhancer (EP1), the genomic DNA fragments of human immunoglobulin constant region (CK and C gamma 1), and murine cDNA fragments of VH and VK region amplified and cloned directly from the B72.3 hybridoma RNA by the polymer chain reaction technique. These two vector DNAs were sequentially transfected into the SP2/0Ag14 cell line. Transfectants were selected in media containing both G418 and mycophenolic acid. The ccM4 antibody was purified from transfectant supernatants with positive binding reactivity for the TAG72 antigen on a protein A column. We demonstrated that ccM4 antibody retained the same high binding reactivity for the TAG72 antigen as its counterpart, the high-affinity chimeric heavy-chain cB72.3m4 antibody. The ccM4 antibody bound specifically to human colon cancer cells, displayed biodistribution patterns similar to cB72.3m4 antibody, and mediated effective antibody-dependent cellular cytotoxicity to human OVCAR3 tumor cells. Therefore, the high-affinity chimeric ccM4 antibody should be useful in cancer immunotherapy.
Mol Biother 1992 Dec
PMID:Construction and characterization of a high-affinity chimeric anti-colorectal carcinoma antibody ccM4. 147 71

In a double blind study, patients with operable carcinoma of the colon and the upper rectum, who have undergone a macroscopically complete resection of their tumor, were randomized to receive either (i) polyadenylic-polyuridylic acid (AU), one i.v. injection of 60 mg (in 50 ml of solution) once a week for 6 weeks, or (ii) a placebo (P) one i.v. injection of 50 ml of a saline solution with the same schedule. From January 1983 to December 1986, 288 patients were enrolled: 145 in AU group and 143 in P group. The main clinical and pathological characteristics were equally distributed throughout the two groups. There was a significant difference (P < 0.02) in the overall survival (OS) between the two groups, in favor of the P group. The 5-year OS rate was 68% (SD = 4%) in the AU group versus 81% (SD = 3%) in the P group. Thus, AU as a single adjuvant, appears to be ineffective and therefore has no indication in the treatment of colorectal carcinoma.
Eur J Surg Oncol 1992 Dec
PMID:Polyadenylic-polyuridylic acid as an adjuvant in resectable colorectal carcinoma: a 6 1/2 year follow-up analysis of a multicentric double blind randomized trial. 147 93

A 50-year-old woman underwent percutaneous ultrasonographic fine needle biopsy of a suspicious liver metastasis of colon cancer. A subcutaneous metastasis developed at the site of the puncture 20 days after biopsy. Tumor recurrence in the needle biopsy track is rarely reported in the literature. The possible causes of this complication are discussed.
Eur J Surg Oncol 1992 Dec
PMID:Subcutaneous implantation of liver metastasis after fine needle biopsy. 147 99

Six members of the International Society for Environmental Epidemiology provide a discussion of the presentations of the authors of six studies dealing with the potential chronic disease side effects of water disinfection. This symposium, which was jointly sponsored by the Society and the United States Environmental Protection Agency (EPA) also involved state epidemiologists and engineers from state drinking water programs. This article summarizes the results of the studies and the comments about them. There was a general consensus that the recent EPA sponsored studies of cancer endpoints have strengthened the evidence linking bladder cancer with long term exposure to chlorinated drinking water. The evidence for links with colon cancer is not convincing and that for serum lipid changes is quite weak. Any risks, if real, are low when compared to the risk of infection from not disinfecting water. This is particularly true for small water systems where chlorination may be the only practical option.
Sci Total Environ 1992 Dec 15
PMID:An evaluation of the role of epidemiology in assessing current and future disinfection technologies for drinking water. 148 Sep 62

Epidemiological studies have consistently demonstrated that either occupational or recreational physical activity is protective against colon cancer. However, it is unclear whether recreational activity is similarly protective among those who engage in high or low occupational activity. We therefore compared 440 male cases of colorectal cancer with 1164 male hospital patients. Occupational activity was defined according to job title, while recreational activity was assessed by questionnaire for three different periods of life. Occupational activity was protective with respect to colorectal cancer irrespective of whether one engaged in recreational activity at any different period of life. In contrast, recreational activity, performed at 20-44 years of age appeared to decrease colon cancer risk by 10-25% irrespective of the intensity of job activity. The present results suggest that, although we observed a larger effect with occupational activity than with recreational activity, middle-aged men may reduce their risk of colorectal cancer if they exercise when they are not working. These findings need to be confirmed in other populations.
Int J Epidemiol 1992 Dec
PMID:Effect of occupational and recreational activity on the risk of colorectal cancer among males: a case-control study. 796 Mar 96

Mannich bases were synthesized and converted to the corresponding arylhydrazones. X-ray analysis of a ketone (1a) and a hydrazone (4d) revealed structural features of interest. All of the compounds showed cytotoxicity toward murine lymphocytic leukemia L1210 cells in the 4.9-25.0-microM range. The correlation coefficients generated by plotting the IC50 values (the concentrations of compounds that inhibit the growth of tumors by 50%) of some hydrazones against certain electronic, hydrophobic, and steric constants of the aryl substituents indicated only weak correlations. A few ketones and hydrazones displayed significant cytotoxicity to the WiDr human colon cancer cells, and these derivatives, especially the ketones, may serve as prototypes for future drug development. The KB tumor (a human epidermoid carcinoma of the nasopharynx) was somewhat refractory to selected compounds. In an in vitro assay conducted by the National Cancer Institute and involving approximately 53 tumor cell lines originating from eight neoplastic diseases, 65% of the compounds showed some selectivity toward one or more groups of cancers, principally leukemia, melanoma, and colon cancer. The bioevaluation of the ketones and hydrazones against the L1210, WiDr, and KB tumors, as well as evidence from proton nuclear magnetic resonance studies did not support the suggestion that hydrazones may be prodrugs of the corresponding ketones.
J Pharm Sci 1992 Dec
PMID:Evaluation of cytotoxicity of some Mannich bases of various aryl and arylidene ketones and their corresponding arylhydrazones. 149 28

Colonic carcinogenesis is probably related to a disturbance in cell proliferation of the colonic mucosa. The present study was designed to determine whether patients with adenomatous polyps of the colon, which have a tendency to develop synchronous malignancies of the colon, have any disturbance in mucosal cell proliferation. Using flow cytometry the proliferative index, and the S and G2M phases of normal mucosa and tumoral tissue of patients with colorectal cancer (synchronous, alone, or associated with adenomatous polyps) were studied. No differences were found between the there groups of study at the level of proliferation pattern of normal mucosa. Our findings do not support the development of synchronous or metachronous colon cancer in patients with polyps on the basis of different patterns of cell proliferation.
Rev Esp Enferm Dig 1992 Dec
PMID:[A cellular proliferation study in patients with colorectal cancer, solitary, synchronous and with polyps]. 149 58

We installed a Kock continent reservoir in 103 patients after radical cystectomy or pelvic exenteration between Feb. 1986 and Dec. 1989. They consisted of 81 male and 22 female patients. Patients' age ranged from 30 to 78 years with the average being 63 years. Their original diseases were bladder cancer (96 patients), prostatic cancer (2), sigmoid colon cancer (2) and others (3), The Kock reservoir was made by the procedure described by D. G. Skinner et al. The mean operation time for reservoir creation was 220 minutes. In 99 patients with a Kock reservoir for more than 3 months, the capacity of the reservoir was 200-900 ml with the average being 490 ml and the frequency of self-catheterization was 4 to 6 times a day. Early complications occurred within 3 months in 27 (26%) patients. Complications directly related to the reservoir were urine leakage (5 patients), intestine reservoir fistula formation (3) and necrosis of the reservoir (1). Late complications occurred after 3 months in 25 (25%) patients. They consisted of difficulty of catheterization (9 patients), ureteral reflux from reservoir (2), hydronephrosis (8), abscess (4), metabolic acidosis (2) and others. The results indicated that this procedure is an appropriate urinary diversion since the quality of life in the patients with a Kock reservoir is better. However, after this procedure surgical complications were not infrequent. Therefore, this procedure should be performed in selected patients.
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PMID:[Complications of Kock continent reservoir. Report of 103 cases]. 159 27


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