UMLS:C0699790 - FACTA Search

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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the mortality of 835 white male and 36 female laboratory workers employed by the U.S. Department of Agriculture who died between January 1, 1970, and December 31, 1979. For males, the mortality odds ratio for all cancers was 1.0 (95% confidence interval = 0.8-1.2). Colon cancer, lymphosarcoma and reticulosarcoma, nonmalignant diseases of the blood and blood-forming organs, and suicide showed elevated mortality odds ratios. Only colon cancer showed an association with duration of employment as a laboratory worker. In an accompanying case-control study, the risk of colon cancer rose to 3.2 among those who had 20 or more years of employment as a laboratory worker. Among females, breast cancer was elevated (mortality odds ratio = 5.3; 95% confidence interval = 2.8-10.1).
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PMID:Mortality among laboratory workers employed at the U.S. Department of Agriculture. 159 26

To evaluate the potential carcinogenic effects of formaldehyde, we examined the proportionate mortality experience of embalmers licensed to practice in California. Mortality was significantly elevated for total cancer, arteriosclerotic heart disease, and suicide, whereas significant deficits were noted in mortality from diseases of the respiratory and genitourinary systems. Deaths from cancers of the brain, colon, and prostate and leukemia were significantly higher than expected. No increased mortality was seen for cancers of the respiratory tract, including the nasal passages, where an effect might be expected based on animal studies. A parallel mortality survey of embalmers from New York State showed similar findings, with excesses of brain tumors, leukemia, colon cancer, arteriosclerotic heart disease, and cirrhosis. Further investigation is needed to determine whether any of these outcomes is related to formaldehyde exposure.
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PMID:Cancer and other causes of death among embalmers. 646 19

The mortality profile of female nurses and teachers in British Columbia (BC) was examined using age-standardized proportional mortality ratios (PMRs) calculated for the period 1950-1984. Lowered overall mortality among nurses was seen for degenerative heart disease and for cerebrovascular accidents. Significantly elevated PMR values were observed for cancer of the breast and ovary in nurses of age 20-65 years. PMRs were significantly elevated for cancer of the pancreas and leukemia among those age 20 years and older. Elevated values were also observed for motor vehicle accidents and suicide among nurses in both age groups. Lower than expected mortality from degenerative heart disease and cerebrovascular accidents was seen in working age teachers (age 20-65 years). However, elevated PMRs were detected for carcinoma of the colon, breast, endometrium, brain, and melanoma. Among those 20 years and over, significantly elevated PMRs were also observed for cancers of the ovary and other digestive organs. Elevated PMRs were found for motor vehicle and aircraft accidents. Mortality from cirrhosis of the liver was lower than anticipated in both teachers and nurses. A number of significant PMRs declined when deaths of "homemakers" were withdrawn from the comparison group used to generate PMR values, suggesting that risk of death from various causes among women working outside the home differ from those seen in women who are predominantly in the home.
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PMID:Mortality among female registered nurses and school teachers in British Columbia. 807 20

This study presents findings from an updated retrospective cohort mortality study of male police officers from January 1, 1950 to December 31, 1990 (n = 2,593; 58,474 person-years; 98% follow-up). Significantly higher than expected mortality rates were found for all cause mortality (Standardized mortality ratio [SMR] = 110; 95% confidence interval [95% CI] = 1.04-1.17), all malignant neoplasms (SMR = 125; 95% CI = 1.10-1.41), cancer of the esophagus (SMR = 213; 95% CI = 1.01-3.91), cancer of the colon (SMR = 187; 95% CI = 1.29-2.59), cancer of the kidney (SMR = 2.08, 95% CI = 100-3.82), Hodgkin's disease (SMR = 313; 95% CI = 1.01-7.29), cirrhosis of the liver (SMR = 150; 95% CI = 1.00-2.16), and suicide (SMR = 153; 95% CI = 1.00-2.24). All accidents were significantly lower (SMR = 53; 95% CI = 0.34-0.79). Mortality by years of police service showed higher than expected rates for (1) all malignant neoplasms in the 1- to 9-years-of-service group; (2) all causes, bladder cancer, leukemia, and arteriosclerotic heart disease in the 10 to 19-year group; and (3) colon cancer and cirrhosis of the liver in the over 30 years of service group. Hypotheses for findings are discussed.
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PMID:Mortality of a police cohort: 1950-1990. 951 43

A bystander effect is described when nontransduced or genetically unmodified cells are killed during death of genetically modified tumor cells transduced with a suicide gene. The "bystander effect" greatly enhances the efficacy of the herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy approach for cancer. The mechanism of the bystander effect is controversial. In this study, we examined the role of intercellular gap junction communication (GJIC) for the bystander effect in human gastrointestinal tumor cells. Our results show that the extent of the bystander effect varied amongst the tumor cell lines; pancreatic cancer cells BXPC-3 exhibited excellent bystander effects in vitro and in vivo studies whereas other gastrointestinal tumor cell lines such as pancreatic cancer cells MIAPACA-2, and colon cancer cells HT-29 showed poor bystander effects. Bystander effects were only found in the presence of cell-to-cell contact. The extent of the bystander effect was independent of the level of HSV-TK activity in the transduced tumor cells and was correlated with GJIC as demonstrated by an in vitro dye-transfer assay. Expression of the mRNA levels of gap junction protein connexin 43 was 8- to 26-fold or greater and connexin 26 gene expression was 2- to 229-fold greater in BXPC-3 cells compared to HT-29, MIAPACA-2, and PANC3 cells. Our results suggest that intercellular communication is essential for the bystander effect. The correlation between GJIC and the extent of the bystander effect suggest a role for GJIC in mediating the bystander effect. Analysis of tumors for GJIC or expression of gap junction proteins may identify the subset of patients suitable for gene therapy with the HSV-TK/GCV approach.
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PMID:Intercellular communication mediates the bystander effect during herpes simplex thymidine kinase/ganciclovir-based gene therapy of human gastrointestinal tumor cells. 955 19

The enormous number of newly diagnosed cases of colorectal cancer that occur each year and the lack of agents that are highly effective for all patients underscore the need for novel approaches to combating the disease. Gene therapy as a developing treatment modality is already well established, with a number of trials ongoing and a vast range of other approaches being assessed in animal and cell culture experiments. In this brief review, we have discussed five gene therapy trials in colon carcinoma that are ongoing or in the approval process in the United States. The gene therapy approaches being employed can be divided into three major categories: (1) enzyme/prodrug systems (HSVtk/ganciclovir; CD/5-fluorocytosine); (2) tumor suppressor gene replacement therapy with wild-type p53; and (3) immune-gene therapy which is based on cytokine or tumor antigen expression to induce tumor immunity (e.g., CEA). Replication-deficient recombinant adenoviral vectors are predominantly used for colon cancer gene therapy, because they can be produced at high titer and they readily infect a number of different cell types. One trial uses polynucleotide therapy for antitumor immunization with intramuscular injection. All of these studies are phase I trials, principally designed to evaluate safety, but they will also provide data on gene delivery. Some trials may provide some insight into potential therapeutic effects. We have alluded to some of the concerns on toxicity related to the use of adenovirus, risks and side effects from transgenes, lack of tumor-specificity of transgene expression, and potential problems with efficient gene delivery to solid tumors. The clinical trials, however, will provide insight that will inform design of future studies with respect to dose, form, and frequency of administration, as well as to the value of biologic and clinical endpoints. The molecular analysis of the fundamental basis of colon cancer has moved at a remarkable pace and that progress seems set to continue. Thus, the basic foundations for gene therapy are undoubtedly in place: a clinical need; growing understanding of basic tumor biology; and ever-improving delivery systems. The field is at a very early stage in its evolution, and one concern is that the considerable hurdles that must be overcome are seen as examples of the failure of cancer gene therapy; however, we believe these challenges will be overcome. The authors also believe that colon cancer gene therapy is likely to take new directions, such as use as adjuvant to radical surgery, rather than attempts to treat end-stage disease when the liver is replaced by metastases. Other new directions might include prophylactic gene-based immunization against a panel of well-characterized tumor antigens, at least for persons shown to be at high risk of colon cancer because of genetic or other predisposition. A marriage between gene therapy approaches and conventional anticancer treatments such as radiotherapy and chemotherapy also seems likely. There is already evidence of this move with demonstration of synergism between p53 replacement and radiotherapy and chemotherapy. It is also likely that therapies will be developed that combine elements from the cancer gene therapies discussed previously, namely, suicide gene transfer, immune modulation, and modulation of defective cancer genes. Perhaps one of the main concerns is not that researchers in cancer gene therapy want to walk before they can run, but that the public and government agencies believe they can. The next 10 years will be an interesting time in the development of novel treatments against colon cancer.
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PMID:Gene therapy for colon cancer. 968

A major obstacle to the successful application of suicide gene therapy strategies that rely on in situ transduction of tumor cells is the poor distribution of the vector throughout the tumor mass. To address this problem, we evaluated the use of Ad.TK(RC), an E1b Mr 55,000 deleted replicating adenoviral vector engineered to express the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) in combination with ganciclovir (GCV) as a treatment for human colon cancer xenografts in nude mice. We compared the efficacy of this system with that of a standard replication-deficient adenovirus expressing HSV-tk (Ad.TK) in mice bearing LS180 tumors. In this system, Ad.TK(RC) alone was as effective as a traditional Ad.TK vector in combination with GCV. The addition of GCV significantly enhanced the antitumor effect of Ad.TK(RC). Furthermore, we demonstrated that the survival of HT-29 human colon cancer xenografted mice treated with Ad.TK(RC) and GCV was prolonged compared with Ad.TK(RC) alone or with administration of a single cycle of topotecan. These data demonstrate that the addition of direct viral oncolysis to the HSV-tk/GCV suicide gene system resulted in a striking improvement in treatment efficacy and that it may offer advantages over the use of chemotherapeutic agents for treatment of localized disease.
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PMID:Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase. 992 55

Health objectives, developed by the United States Department of Health and Human Services, were published recently in the document entitled Healthy People 2000: National Health Promotion and Disease Prevention Objectives. They were developed to guide national and local health policy toward actions to increase the health of the nation. To effectively apply these objectives locally, epidemiologists and health planners must work together. Through collaboration, the Healthy People 2000 objectives can be prioritized to guide health policy and planning on a regional basis. The purpose of this study was to assess certain health status indicators in southwestern Pennsylvania to determine whether it was likely that the year 2000 targets would be met if trends from the past 20 years were to continue. The following mortality rates were analyzed: heart disease, homicide, breast cancer, colon cancer, lung cancer, suicide, motor vehicle accidents, work-related injury, and infant mortality. In addition, incidence of the following diseases was evaluated against the year 2000 targets: gonorrhea, primary and secondary syphilis, measles, tuberculosis, and AIDS. By employing epidemiological principles and considering strategic planning needs, it is possible to prioritize some of the health care needs in local areas for the next decade.
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PMID:Epidemiologic indicators of health status to guide health care management decision making. 1013 Feb 41

Thymidine phosphorylase (dThdPase) is an enzyme that converts 5'-deoxy-5-fluorouridine (5'DFUR) to the toxic substance 5-fluorouracil (5-FU); it is also known to be a platelet-derived endothelial cell growth factor. In order to investigate the feasibility of suicide gene therapy against colorectal cancer by means of the combination of 5'DFUR and the converting enzyme dThdPase, we transfected the dThdPase gene into the human colon cancer cell line SW480 and analyzed the growth pattern as well as the sensitivity to 5-FU or 5'DFUR of the dThdPase-transfected cells. The 50% inhibition (IC50) values of 5-FU against the SW480 parental cells, control vector-transfected cells SW480/V1, and dThdPase-transfected cells SW480/dThdPase were approximately 4.9, 6.3, and 2.9 microM, respectively. The IC50 of SW480/dThdPase was lower than that of SW480 or SW480/V1, although the differences were not statistically significant. The IC50 values of 5'DFUR for SW480, SW480/V1, and SW480/dThdPase were approximately 300, 330, and 3.2 microM, respectively. The sensitivity to 5'DFUR of SW480/dThdPase was increased by about 100-fold compared with that of SW480 or SW480/V1. With only 10% transfection efficacy, a high enough sensitivity to 5'DFUR was obtained to suppress the cell growth, indicating that a strong bystander effect was induced by this system. The in vivo growth of the s.c. transplanted SW480/dThdPase tumor in nude mice was significantly suppressed by i.p. injection of 5'DFUR compared with that in control mice that received phosphate-buffered saline (PBS) treatment. These results suggest that gene therapy using the combination of 5'DFUR and the dThdPase gene may be a useful approach for treatment of colon cancer.
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PMID:Enhancement of the anti-tumor effect of 5'-deoxy-5-fluorouridine by transfection of thymidine phosphorylase gene into human colon cancer cells. 1036 85

Colon carcinoma accounts for 20% of deaths due to malignancies in the Western world. Once metastases occur, therapeutic options are limited, with an approximate 5-year survival of only 5%. To investigate the potential of new gene therapeutic approaches, a hepatic micrometastasis model of colon carcinoma in BALB/c mice was established. Inoculation of syngeneic MCA26 colon carcinoma cells into the spleens of 18- to 20-week-old mice resulted in the formation of multiple hepatic metastases. Selective transduction of developing hepatic metastases was demonstrated using a beta-galactosidase-expressing recombinant adenovirus. Cytosine deaminase (CD) can metabolize 5-fluorocytosine into the chemotherapeutic reagent 5-fluorouracil (5FU). The antitumoral potential of this suicide gene therapy approach was explored by systemic application of a recombinant replication-deficient adenovirus encoding for the bacterial CD gene under the control of the cytomegalovirus promoter (Ad.CMV-CD). Injection into the tail vein of tumor-bearing mice resulted in delayed tumor growth with significant reduction in hepatic metastases. The potential of this experimental approach for possible future clinical applications was evaluated by investigating adenoviral transduction efficiency, 5FU sensitivity, and 5-fluorocytosine-dependent Ad.CMV-CD toxicity in a variety of human colon cancer cell lines. Although the murine cell lines MCA26 and CC36 were highly sensitive to 5FU, the human colon cancer cell lines showed a 1-100 times higher resistance to 5FU. Specific Ad.CMV-CD toxicity correlates with 5FU toxicity. Transduction efficiency in human colon carcinoma cell lines was shown to be 10-1700 times higher compared with murine cell lines, thus compensating for 5FU resistance. In conclusion, suicide gene therapy using CD may be promising as an adjuvant treatment regimen for hepatic micrometastases of human colon carcinoma.
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PMID:Gene therapy of metastatic colon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase. 1076 50

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