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

Concern for a risk of cancer in humans has been prompted by the appearance of hepatocellular carcinomas in tamoxifen-treated rats. However, there is no evidence of excess hepatocellular carcinoma among tamoxifen-treated women. Moreover, liver tumors are not induced in tamoxifen-treated mice or hamsters. An explanation for the species selectivity of this toxic effect may relate to the greater rate of formation of reactive intermediates in rats than either mice or humans. This results in persistent liver DNA adducts in tamoxifen-treated rat liver exceeding those produced in treated mice or in background levels measured in women taking tamoxifen. Another observation that reduces concern for human carcinogenesis is that bioactivation of tamoxifen may be inducible at dosages used in rodent cancer bioassays but not in those used clinically. Suggestions that endometrial cancer may be tamoxifen related are not supported by rodent data for endometrial cancer. Indeed, endometrial tissue lacks the necessary tamoxifen bioactivating capacity of liver consistent with the absence of DNA adducts in the endometrium of women taking tamoxifen. Finally, it seems doubtful that the colon is a target for human carcinogenesis of tamoxifen given the negative epidemiologic studies and high-dose rodent studies. In summary, there is at present no sound scientific basis for extrapolation of rat liver cancer findings to risks of liver, endometrial, and colon cancer in women receiving tamoxifen.
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PMID:Relevance of rat liver tumors to human hepatic and endometrial cancer. 904 9

Fourteen patients with unresectable primary or metastatic liver cancer were divided into two groups: group A, continuous hepatic arterial infusion of 5-FU in 10 cases; group V, continuous intravenous infusion of 5-FU in 4 cases. In group A, 5-FU (360 mg/m2/day x 5 days/week x 4 weeks) was continuously infused into the hepatic artery via femoral or gastroduodenal artery through Infuse A Port. In group V, 5-FU (360 mg/m2/day x 2 weeks) was continuously infused into the subclavian vein through IVH route. On day 1, the concentration of 5-FU in peripheral blood in group A (12.1 +/- 12.8 ng/ml) was significantly lower than in group V (43.8 +/- 19.8 ng/ml, p = 0.004). On day 5, it was also decreased in group A (24.6 +/- 24.1 ng/ml) compared with that in group V (61.8 +/- 34.4 ng/ml, p = 0.039). Side effects of 5-FU like nausea, abdominal discomfort and stomatitis were recognized in 4 out of 10 patients in group A (40%) and 3 out of 4 patients in group V (75%). In group A, a complete response was obtained in one patient with synchronous multiple liver metastases of sigmoid colon cancer. These results suggest that systemic toxicity of 5-FU is alleviated by continuous hepatic arterial infusion in the patients with unresectable liver cancer because of its low concentration in peripheral blood.
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PMID:[Evaluation of 5-fluorouracil concentration in peripheral blood and side effects in continuous hepatic arterial infusion chemotherapy for patients with unresectable liver cancer]. 938 45

Zymosan, a non-specific macrophage-stimulating agent, modifies favourably tumour growth in the liver but has minor effect on renal tumours. The mechanism accounting for variation is still to be clarified. The effect of zymosan on liver cancer may be mediated by the macrophage-monocyte system. Kupffer cells are in vitro cytotoxic against colon cancer cell lines. The kidney is sparse in macrophage elements. The prostaglandin synthesis inhibitor, indomethacin, inhibits tumor growth. In Wistar-FU rats inoculated in the liver and the kidney with an adenocarcinoma cell suspension, pretreatment with zymosan (3 mg x 100 g[-1]) significantly reduced both tumour take and liver volume. This effect was attenuated by concomitant administration of indomethacin (0.2 mg x 100 g[-1]). After 2 weeks there was still reduced liver tumour volume. No significant effects on tumour take or growth were observed when the cells were inoculated into the kidney. There was no significant effect of zymosan on an hepatoma in Lister-Hooded rats. Pretreatment with indomethacin had no effect on tumor take or initial growth.
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PMID:The influence of zymosan and indomethacin on liver and kidney tumor growth. An experimental study in rats. 938 96

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.
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PMID:Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States). 948 66

The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.
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PMID:Surgical and nonsurgical management of primary and metastatic liver tumors. 952 Aug 9

We have been investigating the mathematical nature of intercancer linkage that underlies the mutual regulation of cancer risks between any 2 tumors in their variations in time and space. Applications of both sequential regression test and topological manipulation of age-adjusted incidence rate (AAIR) data set enabled us to prepare the oncogene (Onc) activation profile and the tumor suppressor gene (TSG) inactivation profile for each tumor. The purpose of this study was to investigate the relation between the changes of 2 cancer gene profiles and the sex discrimination of cancer risk in 7 human neoplasias. Results obtained are as follows: i) The sex discrimination of cancer risk could better be defined by the use of log-transformed AAIR data rather than of untransformed AAIR data. ii) The sex discrimination of cancer risk, as calculated with the AAIR data of 47 population units of the world, is as follows: a) breast cancer (Br), M:F=1:120.2; b) thyroid cancer (Thy), M:F=1:2. 64; c) colon cancer (Co), M:F=1.18:1; d) liver cancer (Li), M:F=2. 63:1; e) lung cancer (Lu), M:F=3.66:1; f) esophageal cancer (Eso), M:F=3.68:1; g) laryngeal cancer (Lar), M:F=7.26:1. iii) Female-dominant cancers were associated with inversion (Br) or defectiveness (Thy) of male oncogene profile, whereas male-dominant cancers were associated with inversion (Lar) or defectiveness (Li, Lu and Eso) of female Onc profiles. Sex-indifferent cancer, Co, was distinguished from other tumors by the emergence of defectiveness in the TSG profiles of both sexes. TSG defectiveness was also detectable in female (Br, Thy) and bisexual (Lu) tumors. iv) The Onc vs TSG interaction, as assessed in terms of r value of the reciprocal regression analysis, was increasing in its positivity rate from the top of the female-dominant family (Br) through the sex-indifferent tumor (Co) to the bottom of the male-dominant family (Lar). In conclusion, the emergence of sex discrimination of cancer risk was positively correlated to the extent of integrity of oncogene activation in the dominant gender relative to the recessive gender. Findings with 6 sex-discriminant tumors are discussed in their relevancy to tumorigenesis from the point of view of endocrinological epidemiology.
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PMID:Relation between the changes of oncogene versus tumor suppressor gene interaction and the transition of cancer risk from female dominance through no sex discrimination to male dominance, as investigated by the reciprocal regression analysis of 5 human neoplasias. 968 28

In various types of human malignant tumors, the presence or absence of expression of apoptosis-associated gene products (p53 protein and Bcl-2 protein) and the tumor proliferation activity-related factor (Ki-67) was assessed by immunohistochemical staining and the correlation between this expression and chemosensitivity to anticancer drugs was investigated. Study subjects comprised 55 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 11 with stomach cancer, 11 with colon cancer, 13 with hepatic cancer and 11 with breast cancer). A chemosensitivity test was carried out with the histoculture drug response assay (HDRA) method using 4 drugs, mitomycin C (MMC), 5-fluorouracil (5-FU), doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical staining was used to assess expression of p53 protein, Bcl-2 protein and Ki-67. The tumor growth inhibition index (I.I.) of the 4 drugs was significantly lower in a group of the patients with p53 protein overexpression-type (mutant p53 protein positive expression-type) tumors than in a group with p53 protein negative expression-type tumors (p<0.05). No significant correlation was found between the expression of the Bcl-2 protein by and the I.I. of any drug studied in any type of cancer. A negative correlation was found between the labeling index (L.I.) for Ki-67 in all cases and I.I. for MMC and ADM and thus, chemosensitivity of the tumors with high growth activity was lower. Furthermore, a positive correlation existed between the L.I. for Ki-67 and that for p53 protein. The patients with p53 protein overexpression-type (mutant p53 protein positive) tumors showed low chemosensitivity. In addition, overexpression of p53 protein is suggested to be one of the factors involved in the lowered chemosensitivity of the tumors with high growth activity. Summarizing these findings, the p53 protein can play an important role in cancer therapy.
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PMID:Usefulness of p53 protein, Bcl-2 protein and Ki-67 as predictors of chemosensitivity of malignant tumors. 1020 14

The anti-colon cancer effect of dietary fibre results in part from its fermentation into the short-chain fatty acid butyric acid (BA) by intestinal microflora. BA has potent anti-colon cancer properties owing to its ability to induce apoptosis in colon cancer cells. The colon is not the only location where BA may reach high concentrations, because dietary BA is rapidly absorbed and transported to the liver. We have investigated whether BA could induce apoptosis in transformed human liver (Hep G2) cells. Hep G2 cells treated with BA displayed acetylated histones, increased DNA fragmentation and morphological features consistent with apoptosis. These biochemical features of BA-treated liver cells are identical to those of BA-treated colon cells. In addition, we investigated whether BA present in tributyrin, a triacylglycerol more compatible for inclusion into colloidal lipid structures than BA, could also induce apoptosis in Hep G2 cells. Tributyrin induced DNA fragmentation and morphological features characteristic of apoptotic cells in Hep G2 cells. These results are a significant advance towards delivering BA via colloidal lipid particles to cancerous sites in vivo. This study showed that BA and tributyrin are potent apoptotic agents, and we suggest that sources of dietary BA, such as milk fat, may provide anti-liver cancer properties.
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PMID:Butyric acid and tributyrin induce apoptosis in human hepatic tumour cells. 1061 54

Chemoprevention is a recently introduced and rapidly growing area of oncology that is identifying agents with a potentially preventive role in cancer. Several clinical trials have recently shown the feasibility of this approach in reducing the risk of major human cancers. In the USA, a large trial that demonstrated a reduction of approximately 50% in the risk of developing breast cancer led to Food and Drug Administration (FDA) approval of tamoxifen as a preventive agent in women at increased risk. Although the results could not be reproduced in two smaller European trials, further investigations into this agent are clearly warranted. Raloxifene, another selective oestrogen receptor modulator which has reduced the risk of breast cancer in a trial in women with osteoporosis, is being compared with tamoxifen in a large primary prevention trial in at-risk women. Retinoids are a group of compounds that have proved especially effective in reducing the occurrence of second primary tumours in subjects with skin, head and neck or liver cancer. Fenretinide, a synthetic retinoic acid derivative, has recently been shown to decrease the occurrence of a second breast malignancy in premenopausal women. Results with non-steroidal anti-inflammatory drugs (NSAIDs) have proved consistently encouraging in epidemiological studies in lowering the incidence of colorectal cancer. Clinical trials with selective cyclo-oxygenase inhibitors potentially devoid of gastrointestinal (GI) toxicity are currently underway in at-risk subjects. Calcium and selenium have also received much attention as chemopreventive agents. Originally investigated against skin cancer, selenium showed efficacy in reducing prostate, lung and colon cancer incidence. Similarly, vitamin E was effective in reducing prostate cancer incidence and mortality in a lung cancer prevention trial in heavy smokers. The challenges of conducting well-designed and unequivocal chemoprevention trials are considerable, but advances in techniques of identification of at-risk subjects and establishing surrogate endpoint biomarkers should contribute greatly to future studies. Current knowledge suggests that a pharmacological approach to preventing cancer, using natural or synthetic agents, could become an important way forward.
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PMID:Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer. 1076 41

The complex of poly(I):poly(C) and a new cationic liposome (LIC) has a potent antitumor activity against many tumor cell lines in vitro, whereas poly(I):poly(C) itself has no such activity. In the present study we tested the sensitivity of 21 human colon and pancreatic cancer cell lines to LIC or Adriamycin in vitro. The growth of most of the cell lines was strongly inhibited by both LIC and Adriamycin in vitro, although a few insensitive cell lines were different. We also studied the in vivo antitumor activity of LIC or Adriamycin in three experimental liver metastasis models in nude mice using a human pancreatic cancer cell line (AsPC-1) and two human colon cancer cell lines (Ls174T and HCC-M1544). The administration of LIC or Adriamycin was started 3 days after the injection of tumor cells. Animals received 0.1 mg/kg LIC IV twice weekly or 5 mg/kg Adriamycin IV every 5 days during the experiments. LIC showed potent antitumor activity in all three liver cancer models. Although Adriamycin had potent antitumor activity in the HCC-M1544 model, it had only a moderate effect in the AsPC-1 model and at most a weak effect in the Ls174T model. At the effective doses LIC did not cause detectable pathological changes in the liver and did not elicit toxicity to mice in these models, whereas Adriamycin did exhibit toxic effects. These results suggest that LIC is a promising candidate drug to treat hepatic metastasis.
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PMID:Inhibition of metastatic carcinoma cell growth in livers by poly(I):poly(C)/cationic liposome complex (LIC). 1090 61


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