Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, since it may allow tumors to escape immune surveillance. We studied the expression of HLA class I and II antigens in the colons of 10 patients with familial adenomatous polyposis (FAP), a condition which leads inevitably to colorectal cancer. Expression of HLA class antigens was studied by immunohistochemistry in (a) adenomas from patients with FAP, (b) histologically normal mucosa distant from the adenomas, and (c) histologically normal colonic mucosa from normal subjects. The expression of HLA class I and II antigens was decreased in histologically normal mucosa from FAP patients compared to normal controls. Adenomas showed a similar but quantitatively more pronounced reduction (or loss) of HLA antigen expression. The reduction of HLA expression in adenomas was comparable to that observed in sporadic colon carcinomas. This generalized suppression of HLA gene expression in the colon of FAP patients, which precedes the onset of overt histological manifestations of neoplasia, may be an important early event in colon carcinogenesis.
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PMID:Loss of colonic HLA antigens in familial adenomatous polyposis. 131 51

Specific and nonspecific stimulation of the host immune system to reject cancer is an attractive concept that is just beginning to mature. Results with crude extracts and nonspecific immune stimulation have been variable. However, the recent observations of improved survival after administration of levamisole plus 5-fluorouracil in the adjuvant setting have made an impact on the treatment of colorectal cancer. Animal studies consistently show that immune therapies are most effective for disease that is not advanced. Thus, the small benefit seen with levamisole, a low toxicity immunomodulator, suggests that much more impressive results can be anticipated with more potent and specific agents. Postsurgical autologous tumor cell vaccine has been effective in some prospective randomized trials; in others, no benefit was found. The identification and purification of allogeneic tumor-associated antigens has lead to enhanced antigen-specific host cell-mediated immunity; this may result in more consistent antitumor effects. The current development of chemically defined immune adjuvants of low toxicity allows tumor-specific immune stimulation to be tested in high-risk apparently healthy patients after resection of colorectal cancer (Stages II and III). The influx of information regarding immune cell populations, cell-surface markers, and cytokines has fostered extensive exploration of lymphocyte stimulation, in vitro cell growth and expansion, and in vivo evaluation in patients with advanced cancer. Modest tumor response rates have been documented with adoptive transfer of lymphokine-activated killer cells and interleukin-2. Improved results are anticipated with the more potent tumor-infiltrating lymphocytes and specific in vitro sensitization of draining lymph node cells to autologous and allogeneic tumor antigens. Murine monoclonal antibodies specific for cell-surface markers, such as carcinoembryonic antigen, have been tested for their value in the diagnosis and therapy of colorectal cancer. A small response rate has been seen with single and multiple injections of C017-1A, a monoclonal antibody specific for colonic and pancreatic cancer. The development of antiidiotypic antibodies in these patients may have been important in those that responded to this type of therapy. However, laboratory evidence suggests that monoclonal antibody conjugated to a cytotoxic agent (i.e., radionuclide, drug, or toxin) should be much more effective. Radioimmunotherapy trials in the nude mouse model bearing human colon cancer xenografts showed good tumor incorporation of the radionuclide (yttrium 90 or iodine 131), inhibition of tumor growth, and long-term survival.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunotherapy of colorectal cancer. 151 94

Interleukin-1 alpha (IL-1 alpha) is a low-molecular-weight cytokine that regulates proliferation and differentiation of lymphatic and myeloid cells. It also has pleiotropic activity on a variety of other target cells and acts as an important mediator of inflammation and septic shock. Recombinant human IL-1 alpha (rhIL-1 alpha) is undergoing clinical evaluation of its potential as an anticancer agent. We have studied the growth modulating effects of rhIL-1 alpha on a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.01-100 ng/ml were used in continuous incubation experiments. Of 139 specimens tested, 56 (40%) were evaluable for determination of tumor growth modulating activity. The most common tumor types examined included breast, nonsmall cell lung, ovarian, colorectal cancer, and melanoma. Stimulation of tumor colony-forming units (colony formation greater than or equal to 1.5 x controls) was observed in only 1/56 (2%) tumors. No evidence was found for increased size of individual colonies after incubation with rhIL-1 alpha. At a concentration of 100 ng/ml, colony formation of 9/56 (16%) tumor specimens was significantly inhibited (colony formation less than or equal to 0.5 x controls). We conclude that rhIL-1 alpha is not a major modulator of tumor colony formation in vitro. However, some antitumor effects may be observed at high concentrations.
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PMID:Effects of recombinant human interleukin-1 alpha on clonogenic growth of primary human tumors in vitro. 151 20

The thioether-lipid conjugate of ara-C, ara-CDP-DL-PTBA, was tested for therapeutic activity in vivo on the growth of seven different xenografts of human colorectal cancers in athymic nu/nu mice. Treatment was started approximately 3 weeks after s.c. transplantation of the tumor when the tumors measured about 0.5 x 0.5 cm. The animals were randomly assigned to treatment with the drug or saline vehicle. The conjugate was given at single doses i.p. of 250 mg/kg/week for 3 weeks. There was no toxicity of the drug at this dose level as observed by clinical aspect, weight loss, or decrease in survival at the end of an experiment. However, ara-CDP-DL-PTBA was highly active in three of seven xenografts, almost completely blocking tumor growth as long as treatment continued with specific growth delay greater than 2 and T/C less than 25%. There was minor growth delay in two further xenografts and no activity at all in the other two xenografts. In conclusion, ara-CDP-DL-PTBA is active in the treatment of human colorectal cancer xenografts at a non-toxic dose level and thus should be considered for clinical testing.
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PMID:Therapeutic activity of a thioether-lipid conjugate of 1-beta-D-arabinofuranosylcytosine in human colorectal cancer xenografts. 155 Nov 15

The effects of unsaturated fat and fiber (cellulose) on the growth of human colon cancer explanted to athymic nude mice was evaluated. Eighty-seven male nude mice bearing xenografts of human HT29 or WiDr colon cancer were divided into three groups of equal weight and tumor volume. Each group was fed one of three diets: normal fat/no fiber (N/N), high fat/no fiber (H/N) or high fat/high fiber (H/H). To equalize caloric intake, animals in the H/N group received 4 g of food per day and the other animals were fed 5 g of food per day. At sacrifice tumor volume and weight was recorded, and tumors were analyzed for protein and DNA content and ornithine decarboxylase activity. Tumor volume, weight, and protein were greater in the H/N group compared to the N/N group for both colon cancer cell lines. Tumor DNA content was greater in the HT29 H/N group compared to the N/N group (P less than 0.05) and tumor ornithine decarboxylase activity in the WiDr H/N group was greater than the N/N animals (P less than 0.002). The tumor growth-promoting effects of the high unsaturated fat diet were attenuated by the addition of fiber. Animal weight was higher in the H/N group compared to the N/N and H/H groups. This study suggested that a high-fat diet stimulated and fiber decreased the growth of human colon cancer explanted to athymic nude mice. The growth-promoting effects of a high-fat diet in colorectal cancer may be due in part to a circulating trophic factor since these tumors were remote from the large intestine.
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PMID:Effects of fat and fiber on human colon cancer xenografted to athymic nude mice. 165 57

Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful.
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PMID:Elevated serum gastrin levels in patients with colorectal neoplasia. 174 82

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis and tumor growth in the rodent colon. We assessed NSAID use in relation to risk of human large-bowel cancer in a hospital-based, case-control study of 1326 patients with colorectal cancer and 4891 control patients. For regular NSAID use that continued into the year before interview, the multivariate relative risk estimate was 0.5 (95% confidence interval, 0.4 to 0.8); the estimate decreased as the duration of use increased, but the trend was not statistically significant. Similar results were obtained whether cancer or non-cancer controls were used, and the inverse association was apparent for both colon cancer and rectal cancer in men and women and in subjects younger and older than 60 years. Regular NSAID use that had been discontinued at least 1 year previously and non-regular use were not associated with risk. Almost all regular NSAID use was of aspirin-containing drugs. The present data suggest that the sustained use of NSAIDs reduces the incidence of human large-bowel cancer.
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PMID:A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. 845 5

In order to clarify cell proliferation kinetics of human colorectal cancer, 91 cases were investigated by cytofluorometry and clinicopathological findings. The results showed colorectal cancers could be divided into 3 groups according to the ploidy pattern. Group I was the diploid cell population, group II the polyploid cell populations and group II' the aneuploid cell populations. These ploidy patterns were found not to be related both to the histological types and the gross pathological classification. Most of the intramucosal cancers were found in group I, and the cancers of more advanced growth mainly in groups II and II'. The fraction of diploid cells in the groups I and II' did not show the remarkable change, but in the group II decreased with tumor progression. These results indicate the ploidy patterns appear to change with the submucosal invasion, and also that while the ploidy patterns in the groups I and II' are stable, those in the group II increase the extent of polyploidization with the tumor growth. Lymphatic metastases were found to be more frequent in the group II than in the groups I and II'. It is suggested that the mechanism of lymphatic metastasis would be related to the cell polyploidization.
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PMID:[Cytofluorometric analysis of cell proliferation kinetics of the human colorectal cancer]. 177 Sep 32

An analog of diarylsulfonylurea, LY 186641 has a broad spectrum activity against murine solid tumors including Colon 26 and LX-1. Preclinical evaluation of the anticancer activity of LY 186641 using the subrenal capsule assay was performed in fresh human tumor samples derived from 87 patients with various cancers and 70 (80%) samples were evaluable. The overall chemosensitivity rate of LY 186641 was 37% and the average tumor growth inhibition rates (TGIRs) of malignant lymphoma, esophageal cancer and colorectal cancer were 51 +/- 19%, 51 +/- 20% and 48 +/- 12%, respectively. The antitumor effect obtained by LY 186641 was comparable to that of the standard anticancer drugs including adriamycin, 5-fluorouracil and cisplatin evaluated in this assay simultaneously. Based upon these results, LY 186641 is considered to have antitumor activity against some human cancers.
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PMID:[Antitumor activity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea, LY 186641 against various human cancers using subrenal capsule assay]. 229 41

Clinical features and their prognostic value were evaluated in 83 colorectal cancer patients with liver metastasis. The clinical features analysed included presenting symptoms and signs, liver function tests, extent of liver involvement, associated extrahepatic tumor growth, and physical condition of the patients. Overall median survival time after diagnosis of liver metastases was 8.4 months. Prognostic factors related to survival were symptoms, when referable to liver metastasis, and 5' Nt. Information is supplied to survey what selection of patients should be considered for various treatment options. A predominance of the patients showed bilobar liver involvement (79.6%), extrahepatic tumor growth (49.4%), or had an unresectable primary tumor (30.1%), thus leaving only 6% of the patients with liver metastases for surgical treatment with the intention of cure.
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PMID:Diagnostic evaluation and survival analysis of colorectal cancer patients with liver metastases. 243 48


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