Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of multimodal immunotherapy was studied in WF rats bearing primary gastrointestinal (GI) tumors induced by 1,2-dimethylhydrazine dihydrochloride. The alterations induced in antitumor immune responses of the treated rats were studied in vitro and were correlated with tumor status in vivo. Multimodal immunotherapy consisted of unblocking serum, unblocked lymphoid cells, and levamisole. Such immunologic intervention resulted in significant inhibition of tumor growth, inhibition of metastases, and prolonged survival of the host. Serum blocking activity could be completely counteracted in 6 rats, all of which showed complete tumor regression. Of 20 rats, 8 showed inadequate counteraction of serum blocking activity and transient appearance of cytotoxic antibodies. All 8 rats showed marked tumor inhibition and prolonged survival. Six remaining rats succumbed from either GI or extra-GI tumors, although they survived significantly longer than untreated rats; these 6 rats had only transient counteraction of their serum blocking activity. All 20 tumors in 14 rats of the therapy group showed histologic evidence of tumor rejection. Our studies suggested that a complete counteraction of blocking activity in conjunction with methods capable of improving the specific and nonspecific immune competence of the host may be important to achieve optimal antitumor effects.
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PMID:Effect of unblocking therapy and levamisole on primary gastrointestinal tumors in rats: immunologic and histologic correlation. 36 78

Intestinal carcinomas were induced by repeated subcutaneous injections of 1,2-dimethylhydrazine in syngereic BD-IX strain rats for 12 weeks. At the end of the treatment, one group received 2 doses of 50 mg BCG by a gastric tube, then a dose of 50 mg BCG by rectal instillation. The other group received no BCG. There was no significant difference in survival time, total number of cancers per rat, or cancer localization between the treated or untreated groups. Disseminated peritoneal metastases were more frequently found in BCG-treated animals. These results do not support the use of orally administered BCG in the treatment of human colorectal cancer.
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PMID:Effects of oral and rectal BCG administration on chemically-induced rat intestinal carcinoma. 61 32

In 189 rats N-methyl-N'-nitro-N-nitrosoguanidine or 1,2-dimethylhydrazine (DMH) was given in order to induce colonic tumours. The tumour induction was followed by double contrast examination. At 894 examinations 196 adenomatous tumours were revealed. Autopsy and microscopy revealed 214 macroscopic and 53 microscopic benign or malignant adenomatous tumours. Metastases were found in 17 per cent in the DMH group. The relationship between adenomas and carcinomas is also evaluated.
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PMID:Experimental colonic tumours in the rat. III. Induction time, distribution and appearance of induced tumours. 71 31

The isoenzyme hexokinase (HK) spectrum from normal rat large intestinal mucosa consisted of 3 isoenzymes. In tumours of this localization induced by 1,2-dimethylhydrazine there proved to be a lack or marked decrease in the most rapid anodic isoenzyme. Only one HK isoenzyme was found in the metastases. Km (glucose) for tumour HK was 2--3 times lower than for normal intestinal HK; the HK activity was detected in the serum from the 1st month of the carcinogenic administration, and by the 5th month it was found in 80% of the tumour-bearing animals. No serum HK activity was ever found in control rats.
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PMID:[Change in cell membrane permeability, and composition and properties of hexokinase during induced carcinogenesis]. 122 50

This study examined the influence of the oxygen-derived free radical removing agents allopurinol and dimethyl sulphoxide (DMSO) on the occurrence of hepatic metastases and on the survival rate in the rat with 1,2-dimethylhydrazine (DMH)-induced colonic tumours. At 10 weeks of age, rats were subcutaneously injected every week with 10 mg per kg body weight of DMH for 28 weeks. This produced colonic carcinoma in 80% of animals. The rats that were at this stage continued on their drinking water developed multiple hepatic metastases within 3 months and died at the age of 14.9 +/- 0.3 months (mean +/- SEM). Administration of 1,2 or 5% allopurinol or DMSO for drinking after production of the colonic tumours prevented the development of hepatic metastases 3 months later and significantly (p less than 0.01) extended survival to at least 22.1 +/- 0.1 months of age (mean +/- SEM). The results suggest that in the rat with colonic carcinoma, removing oxyradicals impairs the development of hepatic metastases and prolongs survival.
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PMID:Removing oxygen-derived free radicals delays hepatic metastases and prolongs survival in colonic cancer. A study in the rat. 154 96

A new cell line (RCN-9) was established in culture from a transplantable rat colon adenocarcinoma, which was induced in the colon of a male Fischer F344 rat by subcutaneous administration of 1,2-dimethylhydrazine. When RCN-9 cells were injected subcutaneously or into the cecal subserosa of syngeneic rats, carcinomas with progressive growth were obtained and the development of lung (63.6%) and liver (40.0%) metastases, respectively, ensued. Antitumor effects of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC) against RCN-9 were examined in vivo and in vitro. 5-FU and ADM had antitumor effects both in vivo and in vitro; MMC had antitumor effects in vitro. These results show that the RCN-9 cell line can be used both as a model to study mechanisms of metastasis from colon carcinoma and as a model in chemotherapeutic studies of metastatic disease from colon carcinoma.
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PMID:A new rat colon cancer cell line metastasizes spontaneously: biologic characteristics and chemotherapeutic response. 190 Feb 74

A new technique for the generation of tumour nodules in both liver and peritoneal cavity has been developed in Wistar wag rats. The cell line 192 NRc was derived from a 1,2-dimethylhydrazine (DMH)-induced colonic carcinoma and was cultured on positively charged ion-exchange polystyrene microspheres. The tumour grew to confluence on the spheres, adhering firmly by pseudopodial extensions, enabling washing and injections of spheroids without significant dislodgement of cells. 5 x 10(4) tumour spheroids injected into the portal vein produced a mean of 35 +/- 24 (S.D.) nodules in the liver with an average diameter of 1.5 +/- 0.55 (S.D.) mm at 14 days. The spheroids did not enter the hepatic veins and therefore did not produce pulmonary metastases. Similarly, 5 x 10(3) tumour spheroids injected into the peritoneal cavity, after gently abrading the peritoneum with gauze, produced a mean of 65 +/- 37 (S.D.) nodules with an average diameter of 1.6 +/- 0.39 (S.D.) mm at 14 days. The tumour continued to grow as discrete nodules in both locations until near the time of death at approx. 36 days from inoculation. This animal model is reproducible and will allow the study of a number of treatment modalities for discrete neoplastic lesions in both the liver and peritoneal cavity at any stage of tumour growth without interference from tumour at unwanted sites.
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PMID:A new reproducible model of hepatic and peritoneal metastases from colonic carcinoma. 320 7

Liver metastases were produced in syngeneic BD IX rats by intraportal injection of colon cancer cell aggregates. The cells originated from the DHD/K12 cell line, derived from a 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon adenocarcinoma in BD IX rats. The animals received either cyclosporine A (CSA) or the excipients alone (control) through daily gastric intubation during 6 weeks. Multiple and very large hepatic metastases were observed early in 100% of the CSA-treated rats. The mean tumor volume was approximately 2,000 times higher in the CSA-treated group than in the controls (P less than .01). Survival time in the CSA-treated group was shortened (P less than .01) by generalized metastatic disease. Easy production of metastasis from colon cancer in 100% of the animals and precise estimation of tumor volume may prove useful for future therapeutic studies of secondary hepatic disease.
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PMID:Quantitative study of liver metastases from colon cancer in rats after treatment with cyclosporine A. 345 15

The effect of 13-cis-retinoic acid (13-cis-RA) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male, random bred, Sprague-Dawley (S-D) and inbred Wister/Furth (W/Fu) rats and on isograft tumor growth and metastases in a Brown Norwegian (BN) X W/Fu F1 rat was studied. 13-cis-RA (300 mg/kg diet) was administered to S-D rats 1 week before commencing DMH injections and for the duration of the experiment. W/Fu rats received 13-cis-RA (10 mg/kg weight X 5 days) 6 weeks after DMH injection had begun and monthly thereafter. Primary tumors were detected by serial laparotomy under ether anesthesia in both strains. The time to tumor onset was significantly delayed in treated groups, S-D and W/Fu, P = 0.0339 and 0.0322, respectively (Mantel-Haenszel test), compared with placebo-treated controls. 13-cis-RA (15 mg/kg weight) administered 2 days before and for the duration of isograft tumor growth (DMH 2054, a well-differentiated mucin-producing colon adenocarcinoma that spontaneously metastasized to lung) had no effect on tumor growth or metastasis in the BN X W/Fu F1 rat. The findings suggest that the role of 13-cis-RA is in colon cancer prevention and not in its treatment either in an adjuvant or established setting.
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PMID:Effect of 13-cis-retinoic acid on tumor prevention, tumor growth, and metastasis in experimental colon cancer. 348 Mar 91

A method was described for the generation of cells from tumor-bearing mice; these cells were capable of exhibiting significant antitumor reactivity when adoptively transferred into tumor-bearing hosts. Tumor cell suspensions from a variety of tumors were able to be separated using enzymatic techniques and they were cultured in medium containing recombinant interleukin-2. Activated infiltrating lymphocytes within these tumors expanded; and, by 6-8 days after initiation of culture, lymphocytes predominated and were able to grow to large numbers. The adoptive transfer of these tumor-infiltrating lymphocytes (TILs) made possible mediation of the reduction of established 3-day pulmonary micrometastases from 5 of 7 tumors tested, including two 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, one 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon carcinoma, and the B16 melanoma, all in C57BL/6 mice, as well as the 1660 bladder carcinoma in BALB/c mice. Approximately 2-4 X 10(6) transferred cells were capable of totally eliminating 3-day established metastases. These cells were thus 50 to 100 times more effective than lymphokine-activated killer cells in reducing established metastases; however, they could not be generated from all tumors. The concomitant administration of recombinant interleukin-2 enhanced, by approximately fivefold, the in vivo activity of these cells. The specificity of action of TILs in vivo was different from that determined by classic amputation rechallenge experiments. The tumor-infiltrating lymphocytes that developed this antitumor reactivity appeared to be Thy-1+ and did not bear the asialo GM1 antigen. The potent antitumor effect of these TILs, when transferred in vivo to tumor-bearing hosts, raises the possibility of utilizing similar approaches for the isolation and therapeutic use of lymphocytes with antitumor reactivity from human tumors.
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PMID:In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. 350 Mar 55


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