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 somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
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PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

Precise estimation of the volume and growth rate of hepatic metastases would represent an important step forward not only in clinical oncology but also for the evaluation of experimental treatments in animal models. In the present study, an original method of volumetry of hepatic metastatic tumors in vivo has been tested in rats using magnetic resonance imaging (MRI). Three different hepatic tumor models mimicking liver metastases were established in syngeneic BDIX rats by injection of DHD/K12 rat colon cancer cells either directly under the liver capsule or via the portal system. The liver tumor volumes were estimated in vivo by using MR imaging of the liver and summing the individual tumor volumes in the sequential MR liver sections. The values of the tumor volumes measured by MRI were compared with those determined by a classical method of water displacement in vitro after killing the animals and excising the tumors. At 3 weeks after tumor implantation, liver tumors as small as 1 mm in diameter could be detected by MRI. The difference between the tumor volumes estimated by MRI in vivo and those measured by water displacement in vitro was 9% for single liver tumors and 16% for multiple liver tumors. Close correlation between the values of the tumor volumes measured by MRI and those determined by water displacement was observed in solitary liver tumors (r = 0.985, p less than 0.01) as well as in multiple liver tumors (r = 0.985, p less than 0.01), indicating the high accuracy of MRI volumetry for liver tumors. Estimation of the liver tumor volumes by MRI in the same animals at successive time intervals made it possible to construct tumor growth curves and to calculate tumor growth parameters. These data suggest that MRI volumetry represents an effective means of evaluating the efficacy of experimental treatments in small animals and may have potentially important applications in clinical patients.
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PMID:Quantitative study of the growth of experimental hepatic tumors in rats by using magnetic resonance imaging. 160 27

A simple model for liver metastasis from colon cancer resulted from the intraportal injection of 2 x 10(7) highly tumorigenic DHD/K12/PROb cells into syngeneic BDIX rats. Early detection and development of cancer invasion were studied by conventional microscopy and immunoenzymatic staining using a specific monoclonal antibody. Metastases developed either from isolated cancer cells early disseminated in sinusoid network or from intraportal microthrombi. An intense immune reaction developed until day 15 after injection but decreased and disappeared at the latest stages of evolution.
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PMID:Use of a specific monoclonal antibody for studying the liver metastatic invasion of a rat colon cancer. 297 48

Two-third hepatectomy or sham operation was performed in BD IX rats immediately after intraportal injection of colon adenocarcinoma cells of the DHD-K12-TR strain. A dramatic increase in the incidence and growth of tumor cell colonies formed in the liver was observed in the partially hepatectomized as compared to sham-operated animals. Tumors formed in these conditions, developed in the liver parenchyma within less than 2 weeks and were macroscopically detectable at 1 month, without dissemination to other organs at this time and with little alteration of structural morphology of the liver. The model is particularly adequate for therapeutic assay on liver metastases, as, contrary to other models, it does not involve any drug that might interfere in the evaluation. The mechanism whereby partial hepatectomy is acting to enhance tumor take and growth is still unclear. A similar positive effect of hepatectomy on the growth of adenocarcinoma cells when these were grafted in female accessory glands excludes a simple mechanical cause and suggests the involvement of a circulating factor.
Invasion Metastasis 1988
PMID:Effect of partial hepatectomy on experimental liver invasion by intraportally injected colon carcinoma cells in rats. 317 Jan 15

The REGb tumor cell line is a cloned variant of the DHD-K12 cell line, established from a colon carcinoma chemically induced in the rat. Unlike the parent DHD-K12 cell line, or other clones, which give progressive tumors when inoculated to the syngeneic rat, REGb cells produce tumors which regress in 3 to 5 weeks and never cause metastasis. In order to explore the role of natural killer (NK) cells in REGb tumor regression, each rat was given one injection of anti-asialoGM1 (anti-asGM1) serum, a known inhibitor of NK activity. This injection was done 24 hr before REGb cell challenge. This injection significantly depressed the in vitro cytotoxicity of peripheral blood lymphocytes on REGb cells for 2 weeks. REGb tumors grew larger and regressed later in the treated animals than those in the controls. Furthermore, a progressive or recurrent tumor was observed in 4 out of 10 treated rats, giving lung and/or lymph-node metastases in 2 cases. Immuno-histological study of the cells infiltrating the REGb tumors in control and treated animals showed a decrease number of asGM1+ and OX8+ lymphocytes, presumably NK cells, after anti-asGM1 treatment. An increase in number of macrophages was demonstrated in the progressive tumors of treated animals. These results suggest that NK cells play an important role in the initial stage of the regression TSb tumors in untreated syngeneic rats.
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PMID:Effects of a single injection of anti-asialo GM1 serum on natural cytotoxicity and the growth of a regressive colonic tumor in syngeneic rats. 331 50

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

Genetic detection of tumor cells in blood, lymphatic nodes or bone marrow using reverse transcription and polymerase chain reaction (PCR) is quite attractive because it allows the early diagnosis of cancer dissemination. Unfortunately, this type of detection strategy cannot be applied to solid parenchymas, because they usually share with tumor cells the mRNA markers. To avoid this impediment, we have developed an experimental model of cancer using cells with a genome-associated tag. DHD/K12-PROb cancer cells were stably transfected with pcDNA3.1CAT. Approximately 10(6) transfected cells (DHD-CAT cells) were injected subcutaneously into the chest of BD-IX rats. Animals were divided into 11 groups according to the time between injection of tumor cells and euthanasia. An additional 'untagged group' was injected with untransfected cells (DHD-Wild). Blood and tissues samples were collected after euthanasia. Macroscopic and microscopic analysis was done. To detect circulating tumor cells or their presence in peripheral organs, we performed PCR with nested primers to amplify chloramphenicol acetyl transferase-encoding (CAT-encoding) DNA sequences. The minimum number of cells that yielded detectable cells routinely was 2 in 10(6). No modification of cancer aggressiveness was observed in DHD-CAT cells. DHD-CAT cells were detected by PCR in lung from the 1st week after inoculation, in liver, spleen and kidney from the 3rd week and in the blood from the 5th week. All animals analyzed 12 weeks after injection showed lung metastases. Metastases in liver, spleen or kidney, either microscopic or macroscopic, were never detected. We have developed an experimental model of cancer based on genomic tagging of tumor cells that allows the detection of small numbers of cells in all organs and the blood. The presence of cancer cells in parenchymas detected with molecular technology does not correlate with the development of clinically relevant metastases.
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PMID:Detection of genomically-tagged cancer cells in different tissues at different stages of tumor development: lack of correlation with the formation of metastasis. 1040 36

Matrix metalloproteinases (MMP) are enzymes responsible for extracellular matrix degradation which play a role in cancer progression and metastatic spreading. We investigated the effects of the MMP inhibitor, batimastat, in vitro on the proliferation and invasiveness of the rat colon cancer cell line DHD/K12, and in vivo on the growth of an aggressive model of peritoneal carcinomatosis producing haemorrhagic ascites and metastases, obtained in the rat by i.p. injection of DHD/K12 cells. MMP production was studied in conditioned culture media, solid tumors and ascitic fluid. In vivo, after injection of tumor cells on day 0, rats received i.p. daily either batimastat (30 mg/kg) or equal volume of vehicle from day 2 until killing on day 43 (series I) or from day 13 until death (series II). The grade of peritoneal carcinomatosis, ascite volume, number and size of liver metastases were evaluated in both series, and survival in series II. MMPs-1, -2 and -9 were identified in culture media, tumors and ascites. In vitro, batimastat did not modify DHD/K12 cell proliferation and slightly reduced cell invasion. In vivo, in series I, batimastat treatment totally prevented peritoneal carcinomatosis and liver metastasis development. In series II, it significantly prolonged survival (P < 0.0002) and reduced peritoneal carcinomatosis (P < 0.001) and hepatic metastases number as compared with controls. However, batimastat-treated rats of the two series had peritoneal inflammation with marked ascites. Nevertheless, inhibition of MMP is a new therapeutic approach which may be promising in treatment of microtumors as in more advanced cancer stages.
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PMID:Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in rats. 1042 90

We have used chemo-immunotherapy with 5-fluorouracil (5-FU), thymosin alpha1 (T alpha1) and interleukin-2 (IL-2) to treat multiple liver metastases from colorectal cancer induced by DHD/K12 cells in syngeneic BDIX rats, comparing one and two cycles of treatment, and different treatment combinations. 5-FU was delivered loco-regionally as a continuous infusion via an intraperitoneal (i.p.) catheter from a subcutaneously implanted mini-pump, a method we developed for this study. We show here that two cycles of a triple chemo-immunotherapy regimen significantly increased the average survival time compared to one cycle, and compared to untreated controls or those treated with two cycles of 5-FU alone. At 150 days, two rats treated with two cycles of triple therapy were cured, showing no signs of cancer at autopsy; all the other rats died before this time. Triple chemo-immunotherapy resulted in significantly fewer extra-hepatic metastases than in the controls and in those treated with 5-FU only. Further, we found that two cycles of triple treatment significantly increased the absolute number of peripheral T cells expressing IL-2 receptor, CD4 and CD8 compared to controls. We conclude that two cycles of chemo-immunotherapy with 5-FU, T alpha1 and IL-2 were superior to one cycle of treatment and to other treatments tested. Our results suggest that the triple therapy acts by increasing numbers of effector T cells. This method shows promise for the use of multi-cycle chemo-immunotherapy in the treatment of unresectable metastases of colorectal cancer in humans.
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PMID:Efficacy of repeated cycles of chemo-immunotherapy with thymosin alpha1 and interleukin-2 after intraperitoneal 5-fluorouracil delivery. 1043 86

We evaluated the activity of ruboxyl (Rbx), a nitroxyl analogue of daunorubicin (Dauno), in experimental models of hepatic metastases from colorectal carcinoma (CRC) and compared it with its parent compound and with 5-fluorouracil (5FU). In mice treated by intraperitoneal injections Rbx and 5FU proved more effective than Dauno: the Index of Inhibition of Metastases in comparison with controls was 43% for Dauno, 70% for 5FU and 84% for Rbx. In BDIX rats implanted with the syngeneic cell line DHD K12/TRb, both Rbx and 5FU, administered as a continuous intravenous infusion for 7 days, reduced the development of liver metastases from a median of 23.8 +/- 2.16 for controls to 3.2 +/- 1.3 for 5FU and 1.0 +/- 1.4 for Rbx (p < 0.0001 versus controls for both treatments): the comparison of Rbx and 5FU showed a trend in favour of this new anthracycline. Median survival was prolonged from 40.6 +/- 3.4 days in controls to 56.0 +/- 5.8 days with Rbx and 58.0 +/- 4.69 days with 5FU. Considering that in a phase I study Rbx showed only minor and manageable toxic side effect, its activity in the clinical treatment of CRC metastases may deserve further attention.
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PMID:Activity of ruboxyl, a nitroxyl derivative of daunorubicin, on experimental models of colorectal cancer metastases. 1043 20


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