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

This study evaluates tumor response, survival, and development of resistance to HAI chemotherapy, comparing a combination of bolus MMC and short duration FUdR to short duration FUdR alone or to long duration FUdR alone, using a rat hepatic metastases model. After intrasplenic injection of 10(7) K12/TRb colon cancer cells in BD-IX rats on day 0, hepatic metastases were evaluated and HA catheters were placed on day 14. The response was determined on day 28. Chemosensitivity of the hepatic metastases after HAI treatments was determined using the MTT assay. Bolus MMC with short duration FUdR as well as long-term FUdR alone provided better hepatic tumor response and survival than short-term FUdR alone. However, bolus MMC with short duration FUdR decreased the acquired resistance to FUdR, compared to long-term FUdR, without causing resistance to MMC. These results provide a rationale for using short duration of FUdR in combination with other drugs.
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PMID:Short-term intrahepatic FUdR infusion combined with bolus mitomycin C: reduced risk for developing drug resistance. 800 82

In vivo labelling with bromodeoxyuridine (BrdU) was compared with 3H-thymidine (3HTdR) labelling for the study of cell proliferation in normal colon epithelium and in colon cancer tissue. Twenty-four BDIX rats with implanted subcutaneous tumors of DHD/K12 colon cancer cells were subdivided into 3 groups. Each rat received an intraperitoneal injection of either 5-bromo-2'deoxyuridine (50 mg/kg), or 3H-thymidine (1mCi/kg) or both precursors (double labelling). Immunoperoxidase staining with a monoclonal antibody to BrdU, or autoradiography were used. In the colonic crypts, similar patterns of spatial distributions of the labelled colonic epithelial cells were observed after each kind of labelling. The mean labelling indices (LI) by BrdU and by 3HTdR were similar in the normal colon as well as in the implanted tumors. The validity of BrdU labelling in vivo was further investigated by using BrdU+3HTdR double labelling technique. In the colonic crypts, the total BrdU labelled colonic epithelial cells were 11.85%, whereas the total 3HTdR labelled cells were 11.99% (p > 0.05). In the implanted tumors of colon cancer, the total BrdU and 3HTdR labelled cells accounted for 19.40% and 20.10% respectively of the colon cancer cells (p > 0.05). There was a close correlation between BrdU LI and 3HTdR LI in colonic epithelial cells (r = 0.99, p < 0.0001) as well as in colon cancer cells (r = 0.97, p < 0.001). There data indicate that the labelling index of BrdU is equivalent to that of 3HTdR not only in normal colonic epithelium but also in colon cancer. BrdU may thus be used for measuring proliferation parameters in cancer tissues.
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PMID:Comparison of the classical autoradiographic and the immunohistochemical methods with BrdU for measuring proliferation parameters in colon cancer. 831 5

In order to assess the effect of octreotide, a somatostatin analogue, on the growth of colon peritoneal carcinomatosis, 20 BDIX rats were injected i.p. with 1 x 10(6) colon cancer cells (DHD/K12 tumor cell line) and received octreotide, 65 micrograms/kg s.c. every 12 h (n = 10) or saline (n = 10) for 42 days, starting 3 days after tumor cell injection. Animals were killed at the end of the treatment. The mean volume of ascites was lower in the octreotide group (33.7 +/- 7.6 ml), than in the control group (67.5 +/- 16.3 ml; P < 0.05). The extent of peritoneal carcinomatosis (in five classes according to a previously published classification) was lower in the octreotide group (P < 0.05). Cell proliferation, using the BrdU technique, was markedly inhibited by octreotide (labeling index of tumor cells: 17.0 +/- 0.6% vs. 26.3 +/- 2.2% in controls, P < 0.001). No significant decrease in labeling index was observed in normal colonic mucosa. Two subtypes of somatostatin receptors were found in all tumors, using the 30F3 monoclonal antireceptor antibody. KD and Bmax values were not significantly different in the octreotide and control groups: high affinity, low capacity receptors (KD = 1.4 x 10(-10) M and 0.7 x 10(-10) M, respectively; Bmax = 3.8 and 2.9 pmol/mg protein, respectively); low affinity, high capacity receptors (KD = 1 +/- 0.2 x 10(-9) M and 5.5 +/- 0.05 x 10(-10) M, respectively; Bmax = 27.8 +/- 0.1 and 22.8 +/- 0.05 pmol/mg protein, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Octreotide (SMS 201-995) inhibits the growth of colon peritoneal carcinomatosis in BDIX rats. 844 19

Failure of surgical treatment for gastrointestinal cancers is often caused by recurrence of the tumor in traumatized peritoneal surfaces. This study examined the effect of intraperitoneal administration of doxorubicin and recombinant tissue plasminogen activator (rt-PA), a fibrinolytic agent, on incidence and volume of postoperative tumor implants in peritoneal wounds. Prior to randomization, a surgical wound was created on the right parietal peritoneum of 110 BDIX rats and 6 x 10(5) DHD/K12 colon cancer cells were inoculated intraperitoneally (ip). The control group was given an intraperitoneal injection of saline. Five groups received 1 mg/kg of ip doxorubicin at different times postoperatively: at the end of surgery (D0), 3 hr after surgery (D + 3), postoperative day 1 (D1), postoperative day 3 (D3), and postoperative day 7 (D7). In a second set of experiments, five groups of rats received, in addition to postoperative doxorubicin, 5 mg/kg of intraoperative ip rt-PA. Incidence and volume of tumor implants in peritoneal wounds were assessed for each group 20 days after the tumor inoculation. All rats of the control group (incidence = 100%) developed tumor implants in peritoneal wounds. Mean (SD) volume was 16.2 (4.7) mm3. When administered at D0, D + 3, and D1 intraperitoneal doxorubicin reduced significantly the incidence and volume of tumor implants in wounds. Postoperative administration of doxorubicin at D3 and D7 did not affect significantly the incidence and the volume of tumor implants in peritoneal wounds. When rt-PA was administered intraoperatively, ip injection of doxorubicin at any postoperative timing decreased significantly the incidence and volume of tumor implants. In conclusion, ip doxorubicin administered before postoperative D3 may act on tumor cell implanted in peritoneal wounds. Delayed (D3, D7) ip administration of doxorubicin does not prevent the development of tumor implants in peritoneal wounds. Intraoperative administration of rt-PA may significantly increase the efficacy of delayed ip chemotherapy.
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PMID:Effect of intraperitoneal chemotherapy and fibrinolytic therapy on tumor implantation in wound sites. 864 39

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 used an experimental model in the rat to examine the effects of long-term treatment with crocin, a glycosylated carotenoid from the stigmas of the saffron crocus, on colon cancer. BD-IX rats were divided into four groups: Groups G1 and G2, designated "cancer groups," were used to study the effects of crocin on the progression of colon cancer, and Groups G3 and G4, designated "toxicity groups," were used to study the effects of the treatment on metabolic processes and the parenchyma. DHD/K12-PROb cells were injected subcutaneously into the chest of Group G1 and G2 animals. From 1 to 13 weeks after inoculation, animals in Groups G2 and G4 received a weekly injection of crocin (400 mg/kg body wt s.c.). Animals in Groups G1 and G3 received no treatment. In addition, lines of animal and human colon adenocarcinoma cells (DHD/K12-PROb and HT-29) were used to perform assays in vitro to examine the cytotoxicity of crocin. Life span was extended and tumor growth was slower in crocin-treated female rats, but no significant antitumor effect was found in male rats. Acute tubular necrosis was found in all kidney samples from crocin-treated animals, but slight signs of nephrotoxicity were found by biochemical analysis of the serum. In assays in vitro, crocin had a potent cytotoxic effect on human and animal adenocarcinoma cells (HT-29 and DHD/K12-PROb cells, 50% lethal dose = 0.4 and 1.0 mM, respectively). Treated cells exhibited a remarkable loss of cytoplasm and wide cytoplasmic vacuole-like areas. In conclusion, long-term treatment with crocin enhances survival selectively in female rats with colon cancer without major toxic effects. The effects of crocin might be related to its strong cytotoxic effect on cultured tumor cells.
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PMID:Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. 1069 64

Our goal was to examine the influence of circulatory anatomy on the development of metastases. We compared the dissemination of tumor cells to different tissues at different stages in both an orthotopic and a heterotopic model of colon cancer in the rat. We used DHD/K12-PROb cells and two groups of BD-IX rats: group O (orthotopic), in which tumors were implanted by intramural injection of the cecum; and group H (heterotopic), in which cells were injected subcutaneously into the thoracic wall. Animals were assigned randomly to one of nine subgroups of each group in terms of the time between the injection of cells and euthanasia (from the third to the twelfth week). The presence of lung or liver macrometastases was recorded and tumor DNA was detected in lung and liver samples from all animals. We found that lung metastases developed in rats in groups O and H, but no metastases were found in liver parenchymas. The rates of detection of tumor DNA in lung and in liver samples were similar in the two groups. Our results suggest that the site of inoculation of DHD/K12-PROb cells did not influence the pattern of development of metastases. This does not support the proposed role of the circulatory anatomy in the distribution of metastases.
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PMID:The site of injection of tumor cells in rats does not influence the subsequent distribution of metastases. 1279 43

Knowledge of electrical tissue conductivity is necessary to determine deposition of electromagnetic energy and can further be used to diagnostically differentiate between normal and neoplastic tissue. We measured 17 rats with a total of 24 tumours of the K12/TRb rat colon cancer cell line. In each animal we measured in vivo hepatic tumour and normal tissue conductivity at seven frequencies from 10 Hz to 1 MHz, at different tumour stages between 6 and 12 weeks after induction. Conductivity of normal liver tissue was 1.26 +/- 0.15 mS cm(-1) at 10 Hz, and 4.61 +/- 0.42 mS cm(-1) at 1 MHz. Conductivity of tumour was 2.69 +/- 0.91 mS cm(-1) at 10 Hz, and 5.23 +/- 0.82 mS cm(-1) at 1 MHz. Conductivity was significantly different between normal and tumour tissue (p < 0.05). We determined the percentage of necrosis and fibrosis at the measurement site. We fitted the conductivity data to the Cole-Cole model. For the tumour data we determined Spearman's correlation coefficients between the Cole-Cole parameters and age, necrosis, fibrosis and tumour volume and found significant correlation between necrosis and the Cole-Cole parameters (p < 0.05). We conclude that necrosis within the tumour and the associated membrane breakdown is likely responsible for the observed change in conductivity.
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PMID:In vivo electrical conductivity of hepatic tumours. 1281 12

The aim of the present was to assess the effectiveness of low level direct current therapy in liver metastases and the influence of polarity (anode or cathode in the center of the tumor) or current dose (60 or 80 C/cm3). Colorectal metastases were established in 25 BD IX rats by injection of DHD/K12 colon cancer cells under the liver capsule. After 3 weeks the tumors were treated by low level direct current therapy (applied with five platinum electrodes). Histological examination of the removed livers on postoperative day 7 revealed significant destruction of the metastases with localized necroses. The best treatment results were obtained in the group with an anode in the center and a current dose of 80 C/cm3. We conclude that low level direct current therapy may offer an alternative minimal invasive method in the treatment of liver metastases.
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PMID:[Pilot study of effectiveness of electrotherapy in the experimental liver metastasis model]. 1451 27

Metastatic disease to the liver is one of the major factors determining the outcome of colonic resection with curative interventions in human patients. Therefore, animal models for studies of liver metastasis have been developed. Humane endpoints are needed for the evaluation of the animal condition. Liver metastases were modelled by hepatic subcapsular injection of a syngeneic rat colon cancer cell line (DHD/K12-PROb) in BDIX/OrlIco rats. In this study, we present a detailed description of a laparoscopic technique for the direct inspection of liver metastases. That way a qualitative impression of the metastases was obtained. We suggest, as a new humane endpoint, that one animal should only have 1-2 separately growing metastases, each of a maximum size of 10 mm(2). In future, the method has to be developed further to measure the size of the metastases in a more quantitatively precise manner. Although the animal has to be anaesthetized each time, laparoscopy is considered a minor surgical procedure as only two small puncture wounds are made through the abdominal wall. Because laparoscopy offers a direct view of the hidden tumours and their sizes, as well as of possible complications (e.g. peritoneal tumour growth), one can prevent unnecessary discomfort. We therefore think the advantages outweigh the disadvantages, as laparoscopy helps to avoid the unnecessary suffering due to large tumours which may only be detected at late stages by conventional procedures.
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PMID:Laparoscopy of rats with experimental liver metastases: a method to assess new humane endpoints. 1507 Apr 56


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