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

Renewed interest in cancer immunotherapy has been raised by the availability of a variety of tumor-associated antigens and animal models. We have recently described the presence of a new antigen, TLP, in sera and cancer tissue from lung and colorectal cancer patients. In order to develop an experimental model suitable for preclinical studies on cancer vaccines, we investigated the presence of TLP antigen in vitro, in the DHD-K12 cell line and in vivo, in metastases induced in syngeneic BDIX rats by DHD-K12 cell injection. TLP was not detected in any tissue of healthy rats nor in normal tissues of tumor-bearing rats. This is in agreement with our previous studies, in which we had demonstrated that TLP is expressed in human colorectal cancer and adenomas but not in normal colonic mucosa. Our results indicate TLP as a possible human tumor-specific antigen naturally expressed in DHD-K12 tumor syngeneic to immunocompetent BDIX rats.
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PMID:A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells. 1069 28

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

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

Experimental studies in the therapy of malignant abdominal tumors have shown that different cytotoxic agents suppress the intraperitoneal tumor growth. Nevertheless, a general accepted approach to prevent tumor recurrences does not exist. Following subcutaneous and intraperitoneal injection of 10(4) colon adenocarcinoma cells (DHD/K12/TRb), the influences of both taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumor growth was investigated in 105 rats undergoing midline laparotomy. The animals were randomized into 7 groups and operated on during 30 min. To investigate the intraperitoneal (local) influence of either taurolidine or heparin on tumor growth, the substances were applied intraperitoneally. Systemic and intraperitoneal effects were evaluated after intravenous injection of the substances. Both application forms were also combined to analyze synergistic effects. Tumor weights, as well as the incidence of abdominal wound metastases, were determined four weeks after the intervention. In order to evaluate the effects of the agents, blood was taken to determine the peripheral leukocytes counts. Intraperitoneal tumor growth in rats receiving intraperitoneal application of taurolidine (median 7.0 mg, P = 0.05) and of taurolidine/heparin (median 0 mg, P = 0.02) was significantly reduced when compared to the control group (median 185 mg). The simultaneous instillation of both agents also reduced the intraperitoneal tumor growth (median 4 mg, P = 0.04), while the intravenous injection of the substances caused no local effect. In contrast, the subcutaneous tumor growth did not differ among all groups. In all groups, abdominal wound recurrences were rare and did not differ. Independent of the agents and the application form, the operation itself caused a slight leukopenia shortly after the operation and a leukocytosis in the following course. Intraperitoneal therapy of either taurolidine or in combination with heparin inhibits local tumor growth and abdominal wound recurrences in rats undergoing midline laparotomy. Neither the intraperitoneal nor the intravenous application or the combination of the two agents influenced the subcutaneous tumor growth. The substances did not alter the changes of peripheral leukocytes.
Clin Exp Metastasis 2003
PMID:Local and systemic chemotherapy with taurolidine and taurolidine/heparin in colon cancer-bearing rats undergoing laparotomy. 1452 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

The role and clinical significance of circulating tumor cells and of tumor DNA in the plasma have not yet been clarified. In the present study, we compared rates of detection of tumor-derived DNA in the buffy coat to those in plasma from tumor-bearing rats, and we attempted to correlate these rates with the progression of tumors. We injected DHD/K12-PROb cancer cells subcutaneously into BD-IX rats and divided the animals into six groups according to the time between the injection of tumor cells and euthanasia. After euthanasia, macroscopic metastases were assessed and samples of blood and lung were collected. We used mutant allele-specific amplification by PCR to detect tumor-derived DNA. We detected tumor DNA in lung samples from the first week after inoculation, in plasma from the third week and in the buffy coat from the fifth week. All animals analyzed on the 11th week had macro- or micrometastases in their lungs. Regardless of group, the rate of PCR-positive plasma samples was significantly higher than that of circulating tumor cells (P=0.005). In animals with metastases, this difference was also statistically significant (P=0.008). However, neither the detection of tumor DNA in the plasma nor the presence of circulating tumor cells was strongly correlated with the presence of metastases. Thus, cell-free tumor DNA was detected sooner and more frequently than circulating tumor cells and the dissemination of tumor DNA in the plasma seems to be much more common than detectable hematogenic tumor cells during the spread of colorectal cancer.
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PMID:Detection of circulating tumor cells and of tumor DNA in plasma during tumor progression in rats. 1559 2

The "genometastasis hypothesis" proposes that cell-free tumor nucleic acids might be able to transform host stem cells, and that this might be a pathway for the development of metastases. This theory is supported by previous experimental findings and is consistent with observations of other authors. It has been suggested that tumor DNA might be horizontally transferred by the uptake of apoptotic bodies and initiate the genetic changes that are necessary for tumor formation. In addition, apoptotic bodies have been proposed as possible vehicles that protect the nucleic acids circulating in the plasma from enzymatic degradation. In the present study, we analyzed the presence of apoptotic bodies in serum and its relationship with tumor progression in a heterotopic model of colon cancer in the rat. We injected DHD/K12-PROb cancer cells subcutaneously into BD-IX rats and divided the animals into three groups according to the time between the injection of tumor cells and euthanasia. A control group of healthy animals was included (n = 6). After euthanasia, macroscopic metastases were assessed and samples of blood were collected. To detect apoptotic bodies in the sera, each sample was mixed with FITC-conjugated annexin V antibody in combination with propidium iodide and then analyzed by flow cytometry. Detection of apoptotic bodies was only significantly increased in the sera of a few tumor-bearing animals in late stages of tumor development. Thus, such particles appear not to be the vehicle of the cell-free tumor nucleic acids that are detected at early stages of cancer.
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PMID:Circulating nucleic acids in plasma/serum and tumor progression: are apoptotic bodies involved? An experimental study in a rat cancer model. 1710 7

The effect of somatostatin analogue, lanreotide, and bombesin/GRP antagonist, BIM 26226, on the growth of colon cancer peritoneal carcinomatosis in the rat was studied. BDIX rats were i.p. injected with DHD/K12 rat colon cancer cells at day 0 and received from day 3 either lanreotide, BIM 26226, combination of treatments or peptide solvents. At sacrifice, an day 45, no significant difference between groups was observed for peritoneal tumor growth, hepatic metastases, ascite volume and labeling indices in normal colonic mucosa and tumoral tissues. Survival times were similar in other lanreotide-treated and control groups. However, BIM 26226 decreased plasma gastrin level, consistently with a physiological effect of this peptide. Ln all groups, somatostatin and bombesin receptors were found on mucosal and tumoral tissues. Interestingly, bombesin receptor number was higher in severe than in minor cancer stages, contrarily to that of somatostatin receptors. Moreover, an up-regulation of somatostatin and bombesin receptors was observed in BIM 26226- and lanreotide-treated group tumors, respectively, Despite the presence of these specific receptors, lanreotide and BIM 26226 were inactive on tumor growth in this model.
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PMID:In-vivo effect of somatostatin analog, lanreotide, and/or grp antagonist, bim-26226, on the growth of colon-cancer peritoneal carcinomatosis in the rat. 2155 47

In vitro studies of partially purified virtosomes from rat liver showed inhibition of cell multiplication in four normal and two tumour cell lines. In vivo, the liver virtosomes slowed tumour growth and limited metastases in rats bearing DHD/K12-PROb cell initiated tumours.
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PMID:Non-dividing Cell Virtosomes Affect In Vitro and In Vivo Tumour Cell Replication. 2775 17


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