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)

Although numerous animal tumor models have been used to study colon carcinoma, few display metastatic properties. We have characterized an animal tumor model that has 3 properties essential for the study of metastasis of colon carcinoma cells: epithelial cell origin; a reproducible pattern of metastatic behavior and the ability to be propagated both in vitro and in vivo to facilitate identification of biochemical correlates of metastasis. The K12/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD-1X rat strain. Transmission electron microscopy of K12/TR cells demonstrated junctional complexes, desmosomes and surface microvilli characteristic of gastrointestinal epithelial cells. The epithelial cell origin of K12/TR was confirmed by demonstrating the presence of keratin, a marker of epithelial cells, but not vimentin, a constituent of mesenchymal cells. Secretion of CEA and Ca19-9 antigens by K12/TR cells in vitro was below the sensitivity of the assays (1 ng/ml and 6 U/ml respectively). K12/TR cells produced tumors following s.c. injection into syngeneic BD-1X rats, allogeneic RNU/rnuDF rats and xenogeneic CRL:nu/nuBR mice. Macroscopic lung metastases were observed in animals from all 3 groups. Distal lymph node metastases were more frequent in BD-1X rats than in nude rats or mice. The histological appearances of all tumors and metastases were similar, showing a moderate to poorly differentiated glandular carcinoma. Intrasplenic injections of K12/TR cells in nude mice resulted in liver colonization. Preferential growth of tumor cells at sites of trauma was also observed. The results show that the K12/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions.
 ...
PMID:Characterization of an animal model of metastatic colon carcinoma. 380 94

Radioimmunoassays based on antisera raised against the tachykinins eledoisin (antiserum E7) and kassinin (antiserum K12) were used to measure the concentration of tachykinin-like immunoreactivity (TKLI) in plasma from 52 healthy subjects. 65 patients with carcinoid tumors (of which 46 had symptoms of both flushing and diarrhoea), and 6 patients with endocrine pancreatic tumors. The antisera did not crossreact with substance P (SP). Elevated concentrations of TKLI, as compared with healthy subjects, were found in 75% of the carcinoid patients, but in none of the patients with pancreatic tumors. Tumor metastases from 8 of the carcinoid patients all contained TKLI. Ion-exchange chromatography of plasma samples and tumor tissue extracts indicated the presence of several immunoreactive molecular forms. The elution patterns of the immunoreactivity detected by antisera E7 and K12 were similar, indicating that the same molecular species are measured by these antisera. None of the components coeluted with synthetic SP. One of the immunoreactive components in carcinoid tumor extracts coeluted with synthetic NKA. The major immunoreactive components in plasma from the patients eluted in a position different from that of all currently known mammalian tachykinins. Tachykinin immunoreactive material detected in tumor tissue and plasma of patients with carcinoid tumor may play a role in the symptomatology of the carcinoid syndrome.
 ...
PMID:Antisera raised against eledoisin and kassinin detect elevated levels of immunoreactive material in plasma and tumor tissues from patients with carcinoid tumors. 608 59

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.
 ...
PMID:Short-term intrahepatic FUdR infusion combined with bolus mitomycin C: reduced risk for developing drug resistance. 800 82

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Activity of ruboxyl, a nitroxyl derivative of daunorubicin, on experimental models of colorectal cancer metastases. 1043 20

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.
 ...
PMID:A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells. 1069 28

To provide an investigative tool for the study of osteosarcoma (OSA) biology we have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988; 39: 151-60). This model is characterized by orthotopic primary tumor growth, a period of minimal residual disease, spontaneous pulmonary metastasis, and clonally related variants (K7M2 and K12) that differ in pulmonary metastatic potential. Primary tumor and pulmonary metastasis histology was consistent with OSA in human patients. Expression of bone sialoprotein, biglyan, decorrin, and osteopontin was suggestive of bone lineage cells. The development and use of a more aggressive OSA cell line (K7M2) resulted in spontaneous metastasis to the lungs in over 90% of mice, whereas metastases were seen in only 33% of mice when a less aggressive OSA cell line (K12; Schmidt et al. Differentiation 1988; 39: 151-60) was used. Death from metastasis occurred at a median of 76 days using K7M2 whereas no median was achieved after 140 days using K12. Angiogenic potential, characterized by CD31 and factor VIII staining of primary tumors and pulmonary metastases, was greater in the K7M2 model compared to the K12 model. No significant differences in the in vitro or in vivo expression of angiogenesis associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and K12. This well characterized and relevant model of OSA will be a valuable resource to improve our understanding of the biology and treatment of metastasis in OSA.
Clin Exp Metastasis 2000
PMID:An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. 1131

Stage II colorectal carcinoma is characterized by negative lymph node pathology as determined by conventional microscopic examination. These patients generally do not receive adjuvant therapy although 20%-30% will die from metastatic disease. To determine whether K-ras mutations at codon 12 could be used as a sensitive indicator of occult lymph node metastasis in stage II colon carcinoma, a retrospective study was performed using restriction endonuclease-mediated selective polymerase chain reaction (REMS-PCR) amplification. Of 106 colonic tumors analyzed, 46 were identified as positive for a K12-ras mutation in the primary tumor. Multiple lymph node samples from 38 of these 46 patients were examined by a sensitive nested PCR protocol for the presence of a K12-ras mutation. Of these 38 patients, 14 had 1 or more positive lymph nodes by PCR (37%) and 24 were negative for the mutation (63%). Of the 14 patients with a K12-ras mutation detected in lymph nodes, 8 died of the disease within 5 years (57%) compared to only 4 of the 24 patients with ras-negative lymph nodes (17%). The difference in time to death from disease, stratified using K12-ras status of lymph nodes, was statistically significant (P = 0.036; log-rank test). These results suggest K-ras mutation status of lymph nodes in patients with stage II colon cancer might identify a subgroup of patients who are more likely to develop recurrent and/or metastatic disease and benefit from adjuvant therapy. Larger studies are indicated to determine whether detection of K-ras mutation positivity in histologically negative lymph nodes portends a poor prognosis and to determine whether more aggressive use of adjuvant therapy is warranted.
 ...
PMID:Detection of mutated K12-ras in histologically negative lymph nodes as an indicator of poor prognosis in stage II colorectal cancer. 1244 69


<< Previous 1 2 3 4 Next >>