Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A metastatic model of human colon cancer has been previously established using orthotopic onplantation of histologically intact in tissue nude mice. In this study, effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) on Col-2-JCK, a human colon cancer xenograft, were evaluated using this model. When 5-FU and MMC were administered without OK-432, liver metastases were not reduced even at maximum tolerated doses of both drugs, although cecal tumor growth was significantly reduced. On the other hand, when combined with OK-432, both 5-FU and MMC reduced liver metastases with synergistic reduction of cecal tumor growth, demonstrating the potential of combining immunotherapy with chemotherapy against metastases.
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PMID:Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice. 851 41

Colorectal cancer frequently disseminates through the portal vein into the liver. In this study, outbred Swiss nude mice were adapted to facilitate the induction of liver metastases by a pre-grafting treatment with 6 Gy total body irradiation and i.v. injection of anti-asialo GM1 antibody. One day later, cultured LS 174T human colon cancer cells were injected into the surgically exposed spleen, which was resected 3 min later. In 48 of 65 mice, a few to several hundred liver metastases were macroscopically observed at dissection 3 to 4 weeks after transplantation. Ten of 10 mice, followed-up for survival, died with multiple large confluent liver metastases. By reducing the radiation dose to 4 or 0 Gy, or omitting the anti-asialo GM1 antibody injection, only 60%, 37% or 50% of mice, respectively, had visible metastases 3 weeks after transplantation. Carcinoembryonic antigen (CEA) measured in tumour extracts was in the mean 25.6 micrograms/g in liver metastases compared with 9.2 micrograms/g in s.c. tumours. Uptake of radiolabelled anti-CEA monoclonal antibody (MAb) in the metastases 12, 24 and 48 hr after injection gave a mean value of 39% of the injected dose per gram of tissue (ID/g). In comparison, MAb uptake in s.c. and intrasplenic tumours or lung metastases gave a mean percentage ID/g of 20, 18 and 15, respectively. Laser-induced fluorescence after injection of indocyanin-MAb conjugate allowed direct visual detection of small liver metastases, including some that were not visible under normal light. Preliminary results showed that mice, pre-treated with 4 Gy irradiation and the anti-asialo GM1 injection, were tolerant to radioimmunotherapy with a total dose of 500 muCi 131I labeled anti-CEA intact MAbs given in 3 injections.
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PMID:Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: a model for radioimmunotherapy. 876 Jun 2

Colorectal cancer initiation and progression are associated with stepwise genetic alterations. We and others have shown that a gene encoding for a 32-kDa putative laminin-binding protein (LBP-32) is overexpressed during colorectal cancer progression by Northern blots analysis. Northern blots cannot indicate the heterogeneity of expression from cell to cell and the distribution pattern of gene expression within a given tumor. In order to overcome these problems, we examined the LBP-32 mRNA expression in colorectal carcinomas by in situ hybridization. LBP-32 mRNA expression in 30 cases of primary and metastatic colorectal cancers and their respective adjacent normal tissues were detected by in situ hybridization using 35S-UTP radiolabeled antisense riboprobes. The results showed that LBP-32 mRNA was expressed at a low level in the normal colonic mucosa adjacent to the tumor compared with colon cancer tissues. Its expression in poorly differentiated colorectal cancer was much higher than that in well- and moderately differentiated colorectal cancer. More importantly, the LBP-32 mRNA was expressed more highly in the invasive lesions of the cancer and liver metastases compared with the cancer lesions in situ. Our results imply that in situ hybridization is a powerful tool in evaluating the changes in gene expression in the cancer cells and LBP-32 mRNA expression is related to progression, invasion, and metastasis of colorectal cancer.
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PMID:Expression of 32-kDa laminin-binding protein mRNA in colon cancer tissues. 876 53

Two cases with unresectable multiple liver metastases to both lobes (H3) from colon cancer, in which cases the life expectancy usually does not exceed 1 year, were treated with home hepatic arterial infusion chemotherapy employing implantable port system. They could live over one year with good performance status. Drug treatment consisted of the administration of carboplatin (CBDCA), 150 mg/body, given in a minute for one day and 5-fluorouracil (5-FU), 250 mg/body, given in a 5-hour intra-arterial infusion daily for 5 days. Cycles were administered every 2 weeks. Home hepatic arterial infusion chemotherapy using an implantable port system, which offers good local control of liver metastases, a high patient quality of life without the need for hospitalization, is suitable for treatment of unresectable liver metastases.
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PMID:[Two cases of multiple liver metastases (H3) from colon cancer treated by home hepatic arterial infusion chemotherapy]. 884 93

It is feasible to graft human colon cancer tissue into immuno-deficient nude mice, in order to maintain these tumors in vivo. Analysis of the properties tumors under such conditions might increase our knowledge of their biological characteristics. Xenografts are usually implanted into subcutaneous tissue, a site easily accessible for both graft procedure and observation of tumor growth. However these subcutaneous tumors are usually non-invasive and fail to metastasize. To override these limitations we, as others, have tried to improve the tumor xenograft model by transplanting tumors into their original location, designated as the orthotopic site. Transplanted into the cecum of nude mice, human colon cancers were frequently locally invasive and developed liver metastases. These transplantations may be done by injection of colon cancer cell suspensions into the cecal wall. Alternatively, orthotopic implantations of histologically intact tissue were performed and the thus-obtained tumors were more metastatic than tumors obtained after tumor cell injections. The chemosensibility of tumors xenografted into their orthotopic site was different from that of their subcutaneously implanted counterpart. This, added to the enhancement of invasive and metastatic properties, leads us to conclude that colon cancer xenografted into the caecum might be more representative of the clinical situation. We have reviewed the literature and report on the possibilities and limitations different models of colon cancer in vivo.
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PMID:Efficiency of orthotopic xenograft models for human colon cancers. 889 23

From 1960 to 1993, a total of 1.766 patients with liver metastases from colorectal carcinoma was recorded. Five-hundred-and-eight patients (28.8%) underwent hepatic resection which was performed with curative intent in 473 patients (26.8%). 30-day mortality in this group was 4.5%, being 2.6% (4 out of 155) since 1990. Significant morbidity was observed in 16% of patients with a decrease to 7% for the last 4 years. A 99.5 percent follow-up until January 1, 1996, was achieved. Excluding operative mortality there are 376 patients with "potentially curative" initial liver resection, and 65 corresponding patients with minimal macroscopic (n = 19) or microscopic (n = 46) residual disease. The latter group demonstrated a poor prognosis with median and maximum survival times of 14.8 and 56 months, respectively. Among the 376 patients having potentially curative resection the actuarial five, ten, and twenty year survival was 39 +/- 3, 26 +/- 5 and 21 +/- 13 percent, respectively. Tumor-free survival was 34 +/- 3 percent at 5 years. In the univariate analysis, the following factors were associated with decreased crude survival: Presence and extent of mesenteric lymph node involvement (p = 0.0001), poor grading of the primary tumor (p = 0.008), synchronous diagnosis of metastases (p = 0.004), satellite metastases (p < 0.0001), an increasing metastasis diameter (p < 0.0001), preoperative CEA elevation (p = 0.0002), a resection margin of less than 1 cm (p = 0.018), extrahepatic disease (p = 0.02), non-anatomical procedures (p = 0.008), and an operative blood loss exceeding 2.000 ml (p = 0.02). With respect to disease-free survival, extrahepatic disease (p = 0.09) failed to achieve statistical significance, while patients with colon cancer and with delayed resection of synchronous metastases did significantly better than those with rectal cancer (p = 0.02) and with a simultaneous procedure (p = 0.04), respectively. Multiplicity and bilobar involvement did not affect prognosis. Similarly, no significant predictive value of an increasing number of metastases (1-3 vs > or = 4) on either overall (p = 0.35) or disease free survival (p = 0.55) was found after a radical excision of all detectable disease. Using Cox's multivariate regression analysis, presence of satellite metastases, anatomical vs non-anatomical approach, primary tumor grade and diameter of the largest metastasis all independently affected both crude and tumor-free survival (p < 0.05). With respect to survival, this was complemented by the margin of clearance (0.05 < p < 0.1), while for disease-free survival primary tumor site and time of metastasis diagnosis had some additional influence. Twenty-six patients with R0-reresection of the liver, and 32 patients with radical excision of extrahepatic recurrent disease had a subsequent 5-year survival of 57 +/- 15 percent and 32 +/- 12 percent, respectively. This confirms the effectiveness of a close follow-up policy.
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PMID:[Surgical resection of colorectal liver metastases: Gold standard for solitary and radically resectable lesions]. 896 36

Radioimmunotherapy (RIT) and radiotherapy (RT) were evaluated in nude mice developing liver metastases of human colon cancer. Without treatment, 90% of preconditioned nude mice, injected with LS174T cells intrasplenically and splenectomized, died between 26 and 93 days after grafting with few to several hundred liver metastases. RIT with 500 microCi of 131I-labeled anti-carcinoembryonic antigen monoclonal antibodies, injected i.v. in 3 weekly fractions, was initiated 1 to 3 weeks after grafting. Mean survival increase was 43 days for mice treated at 2 weeks. From 13 mice treated at 1 week, 8 mice showed long-term survival, a significantly better cure rate compared to RIT at 2 weeks. Mice undergoing RIT at 3 weeks showed similar survival as untreated controls. Mice injected with 131I-labeled irrelevant IgG1 or unlabeled antibody showed no significant survival increase. Conventional fractionated external beam RT of the liver showed that 40-50 Gy treatment initiated 1 week after grafting gave long-term survival in 7 of 13 mice, significantly better compared to RT at 2 weeks. With combined RIT + RT initiated 2 weeks after grafting, 5 of 11 mice had long-term survival in the absence of major toxicities. Thus, early RIT and RT were more efficient than later treatments, and combination therapy might give further improvement.
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PMID:Radioimmunotherapy and fractionated radiotherapy of human colon cancer liver metastases in nude mice. 901 72

Hepatic metastasis of colon cancer is an important prognostic factor for survival. In this study, we examined the effect of gene therapy using the herpes simplex virus-thymidine kinase (HS-tk) gene with short-course ganciclovir (GCV) treatment for multiple hepatic metastases of murine colon cancer. Colon26 cells transfected with the HS-tk gene were found to be sensitive to GCV in a concentration-dependent way. On the other hand, induction of the HS-tk gene in the cells had no influence on cell growth in vitro. However, multiple hepatic metastases of Colon26 cells transfected with HS-tk gene were significantly suppressed by the GCV treatment. These results thus suggest that HS-tk gene therapy is useful for the treatment of hepatic metastasis in colon cancer.
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PMID:Effect of gene therapy with the herpes simplex virus-thymidine kinase gene on hepatic metastasis in murine colon cancer. 903 98

Resection of liver metastases in patients with colon cancer increases survival but success depends on removal of all tumour tissue. For this purpose, understanding of spatial relationships between metastases and liver architecture is essential. Because metastatic cancer growth is essentially a three-dimensional (3D) event, we decided to apply 3D reconstruction techniques to study these spatial relationships between metastases and liver structures such as blood vessels, stroma and the liver capsule (Glisson's capsule). Colon carcinoma metastases were experimentally induced in rat liver by injection of colon cancer cells (CC531) into the portal vein. Three weeks later, livers from these animals and control livers were removed and immediately frozen in liquid nitrogen. Thirty-seven to 110 consecutive sections were used for each 3D reconstruction of 26 metastases in eight livers. Contours of different structures were stained by (immuno)histochemical means, traced in each section and stored in a database. From the contour model, a volume model was generated. Among the 26 metastases, seven were found to grow distantly from the liver capsule. They were small and consisted of well-differentiated cancer cells that were totally surrounded by a basement membrane and stroma which was always connected with adjacent blood vessels of a portal tract. The remaining 19 metastases showed a more advanced pattern of development. Infiltration of poorly differentiated colon cancer cells progressed through the stroma at various sites and areas of direct contact between cancer cells and hepatocytes were frequently found. This type of outgrowth of cancer cells was only found when metastases had made contact with the liver capsule. However, some areas in sections of these advanced stages still resembled small metastases. On the basis of these findings, we conclude that stroma-affects the differentiation pattern of cancer cells and has at least a dual role in tumour growth. On the one hand it limits invasion of cancer cells in the surrounding host tissue. On the other hand, stroma formation at the capsule, which consists mainly of granulation tissue, facilitates outgrowth of the tumours. Furthermore, our 3D reconstructions demonstrate the spatial heterogeneity of larger metastases and the importance of a 3D approach to understand growth and development of metastases in general and colon cancer metastases in the liver in particular.
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PMID:Three-dimensional reconstruction of colon carcinoma metastases in liver. 926 37

In recent years, adjuvant therapy for colorectal cancer has advanced considerably. This article reviews these advances and provides an update of the most recent and ongoing trials. In 1990, adjuvant therapy became the "standard of care" for patients with Stage III colon cancer (Dukes C) in the United States. Recent clinical trial data indicate that adjuvant treatment may also be effective in patients with Stage II (Dukes B2) colon cancer. The combination of 5-fluorouracil plus leucovorin may slightly improve survival (5-10 percent) compared with the standard 5-fluorouracil plus levamisole combination. The three-drug regimen (5-fluorouracil plus levamisole plus leucovorin) is more toxic, with no superior effect on survival. Intraportal chemotherapy, although it may significantly improve patient survival, does not decrease the frequency of liver metastases. However, it is still a promising form of adjuvant therapy owing to its short treatment period and relatively equivalent effects in survival compared with that of systemic therapy. For patients with Stage II or Stage III rectal cancer, postoperative systemic 5-fluorouracil plus radiation therapy plus protracted venous 5-fluorouracil infusion is the most effective postoperative adjuvant regimen. However, results from several studies show that preoperative radiation alone or chemoradiation for advanced local rectal cancers might also be effective while also improving resectability, decreasing morbidity, and increasing the chance that a sphincter-sparing procedure may be performed. The role of leucovorin in rectal cancer remains to be determined. Immune therapies with agents such as interferon-alpha-2a, monoclonal antibody 17-1A, and autologous tumor vaccines are being assessed and could further improve survival.
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PMID:Adjuvant therapy for colorectal cancer: present and future perspectives. 926 18


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