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)

K18 is a new drug produced by a combination of Melphalan and human immunoglobulin. K18 produced an inhibitory effect on the proliferation of human gastric and colon cancer transplanted in to nude mice. Also, combination effects of K18 with MMC and 5-FU were recognized in the same system. In a study of distribution after K18 administration, the accumulation and retention of this drug in the tumor region were observed. In the case of Melphalan administration, these phenomena were not observed. The antitumor activity of tumor homogenate was evaluated using a colony-forming assay with KB cells. As to the Melphalan-treated group, a four-hour homogenate reduced the number of colonies but a 48-h one did not. In the K18-treated group, the four-hour homogenate decreased the number slightly and the decrease became obvious with 48-h homogenate. In cell cycle analysis using K18 or Melphalan administration, gathering of S-phase cells was observed, but these changes appeared later with K18 than with Melphalan. This result showed that the effect of K18 was produced by the alkylating activity of Melphalan which was combined with immunoglobulin. For clinical application, K18 was administered to cancer patients at a dose of 60-90 mg every day. Two cases of good response were achieved. No side effect was observed. This remarkable efficacy and low degree of side effects in clinical application is probably due to the higher affinity and accumulation of K18 in the tumor region. K18 is a useful new drug for clinical application alone, or in combination with other chemotherapeutic drugs.
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PMID:[A study of the antineoplastic activity of K18]. 242 38

Highly specific anti-human colorectal carcinoma monoclonal antibody(A7) was developed by fusion of mouse myeloma cells with mouse spleen cells immunized by colon cancer cells. Neocarzinostatin (NCS) was bound to A7 preserving both antibody and drug activities. This conjugate (A7-NCS) was applied for clinical trial. No serious side effects were reported, and half of the eight patients with metastatic liver tumor responded to A7-NCS well. To overcome the variety in the expression of tumor-specific antigen on tumor cells, new types of conjugates were developed. Mitomycin C(MMC) was bound to Dextran sulphate. And this conjugate (M MC-Dex) was bound to A7 with the expectation that MMC would release from Dextran that was delivered to the surface of the cancer cells. This type of conjugate would be effective not only against cancer cells that express antigens detected by A7 but also against any cells around cancer cells detected by A7. The possibility and problems in cancer therapy using immunotoxin are discussed.
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PMID:[Application of immunotoxin in cancer therapy; its usefulness and problems in the future]. 247 54

A 77-year-old man was admitted to our hospital, due to systemic lymph node swelling. Nine months before his admission, he had been given a right hemicolonectomy for a colon cancer, that had been followed by chemotherapy (MMC and Tegafur). Laboratory testing revealed these findings: RBC 217 x 10(4)/mm3, Hb 8.3 g/dl, haptoglobin less than 10 mg/dl, positive Coombs test, cold hemagglutinin titer, 1:512, and polyclonal hyper r-globulinemia. A biopsy of a lymph node specimen exhibited the histological appearance of an IBL-like T-cell lymphoma described by Shimoyama et al. Although treatment with prednisolone was started for autoimmune hemolytic anemia, the patient died of severe anemia two months after the appearance of his lymph node symptoms.
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PMID:[An autopsy study of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma in a patient previously treated with chemotherapy in colon cancer]. 249 73

We investigated the possible sero-therapeutic application of monoclonal antibody-A7 against human colorectal cancer. In complement dependent cytotoxicity, A7 showed 59% cytotoxicity against SW1116 cells. In addition, the killing of tumor cells by A7 and C was enhanced when the tumor cells were pretreated with 2 micrograms/ml mitomycin and 40 micrograms/ml adriamycin. Next, we evaluated the in vivo antitumor effect of A7 alone and combined with MMC on human colon cancer (Colon-6) bearing nude mice. The group injected with A7 alone showed definite antitumor effect compared with the non-treated group. The A7+MMC group (MMC: 4mg/kg, A7: 1 mg/body, two times) showed enhanced antitumor effect compared with the groups administered A7 alone or MMC alone.
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PMID:[Enhancing effect by anti-cancer drugs on growth inhibition of colon carcinoma in nude mice by monoclonal antibody and complement]. 277 87

Fifty-seven patients with non-resectable liver metastases (31 from colon cancer, 26 from gastric cancer) received 5-FU, ADR, MMC combined hepatic arterial infusion therapy. (FAMia: 5-FU 334 mg/m2 qw, ADR 20 mg/m2 q4w, MMC 2.7 mg/m2 q2w; in colon cancer, 5-FU 167 mg/m2/day continuously for 3 months and then 334 mg/m2 qw). Myelo-suppression, hepatic arterial occlusion, gastroduodenal toxicity and elevation of biliary enzyme were observed at 29%, 39%, 32% and 13% in colon cancer, respectively, and at 35%, 8%, 0% and 0% in gastric cancer, respectively. Response rates evaluated by CT-scan were 63% (1 CR + 18 PR/30) in colon cancer and 79% (4 CR + 15 PR/24) in gastric cancer. Overall median survival was 352 days in colon cancer and 449 days in gastric cancer. Concerning background factors, the response rate in the well-differentiated type of colon cancer was significantly higher than in the moderately differentiated type, and significantly low in poorly differentiated medullary type gastric cancer. The existence of extra-hepatic lesions was the most important factor in survival in both cancers. [colon cancer: (-) 740 days vs (+) 267 days; gastric cancer: (-) 517 days vs (+) 245 days]. In conclusion, this therapy yields favorable direct effects on liver metastases from colon and gastric cancer without major side-effects and complications, but effective therapy of extrahepatic lesions is required for longer survival. Now, to release colon cancer patients from restrictions of continuous infusion pumps, a phase I study of weekly high dose 5-FU HAI therapy is under way.
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PMID:[A 5-FU, ADR, MMC combined hepatic arterial infusion therapy in non-resectable liver metastases from colon and gastric cancer]. 278 85

Twenty-two patients with metastatic and primary cancer of the liver were treated with 5-fluoro-2'-deoxyuridine (5FUDR), Mitomycin C (Mito C), and 1 (-2-chlorethyl)-4(methyl-cyclohexyl)-1-nitrosourea (MeCCNU). 5FUDR 0.3 mg/kg/day was administered as a continuous infusion via the hepatic artery. Mito C (10 mg/M2) and MeCCNU (50 mg/M2) were given I.V. and orally, respectively, every 8 weeks. Remission of the neoplastic lesions within the liver was seen in 10 patients (4CR, 6PR). Five patients had stabilization of their lesion neoplasm for at least 4 months. The response rate in this study was 6/15 (40%) in patients with colon cancer metastatic to the liver. Toxicity was mainly hematologic and hepatic. Three patients experienced a platelet count below 25,000 and/or white blood count below 1000. Fifteen patients had hepatic toxicity showing elevation in SGOT and SGPT. The SGOT and SGPT returned to normal when the 5FUDR was discontinued. The combination of 5FUDR intraarterially, and Mito C and MeCCNU systemically, demonstrated activity in malignancies of the liver. This study proved that chemotherapy can be administered systemically and regionally with acceptable toxicity.
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PMID:Hepatic arterial and systemic chemotherapy for the treatment of primary and secondary malignancies of the liver. 293 12

The postoperative survival rate after radical surgery for large intestinal cancer shown to be differentiated adenocarcinoma is relatively good. However, the effect of surgical adjuvant therapy on this cancer is considered to be the least promising. 5-FU, FT-207, MMC, ADR and VCR are used for chemotherapy and OK-432, PSK, BCG, levamisole and lentinan are also used as forms of immune therapy. There are no significant differences in the statistics used for comparison with controls as to the effects of these adjuvant therapies. A more intensive regional therapy has therefore been adopted for local recurrence of rectal cancer and liver metastasis of colon cancer considering the form of postoperative cancer recurrence. MMC was injected into the superior rectal artery for rectal cancer and into the portal vein during surgery for colon cancer in the 1st program of research of the Kajitani group. However, the efficacy of these procedures was not proved. Although immune therapy with OK-432 has also been subsequently added in the second research program, no efficacy was apparent. Taylor and Birmingham have reported that liver metastasis was remarkably decreased by continuous infusion of 5-FU through the portal vein. There is also a report by GITSG in the USA that a reduction of local recurrence was obtained by combination of 5-FU and Me-CCNU with irradiation treatment after surgery for rectal cancer.
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PMID:[Surgery and adjuvant therapy of cancer of the large intestine]. 308 76

In vitro chemosensitivity tests of anticancer agents for 119 fresh human tumors were performed by the human tumor clonogenic assay (HTCA) technique and the following results were obtained. Colony growth (greater than or equal to 5 colonies/dish) was observed in 35 of 50 gastric cancers (70.0%), 10 of 17 colon cancers (58.8%), 13 of 14 breast cancers (92.9%), two of six esophageal cancers (33.3%), three of six sarcomas (50.0%), three of 16 hematological malignancies (18.8%) and seven of 10 other tumors (70.0%). Colony growth rate differed according to the type of tumor. Fifty four tumors formed adequate colony growth (greater than or equal to 30 colonies/dish) for the chemosensitivity test. Mitomycin C (MMC), 5-Fluorouracil (5-FU), 4-hydroperoxy cyclophosphamide (CPM), Adriamycin (ADM), Cis-dichlorodiammineplatinum (CDDP), and alpha-interferon (IFN-alpha) were tested. The average positive rates of MMC, 5-FU, CPM, CDDP, and IFN-alpha were 26.9, 21.6, 10.5, 26.9, 36.8, and 23.3% respectively for all the tumors tested. In gastric cancer, the positive rates of MMC and 5-FU were 24.0 and 21.6% respectively, whereas the rates were 33.3 and 33.3% in colon cancer and 18.2 and 16.7% in breast cancer respectively. Each tumor exhibited its own chemosensitivity rates against various anticancer agents. Eighteen of the results obtained were comparable to clinical responses. The true positive rate was 50.0% (2/4) and the true negative rate 92.9% (13/14). A statistically significant correlation was observed between the results of HTCA and clinical responses (chi 2 test, p less than 0.05). The combined effects of IFN-alpha and MMC were surveyed against 20 gastroenterological tumors. Nine tumors exhibited synergistic effect, though antagonistic effect was observed in three tumors. The effects of oxygen tension (2%, 5%, 20%) on colony growth were investigated. The greatest development of colonies occurred at an oxygen of five percent, which is considered to be physiological oxygen tension, and statistically significant increases of plating efficiencies at 5% O2 as compared to those at 20% O2 were observed (t-test, p less than 0.025).
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PMID:[Experimental and clinical studies on chemosensitivity tests of anticancer agents by human tumor clonogenic assay]. 309 23

The group of research for colorectal cancer treatments-Kajitani-group (chief T. Kajitani) has carried out the co-operative study for the evaluation of adjuvant chemotherapy after curative resection of colorectal cancer. During the period 1975 and 1978, a series of 1,156 cases of cancer of colon and rectum were entered into the prospective randomized controlled study which consisted of three treatment programs. There included chemotherapy of 2 modes of regimen combining MMC with Tegaful and non adjuvant treatment as control. In colon cancer, adjuvant chemotherapy combining MMC with Tegaful was effective on the increasing of survival rates, especially significantly (p = 0.017) in the cases of Dukes B stage (85-88% vs 69.2% in survival rates of 8 year). In rectal cancer, systemic intravenous administration of MMC 4 mg, two times a week for immediately postoperative three weeks, combined with postoperatively prolonged oral administration of Tegaful 800 mg/day more than three months was also significantly effective, especially in the cases of Dukes C stage (52.3% vs 40% in survival rates of 8 year). However, the analysis of recurrence did not prove that the intra-operative local intra vessel administration of MMC 10 mg was useful for the prevention of liver metastasis in colon cancer or pelvic recurrence in rectal cancer respectively.
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PMID:[Adjuvant chemotherapy of colorectal cancer--results of prospective randomized trials]. 309 59

In order to estimate the combined effects of UFT with other anticancer agents, a nude mouse experimental system (NMES), and a subrenal capsule assay (SRCA) were investigated. Three human tumor xenografts were serially transplanted into nude mice and examined. These were; EH-1 established from esophageal cancer, SH-6 from gastric cancer and CH-3 from colon cancer. The antiproliferative effects were estimated in accordance with the NCI therapeutic protocol. Significant antiproliferative effects were obtained only in NMES and a positive relationship was observed between the two assays (p less than 0.05). In the groups which were treated with a single agent, positive tumor responses were observed against mitomycin C in SH-6, against cis-DD platinum in SH-6 and EH-1, and against adriamycin in EH-1, respectively. On this study the synergistic, additive and subadditive effects were defined as the positive combined effects. The combination of MMC and UFT produced positive combined effects for all xenografts in both assays.
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PMID:Combined effects of UFT with other anticancer agents using in vivo chemosensitivity tests. 313 15


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