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)

Peritoneal effusion recurrence is one of the most important problem in the palliative management of patients with gastrointestinal malignancies and ovarian cancer. Ten patients with recurrent malignant ascites (three with ovarian cancer, two with pancreas cancer, two with gastric adenocarcinoma and one affected by colon cancer, one patient with peritoneal carcinomatosis, one subject with pleural mesothelioma surgically treated that after three years showed a peritoneal metastases and ascites), were treated with intraperitoneal beta interferon. In all patients a Tenckoff's catheter for peritoneal dialysis was introduced and peritoneal effusion extracted and measured. Three millions of beta interferon in saline solution was infused in peritoneal cavity every three days for nine days. Successively twenty millions every three days for nine days. In the 50% of patients a significant reduction of peritoneal effusion was observed. The locoregional therapy with beta interferon is proposed in palliative management of malignant ascites.
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PMID:[The locoregional treatment of neoplastic ascites with interferon-beta]. 150 25

A new dosage form of cisplatinum (CDDP), lactic acid oligomer microspheres incorporating cisplatinum (CDDP-ms), is designed to slowly release 70% of contained CDDP. CDDP-ms's acute toxicity is as low as 57% of the toxicity of CDDP aqueous solution, and its therapeutic efficacy is statistically significantly strong as compared with that of CDDP aqueous solution, when examined with experimental peritoneal carcinomatosis induced by mouse M5076 ovarian sarcoma. Clinical trials were carried out in 10 patients with malignant ascites (gastric cancer 6, pseudomyxoma peritonei 2, colon cancer 1, pancreas cancer 1) and in one patient with pleural effusion (lung cancer). CDDP-ms at 100 mg/person in terms of CDDP was injected at bolus into the affected cavity. In the 10 patients with ascites, 7 responded completely, two partially and one did not respond. The patient with pleural effusion responded partially. The response rate was 91%. Five of the 11 patients complained of temporary nausea or vomiting. In 5 patients fever higher than 38 degrees C was seen. No other side effect such as kidney, nor liver-damage or blood cell count abnormality was noted.
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PMID:[Intracavitary microspheres incorporating cisplatinum in the treatment of malignant effusions--clinical trials]. 238 51

The efficacy of intracavitary chemoimmunotoxin therapy for cancer treatment was evaluated using the human colon carcinoma (HT-29) which had been xenografted i.p. into nude mice. Mice bearing HT-29 were treated with an immunotoxin consisting of the monoclonal antibody OVB3 coupled to Pseudomonas exotoxin (OVB3-PE), with cyclophosphamide (Cy), or with both OVB3-PE plus Cy. Mice given injections i.p. of 3 x 10(6) HT-29 ascites cells developed a localized disease that presented as both malignant ascites and solid tumor confined to the peritoneal cavity. All mice died within 30 to 40 days. Mice that received either three or six injections of OVB3-PE at a dose of 0.5 micrograms every other day beginning 3 days post-tumor inoculation exhibited significantly increased median survival times (MSTs) (P = 0.002) of 62 and 68 days, respectively, as compared to a MST of 33 days for the controls. OVB3 alone or an irrelevant monoclonal antibody conjugated to PE exhibited no antitumor activity. The therapeutic effects of the immunotoxin could be blocked by giving a large amount of unconjugated OVB3 at the same time. Treatment of mice with Cy alone at the maximal tolerated dose (250 mg/kg) on Days 10 and 17 after tumor inoculation increased the MST from 33 days to 54 days. The maximum tolerated dose could be increased to 300 mg/kg per injection if the Cy treatment was preceded by 100 mg/kg of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721), a sulfhydryl compound that selectively protects normal tissue against the toxicity of radiation and alkylating agents. Cy plus WR-2721 treatment on Days 10 and 17 increased the MST from 35 to 61 days (P = 0.002). Interestingly, groups of mice that received either two, four, or seven treatments of OVB3-PE following Cy plus WR-2721 therapy exhibited a further increase (P less than 0.002) in MSTs to 81, 87, and 96 days, respectively. Thus, the combination of cytoreductive chemotherapy with the OVB3-PE was significantly more effective for the intracavitary treatment of established HT-29 colon cancer xenografts than either chemotherapy or immunotoxin therapy alone.
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PMID:Chemoimmunotoxin therapy against a human colon tumor (HT-29) xenografted into nude mice. 249 20

Fifty cases of malignant ascites were studied to determine what factors influenced outcome after peritoneovenous shunt. There were 36 women and 14 men. The five most common tumor types were colon, breast, gastric, pancreatic, and unspecified adenocarcinoma. Multivariate analysis between those patients surviving longer than 7 weeks (n = 20) and those who died in less than 7 weeks (n = 30) showed that women did uniformly better than men, even excluding the "female malignancies" (P less than 0.01). An elevated white blood cell count (WBC) and low platelets also were strong predictors of poor outcome (P less than 0.5 for difference in means between the two groups). Patients with pancreatic cancer and ascites fared poorly (80% mortality by 7 weeks) as did those with colon cancer (73% mortality by 7 weeks). By contrast, 50 per cent of the patients with breast and gastric cancer lived more than 7 weeks. Twelve patients had a LaVeen shunt placed, compared with 38 who had a Denver shunt. Fifty per cent of the La Veen shunts failed, with a mean time to failure of 69 days (P less than 0.01). Shunt failure, however, had no influence on overall survival.
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PMID:Peritoneovenous shunt (PVS) for malignant ascites. An analysis of outcome. 274 27

Acivicin pharmacokinetics were studied in Phase I patients receiving i.v. treatment on single-dose or daily x5 (daily times five doses) regimens repeated every 3 weeks. In 14 patients, the time course of plasma concentrations was characterized by a biexponential equation with a terminal (elimination-phase) half-life of 9.92 +/- 3.91 h (mean +/- SD), distribution phase half-life of 0.32 +/- 0.28 h, total body clearance of 1.69 +/- 0.48 liters/h/m2, and volume of distribution of 21.79 +/- 2.94 liters/m2. Acivicin kinetics appeared to be dose-independent over the range of 8.5-150 mg/m2/day. Urinary excretion of intact acivicin in nine patients ranged from 2-42% in the first 24 h following administration; interpatient variability in urinary excretion was large, but daily urinary recovery within patients on the daily x5 schedule was quite consistent. Measurements of acivicin effects on the activity of carbamyl phosphate synthetase II (CPS II) were conducted using leukocytes and/or malignant ascites of three colon cancer patients. Acivicin given to one patient at 8.5 mg/m2/day on the daily x5 schedule caused a 70% reduction in leukocyte CPS II activity within 5 h after therapy was initiated. Leukocyte CPS II activity remained suppressed at this level over the 5-day dosing regimen. In this patient, CPS II activity in malignant ascitic cells had decreased by 75% on day 4 of the daily x5 regimen. On the single dose schedule, treatment of two patients with 100 mg/m2 caused leukocyte CPS II activity to decrease by greater than 90% within 4 h of treatment with gradual recovery over the next 2 days.
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PMID:Pharmacokinetic and biochemical studies on acivicin in phase I clinical trials. 389 81

We attempted to use CDDP for patients with advanced cancers of the gastrointestinal system by intra-arterial infusion, giving consideration to the side effects of CDDP. Of 19 cases treated with CDDP, 17 cases were evaluable. These 17 cases comprised 10 cases of gastric cancer, 1 of pancreatic cancer and 6 of colon cancer. Therapeutic effects were as follows. According to the criteria for judgement of solid cancers, there were 10 evaluable cases which comprised 1 case of PR, 2 of MR, 4 of NC and 3 of PD. According to the criteria for judgement of malignant ascites, there were 6 evaluable cases which comprised 4 effective and 2 non-effective cases. As to side effects, nausea and vomiting were observed in 10 cases, numbness in 1, fever in 1 and aggravation of diabetes in 2. From the above results, intra-arterial infusion of CDDP is considered to be an effective method for the treatment of advanced cancers of the gastrointestinal system, especially of malignant ascites.
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PMID:[Intra-arterial infusion of CDDP in advanced gastrointestinal cancer (combination of general chemotherapy)]. 395 80

We and others have shown decreased expression of T-cell receptor-CD3-associated signal transducing zeta molecules (TCRzeta) in tumor infiltrating and peripheral T cells of patients with advanced cancer. In the present study, we performed adoptive immunotherapy (AIT) with tumor-associated lymphocytes (TAL) in patients with gastric (n = 11) and colon (n = 3) cancer with stage IV and investigated whether the alteration of signal transducing molecules was observed with AIT, compared to an untreated control group (n = 13). Autologous TALs isolated from malignant ascites or pleural effusion were cultured with stimulation of autologous tumor in the presence of interleukin-2 (IL-2) and were transferred to the patients. TCR zeta expression in peripheral T cells was measured by flow cytometric analysis of permeabilized cells with anti-zeta monoclonal antibody (MAb) (TIA-2) before and after AIT. We confirmed the down-regulation of TCR zeta expression in peripheral blood lymphocytes (PBL) of patients with gastric and colon cancer with stage IV compared to healthy donors (n = 15). AIT induced up-regulation of TCR zeta expression in 2 of 14 treated patients, caused no significant change of TCR zeta expression in 7 patients and induced further down-regulation in 5 patients. The patients who achieved clinical responses (n = 3) with AIT showed no significant change of TCR zeta expression. On the other hand, in the control group without adoptive transfer, further down-regulation of TCR zeta expression was observed during the corresponding periods, paralleling disease progression. Taken together, TCR zeta expression in the patients was further down-regulated, corresponding to disease progression in individual cancer patients. In some patients, AIT could induce increased or stable TCR zeta expression. The quantitative analysis of TCR zeta expression might provide vital information that can be used to optimize therapy by preserving immune functions within cancer patients.
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PMID:Expression of signal transducing T-cell receptor zeta molecules after adoptive immunotherapy in patients with gastric and colon cancer. 976 62

We studied the pharmacokinetics of the intraperitoneal administration of CPT-11 for four patients with peritoneal metastasis (2 gastric cancer cases, 2 colon cancer cases). CPT-11 was administrated in a dose of 40-60 mg and the intraperitoneal and serum levels of CPT-11, SN-38 and SN-38 glucuronized (SN-38 Glu) were measured periodically. Intraperitoneal therapy with CPT-11 was effective for the control of malignant ascites. No serious side effects were observed. The levels of CPT-11, SN-38 were no different 30 min afterwards the administration of CPT-11 either intraperitoneally or intravenously. The high concentration of CPT-11 was achieved with intraperitoneal therapy and a small fraction of CPT-11 changed into SN-38 in the abdominal cavity.
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PMID:[Pharmacokinetic study of the intraperitoneal administration of CPT-11 for patients with peritoneal seedings of gastric and colonic cancers]. 1170 65

The prognosis of peritoneal spread from gastrointestinal cancer and subsequent malignant ascites is poor, and current medical treatments available are mostly ineffective. Targeted chemotherapy with intraperitoneal prodrug activation may be a beneficial new approach. L293 cells were genetically modified to express the cytochrome P450 enzyme 2B1 under the control of a cytomegalovirus immediate early promoter. This CYP2B 1 enzyme converts ifosfamide to its active cytotoxic compounds. The cells are encapsulated in a cellulose sulfate formulation (Capcell; Bavarian Nordic, Martinsried, Germany). Adult Balb/c mice were inoculated intraperitoneally (i.p.) with 1 x 10(6) colon cancer cells, previously transfected with GFP to emit a stable green fluorescence, by injection into the left lower abdominal quadrant. Two or five day's later animals were randomly subjected to either i.p. treatment with ifosfamide alone or ifosfamide combined with microencapsulated CYP2B1 expressing cells. Peritoneal tumour volume and tumour viability were assessed 10 days after tumour inoculation by means of fluorescence microscopy, spectroscopy and histology. Early i.p. treatment with ifosfamide and CYP2B1 cells resulted in a complete response. Treatment starting on day five and single-drug treatment with ifosfamide resulted in a partial response. These results suggest that targeted i.p. chemotherapy using a combination of a prodrug and its converting enzyme may be a successful treatment strategy for peritoneal spread from colorectal cancer. In summary, by using GFP-transfected colon 26 tumour cells in mice we established a well reproducible animal model of metastatic peritoneal cancer. Fluorescent imaging of GFP-transfected tumour was used to demonstrate tumour distribution in the peritoneal cavity and to estimate tumour growth and tumour response to treatment in this model. The application of Capcell and ifosfamide into the peritoneal cavity is a safe and well tolerated procedure in animal models and may help to target chemotherapeutic agents specifically at metastatic peritoneal cancer.
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PMID:Targeted intraabdominal chemotherapy for peritoneal carcinomatosis. 1763 75

We assessed the antitumor efficacy of KRN951, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptors, using a rat colon cancer RCN-9 syngeneic model in which the tumor cells are transplanted into the peritoneal cavity of F344 rats. KRN951 treatments that commenced 4 days after tumor transplantation (day 4) significantly inhibited tumor-induced angiogenesis, the formation of tumor nodules in the mesenteric windows, and the accumulation of malignant ascites. Moreover, KRN951 treatments initiated on day 14, by which time angiogenesis and malignant ascites have already been well established, resulted in the regression of newly formed tumor vasculatures with aberrant structures and also in the apparent loss of malignant ascites by the end of the study period. Quantitative analysis of the vessel architecture on mesenteric windows revealed that KRN951 not only regressed, but also normalized the tumor-induced neovasculature. Continuous daily treatments with KRN951 significantly prolonged the survival of rats bearing both early stage and more advanced-stage tumors, compared with the vehicle-treated animals. The results of our current study thus show that KRN951 inhibits colon carcinoma progression in the peritoneal cavity by blocking tumor angiogenesis, ascites formation, and tumor spread, thereby prolonging survival. Moreover, these studies clearly demonstrate the therapeutic effects of KRN951 against established tumors in the peritoneal cavity, including the regression and normalization of the tumor neovasculature. Our findings therefore suggest that KRN951 has significant potential as a future therapeutic agent in the treatment of peritoneal cancers with ascites.
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PMID:Anti-tumor activity and tumor vessel normalization by the vascular endothelial growth factor receptor tyrosine kinase inhibitor KRN951 in a rat peritoneal disseminated tumor model. 1820 Dec 72


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