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)

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
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PMID:A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. 238 96

In the last decade of radioimmunodetection studies the radiolabeled antibody preparations used have gradually changed from polyclonal antibodies labeled predominantly with 131I to monoclonal antibodies labeled with diverse radionuclides including 131I, 111In, 123I, and 99mTc. Over this period progressive improvement in tumor imaging has been observed when one compares the best examples of early studies, performed with 131I labeled heterosera, to the best of modern images, obtained with 123I, 99mTc, or 111In labeled monoclonal antibodies. Important findings in 61 clinical studies reviewed include the reports from several centers which demonstrate occult disease in patients with carcinoma of colon, melanoma, and lymphoma, and the improved sensitivity and specificity of radioimmunodetection in comparison to transmission computerized tomography in the lymph nodes and abdomen, in lymphoma and colon cancer, and ovarian cancer. Evaluation of the liver remains a difficult problem with this technique and standard approaches are superior in most reports. The general principle of targeting radioactivity to tumor with radiolabeled antitumor antibody and the feasibility of developing practical clinical methodology which will add new diagnostic information have clearly been established. Toxicity, particularly for index studies, is reassuringly limited. In all the studies with surgical confirmation after i.v. injection, uptake in tumor is in the range of 0.005% injected dose/g tumor, and this low tumor uptake remains the single greatest limitation of the method. A second important problem is the prompt development of human anti-mouse antibody, which reduces the usefulness of follow-up studies. A serious criticism of the information currently available on radioimmunodetection is that the clinical studies reported to date vary greatly in approach and results. The vast majority of studies are early Phase I clinical trials, from which toxicity information and biodistribution data can be derived but which give limited information about impact on clinical management. Standardization in the study design is needed in order to establish the efficacy of radioimmunodetection in adequate and well controlled clinical trials.
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PMID:Clinical radioimmunodetection, 1978-1988: overview and suggestions for standardization of clinical trials. 240 83

Although many effective anti-cancer agents are now available, their curative potential is compromised by a variety of problems related to tumor sensitivity, drug access, and pharmacokinetics. Central to the problem of inadequate chemotherapy is drug resistance. Drug resistance may be intrinsic, acquired, or induced, and it may develop to one drug or it may occur simultaneously to multiple agents (pleiotropic). Substantial progress has been made in our understanding of the mechanisms of drug resistance and techniques for overcoming that resistance. New evidence has emerged that highlights the importance of dose intensity in achieving successful drug treatment outcomes. Retrospective analysis of studies in breast, ovarian, colon cancer, and lymphoma suggest that new studies designed to optimize dose intensity may yield improved results. Several prospective trials have now corroborated the retrospectively derived importance of dose intensity as an independent factor in achieving improved survival. Finally, new techniques for drug delivery offer considerable promise. Chemotherapy by regional infusion and perfusion, implantable drug delivery systems, and continuous infusion of chemotherapy are unique novel techniques that may improve the efficacy of presently available chemotherapeutic agents even as new agents are developed.
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PMID:Mechanisms to improve chemotherapy effectiveness. 240 4

Several preclinical and clinical studies have documented that dose or dose intensity of chemotherapeutic agents are important factors for response of patients' tumors. This finding has prompted empiric trials of certain chemotherapeutic agents in high-dose or regional administration treatment regimens. The present study was performed to identify agents that would be particularly good candidates for high-dose or regional administration regimens against particular types of tumors. Using a human tumor cloning technique, we constructed dose in vitro response lines for ten different chemotherapeutic agents against seven different histologic types of malignancies. Slopes of the lines indicated the agents with the greatest increases of in vitro response per increment in dose of the agent. Tumors against which the agents gave the steepest dose response lines included lymphoma, head and neck cancer, ovarian cancer, and small-cell lung cancer, while the dose response lines for non-small-cell lung cancer, breast cancer, and colon cancer were quite flat. Suggestions for clinical trials based on these findings include the use of high-dose melphalan for patients with lymphoma, head and neck, and ovarian cancer; the use of mitoxantrone in high-dose regimens for patients with breast cancer; high-dose cisplatin regimens for patients with small-cell lung cancer; high-dose bleomycin regimens for patients with non-small-cell lung and head and neck cancer; and regional perfusion of liver metastases from colorectal cancer with cisplatin. Prospective testing of high-dose or regional administration regimens suggested by this new model should indicate its use for prediction of the best agent to use in high-dose regimens against a particular tumor type.
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PMID:Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens. 243 Nov 10

Monoclonal antibody (MAb) B72.3 detects an epitope carried by high-molecular-weight mucins (tumor-associated glycoprotein, TAG-72) recently identified as sialyl-Tn. B72.3 MAb has a restricted pattern of reactivity with normal tissues but it reacts with a high proportion of epithelial cancers. To determine the possible relationship between neoplastic transformation and reactivity with B72.3 MAb, we have analyzed samples of normal colon, colon cancer and transitional mucosa (mucosa adjacent to colorectal cancer) or reactive mucosa (mucosa adjacent to squamous carcinoma of the anal canal, or mucosa overlying lymphoma). B72.3 MAb reacted strongly with 21/21 specimens of transitional mucosa and with 17/21 specimens of adjacent colon cancer. Reactivity of B72.3 MAb with transitional mucosa was strong and homogeneous, whereas reactivity with cancer tissue was weaker and more heterogeneous. Reactive mucosa adjacent to squamous carcinoma or lymphoma was also reactive with B72.3 MAb. Our findings show that, in the colon, expression of TAG-72 antigen occurs during the process of epithelial cell transformation but is also regulated by factors unrelated to the process of carcinogenesis.
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PMID:Expression of TAG-72 in normal colon, transitional mucosa, and colon cancer. 248 51

This study was conducted to assess the enhanced antitumor effects of natural human tumor necrosis factor alpha (nHuTNF-alpha) and natural human interferon alpha or gamma (nHuIFN-alpha or -gamma), in combination, on ten human cancer cell lines. The cell lines tested were colon cancer (RPMI4788), lung cancer (PC10), gastric cancer (MKN-1 and MKN-28), nasopharyngeal cancer (KB), leukemia (K562), lymphoma (Daudi), Liver cancer (H-7) and breast cancer (ZR-75-30 and ZR-75-1). A mixture of nHuTNF-alpha and nHuIFN-alpha (1:1, by unit) showed cytotoxic effects on nHuTNF-alpha resistant cell lines such as RPMI4788, KB and Daudi or nHuIFN-alpha resistant cell lines such as KB, and ZR-75-1, as well as on nHuTNF-alpha or nHuIFN-alpha sensitive cells. A synergistic antitumor effect occurred in four cell lines (RPMI4788, PC10, Daudi and ZR-75-1) treated with a combination of nHuTNF-alpha and nHuIFN-alpha. Also, a combined treatment with nHuTNF-alpha and nHuIFN-gamma (1:1/100, by unit) showed cytotoxic effects on nHuTNF-alpha or nHuIFN-gamma resistant cell lines such as MKN-1, MKN-28, Daudi, H-7 and ZR-75-1. A synergistic antitumor effect occurred in eight cell lines (RPMI4788, PC10, MKN-1, MKN-28, KB, Daudi, H-7 and ZR-75-1). Thus, the combined treatment with nHuTNF-alpha and nHuIFN-alpha or -gamma expanded the spectrum of sensitive cells. These results indicate that the combined use of nHuTNF and nHuIFN may provide a certain approach to cancer treatment.
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PMID:Synergistic antitumor effects of natural human tumor necrosis factor-alpha and natural human interferon-alpha or -gamma on human cancer cell lines. 250 39

We studied the efficacy of endoscopic ultrasonography (EUS) for malignant tumor of the digestive tract. Materials were 174 cases of gastric cancer, 15 cases of myogenic tumor, 22 cases of gastric malignant lymphoma and 37 cases of colon cancer. A radial sector type GF-UM2 and EUM2 (Olympus-Aloka) were used. Almost all walls of the digestive tract were observed as five layers by EUS, and each layer corresponded to the histological wall structure. Malignant lesions showed the characteristic ultrasonographic images, respectively. It was possible to diagnose easily the depth of tumorous invasion by the degree of wall destruction. Also, the internal structure of tumors could be observed by this method. Since EUS is a new examination which had added ultrasonographic diagnosis to conventional endoscopic diagnosis, the combination of endoscopic and EUS images has improved the accuracy of diagnosis.
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PMID:[Utility of endoscopic ultrasonography of malignant tumors of the gastrointestinal tract]. 265 15

Twenty-five patients with disseminated cancer (nine with renal cell carcinoma, five with melanoma, three with Hodgkin's lymphoma and chronic myelocytic leukemia [CML], two with soft tissue sarcoma, one each with large-cell lymphoma, breast cancer, and colon cancer), 13 males and 12 females, aged 25 to 68, were treated with recombinant human interleukin-2 (rIL2) by continuous infusion and adoptive transfer of autologous lymphocytes activated in vitro with IL2. Patients underwent leukapheresis on days 1, 8, 15, and 22 of the treatment. Cells, bulk activated for 20 hours in serum-free culture medium with 1,000 U IL2/mL in transfusion transfer packs as culture vessels, were transfused the following day. The infusion of IL2 by continuous infusion for six days started immediately after each adoptive transfer for 4 weekly courses. The dose of IL2 was escalated weekly in each patient; starting doses of IL2 were also escalated in subsequent cohorts of patients until maximally tolerated doses were reached. Nine patients had objective tumor regressions (three with renal cell cancer, two with Hodgkin's lymphoma, and one each with melanoma, sarcoma, breast, and colon cancer). Six responses were partial, two were minor, and one was mixed. Responding patients were maintained with IL2 by continuous infusion for six days every 6 to 8 weeks, without adoptive cell transfer. The median duration of responses was 16 weeks (3 to 60 + weeks). Tumor regression was related to the dose of IL2 (greater than or equal to 3.4 x 10(6) U/m2/d for six days) and to the in vivo lymphoproliferative effects of the lymphokine, but not to the total number of cells adoptively transferred. Side effects of treatment were transient and quickly reversible. Renal, hepatic dysfunction, and dyspnea were directly related to the dose of IL2 and to lymphocytosis. Other toxicities were mild hypotension with mild fluid retention, oral mucositis, anemia, thrombocytopenia, fever, and fatigue.
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PMID:Recombinant interleukin-2 by continuous infusion and adoptive transfer of recombinant interleukin-2-activated cells in patients with advanced cancer. 266 33

To elucidate the reliability of subrenal capsule assay, histological take rates of fresh human tumors from 75 clinical cases were studied. (1) Take rates of the clinical materials in immune suppressed ddY mice treated by cyclosporin A (60 mg/kg sc, qd) at 6 day were 71% in colon cancer, 50% in stomach cancer, 43% in breast cancer and 0% in lymphoma. (2) Regarding to the histological type, take rates were better in more differentiated type being around 80%, and worse in poorly differentiated type, around 20%. (3) Factors affecting on the poor take rates, other than organ type and histological type, were such as strong heterogeneity of fragments, paucity of cancer cells and abundant stroma. Good tumor take among poorly differentiated type was observed in medullary type. (4) By the daily observation of the growing pattern of the implants (mainly assessed by the amounts of viable tumor cells) the group with good tumor shows similar number of cells through the experimental days and, on the other hand, group with poor tumor shows an early disappearance of tumor cells at day 1 or 2. (5) By lowering pH of the medium harboring fragments down to pH 6.8-7.0 take rates were improved as well as the quality of viability.
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PMID:[Histological take rates of fresh human tumors in the subrenal capsular space of cyclosporin A treated mice]. 277 92

We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.
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PMID:111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection. 281 44


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