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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of adjuvant trials performed in the United States for osteogenic sarcoma, breast, lung, and colon cancer have achieved encouraging results and are briefly summarized. Trials in osteogenic sarcoma are reporting 2-year disease-free survival rates of 50%. However, they have only been evaluated against historical controls and there is some evidence that other factors might have greatly improved the disease-free survival in the absence of adjuvant therapy. The NSABP breast cancer trial only shows significant improvement for women under 50 years of age with 1 to 3 positive axillary nodes. A very promising trial using intrapleural BCG immunotherapy for squamous cell lung cancer is described. Also, two trials of 5-fluorouracil for colo-rectal cancer, both showing trends suggesting slight improvement among treated patients, are presented. Proper care in the design of adjuvant trials with sufficient attention paid to prognostic variables is urged.
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PMID:Effective adjuvant treatments. A brief review of U.S. clinical trials. 28 26

An experimental model of chemically induced or transplanted rat colon carcinoma has been used to test the effects of specific (cancer cells) or non specific (BCG) immunotherapy. According to the immunization technique and schedule experiemnts resulted in a partial inhibition or definite enhancement of tumour growth. These experimental data emphasize the possible hazards of human colon cancer immunotherapy.
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PMID:[Immunotherapy of chemically induced rat colon cancer]. 32 75

Serial CEA levels have been studied preoperatively, and one day, 10--15 days, four months, and eight months after surgery in a group of colon cancer patients who started soon after surgery a protocol of adjuvant immuno(chemo)therapy with Levamisole R and BCG R. Results showed a decrease of mean values of plasma CEA levels from preoperatively to four months after surgery, while eight months after surgery a slight increase was noted. Some of the patients in whom disease recurred showed persistent high levels of CEA, while one patient was consistently a false-negative notwithstanding a bone recurrence. While the prognostic value of serial CEA determinations is confirmed, the possibility of restarting (or intensifying) a protocol of adjuvant immunochemotherapy given high CEA levels and a negative clinical picture is discussed.
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PMID:Serial CEA levels in colorectal carcinoma on adjuvant immuno (chemo) therapy. 73 34

Our expanding knowledge of the immune system has provided a basis of rationality for immunotherapy. Some non-specific immunotherapy has achieved the status of standard treatment: interferon in hairy cell leukemia and chronic myelogenous leukemia, BCG in bladder cancer, and levamisole in colon cancer adjuvant therapy. Tumor infiltrating lymphocytes, moreover, offer a level of specificity heretofore unknown. Combined with the newly available synthetic cytokines that regulate the normal immune system there is the potential for a major breakthrough in biotherapeutics. Problems remain. We have yet to identify tumor antigens with the precision necessary for effective immunotherapy. Indeed, we have no assurance that tumors will regularly synthesize new antigens. In the broad spectrum of immune deficiency syndromes, we have yet to see an increase in the common epithelial tumors that account for the great bulk of human cancer. This suggests that we still have a great deal more to learn.
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PMID:Immunotherapy of cancer with lymphokines and lymphokine-activated killer cells. 192 49

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

Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.
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PMID:Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. 327 1

Double antibody radioimmunoassay (RIA), using radioiodinated melanoma-associated antigens (MAA), rabbit antiserum raised against 3 M KCl extract of human melanoma (AHMS) and goat antirabbit IgG antibody, was employed for the detection of MAA in tumors as well as in sera of melanoma patients. MAA were partially purified from crude KCl extract of melanoma tissue by affinity column chromatography using AHMS and concanavalin A. A high content of MAA was detected in all but one melanoma extract, while normal tissue and nonmelanoma tumor extracts contained MAA to a much lesser extent than did melanoma extracts. MAA were also found in melanoma patients' sera (20/45) but not in sera of normal donors (0/10) and colon cancer patients (0/10). Immunochemical data suggest that AHMS-defined MAA consist of two major glycoproteins with molecular weights of 37K and 31K daltons, which does not cross-react either with carcinoembryonic antigen or beta 2-microglobulin or with BCG.
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PMID:Immunodiagnosis of human melanoma: characterization of human melanoma antigens and their detection in sera of melanoma patients by radioimmunoassay. 617 26

General immunobiologic studies in cancer patients have stressed measurements of lymphocyte function and have commonly ignored the monocyte-macrophage system. A preliminary study of peripheral blood monocyte-macrophage function was undertaken in a group of 90 cancer patients (18 breast, 32 colon, 13 head and neck, 9 lung, and 18 melanoma) and 70 controls. Studies included enumeration of extractible monocytes (EM), quantitation of differentiation into macrophages (macrophage precursor test: MP), evaluation of antibody-dependent cellular cytotoxicity (ADCC), and spontaneous cellular cytotoxicity (SCC) as measured with human erythrocytes, and measurements of monocyte and serum lysozyme activity. Breast cancer patients had normal profiles. Colon cancer patients showed the most profound abnormalities with decreased EM and MP and increased ADCC and SCC. Patients with Stage I and Stage II melanoma had normal profiles, whereas those with advanced melanoma had significantly decreased MP. This defect was restored in two patients by BCG immunotherapy. Head and neck cancer and benign breast disease patients had decreased EM, whereas patients with lung cancer had increased EM. Monocyte lysozyme production was unchanged in the cancer patients compared to controls. Serum lysozyme levels, however, were significantly increased in patients with cancers of the colon, head and neck, and lung. Although patients with localized breast cancer and melanoma had normal levels, these were increased in both patient groups with advanced disease. It would appear that the source of the increased serum lysozyme is probably not the peripheral blood monocytes, but could have originated in the intra-tumoral or tissue-bound macrophages which were not examined. Selected assays of peripheral blood monocyte function were deranged in certain types of cancer patients but were fully normal in others, and did not show consistent correlations with tumor type or stage. Tissue-bound or intra-tumoral macrophages might provide a more fruitful area for study in these disease categories.
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PMID:Monocyte dysfunction in human cancer. 682 39

Antibody-dependent cell-mediated cytotoxicity (ADCC), medicated by peripheral blood Hypaque-Ficoll separated mononuclear cells, was studied in humans using chicken erythrocytes (CRBC) incubated in a 1:1200 dilution of rabbit anti-CRBC and human B erythrocytes (HRBC) incubation in a 1:20 dilution of isoantibody. At the optimal target effector ratio of 3:1, ADCC to both CRBC and HRBC was significantly higher than normal in 27 lung cancer, 18 malignant melanoma, and seven colon cancer patients, but not in 20 breast cancer patients. Chemotherapy (single-agent or combination) in 12 patients did not effect ADCC in vitro but significantly suppressed ADCC to both targets after only four or five days of therapy in vivo (ADCC to CRBC, 47.4 to 24.1% lysis: ADCC to HRBC, 48.1 to 16.3% lysis). Immunotherapy with intravenous (IV) corynebacterium parvum or IV methanol extraction residue of BCG (MER) boosted ADCC to both targets within four to seven days of the first dose. It was found that ADCC to HRBC but not to CRBC was completely absent in three cases of active hairy cell leukemia but was present in two cases in remission. The ADCC to HRBC showed an age-dependent increase in both the 51 normal subject and the cancer patients. This was not observed for ADCC to CRBC. The ADCC to CRBC was mediated mainly by an Fc-receptor-positive, nonadherent, small lymphocyte, and ADCC to HRBC was mediated entirely by an adherent monocyte. The ADCC did not correlate significantly with the H3 thymidine incorporation of peripheral blood mononuclear cells, cultured without stimulation for either one or seven days. It also did not correlate with the number of residual granulocytes in the mononuclear cell suspensions. Measurement of ADCC is a useful method of characterizing host defense in malignant disease and its modification by therapy.
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PMID:Antibody-dependent cell-mediated cytotoxicity in human cancer: characterization of patient leukocyte activity and treatment effects. 703 82

The story of tumor immunology includes periods of hope followed by ones of disenchantment as far as clinical applications are concerned. In antiquity, cancer was considered "contrary to Nature", a concept which was confirmed by Ehrlich at the beginning of our century when the layed down the foundations of immunology. The latter was defined as the defence against all "non-self" intruders, including cancer, as opposed to the protection of "self". This concept was further accentuated by the theory immune surveillance proposed by Burnet in 1969 which implicated a destruction of nascent neoplastic cells by T lymphocytes. To increase host defence was the basis of tumor immunotherapy with BCG, levamisol and other adjuvants. The appearance of the nude mouse, athymic, and yet free of spontaneous tumors, led to a new paradigm, the network theory proposed by Jerne. This was based on immunological homeostasis implicating that both "self" and "non-self" can be rejected and tolerated. Cancer gradually ceased to be considered as "contrary to Nature". As for the proposed viral etiology of cancer which was the basis of the National Cancer Act signed by Nixon in 1971, this led to various breakthroughs and Nobel Prizes (Table 1), to discoveries such as reverse transcriptase, cellular oncogenes, tumor suppressor genes, which gave a new explanation for neoplastic transformation. The latter can now be considered as the consequence of a cascade of molecular events which include oncogene expression, anti-oncogene deletion, etc... converting, step by step, for instance, a polyp into a colon cancer and its metastases. The availability of monoclonal antibodies capable of attacking tumor cells did not lead to the expected success because of the complexity of the immune system. Attempts at a better understanding of the latter have led to a subdivision of the T lymphocyte CD4 population into Th1 and Th2. Th1 favor rejection (tumoral, fetal or of transplants) through the elaboration of IL-2, IFN and TNF while Th2 led to tolerance or acceptation through the production of IL-4, IL-5 and IL-10: both functions neutralize each other establishing a "normal" equilibrium Th1 vs Th2. This could explain the state of "tumor dormancy" or tumors in situ which are apparently quite frequent. That any immunological stimulation would cause these dormant tumors to proliferate is the basis of the immunostimulation theory proposed by Prehn and supported by the clinical observations of Stewart. This new concept has led some authors to propose that instead of destroying the tumor cells an attempt be made to maintain them in a state of dormancy in congenial company with normal cells.
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PMID:[A retrospective view of tumor immunology]. 922 70


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