Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two previous studies have shown higher circulating gastrin levels in subjects with colonic neoplasia than in colonoscopy-negative controls. In this much larger study, sera were collected from fasting subjects undergoing colonoscopy. Colonoscopy with biopsy classified participants as having colonic adenomas (N = 139), colon carcinoma (N = 29), or controls without colonic neoplasia (N = 150). Frozen, stored sera were later analyzed for gastrin by radioimmunoassay. Serum gastrin values were no higher in subjects with colonic adenomas or carcinoma than in colonoscopy-negative controls. We conclude that elevated serum gastrin levels play little, if any, role in the initiation of colonic neoplasia.
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PMID:Serum gastrin is not higher in subjects with colonic neoplasia. 141 93

Experimental biochemical modulation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co-4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5,10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity.
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PMID:Modulation by l-leucovorin of 1-hexylcarbamoyl-5-fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice. 144 20

Many carcinoma cells secrete transforming growth factor alpha (TGF alpha). A 23 base anti-sense oligonucleotide that recognizes the TGF alpha mRNA inhibits both DNA synthesis and the proliferation of the colon carcinoma cell line LIM 1215. The effects of the anti-sense TGF alpha oligonucleotide are reversed by epidermal growth factor (EGF) at 20 ng/ml. When the LIM 1215 cells are grown under serum free conditions, the anti-sense TGF alpha oligonucleotides have their greatest effects at high cell density (2 x 10(5) cells/cm2), indicating that the secreted TGF alpha is acting as an exogenous growth stimulus. In addition, at higher cell densities, the kinase activity of the EGF receptor is activated and the receptor is down-modulated. The cell density dependent activation of the EGF receptor is inhibited by the application of the antisense TGF alpha oligonucleotides.
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PMID:Anti-sense transforming growth factor alpha oligonucleotides inhibit autocrine stimulated proliferation of a colon carcinoma cell line. 145 28

B cells derived from peripheral-blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein-Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor-reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin-resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, 1F6, produced an antibody reactive with a cell-surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. 1F6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal-cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung-cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, 1 colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor-infiltrating B cells.
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PMID:Analysis of two human monoclonal antibodies against melanoma. 145 38

Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to > 80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth.
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PMID:Interleukin-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells. 147 74

Chemotherapy in disseminated stages of gastro-intestinal tumor only causes remission rates of 20 to 40% in a reproducible manner. Treatment is clearly palliative and does not influence median time of survival in these patients. In limited stages of esophageal or gastric cancer remission rates above 50% are achieved. However there is no evidence that chemotherapy in addition to surgery improves treatment results. Based on prospectively randomized studies, for stage-III colon carcinoma adjuvant chemotherapy using Fluorouracil and Levamisole is recommended. In resected carcinoma of rectum the adjuvant combination of chemotherapy and radiation improves local control of the tumor as well as survival of the patients. This modality of treatment is recommended.
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PMID:[Chemotherapy in solid tumors of the gastrointestinal tract?]. 149 6

We have tried to develop a new model consisting of rats transplanted with syngeneic colon carcinoma PROb cells transfected with cDNA coding for the carcinoembryonic antigen (CEA), the human tumor marker most commonly used as target for MAbs. The antigenic density of the 4 CEA-expressing clones selected for a precise characterization ranged from 5 x 10(4) to 1 x 10(6) CEA molecules per cell. In all clones the CEA was shown to be attached to the membrane by a phosphatidylinositol (PI) anchor. Using a panel of radiolabeled MAbs directed against the 5 major epitopes described on the CEA molecule, we showed that all these CEA epitopes were expressed by the 4 transfectants. Southern-blot analysis showed that the entire CEA cDNA was present in the transfectants. Western-blot analysis, however, showed that the size of the CEA expressed by the 4 transfectants was slightly smaller than that of CEA produced by 2 reference human colon-carcinoma cell lines. Two clones, expressing 1 x 10(5) and 1 x 10(6) CEA molecules per cell, respectively, were grafted s.c. in nude mice and rats. Injection of radiolabeled anti-CEA F(ab')2 fragments into these animals showed specific tumor localization with the highest percentages of injected doses for the transfectants expressing the highest CEA level. When grafted into immunocompetent syngeneic BDIX rats, the CEA-expressing clones induced a strong antibody response against CEA and tumor rejections in a majority of the animals. Although the analysis of the immune response against the CEA-cDNA-transfected carcinoma cells is under investigation, the present results demonstrate that human CEA could function as a rejection antigen when transfected into rat carcinoma cells.
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PMID:Human carcinoembryonic antigen cDNA expressed in rat carcinoma cells can function as target antigen for tumor localization of antibodies in nude rats and as rejection antigen in syngeneic rats. 150 Feb 16

The hematologic and transfusion data of a multicenter randomized trial investigating the effect of blood transfusions on the 5-year survival were used to study the feasibility of an autologous blood donation program in colorectal cancer patients. Three hundred and ten patients were randomized for autologous blood transfusions (predeposition of 2 units) or homologous blood transfusions, and transfusion rules were standardized. The Hb level in the patients who donated blood decreased by 20.1 +/- 1.3 g/l (mean +/- SEM) preoperatively and 4.5 +/- 1.8 g/l postoperatively, and in controls 3.7 +/- 1.1 g/l and 16.5 +/- 1.9 g/l (significantly different between the two groups, both pre- and postoperatively: p less than 0.01). Because blood loss and number of transfusions were similar in both groups, this indicated that either preoperative or postoperative erythropoiesis is stronger in patients who had donated blood. Twenty-three percent of the autologous patients and 61% of the homologous patients were exposed to homologous blood. The effectiveness of the procedure differed per tumor localization. In patients with a right-sided colon carcinoma, 22% of the control patients needed homologous blood, compared to 10% of the autologous patients. In patients with other colon carcinomas, this was 52 and 16%, respectively, and in patients with a rectal carcinoma 85 and 41%. We conclude that predeposition of 2 units of blood for colorectal cancer surgery is feasible and useful to prevent homologous blood usage in a significant number of patients with left colon carcinoma or rectal carcinoma.
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PMID:Feasibility of a predeposit autologous blood donation program in colorectal cancer patients: results from a randomized clinical study. 151 64

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.
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PMID:Pharmacokinetic analysis of antibody localization in human colon cancer: comparison with immunoscintigraphy. 152 May 70

Sulfhydryl boron hydride (BSH) (10B enriched) is presently used for boron neutron capture therapy of malignant gliomas. BSH must be close to the target cells to be effective in the inactivation of cell proliferation because of the short range of the reaction products (5-9 microns). Clinical experience indicates that BSH is taken up in gliomas but it is not known to which structures it binds at the cellular level. In vitro tests on monolayer cultured cells have indicated that BSH does not bind, or only shows very weak binding, to single isolated cells. It is possible that BSH accumulates in tumor regions due to the special conditions in poorly vascularized tumor tissue, such as low pO2, low extracellular pH, metabolic gradients, and degenerative changes. To test this we incubated three types of multicellular tumor spheroids with BSH for different times and analyzed both penetration and binding. The spatial distribution of 10B in sections of the spheroids was analyzed by neutron capture autoradiography. We found extensive accumulation of 10B in the central regions of both glioma and colon carcinoma spheroids. The accumulation closely followed the pattern of the degenerative changes which were characterized by massive necrosis in the central regions of the colon carcinoma spheroids and by a continuously increasing frequency of pyknotic nuclei as a function of depth in the glioma spheroids. The accumulation of 10B in the prostatic carcinoma spheroids was much lower. The penetration assay, based on freeze-drying and vapor fixation, showed that BSH penetrated easily since 10B equilibrated within 5-15 min in the studied spheroids. Thus, the low accumulation in the prostatic carcinoma spheroids was not due to penetration difficulties. The results of the present study on cellular spheroids and the results from previous studies on transplanted tumors support the observation that BSH penetrates easily into the degenerative tumor areas and that 10B, for some tumor types, might accumulate in these regions as a result of the BSH administration.
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PMID:Accumulation of 10B in the central degenerative areas of human glioma and colon carcinoma spheroids after sulfhydryl boron hydride administration. 154 Sep 68


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