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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colon cancer cells in culture synthesize and secrete mucin glycoproteins, which carry a number of cancer-associated antigens. However, the structures and mechanisms of biosynthetic processing are not well understood. Mucins synthesized and secreted by LS174T human colon cancer cells were compared to those in LS174T xenografts in athymic mice. Mucins radiolabeled with glucosamine or sulfate were purified by gel filtration and cesium chloride density gradient centrifugation. The mucins were of high molecular weight and were resistant to chondroitinase ABC, hyaluronidase and HNO2 treatment. They were, however, susceptible to pronase digestion and mild alkaline treatment. Using radiochemical precursors, the cellular mucin was shown to contain fucose, galactose, N-acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid, and sulfate. Oligosaccharides released by beta-elimination had N-acetylgalactosaminitol as the reduced amino sugar and also unreduced galactosamine, indicating that there is N-acetyl-galactosamine O-glycosidically attached to protein core and also peripheral N-acetyl-galactosamine not directly linked to protein. DEAE-cellulose chromatography of mucins showed two major peaks with both intracellular and secreted mucins, but xenograft mucins also had more acidic components. Sulfate-labeled mucins were shifted to less acidic peaks by neuraminidase digestion, which indicates that the same mucin molecules are both sialylated and sulfated. We conclude that the intracellular mucins of cultured colon cancer cells, those secreted into the medium, and those in nude mouse xenografts are chemically similar, but differ in sialic acid and sulfate content. This experimental model system, LS174T cells maintained in culture and as nude mouse xenografts, may be useful for further biosynthetic and structural studies of colon cancer mucin.
Tumour Biol 1989
PMID:Comparison of metabolically labeled mucins of LS174T human colon cancer cells in tissue culture and xenograft. 273 49

Mucin-like cancer-associated antigen (MCA), a new tumor marker using the mouse monoclonal antibody b-12 is thought to be of value in the management of patients with breast cancer. In this study sera from 191 female patients with breast cancer (112 with progressive disease [PD] and 79 with no evidence of disease [NED]) were analyzed for MCA levels and compared with those of cancer antigen 15-3 (CA 15-3) in single determination and in combination with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). A cut-off level of 14 U/ml for MCA seems to be more appropriate than the recommended 11 U/ml to distinguish between PD and NED in patients with breast cancer. Although there was a fairly good correlation of MCA to CA 15-3, MCA was inferior in sensitivity and specificity to CA 15-3. Patients with osseous metastases and those with more than one metastatic site showed higher MCA levels than patients with visceral or soft tissue metastases, a fact which was comparable to CA 15-3. Combining MCA and CA 15-3 resulted in a gain in specificity but marked loss of sensitivity. The combination of MCA and CEA results also in a loss of sensitivity whereas the combination of CA 15-3 and CEA showed an increased specificity and only a negligible loss of sensitivity. The combination of MCA with TPA is of little value in the follow-up of breast cancer, as is the combination of CA 15-3 with TPA. The combination of CA 15-3 with CEA can be still recommended for follow-up for early detection of metastases in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mucin-like cancer-associated antigen (MCA) compared with CA 15-3 in advanced breast cancer. 279 51

Human hereditary diseases such as xeroderma pigmentosum, Fanconi's anemia, ataxia telangiectasia, and Bloom's syndrome are characterized by a proneness for developing cancer associated with abnormalities in the processing of DNA damage. The molecular defects responsible for predisposing human tissues to cancer are still not well understood, despite the fact that a considerable amount of work has already been done on this problem. In this paper, we show that in human tumor cell lines, in cells transformed by DNA tumor viruses, and in cells derived from certain cancer-prone disorders, the level of activity of a 42-kDa deoxyribonuclease is many times higher than in diploid untransformed control cells. This suggests that this activity is linked to, or may play a role in, malignant transformation.
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PMID:Enhanced deoxyribonuclease activity in human transformed cells and in Bloom's syndrome cells. 280 19

ATP and AMP exhibit significant anticancer activities against established footpad CT26 colon adenocarcinoma in CB6F1 mice. Adenosine, inorganic phosphate, and inorganic pyrophosphate were without such effects under identical conditions. Daily intraperitoneal injections of adenine nucleotides in large volumes of saline, starting after the tumors became palpable, resulted in inhibition of tumor growth and a few "cures." The treatment was not toxic to the host as determined by changes in body weights. Weight loss observed in animals upon progression of the fast-growing CT26 tumors was slowed markedly in adenine nucleotide-treated mice. The inhibition of weight loss in tumor-bearing mice was shown to be neither the cause nor the effect of the inhibition of tumor growth. Intraperitoneal injections of AMP or ATP but not of adenosine yielded expansions of erythrocyte ATP pools in host animals. The expanded erythrocyte ATP pools are stable over a period of hours, while slowly releasing micromolar amounts of ATP into the blood plasma compartment, leading to several-fold increases in plasma (extracellular) ATP levels. Based on previous studies in which 1-5 microM extracellular ATP effectively inhibited the growth of a variety of tumor cells in several in vitro systems, it is suggested that similar levels of ATP in blood plasma account for the anticancer activities observed in a murine host.
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PMID:Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. 292 3

A serially transplantable perianal gland carcinoma (CAC-9) was developed in nude mice from a hypercalcemic dog that has been maintained through passage 20. Tumor doubling rate of CAC-9 was 3.1 +/- 0.4 days. Mithramycin (MMC) injected intraperitoneally (8 mg/kg) into nude mice bearing CAC-9 markedly decreased the tumor volume 2 weeks post-injection. MMC returned the elevated serum and urine calcium levels in mice with CAC-9 back to similar values as controls. The few remaining viable tumor cells after MMC were large and had numerous aggregations of intermediate filaments that displaced cytoplasmic organelles. Histomorphometric evaluation of lumbar vertebrae reveled no significant differences in bone resorption of nude mice bearing CAC-9 compared to saline-treated controls. This rapidly growing tumor line in nude mice associated with mild hypercalcemia will be a useful animal model to evaluate combinations of chemotherapy for cancer-associated hypercalcemia.
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PMID:Effects of mithramycin on transplantable canine perianal gland carcinoma (CAC-9) in nude mice: biochemical, histomorphometric, and ultrastructural investigations. 294 19

Human renal carcinoma cell line 786-0 elaborates a protein that is structurally and immunochemically distinct from parathyroid hormone (PTH) and that activates renal cortical adenylate cyclase via an interaction with the PTH receptor. Because of the high frequency of excessive bone resorption and resultant hypercalcemia in patients with malignant disease we evaluated the ability of this 786-0 cell factor to reproduce PTH action in bone-derived cells. The 786-0 factor as well as bovine PTH (BPTH) (1-34) and prostaglandin E1 produced marked increases in cyclic adenosine 3':5'-monophosphate (cAMP) accumulation in the clonal rat osteosarcoma cell line UMR-106. A competitive antagonist of PTH action, [norleucine8, norleucine18, tyrosine34] BPTH(3-34)amide, blocked the cAMP stimulation produced by 786-0 factor and BPTH(1-34) but not that produced by prostaglandin E1. In the presence of forskolin (0.1 microM) UMR-106 cells were extremely sensitive to 786-0 factor, showing significant increases in cAMP production at a concentration 10-fold less than that required to activate adenylate cyclase in renal membranes. In contrast UMR-106 cells were less sensitive to BPTH(1-34) than were renal membranes. This preferential increase in sensitivity to 786-0 factor was not seen in membranes prepared from UMR-106 cells suggesting the importance of cytosolic components. Six additional human genitourinary carcinoma cell lines were found to produce factors that increased cAMP levels in UMR-106 cells. We conclude that 786-0 factor is a potent activator of the PTH receptor-adenylate cyclase system in these bone-derived cells. These findings are consistent with the view that cancer-associated hypercalcemia may frequently be attributable to tumor secretion of proteins (such as 786-0 factor) that are distinct from PTH but are capable of activating skeletal PTH receptors.
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PMID:Activation of the parathyroid hormone receptor-adenylate cyclase system in osteosarcoma cells by a human renal carcinoma factor. 299 59

In order to explore the relationship between the expression of cancer-associated glycolipids such as sialylated Lex (SLEX) and sialylated Lea (SLEA) and the histological subtypes of lung cancers, 30 cases of small cell carcinoma (SCC) and 47 cases of non-small cell carcinoma (non-SCC) were examined immunohistochemically using monoclonal antibodies reacting with SLEX and SLEA. The forty-seven cases of non-SCC included 20 cases of adenocarcinoma, 20 of squamous cell carcinoma and 7 of large cell carcinoma. Tumour cells of most non-SCCs expressed SLEX and SLEA. In adenocarcinomas, the number of tumour cells having SLEX and SLEA was more than that of squamous cell carcinomas, large cell carcinomas and SCC. In SCC, 14 of the 30 cases were found to be positive for both antigens. Although the cancer cells of 11 cases of 17 intermediate cell type SCC had both antigens, the cells of only 3 of 13 oat cell tumours expressed SLEX and SLEA. The present study shows that SLEX and SLEA are useful markers for lung adenocarcinomas, that most cases of intermediate cell type of SCCs have characteristics similar to non-SCC but that many oat cell tumours lack them.
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PMID:Immunohistochemical examination of lung cancers using monoclonal antibodies reacting with sialosylated Lewisx and sialosylated Lewisa. 302 84

To obtain some useful pathologic indicators for predicting the prognosis in carcinomas of the ampulla of Vater, we analyzed 24 surgically resected ampullary carcinomas pathologically with immunohistochemistry of cancer-associated antigens. Pancreatic invasion, lymph node metastasis, and histology of the tumor were significantly correlated with poor prognosis (p less than 0.01), but the size or ulceration of the tumor did not significantly affect the prognosis (p less than 0.05). Immunohistochemically, diffuse positivity for anti-CA19-9 monoclonal antibody was demonstrated in 10 carcinomas and that for anti-carcinoembryonic antigen (CEA), in 10. Eight of them showed synchronously diffuse immunoreactivities for both antigens. Although there was no significant correlation between diffuse positivity for CA19-9 and pathologic factors, CA19-9-positive cases exhibited significantly poor prognoses (p less than 0.01). Diffuse positivity for CEA was correlated with pancreatic invasion (p less than 0.05) and poor prognosis (p less than 0.05). Immunohistochemical study of cancer-associated antigens may disclose some malignant potential of ampullary carcinoma other than that expressed in the morphology. Furthermore, because of the consistency of staining results, immunohistochemistry of cancer-associated antigens may also be useful in predicting preoperatively the prognosis of ampullary carcinoma in biopsied materials.
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PMID:Carcinoma of the ampulla of Vater: expression of cancer-associated antigens inversely correlated with prognosis. 280 89

Several alterations in carbohydrate antigen expression can occur in colon cancers. Modified structures such as extended LeX and LeY antigens could serve as cancer-associated antigens in the human colon, although none is specific only for colon cancer. Since LeX and LeY antigens are present in fetal tissues, but not in adult normal tissues, these antigens appear to be oncodevelopmental in nature. The expression in colon cancers of extended LeX and LeY antigens with internal fucosylation or terminal sialylation is considered rather cancer-specific since normal colonic mucosa does not express these antigens. Furthermore, these molecules may also be "markers" for premalignancy, since adenomatous polyps, but not hyperplastic polyps are capable of exhibiting these changes and antigenic expression often correlates with malignant potential in adenomatous polyps. The precise biochemical and molecular mechanisms for these alterations in LeX and LeY expression and their biological significance are not well understood at the present time. However, it is likely that the regulation of the glycosyltransferase enzymes responsible for the processes of polylactosamine elongation, fucosylation, and sialylation may be aberrant. Obviously further studies are needed to elucidate these mechanisms. However, it appears that the monoclonal antibodies directed against extended LeX and LeY antigens are a useful adjunct in the diagnosis of colonic neoplasia, and may also be helpful in elucidating the molecular and biochemical mechanisms involved in the adenoma-carcinoma sequence.
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PMID:Carbohydrate antigen expression in the adenoma-carcinoma sequence. 305 24

The reasons reduction and replacement of laboratory animals are advancing rapidly in basic biomedical research, and why in industrial toxicology progress is much slower, are analyzed. Reference is made to a previous report from our laboratory, and the general concept of the program is outlined. Encouraging developments concerning acceptance of new concepts in acute toxicity testing by various regulatory agencies are reviewed (OECD, IKS, EEC, and Bureau of Pharmaceutical Affairs, Ministry of Health and Welfare, Japan). On the basis of new concepts proposed by the British Toxicology Society, a program which attempts to evaluate acute toxicity of chemicals as far as possible without causing mortality was started. Continuous in-cage monitoring of motility of animals, regular control of general health, body weight, food and water consumption, and body temperature are used as variables. The possibilities of reducing animal use in toxicology by application of toxicological screening procedures are explained. Screening tests under development include an operant conditioning technique to detect adverse drug interactions with ethanol and a procedure for the detection of nephrotoxic properties. The successful completion of a collaborative program designed to upgrade toxicity testing with contraceptive steroids and to abolish the 7-year beagle and 10-year monkey studies is reported. The application of in vitro cytotoxicity tests for assessment of irritant and corrosive properties of chemicals is discussed and some encouraging progress on regulatory acceptance of such tests (OECD) is reported. A new test developed at the institute is described. An in vitro model for the investigation of chemically induced changes of collagen synthesis in human fibroblasts is presented. Other cell culture methods under development include a culture system of chick brain, retina, and menings cells for the study of neurotoxic chemicals and neurobehavioral teratogens, primary hepatocyte cultures for the study of drug effects on DNA and protein synthesis and ploidy, using flow cytometry, and various in vitro models for the assessment of genotoxic and tumor-promoting activities and malignant cell transformation. The problem of analgesic treatment of animals with chronic pain was investigated. Several analgesics were evaluated, and treatment modalities providing demonstrable analgesia for prolonged periods of time in mice and rats were worked out.
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PMID:Reduction and replacement of laboratory animals in toxicological testing and research. Interim report 1984-1987. 307 63


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