Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A canine adenocarcinoma model (CAC-8) of humoral hypercalcemia of malignancy was evaluated for transforming growth factors (TGF)-alpha and -beta, PTH-like activity [adenylate cyclase-stimulating activity (ACSA)], and in vitro bone-resorbing activity. Biological activities present in CAC-8 were separated by reverse phase or cation exchange HPLC. TGF alpha in tumor extract was separated from TGF beta and ACSA by reverse phase HPLC. TGF alpha eluted between 26-30% acetonitrile and was identified by RIA. After the initial reverse phase separation, TGF beta and ACSA in tumor extract coeluted between 36-38% acetonitrile. Sequential cation exchange followed by reverse phase HPLC separated TGF beta from ACSA. Evaluation of fractions containing ACSA using an in vitro bone-resorbing assay demonstrated copurification of ACSA and bone-resorbing activity. The PTH receptor antagonist [Nle8,18,Tyr34]bovine PTH-(3-34)-amide, but not [Nle8,18,Tyr34]bovine PTH-(7-34)-amide, completely inhibited ACSA in column eluates. Conditioned cell culture medium from CAC-8 primary cultures contained predominantly latent TGF beta that could be activated by acidification. These findings indicate that the CAC-8 model of cancer-associated hypercalcemia produces a PTH-like factor, TGF alpha, and TGF beta that were separable by reverse phase or cation exchange HPLC. This feature should be useful to investigate the role of TGFs and PTH-like proteins in the pathogenesis of humoral hypercalcemia of malignancy.
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PMID:Separation of parathyroid hormone-like activity from transforming growth factor-alpha and -beta in the canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy. 253 81

Cumulative evidence strongly implicates human papillomavirus (HPV) in the genesis of squamous neoplasia of the lower female genital tract, including the vulva. The association of HPV with neoplasms at that site includes the relationship of specific HPV types with neoplasms and evidence that those HPV DNA types can transform epithelial cells in vitro. The capacity for in vitro transformation has been isolated to specific regions of the HPV genome. That may be unique in cancer-associated viruses. Nevertheless, epidemiologic evidence points to additional factors, including immunologic, habitual and environmental, that may play an important role in the development of lower genital tract carcinomas. In particular, the marked differences in mean age and other variables between women with vulvar precancers and invasive cancer suggest that the evolution of invasive cancer involves more than HPV infection alone. Hence, the prevention of invasive vulvar cancer in older age groups will require an understanding of the unique host factors that render a small group of women susceptible to the disease in the face of an epidemic of HPV infection in the population at large.
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PMID:Papillomavirus and vulvovaginal neoplasia. 255 10

We conducted a study to evaluate cancer associated antigen CA-50 and CA 19-9 as tumor markers of gynecological malignancies. The positive rates of CA-50 and CA 19-9 for ovarian cancer were 35.5% and 48.8%, respectively, and thus were not very high. In terms of histological typing, relatively high positive rates were noted in mucinous type-42.9% for CA-50 and 71.4% for CA 19-9. Both antigens showed high false positive rates for benign ovarian tumors, especially for dermoid cyst, but produced few false positive cases of endometrial cyst. For cervical cancer and endometrial cancer, these antigens were positive at low rate. In conclusion, the present evaluation indicated that both CA-50 and CA 19-9 do not necessarily suffice as screening markers for gynecological malignancies; that they could potentially be of help for diagnosis of ovarian cancer of mucinous type; and that their false positive rates for endometrial cyst were very low.
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PMID:[Clinical evaluation of serum CA-50 and CA 19-9 in gynecological tumors]. 255 43

The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.
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PMID:Expression of the pS2 gene in normal, benign and neoplastic human stomach. 258 60

Protein A, a naturally occurring Staphylococcus aureus cell surface protein, has the unusual property of binding circulating immune complexes and immunoglobulin G with high avidity. CIC have played a major role in cancer-associated immunosuppression. Thus, removal of the immunosuppressive agents, ie, the CIC, may lead to a modulation of the immunosuppression and a liberation of the immune system to perform an antitumor effect. In animal studies, protein A has been used in extracorporeal immunoadsorption columns and treatments have resulted in tumor shrinkage and antiviral responses. Our group developed a multicenter clinical trial to assess toxicity and antitumor responses with this biologic response modifier alone. This is an update of our original trial. We have now treated 142 patients for a total of 1,306 treatments. The patients consisted of 74 males and 68 females. Their age ranged from 7 to 83 years, with a mean of 50 years. The Karnofsky performance index values ranged from 40 to 95, with a mean of 80. Patients who received seven or more treatments were considered eligible for tumor response assessment, and all patients with one or more treatments were eligible for toxicity assessment. Thus, there were 101 patients eligible for tumor response and 142 eligible for toxicity response. The total response rate was 22 patients or 21.8% (partial remission [PR], 12 patients, 12%; less than PR, 10 patients, 10%). Response rates were similar in the 13 treatment centers. Toxicity was assessed in 142 patients. One thousand three hundred six treatments were assessed for treatment toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein A immunotherapy in the treatment of cancer: an update. 265 96

Cell surface carbohydrates are important cancer-associated antigens. The carbohydrate antigens which have been proved to be useful for the serum diagnosis of human cancers are classified from their biochemical primary structure into three categories; the type 1 chain antigens, type 2 chain antigens, and core structure-associated antigens. The SPan-1 antigen, the newly-introduced tumor marker for human pancreas cancers, seems to be a type 1 chain antigen, judging from its distribution pattern among human cancers and its good correlation with other type 1 chain antigens. Another newly-introduced tumor marker, the CA54/61 antigen, which is specific for ovarian cancers, seems to belong to the family of the core-structure-associated antigens, since both antibodies (MA54 and MA61) used for the detection of the CA54/61 antigen are shown to recognize the antigen molecule which is closely related to sialyl Tn antigen, the well-known carbohydrate core structure of mucins. There are two approaches for the therapy of human cancers employing carbohydrate antigens as target molecules. One is the direct application of the specific monoclonal antibodies (alone, or in the drug-conjugated forms) in cancer patients. In this case, special attention is paid to the use of murine antibodies in human patients. The other approach is to induce specifically an effective immune response against the cancer-associated carbohydrate antigens. For this approach, further methodological development is necessary to determine how to obtain an effective immune response to carbohydrate antigens, since they have long been known as very poor immunogens which are T-independent.
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PMID:[Clinical application of cancer-associated carbohydrate antigens in the diagnosis and therapy of human cancers]. 265 13

The National Toxicology Program (NTP) rat bioassay on benzyl acetate shows an apparent increase in acinar-cell adenomas of the pancreas in male rats [1]. The statistical significance of the apparent trend is examined using the animal, cage, or rack/shelf location as the statistical independent experimental (sampling) unit. Experimental, statistical, and empirical considerations indicate that, in this experiment, if there is a proper experimental unit, it is the shelf of animals on a rack rather than the individual animal or cage of animals. Using the shelf as the experimental unit, the apparent increase in acinar-cell adenomas is not statistically significant. There is strong evidence for pancreatic tumor rates to differ among shelves which implies that toxicologists should consider cage randomization.
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PMID:What is the proper experimental unit for long-term rodent studies? An examination of the NTP benzyl acetate study. 270 95

The pharmacokinetics of 111In-labeled 260F9, a murine monoclonal antibody directed against a breast-cancer-associated antigen, was determined in seven patients with advanced breast cancer. Six patients were administered 1 mg antibody containing 1 mCi 111In. The seventh patient was administered 20 mg unlabeled antibody followed by 1 mg 111In-labeled antibody all via a peripheral vein. Immunoprecipitation, HPLC and SDS-PAGE gels demonstrated the stability of radiolabel on the antibody. The serum clearance of the radiolabel closely fits (r2 greater than 0.95) a two-compartment model for the first six patients. The apparent volume of distribution of the radiolabel approximated to the plasma volume (31) and its mean residence time was 23.7 h. The radiolabel had an average t 1/2 beta of 22.9 +/- 12.21 h at the 1-mg dose. At the 20-mg dose one-compartment elimination kinetics were observed with the radiolabel and antibody showing similar mean residence times (36-41 h) and a t 1/2 beta of 26-28 h. Whole-body imaging showed that the blood-pool: liver ratio of radioactivity increased fourfold (at 48 h postinfusion) at the higher dose and the percentage of the injected dose of radioactivity in the liver decreased from 25% to 8% (24 h postinfusion). In one patient 7-14 times more radioactivity was localized in a breast tumor than in fat (normal breast). Over the first 25 h an average (cumulative) 7.5% of the total dose was excreted in urine. A study of 260F9 in CDF-1 mice demonstrated that the radiolabel remained associated with the antibody in serum. The antibody, however, cleared 60-fold slower in mice than in patients and showed an increased mean residence time of 191 h. The disparity in the pharmacokinetics of the antibody seen in the mouse and in the clinic, points to the different behavior shown by murine monoclonal antibodies in humans. This points to the need for preliminary studies of antibodies in patients for preclinical evaluations of their effectiveness as drug-targeting agents.
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PMID:A preliminary pharmacokinetic study of 111In-labeled 260F9 anti-(breast cancer) antibody in patients. 270 39

Short-term cultures from three invasive squamous cell carcinomas of the skin were cytogenetically analyzed. Clonal chromosome aberrations were found in all tumors. In the first case, two of three abnormal clones were related, and in the second case, two of five clones demonstrated cytogenetic similarities. Both clones detected in case 3 had a structural rearrangement in common. Several nonclonal changes were seen in all three cases in addition to the clonal aberrations. None of the rearrangements detected, clonal or nonclonal, corresponds to any of the consistently cancer-associated aberrations known from other neoplasms. The remarkably diverse karyotypic picture of the three squamous cell carcinomas, in particular the finding of unrelated clones in two of them, hints that these neoplasms may be poly-rather than monoclonal. The lack of a common cytogenetic denominator argues that if chromosomal changes are of pathogenetic importance in this tumor type, a wide variety of apparently dissimilar changes exist that are roughly equal in their capacity to malignantly transform skin epithelium.
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PMID:Diverse chromosome abnormalities in squamous cell carcinomas of the skin. 273 Nov 50

There is increasing interest in cellular localization of protooncogene, growth factor, and growth factor receptor gene expression in developing or neoplastic human tissue. Establishment of nucleic acid in situ hybridization (ISH) and immunohistochemical (IH) analyses of these genes, however, is compromised by the paucity of available control tissues which have been shown to express these cancer associated genes. The present study evaluated whether proto-oncogene or growth factor gene expressing human control tissues suitable for ISH and IH studies could be produced from malignant cell lines implanted into irradiated nude mice. Tumors rapidly fixed in parafomaldehyde 2 to 4 weeks after xenograft were found optimal for in situ hybridization and immunohistochemistry. Northern blots of frozen tumors confirmed the expression of specific proto-oncogenes in the tissue and the specificity of cDNA and cRNA probes for those transcripts. Production of control tissue from xenografted cell lines should facilitate establishment and long term quality control of in situ hybridization and immunohistochemical analysis of proto-oncogene or growth factor gene expression in laboratories with limited experience in these techniques.
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PMID:Production of proto-oncogene expressing control tissues for in situ hybridization and immunohistochemical studies. 273 11


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