Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity was demonstrated in homogenates of normal ovary and ovarian epithelial adenocarcinomas. The specific activity of the enzyme in ovarian tumors was 3 to 5 times higher than in normal ovaries when the enzyme was assayed under identical conditions. The glycoprotein fetuin, from which terminal sialic acid and penultimate galactose were removed (fetuin minus N-acetylneuraminis acid and galactose), acted as an excellent exogenous acceptor. Galactosyltransferase from normal ovary and ovarian tumor cells had similar properties. Both required Mn2+ and Triton X-100 and had broad pH optima between 5.5 and 7. Galactosyltransferase activity was also measured in serum samples from ovarian cancer patients and normal healthy individuals in the presence of fetuin minus N-acetylneuraminic acid and galactose as exogenous acceptor. The enzyme levels were significantly elevated in the sera of ovarian cancer patients as compared to normal controls. The differences in the levels of this enzyme in the tissues and sera of normal individuals and ovarian cancer patients were not due to differential levels of the degrading enzymes such as uridine 5'-diphosphate-galactose pyrophosphatase or beta-D-galactosidase. Serial determinations were carried out on the sera of 5 ovarian cancer patients over a long period of time. The serum level of galactosyltransferase activity appeared to correlate with tumor volume as well as with the clinical status of the patient, which suggests possible leakage of the tumor enzyme into the host sera. Serial determination of this enzyme level in ovarian cancer patients seems promising in measuring tumor progression or success of therapeutic approaches.
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PMID:Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity in the ovarian cancer patient. 5 28

The literature on tumor distinctive markers in ovarian cancer has been reviewed. Various immunological and biochemical approaches have been attempted for the diagnosis and management of patients with ovarian cancer. The complex spectrum of antigens that can be detected in human ovarian cancer consists of several tumor-associated antigens, fetal or carcinoembryonic antigens, carcinoplacental markers, and normal tissue antigens. We have described and partially characterized two ovarian tumor-associated antigens designated as OCAA and OCAA-1, which seem to have potential for the immunodiagnosis of ovarian cancer. Several other investigators have carried out similar studies, but in general their serological characterization of these antigens has been limited. The well-defined embryonic proteins that have been examined in the ovarian cancer include carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-fp), beta-oncofetal antigen (BOFA), Regan and Nagao isoenzymes and human chorionic gonadotropin (HCG). The presence of pregnancy-zone protein (PZP) has also been reported in ovarian cancer. In addition, several normal tissue components include fibrin-fibrinogen degradation products (FDP), alpha 1-globulin, and urokinase have been found associated with ovarian cancer. Both humoral antibodies and cell-mediated immune responses against tumor-associated antigens can be measured in ovarian cancer patients. In addition, serum factors, which block cellular immune reactions, have been identified. However, progress in this area has been hampered by the complexity of the antigens associated with ovarian tumors and the lack of standardized, well-characterized sources of antigens or target cells. Enzymes, especially those involved in glycoprotein biosynthesis, (eg, glycoprotein:glycosyltransferases and glycosidase) have been explored as possible early biochemical indicators of ovarian neoplasia. A serum specific deficiency of alpha-L-fucosidase has been found in patients with ovarian cancers. Of all the glycoprotein:glycosyltransferases studied, galactosyltransferase has been found to be the best enzyme marker for ovarian adenocarcinoma. The determination of serum levels of this enzyme reflected the clinical status of the patient with respect of tumor progression as well as tumor burden. Recently, assay of a phosphodiesterase, which specifically hydrolyzes cytidine 5'-monophospho-N-acetylneuraminic acid, has been found promising in the detection and management of patients with ovarian cancer.
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PMID:Tumor markers for ovarian cancer. 9 53

Prostatic specific antigen (PSA) can be detected in normal and benign hypertrophic prostates, as well as in prostatic cancer and its metastases. Since it appears in the serum, this glycoprotein has become an established marker for the detection and monitoring of prostate cancer. Using a radioimmunoassay (CIS--Biointernational, France), we found serum PSA levels higher than 4 ng/ml in 55 of 58 patients with prostatic cancer. The concentrations were proportional to tumor stage: significantly higher in stages C and D than in stages A and B (p less than 0.002). In all 6 cases with occult prostatic carcinoma (stage A), levels were higher than 15 ng/ml. PSA was found to be a good indicator of response to therapy, as well as a marker of tumor progression during follow-up. After radical prostatectomy serum PSA levels decreased to below 1 ng/ml. Following radiotherapy levels returned to normal within 1-6 months in 8 of 11 patients. In 21 of 23 with metastases serum PSA decreased during hormonal treatment. In 3 who responded initially to hormonal therapy, levels increased before clinical manifestation of tumor progression. We conclude that PSA is a sensitive serum marker for the diagnosis of prostatic cancer in cases of metastatic disease of unknown origin, as well as for monitoring the response to treatment of prostatic carcinoma. The use of PSA serum levels for screening for prostatic cancer is still controversial.
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PMID:[Prostatic specific antigen for detection and monitoring of prostatic cancer]. 137 29

Prostate-specific antigen (PSA) is a glycoprotein derived from prostatic ductal and acinar epithelial cells. The main clinical use of PSA is as a marker of prostate tumor progression/recurrence. We present a case of a sixty-nine-year-old patient with recurrent endometrioid carcinoma of the prostate (status post-radical prostatectomy, hormonal therapy, and external beam radiation therapy) with normal serum PSA.
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PMID:Nondetectable prostate-specific antigen in moderately differentiated adenocarcinoma of prostate. 137 34

Bladder tumor cell lines derived from male F344 rats treated with N-buthyl N-(4-hydroxybuthyl) nitrosamine (BBN) or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) have been established in vitro and characterized with respect to histology, karyotype, myc and c-Ha-ras oncogene expression or mutation, anchorage-independent growth and tumorigenicity in nude mice. This unique model system comprising 13 cell populations was employed to study common events during development of carcinogen-induced urothelial neoplasia. Differential expression of malignant phenotypes by these cell lines prompted us to examine their expression of carbohydrate structures binding peanut agglutinin (PNA), soy bean agglutinin (SBA) or leukoagglutinin (L-PHA), which are known indicators of tumor progression in rodents and humans. In the present study we analyzed the patterns of glycoproteins reactive with PNA and L-PHA by Western blotting. We also estimated quantitative differences in lectin binding to surfaces of normal rat urothelium and tumor cell lines by flow cytometry. The patterns of PNA or L-PHA reactive glycoproteins expressed by tumor cells were different from that of normal urothelium in culture. They were also different amongst the tumor cells. A unique non-sialylated, PNA binding glycoprotein (117 kD) was seen in the case of the highly tumorigenic F5 cell line and absent in normal urothelium as well as in other tumor cell lines. Normal cells did not express glycoprotein 60 kD binding PNA (only after desialylation), which was found in lysates of some but not all transformed cell lines. A very high molecular weight (much greater than 200), perhaps mucin-like sialoglycoprotein was found in normal urothelium but not in most of the tumor cell lines. Four major L-PHA reactive bands (greater than 200, 190, 100, 80 kD approximately) were found in normal urothelium. Some of those bands were overexpressed or missing in materials isolated from different tumor cell populations. Total cell surface binding of SBA and PNA by different tumor cell lines was very heterogenous (167-2% that of normal urothelium). No simple correlation between expression of the lectin binding glycoconjugates by urothelial carcinoma cells and other known functional, phenotypic or genetic alterations was found. We were also unable to demonstrate carcinogen-specific changes in expression of lectin binding to these tumor cell lines. Thus we conclude that lectin binding patterns are cell line specific. This may reflect distinct pathways of progression of individual cell lines. The potential sources of phenotypic variability between the cell lines were discussed.
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PMID:Cell line specific abnormalities in expression of PNA, SBA and L-PHA binding sites by carcinogen induced rat urothelial carcinomas. 152 17

The BDII/Han rat develops spontaneous endometrial adenocarcinoma, which appears virtually identical histologically to human endometrial adenocarcinoma. The incidence rate of cancer formation in the rat is 90% and the mean lifetime of the animals is 22 months. This animal model therefore, is useful in the study of molecular aspects of spontaneous transformation as well as mammalian neoplastic progression. In this study we address the in-situ expression of tenascin, an extracellular matrix glycoprotein, during normal cyclic growth, during development of proliferative states, and during malignant transformation of the endometrium. Trace amounts of immunocytochemically detectable tenascin were found in 10% of young BDII/Han rats with a normal estrus cycle. In these inbred animals no tenascin was detectable in uteri without neoplastic progressive alterations of the endometrium. Tenascin immunoreactivity first appeared during proliferation in one of three uteri with cystic glandular hyperplasia. Prominent tenascin expression was detectable in all adenomatous hyperplasia, but restricted to the stromal mesenchyme, that surrounded the glands. In all endometrial adenocarcinomas tested, essentially the entire extracellular space of the stromal mesenchyme was immunoreactive with anti-tenascin antibodies while the epithelial glands themselves were negative. This staining pattern was observed independent of the degree of tumor differentiation or extent of myometrial invasion. The tenascin staining pattern was not significantly altered in tumors transplanted into the soft tissues of the neck of female BDII/Han rats. From our studies we conclude that tenascin may be a marker for the early detection of proliferative endometrial states.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered tenascin expression during spontaneous endometrial carcinogenesis in the BDII/Han rat. 171 Aug 55

Colorectal primary carcinomas and metastases from 20 Dukes' stage C or D patients were examined for the immunohistochemical localization and contents of various fucosylated N-acetyl-lactosamine oligomers by specific monoclonal antibodies (MAbs). MAbs used were SH1, specific for Lewis X antigen; FH4, specific for dimeric Lewis X antigen; FH6, specific for sialyl-dimeric Lewis X antigen; and KH1, specific for Lewis Y-Lewis X antigen. The distribution of the carbohydrate antigens identified by these MAbs was heterogeneous within the primary tumor as well as within the metastatic lesion. Examinations of serial sections indicated that areas within an individual tumor which were stained with one MAb were not always reactive with the other MAbs, although these four MAbs identify closely related structures. The degree of MAb reactivity with carcinoma sections was classified by percentage positive carcinoma cells, and primary tumors and metastases from the same patients were compared. An equivalent or higher proportion of carcinoma cells in the metastatic lesions were reactive with MAb FH6 than in the primary colon carcinomas, but each correlation was not seen with the other MAbs. Electrophoretic separation of tumor tissue extracts followed by staining with these MAbs revealed that a component having an approximate molecular weight of 1,000,000 is the major site for the binding of MAbs, FH6, FH4, and KH1. The electrophoretic mobility of the antigenic molecule on polyacrylamide gels as shown by direct MAb bindings was slightly different from that of a major sialomucin revealed by wheat germ agglutinin in the same tissues. MAb FH6 binding to a high molecular weight component was eliminated by prior treatment of the glycoprotein with mild acid or sialidase to remove sialic acid. Simultaneously, binding of MAb SH2, specific for dimeric Lex antigen, to this component increased. An extract was prepared from a liver metastasis, and high molecular weight components were isolated by gel filtration and then fractionated by DEAE-cellulose ion exchange chromatography. A fraction eluted from DEAE-cellulose between 0.10-0.25 M sodium chloride contained most of the MAb FH6 reactivity, as shown by antibody affinity chromatography. These results support a hypothesis that high molecular weight glycoproteins produced by colorectal carcinoma tissues are heterogeneous with regard to their carbohydrate chains and their antigenic structures may change during tumor progression.
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PMID:Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in colorectal cancer metastases. 197 61

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We have previously shown that MDCK epithelial cells, which are deprived of intracellular adhesion by the addition of anti-Arc-1/uvomorulin antibodies, become invasive for collagen gels and embryonal heart tissue (Behrens, J., M. M. Mareel, F. M. Van Roy, and W. Birchmeier. 1989. J. Cell Biol. 108: 2435-2447.). Here we examined whether invasiveness is also induced by scatter factor, which is known to dissociate epithelial cells (Stoker, M., E. Gherardi, M. Perryman, and J. Gray. 1987. Nature (Lond.). 327:239-242.). Scatter factor was purified to homogeneity from conditioned medium of human fibroblasts by heparin-Sepharose chromatography, followed by cation exchange chromatography, gel filtration, or preparative SDS gel electrophoresis. We found that scatter factor represents a 92,000 mol wt glycoprotein which, apparently, is converted by limited proteolysis into disulfide-linked 62,000 and 34/32,000 mol wt subunits. Reversed phase HPLC and sequence analysis of tryptic peptides confirmed the suggested molecular structure, and revealed further that scatter factor exhibits sequence similarities to hepatocyte growth factor and to plasminogen. Purified scatter factor in fact induces the invasiveness into collagen matrices of MDCK epithelial cells, and induces or promotes the invasiveness of a number of human carcinoma cell lines. Apparently, the effect on the human cells depends on their respective degree of differentiation, i.e., cell lines with a less pronounced epithelial phenotype were more susceptible to the factor. Scatter factor does not seem to influence synthesis, steady-state level, and phosphorylation of the cell adhesion molecule Arc-1/uvomorulin. Thus, scatter factor represents a clearly defined molecular species which induces, in vitro, the progression of epithelial cells to a more motile, i.e., invasive phenotype.
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PMID:Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. 214 76

We examined 35 cases of stomach carcinoma and 40 cases of colonic carcinoma with PNA associated with peroxidase (peanut agglutinin, lectin which binds to the terminal disaccharide galactose beta (1,3)-N-acetil-galacto-samine). In this way evaluation of the functional aspects of the normal-neoplastic sequence was undertaken. This method was carried out for histological and ultrastructural investigations. The results obtained in both cases showed a different reactivity in the evolution of neoplastic disease: in fact, positivity in dysplasia is finely granular intracytoplasmic, whereas in well-differentiated neoplastic transformation such a reactivity is preferentially localized along the cellular membranes, with restoration of gross positivity in the cytoplasm for the poorly-differentiated neoplasm. We therefore believe PNA to be a marker not only of neoplastic progression but of differentiation as well: we also hypothesize it to reveal glycoprotein groups with possible antigenic power, involved in immunologic interactions between tumor and host.
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PMID:PNA: a marker of neoplastic progression and differentiation in the gastro-intestinal tract. 228 82

A series of clonal cell lines were derived from rat liver epithelial cells after being infected with a defective retrovirus containing either v-raf (3611-MSV) or v-raf/v-myc(J2) together with a helper virus. These clones exhibited a different morphology from the regular cuboid shape of the control cells, infected only with the helper virus. All of the infected cell lines contained at least one full length copy of appropriate proviral DNA and expressed comparable levels of v-raf mRNA, although only the cells transformed with the v-raf/v-myc combination were capable of anchorage-independent growth in soft agar. All of the clones except the controls formed tumors in nude mice but with markedly different latency periods and growth rates. Thus, these cell lines represent an in vitro model for tumor progression. Two-dimensional polyacrylamide electrophoresis was used to investigate changes in cellular protein expression related to malignant conversion. The expression of three proteins of pI/Mr x 10(-3) 5.9-7.2/205 (RP1), 6.5-7.5/160 (RP2) and 4.0/85 (RP3) consistently matched the transformed phenotype. In particular the expression of RP1 and RP2 correlated with the relative tumorigenicity of the cell lines. Rat liver epithelial cell lines transformed by other protocols that did not involve v-raf also showed downregulation of these three polypeptides. Crude fractionation studies determined RP1 to be soluble and RP2 and RP3 to be membrane associated. RP2 was shown to be a glycoprotein containing mannose and galactose residues. These three proteins are consistent markers for the tumorigenic potential of rat liver epithelial cells.
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PMID:Development of an in vitro model of tumor progression using v-raf and v-raf/v-myc transformed rat liver epithelial cells: correlation of tumorigenicity with the downregulation of specific proteins. 232 86


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