Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer of the ovary is the commonest cause of death from gynaecological neoplasms. As ovarian tumours are relatively inaccessible, there is a great need for methods to improve early diagnosis and to assist with the management of patients with this disease. In this presentation the state of the art is discussed with regard to the usefulness of the presently recognised 'tumour antigens' and other biochemical markers in ovarian cancer. Of the oncodevelopmental antigens, only alpha fetoprotein and chorionic gonadotropin are well established as good markers in tumours with, respectively, yolk sac and trophoblastic elements. Carcinoembryonic antigen seems from our own experience to be an unreliable marker in cancer of the ovary. In epithelial tumours, which constitute the majority of ovarian malignancies, mostly serous and mucinous cystadenocarcinomas, some tumour products have been described, which may have potential as a marker, for example, ovarian cancer associated antigens, some glycoprotein glycosyltransferases, and also carcinoplacental alkaline phosphatases (CPAP). Recently, in patients with epithelial ovarian tumours attending our institute, multiple biochemical markers have been studied, including CPAP, phosphohexose isomerase, and some acute phase reactant proteins. The preliminary results which will be discussed, show that longitudinal studies of some of these markers could have clinical application in follow-up. It must be concluded that, in spite of all efforts so far, and although some markers may become useful, early detection of ovarian cancer is a goal still to be reached by clinical chemistry in the field of oncology.
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PMID:Biochemical markers in ovarian cancer: possibilities and limitations. 675 Dec 3

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) levels were measured in human sera by a modification of Laurell's electroimmunoassay using rabbit anti-alpha 2-PAG serum. Sera were obtained from healthy controls (68 females), patients with myoma uteri (25 cases), patients with benign ovarian tumors (23 cases) and patients with cervical (19 cases), endometrial (4 cases) or ovarian (23 cases) cancers. The mean values of alpha 2-PAG in patients with myoma uteri (7.3 +/- 2.3U/microliters), benign ovarian tumors (5.0 +/- 3.1U/microliters), cervical cancer (8.8 +/- 4.4U/microliters), endometrial cancer (17.5 +/- 7.6U/microliters) and ovarian cancer (12.0 +/- 4.0U/microliters) were statistically significantly higher than that of controls (2.0 +/- 2.8U/microliters). Elevated levels of alpha 2-PAG were found in sera of 44% patients with myoma uteri, 17% of benign ovarian tumors, 63% of cervical cancer, 100% of endometrial cancer and 83% of ovarian cancer. Elevation of alpha 2-PAG was recognized in 100% patients with endometrial cancer and in 67% patients with ovarian cancer in stage I, while no patient with cervical cancer in stage I showed elevated alpha 2-PAG. No clear relationship of the alpha 2-PAG levels with the stages of the patients nor with the histological types of tumor was found. Serial alpha 2-PAG determination appeared to provide a useful marker in cancer patients. The measurement of serum alpha 2-PAG is recommended as an addition to the conventional diagnostic system.
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PMID:[Pregnancy-associated alpha 2-glycoprotein in patients with gynecologic cancer]. 685 93

A glycoprotein antigen (gp40) was previously identified as a major component of immune complexes isolated from sera of patients with Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC). In the present work gp40 was partially purified from a pool of BL/NPC sera. Sera of patients with BL and NPC as well as sera of patients with other malignant and non-malignant diseases were tested for antibodies against gp40, using a double antibody radioimmunoassay. Practically all normal sera and sera of patients with non-malignant diseases had antibodies capable of binding radioiodinated gp40. In contrast, sera of patients with BL or NPC had very low binding, while sera of patients with other malignant diseases had intermediate binding values. The low binding activity of BL/NPC sera was shown to be due to inhibition by excess gp40 present in such sera. Effusions of patients with breast or ovarian cancer also contained demonstrable amounts of gp40. The origin of gp40 is still unknown.
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PMID:Reactivity with patient antibodies of partially purified gp40 antigen from immune complexes in Burkitt's lymphoma and nasopharyngeal carcinoma. 710 67

Two newly established murine monoclonal antibodies (MAbs), OVS1 and OVS2, to human ovarian mucinous cystadenocarcinoma were further characterized for diagnostic efficacy. The specific SA-1 antigen, purified from the tumor extract was identified as a glycoprotein of 29 kDa. A double determinant biotinstreptavidin alkaline phosphatase immunoassay system, containing OVS1 and OVS2 MAbs was used to determine the SA-1 levels in serum. The OVS1 MAb was used as a first antibody because of its high specificity of 96% while OVS2 MAb, with a lower specificity of 8% but greater sensitivity of 78%, was chosen as a second antibody. Matched sera of 64 healthy controls and 90 patients with definite diagnoses of 25 benign diseases, 14 nonovarian cancer and 51 ovarian cancer, were simultaneously measured together with CA 125 values. At cut-off levels of 220 and 360 units/ml, the SA-1 test showed 63% and 43% positive rates respectively in all types of ovarian cancer, compared to 65% and 57% positive rates for CA 125 at cut-off levels of 35 and 60 units/ml, respectively. Sensitivity for SA-1 at 220 units/ml cut-off level in mucinous ovarian cancer was 75% and increased significantly to 85% when the test was combined with CA 125 at 35 units/ml cut-off level. Furthermore, The combination of both tests significantly increased the positive rates to 86% in all types of early stage ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Establishment of OVS1 and OVS2 monoclonal antibodies recognizing human ovarian mucinous cystadenocarcinoma. 748 44

30 years ago an anthracycline antibiotic was shown to have antineoplastic activity. This led to the development of well over 1000 analogues with a vast spectrum of biochemical characteristics. Many biological actions have been described. The original anthracyclines are active against many types of cancer and are an integral part of several curative combinations. They are ineffective against other tumours. Although some analogues show an altered spectrum of activity or an improved therapeutic index relative to the older agents, it is not clear that cardiotoxicity can be totally avoided with these agents. Primary and secondary resistance to anthracyclines remain major clinical problems. Pharmacokinetic studies have been of limited help in explaining this. Overexpression of a surface-membrane permeability glycoprotein (Pgp) was identified in ovarian cancer of patients who had clinical multidrug resistance in 1985. This led the way for the discovery of a number of resistance mechanisms in vitro. Some of these have been found in more than 1 type of cell line, and more than 1 mechanism may exist in a single cell. Additional resistance proteins have been identified, qualitative and quantitative alterations of topoisomerase II have been described, and some mechanisms in other systems have not yet been identified. Some of these may prove to be important in clinical drug resistance. Drugs such as calcium antagonists and cyclosporin, studied initially for their ability to block the Pgp pump, appear to be heterogeneous in this capacity and may have additional sites of action. It will be critical for clinical studies to define the precise resistance mechanism(s) that must be reversed. To date this has been difficult, even in trials ostensibly dealing with the original Pgp. Liposomes can potentially alter toxicity and target drug delivery to specific sites. In addition, they may permit the use of lipophilic drugs that would otherwise be difficult to administer systemically. Resistant tumours may be sensitive to anthracyclines delivered by liposomes. To reduce cardiac toxicity, administering doxorubicin (adriamycin) by slow infusion through a central-venous line should be considered whenever feasible. Monitoring of cardiac ejection fraction and the use of endomyocardial biopsy will permit patients to be treated safely after they reach the dose threshold at which heart failure begins to be a potential risk. A number of structurally modified anthracyclines with the potential advantages of decreased cardiotoxicity and avoidance of multidrug resistance mechanisms are entering clinical trials. Meanwhile, the vast weight of clinical experience leaves doxorubicin as a well tolerated and effective choice for most potentially anthracycline-sensitive tumours.
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PMID:Anthracycline antibiotics in cancer therapy. Focus on drug resistance. 751 99

Proteolytic enzymes could be very important in spread of cancer, but the role of the body's natural inhibitors of these enzymes in this process is unknown. One such inhibitor is the serum glycoprotein, alpha-1-proteinase inhibitor (API). In previous studies we showed that the fucose-specific lectin, lotus tetragonolobus, extracted high amounts of API in cancer when patients were unresponsive to treatment. The aim of this study was to determine whether the carbohydrate structure of API is altered in cancer. API was isolated from the sera of healthy women and women with breast or ovarian cancer. By means of high-performance anion-exchange chromatography, cancer API was shown to contain more fucose and less N-acetylglucosamine than healthy API. Further investigation of the purified specimens using a lectin-binding assay suggested that the cancer API was less branched and contained more alpha 2-6 and less alpha 2-3 sialic acid. Observations from both methods were consistent with an increase in bi-antennary chains terminating in alpha 2-6 sialic acid and possibly more alpha 1-6 fucose in the core of the unit. These distinctive changes could have important consequences for the function of API in cancer and may help to develop more precise markers for monitoring pathological progression in this disease.
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PMID:Decreased branching, increased fucosylation and changed sialylation of alpha-1-proteinase inhibitor in breast and ovarian cancer. 755 83

Molecular modeling and two-dimensional NMR techniques enable us to identify structural features in the third variable region (V3) loop of the human immunodeficiency virus (HIV) surface glycoprotein gp120, in particular the principal neutralizing determinant (PND), that remain conserved despite the sequence variation. The conserved structure of the PND is a solvent-accessible protruding motif or a knob, structurally isomorphous with the immunodominant knobs in the tandem repeat protein of human mucin 1 (MUC1) (a tumor antigen for breast, pancreatic, and ovarian cancer). We have replaced the mucin antigenic knobs by the PND knobs of the HIV MN isolate in a set of chimeric human MUC1/HIV V3 antigens. This produced multivalent HIV antigens in which PNDs are located at regular intervals and separated by extended mucin spacers. In this article we show by two-dimensional NMR spectroscopy that the multivalent antigens preserve the PNDs in their native structure. We also demonstrate by ELISA that the antigens correctly present the PNDs for binding to monoclonal antibodies or polyclonal antisera from HIV-infected patients.
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PMID:Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins. 781 40

Recorded concentrations of the tumour-associated glycoprotein 72 (TAG-72) in ovarian cancer patients after repeated infusion of the antibody B72.3 were found to be falsely elevated when measured with an homologous immunometric assay involving the anti-TAG-72 antibody B72.3 (Test 1), or with an heterologous assay involving CC49 capture and B72.3 detector antibodies (Test 2). Test 1 yielded falsely elevated values up to 10(4) kU/l. Test 2 gave slightly false positive elevations up to 10(2) kU/l for only some of the samples with very high false-positive values in Test 1. The interfering serum components bound to Protein G-Sepharose and could be precipitated with perchloric acid or by heating serum samples to 100 degrees C. Addition of non-specific murine immunoglobulins only partly suppressed false-positive values in both tests. Our results suggest that this interference is caused by human anti-B72.3 IgG induced by B72.3 application, which to some extent specifically binds to determinants of the B72.3 antibody. Heat extraction of serum samples effectively eliminated interferences probably caused by anti-idiotypic antibodies, but did not affect real TAG-72.
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PMID:Specific interference with the determination of the tumour-associated glycoprotein 72 by human anti-idiotypic antibodies formed after treatment with the anti-tumour-associated glycoprotein 72 antibody B72.3. 786 25

Serum levels of cancer-associated antigen 72-4 (CA72-4) (tumor-associated glycoprotein 72; TAG-72) from 106 patients with primary ovarian cancer were measured by an immunoradiometric assay employing the monoclonal antibodies (MAbs) B72.3 and CC49. Immunohistochemical localization of TAG-72 was also investigated using immunoperoxidase methodology in conjunction with both light and electron microscopy. In using a cutoff value of 4.0 U/ml for the serum assay, sensitivity of all primary ovarian carcinomas was 63.2% (67.6% of mucinous cystadenocarcinomas and 66.7% of serous cystadenocarcinomas), while specificity of benign ovarian tumors was 91.1%. Diagnostic characteristics of CA125 and CA72-4 have been demonstrated by receiver-operating-characteristics analysis. Although CA125 expressed a remarkable diagnostic efficiency with serous cystadenocarcinoma, it was less efficient with mucinous cystadenocarcinoma. CA72-4, however, was highly detectable for any histological type of ovarian cancer. Immunohistochemical staining with MAbs B72.3 and CC49 in the cytoplasm was stronger than that in the cell membrane in tissues from mucinous cystadenocarcinomas. Also, histological localization of TAG-72 in the microvilli and apical cytoplasmic membrane was demonstrated by electron microscopy using MAb B72.3 and samples of seromucinous cystadenocarcinoma (mixed type). Consequently, TAG-72 was useful for the detection of ovarian carcinoma, especially for monitoring mucinous cystadenocarcinoma, and it is localized in the microvilli and apical cytoplasmic membrane of cystadenocarcinoma cells.
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PMID:Serum and tissue measurements of CA72-4 in ovarian cancer patients. 838 75

Alkylating agents, natural products and platinum complexes are the primary chemotherapeutic agents used in the treatment of patients with ovarian cancer. Resistance frequently develops to all three classes of drugs and can be functionally separated into distinct biochemical pathways: (1) relative dose intensity plays a role in resistance to platinum complexes and to a lesser degree with alkylating agents; (2) induction of the membrane P-170 glycoprotein confers resistance to natural products and due to the potential usefulness of Taxol (a natural product extracted from the bark of yew trees), this mechanism of resistance may become more clinically relevant in the future; (3) increased levels of cellular glutathione (GSH) and glutathione S-transferases are important in the detoxification of alkylating agents and platinum complexes; and (4) increased DNA repair also is characteristic of resistance to platinum complexes and alkylating agents. Clinical trials have been initiated with agents that may inhibit the biochemical mechanisms of acquired drug resistance. Clinical trials are already in progress with alkylating agents combined with inhibition of GSH biosynthesis (i.e., buthionine sulfoximine) or enzymatic inhibitors of glutathione S-transferase activity (i.e., ethacrynic acid). Furthermore, the combination of aphidicolin, an inhibitor of DNA repair, together with platinum complexes also soon will be clinically tested based on promising results in preclinical models of ovarian cancer. Ovarian cancer is a disease of the elderly. Advances in the pharmacology of platinum compounds and in our understanding of the mechanisms of drug resistance should permit these patients to receive increasingly more effective chemotherapy.
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PMID:Mechanisms of drug resistance in ovarian cancer. 842 Jun 89


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