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

The SHIN-3 cell line producing CA125 was established from an ovarian cancer patient. Using the SHIN-3 cell line, we found that the low-molecular-mass antigen (about 50 KDa) might be the main antigenic determinant in CA125-immunoreactive species. A new monoclonal antibody to this low-molecular-mass was raised to examine a new cancer associated antigen by a hybridoma technique. Using enzyme linked immuno sorbent assay, ten clones were selected from among 398 clones. Two clones were IgG1 and eight were IgM. By immunostaining (ABC assay), a new antibody (named SH-9) reacted with normal pulmonary bronchus and uterine cervical glands. No positivity, however, was observed in endometriosis (adenomyosis). In tumorous lesions of ovary, SH-9 antibody reacted specifically with mucinous cystadenoma-benign, borderline or malignant. However, no positivity was found in serous cystadenocarcinoma. In any other carcinomas, only lung cancer (adenocarcinoma, squamous cell carcinoma) showed a clear positivity. Immuno blotting analysis showed that SH-9 antibody recognized a low molecular mass. Therefore, SH-9 is seen to be an extremely unique antibody when compared with OC125 biochemically and histochemically.
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PMID:[A new monoclonal antibody (SH-9) recognizes the low molecular mass of ovarian cancer antigen CA125]. 169 12

A histopathological and immunohistochemical study has been made on a case of an ovarian cancer that developed into a dermoid cyst with a malignant transformation. The case involved a 64-year-old married woman and her clinical grading was determined as being in Stage Ia (i). The ovarian tumor, weighing 1550 g, consisted of large cystic and small solid parts, and a well-differentiated squamous cell carcinoma (large cell, keratinized type) was observed in the solid part. By using an immunoperoxidase technique (the ABC method), the SCC was found to be positive in many cancer cells and the TPA also was positive in some cancer cells, though both the CEA and AFP were found to be negative.
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PMID:[A case report of ovarian squamous cell carcinoma developing into a dermoid cyst with malignant transformation--immunohistochemical study]. 244 9

The authors compared both therapeutic efficacy and toxicity of two different treatment regimens: ABC = adriamycin, nitrogen mustard (BCNU) and cyclophosphamide (CTX) vs. AC = adriamycin and cyclophosphamide in ovarian cancer. Thirty-one patients were entered under treatment plan ABC and 26 under treatment plan AC simultaneously. Therapeutic evaluation was subdivided into different risk groups (adjuvant therapy, residual disease less than or greater than 2 cm). A similar result could be noted in the two different treatment regimens. Toxicity was more severe and frequent in the group treated with BCNU. The AC regimen was preferred because of its lower incidence of side-effects and for its easier mode of administration.
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PMID:Polychemotherapy in ovarian cancer: treatment with Adriamycin, BCNU and cyclophosphamide vs. Adriamycin and cyclophosphamide. 653 50

CD44 is known as an adhesion molecule which is involved in lymphocyte activation and lymphocyte homing. In recent years, its role in the invasion and metastasis of malignant tumors has attracted the attention of investigators. In this study, the expression of CD44 variants was investigated in primary lesions and metastasis into the lymph node in 53 patients with gynecological cancer. The following patients with various types of gynecological carcinoma, established by operation and pre-treatment biopsy, were included in this study: 19 patients with cancer of the uterine cervix, 23 with cancer of the uterine endometrium, and 11 with ovarian cancer. Tissue samples were obtained from a primary lesion and a nodal metastasis of each patient, and immunohistochemical staining was performed by the ABC method through the use of monoclonal antibodies against CD44v1-10. Specimens proving CD44v1-10 positive were then submitted to immunohistochemical staining through the use of monoclonal antibodies against CD44v6 and CD44v9. Expression of CD44v was judged positive when DAB revealed color development, irrespective of the degree of staining intensity. CD44v were all expressed in the cancer cell membrane. In normal endometrium, expression of CD44v1-10 and v9 was observed in the endometrial gland cell membrane. In normal ovarian tissues, CD44v6 and v9 were not detected. The expression of CD44v6 in patients with endometrial cancer was noted in 13 (72.2%) of 18 patients with vascular invasion and in one (20.0%) of 5 patients without it, indicating a significant relation to vascular invasion. It was also remarkably higher in those for whom the invasion exceeded 1/2 of the myometrium than in those for whom the invasion did not exceed 1/2 of the myometrium, and was higher too in advanced stages and in node-positive patients. In one patient, CD44v6 was detected not in the primary lesion but in the nodal metastasis. The expression of CD44v6 in patients with ovarian cancer occurred more frequently in node-positive patients. Our study results suggest that the expression of CD44v6 in endometrial adenocarcinoma cells is involved in the progression of the carcinoma, nodal metastasis, myometrial invasion, and vascular invasion, and that in ovarian cancer, the expression of CD44v6 is involved in nodal metastasis.
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PMID:Expression of CD44 alternative splicing variants in primary and lymph node metastatic lesions of gynecological cancer. 911 64

BRCA1 is a susceptibility gene for breast and ovarian cancer with growth-inhibitory activity for which the mechanism of action remains unclear. When introduced into cells, BRCA1 inhibits growth of some but not all cell lines. In an attempt to uncover the mechanism of growth suppression by BRCA1, we examined a panel of cell lines for their ability to reduce colony outgrowth in response to BRCA1 overexpression. Of all variables tested, only those cells with wild-type pRb were sensitive to BRCA1-induced growth suppression. In cells with an intact rb gene, inactivation of pRb by HPV E7 abrogates the growth arrest imposed by BRCA1. In accordance with these observations, we found that BRCA1 could not suppress BrdUrd uptake in primary fibroblasts from rb-/- mice and exhibited an intermediate ability to inhibit DNA synthesis in rb+/- as compared with rb+/+ cells. We further found that the BRCA1 protein complexes with the hypophosphorylated form of pRb. This binding is localized to amino acids 304-394 of BRCA1 protein and requires the ABC domain of pRb. In-frame deletion of BRCA1 fragment involved in interaction with pRb completely abolished the growth-suppressive property of BRCA1. Although it has been reported that BRCA1 interacts with p53, we find the p53 status did not affect the ability of BRCA1 to suppress colony formation. Our data suggest that the growth suppressor function of BRCA1 depends, at least in part, on Rb.
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PMID:BRCA1-associated growth arrest is RB-dependent. 1051 42

Polyunsaturated fatty acids such as docosahexaenoic acid (DHA), linolenic acid, and linoleic acid were linked to the C-2' position of the second-generation taxoids that could overcome MDR caused by overexpressed ABC transporters. The new conjugates, tested in vivo, exhibited strong activity against drug-resistant colon cancer and drug-sensitive ovarian cancer xenografts in mice. Two of the new conjugates, DHA-SB-T-1214 and DHA-SB-T-1213, were found to achieve the total regression of drug-resistant and drug-sensitive tumors, respectively, in the animal models with substantially reduced systemic toxicity.
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PMID:Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents. 1629 26

Chondroitin sulfate (CS) proteoglycans are major components of cartilage and other connective tissues. The monoclonal antibody WF6, developed against embryonic shark cartilage CS, recognizes an epitope in CS chains, which is expressed in ovarian cancer and variably in joint diseases. To elucidate the structure of the epitope, we isolated oligosaccharide fractions from a partial chondroitinase ABC digest of shark cartilage CS-C and established their chain length, disaccharide composition, sulfate content, and sulfation pattern. These structurally defined oligosaccharide fractions were characterized for binding to WF6 by enzyme-linked immunosorbent assay using an oligosaccharide microarray prepared with CS oligosaccharides derivatized with a fluorescent aminolipid. The lowest molecular weight fraction recognized by WF6 contained octasaccharides, which were split into five subfractions. The most reactive subfraction contained several distinct octasaccharide sequences. Two octasaccharides, DeltaD-C-C-C and DeltaC-C-A-D (where A represents GlcUAbeta1-3GalNAc(4-O-sulfate), C is GlcUAbeta1-3Gal-NAc(6-O-sulfate), D is GlcUA(2-O-sulfate)beta1-3GalNAc(6-O-sulfate), DeltaCis Delta(4,5)HexUAalpha1-3GalNAc(6-O-sulfate), and DeltaDis Delta(4,5)HexUA(2-O-sulfate)alpha1-3GalNAc(6-O-sulfate)), were recognized by WF6, but other related octasaccharides, DeltaC-A-D-C and DeltaC-C-C-C, were not. The structure and sequences of both the binding and nonbinding octasaccharides were compared by computer modeling, which revealed a remarkable similarity between the shape and distribution of the electrostatic potential in the two different octasaccharide sequences that bound to WF6 and that differed from the nonbinding octasaccharides. The strong similarity in structure predicted for the two binding CS octasaccharides (DeltaD-C-C-C and DeltaC-C-A-D) provided a possible explanation for their similar affinity for WF6, although they differed in sequence and thus form two specific mimetopes for the antibody.
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PMID:Two related but distinct chondroitin sulfate mimetope octasaccharide sequences recognized by monoclonal antibody WF6. 1788 22

Decreased expression of p16 may result from hypermethylation of the promoter or from deletion of the gene. It can lead to intensified proliferation of neoplastic cells and to cytostatic drug resistance. The study was aimed at the examination of prognostic value of p16 expression in relation to Ki67 and caspase-3 in ovarian cancers using immunohistochemistry. The immunohistochemical studies were performed on 73 paraffin-embedded samples of ovarian cancers from 43 patients and samples from 6 healthy ovaries. We have used monoclonal antibodies against p16. ABC method and DAB were used for antigens visualisation. The intensity of the immunohistochemical reactions was appraised using the semi-quantitative IRS scale. In healthy ovaries we have shown strong reaction in the nuclei of surface epithelium. In the case of studied ovarian cancers, the reaction of a nuclear and cytoplasmic localization was obtained. The mean overall immunoreactivity score of nuclear p16 expression amounted to 5.30+/-3.44 SD in primary laparotomy material and 6.61+/-4.34 SD in secondary cytoreduction material. Statistical analysis demonstrated that lower p16 expression was typical of the younger patients and the patients who died. Kaplan-Meier's analysis proved that lower expression of p16 was characteristic of cases with shorter overall survival. In the present study we have demonstrated that lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. Lowered p16 expression was also typical for chemotherapy-resistant ceases (cases of lower caspase-3 and higher Ki67 at secondary cytoreduction expression).
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PMID:Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor. 1828 37

Development of multidrug resistance (MDR) against a variety of conventional and novel chemotherapeutic agents is a significant challenge in effective cancer therapy. Over the last several years, we have focused on a multimodal therapeutic strategy to overcome tumor MDR by enhancing the delivery efficiency to the tumor mass and lowering the apoptotic threshold by modulation of the intracellular signaling mechanisms. In this study, we have examined augmentation of therapeutic efficacy upon coadministration of paclitaxel (PTX) and curcumin (CUR), an inhibitor of nuclear factor kappa B (NFkappaB) as well as a potent down-regulator of ABC transporters, in wild-type SKOV3 and drug resistant SKOV3(TR) human ovarian adenocarcinoma cells. PTX and CUR were encapsulated in flaxseed oil containing nanoemulsion formulations. The results showed that the encapsulated drugs were effectively delivered intracellular in both SKOV3 and SKOV3(TR) cells. CUR administration was shown to inhibit NFkappaB activity and down regulate P-glycoprotein expression in resistant cells. Combination PTX and CUR therapy, especially when administered in the nanoemulsion formulations, was very effective in enhancing the cytotoxicity in wild-type and resistant cells by promoting the apoptotic response. Overall, this cotherapy strategy has significant promise in the clinical management of refractory diseases, especially in ovarian cancer.
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PMID:Coadministration of Paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. 1927 22

Platinum-based chemotherapy, with cytoreductive surgery, is the cornerstone of treatment of advanced ovarian cancer; however, acquired drug resistance is a major clinical obstacle. It has been proposed that subpopulations of tumor cells with stem cell-like properties, such as so-called side populations (SP) that overexpress ABC drug transporters, can sustain the growth of drug-resistant tumor cells, leading to tumor recurrence following chemotherapy. The histone methyltransferase EZH2 is a key component of the polycomb-repressive complex 2 required for maintenance of a stem cell state, and overexpression has been implicated in drug resistance and shorter survival of ovarian cancer patients. We observed higher percentage SP in ascites from patients that have relapsed following chemotherapy compared with chemonaive patients, consistent with selection for this subpopulation during platinum-based chemotherapy. Furthermore, ABCB1 (P-glycoprotein) and EZH2 are consistently overexpressed in SP compared with non-SP from patients' tumor cells. The siRNA knockdown of EZH2 leads to loss of SP in ovarian tumor models, reduced anchorage-independent growth, and reduced tumor growth in vivo. Together, these data support a key role for EZH2 in the maintenance of a drug-resistant, tumor-sustaining subpopulation of cells in ovarian cancers undergoing chemotherapy. As such, EZH2 is an important target for anticancer drug development.
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PMID:Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. 2121 27


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