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)

The usefulness of PCNA staining in paraffin-embedded specimens was assessed. Next, it was clinically assessed in 21 patients treated with radiotherapy alone for cervical cancer and 47 treated with chemotherapy for ovarian cancer whether there was a correlation between GF, DNA ploidy and the effect of radiotherapy or chemotherapy or not. Furthermore, it was assessed whether there was a correlation between GF and prognosis or not. The results were as follows. 1. A strong correlation (p < 0.01) was noted between the rate of labeling with Ki-67 and that with PCNA in fresh specimens from the same patients and between the rate of labeling with PCNA in fresh specimens and that in paraffin-embedded specimens from the same patients. 2. In patients with cervical cancer, GF was significantly higher (p < 0.01) in patients who were in the G4 classification of Oboshi and Shimosato, following radiotherapy at total doses of less than 40Gy than in those who required irradiation at total doses of 40Gy or more to become G4. No significant difference was noted in the incidence of DNA aneuploid between the two groups. 3. In patients with ovarian cancer, GF in patients who showed CR was significantly higher (p < 0.05) than in those who were PR, NC or PD. No significant difference was noted in the incidence of DNA aneuploid between the two groups. The prognosis in patients with cervical cancer and ovarian cancer who had a GF of 35% or more was better than that in those who had a GF of less than 35%.
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PMID:[The correlation between the therapeutic effects and the tumor growth fraction in cervical cancer and ovarian cancer]. 790

Proliferative activity (PA) and p53 over-expression were assessed in 68 cases of primary ovarian epithelial tumors of variable grades of malignancy by immunohistochemical methods using antibodies to PCNA (proliferative cell nuclear antigen) and p53 molecule. First, we compared the values in benign tumors, tumors of borderline malignancy and malignant tumors. Malignant tumors possessed higher PA value (26.8 +/- 14.7%) than benign tumors (1.6 +/- 1.4%), and tumors of borderline malignancy exhibited an intermediate value (11.4 +/- 5.1%). Intranuclear accumulations of p53 product were more frequently observed in malignant tumors (16/32, 50%) than in tumors of borderline malignancy (3/9, 33%). None of the benign tumors exhibited p53 over-expression. In malignant tumors, PA correlated well with the histologic grade of tumors, although the histologic type and stage of the diseases did not correlate significantly with PA. Then, we focussed on the cases of malignant ovarian cancer composed of heterogeneous lesions showing a different grade of malignancy; invasive lesion (IL), non-invasive lesion (NIL), and benign appearing lesion (BAL). PA of NIL was almost identical with that of IL (19.6 +/- 13.5% vs. 23.3 +/- 12.6%), while BAL showed significantly lower PA (2.1 +/- 3.0%, p < 0.001) than the above two lesions and was similar to that of benign tumors. Furthermore, p53 over-expression was never observed in BAL, even in cases in which IL and/or NIL showed p53 over-expression. Thus, the results indicated that histologically benign-appearing lesions of malignant ovarian epithelial tumors possessed a biologic character similar to benign tumors. Collectively, all these findings would support the concept that a part of malignant ovarian epithelial tumors would be derived from benign tumors through progressive transformation.
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PMID:Proliferative activity and p53 over-expression of ovarian epithelial tumors. 854 93

Expression of the epidermal growth factor-receptor (EGF-R) and the proliferating cell nuclear antigen (PCNA) was immunohistochemically studied in 75 ovarian cancer samples using formalin-fixed, parafin-embedded tissue. Correlations between these factors and conventional histomorphologic factors were investigated. 44 (58.7%) tumors were EGF-R positive (> 10% positive cells). 18 tumors (24%) showed a weak EGF-R-expression (< or = 50% positivity) and 26 tumors (34.7%) had a strong EGF-R-expression. Expression of EGF-R did not correlate with any of the other prognostic factors investigated. The PCNA-proliferative fraction was classified using the median value (< or = 34%/ > 34%) and a categorization in three groups (< 20%/20%-50%/ > 50%). PCNA-expression showed no correlation with FIGO-stage, histologic tumor type, lymph node-status and EGF-R. However, both PCNA-classifications correlated with the size of the residual tumor (PCNA < or = 34%/ > 34%/p = 0.046; PCNA < 20%/20%-50%/ > 50%/p = 0.086) and the histologic grading (p = 0.076; p = 0.02 respectively). Thus, the PCNA-proliferative fraction might be an additional indicator for tumor aggressiveness and disease outcome.
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PMID:EGF-R and PCNA expression in ovarian carcinomas--correlation with classic prognostic factors. 870 83

Well-designed and conducted Phase II clinical trials are very important to cancer chemoprevention drug development. Three critical aspects govern the design and conduct of these trials--well-characterized agents, suitable cohorts, and reliable biomarkers for measuring efficacy that can serve as surrogate endpoints for cancer incidence. Requirements for the agent are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the chemopreventive activity observed. Agents that meet these criteria for chemoprevention of cervical cancer include antiproliferative drugs (e.g., 2-difluoromethylornithine), retinoids, folic acid, antioxidant vitamins and other agents that prevent cellular oxidative damage. Because of the significant cervical cancer risk associated with human papilloma virus (HPV) infection, agents that interfere with the activity of HPV products may also prove to be effective chemopreventives. In endometrium, unopposed estrogen exposure has been associated with cancer incidence. Thus, pure antiestrogens and progestins may be chemopreventive in this tissue. Ovarian cancer risk is correlated to ovulation frequency; therefore, oral contraceptives are potentially chemopreventive in the ovary. Recent clinical observations also suggest that retinoids, particularly all-trans-N-4-hydroxyphenylretinamide, may be chemopreventive in this tissue. The cohort should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen. In the cervix, patients with cervical intraepithelial neoplasia (CIN) and in endometrium, patients with atypical hyperplasia, fit these criteria. Defining a cohort for a Phase II trial in the ovary is more difficult. This tissue is less accessible for biopsy; consequently, the presence of precancerous lesions is more difficult to confirm. The criteria for biomarkers are that they fit expected biological mechanisms (i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, modulated by chemopreventive agents, and short latency compared with cancer), may be assayed reliably and quantitatively, measured easily, and correlate to decrease cancer incidence. They must occur in sufficient incidence to allow their biological and statistical evaluation relevant to cancer. Since carcinogenesis is a multipath process, single biomarkers are difficult to validate as surrogate endpoints, perhaps appearing on only one or a few of the many possible causal pathways. Panels of biomarkers, particularly those representing the range of carcinogenesis pathways, may prove more useful as surrogate endpoints. It is important to avoid solely on biomarkers that do not describe cancer but represent isolated events that may or may not be on the causal pathway or otherwise associated with carcinogenesis. These include markers of normal cellular processes that may be increased or expressed during carcinogenesis. Chemoprevention trials should be designed to evaluate fully the two or three biomarkers that appear to be the best models of the cancer. Additional biomarkers should be considered only if they can be analyzed efficiently and the sample size allows more important biomarkers to be evaluated completely. Two types of biomarkers that stand out regarding their high correlation to cancer and their ability to be quantified are measures of intraepithelial neoplasia and indicators of cellular proliferation. Measurements made by computer-assisted image analysis that are potentially useful as surrogate endpoint biomarkers include nuclear polymorphism comprising nuclear size, shape (roundness), and texture (DNA distribution patterns); nucleolar size and number of nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as S-phase fraction and PCNA...
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PMID:Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and ovary. 874 72

Specimens of ovarian cancers, which were obtained through laparotomy from 17 patients who received no preoperative chemotherapy and were examined histopathologically, were immunohistologically stained with anti-PCNA antibody to examine the ability to proliferate. The percent age of stained tumor cells per 1,000 cells was used as a PCNA-labeled rate. This rate was analyzed in relation to the clinical stage/histological type and the presence or absence of lymph node metastasis. 1. Tissue specimens were stained with anti-PCNA antibody in all cases, and the PCNA-labeled rate was 49.5 +/- 13.3%. 2. There were no significant differences in PCNA-labeled rates between different histological types or between clinical stages. 3. The PCNA-labeled rates was significantly higher in cases with metastasis than in those without metastasis (p < 0.01). 4. No metastasis was detected in the cases showing a PCNA-labeled rate of 50% or below. It was indicated that this PCNA-labeled rate, which can be determined with formalin-fixed specimens, is useful for evaluating the degree of biological malignancy of ovarian cancer.
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PMID:[Study on expression of proliferating cell nuclear antigen (PCNA) in ovarian cancer]. 894 Jun 94

The prognostic value of the PCNA-proliferative fraction as compared to conventional clinical and histomorphological factors (FIGO-stage, tumour type, histological grading, lymph node status, size of residual tumour) was investigated in 81 ovarian cancer patients. Categorisation of PCNA-expression into tumours with low and high proliferative activity (< 20%/ > or = 20% according to laboratory standards) had the highest prognostic value. Categorisation on the basis of the median value (< or = 34%/> 34%) or classification of PCNA as a continuous variable did not prove advantageous. PCNA-proliferative fraction was significantly directly correlated with histological grading (p = 0.006). Tumours with a high PCNA expression had a greater frequency of macroscopically detectable residual tumours. In univariate survival analyses patients with highly proliferating tumours had a worse outcome than patients with tumour of low proliferation (PCNA </> or = 20%/20%, p = 0.012; PCNA < or = 34%/ > 34%, p = 0.08). The result was consistent in subgroup of FIGO III-tumours (p = 0.031, PCNA < 20%/> or = 20%), of FIGO l-tumours (p = 0.036, PCNA < 20%/> or = 20%), of carcinomas without post-operative residual tumour (p = 0.03 PCNA < 20%/> or = 20%) and also of FIGO III-tumour without residual tumours (p = 0.041 PCNA < 20%/> or = 20%). Multivariate survival analysis comprising all the patients revealed PCNA expression (< 20%/> or = 20%) as an independent prognostic factor second to the size of the residual tumour. In patients with FIGO III-tumours PCNA proves significant as an independent factor after the size of the residual tumour was removed from the model. Thus, PCNA provides additional information which may prove beneficial in determining prognostic estimates for ovarian cancer.
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PMID:[Significance of PCNA proliferating fraction for prognosis of ovarian carcinoma]. 896 50

Recently, Frey (Cytometry 17:310-318, 1994) demonstrated that TO-PRO-3 iodide (TP3) can be excited indirectly by a 488 nm laser line through energy transfer by propidium iodide (PI). In the present study, we investigated whether PI-TP3 energy transfer can help to overcome spectral cross talk problems associated with the combined use of fluorescein isothiocyanate (FITC), R-phycoerythrin (PE), and PI. Mixtures of keratin 8/18 FITC-labeled, keratin 8/18-PE-labeled, and unlabeled MCF-7 breast carcinoma cells were prepared and stained for DNA with PI (100 microM). The effect of adding a range of TP3 concentrations (0.001 to 16 microM) to these mixtures was evaluated. The combined use of PI and TP3 was further evaluated using mixtures of unlabeled and p53 FITC-labeled COV362.cl4 ovarian cancer cells and mixtures of unlabeled and p53 FITC-labeled COV362.cl4 cells and peripheral blood lymphocytes (PBL), additionally stained for keratin 8/18 (PE). Finally, a human ovarian ascites tumor specimen was triple-stained for keratin 8/18 (PE), vimentin (FITC) and DNA or keratin 8/18 (PE), PCNA (FITC) and DNA. Addition of TP3 allowed complete correction for spectral cross talk of PE/PI into the green fluorescence detector (FL1). Only minimal (FL1 - %FL2) compensation was required at a TP3 concentration of 2.0 microM in the presence of PI (100 microM). The PI spectral cross talk into the orange fluorescence detector (FL2) was reduced by about 50% using the same photomultiplier (PMT) settings. Although addition of TP3 reduced the signal-to-background ratio by about 30%, the advantage gained through full compensation for spectral cross talk resulted in an improved discrimination of p53-positive and -negative subpopulations in a mixture of human PBL and COV362.cl4 cells. Furthermore, vimentin-negative and PCNA-negative cells were better resolved in a human DNA-aneuploid ovarian ascites tumor after staining the DNA with PI/TP3, rather than with PI alone. We conclude that the addition of TP3 to PI improves the combined measurement by single-laser flow cytometry of DNA-ploidy and antigen expression in heterogenous clinical samples.
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PMID:Improved single laser measurement of two cellular antigens and DNA-ploidy by the combined use of propidium iodide and TO-PRO-3 iodide. 926 54

Few biological parameters have been shown to have a prognostic role in patients with advanced ovarian cancer. p27Kip1 is a cyclin-dependent kinase inhibitor, and its loss may contribute to tumor progression. We determined whether p27Kip1 protein expression in advanced ovarian cancer could be associated with prognosis. p27Kip1 status was assessed by immunohistochemical analysis of tissue sections from primary tumors of 99 patients with stages III-IV ovarian carcinoma and was analyzed in relation to clinicopathological variables, time to progression (TTP), and overall survival (OS). p27Kip1 expression was detected in 47 (47%) of the 99 patients. p27 expression did not correlate with any of the classical clinicopathological parameters. Loss of p27 protein was significantly associated with a short TTP (P = 0.0004) and decreased OS (P = 0.0302). The 5-year TTP rate in p27-positive patients was 50% versus 11% in p27-negative patients. p27-positive cases showed a 5-year OS rate of 53% compared with 43% of p27-negative cases. In multivariate analysis, p27 expression was an independent predictor of progression of disease (P = 0.0009) and survival (P = 0.0032) when considered together with stage of disease, presence of ascites, and residual tumor at surgery. Loss of p27Kip1 conferred poor prognosis independently of proliferative index, as assessed by proliferating cell nuclear antigen immunostaining. p27 immunoreactivity can be used to predict progression of disease and survival in patients with advanced epithelial ovarian cancer and therefore may represent a new prognostic marker.
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PMID:p27Kip1 expression is associated with clinical outcome in advanced epithelial ovarian cancer: multivariate analysis. 1115 40

Polo-like kinase (PLK), a cell cycle-regulated, cyclin-independent serine/threonine protein kinase, has been shown in recent reports to play a critical role during tumorigenesis. To investigate whether PLK plays a general role as a tumor marker of ovarian cancers, we examined the expression of PLK protein in ovarian cancers, and analyzed the relationship between PLK protein expression and histological grade. Immunohistochemically, the majority of PLK was found in the cytoplasm (around the nucleus), and a portion was found in the nucleus of ovarian cancer glands and also in the fluid secreted from these glands. PLK was expressed at the basement membrane of cancer glands and partly expressed in the head portion of papillary cancer tissues. A significant correlation was found between percentages of PLK-positive cells and histological grade of ovarian cancer (P<0.001). However, the expression of proliferating cell nuclear antigen, Ki-67, and cyclin B1 was independent of PLK expression. Taken together, these findings suggest that PLK expression may reflect the degree of malignancy rather than the degree of proliferation in ovarian cancer. Thus, in addition to being of diagnostic value, PLK activity in ovarian tumors may be modulated by chemotherapeutic agents or gene therapy to therapeutic effect.
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PMID:Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage. 1116 14

Recent studies suggest that drug induced apoptosis relates to the sensitivity. p53 gene, which has a pivotal role in inducing apoptosis, frequently mutates in ovarian cancer. Therefore, p53 gene status and chemosensitivity in epithelial ovarian cancer is discussed. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-base chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. p53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis in ovarian cancer cells without p53 gene. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer cells with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP in ovarian cancer xenograft. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively lower in an ovarian cancer xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. A significant survival advantage was observed in the combination treatment compared with other treatments in carcinoma peritonitis models. In conclusion, p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene.
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PMID:p53 gene status and chemosensitivity in ovarian cancer. 1177 36


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