National Cancer Institute®
Last Modified: May 1, 2002
UI - 11920956
AU - Bharaj BB; Luo LY; Jung K; Stephan C; Diamandis EP
TI - Identification of single nucleotide polymorphisms in the human kallikrein 10 (KLK10) gene and their association with prostate, breast, testicular, and ovarian cancers.
SO - Prostate 2002 Apr 1;51(1):35-41
AD - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
BACKGROUND: The KLK10 gene (also known as the normal epithelial cell-specific 1 gene) is a member of the expanded human kallikrein gene family. Recently, it has been reported that KLK10 is a tumor suppressor gene and that its expression is downregulated in various forms of cancer and cancer cell lines. KLK10 is also upregulated in ovarian cancer. We thus hypothesized that the KLK10 gene may be a target for mutations in various cancers. METHODS: We sequenced the five coding exons of the KLK10 gene using genomic DNA from various tumors, normal tissues, and blood, by PCR amplification and automated sequencing. RESULTS: In none of the tumor-derived DNAs, we identified somatic mutations that could inactivate this gene. However, we identified a prevalent germline single nucleotide variation at codon 50 (exon 3) of this gene [GCC (alanine) to TCC (serine)]. The GCC genotype was less prevalent in prostatic cancer patients in comparison to control subjects (P = 0.027) but no differences were seen with testicular, ovarian, and breast cancer. We also identified four genetic variations in exon 4, at codons106 [GGC (glycine) to GGA (glycine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and at codon 149 [CCG (proline) to CTG (leucine)]. None of these variations was significantly different between normal subjects and cancer groups. CONCLUSIONS: We found no evidence for somatic mutations of the KLK10 gene in cancers of the prostate, breast, ovary, and testis. The single nucleotide variation at codon 50 appears to be associated with prostate cancer risk. Copyright 2002 Wiley-Liss, Inc.
UI - 11588898
AU - McCann SE; Moysich KB; Mettlin C
TI - Intakes of selected nutrients and food groups and risk of ovarian cancer.
SO - Nutr Cancer 2001;39(1):19-28
AD - Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY 14214, USA. email@example.com
In a hospital-based case-control study, we examined dietary intakes of selected nutrients and food groups and ovarian cancer risk among 496 women with primary, histologically confirmed epithelial ovarian cancer and 1,425 women with nonneoplastic diagnoses, ages 20-87 years, admitted to Roswell Park Cancer Institute between 1982 and 1998. Data on diet and other relevant risk factors in the few years before admission were collected with a self-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for age, education, region of residence, regularity of menstruation, family history of ovarian cancer, parity, age at menarche, oral contraceptive use, and energy intake. Women in the highest vs. the lowest quartile of total energy had a weak increase in risk (OR = 1.25, 95% CI = 0.90-1.73). Significantly reduced risks were associated with higher intakes of dietary fiber (OR = 0.57, 95% CI = 0.38-0.87), vitamin A (OR = 0.66, 95% CI = 0.45-0.98), carotenoid (OR = 0.64, 95% CI = 0.43-0.93), vitamin E (OR = 0.58, 95% CI = 0.38-0.88), beta-carotene (OR = 0.68, 95% CI = 0.46-0.98), and total fruit and vegetable intake (OR = 0.62, 95% CI = 0.42-0.92). Our findings suggest that a diet high in plant foods may be important in reducing risk of ovarian cancer.
UI - 11588899
AU - Tavani A; Gallus S; Dal Maso L; Franceschi S; Montella M; Conti E; La
TI - Vecchia C Coffee and alcohol intake and risk of ovarian cancer: an Italian case-control study.
SO - Nutr Cancer 2001;39(1):29-34
AD - Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milan, Italy. firstname.lastname@example.org
The relation between coffee and alcohol intake and ovarian cancer risk was analyzed in a case-control study conducted in Italy between 1992 and 1999. Cases were 1,031 women, aged 18-79 years, with incident, histologically confirmed invasive epithelial ovarian cancer, and controls were 2,411 women, aged 17-79 years, admitted to the hospital for acute nonneoplastic non-hormone-related diseases. Coffee intake (mostly espresso and mocha) was not associated with ovarian cancer risk, with an odds ratio (OR) of 0.93 [95% confidence interval (CI) = 0.69-1.27] in drinkers of > or = 4 cups/day compared with drinkers of < 1 cup/day. No meaningful relation was observed with cappuccino (OR = 1.06, 95% CI = 0.85-1.32 for drinkers compared with nondrinkers), decaffeinated coffee (OR = 0.64, 95% CI 0.42-0.96), and tea intake (OR = 0.90, 95% CI = 0.75-1.08). Total alcohol intake was not associated with ovarian cancer risk (OR = 1.09, 95% CI = 0.76-1.57 in drinkers of > or = 36 g/day compared with never drinkers). No relationship was found with wine (OR = 1.03, 95% CI = 0.70-1.50 for > 39 g/day compared with never drinkers), beer, amari, grappa, and spirits. No significant heterogeneity was found for coffee or total alcohol intake across strata of age, education, parity, oral contraceptive use, family history of ovarian/breast cancer, body mass index, and calorie intake. This study, based on a large data set; provides no support for a causal association between invasive epithelial ovarian cancer risk and coffee and alcohol intake.
UI - 11873549
AU - Fries MH; Holt C; Carpenter I; Carter CL; Daniels J; Flanagan J; Murphy
TI - K; Hailey BJ; Martin L; Hume R; Hudson G; Cadman M; Weatherly R; Nunes ME Guidelines for evaluation of patients at risk for inherited breast and ovarian cancer: recommendations of the Department of Defense Familial Breast/Ovarian Cancer Research Project.
SO - Mil Med 2002 Feb;167(2):93-8
AD - Air Force Medical Genetics Center, Keesler Air Force Base, MS 39534, USA.
Patients at high risk for inherited breast and/or ovarian cancer are frequently encountered in all medical specialties. Department of Defense, Health Affairs funding as part of the Breast Cancer Education and Awareness Program was used to develop a comprehensive program for the identification, counseling, genetic testing, and long-term follow-up of such high-risk patients. This article reports the recommendations for high-risk patient management based on 4 years of evaluation and care, including discussions of the approach to counseling, indications for genetic testing, post-testing counseling, patient surveillance with examination, imagining, and laboratory testing, and suggested options for surgical and chemoprophylaxis as well as lifestyle modifications.
UI - 11873550
AU - Fries MH; Holt C; Carpenter I; Carter CL; Daniels J; Flanagan J; Murphy
TI - K; Hailey BJ; Martin L; Hume R; Hudson G; Cadman M; Weatherly R; Nunes ME Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project.
SO - Mil Med 2002 Feb;167(2):99-103
AD - Air Force Medical Genetics Center, Keesler Air Force Base, MS 39534, USA.
The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.
UI - 11883264
AU - Czekierdowski A; Bednarek W; Rogowska W; Kotarski J
TI - [Difficulties in differential diagnosis of adnexal masses during pregnancy: the role of greyscale and color doppler sonography]
SO - Ginekol Pol 2001 Dec;72(12A):1281-6
AD - I Katedry i Kliniki Ginekologii Operacyjnej AM w Lublinie.
We have attempted to determine the accuracy of greyscale and color Doppler ultrasound in the differentiation of adnexal masses in pregnancy. The studied group included 2245 pregnant women from low risk population. Following criteria were evaluated: maximal diameter and volume of the tumor, echogenicity, presence of septa and papillary projections in grey scale sonography. Color Doppler analysis included blood vessel presence and arrangement and blood flow characteristics with the use of pulsatility (PI), resistive (RI) and systolic/diastolic (S/D) indices. Preoperative CA-125 serum levels were available in 11 patients. In 66 (2.94%) patients adnexal tumors were detected during routine ultrasound scan at the end of the first trimester. Twenty-seven masses (1.2%) persisted beyond 16 weeks of gestation and were subsequently surgically removed. Pathological diagnosis confirmed 19 serous cystadenomas, 4 endometriomas and 2 dermoids, one pedunculated myoma and one fibrothecoma. Mean size of the tumors was 79 Jmm (range: 43-245 mm), mean volume 166. lml (range: 30-1320 ml). Doppler indices values presented as mean, SD and range were as follows: PI = 1.26 +/- 0.71 (range: 0.57-3.84); RI = 0.61 +/- 0.15 (range: 0.33-0.89) and S/D = 2.62 +/- 0.98 (range: 1.17-4.91). Median serum concentration of CA-125 was 17 IU/ml (range: 8.4-1247 IU/ml). Only 3 of these women had elevated (> 35 IU/ml) levels: 2 endometriomas (344 IU/ml and 1247 IU/ml) and one myoma (37 IU/ml), respectively. Based on the sonographic findings two solid tumors were incorrectly classified as probably malignant (fibrothecoma and subserous myoma). Negative predictive value of ultrasound diagnosis in the studied population was therefore 92.6% (25 of 27). We conclude that although prenatal sonography has the potential to correctly classify most of adnexal masses, caution in risk assessment is needed especially when persistent solid tumor is found.
UI - 11883294
AU - Nowak M; Szpakowski M; Malinowski A; Wieczorek A; Maciolek-Blewniewska
TI - G; Wilczynski JR; Szpakowski A; Wierzbicka E; Malafiej E; Oszukowski P [Serum cytokines in patients with ovarian cancer and benign ovarian cysts]
SO - Ginekol Pol 2001 Dec;72(12A):1444-8
AD - Kliniki Chirurgii Ginekologicznej Instytutu Centrum Zdrowia Matki Polki w Lodzi.
The aim of our study was to evaluate serum interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) as tumor markers--study based on the data about tumor cytokines production and tumor-host interactions. METHODS: We investigated 48 women: 17 with ovarian cancer untreated before, 16 with benign ovarian cysts and 15 healthy controls. Venous blood for cytokines determinations were obtained before operations and during routine screening tests. Titers of cytokines were measured by means of ELISA technique. RESULTS: In the control group the upper limit of normal IL-6 titers (95th percentile) was 5.5 pg/ml; the mean IL-8 concentration was 9.6 +/- 15.1 pg/ml and the upper limit of normal was 37 pg/ml; serum TNF-alpha and IFN-gamma were not detectable. In patients with benign ovarian cysts the levels of all investigated cytokines didn't differ significantly from healthy controls. Women with ovarian cancer had significantly higher serum IL-8 levels (mean: 290.5 +/- 351 pg/ml) than healthy controls or women with benign ovarian cysts; 88% of them had IL-8 titers above the normal. The IL-6 titers in ovarian cancer were also higher but didn't reach statistical significance, 53% of them had IL-8 titers above the normal. TNF-alpha and IFN-gamma levels in ovarian cancer were similar to patients with benign ovarian cysts. CONCLUSION: Serum IL-8 levels in patients with ovarian cancer were significantly higher when compared to healthy controls and benign ovarian cysts and in almost 90% of ovarian cancers the titers of IL-8 were increased. Additionally, 53% of women with ovarian cancer had elevated serum IL-6 levels.
UI - 11883295
AU - Bidzinski M; Krynicki R; Lindner B; Sobiczewski P; Panek G; Wierzba W;
TI - Lewandowski Z [Granulosa cell tumor--the assessment of some clinical and therapeutic parameters as prognostic factors]
SO - Ginekol Pol 2001 Dec;72(12A):1449-54
AD - Kliniki Nowotworow Narzadow Plciowych Kobiecych Centrum Onkologii w Warszawie.
The results of the clinical and therapeutic factors in prognostic mean was presented. 48 cases of granulosa cell tumours treated from 1984 to 1994 in Oncology Centre in Warsaw were analysed. In investigated group 13 patients died, but only 8 because of relapse of the tumour. Among all analysed patients, 79% have reached 5 years free survival period. Tumour rupture, FIGO stage and incidence of irregular bleeding before recognition of the tumour had significant prognostic value. There were surprising that relative risk of relapse between patients stage I and II were similar (1.0 vs 1.01). The relative risk between I and III stage had strong prognostic difference. Additional operation after no radical surgery did not influence on better prognosis, but followed radiotherapy increase treatment results.
UI - 11925113
AU - Andersen MR; Peacock S; Nelson J; Wilson S; McIntosh M; Drescher C;
TI - Urban N Worry about ovarian cancer risk and use of ovarian cancer screening by women at risk for ovarian cancer.
SO - Gynecol Oncol 2002 Apr;85(1):3-8
AD - Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. Rander@fhcrc.org
OBJECTIVE: This study examined reports of perceived risk of ovarian cancer, worry, and screening use in a large sample of women. While screening for asymptomatic women is not generally recommended, in 1994 a consensus conference concluded that women with multiple affected relatives are at high risk for ovarian cancer and should be encouraged to participate in screening. The consensus report also suggested that women with a single affected first-degree relative are at elevated risk and while these women were not encouraged to get screening it was suggested that they may choose to pursue screening outside of a randomized trial [NIH Consensus Conference. JAMA 1995;273(6) 491-7]. METHODS: A total of 3257 women participated in this research by completing a mailed survey on ovarian cancer risk, worry, and use of screening. One hundred forty-two of these women were at high risk for this disease due to a strong family history. An additional 144 women were at elevated risk due to a single first-degree affected relative with ovarian cancer. RESULTS: Family history did predict perceived risk, difficulties due to worry, and use of ovarian cancer screening. However, the group of women most likely to report high levels of perceived risk and to have received screening for ovarian cancer were women with a single affected relative rather than those at high risk, for whom screening is recommended. CONCLUSIONS: These results suggest that many women need additional education about ovarian cancer risk. Most women overestimated their risk for this disease. Some average-risk women get screening although it is not recommended outside of randomized trials, and a significant percentage of women at high risk fail to get recommended screening.
UI - 11925118
AU - Fei R; Shaoyang L
TI - Combination antigene therapy targeting c-myc and c-erbB(2) in the ovarian cancer COC(1) cell line.
SO - Gynecol Oncol 2002 Apr;85(1):40-4
AD - Department of Gynecologic Oncology, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, 430071, People's Republic of China.
OBJECTIVE: Antigene therapy targeting only one oncogene in ovarian cancer has made much progress, although it still has some limitations. To explore the potential for combination antigene therapy in ovarian cancer, we examined the in vitro effects of liposmal antisense phosphorothioate oligodeoxynucleotides targeting c-erbB(2) and c-myc (LF-c-erbB(2)/c-myc AS-ODNs) in the human ovarian cancer COC(1) cell line. METHODS: COC(1) cells were treated differently as follows: group A with single LF-c-erbB(2) AS-ODNs; group B with single LF-c-myc AS-ODNs; group C with combination LF-c-erbB(2)/c-myc AS-ODNs; and group D as untreated control. Cell proliferation was studied by MTT assay and clonal cultures. RT-PCR was used to measure gene expression of c-erbB(2) and c-myc before and after transfection. Morphologic changes in the COC(1) cells were observed with the electron microscope. RESULTS: Single antigene therapy targeting c-erbB(2) or c-myc could reduce target gene expression and inhibit COC(1) cell growth by 61.9 +/- 9.3 and 64.5 +/- 11.2%, respectively. However, combination antigene therapy could not only suppress expression of c-erbB(2) and c-myc simultaneously, but also inhibit COC(1) cell proliferation with a higher inhibitory rate of 82.6 +/- 12.1%. Apart from that, the combination agents could induce COC(1) cell apoptosis. CONCLUSIONS: Our study suggests that combination antigene therapy targeting c-erbB(2) and c-myc can inhibit COC(1) cell proliferation and gene expression of c-erbB(2) and c-myc. Furthermore, its effectiveness is much higher than that of individual antigene therapy.
UI - 11925120
AU - Makhija S; Howden N; Edwards R; Kelley J; Townsend DW; Meltzer CC
TI - Positron emission tomography/computed tomography imaging for the detection of recurrent ovarian and fallopian tube carcinoma: a retrospective review.
SO - Gynecol Oncol 2002 Apr;85(1):53-8
AD - Division of Gynecologic Oncology, University of Alabama at Birmingham, 35243, USA.
PURPOSE: Imaging modalities to evaluate ovarian/fallopian tube cancer patients for recurrence are limited. Positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound lack the sensitivity to consistently detect recurrence or measurable disease in these patients. A new technique combines PET and CT (PET/CT) images to identify increased metabolic activity and to locate that signal with improved anatomic specificity. The objective of this study is to compare PET/CT, CT, and histologic findings in patients with recurrent ovarian/fallopian tube cancers. METHODS: Retrospective chart review of eight patients with primary ovarian (n = 6) or fallopian tube (n = 2) cancer was performed. All eight patients underwent initial cytoreductive surgery. Five patients initially received chemotherapy, one received radioactive phosphorus ((32)P), one received tamoxifen, and one received no therapy. Seven of eight patients had a suspected recurrence based on clinical examination, elevated CA-125 level, and/or abnormal CT findings; one patient requested a PET/CT. Histologic findings from surgery were correlated with PET/CT and CT findings. RESULTS: All eight patients had positive histology, and of these, seven patients had a negative CT and five patients had lesions that were correctly identified by PET/CT. CONCLUSIONS: Five of the eight (62%) patients had recurrent disease based on correlative histology with a positive PET/CT and a negative CT. These preliminary findings suggest that combined PET/CT may be an effective means of identifying patients with recurrent ovarian/fallopian tube cancer. Such patients could potentially proceed to salvage treatment and avoid the morbidity and expense of surgical assessment. Pilot studies comparing CT, PET, PET/CT, and histologic findings are underway.
UI - 11925114
AU - Piver MS
TI - Hereditary ovarian cancer. Lessons from the first twenty years of the Gilda Radner Familial Ovarian Cancer Registry.
SO - Gynecol Oncol 2002 Apr;85(1):9-17
AD - Founder and Director of the Gilda Radner Familial Ovarian Cancer Registry, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. email@example.com
UI - 11985374
AU - Anonymous
TI - Management of advanced-stage ovarian cancer: median survival rate about 2-3 years.
SO - Prescrire Int 2002 Feb;11(57):24-5
(1) Most cases of ovarian cancer are diagnosed at an advanced stage (peritoneal extension beyond the pelvis or distant metastases). (2) The standard treatment is surgery followed by chemotherapy with paclitaxel + platinum salt. Data favouring carboplatin over cisplatin in this setting are of poor quality. (3) There is no standard second-line chemotherapy regimen.
UI - 11966485
AU - Sayedur Rahman M; Al-Sibai MH; Rahman J; Al-Suleiman SA; El-Yahia AR;
TI - Al-Mulhim AA; Al-Jama F Ovarian carcinoma associated with pregnancy. A review of 9 cases.
SO - Acta Obstet Gynecol Scand 2002 Mar;81(3):260-4
AD - Department of Obstetrics, University of Garyounis, Benghazi, Libya. firstname.lastname@example.org
BACKGROUND: The purpose of this study was to review patients with ovarian cancer in pregnancy, the effectiveness of the available methods of treatment and their prognosis. METHODS: A retrospective review of all women diagnosed to have cancer of the ovary associated with pregnancy diagnosis, treatment, pregnancy outcome and maternal survival were noted. RESULTS: The incidence of ovarian carcinoma in pregnancy in the series was 0.08/1000 deliveries. Of the 9 patients, 7 had epithelial cancers; 4 serous cystadenocarcinoma, 2 mucinous cystadenocarcinomas and one undifferentiated cancer. One patient each had dysgerminoma and granulosa cell tumor. Six patients were in FIGO stage Ia, one Ic, one IIa. One patient was in stage III. Five patients were treated by unilateral salpingo-oophorectomy during pregnancy. Three patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy followed by chemotherapy. Debulking of the tumor was done in a patient in stage III with subsequent chemotherapy. This patient died 13 months from the time of diagnosis of the tumor. The overall 5-year survival rate in the series was 78% and 100% for stage Ia. CONCLUSIONS: Association of ovarian cancer with pregnancy is a rare occurrence. Early diagnosis and appropriate treatment offers the best prognosis for the patient. The higher survival rates in the series was attributed to a larger number of patients in stage I of the disease and 2 patients with a germ cell tumor and dysgerminoma which have the best prognosis. Aggressive postoperative chemotherapy also contributed to the better outcome.
UI - 11965550
AU - Bingle L; Singleton V; Bingle CD
TI - The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms.
SO - Oncogene 2002 Apr 18;21(17):2768-73
AD - Respiratory Medicine Unit, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UK.
The whey acidic protein (WAP) domain is a conserved motif, containing eight cysteines found in a characteristic 4-disulphide core arrangement, that is present in a number of otherwise unrelated proteins. WAP motifs are present in SLPI and elafin, two antiproteinases located on chromosome 20q12-13, in a locus rich in poorly characterized WAP domain proteins. One of these proteins, which contains two WAP domains, is HE4 (also known as WFDC2), originally described as an epididymis specific protein but more recently suggested to be a putative serum tumour marker for ovarian cancer. We have shown that HE4 is expressed in a number of normal human tissues outside of the male reproductive system, including regions of the respiratory tract and nasopharynx, as well as in a subset of lung tumour cell lines. Comparison of multiple HE4 cDNAs and RT-PCR products with genomic sequence allowed the elucidation of the genomic organization. These studies revealed that HE4 can undergo a complex series of alternative splicing events that can potentially yield five distinct WAP domain containing protein isoforms. These results cast doubt on the potential role of HE4 as a serum tumour marker specific for ovarian cancer and open the door to understanding the function of multiple WAP domain containing protein isoforms arising from a single gene.
UI - 11904463
AU - Nielsen B; Albregtsen F; Kildal W; Danielsen HE
TI - Prognostic classification of early ovarian cancer based on very low dimensionality adaptive texture feature vectors from cell nuclei from monolayers and histological sections.
SO - Anal Cell Pathol 2001;23(2):75-88
AD - Department of Informatics, University of Oslo, P.O.Box 1080 Blindern, N-0316 Oslo, Norway. email@example.com
In order to study the prognostic value of quantifying the chromatin structure of cell nuclei from patients with early ovarian cancer, low dimensionality adaptive fractal and Gray Level Cooccurrence Matrix texture feature vectors were extracted from nuclei images of monolayers and histological sections. Each light microscopy nucleus image was divided into a peripheral and a central part, representing 30% and 70% of the total area of the nucleus, respectively. Textural features were then extracted from the peripheral and central parts of the nuclei images.The adaptive feature extraction was based on Class Difference Matrices and Class Distance Matrices. These matrices were useful to illustrate the difference in chromatin texture between the good and bad prognosis classes of ovarian samples. Class Difference and Distance Matrices also clearly illustrated the difference in texture between the peripheral and central parts of cell nuclei. Both when working with nuclei images from monolayers and from histological sections it seems useful to extract separate features from the peripheral and central parts of the nuclei images.
UI - 11809533
AU - Baxter SW; Choong DY; Campbell IG
TI - Microsomal epoxide hydrolase polymorphism and susceptibility to ovarian cancer.
SO - Cancer Lett 2002 Mar 8;177(1):75-81
AD - VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Institute, Locked Bag No. 1 A'Beckett Street, Melbourne, Victoria, 8006, Australia.
Polymorphic variants of microsomal epoxide hydrolase (mEPHX) with altered enzyme activity have been associated with an increased risk for ovarian cancer. We assessed the frequency of exon 3 and exon 4 variants of mEPHX among 291 ovarian cancers and 257 controls from a UK-based population. The distribution of the exon 3 alleles among both the cancer and control groups was significantly different from that expected under Hardy-Weinberg equilibrium suggesting that the PCR restriction fragment length polymorphism (PCR-RFLP) genotyping assay might be flawed. The codon 113 polymorphism was reassessed using a two-color allele-specific PCR-based assay. We found that a codon 119 G>A polymorphism, present in 20% of the British population and linked to the wild-type exon 3 allele, resulted in some Tyr113/His113 heterozygotes being falsely classified as His113/His113 homozygotes when using the PCR-RFLP assay. Consequently, we reassessed all our codon 113 data using the new allele-specific assay. We found no evidence of an association of ovarian cancer risk with the exon 3 Tyr113>His113 variant. Similarly the frequencies of the exon 4 His139>Arg139 genotypes were not significantly different between cases and controls. Stratifying the genotyping data according to the predicted mEPHX activity revealed a highly significant decrease in high mEPHX activity among the serous ovarian cancers (P=0.01) suggesting that high mEPHX activity may be protective for this histological sub-type. Furthermore previous disease association studies of exon 3 alleles which utilized the PCR-RFLP assay may be compromised by the existence of a codon 119 G>A polymorphism which may be common in Caucasian populations.
UI - 11977628
AU - Yan C; Tian F; Xiao F; Li K; Li C
TI - [Adhesion induces matrix metalloproteinase-9 gene expression in ovarian cancer cells]
SO - Zhonghua Zhong Liu Za Zhi 2002 Jan;24(1):17-9
AD - Department of Tumor Molecular Biology, Reseach Clinic, Academy of Military Medical Sciences, Beijing 100039, China.
OBJECTIVE: This work was conducted to investigate the expression of matrix metalloproteinase 9 (MMP 9) gene in cancer cells by fibronectin adhesion and the underlying mechanism of cell invasion. METHODS: Following adhesion of ovarian cancer cells A2780 to fibronectin, mRNA expression of MMP cells were assayed by reverse transcription-polymerase chain reaction (RT-PCR). MMP9 promoter was cloned from genomic DNA of HT1080 cells with PCR. The MMP-9-pGL2 reporter gene vector was constructed and then transiently transfected into A2780 cells. RESULTS: Adhesion induced the increase of cellular MMP9 mRNA content in A2780 cells, not affecting the expression of MMP2 or TIMP-1 gene. The stimulation was enhanced with the increase adhesion time. When the transfected cells were allowed to adhere and spread on FN-coated surface, the promoter activity of MMP9 gene was also enhanced dramatically. CONCLUSION: Cell-ECM adhesion may stimulate the expression of MMP9 gene through stimulating the promoter activity, thereby enhancing cancer cell invasion and metastasis.
UI - 11979089
AU - Slomovitz BM; Caputo TA; Gretz HF 3rd; Economos K; Tortoriello DV;
TI - Schlosshauer PW; Baergen RN; Isacson C; Soslow RA A comparative analysis of 57 serous borderline tumors with and without a noninvasive micropapillary component.
SO - Am J Surg Pathol 2002 May;26(5):592-600
AD - Department of Obstetrics and Gynecology, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, New York, USA.
The literature concerning serous borderline tumors with a noninvasive micropapillary component suggests an association with invasive implants. We compared the clinicopathologic features of micropapillary serous borderline tumors (MSBTs) with typical SBTs to determine the following: 1) the importance of focal micropapillary architecture in an otherwise typical SBT, 2) the behavior of low-stage MSBTs, 3) whether high-stage MSBTs are inherently more aggressive than high-stage SBTs, and 4) whether invasive implants are prevalent in an MSBT cohort without referral selection bias. The 57 borderline tumors studied were diagnosed at a university hospital between 1981 and 1998; they included 14 MSBTs, 35 SBTs, and 8 SBTs with focal micropapillary features. None of the specimens were referrals for expert pathologic consultation, thus distinguishing our study group from most of those previously reported. Neither MSBTs nor SBTs were associated with invasive implants at diagnosis (0 of 14 and 0 of 43, respectively). They also did not differ with respect to overall stage at diagnosis, but MSBTs were more frequently bilateral than SBTs (71% versus 23%, p = 0.001). There was an increased risk of recurrence in MSBT versus SBT (3 of 14 versus 1 of 43, p = 0.035), but this was stage related; there was no difference between groups when evaluating recurrence in stage I disease (0 of 8 versus 0 of 27). There was no difference in recurrence or stage at diagnosis between SBTs with focal micropapillary features and other SBTs. There was 100% survival in all groups. We conclude that high-stage MSBTs with noninvasive implants should be considered a subtype of SBTs with an increased risk of recurrence. Stage I MSBTs demonstrate clinical features that are similar to low-stage SBTs. Focal micropapillary architecture (<5 mm) has no bearing on outcome. MSBTs in the general population are not strongly associated with invasive implants.
UI - 11774353
AU - Smith DI
TI - Transcriptional profiling develops molecular signatures for ovarian tumors.
SO - Cytometry 2002 Jan 1;47(1):60-2
AD - Mayo Clinic Cancer Center, Rochester, Minnesota 55905, USA. firstname.lastname@example.org
Of the cancers unique to women, ovarian cancer has the highest mortality rate. Over 26,000 women are diagnosed with this disease in the U.S. annually, and 60% of those diagnosed will die of the disease. One of the greatest problems with this disease is the lack of strong early warning signs or symptoms resulting in advanced stage at presentation in most women, followed by the outgrowth of chemotherapy-resistant disease in the majority of patients. The 5-year survival for patients with early stage disease ranges from 50-90%, but it is less than 25% for advanced-stage disease. In collaboration with researchers at Millennium Predictive Medicine (Cambridge, MA), the Ovarian Cancer Program of the Mayo Clinic Cancer Center analyzed gene expression in over 50 primary ovarian tumors, as compared with normal ovarian epithelial cells. The technologies utilized included microarray analysis with nitrocellulose filters containing 25,000 arrayed human cDNAs, as well as the construction of subtraction suppression hybridization cDNA libraries and their subsequent sequencing. Our specific focus has been on genes that are underexpressed during the development of ovarian cancer, although this analysis has revealed a large number of consistently up- and down-regulated genes. There were more down-regulated genes in ovarian tumors than up-regulated genes. In addition, the number of genes that had altered expression levels was quite large. For example, we found 409 genes down-regulated at least 5-fold, and 72 genes up-regulated at least 5-fold in 33% of the tumors analyzed. We also observed that most of the expression alterations observed in later stage (Stages III/IV) tumors were also observed in early-stage tumors (Stages I/II). This was corroborated using comparative genomic hybridization analysis on the same tumors that were expression profiled. This analysis revealed that the late-stage tumors had more gene amplification than early-stage tumors, but most regions of change (either increases or decreases) were in common between different stage tumors. We also have verified the altered expression levels of several of these genes using several complementary strategies. Finally, we are taking top candidate genes that are consistently under-expressed in ovarian tumors and attempting to determine their functional role in the development of ovarian cancer. Copyright 2001 Wiley-Liss, Inc.
UI - 11992642
AU - Kolfschoten GM; Hulscher TM; Duyndam MC; Pinedo HM; Boven E
TI - Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and apoptotic morphology in unselected human ovarian cancer cell lines as a response to docetaxel.
SO - Biochem Pharmacol 2002 Feb 15;63(4):733-43
AD - Department of Medical Oncology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
Paclitaxel is able to cause cell death through the induction of apoptosis. Cell death characteristics for docetaxel have not yet been described in detail. We investigated four unselected human ovarian cancer cell lines for the sensitivity to a 1hr exposure to docetaxel and calculated the concentrations inhibiting 50% (IC(50)) and 90% (IC(90)) of cell growth. Of the cell lines A2780, H134, IGROV-1 (all wild-type p53) and OVCAR-3 (mutant, mt p53) A2780 was most sensitive and OVCAR-3 least sensitive. Equitoxic drug concentrations representing IC(90) values (25-510nM) were applied for 1hr to measure cell cycle distribution, DNA degradation, and to count apoptotic cell bodies and cells with multifragmented nuclei at various time-points after drug exposure. H134, IGROV-1 and OVCAR-3 showed a continued mitotic block up to at least 72hr and prolonged presence of cells with multifragmented nuclei. High percentages of apoptosis were calculated at 48hr and at later time-points. In contrast, A2780 cells accumulated in the S-phase of the cell cycle and apoptosis was hardly present. The changes in the expression levels of p53, p21/WAF1, Bax and Bcl-2, were not predictive for docetaxel-induced apoptosis. Caspase-3 activation occurred only in cells with accumulation in the G2/M phase starting as early as 8hr in OVCAR-3. Prolonged Bcl-2 phosphorylation was evident in OVCAR-3, visible at 24hr in H134 and IGROV-1, while this phenomenon did not occur in A2780. The mitogen-activated protein kinase pathway (JNKs/SAPKs or c-Jun N-terminal kinases/stress-activated protein kinases, JNK1/2; extracellular response kinase, ERK1/2; p38) did not seem to be directly involved in Bcl-2 phosphorylation or apoptosis. We conclude that docetaxel is able to activate caspase-3, induce Bcl-2 phosphorylation and apoptosis in cells that show a prolonged G2/M arrest, but cells may also die by a caspase-3-independent cell death mechanism.
UI - 11570410
AU - Gjorgov AN
TI - Tubal ligation and risk of ovarian cancer.
SO - Lancet 2001 Sep 8;358(9284):843-4; discussion 844
UI - 11799032
AU - Kirwan JM; Tincello DG; Herod JJ; Frost O; Kingston RE
TI - Effect of delays in primary care referral on survival of women with epithelial ovarian cancer: retrospective audit.
SO - BMJ 2002 Jan 19;324(7330):148-51
AD - Liverpool Women's Hospital. email@example.com
OBJECTIVE: To examine referral pathways from primary care for patients with epithelial ovarian cancer and to identify factors related to survival at 18 months. DESIGN: Retrospective review of patient notes. SETTING: General practices and receiving hospitals within Mersey region. SUBJECTS: 135 patients with epithelial ovarian cancer identified from an audit in the Mersey area between 1992 and 1994. MAIN OUTCOME MEASURES: Delays between onset of symptoms and treatment attributable to patient, general practitioner, and hospital. RESULTS: 105 (78%) women first presented to their general practitioner within four weeks of the onset of symptoms. 99 (73%) women were referred to hospital by their general practitioners within four weeks of presentation, and 95 (70%) were seen in hospital within two weeks of referral. Multivariate analysis with survival as the dependent variable identified age (odds ratio 0.96, 95% confidence interval 0.93 to 0.99) cancer stage III or more (0.15, 0.05 to 0.43), and non-specific symptoms (0.36, 0.14 to 0.89) as significant variables. CONCLUSION: Most patients attended their general practitioner within four weeks and were referred within two weeks. No evidence was found that delays in referral or diagnosis adversely affected survival at 18 months. Stage of disease at surgery was the most important adverse factor. An effective screening programme is the most likely method to improve survival.
UI - 11860053
AU - Benazon NR; Coyne JC; Calzone KA; Weber BL
TI - Why not to screen high-risk women anticipating BRCA1/BRCA2 testing for psychological distress.
SO - J Consult Clin Psychol 2002 Feb;70(1):258
UI - 11930570
AU - Seiser BV
TI - Ovarian cancer strategies for nurse practitioners.
SO - J Am Acad Nurse Pract 2001 Aug;13(8):359-63
AD - Wausau Family Practice Center, Wausau, WI, USA. firstname.lastname@example.org
PURPOSE: To review and outline practical strategies for the effective detection and prevention of ovarian cancer. DATA SOURCES: Selected scientific literature, government consensus findings, and the author's experience. CONCLUSIONS: Ovarian cancer is the fourth most common cause of cancer death in American women, ranking behind lung, breast, and colorectal cancer. Seventy-five percent of ovarian cancers are currently diagnosed at an advanced stage. IMPLICATIONS FOR PRACTICE: No cost-effective screening methods are currently available. The battle to beat ovarian cancer is based on four strategies: identification of risk factors, appropriate screening methods, early detection, and prevention.
UI - 11995270
AU - Alexander-Sefre F; Menon U; Jacobs IJ
TI - Ovarian cancer screening.
SO - Hosp Med 2002 Apr;63(4):210-3
AD - Department of Gynaecological Oncology, St Bartholomew's and the Royal London Medical and Dental School, London EC1A 7BE.
Ovarian cancer is the fourth commonest cause of cancer deaths in women. Multimodal screening with serum CA125 and transvaginal ultrasonography have been shown to improve survival. However, the results so far do not justify routine screening until the impact of screening on mortality has been assessed in larger randomized trials.
UI - 11932746
AU - Judson H; Hayward BE; Sheridan E; Bonthron DT
TI - A global disorder of imprinting in the human female germ line.
SO - Nature 2002 Apr 4;416(6880):539-42
AD - University of Leeds, Molecular Medicine Unit, St. James's University Hospital, UK.
Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment.
UI - 11982262
AU - Cummings S
TI - Weighing the risks. Genetic counseling for hereditary breast and ovarian cancer.
SO - AWHONN Lifelines 2001 Jun-Jul;5(3):42-7
AD - Cancer Risk Clinic, University of Chicago, Chicago, IL, USA.
UI - 12023992
AU - Kauff ND; Satagopan JM; Robson ME; Scheuer L; Hensley M; Hudis CA; Ellis
TI - NA; Boyd J; Borgen PI; Barakat RR; Norton L; Castiel M; Nafa K; Offit K Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation.
SO - N Engl J Med 2002 May 23;346(21):1609-15
AD - Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
BACKGROUND: Risk-reducing salpingo-oophorectomy is often considered by carriers of BRCA mutations who have completed childbearing. However, there are limited data supporting the efficacy of this approach. We prospectively compared the effect of risk-reducing salpingo-oophorectomy with that of surveillance for ovarian cancer on the incidence of subsequent breast cancer and BRCA-related gynecologic cancers in women with BRCA mutations. METHODS: All women with BRCA1 or BRCA2 mutations identified during a six-year period were offered enrollment in a prospective follow-up study. A total of 170 women 35 years of age or older who had not undergone bilateral oophorectomy chose to undergo either surveillance for ovarian cancer or risk-reducing salpingo-oophorectomy. Follow-up involved an annual questionnaire, telephone contact, and reviews of medical records. The time to cancer in the two groups was compared by Kaplan-Meier analysis and a Cox proportional-hazards model. RESULTS: During a mean follow-up of 24.2 months, breast cancer was diagnosed in 3 of the 98 women who chose risk-reducing salpingo-oophorectomy and peritoneal cancer was diagnosed in 1 woman in this group. Among the 72 women who chose surveillance, breast cancer was diagnosed in 8, ovarian cancer in 4, and peritoneal cancer in 1. The time to breast cancer or BRCA-related gynecologic cancer was longer in the salpingo-oophorectomy group, with a hazard ratio for subsequent breast cancer or BRCA-related gynecologic cancer of 0.25 (95 percent confidence interval, 0.08 to 0.74). CONCLUSIONS: Salpingo-oophorectomy in carriers of BRCA mutations can decrease the risk of breast cancer and BRCA-related gynecologic cancer.
UI - 12023993
AU - Rebbeck TR; Lynch HT; Neuhausen SL; Narod SA; Van't Veer L; Garber JE;
TI - Evans G; Isaacs C; Daly MB; Matloff E; Olopade OI; Weber BL; The Prevention and Observation of Surgical End Points Study Group Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.
SO - N Engl J Med 2002 May 23;346(21):1616-22
AD - Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA. email@example.com <