Jean A Hurteau

NorthShore University HealthSystem, Chicago, Illinois, United States

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Publications (35)126.88 Total impact

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    ABSTRACT: Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (L(d) ). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in L(d) (% fold-increase > 50%, P-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with mico-RNA expression data. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 02/2013; · 6.20 Impact Factor
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    ABSTRACT: There is growing evidence that progestins and nonsteroidal antiinflammatory drugs (NSAIDs) may prevent ovarian cancer. Because both induce apoptosis, we investigated the potential for synergistic impact of combined drug treatment on cell death. Using normal and malignant human ovarian epithelial cells and an NSAID-sensitive human colon cancer cell line, we evaluated the effects of progestins and NSAIDs alone and in combination on apoptosis. Both progestins and NSAIDs dose dependently inhibited cell growth (P < .0001). Doses of NSAIDs or progestins that independently reduced cell viability by less than 30% synergistically reduced cell viability by 70-95% when combined. Similarly, the NSAID/progestin combination conferred 4- to 18-fold (P < .05) increased apoptosis over either treatment alone. Our results suggest it may be possible to combine progestins and NSAIDs to achieve ovarian cancer prevention at lower doses of each than are required for single administration, thereby lessening the risk of side effects posed by these agents.
    American journal of obstetrics and gynecology 11/2011; 206(3):253.e1-9. · 3.97 Impact Factor
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    ABSTRACT: Protein kinase C (PKC) activation contributes to proliferation and angiogenesis in epithelial ovarian or primary peritoneal carcinoma (EOC/PPC). A multi-institutional phase II trial was conducted to evaluate the efficacy and safety of PKCβ inhibitor enzastaurin in persistent or recurrent EOC/PPC and to explore potential prognostic and predictive biomarkers. Eligible women with measurable platinum-sensitive and resistant EOC/PPC were treated with continuous administration of oral enzastaurin until disease progression or unacceptable toxicity. A two-stage sequential design was used to evaluate progression-free survival (PFS) ≥6-months, tumor response, and toxicity. Translational studies included sequencing of the TP53, PTEN, PIK3CA and PKCβII genes for somatic mutations, quantitative PCR assays for AKT2 and PTEN copy number alterations, and measurement of circulating VEGF-A plasma levels. Among 27 eligible and evaluable patients, 3 women with PFS≥6-months (11%) and 2 women with partial responses (7%) were observed. One of them achieved a durable response and remains on the study. No grade 4 adverse events were observed. Most common grade 3 adverse events were constitutional (4) and gastrointestinal (3). Mutations in the TP53 gene and abnormal copy number in the PTEN gene were common (56% and 48% of cases, respectively). Enzastaurin was tolerable but had insufficient activity to proceed with the second stage of accrual. However, 1 patient has been progression-free for 44 months. No association between a biomarker and response to enzastaurin has been found. Exploratory analysis suggested an association between survival and PTEN copy number losses.
    Gynecologic Oncology 03/2011; 121(3):455-61. · 3.69 Impact Factor
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    ABSTRACT: To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC). Biochemical recurrence was defined as a rising CA-125 exceeding twice the upper limit of normal without evidence of disease as defined by RECIST 1.0 criteria. Women with FIGO stages III and IV, histologically confirmed EOC/PPC/FTC who were free of disease following first-line chemotherapy were randomized to oral thalidomide 200mg daily with escalation to a maximum of 400 mg or tamoxifen 20mg orally twice daily for up to 1 year, progression or adverse effect prohibited further treatment. VEGF was quantified by ELISA in pre and post-treatment serum. Of the 139 women randomized, 138 were eligible. Interim analysis showed that thalidomide did not reduce the recurrence rate relative to tamoxifen, and the trial was closed. Thalidomide versus tamoxifen was associated with a similar risk of progression (HR = 1.31, 95% confidence interval [CI] = 0.93-1.85), an increased risk of death (HR = 1.76, 95% CI = 1.16-2.68) and more grades 3 and 4 toxicities (55% versus 3%). The most common grades 3 and 4 toxicities were constitutional (12%), somnolence (12%), pulmonary (9%), venous thromboembolism (VTE) (6%) and peripheral neurologic (6%) for thalidomide, with VTE (1.4%) and gastrointestinal (1.4%) for tamoxifen. Serum VEGF was not associated with clinical characteristics, treatment, PFS or OS. Thalidomide was not more effective than tamoxifen in delaying recurrence or death but was more toxic. VEGF was not prognostic in this cohort.
    Gynecologic Oncology 12/2010; 119(3):444-50. · 3.69 Impact Factor
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    ABSTRACT: The current management of advanced ovarian cancer consists of aggressive primary cytoreductive surgery (PCS) followed by combination platinum based chemotherapy. Recent studies have suggested that platinum-based chemotherapy may be of benefit in patients with advanced ovarian cancer prior to cytoreductive surgery (neoadjuvant chemotherapy, NACT). The concept of NACT has not been completely validated in the treatment of ovarian cancer. This review will discuss the role of NACT in patients with advanced epithelial ovarian cancer.
    Journal of Surgical Oncology 02/2010; 101(4):334-43. · 2.84 Impact Factor
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    ABSTRACT: To evaluate the response rate and toxicity of a regimen comprised of monthly carboplatin and weekly paclitaxel for recurrent ovarian cancer. We performed a retrospective chart review of patients with recurrent ovarian cancer treated between 2001 and 2006 at a single institution with carboplatin AUC 5 (day 1), and paclitaxel 80 mg/m(2) (days 1, 8, 15) of a 28-day cycle. Primary endpoints were response rate, progression-free survival and overall survival. Twenty patients were treated with this regimen from 2001 to 2006. Stage ranged from stages IC to IV. All received intravenous platinum and taxane as their initial therapy. Histologic subtypes included papillary serous (17), carcinosarcoma (1), and clear cell (2). The median number of prior regimens was 1 (range 1-3). The overall response rate was 85.0% (15 complete responses, 2 partial responses). Patients with tumors categorized as platinum sensitive had a response rate of 93.3% (14/15) and those with tumors deemed platinum resistant had a response rate of 60.0% (3/5). The median survival has not yet been reached after a median follow-up of 28 months. Neutropenia was the only grade 3/4 toxicity, occurring in 7 patients (35.0%). Platinum hypersensitivity reactions occurred in 5 patients (25.0%) who all successfully continued treatment using a carboplatin desensitization protocol. A monthly carboplatin and weekly paclitaxel regimen is highly active for women with recurrent platinum-sensitive and platinum-resistant epithelial ovarian cancer. The regimen is well tolerated. This pilot series demonstrates the potential for this regimen as treatment of choice among doublet first salvage regimens for patients with recurrent epithelial ovarian cancer, thus warranting multi-institutional study.
    Gynecologic Oncology 09/2009; 115(3):377-81. · 3.69 Impact Factor
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    ABSTRACT: We previously demonstrated that omega-3 fatty acids (OM-3FAs) have definitive inhibitory effects on ovarian cancer cell lines. We sought to determine whether the inhibitory effects of OM-3FAs were mediated by the transforming growth factor (TGF)-beta1 signaling pathway. Ovarian cancer cell lines were grown at 37 degrees C in 5% CO(2) and treated with OM-3FAs, omega-6 fatty acids, and control at different concentrations for 24-72 hours. Enzyme-linked immunosorbent assay (ELISA) assay and Western blot analysis were used to measure TGF-beta1, phosphorylated mothers against decapentaplegic (Smad)-3 and p21 protein levels. An ELISA assay demonstrated that OM-3FA treatment increased TGF-beta1 in all 3 Hey cell lines (P < .05). In both SKOV-3 and OVCAR-3 cells, TGF-beta1 levels were not significantly increased. Western blots confirmed increases in TGF-beta1, Smad-3 and p21 protein levels in Hey and HeyC2 but not SKOV-3 and OVCAR-3 cells. OM-3FAs increased the level of TGF-beta1, Smad-3, and p21 protein in ovarian cancer cells known to be more sensitive to their inhibitory effect.
    American journal of obstetrics and gynecology 03/2009; 200(5):516.e1-6. · 3.97 Impact Factor
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    ABSTRACT: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m(2)/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and > or =40 Gy (V(10), V(20), V(30), and V(40), respectively) was calculated. HT was graded according to the Radiation Therapy Oncology Group system. Multivariate regression models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. Increased pelvic BM V(10) (BM-V(10)) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V(10) > or =90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V(10) <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V(30) and V(40) were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.
    International Journal of Radiation OncologyBiologyPhysics 12/2006; 66(5):1356-65. · 4.18 Impact Factor
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    ABSTRACT: Omega-3 fatty acids (OM-3FAs) have been shown to possess anti-carcinogenic properties. We investigated the effect of OM-3FAs on epithelial ovarian cancer cell lines to determine if a growth suppressive effect existed and to gain a better insight on the potential molecular mechanisms that may be involved. Three epithelial ovarian cancer cell lines (SKOV-3 [p53 null], TOV-21G [wt p53] and OVCAR-3 [mutant p53]) and one immortalized ovarian surface epithelial cell line (IOSE-29 [wt p53]) were treated with OM-3FAs and evaluated for cellular proliferation (WST-1 assay), apoptosis (Annexin V-FITC/PI method) and VEGF expression (VEGF ELISA assay). A statistically significant inhibitory effect under the influence of OM-3FAs was detected in all four cell lines. Apoptosis and VEGF down-regulation were either limited or not detected in the p53 null and mutant cell lines, SKOV-3 and OVCAR-3 respectively. Apoptosis and/or VEGF down-regulation was strongly evident in the wt p53 cell lines TOV-21G and IOSE-29. These data suggest that, under the influence of OM-3FAs, there are definitive growth suppressive mechanisms at work and that the biologic effects of OM-3FAs may in part be mediated by the p53 status.
    Gynecologic Oncology 11/2005; 99(1):58-64. · 3.69 Impact Factor
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    ABSTRACT: The purpose of this pilot study was to evaluate the efficacy of the clitoral therapy device (Eros Therapy) in alleviating sexual dysfunction in irradiated cervical cancer patients. Eligible patients had a history of cervical cancer treated with radiotherapy and self-reported sexual dysfunction of sexual arousal and/or orgasmic disorders. Patients used the noninvasive, nonpharmacologic clitoral therapy device using a hand-held, battery-powered vacuum to cause clitoral engorgement four times weekly for 3 months during foreplay and self-stimulation. Study instruments included the Female Sexual Function Index, Derogatis Interview for Sexual Functioning, and Dyadic Adjustment Scale. The outcome evaluation was performed at 3 months. Between 2001 and 2002, 15 women were enrolled and 13 completed the study. The median patient age and radiotherapy-enrollment interval was 43.5 years and 2 years, respectively. At baseline, all patients reported symptoms of sexual arousal and/or orgasmic disorders, and some also had sexual desire and pain disorders. At 3 months, statistically significant improvements were seen in all domains tested, including sexual desire, arousal, lubrication, orgasm, sexual satisfaction, and reduced pain. The median Female Sexual Function Index total score increased from 17 to 29.4 (maximal score, 36; p <0.001). The median Derogatis Interview for Sexual Functioning total raw score increased from 46 to 95 (maximal score, 118; p <0.001). At baseline, the Derogatis Interview for Sexual Functioning total T-score corresponded to the bottom 10th percentile of normal sexual functioning. At 3 months, the total T-score placed the patients at the normalcy cutoff. Gynecologic examinations revealed improved mucosal color and moisture and vaginal elasticity and decreased bleeding and ulceration. Our results from this pilot study suggest that the clitoral therapy device may alleviate sexual dysfunction in irradiated cervical cancer patients. A randomized, controlled trial is warranted to assess the full benefits of this approach.
    International Journal of Radiation OncologyBiologyPhysics 04/2005; 61(4):1078-86. · 4.18 Impact Factor
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    ABSTRACT: A functional and widely accepted definition of microinvasive cervical adenocarcinoma remains elusive. The purpose of this study was to determine at which depth of invasion the likelihood of lymph node metastasis or disease recurrence was so small that conservative surgery could be considered appropriate. Charts of patients with adenocarcinoma of the cervix (ACC) who underwent radical hysterectomy and pelvic lymphadenectomy (n = 98) at Indiana University Medical Center from 1987 to 1998 were retrospectively reviewed. Patients with stage IA1-IB1 lesions were included in the study. Patients treated with preoperative radiotherapy were excluded. Pathologic parameters evaluated included histologic type, depth of stromal invasion (DOI), and the presence of lymphatic vascular space invasion, or lymph node metastases. The patient median age was 39 years (20-65). The median time of follow-up was 30 months (4-124). Lymph node metastases were found in ten patients and 11 developed recurrences. The precise DOI could be measured in 84 patients. Of the 48 patients with cancers with a DOI </= 5 mm, none had involved parametria or nodes; whereas eight of the 36 with a DOI > 5 mm had nodal metastases (P = 0.00069). None of these 48 patients with a tumor DOI </= 5 mm developed a recurrence whereas six of the 36 patients with a tumor DOI > 5 mm developed recurrent disease (P = 0.0048). The risk of nodal metastases and recurrence is so low in patients with ACC and DOI </= 5 mm that for patients with such depth documented on conization with negative margins pelvic lymphadenectomy may be omitted.
    International Journal of Gynecological Cancer 01/2004; 14(1):104-9. · 1.95 Impact Factor
  • Jean A Hurteau
    Clinical Obstetrics and Gynecology 10/2003; 46(3):557-69. · 1.53 Impact Factor
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    ABSTRACT: Transillumination and laparoscopic visualization are two techniques recommended to minimize the risks of injury to abdominal wall structures during insertion of secondary trocars. This study was designed to determine the effectiveness of these techniques to locate the epigastric vessels and superior bladder margin. Prospective observational. Academic medical centers. One hundred five women undergoing laparoscopy for tubal sterilization, infertility, pelvic masses, or pelvic pain. None. The ability to visualize the superficial and inferior epigastric vessels, and bladder margin; body mass index (BMI; in kilograms per meter squared); and skin color. Transillumination successfully visualized 64% of superficial epigastric vessels and was less effective both as weight increased (BMI <25 kg/m(2): 86%; BMI = 25-30 kg/m(2): 61%; BMI >30 kg/m(2): 25%) and in dark-skinned women (69%) compared to those with lighter skin (42%). Laparoscopic visualization successfully identified 82% of inferior epigastric vessels and 46% of bladder margins, and was less effective as weight increased. Transillumination can successfully locate superficial epigastric vessels, and laparoscopic visualization can locate inferior epigastric vessels and the superior bladder margin in the majority of women undergoing laparoscopy. Transillumination is less effective in dark-skinned women, and both techniques are less effective with increasing body weight.
    Fertility and Sterility 08/2003; 80(1):209-12. · 4.30 Impact Factor
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    ABSTRACT: The purpose of this study was to test the hypothesis that the expression of the mutant p27(Kip1) protein enhances cell growth inhibition and is more stable than that of the wild-type p27(Kip1). Site-directed mutagenesis was used to mutate threonine 187 to an alanine residue, generating the mutant p27(Kip1). To study the effects of the p27(Kip1) mutant on cell growth, luciferase assays were performed. Cells were transiently transfected with the Renilla luciferase reporter construct and empty vector, wild-type p27(Kip1), or mutant p27(Kip1) using Fugene 6. The transfected cells were lysed and assayed for luciferase activity 24 h later with a dual-luciferase reporter assay system. To further assess the effects of the p27(Kip1) mutant on cell growth, colony count assays were performed. The experiments were repeated in duplicate and a standard two-tailed Student t test was use to analyze the data. Wild-type p27(Kip1) protein has a half-life of approximately 2 h while the p27(Kip1) mutant has a half-life of greater than 12 h. Furthermore, the p27(Kip1) mutant retained the ability to inhibit CDK2-associated H1 kinase activity. Cells expressing the p27(Kip1) mutant had an 88% reduction in luciferase activity compared to cells expressing the wild-type p27(Kip1) (P = 0.001). Colony assays revealed that cells expressing the p27(Kip1) mutant had fewer colonies compared to cells expressing the wild-type p27(Kip1) (P = 0.04). These data are consistent with the hypothesis that the mutated form of p27(Kip1) is more effective in cell growth inhibition than the wild-type p27(Kip1) protein.
    Gynecologic Oncology 08/2002; 86(1):19-23. · 3.69 Impact Factor
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    ABSTRACT: Laparoscopy may be associated with increased risk of ovarian carcinoma wound metastases. This study was designed to determine whether carbon dioxide exposure increases the growth of human ovarian cancer cells in vitro. Immortalized ovarian epithelial carcinoma cell (SKOV-3 cell line) cultures were exposed to carbon dioxide, nitrous oxide, or culture media with decreased pH for up to 3 hours. Cell growth was determined with the use of a spectrophotometric assay, and the results were compared with control cells by paired t tests and linear regressions analysis. Carbon dioxide exposure increased SKOV-3 cell growth by 52% after 4 days in culture. The increased cell growth had a linear relationship to the length of carbon dioxide exposure. Cells that were exposed to either nitrous oxide or media with pH 6.3 showed a trend toward decreased growth. Carbon dioxide exposure increases the in vitro growth of human ovarian carcinoma cells by an effect that is independent of the carbon dioxide-related decrease in the culture media pH.
    American Journal of Obstetrics and Gynecology 01/2002; 185(6):1314-7. · 3.97 Impact Factor
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    ABSTRACT: To determine if p27(Kip1) expression was altered in epithelial ovarian cancers as compared to normal ovarian surface epithelial (NOSE) cells and to determine if subcellular localization of p27(Kip1) was an important feature. Thirteen tumor samples (1 Stage IC [early] and 12 Stage III/IV [advanced]) from patients with epithelial ovarian cancer and five NOSE samples were evaluated. Samples were surgically dissected to obtain an enriched population (90%) of cancer cells. The level of p27(Kip1) protein expression was determined by Western blot analysis. Actin was used as a loading control, and results were quantified by scanning densitometry using the ratio of the p27(Kip1) signal to the actin signal for comparison. To evaluate the subcellular localization of p27(Kip1), immunocytochemical staining was performed. Clinical pathological parameters were correlated to nuclear p27(Kip1) staining to establish if any association existed. When comparing the expression of p27(Kip1) between NOSE and ovarian cancer samples, only 2 of 13 ovarian cancer samples had altered p27(Kip1) expression. No correlation was found between the expression level of p27(Kip1) on Western blot and clinical pathological correlates. While no correlation between expression level of p27(Kip1) and subcellular localization was found, decreased nuclear staining (1+) was associated with shorter survivals using the log-rank test (P < 0.001). More importantly, in all tumor samples examined under the microscope, no nuclear p27(Kip1) staining was noted in cells that were undergoing mitosis. p27(Kip1) protein degradation may not be modified in ovarian cancer cells undergoing mitosis. Altered expression of p27(Kip1) is not an overwhelming feature in certain epithelial ovarian cancers. Decreased nuclear staining of p27(Kip1) is associated with poor survival in some epithelial ovarian cancers.
    Gynecologic Oncology 11/2001; 83(2):292-8. · 3.69 Impact Factor
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    ABSTRACT: Primitive neuroectodermal tumors (PNETs) are rare and potentially aggressive malignancies. A 24-year-old woman in her eighth week of pregnancy presented with a cervical mass. Tissue biopsy demonstrated poorly differentiated carcinosarcoma with neuroendocrine features. Immunohistochemical studies confirmed the diagnosis of PNET. Treatment included alternating courses of cyclophosphamide, adriamycin, vincristine (CAV) and ifosfamide, etoposide (IE). A radical hysterectomy with bilateral ovarian transposition and periaortic lymphadenectomy was performed with postoperative chemotherapy and radiotherapy. The patient remains disease free 2 years from therapy. This is a rare case of cervical PNET occurring in a pregnant patient. A review of the literature indicates that cervical PNET is distinguishable from uterine PNET. This tumor affects younger women and may have a different histogenesis. Pregnancy should not delay diagnosis of this potentially aggressive tumor.
    Gynecologic Oncology 11/2001; 83(1):138-42. · 3.69 Impact Factor
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    ABSTRACT: The aim of this study was to investigate whether expression of the enzymes that catalyze cytosine CpG island methylation, DNA methyltransferases, DNMT1, DNMT3a, and DNMT3b is altered in human ovarian cancer. Aberrations in DNA methylation are common in cancer and have important roles in tumor initiation and progression. Tumors that display frequent and concurrent inactivation of multiple genes by methylation are designated as having a CpG Island methylator phenotype, or CIMP. To date, colon, gastric, and most recently ovarian cancers meet the CIMP criteria for cancer. We hypothesized that altered expression of DNA methyltransferases can result in hypermethylation events seen in CIMP cancers. DNMT1, DNMT3a, and DNMT3b mRNA levels in eight ovarian cancer cells lines (Hey, HeyA8, HeyC2, OVCAR-3, SK-OV-3, PA-1, A2780, and A2780-P5) were compared to DNMT expression in normal ovarian surface epithelial cells using semi-quantitative reverse transcription-polymerase chain reaction. In HeyA8 and HeyC2 ovarian cancer cells, DNMT1 expression levels were up to threefold higher (P < 0.05) than in normal ovarian surface epithelial cells. SK-OV-3 and PA-1 displayed increased DNMT3b expression (P < 0.05) compared to normal ovarian surface epithelial cells. Transcript levels for DNMT3a, however, were similar in cancer and normal ovarian cells. We observed differential expression of the DNMT genes in some ovarian cancer cell lines and conclude that alterations in DNMT expression might contribute to the CIMP phenotype in ovarian cancer. However, based on the lack of aberrant DNMT expression in some of the cancer cell lines examined, we further suggest that another mechanism(s), in addition to DNMT overexpression, accounts for methylation anomalies commonly observed in ovarian cancer.
    Gynecologic Oncology 08/2001; 82(2):299-304. · 3.69 Impact Factor
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    ABSTRACT: Objective. The goal of this study was to estimate the antitumor activity and toxicity of recombinant human interleukin-12 (rhIL-12) in patients with recurrent or refractory epithelial ovarian cancer. Methods. From December 1997 to March 1999, patients with recurrent or refractory epithelial ovarian cancer were entered on a Gynecologic Oncology Group phase II study of intravenous rhIL-12. All patients had measurable disease, had a performance status of 0-2, and had failed first-line platinum-based chemotherapy regimen. Eligible patients received rhIL-12, 250 ng/kg IV bolus, as a single dose on Day 1 followed by a 2-week rest period, with subsequent cycles administered daily for 5 days followed by a 16-day rest period per cycle, until disease progression or adverse effects prohibited further therapy. Results. Twenty-eight patients were entered and evaluable for toxicity, while 26 were evaluable for response. The median age was 59.5 years (range: 45-77). The median number of cycles was 2 (range: 1-9). There were no complete responders; however, one patient (3.8%) was a partial responder and 13 patients (50%) had stable disease. Grade 4 myelotoxicity occurred in 21% of patients. Two patients experienced capillary leak syndrome: one grade 2 and one grade 4. Conclusion. As a single agent, rhIL-12 is tolerable and shows a low response rate in recurrent epithelial cancer with measurable disease.
    Gynecologic Oncology 08/2001; 82(1):7-10. · 3.69 Impact Factor
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    ABSTRACT: The aim of this study was to examine CpG island methylation patterns in ovarian cancer and determine whether epigenetic information can be related to clinical data of patients. CpG island (CpGI) hypermethylation is commonly associated with cancer progression, but little is currently known about the role of methylation in ovarian cancer. Differential methylation hybridization (DMH) analysis at 742 loci was performed to determine methylation signatures for 20 primary epithelial ovarian carcinomas (Stages II, III, and IV adenocarcinomas, serous papillary), 6 ovarian cancer cell lines, and normal ovarian surface epithelial cells. Between 23 and 108 methylated CpGIs were seen in the ovarian carcinomas. Fewer (P < 0.05) methylated CpGIs were observed in the ovarian cancer cell lines; however, a number of CpGIs were commonly hypermethylated in both the cell lines and the tumor samples. A methylation signature, consisting of frequently (P < 0.05) methylated CpGIs, was determined for the samples. The observed pattern of methylation in ovarian cancers included several (11) CpGI tags that were previously reported to be hypermethylated in human breast cancer. Epigenetic signatures in ovarian cancer were determined using DMH. This proof-of-concept study lays the foundation for genome-wide screening of methylation to examine epigenotype-phenotype relationships in ovarian cancer.
    Gynecologic Oncology 08/2001; 82(2):261-8. · 3.69 Impact Factor

Publication Stats

759 Citations
126.88 Total Impact Points


  • 2013
    • NorthShore University HealthSystem
      Chicago, Illinois, United States
  • 2010–2011
    • North Shore-LIJ Health System
      Manhasset, New York, United States
    • University of Chicago
      • Department of Obstetrics & Gynecology
      Chicago, IL, United States
    • Northwestern University
      • Department of Obstetrics and Gynecology
      Evanston, IL, United States
  • 2002–2009
    • University of Illinois at Chicago
      • • Department of Obstetrics and Gynecology (Chicago)
      • • Department of Obstetrics and Gynecology (Peoria)
      Chicago, IL, United States
  • 2003
    • Wright State University
      • Department of Obstetrics and Gynecology
      Dayton, OH, United States
  • 2001
    • Indiana University-Purdue University School of Medicine
      Indianapolis, Indiana, United States
    • University of California, San Diego
      San Diego, California, United States
  • 1999–2001
    • Indiana University-Purdue University Indianapolis
      • Department of Obstetrics and Gynecology
      Indianapolis, IN, United States
  • 1994
    • Duke University Medical Center
      • Department of Obstetrics and Gynecology
      Durham, NC, United States