Abstract:
OBJECTIVE:To identify novel prognostic and therapeutic markers for PARP inhibitors in BRCA wild type ovarian cancer (OvCa). METHODS:BRCAness status was defined by analyzing whole-exome deep sequencing data from 220 BRCAwt OvCa cases in TCGA. Thirty-three DNA-repair genes were screened in an integrated manner for BRCA-independent mechanism of BRCAness using multiple-dimensional genomic data. Publicly available databases and siRNA knock-down were used for external validation and evaluation of drug response in OvCa cell lines. RESULTS:In 220 BRCAwt OvCa patients, tumors exhibiting the BRCAness signature have enhanced OS (HR [95% CI]=0.33 [0.15-0.69], P=0.004) and PFS (HR [95% CI]=0.51 [0.24-1.08], P=0.077), strongly suggesting a BRCA-independent mechanism of drug sensitivity in those patients. Systematic screening of driving molecular events of BRCAness revealed that RAD50 deletion is a marker of BRCAness. The RAD50 deletion occurred in 18% of BRCAwt OvCa patients. RAD50 deletion led to its decreased mRNA expression in tumors (fold change=0.63, P=3.56×10(-13)). In BRCAwt patients, RAD50 deletion was associated with significantly better OS (HR [95% CI]=0.44 [0.25-0.78], P=0.005) and PFS (HR [95% CI]=0.60 [0.37-0.99], P=0.044), adjusted by age and stage. Knockdown of RAD50 expression augmented OvCa cell's responses to cisplatin and olaparib. Among 19 OvCa cell lines, the RAD50 copy number deletion is significantly associated with better responses to two structurally distinct PARPis (i.e. olaparib and rucaparib). CONCLUSION:Our study identified the copy number deletion of RAD50 as a candidate marker for survival and response to PARPis in BRCAwt OvCa tumors.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Zhang M,Liu G,Xue F,Edwards R,Sood AK,Zhang W,Yang Ddoi
10.1016/j.ygyno.2016.01.004subject
Has Abstractpub_date
2016-04-01 00:00:00pages
57-64issue
1eissn
0090-8258issn
1095-6859pii
S0090-8258(16)30004-Xjournal_volume
141pub_type
杂志文章abstract:OBJECTIVE:Preoperative identification of cervical stromal invasion in endometrial carcinoma is important to select patients for primary radical hysterectomy. The objective of this prospective implementation study was to assess if introduction of magnetic resonance imaging (MRI) in addition to the standardly applied end...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.05.009
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVE:About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2019.05.029
更新日期:2019-08-01 00:00:00
abstract:OBJECTIVE:Most precancerous lesions of the cervix are treated with surgery or ablative therapy. Chemoprevention, using natural and synthetic compounds, may intervene in the early precancerous stages of carcinogenesis and prevent the development of invasive disease. Our trial used indole-3-carbinol (I-3-C) administered ...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1006/gyno.2000.5847
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Although overall cervical cancer incidence rates have decreased in both black and white women in the U.S. since the mid 1950s due to widespread screening, rates continue to be higher among blacks than among whites. However, whether this pattern differs by age is unknown. METHODS:Cervical cancer cases (1975-...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.08.021
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Although most patients at high risk of Gestational Trophoblastic Neoplasia (GTN) respond to standard treatments, there is a group of patients that will die because of it. The use of new single or combination drugs in this population has become a priority. CASE REPORT:We present the case of a relapsed high r...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2007.04.002
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to relate hysteroscopic features of endometrioid endometrial adenocarcinoma to stage, grade and overall survival. METHODS:Sixty women with endometrioid adenocarcinoma underwent laparotomy and staging according to current FIGO classification. Before surgery hysteroscopy was performed...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6173
更新日期:2001-06-01 00:00:00
abstract::Sizes of the largest metastatic nodes were evaluated as a prognostic factor in 152 patients with Stage IB to IIB cervical carcinomas treated by radical hysterectomy and postoperative irradiation. Of the 152 cases, the largest positive nodes were less than 10 mm in 24 (16%), 10-20 mm in 74 (49%), greater than or equal ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(84)90179-3
更新日期:1984-10-01 00:00:00
abstract:BACKGROUND:Low-grade endometrial stromal sarcoma is generally an indolent tumor rich in estrogen and progesterone receptors. Objective responses to hormonal therapy, most commonly with megestrol acetate, have been reported. CASE:The patient is a 51-year-old woman who presented with low-grade endometrial stromal sarcom...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6238
更新日期:2001-08-01 00:00:00
abstract::Abnormal nuclear DNA content, as determined by flow cytometry, when combined with conventional prognostic variables such as tumor grade or stage at diagnosis, appears to identify patients who are at increased risk for recurrence of disease. The DNA content of ovarian dysgerminoma, a tumor that is homologous to testicu...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(92)90004-3
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:To identify patients with endometrial cancer at risk for hematogenous, lymphatic, or peritoneal recurrence (or combinations of them) who might potentially benefit from target-based therapies. METHODS:During a 13-year period, 915 patients had endometrial cancer managed with hysterectomy and standard adjuvant ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.06.042
更新日期:2004-10-01 00:00:00
abstract:OBJECTIVES:The presence of an eosinophilic infiltrate in patients with cervical squamous carcinoma has been shown to correlate with a worse overall survival, suggesting a less effective immune response in these cases. Since type 2 cytokines such as IL-4 and IL-5 are known to attract eosinophilic granulocytes, an immuno...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5431
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVES:To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI). METHODS:A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical rec...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2018.10.035
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:The aim of this study was to assess prognostic factors and implications on further management in a large series of stage-II or III Atypical Proliferative Serous Tumors (APST) with a long-term follow-up. PATIENTS AND METHODS:Patients with APSTs and peritoneal implants treated in, or referred to, our institut...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2020.06.489
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:The objective of this study is to determine the incidence of endometrial cancer in young postmenopausal women presenting with vaginal bleeding. METHODS:Cross-sectional study of postmenopausal women presenting with vaginal bleeding in a gynaecological oncology centre in the United Kingdom. All women underwent...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2011.12.453
更新日期:2012-04-01 00:00:00
abstract::Forty-two of sixty-seven patients (62.7%) treated for high-risk metastatic trophoblastic disease achieved and maintained complete remissions. The survival rate was significantly improved in those patients with scores lower than 8 according to a modification of the World Health Organization (WHO) prognostic scoring sys...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(89)90106-6
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVE:The aim of this retrospective multicenter study was to assess whether the pre-chemotherapy hemoglobin levels have any impact on the clinical outcome of patients with advanced epithelial ovarian cancer who received a first-line taxane/platinum-based regimen. METHODS:The study was conducted on 315 patients who...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2005.04.012
更新日期:2005-07-01 00:00:00
abstract:OBJECTIVE:This study sought to develop and examine preliminary validity of the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), a new ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. METHODS:Fifty-one women wit...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.09.025
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:The objective was to identify the factors, if any, that may predict long-term results of CIN treatment and HPV clearance/persistence after locally excisional therapy. METHODS:A series of 252 women with CIN lesions treated by conization were subjected to sequential HPV detection by repeated PCR during the pro...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(03)00268-3
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVES:In the present study (EDiTH III study), the genotype-specific prevalence of HPV in low-grade squamous intraepithelial lesions (LSIL) was estimated to predict the potential benefit of HPV vaccination in France. This prevalence was compared to that previously reported in France in high-grade cervical intraepit...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2008.04.012
更新日期:2008-08-01 00:00:00
abstract::Two patients with resistant gestational choriocarcinoma were treated w with Taxol after extensive prior chemotherapy including EMACO and platinum-based salvage chemotherapy. Both patients showed significant responses to Taxol. One patient relapsed in the brain and liver after treatment and died. Taxol was combined wit...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1996.0110
更新日期:1996-04-01 00:00:00
abstract: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 t...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2002.6606
更新日期:2002-04-01 00:00:00
abstract::From July 1975 through December 1985, 328 patients with ovarian malignancies were treated. Of these, 302 had epithelial invasive malignancies and constitute the study group. The impact of the operative procedure, findings, and subsequent treatment is evaluated. Patients who underwent extensive debulking procedures suc...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90277-r
更新日期:1991-03-01 00:00:00
abstract::Twelve patients with recurrent squamous cell carcinoma of the cervix restricted to the pelvis were treated with intra-arterial infusion of carboplatin. The initial carboplatin dose was 300 mg/m2, every 4 weeks, and the dose was escalated to 450 mg/m2. Myelosuppression was the dose-limiting toxicity at the 450 mg/m2 do...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1006/gyno.1994.1136
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:We report an isolated recurrence at the residual cervix shortly after abdominal radical trachelectomy for cervical cancer. CASE:A 34-year-old woman underwent radical abdominal trachelectomy and pelvic lymphadenectomy for FIGO stage IB1 squamous cell cervical cancer. The tumor measured 10 mm in maximum diame...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.07.107
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVE:To determine if preoperative metabolic tumor volume (MTV) measured by integrated (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) imaging has prognostic value in patients with cervical cancer treated primarily with radical hysterectomy. METHODS:Patients with FIGO s...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.11.002
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:To compare the oncologic outcomes of women who underwent a fertility-sparing radical trachelectomy (RT) to those who underwent a radical hysterectomy (RH) for stage IB1 cervical carcinoma. METHODS:We performed a case-control study of all patients with stage IB1 cervical carcinoma who underwent a vaginal or a...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.07.014
更新日期:2008-11-01 00:00:00
abstract:OBJECTIVE:Endometrial carcinoma is the most common malignancy of the female reproductive tract. Most cases are diagnosed at an early stage due to the appearance of symptoms such as postmenopausal bleeding. However, endometrial carcinoma carries a poor prognosis when it recurs after previous definitive treatment or when...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2010.02.007
更新日期:2010-05-01 00:00:00
abstract:OBJECTIVE:Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.12.016
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:Benefits of laparoscopy over laparotomy in patients with endometrial cancer (EC) are well known. As many patients with EC carry co-morbid conditions, surgery is exposing them to increased risk of complications. A review of the patients with EC recruited so far in a clinical trial comparing laparoscopy to lapa...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.ygyno.2004.12.048
更新日期:2005-04-01 00:00:00
abstract::A case of Stage IIIC primary ovarian leiomyosarcoma in a premenopausal woman with multiple recurrences alive and well 7 years after diagnosis is presented. In addition to the typical light microscopic, immunohistochemical, and electron microscopic features of ovarian leiomyosarcoma, the tumor was progesterone receptor...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1006/gyno.1997.4824
更新日期:1997-09-01 00:00:00