Abstract:
OBJECTIVE:Aberrant expression of HER2/neu and PIK3CA gene products secondary to amplification/mutations are common in high-grade-serous-endometrial (USC) and ovarian-cancers (HGSOC). Because scant information is currently available in the literature on the potential negative effect of PIK3CA mutations on the activity of afatinib, in this study we evaluate for the first time the role of oncogenic PIK3CA mutations as a potential mechanism of resistance to afatinib in HGSOC and USC overexpressing HER2/neu. METHODS:We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC. Primary-USC harboring wild-type-PIK3CA gene was transfected with plasmids encoding oncogenic PIK3CA-mutations (H1047R/E545K). The effect of afatinib on HER2/PI3K/AKT/mTOR pathway was evaluated by immunoblotting. RESULTS:We found PI3K wild-type cell-lines to be significantly more sensitive (lower IC50) than PI3K-mutated cell-lines p = 0.004). In vivo, xenografts of primary cell-line USC-ARK2, transfected with the PIK3CA-H1047R or E545K hotspot-mutations, exhibited significantly more rapid tumor growth when treated with afatinib, compared to mice harboring ARK2-tumors transfected with wild-type-PIK3CA (p = 0.041 and 0.001, respectively). By western-blot, afatinib effectively reduced total and phospho-HER2 proteins in all cell-lines. However, H1047R/E545K-PIK3CA-transfected-ARK2-cells demonstrated a greater compensatory increase in phosphorylated-AKT proteins after afatinib exposure when compared to controls ARK2. CONCLUSIONS:Oncogenic PI3K mutations may represent a major mechanism of resistance to afatinib. Combinations of c-erb with PIK3CA, AKT or mTOR inhibitors may be necessary to more efficiently block the PIK3CA/AKT/mTOR pathway.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Bonazzoli E,Cocco E,Lopez S,Bellone S,Zammataro L,Bianchi A,Manzano A,Yadav G,Manara P,Perrone E,Haines K,Espinal M,Dugan K,Menderes G,Altwerger G,Han C,Zeybek B,Litkouhi B,Ratner E,Silasi DA,Huang GS,Azodi M,doi
10.1016/j.ygyno.2019.01.002subject
Has Abstractpub_date
2019-04-01 00:00:00pages
158-164issue
1eissn
0090-8258issn
1095-6859pii
S0090-8258(19)30004-6journal_volume
153pub_type
杂志文章abstract::Angiomyofibroblastoma is a rare, myxoid tumor of the vulva. To date only 12 cases have been reported in the world literature. Patients are usually premenopausal and present with a vulval mass initially diagnosed as a Bartholin's cyst. The lesions are well circumscribed and range from 0.5 to 12 cm in size. Microscopica...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1994.1230
更新日期:1994-09-01 00:00:00
abstract::Three hundred and sixty-two cases of primary vaginal carcinoma were treated at the Irradiation Department of the University Clinic for Obstetrics and Gynecology, Vienna, from 1950 to 1977. As the method of choice an individually dosed, fractioned, and protracted radium-telecobalt therapy was employed. Comparing the la...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(85)90236-7
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:To identify molecular prognosticators and therapeutic targets for high-grade serous epithelial ovarian cancers (EOCs) using genetic analyses driven by biologic features of EOC pathogenesis. METHODS:Ovarian tissue samples (n = 172; 122 serous EOCs, 30 other EOCs, 20 normal/benign) collected prospectively from...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2013.12.021
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVES:Laminin-5 is an attachment protein for epithelial cells. Several studies of a variety of cancers have reported increased expression of laminin-5 in carcinoma in situ and invasive cancer. This study was designed to investigate the correlation between the grade of cervical intraepithelial neoplasia and the imm...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(03)00086-6
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:Determining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2018.10.033
更新日期:2019-01-01 00:00:00
abstract::Between October 1961, and November 1978, 31 patients with intraperitoneal metastatic adenocarcinoma of the endometrium were treated by whole-abdomen moving-strip technique and pelvic boost irradiation. In 27 patients, with residual disease less than or equal to 2 cm, the corrected 5-year survival rate was 80%. The abs...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(83)90164-6
更新日期:1983-12-01 00:00:00
abstract:OBJECTIVES:To compare survival of Hispanic white (HW) and non-Hispanic white (NHW) women with type II endometrial adenocarcinoma (EC). METHODS:Patients with serous, clear cell or grade 3 endometrioid EC were identified from the Surveillance, Epidemiology, and End Results (SEER) program 1988-2009 and were divided into ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2014.03.562
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVES:We aimed to evaluate whether carboplatin has a comparable efficacy with cisplatin as part of weekly concurrent chemoradiotherapy for cervical cancer (Car-RT vs. Cis-RT). METHODS:A literature search was conducted and both prospective and retrospective studies that evaluated the efficacy of Car-RT for cervica...
journal_title:Gynecologic oncology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.ygyno.2018.07.005
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:The consequences of defective homologous recombination and other DNA repair pathways are important in disease outcomes of numerous tumor types. The objective of this study was to explore BRCA1, PARP, FANCD2, PTEN, H2AX, and ATM protein expression in endometrial cancer (EC). METHODS:PARP1, γH2AX, ATM, FANCD2,...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2014.02.002
更新日期:2014-03-01 00:00:00
abstract::Dermatofibrosarcoma protuberans (DFSP) of the vulva is a rare, low- to intermediate-grade sarcoma of dermal origin. This case report represents the 13th reported patient with vulvar DFSP and the first reported patient with metastatic vulvar DFSP. Although metastasis is rare, the possibility remains that the frequent r...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1998.5173
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND:Obesity confers an overall increased risk for development of endometrial cancer. However there are conflicting reports regarding the effect of obesity on patients' overall and disease specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial canc...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2019.03.258
更新日期:2019-07-01 00:00:00
abstract:PURPOSE:To examine the relative efficacy of cisplatin-based intraperitoneal (IP) therapy versus carboplatin-based IP therapy as salvage treatment of small-volume residual ovarian cancer. PATIENTS AND METHODS:We retrospectively examined the surgically defined response rates of patients with ovarian cancer treated at th...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1993.1171
更新日期:1993-07-01 00:00:00
abstract:OBJECTIVES:Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined u...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2000.5784
更新日期:2000-06-01 00:00:00
abstract:OBJECTIVES:To investigate survival disparities and prognostic factors in vulvar cancer by age at diagnosis. METHODS:Women who underwent surgery and were diagnosed with stage I-IV vulvar cancer from 2004 to 2014 in the National Cancer Database were eligible. Proportions were compared using Chi-Square test. Survival was...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2019.11.025
更新日期:2020-04-01 00:00:00
abstract::Experience with the P.A.S.-PORT, a peripherally implanted central venous access device, is evaluated in a retrospective review of 154 patients from July 1991 to June 1994. Blood could not be aspirated from six patients. Complications included temporary minor thrombophlebitis in seven patients (4.5%), symptomatic axill...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1996.0246
更新日期:1996-09-01 00:00:00
abstract:OBJECTIVE:To evaluate the clinical accuracy and clinical impact of positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) in detecting and treating tumor recurrence in patients with treated uterine sarcoma. METHODS:Results of 36 patients who underwent PET or PET/CT in post-ther...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.01.030
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Vulvar synovial cell sarcomas are rare, with only four previously published cases in the literature. Traditionally, the primary management for these tumors has been surgery alone. CASE:We report a case of a large vulvar synovial cell sarcoma in a 50-year-old woman treated with comprehensive combined multimo...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.09.018
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:We demonstrate the feasibility of implementing a referral and management system for cryotherapy-ineligible women in a "screen-and-treat" cervical cancer prevention program targeting HIV-infected women in Zambia. METHODS:We established criteria for patient referral, developed a training program for loop elect...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.04.031
更新日期:2008-09-01 00:00:00
abstract::Reconstructive procedures are being performed with increasing frequency in conjunction with pelvic exenterations and other radical gynecologic surgeries. The most common reconstructive procedures include continent urinary diversion, rectosigmoid anastomosis, and vaginal reconstruction. Historically, the gracilis myocu...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1993.1298
更新日期:1993-12-01 00:00:00
abstract::The role of elective lymphadenectomy in the treatment of patients with early-stage malignancies, although still commonly performed, remains a matter of controversy. This issue is important in the management of cancers and raises questions about the biologic interpretation of their natural history and about motives for...
journal_title:Gynecologic oncology
pub_type: 社论
doi:10.1006/gyno.1997.4900
更新日期:1998-01-01 00:00:00
abstract::Management of younger patients with early stage ovarian endodermal sinus tumor who desire to have children can be a challenging problem. However, after an adequate and thorough staging procedure for the patient's tumor status, a Stage Iai endodermal sinus tumor may be treated with conservative surgery only, followed b...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(84)90184-7
更新日期:1984-10-01 00:00:00
abstract:BACKGROUND:Granulosa cell tumors of the ovary are rare, primarily treated surgically. In advanced or recurrent disease, data are inconclusive regarding the benefit of either primary or adjuvant chemotherapy. Hormonal therapy has been suggested as an alternative treatment. CASE:Our patient had three recurrences of estr...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2004.10.042
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:To evaluate the feasibility of an electronic symptom-tracking platform for patients recovering from ambulatory surgery. METHOD:We assessed user response to an electronic system designed to self-report symptoms. Endpoints included compliance, postoperative symptoms, patient satisfaction. An 8-item symptom inv...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2020.07.004
更新日期:2020-10-01 00:00:00
abstract::Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papi...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1006/gyno.1997.4697
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND:Malignant acanthosis nigricans is a mucocutaneous eruption associated with internal malignancies. Tripe palms refers to a characteristic velvety thickening of the palms, with exaggeration of normal skin markings. The sign of Leser-Tre'lat is the presence of multiple seborrheic keratoses and scattered skin ta...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.12.024
更新日期:2006-05-01 00:00:00
abstract::The cell line HTOA was established from a well-differentiated human ovarian serous cystadenocarcinoma. This line grew well and without interruption for 51 months and was subcultivated over 130 times. The cells were epithelial in shape, and neoplastic and pleomorphic features, a jigsaw puzzle-like arrangement, desmosom...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(87)90026-6
更新日期:1987-03-01 00:00:00
abstract::The role of adjuvant chemotherapy in surgically staged stage I clear cell ovarian cancer (OCCC) is unclear. Here, we performed a systematic review and meta-analysis in order to evaluate the role of chemotherapy vs. observation in stage I OCCC. This systematic review was registered in the International Prospective Regi...
journal_title:Gynecologic oncology
pub_type: 杂志文章,meta分析
doi:10.1016/j.ygyno.2019.12.045
更新日期:2020-04-01 00:00:00
abstract::Only one case of endometrial transitional cell carcinoma (TCC) has been previously reported in the literature. We report a second case. In both the previously reported case and in this case there was a separate focus of TCC in the adnexa. Both patients were treated with adjuvant whole pelvic radiation and are alive an...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1996.0047
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:Although the antiproliferative and differentiating properties of vitamin D have been demonstrated, its effects on cancer cells are variable. Little is known about vitamin D receptor (VDR) levels in patients with ovarian cancer. In this population we sought to determine correlations between VDR expression, cli...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.06.008
更新日期:2010-10-01 00:00:00
abstract:OBJECTIVE:The long-term survival of patients with epithelial ovarian cancer is limited by the emergence of tumor cells that are resistant to chemotherapy. We hypothesized that expression of Bcl-x(L), a homologue of Bcl-2 that confers protection from chemotherapy-induced apoptosis, may be predictive of patients' clinica...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.10.026
更新日期:2005-02-01 00:00:00