Abstract:
OBJECTIVE:The aberrant expression of hepatocyte growth factor and its receptor c-Met are associated with aggressive disease and poor prognosis in a variety of human malignancies including ovarian cancer (OC). Specificity protein (Sp) transcription factors have high relevance in the signaling cascade associated with c-Met activation. Tolfenamic acid (TA), a NSAID, is known to induce the degradation of Sp proteins, which have been negatively associated with survival in some cancer patients. Our aim was to examine the anti-OC activity of TA using in vitro and in vivo models and asses the inhibitory effects of this novel compound. METHODS:We developed OC sub-cell lines (AF1-3) derived from the original SKOV3 that are more resistant to IFNα-2b and more tumorigenic in nude mice than the original cells. We tested the anti-cancer activity of TA using ovarian cancer cells, SKOV3-AF2 and ES-2. The cells were treated with DMSO (vehicle) or TA (25/50/100 μM) and cell viability was measured at 24, 48, and 72 h. Cell lysates were prepared following 48 h treatment (50μM) and evaluated the expression of Sp proteins (Sp1/Sp3/Sp4), c-Met, survivin, Bcl2, and cleaved polyADP-ribose polymerase (c-PARP) through Western blot analysis. Caspase-3 activity was assessed with Caspase-Glo kit. Cell cycle distribution and apoptosis were analyzed using BD FACSCalibur flow cytometer. For in vivo studies mice were subcutaneously injected with ES-2 cells and treated with vehicle or TA (50 mg/kg/thrice weekly). RESULTS:TA significantly inhibited the growth of SKOV3 (AF1-3) and ES-2 cells. The expression of Sp proteins and c-Met was significantly decreased suggesting that TA could be targeting c-Met through degradation of Sp proteins. TA greatly increased the apoptotic fraction (Annexin V positive), c-PARP expression and caspase-3 activity. TA significantly decreased Bcl2 expression and induced G0/G1 cell cycle arrest. In vivo studies revealed that TA significantly inhibited tumor weight and volume in mice. These results show that TA has a profound inhibitory effect on tumor growth in mice, reduces OC cells proliferation, induces apoptosis, cell cycle arrest and Sp proteins degradation. TA also inhabited the expression of survivin that is associated with radiation resistance and suggests that apart from its tumor suppressant effects, TA can also enhance the tumor response to radiotherapy. CONCLUSIONS:These data clearly show that TA effectively inhibits OC cell growth in vitro and in vivo. This study represents potential role(s) of TA that suppresses OC cell growth, and may enhance tumor response to radiotherapy, and have implications in OC treatment.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Basha R,Ingersoll SB,Sankpal UT,Ahmad S,Baker CH,Edwards JR,Holloway RW,Kaja S,Abdelrahim Mdoi
10.1016/j.ygyno.2011.03.014subject
Has Abstractpub_date
2011-07-01 00:00:00pages
163-70issue
1eissn
0090-8258issn
1095-6859pii
S0090-8258(11)00189-2journal_volume
122pub_type
杂志文章abstract:OBJECTIVE:The aim of this study was to evaluate the 5-year survival probability (SP) of patients treated for ovarian clear cell adenocarcinoma (OCCA) at a single tertiary institution and to compare it to the 5-year SP of patients with other histologic subtypes of epithelial ovarian cancer. METHODS:Sixty-four patients ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5445
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND:The aim of this study was to report an exceptional case of a patient presenting with intracaval and intracardiac leiomyomatosis treated by combined surgical and medical treatment. CASE:A 48-year-old presented with intracaval and intracardiac leiomyomatosis (IL) discovered 6 years following a total hysterect...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6389
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVES:To investigate access to surgical care for endometrial cancer in Arizona. METHODS:The Arizona HealthQuery (AZHQ) data warehouse with claims information on over 7 million patients in Arizona was searched using the International Classification of Disease (ICD-9) codes and Current Procedural Terminology (CPT) ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.11.028
更新日期:2011-04-01 00:00:00
abstract:UNLABELLED:Surgical staging of apparent early stage adnexal carcinoma provides indispensable information. A significant number of patients are referred to tertiary centers with inadequate staging information. We report on our experience with late results of laparoscopic restaging procedure in uncompletely managed early...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.05.052
更新日期:2004-09-01 00:00:00
abstract:OBJECTIVE:High-risk (HR) human papillomavirus (HPV) testing is important in cervical cancer screening for triage to colposcopy. This study evaluated the clinical performance of the Cervista HPV HR and 16/18 genotyping tests for detection of HPV in cervical cytology specimens. METHODS:The tests were prospectively evalu...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2010.04.013
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:Angiomyolipoma is a distinctive benign neoplasm of the renal origin. Rare extrarenal instances of angiomyolipoma have been documented at various body sites. A case of extrarenal angiomyolipoma arising from the parametrial soft tissues is described in the present report. CASE:A woman, age 40 years, presented...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(03)00251-8
更新日期:2003-07-01 00:00:00
abstract:OBJECTIVES:The efficacy and safety of bevacizumab and docetaxel were evaluated in women who developed recurrent epithelial ovarian, fallopian, or peritoneal cancer within 12 months of platinum-based therapy. METHODS:Patients received docetaxel (40 mg/m(2)) on days 1 and 8 and bevacizumab (15 mg/kg) on day 1 of a 21-da...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2013.04.049
更新日期:2013-07-01 00:00:00
abstract::Ovarian germ cell tumors (GCTs) are rare in adults, but are more common in adolescents and young adults. Contemporary management of ovarian GCTs is evolving as collaboration among pediatric, medical, and gynecologic oncologists increases, and studies increasingly incorporate female adult patients. Despite an improved ...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2020.05.007
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:To review the clinical features, diagnosis, management, and outcomes for the 50 cases of Paget's disease (PD) of the vulva referred to Queensland Centre for Gynaecological Cancer between 1986 and 2009. METHODS:Vulvar PD cases from QCGC were reviewed and analyzed using the computer software Statistical Packag...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2011.03.033
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVES:Endometriosis-associated ovarian carcinoma (EAOC) has recently received increasing attention due to its suggested biological behavior, distinctive from those of usual epithelial ovarian cancer. To elucidate some of the controversies on this intriguing entity, a series of patients with EAOC were compared to o...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6382
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVES:The goal of this work was to test the hypotheses that S-phase fraction (SPF) by DNA labeling index (SPF-LI) would predict the course of the disease for ovarian/peritoneal carcinomas and that SPF-LI would correlate better with pathologic classification and outcome than SPF by DNA flow cytometry (SPF-F). METH...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6184
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:This study aimed to determine if there is a causal relationship between removal of the circumflex iliac nodes distal to the external iliac nodes (CINDEIN) and postoperative lower-extremity lymphedema (POLEL) after systematic lymphadenectomy in patients with cervical cancer. METHODS:A retrospective chart revi...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2015.09.007
更新日期:2015-11-01 00:00:00
abstract:OBJECTIVE:The study aims at identifying novel markers for circulating tumor cells (CTCs) in patients with epithelial ovarian cancer (EOC), and at evaluating their impact on outcome. METHODS:Microarray analysis comparing matched EOC tissues and peripheral blood leucocytes (N=35) was performed to identify novel CTC mark...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.09.021
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial. METHODS:Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, ...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2018.11.017
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Cervical cancer on the mucosal surface of a pedunculated cervical leiomyoma has not been reported. CASE:A 54-year-old woman who had a bulky protruding cervical tumor with a history of a vaginal bleeding was diagnosed as having squamous cell cancer of the cervix. She received a total of 45 Gy (1.8 Gy daily u...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.12.021
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to examine whether comorbidity is an independent prognostic factor for 3129 women diagnosed with ovarian cancer from 2005 to 2011. As Performance status (PS) might capture the impact of comorbidity we addressed whether comorbidity can be explained by PS or whether comorbidity has an i...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.12.039
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVES:The objectives of this phase II trial were to assess the activity and tolerability of the combination of bevacizumab and erlotinib in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer. METHODS:This was a single arm, multicenter phase II trial with overall objective response as the...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2008.02.009
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial. METHODS:Prior to surgery, par...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2015.08.022
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:The simultaneous occurrence of advanced cervical cancer and a pelvic kidney is uncommonly reported. It is an interesting clinical problem because the pelvic kidney lies within the radiation field. CASE:A patient found to have bilateral pelvic kidneys and stage II-B cervical cancer underwent an anterior exen...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2003.09.033
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection. METHODS:A differential MS-based proteomic analysis was conducted from discrete epithelial cell p...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2011.02.031
更新日期:2011-06-01 00:00:00
abstract::Three cases of postoperative enterocutaneous fistula formation following use of the Dexon mesh sling are reported from two gynecologic oncology services. Two patients had intestinal trauma or bowel resection at the time of mesh placement. Postoperative submesh abscess formation was noted in only one patient. Factors w...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90030-o
更新日期:1990-07-01 00:00:00
abstract:OBJECTIVES:To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). METHODS:51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA e...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2015.08.001
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVES:The objective of this pilot study was to determine if frailty predicts surgical complications among elderly women undergoing gynecologic oncology procedures. METHODS:A cohort of gynecologic oncology patients age ≥ 65, undergoing surgery between March and December 2011 was identified. Frailty was evaluated u...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.04.019
更新日期:2012-07-01 00:00:00
abstract::Two cases are presented which demonstrate histologically an endometrial response to endogenous hormones after pelvic teletherapy and brachytherapy in patients who have undergone lateral ovarian transposition. Reasons for such a response are briefly discussed. ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90118-5
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:Ovarian cancer arising from an endometriotic cyst in a postmenopausal woman under tamoxifen therapy is rare. CASE:We herein report the case of a 67-year-old woman with a history of breast cancer, taking tamoxifen citrate 20 mg/day for 4 years, who underwent an operation for left ovarian tumor. The postopera...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1006/gyno.2002.6824
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE:This study aims to estimate the activity of docetaxel 60mg/m(2) IV over 1h followed by trabectedin 1.1mg/m(2) over 3h with filgrastim, pegfilgrastim, or sargramostim every 3weeks (one cycle). METHODS:Patients with recurrent and measurable disease, acceptable organ function, PS≤2, and ≤3 prior regimens were e...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.11.012
更新日期:2011-03-01 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:OBJECTIVE:Metformin is one of the most widely used drugs for the treatment of type 2 diabetes. Recent investigations demonstrated that application of metformin reduces cancer risk. The present study aimed to determine the role of liver kinase B1 (LKB1) in the response of cervical cancer cells to metformin. METHODS:LKB...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.06.032
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:To compare the frequencies of somatic homologous recombination (HR) gene mutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs). METHODS:Data for this analysis was obtained from AACR Project GENIE, a mul...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2020.08.012
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:To investigate whether alteration of BRCA1 tumor suppressor gene occurs in sporadic endometrial carcinomas. METHODS:Genomic DNAs were prepared from 33 consecutively collected endometrial carcinoma tissues for BRCA1 mutational analysis. To screen for BRCA1 mutation, polymerase chain reaction (PCR) amplificati...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1997.4800
更新日期:1997-09-01 00:00:00