Abstract:
OBJECTIVE:To evaluate the utility of amiodarone and its derivative dronedarone as novel drug repositioning candidates in EOC and to determine the potential pathways targeted by these drugs. METHODS:Drug-predict bioinformatics platform was used to assess the utility of amiodarone as a novel drug-repurposing candidate in EOC. EOC cells were treated with amiodarone and dronedarone. Cell death was assessed by Annexin V staining. Cell viability and cell survival were assessed by MTT and clonogenics assays respectively. c-MYC and mTOR/Akt axis were evaluated as potential targets. Effect on autophagy was determined by autophagy flux flow cytometry. RESULTS:"DrugPredict" bioinformatics platform ranked Class III antiarrhythmic drug amiodarone within the top 3.9% of potential EOC drug repositioning candidates which was comparable to carboplatin ranking in the top 3.7%. Amiodarone and dronedarone were the only Class III antiarrhythmic drugs that decreased the cellular survival of both cisplatin-sensitive and cisplatin-resistant primary EOC cells. Interestingly, both drugs induced degradation of c-MYC protein and decreased the expression of known transcriptional targets of c-MYC. Furthermore, stable overexpression of non-degradable c-MYC partially rescued the effects of amiodarone and dronedarone induced cell death. Dronedarone induced higher autophagy flux in EOC cells as compared to amiodarone with decreased phospho-AKT and phospho-4EBP1 protein expression, suggesting autophagy induction due to inhibition of AKT/mTOR axis with these drugs. Lastly, both drugs also inhibited the survival of EOC tumor-initiating cells (TICs). CONCLUSIONS:We provide the first evidence of class III antiarrhythmic agents as novel c-MYC targeting drugs and autophagy inducers in EOC. Since c-MYC is amplified in >40% ovarian tumors, our results provide the basis for repositioning amiodarone and dronedarone as novel c-MYC targeting drugs in EOC with potential extension to other cancers.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Belur Nagaraj A,Joseph P,Kovalenko O,Wang Q,Xu R,DiFeo Adoi
10.1016/j.ygyno.2018.09.019subject
Has Abstractpub_date
2018-12-01 00:00:00pages
525-532issue
3eissn
0090-8258issn
1095-6859pii
S0090-8258(18)31238-1journal_volume
151pub_type
杂志文章abstract::Ovarian carcinoma usually presents in an indolent manner, most often nonspecifically with complaints of abdominal pain or swelling, bloating, constipation, anorexia, early satiety, and evidence of ascites. We present a case of ovarian cancer with a cerebrovascular accident (CVA) as the presenting symptom, with minimal...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1998.5053
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND:Patients who undergo pelvic floor resection as treatment for recurrent cancer following radiation therapy have increased rates of complications, particularly if permanent prosthetic mesh is used for reconstruction. Human acellular dermal matrix (HADM), commonly used for reconstruction in other torso location...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2007.08.063
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:There are a few cases of "small cell neuroendocrine carcinoma" of the Bartholin's gland as well as Merkel cell carcinoma of the vulva reported in the gynecologic oncology literature, most with aggressive clinical behavior. Merkel cells were originally described in the epidermis with neuroendocrine properties...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.12.064
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:To prospectively evaluate the feasibility of detecting human papillomavirus (HPV) type 16, 18 and 52 DNA in the peripheral blood of patients with cervical cancer using real-time polymerase chain reaction (PCR) and to determine its prognostic importance. METHODS:Blood and cervical swab specimens from 135 cons...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.07.004
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Brain metastases (BM) from epithelial ovarian cancer (EOC) are considered a rare and unfavourable event. There is no consensus regarding the best management of these patients. METHODS:A multicenter retrospective analysis of patients with BM from EOC treated between 1997 and 2014 in 18 institutions of the MI...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2016.09.025
更新日期:2016-12-01 00:00:00
abstract:OBJECTIVE:To compare the short-term surgical outcome of patients undergoing robotic radical hysterectomy (RRH) versus open radical hysterectomy (ORH) for the treatment of early stage cervical cancer. METHODS:IRB approval was obtained for a retrospective chart review of all radical hysterectomies (RHs) for Stage I and ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.08.016
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Primary non-gestational choriocarcinoma of the female genital tract has been described in the ovaries and is very unusual in other genital sites. CASE:Primary non-gestational uterine cervical choriocarcinoma was diagnosed in a patient, 32, single, without previous sexual contact nor antecedent pregnancy, ad...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.03.045
更新日期:2005-07-01 00:00:00
abstract::Radical vulvectomy using warm-knife and open-wound techniques was performed as the first step in a two-phase surgical approach in 274 patients with malignant vulvar tumors. Crude 5-year survival was registered in 133/223 (60%) patients. The complication rate was low and the hospitalization period was short (mean 16 da...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(84)90056-8
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVE:To evaluate testing for high-risk human papillomavirus (HR HPV) E6/E7 mRNA transcripts 6 months after conisation for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) to determine the risk of residual CIN2+. METHODS:We prospectively followed 344 women treated for CIN2+ by conisation. HR HPV mRNA te...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2011.07.032
更新日期:2011-11-01 00:00:00
abstract::A total of 246 endocervical samples were collected for Papanicolaou staining and one-parameter flow cytometric DNA analysis (FCDA) using 4',6-diamidino-2-phenylindole as a DNA stain. Typical histograms derived from FCDA analysis were designated class I, II, III, and V. Two groups of patients were studied: 135 women re...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(83)90049-5
更新日期:1983-06-01 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:OBJECTIVE:Vulvar reconstruction following oncologic resection is challenging. Some flaps used for reconstruction can show adverse characteristics such as excessive tissue bulk or increased distance to the defect. Region of the sulcus genitofemoralis is of thin and pliable tissue proximate to the vulva. Vasculature and ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.08.033
更新日期:2010-12-01 00:00:00
abstract::Primary lymphoma of the cervix is very rare. A case report is presented and 24 cases published in the English literature are reviewed. Evaluation, staging, treatment, and prognosis of this rare tumor are discussed. ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(87)90080-1
更新日期:1987-01-01 00:00:00
abstract::This report presents 13 patients with epithelial ovarian neoplasms of low malignant potential. Ten patients had serous tumors, 1 had a mucinous tumor, and 2 had endometrioid tumors. Two had Stage I disease, 4 had Stage II disease, and 7 had Stage III disease. All were treated with melphalan. Second-look laparotomy was...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(85)90250-1
更新日期:1985-06-01 00:00:00
abstract:OBJECTIVES:The aim of the study is to determine whether critical pathways can be implemented at an academic institution to limit cost, without compromising patient satisfaction and quality of care. PATIENTS AND METHODS:Patients undergoing a hysterectomy with either cervical or endometrial cancer were placed on specifi...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6428
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND:Chylous ascites is an uncommon complication following para-aortic lymph node dissection in the management of gynecologic malignancies. Treatment options are serial paracentesis, medium-chain triglyceride diet, total parenteral nutrition and somatostatin as conservative management and peritoneovenous shunting...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.03.022
更新日期:2004-06-01 00:00:00
abstract:OBJECTIVE:To determine if lymphadenectomy, chemotherapy and radiotherapy are associated with survival benefit among women with stage I uterine carcinosarcoma. METHODS:Women with stage I uterine carcinosarcoma (n=5614) were identified from the 1998-2013 National Cancer Data Base. Kaplan-Meier survival estimates and Cox...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2017.01.010
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVES:Although the reported incidence of carboplatin hypersensitivity is low, its occurrence is important to characterize because of potential fatal complications. The purpose of this study was to determine the current incidence of carboplatin hypersensitivity in the ovarian cancer patients compared to other oncol...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.04.002
更新日期:2006-11-01 00:00:00
abstract::Forty patients with locally advanced cervical carcinoma were entered into a protocol utilizing the bolus administration of both mitomycin C (10 or 15 mg) on Day 1 and 5-fluorouracil (400 mg) on Day 1-5 followed by sequential pelvic irradiation on Day 6 between September 1980 and October 1985. All patients had poor-pro...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,评审
doi:10.1006/gyno.1996.0013
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:The aim of this paper was to report two cases of extrauterine disease in patients with early stage endometrial cancer (EC) who desired fertility-sparing management. CASES:Two patients presenting an apparent early stage EC and desiring conservative management. The two patients, aged 35 and 36 years old, had ...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2004.09.034
更新日期:2005-01-01 00:00:00
abstract::Classification of ovarian tumors according to FIGO does not take into account involvement of spleen. A patient who appears to be the first reported case of widespread carcinoma of the ovary with involvement of the splenic parenchyma is presented. ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(88)90058-3
更新日期:1988-05-01 00:00:00
abstract:OBJECTIVES:The goal of this case review was to evaluate the influence of complete surgical versus clinical staging, including the impact of ovarian preservation, on the outcome of young patients with endometrial carcinoma. METHODS:A retrospective chart review was performed on all patients with endometrial cancer diagn...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2009.03.032
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:Tumor lysis syndrome (TLS) is characterized by biochemical changes such as hyperuricemia and hyperkalemia due to rapid tumor lysis of malignant cells, usually after chemotherapy. TLS is a rare complication in nonhematological malignancies. CASE:A 53-year-old female received intravenous weekly paclitaxel for...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.06.003
更新日期:2006-11-01 00:00:00
abstract:INTRODUCTION:Non-Hispanic black women are less often diagnosed with endometrial cancer than are non-Hispanic white women, but are more likely to die of their disease. Reasons for this disparity in outcome are not well understood. METHODS:The Surveillance, Epidemiology, and End-Results Program data were used to sample ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2004.11.041
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:To describe our early experience with robotic-assisted laparoscopy for extraperitoneal para-aortic lymphadenectomy up to the left renal vein, including Da Vinci robot positioning. METHODS:Six patients underwent robotic-assisted laparoscopy using the Da Vinci apparatus. The patients included a man with a pT2 ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2009.04.032
更新日期:2009-10-01 00:00:00
abstract::Between 1972 and 1977, 141 patients with benign gynecologic disease and 149 patients with carcinoma of the cervix were evaluated with peritoneal fluid cytology at time of celiotomy. There was no positive cytology (malignant cells) in the benign disease group. The overall incidence of positive peritoneal cytology in th...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(84)90069-6
更新日期:1984-02-01 00:00:00
abstract:OBJECTIVE:The Toll-like receptors (TLRs) have been implicated in inflammation, innate immunity and cancer. The goal of this paper is to review the available published research about Toll-like receptors and their roles in gynecologic malignancies. METHODS:A Medline search was conducted and published articles from the l...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2014.08.013
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVE:In advanced ovarian cancer, patients cytoreduced to no visible disease appear to have improved survival compared to patients with visible residual tumor < or = 10 mm. It remains unresolved whether this is due to better chemotherapy response and/or simply "re-setting the clock," such that patients with less re...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2007.10.022
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVES:Surgical resection of enlarged cardiophrenic lymph nodes (CPLNs) in primary treatment of advanced ovarian cancer has not been widely studied. We report on a cohort of patients undergoing CPLN resection during primary cytoreductive surgery (CRS), examining its feasibility, safety, and potential impact on clin...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2017.09.001
更新日期:2017-11-01 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