Abstract:
OBJECTIVES:The PI3K/AKT/mTOR pathway is frequently overactivated in endometrial cancer (EC). We assessed the efficacy of ABTL0812, a novel first-in-class molecule presenting a unique mechanism of action inhibiting this pathway. METHODS:We investigated the effects of ABTL0812 on proliferation, cell death and modulation of intracellular signaling pathways in a wide panel of endometrioid and non-endometrioid cell lines, an inducible PTEN knock-out murine model, and two patient-derived xenograft murine models of EC. Then, TRIB3 expression was evaluated as potential ABTL0812 pharmacodynamic biomarker in a Phase 1b/2a clinical trial. RESULTS:ABTL0812 induced an upregulation of TRIB3 expression, resulting in the PI3K/AKT/mTOR axis inhibition and autophagy cell death induction on EC cells but not in healthy endometrial cells. ABTL0812 treatment also impaired PTEN knock-out cells to progress from hyperplasia to cancer. The therapeutic effects of ABTL0812 were demonstrated in vivo. ABTL0812 increased TRIB3 mRNA levels in whole blood samples of eight EC patients, demonstrating that TRIB3 mRNA could be used as a pharmacodynamic biomarker to monitor the ABTL0812 treatment. CONCLUSIONS:ABTL0812 may represent a novel and highly effective therapeutic agent by inducing TRIB3 expression and autophagy in EC patients, including those with poorer prognosis.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Felip I,Moiola CP,Megino-Luque C,Lopez-Gil C,Cabrera S,Solé-Sánchez S,Muñoz-Guardiola P,Megias-Roda E,Pérez-Montoyo H,Alfon J,Yeste-Velasco M,Santacana M,Dolcet X,Reques A,Oaknin A,Rodríguez-Freixinos V,Lizcano JM,Domèndoi
10.1016/j.ygyno.2019.03.002subject
Has Abstractpub_date
2019-05-01 00:00:00pages
425-435issue
2eissn
0090-8258issn
1095-6859pii
S0090-8258(19)30150-7journal_volume
153pub_type
杂志文章abstract:OBJECTIVE:To evaluate the value of the combination of p16 and HPV detection in the screening for cervical cancer. METHODS:186 patients with previous abnormal cervical lesion were studied. After colposcopic examination, two conventional Pap slides were prepared: the first was Papanicolaou-stained and examined by cytolo...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.01.033
更新日期:2006-10-01 00:00:00
abstract::Ascitic fluid was obtained from a patient with ovarian endometrioid carcinoma. The cells obtained from the fluid were cultured in Eagle's minimum essential medium containing 15% fetal calf serum at 37 degrees C under humidified 5% CO2 and 95% air. Epithelial colonies grew rapidly in the primary culture and we were abl...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(84)90217-8
更新日期:1984-03-01 00:00:00
abstract:OBJECTIVE:Epithelial ovarian cancer (EOC) spreads intra-abdominally and to the retroperitoneal lymph nodes. A greater number of distant metastases are revealed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) compared to conventional imaging methods. We aimed to investigate th...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1016/j.ygyno.2012.04.023
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:Metastatic bone involvement in vulvar squamous carcinoma is very rare. Here, we present a case of primary adenocarcinoma of the Bartholin's gland giving rise to isolated skull metastasis. CASE:A 74-year-old woman was referred with a diagnosis of primary vulvar adenocarcinoma of the right labium minus. A rig...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.04.019
更新日期:2005-08-01 00:00:00
abstract::To determine the best noninvasive means of evaluating response in patients with advanced ovarian carcinoma, 50 abdominal ultrasound (US) and computed tomography (CT) scans were performed in clinically disease-free ovarian cancer patients. The scans were correlated with the results obtained at a subsequent second- or t...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90348-o
更新日期:1990-05-01 00:00:00
abstract::Melanoma represents the second most frequent vulvar malignancy, and yet is still considered to be an uncommon neoplasm. Several varieties of melanoma exist. A patient who was diagnosed with a rare subtype of melanoma as a primary vulvar process is presented here. To date, there is only one other reported case of neuro...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1995.1048
更新日期:1995-02-01 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:OBJECTIVE:Previous studies by the Gynecologic Oncology Group have demonstrated a 7% response rate with bolus etoposide as second-line therapy in nonsquamous cell carcinoma of the cervix. Prolonged oral etoposide, which exploits the schedule dependency of this agent, has demonstrated increased activity in squamous carci...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0090-8258(03)00079-9
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVES:The objective of this study was to determine whether the length of the interval from primary surgery to commencement of chemotherapy has any direct effect on progression-free survival in ovarian cancer. METHODS:The progression-free survival of 472 patients enrolled in four trials who had all received platin...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2002.6750
更新日期:2002-09-01 00:00:00
abstract::A phase II trial of ifosfamide (IFX) and mesna was conducted by the GOG in patients with recurrent or advanced nonsquamous carcinoma of the cervix. A starting dose of 1.5 g/m2 IFX iv daily for 5 days and 300 mg/m2 mesna iv every 4 hr with three doses daily after IFX were given. In patients who had received prior radio...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1006/gyno.1993.1084
更新日期:1993-04-01 00:00:00
abstract:OBJECTIVE:To determine if there is an advantage to combination chemotherapy and radiation for optimally resected stage IIIC endometrial cancer (EC). METHODS:A multicenter retrospective analysis of patients with EC from 1991 to 2008 was conducted. Inclusion criteria were lymph node assessment and optimally resected dis...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2012.10.010
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to retrospectively analyze the prognostic importance of age, histologic type and grade, ascites, lymph node status, size and type of postoperative residual disease, and radiation dose on disease-specific (DSS) and progression-free survival (PFS) in stage III epithelial ovarian cancer...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5477
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:To correlate findings on pathologic examination of loop electroexcisional procedure (LEEP) or cone biopsy specimens with residual disease in radical hysterectomy specimens in patients with stage IA2 cervical cancer to determine whether a subset of such patients may be eligible for conservative, fertility-spar...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.09.011
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Five-Year survival after pelvic exenteration for gynecologic malignancies has been reported as high as 60%. The objective of this study was to determine overall survival (OS) after pelvic exenteration and evaluate factors impacting outcome. METHODS:A retrospective review of all women who underwent pelvic ex...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2014.06.034
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVE:To update the demographic data, treatment details and outcomes for GTN patients with brain metastases managed with the modern treatment protocols at the UK centre for gestational trophoblast neoplasia at Charing Cross Hospital in London. METHODS:The hospital database and pharmacy records were reviewed to ide...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2015.01.530
更新日期:2015-04-01 00:00:00
abstract:OBJECTIVE:Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that strongly inhibits epithelial cell growth. Disabling of TGF-beta signaling is thought to be involved in development of a variety of tumors in which abnormal expression or function of TGF-beta receptor plays critical roles. In the pre...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.04.031
更新日期:2005-09-01 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::Between 1965 and 1988, 125 patients with primary invasive vaginal carcinoma were treated with radiation therapy at the Center of Oncology in Kraków. Twenty-two superficial stage I patients received radium or cesium intracavitary radiation alone. The remaining 11 patients with stage I disease whose lesions were either ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1996.0004
更新日期:1996-01-01 00:00:00
abstract::Gastrointestinal stromal tumors (GISTs) are c-kit-positive tumors that may arise anywhere in the tubular gastrointestinal tract. Around 5% of the cases arise elsewhere in the abdominal cavity. Tumors originating in the omentum and mesentery have been reported.A 31-year-old woman presented with pelvic pain, a palpable ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2003.08.025
更新日期:2003-12-01 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:OBJECTIVES:The presence of disseminated tumor cells (DTC) in breast cancer patients is associated with poor prognosis. However, there are limited data about the prevalence and prognostic impact of DTC in patients with gynecological tumors. The aim of this study was to evaluate the presence of DTC in the bone marrow (BM...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.05.049
更新日期:2006-12-01 00:00:00
abstract::A 65-year-old woman had a total abdominal hysterectomy and bilateral salpingo-oophorectomy through a Pfannenstiel incision for a Stage Ib, Grade 2 endometrial adenocarcinoma with extension to the middle third of the myometrium. No adjuvant treatment was given. She presented 7 years later with a large suprapubic mass a...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1994.1147
更新日期:1994-06-01 00:00:00
abstract:OBJECTIVE:Upper abdominal spreading of advanced-stage ovarian cancer often involves the diaphragm. In addition, bulky diaphragmatic tumors occasionally infiltrate the liver. Here, we describe our early experiences with a ventral liver mobilization technique to remove diaphragmatic tumors with liver involvement. METHOD...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2016.01.017
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:Central nervous system (CNS) metastases from an ovarian malignancy are uncommon. The long-term prognosis for these patients is poor, with studies reporting a mean survival of less than 12 months. CASES:We present three ovarian cancer patients who developed metastatic disease to the brain. All patients were ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.02.019
更新日期:2005-06-01 00:00:00
abstract::Human ovarian carcinomas (n = 215) were xenotransplanted into thymus-aplastic female nu/nu mice (NMRI). Growth of transplants was defined as take-off rate, growth rapidity, and feasibility of passages. In 204 cases these growth characteristics could be correlated with survival time of the individual tumor-donor patien...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(86)90066-1
更新日期:1986-09-01 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:OBJECTIVES:Lack of exercise and excess body weight may exacerbate treatment-related declines in quality of life (QoL) in endometrial cancer survivors. The primary purpose of this study was to examine the associations among exercise, body weight, and QoL in a population-based sample of endometrial cancer survivors. MET...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.01.007
更新日期:2005-05-01 00:00:00
abstract::The rate of regression of the beta subunit of human chorionic gonadotropin in patients successfully treated by single-agent chemotherapy with methotrexate (MTX) for postmolar nonmetastatic gestational trophoblastic neoplasia (NMGTN) has not previously been described. In 21 patients with NMGTN treated with MTX, the rat...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1016/0090-8258(88)90150-3
更新日期:1988-01-01 00:00:00
abstract::From 1978 to 1982, 49 patients with intraepithelial neoplasia in the vulvar region were included in a prospective investigation. The main purpose was to evaluate the effect of treatment by local excision with a free margin of 2 mm and to estimate the importance of colposcopy. In 28% of the patients, the disease recurr...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(85)90267-7
更新日期:1985-07-01 00:00:00
abstract:OBJECTIVE:Ras gene mutations have been identified in squamous cell carcinomas of the cervix and are associated with advanced-stage tumors. The current study was designed to determine the prevalence of c-Ki-ras mutations in invasive endocervical adenocarcinomas and associations between mutations, HPV status, and known p...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1993.1064
更新日期:1993-03-01 00:00:00