Abstract:
:Cancers with deficiencies in homologous recombination-mediated DNA repair (HRR) demonstrate improved clinical outcomes and increased survival. Approximately 50% of high-grade serous ovarian cancers (HGSOC) exhibit homologous recombination deficiency (HRD). HRD can be caused by germline or somatic mutations of genes involved in the HR pathway. Given platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARPis) are used in HGSOC, double-strand breaks (DSBs) are common. Unrepaired DSBs are toxic to cells as genomic instability ensues and cells eventually die. Thus, tumor cells with DSBs utilize the high-fidelity HRR as one of the central pathways for repair. In tumors that have HRD, an alternate pathway such as non-homologous end-joining (NHEJ) is used and leads to error-prone repair. To date, methods for clinical detection of homologous recombination deficiency (HRD) are limited to genomic changes of HRR genes and genomic mutation patterns resulting from HRD genes involved in HR-mediated DNA repair. However, these tests detect genomic scars that might not always correlate well with PARP inhibitor or platinum sensitivity in the current state. Therefore, a functional HRD assay should be able to more accurately predict tumor response in real-time. RAD51 foci formation has been used as a functional assay to define HRD and closely correlates with chemotherapy and PARPi sensitivity. The inability to form RAD51 foci is a common feature of HRD. DNA damage can also cause transient slowing or stalling of replication forks defined as replication stress. Replication fork stalling can lead to fork degradation and decreased cell viability if forks do not resume DNA synthesis. Fork degradation has been found to lead to chemosensitivity in BRCA-deficient tumors. To determine this fork degradation phenotype, replication fork/DNA fiber assays are utilized. This review will highlight functional assays for HRD in the context of translating these to real-time clinical assays.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Fuh K,Mullen M,Blachut B,Stover E,Konstantinopoulos P,Liu J,Matulonis U,Khabele D,Mosammaparast N,Vindigni Adoi
10.1016/j.ygyno.2020.08.035subject
Has Abstractpub_date
2020-12-01 00:00:00pages
877-886issue
3eissn
0090-8258issn
1095-6859pii
S0090-8258(20)33852-Xjournal_volume
159pub_type
杂志文章,评审abstract:OBJECTIVES:To determine the importance of margin status and other prognostic factors associated with the recurrence and survival of patients with squamous cell vulvar carcinoma. METHODS:Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. All slides were re-reviewed by two gynecologic...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2006.10.004
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVES:We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer. METHODS:A prospective, non-randomiz...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.12.334
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Ovarium cancer is the fifth most common cause of cancer-related death in women and is the most common fatal gynecologic malignancy. So far, ovarium carcinoma has not been reported to have occurred in female-to-male transsexuals. OBJECTIVE AND METHOD:We report on two such cases. Long-term exposure to increas...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5720
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVE:To investigate the influence of human anti-mouse antibodies (HAMA) on serial CA 125 measurements in serum of patients with epithelial ovarian cancer following single intraperitoneal (IP) therapy with Yttrium-90-labeled human milk fat globule 1 murine monoclonal antibody ((90)Y-muHMFG1) as part of a large inte...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.ygyno.2008.01.025
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVE:The correlation between p53 tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with the in vitro radiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients. METHODS:Comparison of the intrinsic radiose...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1998.5194
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND:Malignant germ cell tumors of the ovary are often curative after conservative surgery and adjuvant chemotherapy. Persistent tumors despite normalization of serum tumor markers may represent retroconversion to benign masses, but this is rare in ovarian tumors without teratoma elements. The management in such ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2001.6541
更新日期:2002-03-01 00:00:00
abstract:OBJECTIVE:Inappropriate telomerase expression has been reported to be associated with the development and/or progression of malignancies. Therefore, the purpose of the study was to determine and evaluate the levels of telomerase activity in normal ovary, cystadenomas, low-malignant-potential tumors, and carcinomas of t...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5506
更新日期:1999-09-01 00:00:00
abstract::Copyright ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1998.5026
更新日期:1998-07-01 00:00:00
abstract:OBJECTIVE:In Denmark, the proportion of women with ovarian cancer treated with neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among center hospitals. We aimed to evaluate the impact of first-line treatment on surgical outcome and median overall survival (MOS). METHODS:All patients treated in...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2013.11.035
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:Recurrent and advanced cervical cancers are associated with high mortality and a lack of effective treatment options, especially for women who are poor candidates for surgery or radiation therapy. The broad clinical effectiveness and low toxicity of gemcitabine in other human malignancies suggest that it migh...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/s0090-8258(03)00338-x
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVE:To estimate the likelihood of occult cancer diagnosis at prophylactic oophorectomy in BRCA1 and BRCA2 carriers in different age groups and to determine the histopathology of these lesions. METHODS:We describe a series of 159 female BRCA1 or BRCA2 carriers who underwent prophylactic oophorectomy at the Univer...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.06.065
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to validate the role of p16(INK4a) immunocytochemistry as a marker of cervical epithelial neoplasia in cytology and biopsy samples. METHODS:During the period of 4 years a total of 501 immunocytochemistry stains in cytology and biopsy samples were performed. The cytology smears were ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2009.06.020
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:Ovarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovar...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2014.01.005
更新日期:2014-03-01 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:To determine whether single agent chemotherapy with intramuscular methotrexate 50mg administered on days 1, 3, 5, and 7 and oral folinic acid 15mg administered on days 2, 4, 6, and 8 in 2 weekly cycles (IM MTX/FA) is an effective treatment regimen for patients with low risk gestational choriocarcinoma. METHO...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2014.12.024
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Leiomyosarcoma (LMS) of the uterus is a rare neoplasm with an aggressive growth pattern. Although the majority of uterine LMS is diagnosed with disease confined to the uterus, the rate of recurrent disease is high. The most common sites of recurrent disease are lung, liver, and peritoneal cavity. The rate of...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2003.10.043
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. METHODS:Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500mg oral gefitinib daily until progression or severe toxicity, wit...
journal_title:Gynecologic oncology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ygyno.2013.02.019
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVE:Estimate the prevalence of cardiovascular disease risk factors and endpoints in women with BRCA mutations. METHODS:Women, age 40 and older, with BRCA mutations identified in Kaiser Permanente Northern California completed a questionnaire and underwent a lipid and fasting glucose panel. Bivariable analysis of...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2018.10.010
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVE:Large cell neuroendocrine carcinoma of the cervix (LCNEC) is a rare cervical neoplasm associated with poor survival. Our objective was to identify treatments associated with improved survival. METHODS:Relevant data were abstracted from an English literature MEDLINE search, SEER database, and a patient treate...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2010.11.007
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVES:The search for effective systemic chemotherapy for endometrial cancer is ongoing. Complete responses to current drugs or regimens are infrequent, and overall survival for patients with disease not amenable to surgery or radiation therapy is poor. Dactinomycin has proven activity against a wide variety of sol...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章
doi:10.1006/gyno.1999.5652
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:To profile long non-coding RNA (lncRNA) expression at the various anatomic sites of high-grades serous carcinoma (HGSC) and in effusion-derived exosomes. METHODS:LncRNA profiling was performed on 60 HGSC specimens, including 10 ovarian tumors, 10 solid metastases and 10 malignant effusions, as well as exosom...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2018.01.004
更新日期:2018-03-01 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:Small cell carcinoma (SmCC) of the female genital tract constitutes a diagnostic and clinical challenge given its rarity and the lack of standardized therapeutic approaches. Here we review the morphological, clinical and molecular features of gynecologic SmCCs and discuss potential areas for future research. ...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2014.05.017
更新日期:2014-08-01 00:00:00
abstract:PURPOSE:The purpose of this study was to survey the brachytherapy practice for cervical cancer in the United States. METHODS:The Clinical Research Committee of the American Brachytherapy Society (ABS) performed a retrospective survey of individual physicians of the ABS and American Society of Therapeutic Radiologists ...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1998.5334
更新日期:1999-04-01 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: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::Human papillomavirus (HPV) types 16 and 18 are associated with cervical dysplasia and carcinoma. In vitro integration of HPV-16 or HPV-18 DNA into cultured human cervical cells results in their immortalization. In this study, in vivo differentiation of human cervical cells immortalized with recombinant HPV-16 or HPV-1...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90082-v
更新日期:1990-09-01 00:00:00
abstract::Gynecologic oncology patients are at a high-risk of postoperative venous thromboembolism and these events are a source of major morbidity and mortality. Given the availability of prophylaxis regimens, a structured comprehensive plan for prophylaxis is necessary to care for this population. There are many prophylaxis s...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
doi:10.1016/j.ygyno.2016.11.036
更新日期:2017-02-01 00:00:00
abstract::Primary adenocarcinoma of the vulva is rare, and cloagocenic adenocarcinoma of the vulva is extremely rare. Here we report a vulvar tumor characterized by columnar cells with prominent brush border and the presence of goblet cells and endocrine cells, presenting the tubulovillous pattern and mucin histochemistry of en...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1999.5433
更新日期:1999-08-01 00:00:00
abstract::A patient with Stage IIB squamous cell cancer of the cervix presented 10 days into her primary radiation therapy with neutropenic fever and diarrhea requiring hospitalization and delay in treatment. The patient's history revealed extensive use of alternative therapies including potential toxic botanicals. This case ra...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2000.5743
更新日期:2000-04-01 00:00:00