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Davidson, Brittany A

Positions:

Assistant Professor of Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2009

M.D. — University of Virginia

University of Texas Southwestern Medical Center at Dallas Southwestern Medical School

Duke University

Grants:

CL-PTL-119: Double-Blind, Placebo Controlled Phase III Trial of Maintenance FANG

Administered By
Duke Cancer Institute
AwardedBy
Gradalis, Inc.
Role
Principal Investigator
Start Date
August 01, 2015
End Date
July 31, 2020

Awards:

Fellow Teacher of the Year. Department of OB/GYN.

Type
Department
Awarded By
Department of OB/GYN
Date
January 01, 2016

Publications:

Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer.

To determine whether the processing of additional adipose tissue collected during lymph node (LN) dissection results in the identification of additional LNs during endometrial cancer (EC) staging and to determine if the division of LNs into nodal basin-specific specimens has an effect on the number of LNs identified during EC staging. A prospective randomized controlled trial was performed on women with high-grade EC undergoing surgical staging. Subjects were randomized to collection of LNs into nodal basin-specific containers on the randomized side versus simple labeling on the nonrandomized side. The total number of LNs and total number of LNs with metastases on the randomized versus the nonrandomized side were compared. The remaining adipose tissue from each LN specimen was submitted for histologic examination. We analyzed the number of LNs with and without metastases identified from additional adipose tissue. Of 120 consented subjects, 56 had sufficient data for analysis. The additional adipose tissue contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose contained LNs with metastases. In both cases, metastases were also detected in grossly identified LN candidates. The mean number of LNs identified was not significantly different based on method of collection (P=0.22). The mean number of LNs containing metastases per side was not significantly different (P=0.58). Processing of adipose tissue does increase the total number of LNs identified, however, it does not influence EC stage. No difference in LN counts was noted with basin-specific collection.

Authors
Davidson, BA; Ehrisman, J; Abbott, S; Harmon, Z; Secord, AA; Berchuck, A; Lee, PS; Valea, FA; Li, X; Havrilesky, LJ; Hall, AHS
MLA Citation
Davidson, BA, Ehrisman, J, Abbott, S, Harmon, Z, Secord, AA, Berchuck, A, Lee, PS, Valea, FA, Li, X, Havrilesky, LJ, and Hall, AHS. "Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer. (Accepted)" International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 37.3 (May 2018): 252-255.
PMID
28700428
Source
epmc
Published In
International Journal of Gynecological Pathology
Volume
37
Issue
3
Publish Date
2018
Start Page
252
End Page
255
DOI
10.1097/pgp.0000000000000418

Top 10 Tips Palliative Care Clinicians Should Know When Caring for Patients with Endometrial Cancer.

Endometrial cancer incidence has been increasing over the last two decades, likely due to the obesity epidemic. The majority of these cancers are confined to the uterus at diagnosis and can be cured with surgery. Overall, five-year disease-specific survival is about 80%, but some patients have locally advanced or metastatic disease that is not amenable to control with radiation and/or chemotherapy. Disease-related symptoms are most common in this subset of patients with endometrial cancer, although women with early-stage disease may also experience side effects related to surgical menopause or adjuvant treatment. In recent years, professional societies have been increasingly vocal about the importance of incorporating palliative care early in a patient's disease course. As these calls increase, palliative care clinicians will likely increasingly comanage patients with advanced or recurrent endometrial cancer. We brought together a team of gynecologic oncology and palliative care experts to assemble practical tips for the care of women with endometrial cancer. In this article, we use a "Top 10" format to highlight issues that may help palliative care physicians understand a patient's prognosis, address common misconceptions about endometrial cancer, and improve the quality of shared decision making and goals of care discussions.

Authors
Davidson, BA; Moss, HA; Arquiette, J; Kamal, AH
MLA Citation
Davidson, BA, Moss, HA, Arquiette, J, and Kamal, AH. "Top 10 Tips Palliative Care Clinicians Should Know When Caring for Patients with Endometrial Cancer." Journal of palliative medicine (March 13, 2018).
PMID
29649395
Source
epmc
Published In
Journal of Palliative Medicine
Publish Date
2018
DOI
10.1089/jpm.2018.0053

Top 10 Tips Palliative Care Clinicians Should Know When Caring for Patients with Ovarian Cancer.

The vast majority of women diagnosed with ovarian cancer present with advanced-stage disease with a five-year survival rate less than 50%. Studies have shown that in the past, gynecologic oncologists were not routinely collaborating with palliative care physicians resulting in goals of care planning often not occurring until the last 30 days before death. In recent years, professional societies have been increasingly more vocal about the importance of incorporating palliative care early in a patient's disease course. As these calls increase, palliative care clinicians will be likely to comanage patients with ovarian cancer and may benefit from additional targeted education on this unique population. We brought together a team of gynecologic oncology and palliative care experts to collate practical pearls for the care of women with epithelial ovarian cancer. In this article, we use a "Top 10" format to highlight issues that may help palliative care physicians understand a patient's prognosis, address common misconceptions about ovarian cancer, and improve the quality of shared decision making and goals-of-care discussions.

Authors
Davidson, BA; Moss, HA; Kamal, AH
MLA Citation
Davidson, BA, Moss, HA, and Kamal, AH. "Top 10 Tips Palliative Care Clinicians Should Know When Caring for Patients with Ovarian Cancer." Journal of palliative medicine 21.2 (February 2018): 250-254.
PMID
29319389
Source
epmc
Published In
Journal of Palliative Medicine
Volume
21
Issue
2
Publish Date
2018
Start Page
250
End Page
254
DOI
10.1089/jpm.2017.0679

Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC).Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis.Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001).Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC.

Authors
Phippen, NT; Secord, AA; Wolf, S; Samsa, G; Davidson, B; Abernethy, AP; Cella, D; Havrilesky, LJ; Burger, RA; Monk, BJ; Leath, CA
MLA Citation
Phippen, NT, Secord, AA, Wolf, S, Samsa, G, Davidson, B, Abernethy, AP, Cella, D, Havrilesky, LJ, Burger, RA, Monk, BJ, and Leath, CA. "Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study." Gynecologic oncology 147.1 (October 2017): 98-103.
PMID
28743369
Source
epmc
Published In
Gynecologic Oncology
Volume
147
Issue
1
Publish Date
2017
Start Page
98
End Page
103
DOI
10.1016/j.ygyno.2017.07.121

How Can We Effectively Address the Medical and Psychological Concerns of Survivors of Pelvic Malignancies?

Sexual and urinary morbidities resulting from treatment of pelvic malignancies are common. These treatment sequelae are significantly bothersome to patients and challenging to address. Awareness of these complications is critical in order to properly counsel patients regarding potential side effects and to facilitate prompt diagnosis and management. Addressing these issues often necessitates a coordinated multidisciplinary approach; however, the effort required often translates into improvement in patient quality of life. Herein we review the sexual and urinary side effects that may arise during or after treatment of pelvic malignancies.

Authors
Madden-Fuentes, RJ; Koontz, BF; Harrison, MR; George, DJ; Davidson, B; Gilmore, BF; Moul, JW; Mantyh, C; Peterson, AC
MLA Citation
Madden-Fuentes, RJ, Koontz, BF, Harrison, MR, George, DJ, Davidson, B, Gilmore, BF, Moul, JW, Mantyh, C, and Peterson, AC. "How Can We Effectively Address the Medical and Psychological Concerns of Survivors of Pelvic Malignancies?." Oncology (Williston Park) 31.4 (April 15, 2017): 286-294. (Review)
PMID
28412780
Source
pubmed
Published In
Oncology
Volume
31
Issue
4
Publish Date
2017
Start Page
286
End Page
294

Disparities in the surgical staging of high-grade endometrial cancer in the United States.

The National Comprehensive Cancer Network (NCCN) and the Society of Gynecologic Oncology (SGO) recommend lymph node sampling (LNS) as a key component in the surgical staging of high-grade endometrial cancer. Our goal was to examine surgical staging patterns for high-grade endometrial cancer in the United States.The National Cancer Data Base (NCDB) was searched for patients who underwent surgery for serous, clear cell, or grade 3 endometrioid endometrial cancer. Outcomes were receipt of LNS and overall survival (OS). Multivariate logistic regression was used to examine receipt of LNS in Stage I-III disease based on race (White vs. Black), income, surgical volume, and distance traveled to care. Multivariate Cox proportional hazards regression modeling was used to assess OS based on stage, race, income, LNS, surgical volume, and distance traveled.Forty-two thousand nine hundred seventy-three patients were identified: 76% White, 53% insured by Medicare/Medicaid, 24% traveled >30 miles, and 33% stage III disease. LNS was similar among White and Black women (81% vs 82%). LNS was more common among >30 miles traveled (84% vs 81%, p < 0.001), higher surgical volume (83% vs 80%, p < 0.001), and academic centers (84% vs 80%, p < 0.001). In multivariate analysis, higher income, higher surgical volume, Charlson-Deyo score, and distance traveled were predictors of LNS. Stage III disease (HR 3.39, 95% CI 3.28-3.50), age (10-year increase; HR 1.63, 95% CI 1.61-1.66), lack of LNS (HR 1.64, 95% CI 1.56-1.69), and low income (HR 1.20, 95% CI 1.14-1.27) were predictors of lower survival.Surgical care for high-grade endometrial cancer in the United States is not uniform. Improved access to high quality care at high volume centers is needed to improve rates of recommended LNS.

Authors
Foote, JR; Gaillard, S; Broadwater, G; Sosa, JA; Davidson, B; Adam, MA; Secord, AA; Jones, MB; Chino, J; Havrilesky, LJ
MLA Citation
Foote, JR, Gaillard, S, Broadwater, G, Sosa, JA, Davidson, B, Adam, MA, Secord, AA, Jones, MB, Chino, J, and Havrilesky, LJ. "Disparities in the surgical staging of high-grade endometrial cancer in the United States." Gynecologic oncology research and practice 4 (January 19, 2017): 1-.
Website
http://hdl.handle.net/10161/14627
PMID
28116108
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
4
Publish Date
2017
Start Page
1
DOI
10.1186/s40661-016-0036-3

Tumor grade and chemotherapy response in endometrioid endometrial cancer.

The objective of this study is to evaluate the association between tumor grade and response to chemotherapy in patients with endometrioid endometrial adenocarcinoma. Patients with advanced or recurrent endometrioid endometrial adenocarcinoma of known tumor grade who received at least 3 cycles of chemotherapy were retrospectively identified at three institutions. RECIST 1.1 criteria were used to assess response to neoadjuvant, postoperative or salvage chemotherapy. Chi-square testing was used to evaluate the association between tumor grade and chemotherapy response. Ninety-one patients met inclusion criteria: 13 with grade 1, 29 with grade 2 and 49 with grade 3 tumors. Eighty-four percent of patients received chemotherapy for recurrence, 12% for postoperative residual disease, and 4% in the neoadjuvant setting. The majority (85%) received carboplatin and paclitaxel. Forty-six percent (6/13) of grade 1, 72% (21/29) of grade 2 and 43% (21/49) of grade 3 tumors achieved an objective response. Grade 2 tumors were more likely to respond to chemotherapy compared to grade 3 tumors (72% vs. 43%, p = 0.02; Table 2), and specifically more likely to respond to carboplatin/paclitaxel (72% vs. 41%, p = 0.016). Median progression-free survival for patients receiving chemotherapy for recurrence or progression was 9 months for grade 1, 8 months for grade 2, and 5 months for grade 3 tumors. Similar results between grade and treatment response were apparent in the subset of 37 patients with a recently re-assigned tumor grade (G2 88% vs. G3 44%, p = 0.032). In this series of endometrioid endometrial cancers, grade 2 tumors had the best measurable response to chemotherapy.

Authors
Davidson, BA; Foote, J; Clark, LH; Broadwater, G; Ehrisman, J; Gehrig, P; Graybill, W; Alvarez Secord, A; Havrilesky, LJ
MLA Citation
Davidson, BA, Foote, J, Clark, LH, Broadwater, G, Ehrisman, J, Gehrig, P, Graybill, W, Alvarez Secord, A, and Havrilesky, LJ. "Tumor grade and chemotherapy response in endometrioid endometrial cancer." Gynecologic oncology reports 17 (August 2016): 3-6.
PMID
27354990
Source
epmc
Published In
Gynecologic Oncology Reports
Volume
17
Publish Date
2016
Start Page
3
End Page
6
DOI
10.1016/j.gore.2016.04.006

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis.

Chemotherapy plays a role in the treatment of endometrioid endometrial cancer (EEC); however, tumor grade may affect response. Our objective was to evaluate associations between tumor grade and in vitro chemoresponse.We conducted an analysis of primary tumor samples from women with EEC undergoing in vitro chemoresponse testing. Results were classified as sensitive (S), intermediate (I), or resistant (R) to each drug tested. Correlations between tumor grade and response were examined.Data was collected from 159 patients: 28 with grade 1 (18%), 52 with grade 2 (32%), and 79 (50%) with grade 3 tumors. Median age of patients was 62 (range 31-92). Most patients were Caucasian (83%) with advanced disease (Stage III: 50.9%; Stage IV: 13.2%). Overall chemoresponse was similar across all grades. Fifty percent, 56 and 51% for grade 1, 2, and 3 tumors, respectively, demonstrated S results to at least 1 agent. There was no association between grade and in vitro response to chemotherapy agents (p > 0.05) except a marginal association between grade and doxorubicin response (p = 0.08). Grade 1 and 2 cancers were more likely to demonstrate R results for doxorubicin compared to grade 3 cancers (G1: 19% vs G2: 25% vs G3: 8%; p = 0.08). In a subset tested for all 7 agents, only one patient tumor was pan-R and 4 were pan-S.Based on our data, grades 1-3 EEC have similar in vitro chemoresponse. These findings suggest that chemotherapy may be useful in advanced low grade EECs, but further clinical correlation is needed.

Authors
Davidson, BA; Foote, J; Brower, SL; Tian, C; Havrilesky, LJ; Secord, AA
MLA Citation
Davidson, BA, Foote, J, Brower, SL, Tian, C, Havrilesky, LJ, and Secord, AA. "Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis." Gynecologic oncology research and practice 3 (January 2016): 13-.
Website
https://hdl.handle.net/10161/16504
PMID
27980799
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
3
Publish Date
2016
Start Page
13
DOI
10.1186/s40661-016-0032-7

Benefits and Harms of Breast Cancer Screening: A Systematic Review.

Patients need to consider both benefits and harms of breast cancer screening.To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy.We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews.Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE.For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.

Authors
Myers, ER; Moorman, P; Gierisch, JM; Havrilesky, LJ; Grimm, LJ; Ghate, S; Davidson, B; Mongtomery, RC; Crowley, MJ; McCrory, DC; Kendrick, A; Sanders, GD
MLA Citation
Myers, ER, Moorman, P, Gierisch, JM, Havrilesky, LJ, Grimm, LJ, Ghate, S, Davidson, B, Mongtomery, RC, Crowley, MJ, McCrory, DC, Kendrick, A, and Sanders, GD. "Benefits and Harms of Breast Cancer Screening: A Systematic Review." JAMA 314.15 (October 2015): 1615-1634. (Review)
PMID
26501537
Source
epmc
Published In
JAMA : the journal of the American Medical Association
Volume
314
Issue
15
Publish Date
2015
Start Page
1615
End Page
1634
DOI
10.1001/jama.2015.13183

Outcomes of Treatment of Gestational Trophoblastic Neoplasia in a Primarily Indigent Urban Population.

Authors
Davidson, BA; Nagel, CI; Richardson, DL; Kehoe, SM; Miller, DS; Lea, JS
MLA Citation
Davidson, BA, Nagel, CI, Richardson, DL, Kehoe, SM, Miller, DS, and Lea, JS. "Outcomes of Treatment of Gestational Trophoblastic Neoplasia in a Primarily Indigent Urban Population." Journal of Reproductive Medicine 60.5-6 (2015): 243-248.
Source
manual
Published In
The Journal of reproductive medicine
Volume
60
Issue
5-6
Publish Date
2015
Start Page
243
End Page
248

Risk-benefit assessment of the combined oral contraceptive pill in women with a family history of female cancer.

INTRODUCTION: Oral contraceptive pills (OCPs) are the most frequently used form of effective, reversible contraception among women of childbearing potential. In the average risk population, OCPs may offer a protective benefit against ovarian, endometrial and colorectal malignancies. In women at high risk for breast, ovarian, endometrial or colorectal malignancies, the risk-benefit profile is less well studied. AREAS COVERED: In this article, we review pertinent literature on the use of OCPs in patients with genetic susceptibilities due to mutations in BRCA1, BRCA2 or mismatch repair genes implicated in hereditary nonpolyposis colorectal cancer as well as those with a strong family history of malignancies associated with these syndromes. EXPERT OPINION: For women at high risk for ovarian, endometrial and/or colorectal malignancies due to genetic susceptibilities or a strong family history, the possibility of chemoprevention with OCPs may be an attractive option; however, the potential increase in breast cancer, although small, must be considered in clinical decision-making. The ultimate decision to use OCPs in a high-risk woman should be based on a consideration of her specific genetic risk, her age, her reproductive plans and her willingness to consider surgical prophylaxis options.

Authors
Davidson, BA; Moorman, PG
MLA Citation
Davidson, BA, and Moorman, PG. "Risk-benefit assessment of the combined oral contraceptive pill in women with a family history of female cancer." Expert opinion on drug safety 13.10 (October 2014): 1375-1382. (Review)
PMID
25146351
Source
epmc
Published In
Expert Opinion on Drug Safety
Volume
13
Issue
10
Publish Date
2014
Start Page
1375
End Page
1382
DOI
10.1517/14740338.2014.951327

Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Recently, clinical trials have focused on novel antiangiogenic agents in combination with chemotherapy or alone in women with primary and recurrent ovarian cancer. Antiangiogenic agents include monoclonal antibodies, tyrosine-kinase inhibitors, and peptibodies. Many of these agents, including bevacizumab, pazopanib, nintedanib, cediranib, and trebananib, have been evaluated in randomized Phase III clinical trials, and all have demonstrated a progression-free survival (PFS) benefit. Specifically, maintenance pazopanib was shown to improve PFS in women with newly diagnosed EOC. Pazopanib, an oral TKI, inhibits several kinase receptors, including those for vascular endothelial growth factor (-1,-2,-3), platelet-derived growth factor (-α and -β), and fibroblast growth factor. It also targets stem cell-factor receptor (c-kit), interleukin 2-inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase, and colony-stimulating factor 1 receptor. Pazopanib has been investigated in several Phase II and III clinical trials, with results indicating a potential role in the management of EOC. This article provides an overview of pazopanib in the treatment of EOC.

Authors
Davidson, BA; Secord, AA
MLA Citation
Davidson, BA, and Secord, AA. "Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer." International Journal of Women's Health 6 (January 2014): 289-300. (Review)
Website
http://hdl.handle.net/10161/15735
PMID
24648773
Source
epmc
Published In
International Journal of Women's Health
Volume
6
Publish Date
2014
Start Page
289
End Page
300
DOI
10.2147/ijwh.s49781

Differential Angiogenic Gene Expression in TP53 Wild-Type and Mutant Ovarian Cancer Cell Lines.

Underlying mechanisms regulating angiogenesis in ovarian cancer have not been completely elucidated. Evidence suggests that the TP53 tumor suppressor pathway and tumor microenvironment play integral roles. We utilized microarray technology to study the interaction between TP53 mutational status and hypoxia on angiogenic gene expression.Affymetrix U133A arrays were analyzed for angiogenic gene expression in 19 ovarian cancer cell lines stratified both by TP53 mutation status and A2780 wild-type (wt) TP53 vs. mutated (m) TP53 cell lines after treatment under hypoxic conditions or with ionizing radiation.Twenty-eight differentially expressed angiogenic genes were identified in the mTP53 cell lines compared to wtTP53 lines. Five genes were upregulated in mTP53 cells: 40% involved in extracellular matrix (ECM) degradation [matrix metalloproteinase 10 (MMP10)/15] and 60% in angiogenesis (fibroblast growth factor receptor 3/VEGFA/ephrin receptor-B4). Twenty-three genes were upregulated in wtTP53: nearly 22% were ECM constituents or involved in ECM degradation; over 40% were growth factors or mediators of angiogenesis. Five genes were upregulated in the A2780mTP53 cells: 40% involved in ECM remodeling (MMP10, ADAMTS1), 40% with pro-angiogenic activity (EFNB2, factor 2 receptor), and 20% with anti-angiogenic properties (ADAMTS1). Three genes were upregulated in hypoxia treated cells compared to controls: one with anti-angiogenic activity (angiopoietin-like 4) and two with pro-angiogenic activity (VEGFA, EFNA3). No significant gene fold changes were noted after exposure to radiation. Four genes continued to demonstrate significant differential expression (p ≤ 0.05) after adjusting for multiple comparisons. These genes included endoglin upregulation in wt lines (pro-angiogenesis) and upregulation of FGF20 (growth factor), ADAMTS1 (anti-angiogenesis) and MMP10 (ECM degradation) in mTP53 cell lines.Our exploratory findings indicate that non-overlapping angiogenic pathways may be altered by TP53 mutations and hypoxic conditions in the tumor microenvironment. Further evaluation is needed for confirmation.

Authors
Davidson, BA; Rubatt, JM; Corcoran, DL; Teoh, DK; Bernardini, MQ; Grace, LA; Soper, WJ; Berchuck, A; Siamakpour-Reihani, S; Chen, W; Owzar, K; Murphy, SK; Secord, AA
MLA Citation
Davidson, BA, Rubatt, JM, Corcoran, DL, Teoh, DK, Bernardini, MQ, Grace, LA, Soper, WJ, Berchuck, A, Siamakpour-Reihani, S, Chen, W, Owzar, K, Murphy, SK, and Secord, AA. "Differential Angiogenic Gene Expression in TP53 Wild-Type and Mutant Ovarian Cancer Cell Lines." Frontiers in Oncology 4 (January 2014): 163-.
PMID
24999452
Source
epmc
Published In
Frontiers in Oncology
Volume
4
Publish Date
2014
Start Page
163
DOI
10.3389/fonc.2014.00163
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