Angeles Secord

Overview:

My primary research interest has focused on angiogenesis, molecular signatures, clinical trial development, and ovarian cancer. My fundamental goal is to develop a strong translational research program at Duke University in the Gynecologic Oncology Division where knowledge we glean from our basic science research can be incorporated into our clinical trial program. Specifically on anti-angiogenic therapy and molecular tumor signatures to direct therapy in patients with ovarian cancer to determine if a strategy that incorporates both clinical and genomic information can improve clinical outcome, minimize unnecessary toxicity, and impact positively on quality of life.
In addition I am interested in robotic-assisted laparoscopic surgery for women with endometrial, ovarian, and cervical cancers as well as for benign gynecologic conditions.

Positions:

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. 1994

University of Washington

Resident, Obstetrics & Gynecology

Duke University

Grants:

Predictive value of the IL6 pathway to direct anti-angiogenic therapy in advanced ovarian cancer

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
Awarded By
American Association of Obstetricians and Gynecologists Foundation
Role
Principal Investigator
Start Date
End Date

Biomarker Discovery to Direct Bevacizumab Therapy in Ovarian Cancer - Blood-based Angiome Profiling

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

TESARO LUNG AND ENDOMETRIAL CANCER PRACTICUM

Administered By
Medicine, Medical Oncology
Awarded By
TESARO
Role
Co-Principal Investigator
Start Date
End Date

SGNTV-002: Open Label Phase 2 Study of Tisotumab Vedotin for Patients with Platinum-Resistant Ovarian Cancer with a Safety Run-in of a Dose-Dense Regimen

Administered By
Duke Cancer Institute
Awarded By
Seattle Genetics, Inc
Role
Principal Investigator
Start Date
End Date

A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination with Pembrolizumab Versus Treatment of Physician¿s Choice in Participants with Adva

Administered By
Duke Cancer Institute
Awarded By
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
End Date

Publications:

Obesity and altered angiogenic-related gene expression in endometrial cancer.

OBJECTIVES: Evaluate association between obesity and angiogenic-related gene expression in endometrial cancer (EC). Evaluate interaction between diet and metformin on angiogenic-related gene expression. METHODS: We evaluated the association between 168 human angiogenic-related genes and body mass index (BMI) in the TCGA Uterine Corpus Endometrial Carcinoma cohort (endometrioid endometrial cancer (EEC) cohort n = 290, and copy number high cohort n = 55), an independent validation cohort from Gynecologic Cancer Center of Excellence (GYN-COE) (n = 62) and corresponding 185 homologous mouse genes in an LKB1fl/flp53fl/fl mouse model of EC (n = 20). Mice received 60% of calories from fat in a high-fat diet (HFD), mimicking diet-induced obesity, versus 10% of calories from fat in a low-fat diet (LFD). After tumor growth, HFD (n = 5) and LFD (n = 5) mice were treated with metformin (200 mg/kg/day) or control. Whole transcriptome analysis of mouse tumors was performed using RNA-Seq. RESULTS: At a false-discovery rate of 10%, twenty-one angiogenic-related genes were differentially expressed with respect to BMI when adjusting for grade in the TCGA EEC cohort. Evaluation of these genes in the mouse model control group revealed association between increased Edil3 expression in HFD versus LFD mice (2.5-fold change (FC); unadjusted p = 0.03). An interaction was observed for expression of Edil3 between diet and metformin treatment (unadjusted p = 0.009). Association between BMI and increased expression of EDIL3 was validated in one of four EDIL3 probesets in the GYN-COE cohort (p = 0.0011, adjusted p = 0.0342). CONCLUSIONS: Obesity may promote tumor progression via differential modulation of angiogenic pathways in EEC. Our exploratory findings demonstrated that EDIL3 may be a candidate gene of interest.
Authors
Cobb, LP; Siamakpour-Reihani, S; Zhang, D; Qin, X; Owzar, K; Zhou, C; Conrads, TP; Maxwell, GL; Darcy, KM; Bateman, NW; Litzi, T; Bae-Jump, V; Secord, AA
MLA Citation
Cobb, Lauren Patterson, et al. “Obesity and altered angiogenic-related gene expression in endometrial cancer.Gynecol Oncol, Sept. 2021. Pubmed, doi:10.1016/j.ygyno.2021.08.010.
URI
https://scholars.duke.edu/individual/pub1497547
PMID
34538531
Source
pubmed
Published In
Gynecol Oncol
Published Date
DOI
10.1016/j.ygyno.2021.08.010

The preferences of women with ovarian cancer for oral versus intravenous recurrence regimens.

OBJECTIVE: To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. METHODS: A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%-60%); probability of PFS at 2 years (10%-20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). RESULTS: Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. CONCLUSIONS: These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens.
Authors
Havrilesky, LJ; Scott, AL; Davidson, BA; Secord, AA; Yang, J-C; Johnson, FR; Gonzalez, JM; Reed, SD
MLA Citation
Havrilesky, Laura J., et al. “The preferences of women with ovarian cancer for oral versus intravenous recurrence regimens.Gynecol Oncol, vol. 162, no. 2, Aug. 2021, pp. 440–46. Pubmed, doi:10.1016/j.ygyno.2021.05.022.
URI
https://scholars.duke.edu/individual/pub1484394
PMID
34053748
Source
pubmed
Published In
Gynecol Oncol
Volume
162
Published Date
Start Page
440
End Page
446
DOI
10.1016/j.ygyno.2021.05.022

H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.

Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3 •-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-κB and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001), and MnTnHex-2-PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP5+ into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.
Authors
Batinic-Haberle, I; Tovmasyan, A; Huang, Z; Duan, W; Du, L; Siamakpour-Reihani, S; Cao, Z; Sheng, H; Spasojevic, I; Alvarez Secord, A
MLA Citation
Batinic-Haberle, Ines, et al. “H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.Oxid Med Cell Longev, vol. 2021, 2021, p. 6653790. Pubmed, doi:10.1155/2021/6653790.
URI
https://scholars.duke.edu/individual/pub1478217
PMID
33815656
Source
pubmed
Published In
Oxid Med Cell Longev
Volume
2021
Published Date
Start Page
6653790
DOI
10.1155/2021/6653790

Placental uterine artery embolization followed by delayed hysterectomy for placenta percreta: A case series.

We describe outcomes of patients with suspected placenta percreta treated with placental uterine artery embolization (P-UAE) followed by delayed hysterectomy. This is a prospective case series of subjects from 2005 to 2018 with suspected placenta percreta who underwent P-UAE at the time of cesarean delivery followed by delayed hysterectomy. Both scheduled and unscheduled surgical cases were included. Maternal characteristics, surgical approaches, intra- and postoperative outcomes were abstracted from medical records. In total, twenty-two subjects were included. Median (interquartile range, IQR) delivery gestational age was 34.6 (31.9, 35.7) weeks, occurring as scheduled in 17 (77.3%) subjects and unscheduled in 5 (22.7%). Delayed hysterectomy was performed as scheduled in 17 (77.3%) subjects at a median (IQR) 40.5 (38.0, 44.0) days after delivery, and 5 (22.7%) subjects had a hysterectomy prior to scheduled date, median (IQR) 27.0 (17.0, 35.0) days after delivery. Indications for the 5 unscheduled hysterectomies included bleeding (n = 3) and suspected endometritis (n = 2). Three subjects (13.6%) received a blood transfusion (1, 3, 3 units) during delivery, and 7 (31.8%) were transfused during delayed hysterectomy (median [IQR] 2 [1,3] units). Three (13.6%) subjects had bladder resection at the time of hysterectomy; 1 (4.5%) had an unintentional cystotomy and 1 (4.5%) had a ureteral injury. P-UAE followed by delayed hysterectomy appears to be a safe and feasible, although appropriate patient selection and close surveillance are imperative, as 22.7% of patients underwent unscheduled hysterectomy.
Authors
Gatta, LA; Lee, PS; Gilner, JB; Weber, JM; Adkins, L; Salinaro, JR; Habib, AS; Pabon-Ramos, W; Strickland, KC; Ronald, J; Erkanli, A; Mehdiratta, JE; Grotegut, CA; Secord, AA
MLA Citation
Gatta, Luke A., et al. “Placental uterine artery embolization followed by delayed hysterectomy for placenta percreta: A case series.Gynecol Oncol Rep, vol. 37, Aug. 2021, p. 100833. Pubmed, doi:10.1016/j.gore.2021.100833.
URI
https://scholars.duke.edu/individual/pub1493074
PMID
34368412
Source
pubmed
Published In
Gynecologic Oncology Reports
Volume
37
Published Date
Start Page
100833
DOI
10.1016/j.gore.2021.100833

A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors.

Introduction: To assess the feasibility of a home-based aerobic exercise and nutrition counseling intervention and effect on cardiorespiratory fitness, cardiovascular disease risk profile, and immune response in obese endometrial cancer survivors. Methods: A longitudinal pilot study assessed a 12-week home-based aerobic exercise and nutrition counseling intervention in obese endometrial cancer survivors. The primary outcome was feasibility defined as 80% adherence to weekly walking sessions calculated among individuals that completed the intervention. Secondary outcomes comprised pre- and post-intervention differences in cardiorespiratory fitness, cardiovascular risk factors, and T-cell function. Descriptive statistics summarized data. Wilcoxon sign tests identified differences between and pre and post-intervention variables. Results: Nineteen women with stage 1 endometrial cancer consented; 9 withdrew and one was a screen failure. Median adherence to weekly walking sessions was 83.3%. Body composition was significantly altered with a reduction in median fat mass from 52.5 kg to 46.9 kg (p=0.04), and BMI from 37.5 kg/m2 to 36.2 kg/m2 (p = 0.004). There was no significant difference in cardiorespiratory fitness or cardiovascular parameters. The percentage of CD4+ and CD8+ T-cells producing IFNγ towards MAGE-A4 significantly increased from and 5.9% to 7.2% (p=0.043) and 13.9% to 14.8% (p=0.046), respectively. There were 3 related adverse events: hip pain, back sprain, and abdominal pain. Discussion: Our home-based exercise and nutrition counseling program was feasible based on 80% adherence to walking sessions and favored altered body composition. However, the discontinuation rate was high and further research is needed to overcome barriers to implementation. Improvement in cardiovascular parameters will most likely require longer and more intensive programs.
Authors
Schwartz, AR; Bartlett, DB; Johnson, JL; Broadwater, G; Channell, M; Nolte, KC; Wilkes, PA; Huffman, KM; Secord, AA
MLA Citation
Schwartz, Amanda R., et al. “A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors.Front Oncol, vol. 11, 2021, p. 669961. Pubmed, doi:10.3389/fonc.2021.669961.
URI
https://scholars.duke.edu/individual/pub1487557
PMID
34178654
Source
pubmed
Published In
Frontiers in Oncology
Volume
11
Published Date
Start Page
669961
DOI
10.3389/fonc.2021.669961