Gary L Goldberg

Montefiore Medical Center, New York, New York, United States

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Publications (208)863.71 Total impact

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    ABSTRACT: In spite of profound reduction in incidence, cervical cancer claims >275,000 lives annually. Previously we demonstrated efficacy and safety of radioimmunotherapy directed at HPV16 E6 oncoprotein in experimental cervical cancer. We undertook a direct comparison of targeting E7 and E6 oncoproteins with specific (188)Rhenium-labeled monoclonal antibodies in CasKi subcutaneous xenografts of cervical cancer cells in mice. The most significant tumor inhibition was seen in radioimmunotherapy-treated mice, followed by the unlabeled monoclonal antibodies to E6 and E7. No hematological toxicity was observed. Immunohistochemistry suggests that the effect of unlabeled antibodies is C3 complement mediated. We have demonstrated for the first time that radioimmunotherapy directed toward E7 oncoprotein inhibits experimental tumors growth, decreases E7 expression and may offer a novel approach to cervical cancer therapy.
    Immunotherapy 06/2015; DOI:10.2217/imt.15.18 · 2.44 Impact Factor
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    ABSTRACT: To evaluate HPV16 CpG methylation and methyl-haplotypes and their association with cervix precancer and cancer utilizing massively parallel single molecule next-generation sequencing (NGS). A nested case-control study of HPV16 positive women was performed in a prospective cohort from Guanacaste, Costa Rica designed to study the natural history of HPV and cervical neoplasia. Controls encompassed 31 women with transient infections; there were 44 cases, including 31 women with CIN3 and 13 with cervical cancer. DNA samples from exfoliated cervical cells were treated with bisulfite and four regions (E6, E2, L2 and L1) were amplified with barcoded primers and tested by NGS. CpG methylation was quantified using a bioinformatics pipeline. Median methylation levels were significantly different between the CIN3+ cases versus controls in the E2, L2, and L1 regions. Methyl-haplotypes, specifically in 5 CpG sites included in the targeted L2 region, with the pattern "--+-+" had the highest Area Under the Curve value (AUC = 88.40%) observed for CIN3 vs. The most significant CpG site, L2 4277, determined by bisulfite NGS had an AUC = 78.62%. This study demonstrates that NGS of bisulfite treated HPV DNA is a useful and efficient technique to survey methylation patterns in HPV16. This procedure provides quantitative information on both individual CpG sites and methyl-haplotypes that identify women with elevated present or subsequent risk for HPV16 CIN3 and cancer. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 05/2015; 138(1). DOI:10.1016/j.ygyno.2015.05.001 · 3.69 Impact Factor
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    ABSTRACT: To test if TP53 hot spot mutations (HSMs) confer differential chemotherapy resistance or survival outcomes, the effects of microtubule stabilizers on human ovarian carcinoma cells (OCCs) expressing TP53 HSMs were studied in vitro. Survival outcomes of patients with high grade serous epithelial ovarian carcinoma (HGS EOC) expressing matched HSMs were compared using The Cancer Genome Atlas (TCGA) data. Growth inhibition of OCCs transfected with a HSM (m175, m248 or m273) was measured during treatment with paclitaxel, epothilone B (epoB), or ixabepilone. Effects of epoB on p53 expression, phosphorylation, and acetylation, as well as p53-regulated expression of p21 and mdm2 proteins, were determined by Western blot analysis. Expression of p53 target genes P21, GADD45, BAX, PIDD, NF-kB2, PAI-1, and MDR1 was measured by RT-PCR. cBioPortal.org identified patients with codon R175, R248 or R273 HSMs from TCGA data. Survival outcomes were characterized. p53-m248 confers chemoresistance and is not acetylated during epoB treatment. m273 demonstrated high MDR1 expression and resistance to paclitaxel. P21, GADD45 and PAI-1 expression was down-regulated in mutant OCCs. Optimally cytoreduced patients with codon R273 (n=17), R248 (n=13), R175 (n=7) HSMs, or any other TP53 mutation demonstrated median 14.9, 17.6, 17.8 and 16.9 months (p=0.806) progression free survival and 84.1, 33.6, 62.1 and 44.5 months (p=0.040) overall survival, respectively. Human OCCs harboring different TP53 HSMs were selectively resistant to microtubule stabilizers. Patients with different HSMs had significantly different overall survival. Both in vitro data and clinical experience support further studying the outcomes of particular TP53 HSMs. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 05/2015; 138(1). DOI:10.1016/j.ygyno.2015.04.039 · 3.69 Impact Factor
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    Gynecologic Oncology 04/2015; 137:193-194. DOI:10.1016/j.ygyno.2015.01.487 · 3.69 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. METHODS: A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. RESULTS: At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. CONCLUSION: Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.
    Gynecologic Oncology 04/2015; 137. DOI:10.1016/j.ygyno.2015.01.074 · 3.69 Impact Factor
  • Gynecologic Oncology 04/2015; 137:131. DOI:10.1016/j.ygyno.2015.01.326 · 3.69 Impact Factor
  • Gynecologic Oncology 04/2015; 137:79-80. DOI:10.1016/j.ygyno.2015.01.195 · 3.69 Impact Factor
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    ABSTRACT: To determine the physical activity (PA) behavior, needs and preferences for underserved, ethnically diverse women with a history of endometrial cancer (EC). Women with a history of EC (41 non-Hispanic black, 40 non-Hispanic white, and 18 Hispanic) completed a needs assessment during their regular follow-up appointments at Montefiore Medical Center in Bronx, NY, USA. An 8-week pilot PA intervention based on the results of the needs assessment was conducted with 5 EC survivors. Mean body mass index (BMI) among the 99 respondents was 34.1±7.6 kg/m², and 66% did not exercise regularly. Self-described weight status was significantly lower than actual BMI category (p<0.001). Of the 86% who were interested in joining an exercise program, 95% were willing to attend at least once weekly. The primary motivations were improving health, losing weight, and feeling better physically. Despite the high interest in participation, volunteer rate was very low (8%). However, adherence to the 8-week pilot PA intervention was high (83%), and there were no adverse events. Body weight decreased in all pilot participants. These data show that ethnically diverse EC survivors have a great need for, and are highly interested in, PA interventions. However, greater care needs to be taken to assess and identify barriers to increase participation in such programs.
    Journal of Gynecologic Oncology 04/2015; 26(2):141-7. DOI:10.3802/jgo.2015.26.2.141 · 1.60 Impact Factor
  • Gynecologic Oncology 04/2015; 137. DOI:10.1016/j.ygyno.2015.01.072 · 3.69 Impact Factor
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    Gynecologic Oncology 04/2015; 137:155-156. DOI:10.1016/j.ygyno.2015.01.389 · 3.69 Impact Factor
  • Gynecologic Oncology 04/2015; 137:60-61. DOI:10.1016/j.ygyno.2015.01.141 · 3.69 Impact Factor
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    ABSTRACT: Background To date there have been no comprehensive, comparative assessments of the environmental impact of surgical modalities. Our study seeks to quantify and compare the total greenhouse gas emissions, or 'carbon footprint', attributable to three surgical modalities.MethodsA review of 150 staging procedures, employing laparotomy (LAP), conventional laparoscopy (LSC) or robotically-assisted laparoscopy (RA-LSC), was performed. The solid waste generated (kg) and energy consumed (kWh) during each case were quantified and converted into their equivalent mass of carbon dioxide (kg CO2e) release into the environment. The carbon footprint is the sum of the waste production and energy consumption during each surgery (kg CO2e).ResultsThe total carbon footprint of a RA-LSC procedure is 40.3 kg CO2e/patient (p < 0.01). This represents a 38% increase over that of LSC (29.2 kg CO2e/patient; p < 0.01) and a 77% increase over LAP (22.7 kg CO2e/patient; p < 0.01).Conclusions Our results provide clinicians, administrators and policy-makers with knowledge of the environmental impact of their decisions to facilitate adoption of sustainable practices. Copyright © 2015 John Wiley & Sons, Ltd.
    International Journal of Medical Robotics and Computer Assisted Surgery 02/2015; DOI:10.1002/rcs.1640 · 1.53 Impact Factor
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    ABSTRACT: To evaluate the performance of simultaneous endometrial aspiration at the time of sonohysterography for screening postmenopausal women at risk for endometrial cancer. A retrospective cohort study of women older than 50 years who underwent saline-infusion sonohysterography for the evaluation of their endometrium. On completion of imaging, the remaining intracavitary saline and endometrial tissue were aspirated through the saline-infusion sonohysterography catheter and submitted for pathologic evaluation. Based on the clinical, pathologic, and ultrasonographic results, the patients underwent surgical treatment with hysteroscopy, hysterectomy, or clinical observation. Follow-up results and outcomes were collected using electronic medical records. Sensitivity, specificity, and predictive values of saline-infusion sonohysterography, endometrial aspiration, and combined approaches for endometrial aspiration and sonohysterography were assessed. Six hundred three patients underwent endometrial aspiration at the time of sonohysterography. Endometrial tissue was present in 567 (94.0%) and outcome data were available for 540 (89.5%). In 194 (35.9%) patients, final pathology was obtained by surgical intervention. The remaining 346 (64.1%) patients were monitored for at least 6 months. Thirty patients (5.6%) had cancer or endometrial hyperplasia. A sequential model, in which endometrial aspiration was done only for positive saline-infusion sonohysterography findings, yielded sensitivity of 86.7% (95% confidence interval [CI] 69-96%) and specificity of 100% (95% CI 99-100%) for detecting endometrial hyperplasia or cancer (area under the curve 0.93). Considering proliferative endometrium as abnormal endometrial aspiration reduced specificity to 88.3% (95% CI 85-91%, P<.01) without significant increase in sensitivity (100%, 95% CI 88-100%, P=.13). The high sensitivity and specificity of the sequential endometrial aspiration at the time of sonohysterography make this approach a useful and reliable screening algorithm for detecting endometrial cancer or hyperplasia in postmenopausal women at risk. Endometrial aspiration at the time of sonohysterography should be considered as an initial one-stop endometrial evaluation in this population. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 01/2015; DOI:10.1097/AOG.0000000000000631 · 4.37 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):4687-4687. DOI:10.1158/1538-7445.AM2014-4687 · 9.28 Impact Factor
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    ABSTRACT: Objective: To present a case of recurrent vulvar fibromatosis in an adolescent, discuss the specific difficulties of treating adolescents, and review the literature on available treatment. Methods: We present a case of recurrent vulvar fibromatosis in a 14-year-old girl, requiring several treatment modalities, including multiple surgeries, radiation therapy, and multiagent chemotherapy. We then discuss management strategies for these tumor types, and specifically examine how tumor location may impact their treatment. Results: Vulvar desmoids are extremely uncommon and they can be disfiguring and cause significant discomfort for women. Initial management of these tumors is surgical excision, yet failed surgery is often followed by other treatment modalities, including radiation, tyrosine kinase inhibitors, nonsteroidal anti-inflammatory drugs, hormonal therapy, and chemotherapy. This case clearly highlights the difficulties in managing these rare tumors, particularly in the adolescent population. Conclusions: Desmoid tumors are nonmalignant, locally aggressive neoplasms most common in the 15 to 60 years age group. They are associated with high estrogen states, prior surgical trauma, and Gardner syndrome. Most commonly, desmoid tumors present in the abdominal wall, shoulder, neck, and chest, but can occur anywhere in the body. Given their rarity and lack of definitive therapy, vulvar desmoid tumors can be exceedingly difficult to treat, and are best managed with an interdisciplinary approach.
    Journal of Pediatric Hematology/Oncology 09/2014; 37(1). DOI:10.1097/MPH.0000000000000261 · 0.96 Impact Factor
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    ABSTRACT: Objective: To determine the efficacy of image-guided drainage versus antibiotic-only treatment of pelvic abscesses. Design: Retrospective cohort analysis. Setting: An academic, inner-city medical center. Patient(s): Women ages 11-49, admitted between 1998 and 2008 with ICD9 code 614.x (inflammatory diseases of ovary, fallopian tube, pelvic cellular tissue, and peritoneum). Intervention(s): Medical records search, chart review, and phone survey. Main Outcome Measure(s): Surgical intervention. Result(s): We identified 6,151 initial patients, of whom 240 patients met inclusion criteria. Of the included patients, 199 women received antibiotic-only treatment, and 41 received additional image-guided drainage. There was no statistically significant difference between the two groups in terms of age, body mass index, parity, incidence of diabetes, obesity, endometriosis, or history of sexually transmitted infection excluding human immunodeficiency virus (HIV). Abscesses in the drainage cohort were noted to be larger in dimension (5.9 cm vs. 8.5 cm); 16.1% of patients who received antibiotics alone required surgical intervention versus only 2.4% of the drainage cohort. Patients who received drainage had longer hospital stays, but the time from treatment to discharge was similar in both groups (7.4 days vs. 6.7 days). We successfully contacted 150 patients, and the differences in long-term pregnancy outcomes, pain, or infertility were not statistically significant. Conclusion(s): Patients who received antibiotics alone were more likely to require further surgical intervention when compared with patients who additionally received image-guided drainage. There were no observable long-term differences. (C) 2014 by American Society for Reproductive Medicine.
    Journal of Minimally Invasive Gynecology 07/2014; 102(4). DOI:10.1016/j.fertnstert.2014.06.025 · 1.58 Impact Factor
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    ABSTRACT: OBJECTIVE: Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. METHODS: A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. RESULTS: A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (+/- 11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (+/- 10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R-2=0.049, P<.001). This association persisted after multivariable adjustment (R-2=0.181, P=.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. CONCLUSIONS: Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis.
    Obstetrics and Gynecology 07/2014; 124(2). DOI:10.1097/AOG.0000000000000381 · 4.37 Impact Factor
  • Gynecologic Oncology 06/2014; 133:123. DOI:10.1016/j.ygyno.2014.03.323 · 3.69 Impact Factor
  • Gynecologic Oncology 06/2014; 133:78-79. DOI:10.1016/j.ygyno.2014.03.212 · 3.69 Impact Factor

Publication Stats

3k Citations
863.71 Total Impact Points

Institutions

  • 2001–2015
    • Montefiore Medical Center
      • • Department of Obstetrics and Gynecology (Women's Health)
      • • Department of Oncology
      • • Albert Einstein College of Medicine
      New York, New York, United States
  • 1989–2015
    • Albert Einstein College of Medicine
      • • Department of Obstetrics & Gynecology & Women's Health
      • • Department of Radiology
      • • Department of Medicine
      New York, New York, United States
  • 1992–2013
    • Albert Einstein Medical Center
      Philadelphia, Pennsylvania, United States
    • City University of New York - Bronx Community College
      New York, New York, United States
  • 2006
    • Shahid Beheshti University of Medical Sciences
      Teheran, Tehrān, Iran
  • 2003
    • Cornell University
      Итак, New York, United States
  • 2002
    • Women’s Health Institute of Illinois
      Oak Lawn, Illinois, United States