4 results on '"Zoila Areli Lopez Bujanda"'
Search Results
2. 168 A novel prostate-restricted tumor-associated antigen: a potential therapeutic target
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Zoila (Areli) Lopez Bujanda, Aleksandar Obradovic, Thomas Nirschl, Timothy O’Donnell, Uri Laserson, Rodney Macedo-Gonzales, Ran Reshef, Tiezheng Yuan, Mithil Soni, Emmanuel Antonarakis, Benjamin Larman, Pawel Muranski, and Charles Drake
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biology ,business.industry ,Immunogenicity ,Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,GVAX ,Prostate cancer ,medicine.anatomical_structure ,Antigen ,Prostate ,Cancer research ,biology.protein ,Medicine ,Antibody ,business ,CD8 - Abstract
Background Prostate cancer is the second leading cause of cancer related death in men in the United States, mainly due to disease progression to metastatic castration-resistant prostate cancer (mCRPC). Although immunological treatment with the FDA-approved vaccine sipuleucel-T extends survival for 2–4 months by targeting the prostate-restricted antigen PAP, the identification of more immunogenic tumor-associated antigens (TAAs) continues to be an unmet need. Methods We evaluated the differential expression profile of the subset of epithelial cells reported to give rise to CRPC from mice following an androgen deprivation/repletion cycle. The expression levels of a set of androgen-responsive genes was further evaluated in prostate, brain, colon, liver, lung, and skin normal tissues from murine and human databases. The expression of a novel prostate-restricted TAA was then analyzed in primary tumors across all human cancer types in The Cancer Genome Atlas (TCGA). Finally, the immunogenicity of this novel prostate-restricted TAA was evaluated in vitro by autologous co-culture assays with cells from healthy donors and in vivo by antibody profiling (PhIP-Seq) in the sera of a cohort of prostate cancer patients treated with AR blockade alone or in combination with the cell-based vaccine GVAX. Results Here, we discovered a set of androgen-responsive genes exclusively expressed by the putative cell-of-origin for prostate cancer. We confirmed prostate-restricted enrichment of these androgen-responsive genes in normal tissues from murine and human databases. Among these prostate-restricted genes, we identified PAP, PSA, and a novel non-mutated TAA. This novel TAA was confirmed to be expressed in prostate cancer. Furthermore, its expression was associated with survival in patients with primary prostate cancer. Interestingly, we found that pro-inflammatory activated TBET+ EM CD8 and CD4 T cells were expanded by moDCs pulsed with our novel TAA to a greater extent than moDCs pulsed with either PAP or PSA were used. An IgG antibody response to this novel TAA was detected in 30% of vaccinated patients, while fewer than 8% of vaccinated patients developed antibody responses to PSA or PSMA. Conclusions Taken together, these results suggest we have found a novel immunogenic prostate-restricted TAA that represents a promising therapeutic target for treating mCRPC.
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- 2020
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3. Gene Methylation and Cytological Atypia in Random Fine-Needle Aspirates for Assessment of Breast Cancer Risk
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Carola M. Zalles, Christina Shehata, Stacie Jeter, Peng Huang, Vered Stearns, Mary Jo Fackler, Robert T. Chatterton, David Ivancic, Zoila Areli Lopez Bujanda, Seema A. Khan, Judith A. Wolfman, Sidra Hafeez, Nagi F. Khouri, Kara Kenney, Lisa K. Jacobs, and Saraswati Sukumar
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Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Biopsy, Fine-Needle ,Breast Neoplasms ,Article ,Body Mass Index ,Cohort Studies ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,Atypia ,Humans ,Medicine ,Mammography ,Breast ,Prospective Studies ,skin and connective tissue diseases ,Prospective cohort study ,Progesterone ,Breast Density ,Gynecology ,Estradiol ,medicine.diagnostic_test ,business.industry ,Age Factors ,Cancer ,DNA Methylation ,Middle Aged ,medicine.disease ,Menstrual cycle phase ,030104 developmental biology ,030220 oncology & carcinogenesis ,Multivariate Analysis ,DNA methylation ,Regression Analysis ,Biomarker (medicine) ,Female ,Follicle Stimulating Hormone ,business - Abstract
Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density and obtained random fine-needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole-genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (P < 0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number, and body mass index. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus, CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. Cancer Prev Res; 9(8); 673–82. ©2016 AACR.
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- 2016
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4. Abstract 267: Combining androgen deprivation with immune checkpoint blockade delays the development of castration resistance in a murine model of prostate cancer
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Angela Alme, Alan J. Korman, Christopher J. Nirschl, Brian Francica, Mark J. Selby, Thomas R. Nirschl, Charles G. Drake, Maria A. Carrera H, Zoila Areli Lopez Bujanda, Ying-Chun Shen, and Christina M. Kochel
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Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,Cancer ,Immunotherapy ,medicine.disease ,Androgen ,Immune checkpoint ,Blockade ,Androgen deprivation therapy ,Prostate cancer ,Endocrinology ,Oncology ,Castration Resistance ,Internal medicine ,medicine ,Cancer research ,business - Abstract
Androgen deprivation therapy induces immune cell infiltration in human prostate cancer. These findings suggest that immunotherapy may be most efficacious when administered concurrently with androgen deprivation, early in disease progression. We used a subcutaneous allograft model of murine prostate cancer (Myc-Cap), which mimics the development of human castration-resistant prostate cancer (CRPC) progression to study the anti-tumor effects of concurrent hormonal/immunotherapy. Implanted Myc-Cap tumors initially respond to androgen deprivation (degarelix acetate or bilateral orchiectomy), but mice eventually progress with CRPC. To test the hypothesis that the combination of androgen deprivation and immune checkpoint blockade could mediate pre-clinical benefit, we treated mice with either anti-PD-1, a depleting anti-CTLA-4 antibody (IgG2A), a non-depleting anti-CTLA-4 antibody (IgG1 D265A) or antibody combinations in the peri-castration period, then followed mice for the development of castration-resistant disease. Interestingly, the depleting anti-CTLA-4 antibody with/without anti-PD-1 antibody was strikingly effective in preventing the emergence of castration-resistant disease. The median castration-resistance free survival was 22 days in mice treated with androgen deprivation alone versus 32 days in mice treated with androgen deprivation and depleting anti-CTLA-4 antibody (P Citation Format: Ying-Chun Shen, Christina Kochel, Brian J. Francica, Angela Alme, Christopher Nirschl, Thomas Nirschl, Zoila Areli Lopez Bujanda, Maria A. Carrera H, Mark Selby, Alan Korman, Charles G. Drake. Combining androgen deprivation with immune checkpoint blockade delays the development of castration resistance in a murine model of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 267. doi:10.1158/1538-7445.AM2015-267
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- 2015
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