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Dive into the research topics where Vy Ngo is active.

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Featured researches published by Vy Ngo.


Nature Medicine | 2014

Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma

Rintaro Hashizume; Noemi Andor; Yuichiro Ihara; Robin Lerner; Haiyun Gan; Xiaoyue Chen; Dong Fang; Xi Huang; Maxwell Tom; Vy Ngo; David A. Solomon; Sabine Mueller; Pamela L. Paris; Zhiguo Zhang; Claudia Petritsch; Nalin Gupta; Todd Waldman; C. David James

Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.


Cancer Research | 2012

Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer

Terence W. Friedlander; Ritu Roy; Scott A. Tomlins; Vy Ngo; Yasuko Kobayashi; Aruna Azameera; Mark A. Rubin; Kenneth J. Pienta; Arul M. Chinnaiyan; Michael Ittmann; Charles J. Ryan; Pamela L. Paris

Progression of primary prostate cancer to castration-resistant prostate cancer (CRPC) is associated with numerous genetic and epigenetic alterations that are thought to promote survival at metastatic sites. In this study, we investigated gene copy number and CpG methylation status in CRPC to gain insight into specific pathophysiologic pathways that are active in this advanced form of prostate cancer. Our analysis defined and validated 495 genes exhibiting significant differences in CRPC in gene copy number, including gains in androgen receptor (AR) and losses of PTEN and retinoblastoma 1 (RB1). Significant copy number differences existed between tumors with or without AR gene amplification, including a common loss of AR repressors in AR-unamplified tumors. Simultaneous gene methylation and allelic deletion occurred frequently in RB1 and HSD17B2, the latter of which is involved in testosterone metabolism. Lastly, genomic DNA from most CRPC was hypermethylated compared with benign prostate tissue. Our findings establish a comprehensive methylation signature that couples epigenomic and structural analyses, thereby offering insights into the genomic alterations in CRPC that are associated with a circumvention of hormonal therapy. Genes identified in this integrated genomic study point to new drug targets in CRPC, an incurable disease state which remains the chief therapeutic challenge.


International Journal of Cancer | 2014

Detection and characterization of invasive circulating tumor cells derived from men with metastatic castration‐resistant prostate cancer

Terence W. Friedlander; Vy Ngo; Huan Dong; Gayatri Premasekharan; Vivian Weinberg; Shaun Doty; Qiang Zhao; Elizabeth Gilbert; Charles J. Ryan; Wen-Tien Chen; Pamela L. Paris

The Vitatex cell‐adhesion matrix (CAM) platform allows for isolation of invasive circulating tumor cells (iCTCs). Here we sought to determine the utility of prostate‐specific membrane antigen (PSMA) as a metastatic castration‐resistant prostate cancer (mCRPC) iCTC biomarker, to identify solitary cells and clusters of iCTCs expressing either epithelial, mesenchymal, or stem cell markers, and to explore the feasibility of iCTC epigenomic analysis. CTCs were isolated and enumerated simultaneously using the Vitatex and CellSearch platforms in 23 men with mCRPC. CAM‐avid iCTCs were identified as nucleated cells capable of CAM uptake, but without detectable expression of hematopoietic lineage (HL) markers including CD45. iCTCs were enumerated immunocytochemically (ICC) and by flow cytometry. Whole‐genome methylation status was determined for iCTCs using the Illumina HumanMethylation27 BeadChip. Thirty‐four samples were collected for iCTC analysis. A median of 27 (range 0–800) and 23 (range 2–390) iCTCs/mL were detected by ICC and flow, respectively. In a subset of 20 samples, a median of seven CTCs/mL (range 0–85) were detected by the CellSearch platform compared to 26 by the CAM platform. iCTC clusters were observed in 17% of samples. iCTCs expressing PSMA as well as markers of EMT and stemness were detectable. The iCTC methylation profile highly resembled mCRPC. More CTCs were recovered using the CAM platform than the CellSearch platform, and the CAM platform allowed for the detection of iCTC clusters, iCTCs expressing EMT and stem‐cell markers, and characterization of the iCTC methylome. Correlation with clinical data in future studies may yield further insight into the functional significance of these findings.


Cancer Letters | 2015

Next generation sequencing of pancreatic cyst fluid microRNAs from low grade-benign and high grade-invasive lesions

Jin Wang; Pamela L. Paris; Jinyun Chen; Vy Ngo; Hui Yao; Marsha L. Frazier; Ann M. Killary; Chang Gong Liu; Han Liang; Christian Mathy; Sandhya Bondada; Kimberly S. Kirkwood; Subrata Sen

Intraductal papillary mucinous neoplasm (IPMN) is a precursor cystic lesion to pancreatic cancer. With the goal of classifying IPMN cases by risk of progression to pancreatic cancer, we undertook an exploratory next generation sequencing (NGS) based profiling study of miRNAs (miRNome) in the cyst fluids from low grade-benign and high grade-invasive pancreatic cystic lesions. Thirteen miRNAs (miR-138, miR-195, miR-204, miR-216a, miR-217, miR-218, miR-802, miR-155, miR-214, miR-26a, miR-30b, miR-31, and miR-125) were enriched and two miRNAs (miR-451a and miR-4284) were depleted in the cyst fluids derived from invasive carcinomas. Quantitative real-time polymerase chain reaction analysis confirmed that the relative abundance of tumor suppressor miR-216a and miR-217 varied significantly in these cyst fluid samples. Ingenuity Pathway Analysis (IPA) analysis indicated that the genes targeted by the differentially enriched cyst fluid miRNAs are involved in five canonical signaling pathways, including molecular mechanisms of cancer and signaling pathways implicated in colorectal, ovarian and prostate cancers. Our findings make a compelling case for undertaking in-depth analyses of cyst fluid miRNomes for developing informative early detection biomarkers of pancreatic cancer developing from pancreatic cystic lesions.


Cancer Research | 2016

Mutational Landscape of Aggressive Prostate Tumors in African American Men.

Karla Lindquist; Pamela L. Paris; Thomas J. Hoffmann; Niall J. Cardin; Rémi Kazma; Joel Mefford; Jeff Simko; Vy Ngo; Yalei Chen; A. Levin; Dhananjay Chitale; Brian T. Helfand; William J. Catalona; Benjamin A. Rybicki; John S. Witte

Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason ≥7, stage ≥T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR.


The Prostate | 2016

Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer.

Tobias Nordström; Erin L. Van Blarigan; Vy Ngo; Ritu Roy; Vivian Weinberg; Xiaoling Song; Jeffry Simko; Peter R. Carroll; June M. Chan; Pamela L. Paris

Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers.


Cancer Letters | 2016

An improved CTC isolation scheme for pairing with downstream genomics: Demonstrating clinical utility in metastatic prostate, lung and pancreatic cancer

Gayatri Premasekharan; Elizabeth Gilbert; Ross A. Okimoto; Ashiya Hamirani; Karla Lindquist; Vy Ngo; Ritu Roy; Jeffrey Hough; Matthew Edwards; Rosa Paz; Adam Foye; Riddhi Sood; Kirsten Copren; Matthew A. Gubens; Eric J. Small; Trever G. Bivona; Eric A. Collisson; Terence W. Friedlander; Pamela L. Paris

Improvements in technologies to yield purer circulating tumor cells (CTCs) will enable a broader range of clinical applications. We have previously demonstrated the use of a commercially available cell-adhesion matrix (CAM) assay to capture invasive CTCs (iCTCs). To improve the purity of the isolated iCTCs, here we used fluorescence-activated cell sorting (FACS) in combination with the CAM assay (CAM + FACS). Our results showed an increase of median purity from the CAM assay to CAM + FACS for the spiked-in cell lines and patient samples analyzed from three different metastatic cancer types: castration resistant prostate cancer (mCRPC), non-small cell lung cancer (mNSCLC) and pancreatic ductal adenocarcinoma cancer (mPDAC). Copy number profiles for spiked-in mCRPC cell line and mCRPC patient iCTCs were similar to expected mCRPC profiles and a matched biopsy. A somatic epidermal growth factor receptor (EGFR) mutation specific to mNSCLC was observed in the iCTCs recovered from EGFR(+) mNSCLC cell lines and patient samples. Next-generation sequencing (NGS) of spiked-in pancreatic cancer cell line and mPDAC patient iCTCs showed mPDAC common mutations. CAM + FACS iCTC enrichment enables multiple downstream genomic characterizations across different tumor types.


The Journal of Urology | 2017

Validation of GEMCaP as a DNA Based Biomarker to Predict Prostate Cancer Recurrence after Radical Prostatectomy

Hao G. Nguyen; Christopher J. Welty; Karla Lindquist; Vy Ngo; Elizabeth Gilbert; Henrik Bengtsson; Cristina Magi-Galluzzi; Jerome Jean-Gilles; Jorge L. Yao; Matthew R. Cooperberg; Edward M. Messing; Eric A. Klein; Peter R. Carroll; Pamela L. Paris

Purpose We aimed to validate GEMCaP (Genomic Evaluators of Metastatic Cancer of the Prostate) as a novel copy number signature predictive of prostate cancer recurrence. Materials and Methods We randomly selected patients who underwent radical prostatectomy at Cleveland Clinic or University of Rochester from 2000 to 2005. DNA isolated from the cancer region was extracted and subjected to high resolution array comparative genomic hybridization. A high GEMCaP score was defined as 20% or greater of genomic loci showing copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and the risk of biochemical recurrence. Results We report results in 140 patients. Overall 38% of patients experienced recurrence with a median time to recurrence of 45 months. Based on the CAPRA‐S (Cancer of the Prostate Risk Assessment Post‐Surgical) score 39% of the patients were at low risk, 42% were at intermediate risk and 19% were at high risk. The GEMCaP score was high (20% or greater) in 31% of the cohort. A high GEMCaP score was associated with a higher risk of biochemical recurrence (HR 2.69, 95% CI 1.51–4.77) and it remained associated after adjusting for CAPRA‐S score and age (HR 1.94, 95% CI 1.06–3.56). The C‐index of GEMCaP alone was 0.64, which improved when combined with the CAPRA‐S score and patient age (C‐index = 0.75). Conclusions A high GEMCaP score was associated with biochemical recurrence in 2 external cohorts. This remained true after adjusting for clinical and pathological factors. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify patients with prostate cancer for early adjuvant therapy.


Clinical Cancer Research | 2015

Abstract IA20: Molecular and genomic characterization of invasive circulating tumorcells (iCTCs) from men with metastatic castration-resistant prostate cancer (mCRPC)

Terence W. Friedlander; Gayatri Premasekharan; Archana Dilip; Jaime Tawney; Vy Ngo; Elizabeth Gilbert; Charles J. Ryan; Eric J. Small; Pamela L. Paris

Background: Molecular characterization and genomic analysis of circulating tumor cells (CTCs) may allow for a better understanding of the mechanisms of resistance to therapies in metastatic castration resistant prostate cancer (mCRPC). The Vitatex VitaAssay platform captures invasive CTCs (iCTCs) in a cell surface marker-independent fashion based on their ability to invade a fluorescently-labeled cell adhesion matrix (CAM), allowing for the analysis of multiple CTC subpopulations. We recently demonstrated our ability to detect EMT and stem-like CTC subpopulations with the CAM platform (Friedlander et al., Int J Cancer 2014). We hypothesize that CTC subpopulation diversity is associated with a shorter period of time to resistance for men with mCRPC. Here we sought to estimate epithelial, mesenchymal, stem-like and neuroendocrine iCTC subpopulation diversity in men with CRPC starting abiraterone acetate or enzalutamide therapy and to report the genomic profiles of iCTCs and matched metastatic biopsies. Methods: Blood is being obtained with informed consent from men with mCRPC partaking in either a dose escalation abiraterone trial or the West Coast Dream Team (WCDT) trial. iCTCs are being isolated from the blood samples using the CAM platform coupled with FACS. Paired metastatic biopsies are being obtained as part of the WCDT, when available. For CTC enrichment, iCTCs are defined as CAM+/CD45-/CD14-. For subpopulation characterizations, mesenchymal iCTCs are defined as vimentin+, stem-like iCTCs as CD44+ and neuroendocrine iCTCs as chomogranin (CgA)+. Agilent array comparative genomic hybridization (aCGH) of iCTCs and paired biopsies is being performed. Results: iCTCs were isolated using the CAM platform from 96 men, to date. The average baseline iCTC count per 7.5ml was 160 (range 0-1255). In a subset of 69 subjects, the average baseline CD44+ iCTC count per 7.5ml was 153 (range 0 -1423), and in a subset of 31 patients the median vimentin+ iCTC count per 7.5ml was 116 (range 5-538) and in a subset of 5 patients the median CgA+ iCTC counts per 7.5ml was 79 (range 46 - 185). Using aCGH, copy number aberration is detectable in iCTCs. Some iCTC aCGH profiles resemble paired metastatic biopsy aCGH profiles. Conclusions: Multiple CRPC iCTC subpopulations are identifiable from men with mCRPC, reflecting the heterogeneity of the disease. Data will continue to be collected as part of these two ongoing clinical trials to identify biomarkers of resistance and shed light on resistance pathways. Citation Format: Terence W. Friedlander, Gayatri Premasekharan, Archana Dilip, Jaime Tawney, Vy Ngo, Elizabeth Gilbert, Charles J. Ryan, Eric Small, Pamela L. Paris. Molecular and genomic characterization of invasive circulating tumorcells (iCTCs) from men with metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA20.


Molecular Cancer Therapeutics | 2013

Abstract A153: Isolation and characterization of high-purity invasive CTCs from men with metastatic castration-resistant prostate cancer (mCRPC).

Gayatri Premasekharan; Terence W. Friedlander; Vy Ngo; Elizabeth Gilbert; Priya Sathaye; Anna Harris; Charles J. Ryan; Pamela L. Paris

Introduction: As metastatic biopsies are often difficult and impractical to obtain; isolation, characterization, and genomic profiling of circulating tumor cells (CTCs) from men with metastatic castration resistant prostate cancer (mCRPC) is critical for understanding tumor progression and mechanisms of resistance to treatment. The Vitatex cell-adhesion matrix (CAM) platform captures invasive CTCs in both a cell surface marker- and size-independent manner based on the ability of CTCs to invade a fluorescently-labeled CAM. This platform allows for isolation and characterization of viable CTC sub-populations from individual patients with mCRPC. In this study, we sought to optimize CTC isolation and purification for downstream genomics and to explore epithelial-mesenchymal and stem-like CTC subtypes, all in the context of treatment resistance to Abiraterone, a novel inhibitor of androgen synthesis. Methods: Forty ml of blood was collected from 23 patients with mCRPC. The CTCs were isolated using the VitaAssay platform and paired metastatic biopsies were obtained for a subset of men. Fluorescence-activated cell sorting (FACS) was coupled with the VitaAssay platform to increase cell purity. Invasive CTCs having ingested the fluorescent CAM were sorted based on CAM+/CD45-/CD14-/DAPI- staining. To complement the FACS data and for quality control, a subset of cases (N=11) were also enumerated using Immunocytochemistry (ICC), where CTCs were identified as CAM+/CD45-/CD14-/DAPI+. Healthy donor blood was used as a control. FACS-sorted stem-like CTCs were defined as CD44+/CAM+/CD45-/CD14-/DAPI- and mesenchymal CTCs were identified with ICC as vimentin+/CAM+/CD45-/DAPI+. Array comparative genomic hybridization (aCGH) of FACS-sorted CAM-avid amplified CTCs using Agilent microarrays was performed to obtain the CTC and matched biopsy genomic profiles. Results: Enumeration of CTCs by VitaAssay coupled with FACS yielded an average of 72 CTCs per 7.5 ml blood (range 1 to 338) for the 23 patients. Only 4 of the 23 patients had ≤ 2 CTCs per 7.5 ml blood. No CTCs were detected in the healthy control subject after cell sorting. The CTC purity increased post-FACS to ∼90% from ∼1% pre-FACS. Enumeration along with genomic analysis (copy number aberrations) of CTCs and their subpopulations, comparison with matched biopsies and clinical data are currently being investigated. Conclusions: Combining the VitaAssay platform with FACS allows for recovery of high purity mCRPC CTC subpopulations suitable for downstream molecular and genomic analysis. Ultimately, studies incorporating these optimized CTC methods will allow for better understanding of mechanisms of treatment resistance, disease progression and potentially identify new drug targets for CRPC. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A153. Citation Format: Gayatri Premasekharan, Terence W. Friedlander, Vy T. Ngo, Elizabeth Gilbert, Priya Sathaye, Anna Harris, Charles J. Ryan, Pamela L. Paris. Isolation and characterization of high-purity invasive CTCs from men with metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A153.

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Ritu Roy

University of California

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Shaun Doty

University of California

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Anna Harris

University of California

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