Publications by authors named "Vy Ngo"

15 Publications

  • Page 1 of 1

Development of a low-cost colorimeter and its application for determination of environmental pollutants.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 14;249:119212. Epub 2020 Nov 14.

Hochiminh City Institute of Resources Geography, Vietnam Academy of Science and Technology, 01 Mac Dinh Chi, District 1, Ho Chi Minh City, Viet Nam. Electronic address:

Herein, a novel colorimeter based on the Beer-Lambert law was designed for detection of environmental pollutants in water with a high precision, simple, and miniaturized device using a tetracycline-Eu complex, cadmium reduction, diazotization, 1,10-phenanthroline, and periodate oxidation. The newly developed colorimeter could detect many environmental pollutants including tetracycline, nitrate, nitrite, Fe, and Mn, which were used to evaluate its performance. Simultaneously, a modified algorithm was applied to extend the linear response range. The colorimeter was comprised of an Red Green Blue Light Emitting Diode (RGB LED) light, focusing len, 3D printed stand for the cuvette, and light-sensitive photodiode detector. Microcontroller Arduino Uno processing technology was used to form a stable integrated structure. With the use of a novel algorithm, the device exhibited a wide linear response, ranging from 0-20, 0-17, 0-0.3, 0-1.75, and 0-15 mg/L for tetracycline, N-NO, N-NO, Fe, and Mn, respectively, and low limits of detection (0.88, 0.34, 0.031, 0.08, and 0.47 mg/L for tetracycline, N-NO, N-NO, Fe, and Mn, respectively). The advantages of high precision and low cost allow the novel design to be used for the detection of environmental pollutants.
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http://dx.doi.org/10.1016/j.saa.2020.119212DOI Listing
March 2021

Multiple Tissue Biomarkers Independently and Additively Predict Prostate Cancer Pathology Outcomes.

Eur Urol 2021 Jan 2;79(1):141-149. Epub 2020 Nov 2.

Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; Division of Hematology and Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.

Background: Distinguishing indolent from aggressive prostate cancer remains a key challenge for decision making regarding prostate cancer management. A growing number of biomarkers are now available to help address this need, but these have rarely been examined together in the same patients to determine their potentially additive value.

Objective: To determine whether two previously validated plasma markers (transforming growth factor β1 [TGFβ1] and interleukin-6 soluble receptor [IL6-SR]) and two validated tissue scores (the Genomic Evaluators of Metastatic Prostate Cancer [GEMCaP] and cell cycle progression [CCP] scores) can improve on clinical parameters in predicting adverse pathology after prostatectomy, and how much they vary within tumors with heterogeneous Gleason grade.

Design, Setting, And Participants: A case-control study was conducted among men with low-risk cancers defined by biopsy grade group (GG) 1, prostate-specific antigen (PSA) ≤10 ng/mL, and clinical stage ≤ T2 who underwent immediate prostatectomy. We collected paraffin-fixed prostatectomy tissue and presurgical plasma samples from 381 cases from the University of California, San Francisco, and 260 cases from the University of Washington.

Outcome Measurements And Statistical Analysis: Pathologic outcomes were minor upgrading/upstaging (GG 2 or pT3a) or major upgrading/upstaging (GG ≥ 3 or ≥ pT3b), and multinomial regression was performed to determine putative markers' ability to predict these outcomes, controlling for PSA, percent of positive biopsy cores, age, and clinical site. For upgraded tumors, a secondary analysis of the GEMCaP and CCP scores from the higher-grade tumor was also performed to evaluate for heterogeneity.

Results And Limitations: Overall, 357 men had no upgrading/upstaging event at prostatectomy, 236 had a minor event, and 67 had a major event. Neither TGFβ1 nor IL6-SR was statistically significantly associated with any upgrading/upstaging. On the contrary, both the CCP and the GEMCaP score obtained from Gleason pattern 3 tissue were directly associated with minor and major upgrading/upstaging on univariate analysis. The two scores correlated with each other, but weakly. On multinomial analysis including both scores in the model, the CCP score predicted minor upgrading/upstaging (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.05-2.49) and major upgrading/upstaging (OR 2.26, 95% CI 1.05-4.90), p =  0.04), and the GEMCaP score also predicted minor upgrading/upstaging (OR 1.05, 95% CI 1.03-1.08) and major upgrading/upstaging (OR 1.07, 95% CI 1.04-1.11), p <  0.01). The other clinical parameters were not significant in this model. Among upgraded tumors including both Gleason patterns 3 and 4, both the GEMCaP and the CCP score tended to be higher from the higher-grade tumor. The main limitation was the use of virtual biopsies from prostatectomy tissue as surrogates for prostate biopsies.

Conclusions: Biomarker signatures based on analyses of both DNA and RNA significantly and independently predict adverse pathology among men with clinically low-risk prostate cancer undergoing prostatectomy.

Patient Summary: Validated biomarker scores derived from both prostate cancer DNA and prostate cancer RNA can add independent information to help predict outcomes after prostatectomy.
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http://dx.doi.org/10.1016/j.eururo.2020.09.003DOI Listing
January 2021

Circadian Entrainment of Drosophila Melanogaster.

J Vis Exp 2020 06 3(160). Epub 2020 Jun 3.

School of Biological and Chemical Sciences, University of Missouri - Kansas City;

Nearly universal among organisms, circadian rhythms coordinate biological activity to earth's orbit around the sun. To identify factors creating this rhythm and to understand the resulting outputs, entrainment of model organisms to defined circadian time-points is required. Here we detail a procedure to entrain many Drosophila to a defined circadian rhythm. Furthermore, we detail post-entrainment steps to prepare samples for immunofluorescence, nucleic acid, or protein extraction-based analysis.
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http://dx.doi.org/10.3791/61176DOI Listing
June 2020

Brief freezing steps lead to robust immunofluorescence in the nervous system.

Biotechniques 2019 12 5;67(6):299-305. Epub 2019 Nov 5.

University of Missouri - Kansas City, School of Biological & Chemical Sciences, 5009 Rockhill Rd, Kansas City, MO 64110, USA.

possesses a complex nervous system, regulating sophisticated behavioral outputs, that serves as a powerful model for dissecting molecular mechanisms underlying neuronal function and neurodegenerative disease. Immunofluorescence techniques provide a way to visualize the spatiotemporal organization of these networks, permitting observation of their development, functional location, remodeling and, eventually, degradation. However, basic immunostaining techniques do not always result in efficient antibody penetration through the brain, and supplemental techniques to enhance permeability can compromise structural integrity, altering spatial organization. Here, slow freezing of brains is shown to facilitate antibody permeability without loss of antibody specificity or brain integrity. To demonstrate the advantages of this freezing technique, the results of two commonly used permeation methods - detergent-based and partial proteolytic digestion - are compared.
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http://dx.doi.org/10.2144/btn-2018-0067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031821PMC
December 2019

A subset of calcium-binding S100 proteins show preferential heterodimerization.

FEBS J 2019 05 21;286(10):1859-1876. Epub 2019 Feb 21.

Department of Biochemistry, The University of Western Ontario, London, Canada.

The assembly of proteins into dimers and oligomers is a necessary step for the proper function of transcription factors, muscle proteins, and proteases. In uncontrolled states, oligomerization can also contribute to illnesses such as Alzheimer's disease. The S100 protein family is a group of dimeric proteins that have important roles in enzyme regulation, cell membrane repair, and cell growth. Most S100 proteins have been examined in their homodimeric state, yet some of these important proteins are found in similar tissues implying that heterodimeric molecules can also be formed from the combination of two different S100 members. In this work, we have established co-expression methods in order to identify and quantify the distribution of homo- and heterodimers for four specific pairs of S100 proteins in their calcium-free states. The split GFP trap methodology was used in combination with other GFP variants to simultaneously quantify homo- and heterodimeric S100 proteins in vitro and in living cells. For the specific S100 proteins examined, NMR, mass spectrometry, and GFP trap experiments consistently show that S100A1:S100B, S100A1:S100P, and S100A11:S100B heterodimers are the predominant species formed compared to their corresponding homodimers. We expect the tools developed here will help establish the roles of S100 heterodimeric proteins and identify how heterodimerization might alter the specificity for S100 protein action in cells.
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http://dx.doi.org/10.1111/febs.14775DOI Listing
May 2019

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

J Urol 2018 03 20;199(3):719-725. Epub 2017 Sep 20.

Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California. Electronic address:

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.
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http://dx.doi.org/10.1016/j.juro.2017.09.071DOI Listing
March 2018

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

Cancer Lett 2016 09 22;380(1):144-52. Epub 2016 Jun 22.

Department of Urology, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology & Oncology, University of California, San Francisco (UCSF), San Francisco, CA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.canlet.2016.06.017DOI Listing
September 2016

Tactile length contraction as Bayesian inference.

J Neurophysiol 2016 08 27;116(2):369-79. Epub 2016 Apr 27.

Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario, Canada; McMaster Integrative Neuroscience Discovery and Study, Hamilton, Ontario, Canada; and McMaster University Origins Institute, Hamilton, Ontario, Canada

To perceive, the brain must interpret stimulus-evoked neural activity. This is challenging: The stochastic nature of the neural response renders its interpretation inherently uncertain. Perception would be optimized if the brain used Bayesian inference to interpret inputs in light of expectations derived from experience. Bayesian inference would improve perception on average but cause illusions when stimuli violate expectation. Intriguingly, tactile, auditory, and visual perception are all prone to length contraction illusions, characterized by the dramatic underestimation of the distance between punctate stimuli delivered in rapid succession; the origin of these illusions has been mysterious. We previously proposed that length contraction illusions occur because the brain interprets punctate stimulus sequences using Bayesian inference with a low-velocity expectation. A novel prediction of our Bayesian observer model is that length contraction should intensify if stimuli are made more difficult to localize. Here we report a tactile psychophysical study that tested this prediction. Twenty humans compared two distances on the forearm: a fixed reference distance defined by two taps with 1-s temporal separation and an adjustable comparison distance defined by two taps with temporal separation t ≤ 1 s. We observed significant length contraction: As t was decreased, participants perceived the two distances as equal only when the comparison distance was made progressively greater than the reference distance. Furthermore, the use of weaker taps significantly enhanced participants' length contraction. These findings confirm the model's predictions, supporting the view that the spatiotemporal percept is a best estimate resulting from a Bayesian inference process.
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http://dx.doi.org/10.1152/jn.00029.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969385PMC
August 2016

Mutational Landscape of Aggressive Prostate Tumors in African American Men.

Cancer Res 2016 04 26;76(7):1860-8. Epub 2016 Feb 26.

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California. Department of Urology, University of California San Francisco, San Francisco, California. Institute for Human Genetics, University of California San Francisco, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.

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.
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http://dx.doi.org/10.1158/0008-5472.CAN-15-1787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772140PMC
April 2016

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

Prostate 2016 Mar 20;76(4):339-48. Epub 2015 Nov 20.

Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.

Background: 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.

Objective: To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability.

Methods: We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression.

Results: Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P < 0.001). Among men with Gleason score ≤ 3 + 4, higher lycopene levels were associated with lower FGA (P = 0.04).

Conclusion: Circulating carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and supports the hypothesis that lycopene may inhibit progression of prostate cancer early in its natural history.
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http://dx.doi.org/10.1002/pros.23125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493324PMC
March 2016

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

Nat Med 2014 Dec 17;20(12):1394-6. Epub 2014 Nov 17.

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

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.
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http://dx.doi.org/10.1038/nm.3716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257862PMC
December 2014

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

Cancer Lett 2015 Jan 7;356(2 Pt B):404-9. Epub 2014 Oct 7.

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Program in Human and Molecular Genetics, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.canlet.2014.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200344PMC
January 2015

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

Int J Cancer 2014 May 2;134(10):2284-93. Epub 2014 Jan 2.

Division of Genitourinary Medical Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.

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.
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http://dx.doi.org/10.1002/ijc.28561DOI Listing
May 2014

Common structural and epigenetic changes in the genome of castration-resistant prostate cancer.

Cancer Res 2012 Feb 7;72(3):616-25. Epub 2011 Dec 7.

Division on Genitourinary Medical Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA.

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.
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http://dx.doi.org/10.1158/0008-5472.CAN-11-2079DOI Listing
February 2012

Negative regulation of Caenorhabditis elegans epidermal damage responses by death-associated protein kinase.

Proc Natl Acad Sci U S A 2009 Feb 21;106(5):1457-61. Epub 2009 Jan 21.

Department of Molecular, Cell and Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA.

Wounding of epidermal layers triggers multiple coordinated responses to damage. We show here that the Caenorhabditis elegans ortholog of the tumor suppressor death-associated protein kinase, dapk-1, acts as a previously undescribed negative regulator of barrier repair and innate immune responses to wounding. Loss of DAPK-1 function results in constitutive formation of scar-like structures in the cuticle, and up-regulation of innate immune responses to damage. Overexpression of DAPK-1 represses innate immune responses to needle wounding. Up-regulation of innate immune responses in dapk-1 requires the TIR-1/p38 signal transduction pathway; loss of function in this pathway synergizes with dapk-1 to drastically reduce adult lifespan. Our results reveal a previously undescribed function for the DAPK tumor suppressor family in regulation of epithelial damage responses.
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http://dx.doi.org/10.1073/pnas.0809339106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629440PMC
February 2009