Full Text Journal Articles by
Author Evan T Keller

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Single-Cell Transcriptomics Analysis Identifies Nuclear Protein 1 as a Regulator of Docetaxel Resistance in Prostate Cancer Cells.

Patricia M Schnepp, Greg Shelley, Jinlu Dai, Nicole Wakim, Hui Jiang, Atsushi Mizokami, Evan T Keller,

The majority of patients with prostate cancer treated with docetaxel develop resistance to it. To better understand the mechanism behind the acquisition of resistance, we conducted single-cell RNA-sequencing (scRNA-seq) of docetaxel-sensitive and -resistant variants of DU145 and PC3 prostate cancer cell lines. Overall, sensitive and resistant cells clustered separately. Differential ... Read more >>

Mol. Cancer Res. (Molecular cancer research : MCR)
[2020, 18(9):1290-1301]

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Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC.

Yaxiu Guo, Jingyu Wang, Kaichen Zhou, Junqiang Lv, Lei Wang, Shan Gao, Evan T Keller, Zhi-Song Zhang, Quan Wang, Zhi Yao,

Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract infections, is associated with prostate and bladder cancers. Cytotoxic necrotizing factor 1 (CNF1) is a key UPEC toxin; however, its role in bladder cancer is unknown. In the present study, we found CNF1 induced bladder cancer cells to secrete vascular endothelial ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2020, 34(6):7927-7940]

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Integrative differential expression and gene set enrichment analysis using summary statistics for scRNA-seq studies.

Ying Ma, Shiquan Sun, Xuequn Shang, Evan T Keller, Mengjie Chen, Xiang Zhou,

Differential expression (DE) analysis and gene set enrichment (GSE) analysis are commonly applied in single cell RNA sequencing (scRNA-seq) studies. Here, we develop an integrative and scalable computational method, iDEA, to perform joint DE and GSE analysis through a hierarchical Bayesian framework. By integrating DE and GSE analyses, iDEA can ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):1585]

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Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer.

David C Smith, Stephanie Daignault-Newton, Petros Grivas, Zachery R Reichert, Maha Hussain, Kathleen A Cooney, Megan Caram, Ajjai Alva, Jon Jacobson, Corrie Yablon, Rohit Mehra, June Escara-Wilke, Greg Shelley, Evan T Keller,

BACKGROUND:Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes in bone lesions in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib. PATIENTS AND METHODS:Eligible patients with mCRPC involving bone underwent biopsy of ... Read more >>

Clin Genitourin Cancer (Clinical genitourinary cancer)
[2020, 18(4):332-339.e2]

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Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases.

Lingxin Zhu, Yi Tang, Xiao-Yan Li, Evan T Keller, Jingwen Yang, Jung-Sun Cho, Tamar Y Feinberg, Stephen J Weiss,

Osteoclasts actively remodel both the mineral and proteinaceous components of bone during normal growth and development as well as pathologic states ranging from osteoporosis to bone metastasis. The cysteine proteinase cathepsin K confers osteoclasts with potent type I collagenolytic activity; however, cathepsin K-null mice, as well as cathepsin K-mutant humans, ... Read more >>

Sci Transl Med (Science translational medicine)
[2020, 12(529):]

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Macrofluidic recirculating model of skeletal metastasis.

Takahiro Osawa, Wenchu Wang, Jinlu Dai, Evan T Keller,

While microfluidic systems model aspects of metastasis, they are limited to artificially created tissues of limited complexity. We set out to develop an in vitro model of tumor cell migration from a primary tumor to a distant site that allows use of tissue. Accordingly, we created a macrofluidic model using ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):14979]

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SNV identification from single-cell RNA sequencing data.

Patricia M Schnepp, Mengjie Chen, Evan T Keller, Xiang Zhou,

Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being able to call single nucleotide variants (SNVs) from scRNA-seq data ... Read more >>

Hum. Mol. Genet. (Human molecular genetics)
[2019, 28(21):3569-3583]

Cited: 1 time

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Notch3 promotes prostate cancer-induced bone lesion development via MMP-3.

Sourik S Ganguly, Galen Hostetter, Lin Tang, Sander B Frank, Kathylynn Saboda, Rohit Mehra, Lisha Wang, Xiaohong Li, Evan T Keller, Cindy K Miranti,

Prostate cancer metastases primarily localize in the bone where they induce a unique osteoblastic response. Elevated Notch activity is associated with high-grade disease and metastasis. To address how Notch affects prostate cancer bone lesions, we manipulated Notch expression in mouse tibia xenografts and monitored tumor growth, lesion phenotype, and the ... Read more >>

Oncogene (Oncogene)
[2020, 39(1):204-218]

Cited: 2 times

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Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA.

Huajiao Guo, Fuhao Wang, Yuwen Diao, Zhe Zhang, Qiuyan Chen, Chao-Nan Qian, Evan T Keller, Jian Zhang, Yi Lu,

Notch pathway is a highly conserved cell signaling system that plays very important roles in controlling multiple cell differentiation processes during embryonic and adult life. Multiple lines of evidence support the oncogenic role of Notch signaling in several human solid cancers; however, the pleiotropic effects and molecular mechanisms of Notch ... Read more >>

Mol. Carcinog. (Molecular carcinogenesis)
[2019, 58(10):1886-1896]

Cited: 2 times

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Targeted Notch1 inhibition with a Notch1 antibody, OMP-A2G1, decreases tumor growth in two murine models of prostate cancer in association with differing patterns of DNA damage response gene expression.

Aqila A Ahmed, Tyler Robinson, Monica Palande, June Escara-Wilke, Jinlu Dai, Evan T Keller,

Notch plays a protumorigenic role in many cancers including prostate cancer (PCa). Global notch inhibition of multiple Notch family members using γ-secretase inhibitors has shown efficacy in suppressing PCa growth in murine models. However, global Notch inhibition is associated with marked toxicity due to the widespread function of many different ... Read more >>

J. Cell. Biochem. (Journal of cellular biochemistry)
[2019, 120(10):16946-16955]

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Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone.

Weiping Liang, Fuhao Wang, Qiuyan Chen, Jinlu Dai, June Escara-Wilke, Evan T Keller, Johann Zimmermann, Ni Hong, Yi Lu, Jian Zhang,

BACKGROUND:The processes of prostate cancer (PCa) invasion and metastasis are facilitated by proteolytic cascade involving multiple proteases, such as matrix metalloproteinases, serine proteases and cysteine proteases including cathepsin K (CatK). CatK is predominantly secreted by osteoclasts and specifically degrades collagen I leading to bone destruction. PCa and breast cancer preferentially ... Read more >>

J. Cancer Res. Clin. Oncol. (Journal of cancer research and clinical oncology)
[2019, 145(8):1999-2012]

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A surgical orthotopic approach for studying the invasive progression of human bladder cancer.

Guadalupe Lorenzatti Hiles, Angelica L Cates, Layla El-Sawy, Kathleen C Day, Luke J Broses, Amy L Han, Hannah L Briggs, Amir Emamdjomeh, Andrew Chou, Ethan V Abel, Monica Liebert, Phillip L Palmbos, Aaron M Udager, Evan T Keller, Mark L Day,

The invasion of bladder cancer into the sub-urothelial muscle and vasculature are key determinants leading to lethal metastatic progression. However, the molecular basis is poorly understood, partly because of the lack of uncomplicated and reliable models that recapitulate the biology of locally invasive disease. We developed a surgical grafting technique, ... Read more >>

Nat Protoc (Nature protocols)
[2019, 14(3):738-755]

Cited: 2 times

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Prostate cancer promotes a vicious cycle of bone metastasis progression through inducing osteocytes to secrete GDF15 that stimulates prostate cancer growth and invasion.

Wenchu Wang, Xin Yang, Jinlu Dai, Yi Lu, Jian Zhang, Evan T Keller,

Bone is the most frequent site of prostate cancer (PCa) metastasis; however, little is known about the role of the most common cell in bone, the osteocyte (OCy), in cancer biology. In this study we explored the crosstalk between PCa cells and OCys to determine if it contributes to PCa ... Read more >>

Oncogene (Oncogene)
[2019, 38(23):4540-4559]

Cited: 3 times

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Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-κB signaling.

Hai-Bo Tong, Chun-Lin Zou, Si-Yuan Qin, Jie Meng, Evan T Keller, Jian Zhang, Yi Lu,

Prostate cancer preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. To explore the effects of a bone-mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we used osteoblast differentiation medium (ODM; minimal essential medium alpha supplemented with L-ascorbic acid) to mimic the bone microenvironment. ... Read more >>

J Biomed Res (Journal of biomedical research)
[2018, 32(5):343-353]

Cited: 2 times

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Novel CIL-102 derivatives as potential therapeutic agents for docetaxel-resistant prostate cancer.

Dannah R Miller, Cherng-Chyi Tzeng, Trey Farmer, Evan T Keller, Steve Caplan, Yu-Shuin Chen, Yeh-Long Chen, Ming-Fong Lin,

The standard-of-care treatment for metastatic prostate cancer (PCa) is androgen deprivation therapy (ADT). Nevertheless, most tumors eventually relapse and develop into lethal castration-resistant prostate cancer (CRPC). Docetaxel is a FDA-approved agent for the treatment of CRPC; however, the tumor often quickly develops resistance to this drug. Thus, there is an ... Read more >>

Cancer Lett. (Cancer letters)
[2018, 436:96-108]

Cited: 1 time

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Targeted DNA and RNA Sequencing of Paired Urothelial and Squamous Bladder Cancers Reveals Discordant Genomic and Transcriptomic Events and Unique Therapeutic Implications.

Daniel H Hovelson, Aaron M Udager, Andrew S McDaniel, Petros Grivas, Phillip Palmbos, Shuzo Tamura, Lorena Lazo de la Vega, Ganesh Palapattu, Brendan Veeneman, Layla El-Sawy, Seth E Sadis, Todd M Morgan, Jeffrey S Montgomery, Alon Z Weizer, Kathleen C Day, Nouri Neamati, Monica Liebert, Evan T Keller, Mark L Day, Rohit Mehra, Scott A Tomlins,

BACKGROUND:Integrated molecular profiling has identified intrinsic expression-based bladder cancer molecular subtypes. Despite frequent histological diversity, robustness of subtypes in paired conventional (urothelial) and squamous components of the same bladder tumor has not been reported. OBJECTIVE:To assess the impact of histological heterogeneity on expression-based bladder cancer subtypes. DESIGN, SETTING, AND PARTICIPANTS:We ... Read more >>

Eur. Urol. (European Urology)
[2018, 74(6):741-753]

Cited: 8 times

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Crosstalk Between Androgen-sensitive and Androgen-insensitive Prostate Cancer Cells.

Yuta Takezawa, Kouji Izumi, Kazuaki Machioka, Hiroaki Iwamoto, Renato Naito, Tomoyuki Makino, Suguru Kadomoto, Ariunbold Natsagdorj, Yoshifumi Kadono, Evan T Keller, Jian Zhang, Atsushi Mizokami,

To investigate how androgen-sensitive LNCaP cells crosstalk with androgen-insensitive DU145 or PC-3 cells.The numbers of LNCaP cells were counted when co-cultured with DU145 or PC-3 cells and vise versa. Androgen receptor (AR) activity in LNCaP cells was examined by luciferase reporter assay after transfection with a luciferase reporter driven by ... Read more >>

Anticancer Res. (Anticancer research)
[2018, 38(4):2045-2055]

Cited: 2 times

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Establishment and characterization of two cabazitaxel-resistant prostate cancer cell lines.

Kazuaki Machioka, Kouji Izumi, Yoshifumi Kadono, Hiroaki Iwamoto, Renato Naito, Tomoyuki Makino, Suguru Kadomoto, Ariunbold Natsagdorj, Evan T Keller, Jian Zhang, Atsushi Mizokami,

Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel treatment, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. Then we tried to establish cabazitaxel-resistant CRPC cell lines and ... Read more >>

Oncotarget (Oncotarget)
[2018, 9(22):16185-16196]

Cited: 7 times

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Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone.

Hernan Roca, Jacqueline D Jones, Marta C Purica, Savannah Weidner, Amy J Koh, Robert Kuo, John E Wilkinson, Yugang Wang, Stephanie Daignault-Newton, Kenneth J Pienta, Todd M Morgan, Evan T Keller, Jacques E Nör, Lonnie D Shea, Laurie K McCauley,

During tumor progression, immune system phagocytes continually clear apoptotic cancer cells in a process known as efferocytosis. However, the impact of efferocytosis in metastatic tumor growth is unknown. In this study, we observed that macrophage-driven efferocytosis of prostate cancer cells in vitro induced the expression of proinflammatory cytokines such as ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(1):248-266]

Cited: 22 times

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Cytotoxic necrotizing factor 1 promotes prostate cancer progression through activating the Cdc42-PAK1 axis.

Yaxiu Guo, Zhisong Zhang, Huiting Wei, Jingyu Wang, Junqiang Lv, Kai Zhang, Evan T Keller, Zhi Yao, Quan Wang,

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections and plays a role in prostatic carcinogenesis and prostate cancer (PCa) progression. However, the mechanisms through which UPEC promotes PCa development and progression are unclear. Cytotoxic necrotizing factor 1 (CNF1) is one of the most important UPEC toxins ... Read more >>

J. Pathol. (The Journal of pathology)
[2017, 243(2):208-219]

Cited: 6 times

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Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling.

Wenchu Wang, Lihui Wang, Atsushi Mizokami, Junlin Shi, Chunlin Zou, Jinlu Dai, Evan T Keller, Yi Lu, Jian Zhang,

The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker ... Read more >>

Chin J Cancer (Chinese journal of cancer)
[2017, 36(1):35]

Cited: 13 times

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Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression.

Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller,

Integrins that contain an integrin αV subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine whether abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin αV impacts, prostate cancer progression. To evaluate this, prostate cancer cells were treated with DI17E6 ... Read more >>

Mol. Cancer Res. (Molecular cancer research : MCR)
[2017, 15(7):875-883]

Cited: 7 times

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Litchi seed extracts diminish prostate cancer progression via induction of apoptosis and attenuation of EMT through Akt/GSK-3β signaling.

Hongwei Guo, Hua Luo, Hebao Yuan, Yudui Xia, Pan Shu, Xin Huang, Yi Lu, Xia Liu, Evan T Keller, Duxin Sun, Jiagang Deng, Jian Zhang,

Litchi (Litchi chinensisSonnnerat, Sapindaceae), known as Chinese Cherry, is a subtropical fruit tree originating from southern China. Litchi seed extracts have diverse pharmacological effects, including anticancer. However, its anticancer effects and mechanisms on prostate cancer have not been determined. In this study, we used n-butyl alcohol extract of Litchi seed ... Read more >>

Sci Rep (Scientific reports)
[2017, 7:41656]

Cited: 14 times

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Immune mediators in the tumor microenvironment of prostate cancer.

Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller,

Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through ... Read more >>

Chin J Cancer (Chinese journal of cancer)
[2017, 36(1):29]

Cited: 14 times

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Metformin targets multiple signaling pathways in cancer.

Yong Lei, Yanhua Yi, Yang Liu, Xia Liu, Evan T Keller, Chao-Nan Qian, Jian Zhang, Yi Lu,

Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, ... Read more >>

Chin J Cancer (Chinese journal of cancer)
[2017, 36(1):17]

Cited: 26 times

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