Prostate Cell News Volume 4.22 | Jun 14 2013

LABORATORY RESEARCH

Knockdown of the Co-Chaperone SGTA Results in the Suppression of Androgen and PI3K/AKT Signaling and Inhibition of Prostate Cancer Cell Proliferation
Scientists utilized siRNA coupled with genome-wide expression profiling to investigate the biological significance of small glutamine-rich tetratricopeptide repeat containing protein alpha (SGTA) in prostate cancer (PCa), and its influence on androgen receptor signaling. Knockdown of SGTA for 72h in PCa C4-2B cells significantly altered expression of >1900 genes and reduced cell proliferation. [Int J Cancer] Abstract

Redox Cycling of Endogenous Copper by Thymoquinone Leads to ROS-Mediated DNA Breakage and Consequent Cell Death: Putative Anticancer Mechanism of Antioxidants
Using human peripheral lymphocytes and comet assay, scientists showed that thymoquinone (TQ) is able to cause oxidative cellular DNA breakage. Such a DNA breakage can be inhibited by copper-chelating agents, neocuproine and bathocuproine, and scavengers of reactive oxygen species (ROS). Further, it was seen that TQ targets cellular copper in prostate cancer cell lines leading to a prooxidant cell death. [Cell Death Dis]
Full Article

The Antitumor Lignan Nortrachelogenin Sensitizes Prostate Cancer Cells to TRAIL-Induced Cell Death by Inhibition of the AKT Pathway and Growth Factor Signaling
Scientists report that the lignan nortrachelogenin (NTG) is the most efficient of the 27 tested lignan compounds in sensitizing prostate cancer cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-induced apoptosis. Importantly, pretreatment with NTG does not sensitize a non-malignant prostate cell line to TRAIL-induced cell death. [Biochem Pharmacol] Abstract | Graphical Abstract

Aptamer-Conjugated Nanorods for Targeted Photothermal Therapy of Prostate Cancer Stem Cells
Aptamers selected against DU145 prostate cancer cells and their subpopulation of cancer stem cells were linked to the surfaces of gold nanorods, and the resulting conjugates were successfully used to target and kill both cancer cells and cancer stem cells by near-infrared laser irradiation. [Chem Asian J] Abstract

PSMA Specific Single Chain Antibody-Mediated Targeted Knockdown of Notch1 Inhibits Human Prostate Cancer Cell Proliferation and Tumor Growth
Researchers evaluated whether small interfering RNA (siRNA) can be efficiently delivered into prostate-specific membrane antigen (PSMA)-positive prostate cancer cells using two fusion proteins, s-tP and sFH-tP. These fusion proteins are composed of an anti-PSMA single chain antibody (scFv, abbreviated as an “s”) and a truncated protamine (tP); and in sFH-tP a furin cleavage site and an HA2 fragment sequence (FH) were inserted between the scFv and tP domains. Their results showed that siRNA can be specifically delivered into PSMA-positive LNCaP cells by these two fusion proteins, with the sFH-tP fusion protein being more effective. [Cancer Lett] Abstract

Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy
Researchers evaluated the use of the insect virus, baculovirus (BV), as a novel vector for human prostate cancer gene therapy. BV was capable of preferentially transducing invasive malignant prostate cancer cell lines compared to early stage cancers and non-malignant samples, a restriction that was not a function of nuclear import. [PLoS One] Full Article

Different Expression Patterns and Functions of Acetylated and Unacetylated Klf5 in the Proliferation and Differentiation of Prostatic Epithelial Cells
Investigators evaluated the expression and function of KLF5 in prostatic epithelial homeostasis and tumorigenesis using mouse prostates and human prostate epithelial cells in 3-D culture. Histological and molecular analyses demonstrated that unacetylated-Klf5 was expressed in basal or undifferentiated cells, whereas acetylated-Klf5 was expressed primarily in luminal and/or differentiated cells. [PLoS One]
Full Article

Cathepsin L Inhibition by the Small Molecule KGP94 Suppresses Tumor Microenvironment Enhanced Metastasis Associated Cell Functions of Prostate and Breast Cancer Cells
Investigators evaluated the ability of KGP94, a small molecule inhibitor of Cathepsin L, to impair the metastatic phenotype of prostate and breast cancer cells both under normal and aberrant microenvironmental conditions. [Clin Exp Metastasis] Abstract

CLINICAL RESEARCH

Pre-Diagnostic Circulating Markers of Inflammation and Risk of Prostate Cancer
The authors investigated the associations of three common markers of inflammation and the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow-up period of 24 years, 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. [Int J Cancer] Abstract

Fat Intake after Diagnosis and Risk of Lethal Prostate Cancer and All-Cause Mortality
Researchers examined postdiagnostic fat intake in relation to lethal prostate cancer and all-cause mortality. Among men with nonmetastatic prostate cancer, replacing carbohydrates and animal fat with vegetable fat may reduce the risk of all-cause mortality. [JAMA Intern Med] Abstract | Press Release

Prostate Cancer Progression after Androgen Deprivation Therapy: Mechanisms of Castrate Resistance and Novel Therapeutic Approaches
The authors summarize the current literature on the biology and treatment of castrate-resistant prostate cancer. [Oncogene] Full Article

Androgen Receptor Functions in Castration-Resistant Prostate Cancer and Mechanisms of Resistance to New Agents Targeting the Androgen Axis
The authors outline androgen receptor (AR) functions that contribute to prostate cancer (PCa) development and progression, the roles of intratumoral androgen synthesis and AR structural alterations in driving AR activity in castration-resistant PCa, mechanisms of action for abiraterone and enzalutamide, and possible mechanisms of resistance to these agents. [Oncogene] Abstract

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Tumor Immunotherapy Efficacy Increased in Both Breast and Prostate Cancer Preclinical Models with Addition of Galectin Inhibitor
Galectin Therapeutics announced that preclinical studies have shown that combining the galectin inhibitor GR-MD-02 with monoclonal antibodies that function as immune checkpoint blockade inhibitors enhance shrinkage of prostate and breast cancer tumors. [Galectin Therapeutics Inc.] Press Release

Prostate Cancer Canada Awards $5 Million Inaugural Movember Team Grant to Dr. Ralph Buttyan at the Vancouver Prostate Centre
The 2013 Movember Team Grant has been awarded to Dr. Ralph Buttyan of the Vancouver Prostate Centre, who leads a team of 22 co-investigators. [Vancouver Prostate Centre] Press Release

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US Supreme Court Rules Patents on ‘Natural’ Human Genes Invalid
In one of the most anxiously awaited court decisions of the year, the US Supreme Court unanimously struck down patents on isolated, natural human genes. [Supreme Court, United States] Press Release | Syllabus

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW American Association for Cancer Research (AACR): Frontiers in Basic Cancer Research
September 18-22, 2013
National Harbor, United States

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NEW Postdoctoral Fellow – Drug Discovery/GU Oncology (Moffitt Cancer Center & Research Institute)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Research Scientist – Prostate Cancer Vaccine Development (Nuffield Department of Clinical Medicine, The Jenner Institute)

Postdoctoral Position – Mechanisms that Govern Prostate Cancer Progression (University of Copenhagen)

Postdoctoral Position – Castrate Resistant Prostate Cancer (Mount Sinai School)

PCUK Funded PhD Studentship – Prostate Cancer (Barts Cancer Institute, Queen Mary University of London)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Studentship – Investigation into Chemokine Receptor Induced Cell Migration (University of East Anglia)

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