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https://www.readbyqxmd.com/read/28319065/the-drebrin-eb3-pathway-drives-invasive-activity-in-prostate-cancer
#1
A E Dart, D C Worth, G Muir, A Chandra, J D Morris, C McKee, C Verrill, R J Bryant, P R Gordon-Weeks
Prostate cancer is the most common cancer in men and the metastatic form of the disease is incurable. We show here that the drebrin/EB3 pathway, which co-ordinates dynamic microtubule/actin filament interactions underlying cell shape changes in response to guidance cues, plays a role in prostate cancer cell invasion. Drebrin expression is restricted to basal epithelial cells in benign human prostate but is upregulated in luminal epithelial cells in foci of prostatic malignancy. Drebrin is also upregulated in human prostate cancer cell lines and co-localizes with actin filaments and dynamic microtubules in filopodia of pseudopods of invading cells under a chemotactic gradient of the chemokine CXCL12...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28303694/lutetium-177-psma-radionuclide-therapy-for-men-with-prostate-cancer-a-review-of-the-current-literature-and-discussion-of-practical-aspects-of-therapy
#2
REVIEW
Louise Emmett, Kathy Willowson, John Violet, Jane Shin, Ashley Blanksby, Jonathan Lee
Prostate-specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high-binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides...
March 2017: Journal of Medical Radiation Sciences
https://www.readbyqxmd.com/read/28301262/-213-bi-labeled-prostate-specific-membrane-antigen-targeting-agents-induce-dna-double-strand-breaks-in-prostate-cancer-xenografts
#3
Julie Nonnekens, Kristell L S Chatalic, Janneke D M Molkenboer-Kuenen, Cecile E M T Beerens, Frank Bruchertseifer, Alfred Morgenstern, Joke Veldhoven-Zweistra, Margret Schottelius, Hans-Jürgen Wester, Dik C van Gent, Wytske M van Weerden, Otto C Boerman, Marion de Jong, Sandra Heskamp
BACKGROUND: Up to now, prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy mainly focused on β-emitting radionuclides. Herein, two new (213)Bi-labeled agents for PSMA-targeted α therapy of prostate cancer (PCa) are reported. METHODS: The biodistribution of (213)Bi-labeled small-molecule inhibitor PSMA I&T and nanobody JVZ-008 was evaluated in mice bearing PSMA-positive LNCaP xenografts. DNA damage response was followed using LNCaP cells and LNCaP xenografts...
March 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28296775/giant-hepatic-metastasis-in-a-patient-with-coin-like-small-cell-lung-carcinoma-incidentally-diagnosed-at-autopsy-a-case-report
#4
Decebal Fodor, Simona Gurzu, Anca Otilia Contac, Ioan Jung
RATIONALE: Encephalopathy is a rare complication of hepatic metastases. In this paper we present a case of a patient with lung cancer and metastatic-related giant hepatomegaly. PATIENT CONCERNS: A 78-year-old previously healthy male was admitted in the Emergency room in hepatic coma. DIAGNOSES: The abdominal CT scan examination revealed a huge liver filled with solid nodules. INTERVENTIONS: No interventions were performed...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28292895/diagnosis-of-prostate-cancer-by-desorption-electrospray-ionization-mass-spectrometric-imaging-of-small-metabolites-and-lipids
#5
Shibdas Banerjee, Richard N Zare, Robert J Tibshirani, Christian A Kunder, Rosalie Nolley, Richard Fan, James D Brooks, Geoffrey A Sonn
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28289210/phosphorylation-induced-conformational-dynamics-in-an-intrinsically-disordered-protein-and-potential-role-in-phenotypic-heterogeneity
#6
Prakash Kulkarni, Mohit Kumar Jolly, Dongya Jia, Steven M Mooney, Ajay Bhargava, Luciane T Kagohara, Yihong Chen, Pengyu Hao, Yanan He, Robert W Veltri, Alexander Grishaev, Keith Weninger, Herbert Levine, John Orban
Intrinsically disordered proteins (IDPs) that lack a unique 3D structure and comprise a large fraction of the human proteome play important roles in numerous cellular functions. Prostate-Associated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcription factor. Homeodomain-Interacting Protein Kinase 1 (HIPK1) phosphorylates PAGE4 at S9 and T51, but only T51 is critical for its activity. Here, we identify a second kinase, CDC-Like Kinase 2 (CLK2), which acts on PAGE4 and hyperphosphorylates it at multiple S/T residues, including S9 and T51...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28285791/immunohistochemical-study-of-the-neural-development-transcription-factors-ttf1-ascl1-and-brn2-in-neuroendocrine-prostate-tumours
#7
E Rodríguez-Zarco, A Vallejo-Benítez, S Umbría-Jiménez, S Pereira-Gallardo, S Pabón-Carrasco, A Azueta, R González-Cámpora, P S Espinal, A García-Escudero
OBJECTIVE: Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate...
March 9, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28282546/overexpression-of-the-a-disintegrin-and-metalloproteinase-adam15-is-linked-to-a-small-but-highly-aggressive-subset-of-prostate-cancers
#8
Christoph Burdelski, Michael Fitzner, Claudia Hube-Magg, Martina Kluth, Asmus Heumann, Ronald Simon, Till Krech, Till Clauditz, Franziska Büscheck, Stefan Steurer, Corinna Wittmer, Andrea Hinsch, Andreas M Luebke, Frank Jacobsen, Sarah Minner, Maria Christina Tsourlakis, Burkhard Beyer, Thomas Steuber, Imke Thederan, Guido Sauter, Jakob Izbicki, Thorsten Schlomm, Waldemar Wilczak
The A Disintegrin and Metalloproteinase (ADAM) family of endopeptidases plays a role in many solid cancers and includes promising targets for anticancer therapies. Deregulation of ADAM15 has been linked to tumor aggressiveness and cell line studies suggest that ADAM15 overexpression may also be implicated in prostate cancer. To evaluate the impact of ADAM15 expression and its relationship with key genomic alterations, a tissue microarray containing 12,427 prostate cancers was analyzed by immunohistochemistry...
March 7, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28280929/molecular-mechanisms-of-therapy-resistance-in-solid-tumors-chasing-moving-targets
#9
REVIEW
Laura J Tafe
The goal of personalized cancer therapy is to treat tumors based on genomic aberrations that drive their survival and progression. Most patients who receive targeted therapies typically develop resistance and disease progression within a year's time. This review focuses on the heterogeneous mechanisms of therapy resistance to tyrosine kinase inhibitors, endocrine/hormone therapy and checkpoint blockade using non-small cell lung cancer, breast and castration-resistant prostate cancer, and melanoma as classical examples, respectively...
March 10, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28273495/-99m-tc-labeling-and-evaluation-of-a-hynic-modified-small-molecular-inhibitor-of-prostate-specific-membrane-antigen
#10
Xiaoping Xu, Jianping Zhang, Silong Hu, Simin He, Xiao Bao, Guang Ma, Jianmin Luo, Jingyi Cheng, Yingjian Zhang
INTRODUCTION: Prostate-specific membrane antigen (PSMA) is a well-established target in the development of radiopharmaceuticals for the diagnosis and therapy of prostate cancer (PCa). In this study, we evaluated a novel (99m)Tc-labeled small molecular inhibitor of PSMA. METHODS: This new small-molecular inhibitor of PSMA, 6-hydrazinonicotinate-Aminocaproic acid-Lysine-Urea-Glutamate (HYNIC-ALUG) was radiolabeled by (99m)Tc and was evaluated both in vitro and in vivo using PCa models (PC-3 and LNCaP)...
January 28, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28273073/src-2-mediated-coactivation-of-anti-tumorigenic-target-genes-suppresses-myc-induced-liver-cancer
#11
Shruthy Suresh, Deniz Durakoglugil, Xiaorong Zhou, Bokai Zhu, Sarah A Comerford, Chao Xing, Xian-Jin Xie, Brian York, Kathryn A O'Donnell
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28272894/1-4-substituted-triazoles-as-nonsteroidal-anti-androgens-for-prostate-cancer-treatment
#12
Claudia Ferroni, Antonella Pepe, Yeong Sang Kim, Sunmin Lee, Andrea Guerrini, Marco Daniele Parenti, Anna Tesei, Alice Zamagni, Michela Cortesi, Nadia Zaffaroni, Michelandrea De Cesare, Giovanni Luca Beretta, Jane B Trepel, Sanjay V Malhotra, Greta Varchi
Prostate cancer (PC) is the fifth leading cause of cancer death in men, and the androgen receptor (AR) represents the primary target for PC treatment, even though the disease frequently progresses toward androgen-independent forms. Most of the commercially available nonsteroidal antiandrogens show a common scaffold consisting of two aromatic rings connected by a linear or a cyclic spacer. By taking advantage of a facile, one-pot click chemistry reaction, we report herein the preparation of a small library of novel 1,4-substituted triazoles with AR antagonistic activity...
March 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28270206/meis1-inhibits-clear-cell-renal-cell-carcinoma-cells-proliferation-and-in-vitro-invasion-or-migration
#13
Jie Zhu, Liang Cui, Axiang Xu, Xiaotao Yin, Fanglong Li, Jiangping Gao
BACKGROUND: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. METHODS: MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28267456/clinical-experience-with-18-f-labeled-small-molecule-inhibitors-of-prostate-specific-membrane-antigen
#14
REVIEW
Steven P Rowe, Michael A Gorin, Roberto A Salas Fragomeni, Alexander Drzezga, Martin G Pomper
Prostate cancer (PCa) is the most common noncutaneous malignancy diagnosed in men. Despite the large number of men who will suffer from PCa at some point during their lives, conventional imaging modalities for this important disease (contrast-enhanced computed tomography, bone scan, and MR imaging) have provided only marginal to moderate success in appropriately guiding patient management in certain clinical contexts. In this review, the authors discuss radiofluorinated small molecule radiotracers that have been developed to bind to the transmembrane glycoprotein prostate-specific membrane antigen, a target that is nearly universally overexpressed on PCa epithelial cells...
April 2017: PET Clinics
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#15
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28255844/nanosomal-docetaxel-lipid-suspension-a-guide-to-its-use-in-cancer
#16
Kate McKeage
Nanosomal docetaxel lipid suspension (NDLS) [DoceAqualip] is a novel formulation of docetaxel approved in India for the treatment of breast cancer, hormone-refractory prostate cancer, locally advanced squamous cell carcinoma of the head and neck, non-small cell lung cancer and advanced gastric adenocarcinoma. The lipid-based delivery system of NDLS eliminates the need for polysorbate 80 and ethanol, which are contained in the conventional docetaxel formulation and are associated with hypersensitivity reactions and infusion-related toxicities...
March 2, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28255242/braf-v600-mutations-in-solid-tumors-other-than-metastatic-melanoma-and-papillary-thyroid-cancer-or-multiple-myeloma-a-screening-study
#17
Allen L Cohn, Bann-Mo Day, Sarang Abhyankar, Edward McKenna, Todd Riehl, Igor Puzanov
BACKGROUND: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma harboring activating BRAF(V600) mutations for enrollment in a vemurafenib clinical study. METHODS: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAF(V600) mutations by bidirectional direct Sanger sequencing...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28249898/defining-cancer-subpopulations-by-adaptive-strategies-rather-than-molecular-properties-provides-novel-insights-into-intratumoral-evolution
#18
Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro Enrizues-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C Lloyd, Marilyn M Bui, Joel S Brown, Alexander Ra Anderson, Robert J Gillies, Robert A Gatenby
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche-construction adaptive strategies that remained stable in culture: (1) Invasive cells that produce an acidic environment via upregulated aerobic glycolysis, and (2) Non-invasive cells that were angiogenic and metabolically near-normal...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28245430/man2a1-fer-fusion-gene-is-expressed-by-human-liver-and-other-tumor-types-and-has-oncogenic-activity-in-mice
#19
Zhang-Hui Chen, Yan P Yu, Junyan Tao, Silvia Liu, George Tseng, Michael Nalesnik, Ronald Hamilton, Rohit Bhargava, Joel B Nelson, Arjun Pennathur, Satdarshan P Monga, James D Luketich, George K Michalopoulos, Jian-Hua Luo
BACKGROUND & AIMS: Human tumors and liver cancer cell lines express the product of a fusion between the first 13 exons in the mannosidase α class 2A member 1 gene (MAN2A1) and the last 6 exons in the FER tyrosine kinase gene (FER), called MAN2A1-FER. We investigated whether MAN2A1-FER is expressed by human liver tumors and its role in liver carcinogenesis. METHODS: We performed reverse transcription polymerase chain reaction analyses of 102 non-small cell lung tumors, 61 ovarian tumors, 70 liver tumors, 156 glioblastoma multiform samples, 27 esophageal adenocarcinomas, and 269 prostate cancer samples, as well as 10 nontumor liver tissues and 20 nontumor prostate tissues, collected at the University of Pittsburgh...
February 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28240870/a-multifunctional-envelope-type-sirna-delivery-nanoparticle-platform-for-prostate-cancer-therapy
#20
Xiaoding Xu, Jun Wu, Yanlan Liu, Phei Er Saw, Wei Tao, Mikyung Yu, Harshal R Zope, Michelle Si, Amanda Victorious, Jonathan Rasmussen, Dana Ayyash, Omid C Farokhzad, Jinjun Shi
With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular non-liver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery...
February 27, 2017: ACS Nano
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