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https://www.readbyqxmd.com/read/28327152/trim8-restores-p53-tumour-suppressor-function-by-blunting-n-myc-activity-in-chemo-resistant-tumours
#1
Francesca Mastropasqua, Flaviana Marzano, Alessio Valletti, Italia Aiello, Giuseppe Di Tullio, Annalisa Morgano, Sabino Liuni, Elena Ranieri, Luisa Guerrini, Giuseppe Gasparre, Elisabetta Sbisà, Graziano Pesole, Antonio Moschetta, Mariano Francesco Caratozzolo, Apollonia Tullo
BACKGROUND: TRIM8 plays a key role in controlling the p53 molecular switch that sustains the transcriptional activation of cell cycle arrest genes and response to chemotherapeutic drugs. The mechanisms that regulate TRIM8, especially in cancers like clear cell Renal Cell Carcinoma (ccRCC) and colorectal cancer (CRC) where it is low expressed, are still unknown. However, recent studies suggest the potential involvement of some microRNAs belonging to miR-17-92 and its paralogous clusters, which could include TRIM8 in a more complex pathway...
March 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28325666/development-of-novel-patient-derived-preclinical-models-from-malignant-effusions-in-patients-with-tyrosine-kinase-inhibitor-resistant-clear-cell-renal-cell-carcinoma
#2
Jiryeon Jang, Oliver Rath, Julia Schueler, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Ghee-Young Kwon, Woong Yang Park, Jeeyun Lee, Se Hoon Park
PURPOSE: Although targeting angiogenesis with tyrosine kinase inhibitors (TKIs) has become standard of care in the treatment of clear cell renal cell carcinoma (RCC), resistance mechanism are not fully understood, and there is a need to develop new therapeutic options overcoming them. METHODS AND MATERIALS: To develop a preclinical model that predicts clinical activity of novel agents in 19 RCC patients, we established patient-derived cell (PDC) and xenograft (PDX) models derived from malignant effusions or surgical specimen...
March 15, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28325293/a-pirna-like-small-rna-induces-chemoresistance-to-cisplatin-based-therapy-by-inhibiting-apoptosis-in-lung-squamous-cell-carcinoma
#3
Yuyan Wang, Tyler Gable, Mark Z Ma, David Clark, Jun Zhao, Yi Zhang, Wei Liu, Li Mao, Yuping Mei
Lung cancer is the leading cause of cancer-related death worldwide. Although advanced drugs have benefitted patients, therapeutic success has largely been hampered because of rapid development of resistance. Here we report that PIWI-interacting RNA likes (piR-Ls), a novel type of functional sncRNAs, play key roles in chemoresistance to cisplatin (CDDP)-based chemotherapy in lung squamous cell carcinoma (LSCC). piR-L-138 was upregulated upon CDDP-based chemotherapy both in LSCC cells and in patient-derived xenograft (PDX) LSCC models...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28321824/therapeutic-hypothesis-testing-with-rodent-brain-tumor-models
#4
REVIEW
Derek A Wainwright, Craig M Horbinski, Rintaro Hashizume, C David James
The development and application of rodent models for preclinical testing of novel therapeutics and approaches for treating brain tumors has been a mainstay of neuro-oncology preclinical research for decades, and is likely to remain so into the foreseeable future. These models serve as an important point of entry for analyzing the potential efficacy of experimental therapies that are being considered for clinical trial evaluation. Although rodent brain tumor models have seen substantial change, particularly since the introduction of genetically engineered mouse models, certain principles associated with the use of these models for therapeutic testing are enduring, and form the basis for this review...
March 20, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28320429/chrysin-inhibited-tumor-glycolysis-and-induced-apoptosis-in-hepatocellular-carcinoma-by-targeting-hexokinase-2
#5
Dong Xu, Junzhe Jin, Hao Yu, Zheming Zhao, Dongyan Ma, Chundong Zhang, Honglei Jiang
BACKGROUND: Hexokinase-2(HK-2) plays dual roles in glucose metabolism and mediation of cell apoptosis, making it an attractive target for cancer therapy. Chrysin is a natural flavone found in plant extracts which are widely used as herb medicine in China. In the present study, we investigated the antitumor activity of chrysin against hepatocellular carcinoma (HCC) and the role of HK-2 played for chrysin to exert its function. METHODS: The expression of HK-2 in HCC cell line and tumor tissue was examined by western blotting and immunohistochemistry staining...
March 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#6
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28315652/detection-and-elimination-of-corynebacterium-bovis-from-barrier-rooms-by-using-an-environmental-sampling-surveillance-program
#7
Christopher A Manuel, Umarani Pugazhenthi, Shannon P Spiegel, Jori K Leszczynski
Rodent health-monitoring programs based on sampling an IVC system's exhaust air dust (EAD) has enhanced and even replaced traditional sentinels for some rodent pathogens. EAD testing by qPCR assay is an optimal surveillance method for the rapid detection of Corynebacterium bovis-infected immunodeficient mice. Here we demonstrate that an active EAD surveillance program for C. bovis can be used to maintain nude mice C. bovis-free after the transition from historically enzootically infected colonies. During 3 events over 3 y, rapid detection of infection, elimination of infected mice, aggressive quarantine measures, and local decontamination prevented the spread of C...
March 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28315646/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#8
Christopher A Manuel, Stacey M Bagby, Julie A Reisinger, Umarani Pugazhenthi, Todd M Pitts, Stephen B Keysar, John J Arcaroli, Jori K Leszczynski
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as a model for cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retain many of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strains used to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At our institution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infected with C...
March 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28315377/patient-derived-xenografts-a-platform-for-accelerating-translational-research-in-prostate-cancer
#9
Alastair H Davies, Yuzhuo Wang, Amina Zoubeidi
Recently, there has been renewed interest in the development and characterization of patient-derived tumour xenograft (PDX) models. Numerous PDX models have been established for prostate cancer and, importantly, retain the principal molecular, genetic, and histological characteristics of the donor tumour. As such, these models provide significant improvements over standard cell line xenograft models for biological studies, preclinical drug development, and personalized medicine strategies. This review summarizes the current state of the art in this field, illustrating the opportunities and limitations of PDX models in translational prostate cancer research...
March 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#10
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28314175/choosing-wisely-preclinical-test-models-in-the-era-of-precision-medicine
#11
REVIEW
Konrad Klinghammer, Wolfgang Walther, Jens Hoffmann
Through the introduction of a steadily growing variety of preclinical test models drug development and biomarker research has advanced. Next to classical used 2D cell line cultures, tissue-slice cultures, 3D organoid cell cultures, genetically engineered mouse models, cell line derived mouse models and patient derived xenografts may be selected for a specific question. All models harbor advantages and disadvantages. This review focuses on the available preclinical test models, novel developments such as humanized mice and discusses for which question a particular model should be employed...
March 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28302866/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#12
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gomez-Lopez, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs).Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex.Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers...
March 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#13
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28300287/analysis-of-stroma-labeling-during-multiple-passage-of-a-sarcoma-imageable-patient-derived-orthotopic-xenograft-ipdox-in-red-fluorescent-protein-transgenic-nude-mice
#14
Tasuku Kiyuna, Takashi Murakami, Yasunori Tome, Kei Kawaguchi, Kentaro Igarashi, Kentaro Miyake, Fuminori Kanaya, Arun Singh, Fritz C Eilber, Robert M Hoffman
A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice...
March 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28298418/disrupting-the-cd47-sirp%C3%AE-anti-phagocytic-axis-by-a-humanized-anti-cd47-antibody-is-an-efficacious-treatment-for-malignant-pediatric-brain-tumors
#15
Sharareh Gholamin, Siddhartha S Mitra, Abdullah H Feroze, Jie Liu, Suzana A Kahn, Michael Zhang, Rogelio Esparza, Chase Richard, Vijay Ramaswamy, Marc Remke, Anne K Volkmer, Stephen Willingham, Anitha Ponnuswami, Aaron McCarty, Patricia Lovelace, Theresa A Storm, Simone Schubert, Gregor Hutter, Cyndhavi Narayanan, Pauline Chu, Eric H Raabe, Griffith Harsh, Michael D Taylor, Michelle Monje, Yoon-Jae Cho, Ravi Majeti, Jens P Volkmer, Paul G Fisher, Gerald Grant, Gary K Steinberg, Hannes Vogel, Michael Edwards, Irving L Weissman, Samuel H Cheshier
Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28298340/pre-clinical-validation-of-a-selective-anti-cancer-stem-cell-therapy-for-numb-deficient-human-breast-cancers
#16
Daniela Tosoni, Sarah Pambianco, Blanche Ekalle Soppo, Silvia Zecchini, Giovanni Bertalot, Giancarlo Pruneri, Giuseppe Viale, Pier Paolo Di Fiore, Salvatore Pece
The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cells (CSCs). Strikingly, CSC phenotypes in a Numb-knockout mouse model can be reverted by Numb/p53 restoration. Thus, targeting Numb/p53 dysfunction in Numb-deficient human BCs could represent a novel anti-CSC therapy...
March 15, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28296559/the-irony-of-highly-effective-bacterial-therapy-of-a-patient-derived-orthotopic-xenograft-pdox-model-of-ewing-s-sarcoma-which-was-blocked-by-ewing-himself-80%C3%A2-years-ago
#17
Takashi Murakami, Tasuku Kiyuna, Kei Kawaguchi, Kentaro Igarashi, Arun S Singh, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Kentaro Miyake, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jonathan C DeLong, Thinzar M Lwin, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Fritz C Eilber, Robert M Hoffman
William B. Coley developed bacterial therapy of cancer more than 100 years ago and had clinical success. James Ewing, a very famous cancer pathologist for whom the Ewing sarcoma is named, was Coley's boss at Memorial Hospital in New York and terminated Coley's bacterial therapy of cancer. A tumor from a patient with soft-tissue Ewing's sarcoma, who failed doxorubicin (DOX) therapy, was previously implanted in nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the Ewing's sarcoma PDOX was treated with tumor-targeting S...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28292941/preclinical-anti-tumor-efficacy-of-bay-1129980-a-novel-auristatin-based-anti-c4-4a-lypd3-antibody-drug-conjugate-for-the-treatment-of-non-small-cell-lung-cancer
#18
Jörg Willuda, Lars Linden, Hans-Georg Lerchen, Charlotte Kopitz, Beatrix Stelte-Ludwig, Carol Pena, Claudia Lange, Sven Golfier, Christoph Kneip, Patricia E Carrigan, Kirk Mclean, Joachim Schuhmacher, Oliver von Ahsen, Jörg Müller, Frank Dittmer, Rudolf Beier, Sherif El-Sheikh, Jan Tebbe, Gabriele Leder, Heiner Apeler, Rolf Jautelat, Karl Ziegelbauer, Bertolt Kreft
C4.4A (LYPD3) has been identified as a cancer- and metastasis-associated internalizing cell surface protein that is expressed in non-small cell lung cancer (NSCLC), with particularly high prevalence in the squamous cell carcinoma (SCC) subtype. With the exception of skin keratinocytes and esophageal endothelial cells, C4.4A expression is scarce in normal tissues, presenting an opportunity to selectively treat cancers with a C4.4A-directed antibody-drug conjugate (ADC). We have generated BAY 1129980 (C4.4A-ADC), an ADC consisting of a fully human C4...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28292934/maltotriose-conjugation-to-a-chlorin-derivative-enhances-the-antitumor-effects-of-photodynamic-therapy-in-peritoneal-dissemination-of-pancreatic-cancer
#19
Akihisa Kato, Hiromi Kataoka, Shigenobu Yano, Kazuki Hayashi, Noriyuki Hayashi, Mamoru Tanaka, Itaru Naitoh, Tesshin Ban, Katsuyuki Miyabe, Hiromu Kondo, Michihiro Yoshida, Yasuaki Fujita, Yasuki Hori, Makoto Natsume, Takashi Murakami, Atsushi Narumi, Akihiro Nomoto, Aya Naiki-Ito, Satoru Takahashi, Takashi Joh
Peritoneal dissemination is a major clinical issue associated with dismal prognosis and poor quality of life for patients with pancreatic cancer; however, no effective treatment strategies have been established. Herein, we evaluated the effects of photodynamic therapy (PDT) with maltotriose-conjugated chlorin (Mal3-chlorin) in culture and in a peritoneal disseminated mice model of pancreatic cancer. The Mal3-chlorin was prepared as a water-soluble chlorin derivative conjugated with four Mal3 molecules to improve cancer selectivity...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28292264/establishment-of-patient-derived-gastric-cancer-xenografts-a-useful-tool-for-preclinical-evaluation-of-targeted-therapies-involving-alterations-in-her-2-met-and-fgfr2-signaling-pathways
#20
Haiyong Wang, Jun Lu, Jian Tang, Shitu Chen, Kuifeng He, Xiaoxia Jiang, Weiqin Jiang, Lisong Teng
BACKGROUND: Targeted therapies are emerging treatment options for gastric cancer (GC). Patient-derived tumor xenograft(PDX) models of GC closely retain the features of the original clinical cancer, offering a powerful tool for preclinical drug efficacy testing. This study aimed to establish PDX GC models, and explore therapeutics targeting Her2, MET(cMet), and FGFR2, which may assist doctor to select the proper target therapy for selected patients. METHODS: GC tissues from 32 patients were collected and implanted into immuno-deficient mice...
March 14, 2017: BMC Cancer
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