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https://www.readbyqxmd.com/read/28715967/hyperthermia-enhanced-targeted-drug-delivery-using-magnetic-resonance-guided-focussed-ultrasound-a-pre-clinical-study-in-a-genetic-model-of-pancreatic-cancer
#1
Navid Farr, Yak-Nam Wang, Samantha D'Andrea, Frank Starr, Ari Partanen, Kayla M Gravelle, Jeannine S McCune, Linda J Risler, Stella G Whang, Amy Chang, Sunil R Hingorani, Donghoon Lee, Joo Ha Hwang
PURPOSE: The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer. MATERIALS AND METHODS: Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre)...
July 17, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28706193/polydextrose-changes-the-gut-microbiome-and-attenuates-fasting-triglyceride-and-cholesterol-levels-in-western-diet-fed-mice
#2
Ghulam Shere Raza, Heli Putaala, Ashley A Hibberd, Esa Alhoniemi, Kirsti Tiihonen, Kari Antero Mäkelä, Karl-Heinz Herzig
Obesity and dyslipidemia are hallmarks of metabolic and cardiovascular diseases. Polydextrose (PDX), a soluble fiber has lipid lowering effects. We hypothesize that PDX reduces triglycerides and cholesterol by influencing gut microbiota, which in turn modulate intestinal gene expression. C57BL/6 male mice were fed a Western diet (WD) ±75 mg PDX twice daily by oral gavage for 14 days. Body weight and food intake were monitored daily. Fasting plasma lipids, caecal microbiota and gene expression in intestine and liver were measured after 14 days of feeding...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701182/do-we-really-need-to-differentiate-mesenchymal-stem-cells-into-insulin-producing-cells-for-attenuation-of-the-autoimmune-responses-in-type-1-diabetes-immunoprophylactic-effects-of-precursors-to-insulin-producing-cells
#3
Anshu Sharma, Rajni Rani
BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? METHODS: Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines...
July 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28698205/an-fc-engineered-cd19-antibody-eradicates-mrd-in-patient-derived-mll-rearranged-acute-lymphoblastic-leukemia-xenografts
#4
Denis M Schewe, Ameera Alsadeq, Cornelia Sattler, Lennart Lenk, Fotini Vogiatzi, Gunnar Cario, Simon Vieth, Thomas Valerius, Sophia Rosskopf, Fabian Meyersieck, Julia Alten, Martin Schrappe, Martin Gramatzki, Matthias Peipp, Christian Kellner
Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, an Fc engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE) was tested. Patient derived xenografts (PDX) of pediatric MLL-rearranged ALL were established in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28694526/intrapatient-functional-clonality-deconvoluted-by-coupling-intracellular-flow-cytometry-and-next-generation-sequencing-in-human-leukemia
#5
Q Zhang, M C Ball, Y Zhao, M Balasis, C Letson, A Vedder, A F List, P K Epling-Burnette, R S Komrokji, E Padron
The interplay between tumor heterogeneity and microenvironmental factors is a critical mechanism for clonal selection in leukemia. Evidence of unique clonal capacities to engraft within patient-derived xenograft (PDX) models suggests that intrapatient genetic architecture may be defined by functional differences at the clonal level. However, methods to detect functional differences assigned to genetically defined clones remain limited. Here, we describe a scalable method to directly measure the functional properties of clones within the same leukemia patient by coupling intracellular flow cytometry and next-generation sequencing (NGS)...
June 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28692296/leaching-from-palladium-nanoparticles-in-an-ionic-liquid-leads-to-the-formation-of-ionic-monometallic-species
#6
Elena E Zvereva, Sergey A Katsyuba, Paul J Dyson, Alexey V Aleksandrov
Molecular dynamics simulations and DFT calculations suggest that leaching of palladium species from Pd nanoparticles in ionic liquids does not involve "naked" Pd(0) atoms or neutral ArPdX species formed by oxidative addition of arylhalides. Instead, the ionic liquid contributes largely to leaching of ionic PdX(-) or PdAr(+) species.
July 12, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28692052/disrupting-g6pd-mediated-redox-homeostasis-enhances-chemosensitivity-in-colorectal-cancer
#7
H-Q Ju, Y-X Lu, Q-N Wu, J Liu, Z-L Zeng, H-Y Mo, Y Chen, T Tian, Y Wang, T-B Kang, D Xie, M-S Zeng, P Huang, R-H Xu
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28679774/syd985-a-novel-duocarmycin-based-her2-targeting-antibody-drug-conjugate-shows-antitumor-activity-in-uterine-and-ovarian-carcinosarcoma-with-her2-neu-expression
#8
Gulden Menderes, Elena Bonazzoli, Stefania Bellone, Jonathan D Black, Federica Predolini, Francesca Pettinella, Alice Masserdotti, Luca Zammataro, Gary Altwerger, Natalia Buza, Pei Hui, Serena Wong, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
Purpose: Carcinosarcomas (CS) are highly aggressive gynecologic malignancies containing both carcinomatous and sarcomatous elements with heterogeneous HER2/neu expression. We compared the efficacy of SYD985, (Synthon Biopharmaceuticals BV), a novel HER2-targeting antibody-drug conjugate (ADC), to Trastuzumab emtansine (T-DM1, Genentech-Roche) against primary uterine and ovarian CS. <p>Experimental Design: Eight primary CS cell lines were evaluated for HER2/neu surface expression by IHC and gene amplification by FISH assays...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28676760/combined-oral-administration-of-gaba-and-dpp-4-inhibitor-prevents-beta-cell-damage-and-promotes-beta-cell-regeneration-in-mice
#9
Wenjuan Liu, Dong Ok Son, Harry K Lau, Yinghui Zhou, Gerald J Prud'homme, Tianru Jin, Qinghua Wang
γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this hypothesis in a multiple low-dose streptozotocin (STZ)-induced beta cell injury mouse model (MDSD). Male C57BL/6J mice were assigned randomly into four groups: non-treatment diabetic control, GABA, sitagliptin, or GABA plus sitagliptin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28672195/combination-treatment-with-the-gsk-3-inhibitor-9-ing-41-and-ccnu-cures-orthotopic-chemoresistant-glioblastoma-in-patient-derived-xenograft-models
#10
Andrey Ugolkov, Wenan Qiang, Gennadiy Bondarenko, Daniel Procissi, Irina Gaisina, C David James, James Chandler, Alan Kozikowski, Hendra Gunosewoyo, Thomas O'Halloran, Jeffrey Raizer, Andrew P Mazar
Resistance to chemotherapy remains a major challenge in the treatment of human glioblastoma (GBM). Glycogen synthase kinase-3β (GSK-3β), a positive regulator of NF-κB-mediated survival and chemoresistance of cancer cells, has been identified as a potential therapeutic target in human GBM. Our objective was to determine the antitumor effect of GSK-3 inhibitor 9-ING-41 in combination with chemotherapy in patient-derived xenograft (PDX) models of human GBM. We utilized chemoresistant PDX models of GBM, GBM6 and GBM12, to study the effect of 9-ING-41 used alone and in combination with chemotherapy on tumor progression and survival...
June 30, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28668828/patient-derived-xenografts-from-colorectal-carcinoma-a-temporal-and-hierarchical-study-of-murine-stromal-cell-replacement
#11
Celia Chao, Steve G Widen, Thomas G Wood, John R Zatarain, Paul Johnson, Aakash Gajjar, Guillermo Gomez, Suimin Qiu, Jill Thompson, Heidi Spratt, Mark R Hellmich
BACKGROUND/AIM: Patient-derived xenografting (PDX) of human colorectal cancer (CRC) is the preferred experimental model to study tumor response to therapeutic agents. Gradually, human stromal cells are replaced by mouse stromal cells; however, the exact timing of the replacement of human with murine stromal cells in human CRC xenograft has not been fully elucidated. We hypothesize that orthologous murine transcripts functionally substitutes for the loss due to replacement of human stromal genes...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28668826/inhibition-of-erg-activity-in-patient-derived-prostate-cancer-xenografts-by-yk-4-279
#12
Brian Winters, Lisha Brown, Ilsa Coleman, Holly Nguyen, Tsion Zewdu Minas, Lori Kollath, Valeri Vasioukhin, Peter Nelson, Eva Corey, Aykut Üren, Colm Morrissey
BACKGROUND/AIM: The aim of the current study was to determine the effects of the ERG small-molecule inhibitor YK-4-279 on ERG(+) prostate cancer patient-derived xenografts (PDX). MATERIALS AND METHODS: ERG activity was blocked using YK-4-279 in three subcutaneously-implanted ERG(+) (LuCaP 23.1, 86.2 and 35) and one ERG(-) (LuCaP 96) PDX. Treated animals tumor volume (TV), body weight (BW) and serum prostate-specific antigen (PSA) were compared to vehicle-treated control animals...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28664456/pancreas-specific-expression-of-oncogenes-in-a-porcine-model
#13
Martin F Berthelsen, Morten M Callesen, Tanja S Østergaard, Ying Liu, Rong Li, Henrik Callesen, Frederik Dagnæs-Hansen, Stephen Hamilton-Dutoit, Jannik E Jakobsen, Martin K Thomsen
Pancreatic cancer is the fourth leading course of cancer death and early detection of the disease is crucial for successful treatment. However, pancreatic cancer is difficult to detect in its earliest stages and once symptoms appear, the cancer has often progressed beyond possibility for curing. Research into the disease has been hampered by the lack of good models. We have generated a porcine model of pancreatic cancer with use of transgenic overexpression of an oncogene cassette containing MYC, KRAS (G12D) and SV40 LT...
June 29, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28661054/platelet-derived-growth-factor-regulates-yap-transcriptional-activity-via-src-family-kinase-dependent-tyrosine-phosphorylation
#14
Rory L Smoot, Nathan W Werneburg, Takaaki Sugihara, Matthew C Hernandez, Lin Yang, Christine Mehner, Rondell P Graham, Steven F Bronk, Mark J Truty, Gregory J Gores
The Hippo pathway effector YAP is implicated in the pathogenesis of cholangiocarcinoma (CCA). The Hippo pathway relies on signaling cross talk for its regulation. Given the importance of platelet derived growth factor receptor (PDGFR) signaling in CCA biology, our aim was to examine potential YAP regulation by PDGFR. We employed human and mouse CCA specimens and cell lines for these studies. Initially, we confirmed upregulation of PDGFRβ and PDGFR ligands in human and mouse CCA specimens and cell lines. YAP, a transcriptional co-activator, was localized to the nucleus in human CCA specimens and a cell line, as well as patient derived xenografts (PDX)...
June 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28659312/radiosensitization-of-adenoid-cystic-carcinoma-with-mdm2-inhibition
#15
Prashanth J Prabakaran, Amal M Javaid, Adam D Swick, Lauryn R Werner, Kwangok P Nickel, Emmanuel Sampene, Rong Hu, Irene M Ong, Justine Y Bruce, Gregory K Hartig, Aaron Wieland, Jude Canon, Paul M Harari, Randall J Kimple
Adenoid cystic carcinoma (ACC) is a rare cancer arising from the major or minor salivary gland tissues of the head and neck. There are currently no approved systemic agents or known radiosensitizers for ACC. Unlike the more common head and neck squamous cell carcinomas that frequently harbor TP53 mutations, ACC contain TP53 mutations at a rate of <5%, rendering them an attractive target for MDM2 inhibition. <p>Experimental Design: We report the successful establishment and detailed characterization of a TP53-WT ACC patient derived xenograft (PDX) which retained the histologic features of the original patient tumor...
June 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28658648/prevention-of-human-lymphoproliferative-tumor-formation-in-ovarian-cancer-patient-derived-xenografts
#16
Kristina A Butler, Xiaonan Hou, Marc A Becker, Valentina Zanfagnin, Sergio Enderica-Gonzalez, Daniel Visscher, Kimberly R Kalli, Piyawan Tienchaianada, Paul Haluska, S John Weroha
Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)-infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice...
June 25, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28654908/apio-ee-9-is-a-novel-aurora-a-and-b-antagonist-that-suppresses-esophageal-cancer-growth-in-a-pdx-mouse-model
#17
Guoguo Jin, Ke Yao, Zhiping Guo, Zhenjiang Zhao, Kangdong Liu, Fangfang Liu, Hanyong Chen, Dhilli Rao Gorja, Kanamata Reddy, Ann M Bode, Ziming Dong, Zigang Dong
Esophageal cancer (EC) is one of the most aggressive malignancies of the upper aerodigestive tract. Over the past three decades, with advances in surgical techniques and treatment, the prognosis of esophageal cancer has only slowly improved. Thus identifying novel molecular targets and developing therapeutic agents are critical. Aurora kinases play a crucial role in mitosis and selective inhibitors might provide an effective therapeutic treatment for cancer. However, the role of Aurora kinases in EC is still inadequately studied...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652835/a-randomized-controlled-trial-to-validate-the-alice-pdx-ambulatory-device
#18
Georg Nilius, Ulrike Domanski, Maik Schroeder, Karl-Josef Franke, Anke Hogrebe, Laurent Margarit, Maria Stoica, Marie-Pia d'Ortho
BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent condition; however, the majority of patients remain undiagnosed. There is a potential to expand the diagnostic capacity of sleep laboratories. The study objective was to validate a portable respiratory monitoring device (Alice PDX) against polysomnography (PSG) in the laboratory and to assess its reliability at home. METHODS: A total of 85 patients with suspected OSA (80% male, mean age 49.1±13.5 years, body mass index 29...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28651692/long-chain-fatty-acids-and-related-pro-inflammatory-specialized-pro-resolving-lipid-mediators-and-their-intermediates-in-preterm-human-milk-during-the-first-month-of-lactation
#19
D T Robinson, H L Palac, V Baillif, E Van Goethem, M Dubourdeau, L Van Horn, C R Martin
This study aimed to measure longitudinal quantities of the long chain fatty acids, their biologically active terminal metabolites and related intermediates (also called oxylipins) in preterm human milk expressed during the first month of lactation. In a prospective cohort, breast milk was collected throughout the first month of lactation in 30 women who delivered preterm infants. Eighteen bioactive lipids and their intermediates were quantified via solid phase extraction and LC-MS/MS. Analysis by GC-FID quantified the fatty acid precursors...
June 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28650393/orthotopic-patient-derived-pancreatic-cancer-xenografts-engraft-into-the-pancreatic-parenchyma-metastasize-and-induce-muscle-wasting-to-recapitulate-the-human-disease
#20
Kristina L Go, Daniel Delitto, Sarah M Judge, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Andrew R Judge, Jose G Trevino
OBJECTIVE: Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model...
June 22, 2017: Pancreas
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