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https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#1
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28073890/pancreatic-cancer-cell-lines-as-patient-derived-avatars-genetic-characterisation-and-functional-utility
#2
Erik S Knudsen, Uthra Balaji, Brian Mannakee, Paris Vail, Cody Eslinger, Christopher Moxom, John Mansour, Agnieszka K Witkiewicz
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. DESIGN: 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28073843/active-estrogen-receptor-alpha-signaling-in-ovarian-cancer-models-and-clinical-specimens
#3
Courtney L Andersen, Matthew J Sikora, Michelle M Boisen, Tianzhou Ma, Alec Christie, George Tseng, Yong Seok Park, Soumya Luthra, Uma Chandran, Paul Haluska, Gina Mantia-Smaldone, Kunle Odunsi, Karen McLean, Adrian V Lee, Esther Elishaev, Robert P Edwards, Steffi Oesterreich
PURPOSE: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha in ~80% of HGSOC and some small but promising clinical trials of endocrine therapy, estrogen receptor-alpha has been understudied as a target in this disease. We sought to identify hormone-responsive, estrogen receptor-alpha-dependent HGSOC. EXPERIMENTAL DESIGN: We characterized endocrine response in HGSOC cells across culture conditions (2-D, 3-D, forced suspension) and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28070859/mouse-bone-marrow-vsels-exhibit-differentiation-into-three-embryonic-germ-lineages-and-germ-hematopoietic-cells-in-culture
#4
Ambreen Shaikh, Sandhya Anand, Sona Kapoor, Ranita Ganguly, Deepa Bhartiya
Very small embryonic-like stem cells (VSELs) have been reported in various adult tissues, express pluripotent and primordial germ cells (PGCs) specific markers, are mobilized under stress/disease conditions, give rise to tissue committed progenitors and thus help regenerate and maintain homeostasis. The aim of the present study was to evaluate in vitro differentiation potential of VSELs using a quantitative approach. VSELs were collected from mouse bone marrow after 4 days of 5-fluorouracil (5-FU, 150 mg/Kg) treatment, further enriched by size based filtration and cultured on a feeder support in the presence of specific differentiation media...
January 9, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28060420/multimetallic-hierarchical-aerogels-shape-engineering-of-the-building-blocks-for-efficient-electrocatalysis
#5
Bin Cai, Arezoo Dianat, René Hübner, Wei Liu, Dan Wen, Albrecht Benad, Luisa Sonntag, Thomas Gemming, Gianaurelio Cuniberti, Alexander Eychmüller
A new class of multimetallic hierarchical aerogels composed entirely of interconnected Ni-Pdx Pty nano-building blocks with in situ engineered morphologies and compositions is demonstrated. The underlying mechanism of the galvanic shape-engineering is elucidated in terms of nanowelding of intermediate nanoparticles. The hierarchical aerogels integrate two levels of porous structures, leading to improved electrocatalysis performance.
January 6, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28052650/patient-derived-xenograft-models-of-epithelial-ovarian-cancer-for-preclinical-studies
#6
Eun Jin Heo, Young Jae Cho, William Chi Cho, Ji Eun Hong, Hye-Kyung Jeon, Doo-Yi Oh, Yoon-La Choi, Sang Yong Song, Jung-Joo Choi, Duk-Soo Bae, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Woong-Yang Park, Byoung-Gie Kim, Jeong-Won Lee
Purpose: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. Materials and Methods: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice...
January 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28042317/cd54-notch1-axis-controls-tumor-initiation-and-cancer-stem-cell-functions-in-human-prostate-cancer
#7
Chong Li, Shengwu Liu, Ruping Yan, Ning Han, Kwok-Kin Wong, Lei Li
Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration...
2017: Theranostics
https://www.readbyqxmd.com/read/28039356/immunophenotyping-and-transcriptomic-outcomes-in-pdx-derived-tnbc-tissue
#8
Eileen Snowden, Warren Porter, Friedrich Hahn, Mitchell Ferguson, Frances Tong, Joel S Parker, Aaron Middlebrook, Smita Ghanekar, W Shannon Dillmore, Rainer Blaesius
: Cancer tissue functions as an ecosystem of a diverse set of cells that interact in a complex tumor microenvironment (TME). Genomic tools applied to biopsies in bulk fail to account for this tumor heterogeneity while single cell imaging methods limit the number of cells which can be assessed or are very resource intensive. The current study presents methods based on flow cytometric analysis and cell sorting using known cell surface markers (eg, CD184, CD24, CD90) to identify and interrogate distinct groups of cells in triple-negative breast cancer (TNBC) clinical biopsy specimens from patient-derived xenograft (PDX) models...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28036027/the-phosphorylation-of-pdx-1-by-protein-kinase-ck2-is-crucial-for-its-stability
#9
Sabrina Klein, Rui Meng, Mathias Montenarh, Claudia Götz
The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, such as differentiation, proliferation, and survival. The CK2 phosphorylation site of PDX-1 is located within the binding region of the E3 ubiquitin ligase adaptor protein PCIF1. To study the interaction between PDX-1 and PCIF1 we used immunofluorescence analysis, co-immunoprecipitation, GST-pull-down studies, and proximity ligation assay (PLA)...
December 28, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/28035373/cancer-associated-peritoneal-mesothelial-cells-lead-the-formation-of-pancreatic-cancer-peritoneal-dissemination
#10
Toshiya Abe, Kenoki Ohuchida, Kazuhiro Koikawa, Sho Endo, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura
The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between thr pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs...
December 30, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28025748/patient-derived-xenograft-pdx-models-in-basic-and-translational-breast-cancer-research
#11
Lacey E Dobrolecki, Susie D Airhart, Denis G Alferez, Samuel Aparicio, Fariba Behbod, Mohamed Bentires-Alj, Cathrin Brisken, Carol J Bult, Shirong Cai, Robert B Clarke, Heidi Dowst, Matthew J Ellis, Eva Gonzalez-Suarez, Richard D Iggo, Peter Kabos, Shunqiang Li, Geoffrey J Lindeman, Elisabetta Marangoni, Aaron McCoy, Funda Meric-Bernstam, Helen Piwnica-Worms, Marie-France Poupon, Jorge Reis-Filho, Carol A Sartorius, Valentina Scabia, George Sflomos, Yizheng Tu, François Vaillant, Jane E Visvader, Alana Welm, Max S Wicha, Michael T Lewis
Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC))...
December 27, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28024726/defining-the-boundaries-and-expanding-the-utility-of-head-and-neck-cancer-patient-derived-xenografts
#12
Adam D Swick, Andrew P Stein, Timothy M McCulloch, Gregory K Hartig, Irene M Ong, Emmanuel Sampene, Prashanth J Prabakaran, Cheng Z Liu, Randall J Kimple
BACKGROUND: Patient derived xenografts (PDXs) represent an essential tool in oncologic research, and we sought to further expand our repertoire of head and neck squamous cell carcinoma (HNSCC) while determining potential boundaries for this system. METHODS: We consented new patients for PDX development and determined if a 24-h time delay from tumor excision to xenograft implantation affected PDX establishment. We developed a tissue microarray (TMA) from formalin fixed, paraffin embedded PDXs and their subsequent passages and carried out quantitative immunohistochemistry for EGFR, pEGFR, pAkt, pERK and ERCC1...
January 2017: Oral Oncology
https://www.readbyqxmd.com/read/28024317/induction-of-nestin-early-expression-as-a-hallmark-for-mesenchymal-stem-cells-expression-of-pdx-1-as-a-pre-disposing-factor-for-their-conversion-into-insulin-producing-cells
#13
Marisela Martinez-Gamboa, Delia Elba Cruz-Vega, Jorge Moreno Cuevas, Maria Teresa Gonzalez-Garza
Diabetes constitutes a worldwide epidemic that affects all ethnic groups. Cell therapy is one of the best alternatives of treatment, by providing an effective way to regenerate insulin-producing cells lost during the course of the disease, but many issues remain to be solved. Several groups have been working in the development of a protocol capable of differentiating Mesenchymal Stem Cells (MSCs) into physiologically sound Insulin Producing Cells (IPCs). In order to obtain a simple, fast and direct method, we propose in this manuscript the induction of MSCs to express NESTIN in a short time period (2 h), proceeded by incubation in a low glucose induced medium (24 h) and lastly by incubation in a high glucose medium...
December 31, 2016: International Journal of Stem Cells
https://www.readbyqxmd.com/read/27999790/tumor-take-rate-optimization-for-colorectal-carcinoma-patient-derived-xenograft-models
#14
Michael Gock, Florian Kühn, Christina Susanne Mullins, Mathias Krohn, Friedrich Prall, Ernst Klar, Michael Linnebacher
Background. For development of individualized treatment on a routine basis, transfer of patients' tumor tissue in a xenograft model (i.e., generation of patient-derived xenografts (PDX)) is desirable for molecular, biochemical, or functional analyses. Drawbacks are dissatisfactory tumor take rates, the necessity of fast tumor tissue processing, and extensive logistics demanding teamwork of surgeons, pathologists, and laboratory researchers. Methods. The take rates of ten colorectal cancer (CRC) tissue samples in immunodeficient mice were compared after direct cryopreservation and after a 24 h cooling period at 4°C prior to cryopreservation...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27993965/targeting-the-atr-chk1-axis-with-parp-inhibition-results-in-tumor-regression-in-brca-mutant-ovarian-cancer-models
#15
Hyoung Kim, Erin George, Ryan L Ragland, Stavros Rafail, Rugang Zhang, Clemens Krepler, Mark Morgan, Meenhard Herlyn, Eric J Brown, Fiona Simpkins
PURPOSE: PARP inhibition (PARPi) has modest clinical activity in recurrent BRCA mutant (BRCAMUT) high-grade serous ovarian cancers (HGSOC). We hypothesized that PARPi increases dependence on ATR/CHK1 such that combination PARPi with ATR/CHK1 blockade results in increased cell death and tumor regression. EXPERIMENTAL DESIGN: Effects of PARPi (olaparib), CHK1 inhibition (CHK1i;MK8776) or ATR inhibition (ATRi;AZD6738) alone or in combination on survival, colony formation, cell-cycle, genome instability and apoptosis were evaluated in BRCA1/2MUT HGSOC cells...
December 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27992226/first-principles-molecular-dynamics-analysis-of-ligand-free-suzuki-miyaura-cross-coupling-in-water-solvent-oxidative-addition-step
#16
Teruo Hirakawa, Yuta Uramoto, Daisuke Mimura, Atsuya Takeda, Susumu Yanagisawa, Takashi Ikeda, Kouji Inagaki, Yoshitada Morikawa
We investigated the oxidative addition of PhX (X = Cl, Br) to a single Pd(0) atom or a PdX(-) complex in water using first-principles molecular dynamics simulations, with solvent H2O molecules explicitly included in the calculation models, to clarify the origin of the extremely high reactivity of a ligand-free Pd catalyst in an aqueous solution for the Suzuki-Miyaura reaction. The free-energy profiles are estimated using blue moon ensemble sampling to include the entropy effect in chemical reactions in a water solvent...
January 4, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27988338/dha-derived-oxylipins-neuroprostanes-and-protectins-differentially-and-dose-dependently-modulate-the-inflammatory-response-in-human-macrophages-putative-mechanisms-through-ppar-activation
#17
Rémy Bosviel, Laurie Joumard-Cubizolles, Giulia Chinetti-Gbaguidi, Dominique Bayle, Corinne Copin, Nathalie Hennuyer, Isabelle Duplan, Bart Staels, Giuseppe Zanoni, Alessio Porta, Laurence Balas, Jean-Marie Galano, Camille Oger, Andrzej Mazur, Thierry Durand, Cécile Gladine
Whereas the anti-inflammatory properties and mechanisms of action of long chain ω3 PUFAs have been abundantly investigated, research gaps remain regarding the respective contribution and mechanisms of action of their oxygenated metabolites collectively known as oxylipins. We conducted a dose-dependent and comparative study in human primary macrophages aiming to compare the anti-inflammatory activity of two types of DHA-derived oxylipins including the well-described protectins (NPD1 and PDX), formed through lipoxygenase pathway and the neuroprostanes (14-A4t- and 4-F4t-NeuroP) formed through free-radical mediated oxygenation and expected to be new anti-inflammatory mediators...
December 14, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27986750/human-papillomavirus-regulates-her3-expression-in-head-and-neck-cancer-implications-for-targeted-her3-therapy-in-hpv-patients
#18
Toni M Brand, Stefan Hartmann, Neil E Bhola, Noah D Peyser, Hua Li, Yan Zeng, Erin Isaacson Wechsler, Max V Ranall, Sourav Bandyopadhyay, Umamaheswar Duvvuri, Theresa M LaVallee, Richard C K Jordan, Daniel E Johnson, Jennifer R Grandis
PURPOSE: Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of HNSCCs, where viral expression of the E6 and E7 oncoproteins are necessary for tumor growth and maintenance. Although patients with HPV(+) tumors have a more favorable prognosis, there are currently no HPV-selective therapies. Recent studies identified differential receptor tyrosine kinase (RTK) profiles in HPV(+) vs. HPV(-) tumors. One such RTK, HER3, is overexpressed and interacts with phosphoinositide 3-kinase (PI3K) in HPV(+) tumors...
December 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27982543/in-vivo-bioluminescence-imaging-using-orthotopic-xenografts-towards-patient-s-derived-xenograft-medulloblastoma-models
#19
Fatemeh Asadzadeh, Veronica Ferrucci, Pasqualino DE Antonellis, Massimo Zollo
BACKGROUND: Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment...
March 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27980108/dual-hdac-and-pi3k-inhibitor-cudc-907-downregulates-myc-and-suppresses-growth-of-myc-dependent-cancers
#20
Kaiming Sun, Ruzanna Atoyan, Mylissa A Borek, Steven DellaRocca, Maria Elena S Samson, Anna W Ma, Guang-Xin Xu, Troy Patterson, David P Tuck, Jaye L Viner, Ali Fattaey, Jing Wang
Upregulation of MYC is a common driver event in human cancers, and some tumors depend on MYC to maintain transcriptional programs that promote cell growth and proliferation. Preclinical studies have suggested that individually targeting upstream regulators of MYC, such as histone deacetylases (HDACs) and phosphoinositide 3-kinases (PI3Ks), can reduce MYC protein levels and suppress the growth of MYC-driven cancers. Synergy between HDAC and PI3K inhibition in inducing cancer cell death has also been reported, but the involvement of MYC regulation is unclear...
December 15, 2016: Molecular Cancer Therapeutics
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