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https://www.readbyqxmd.com/read/29028354/nanosheet-array-like-palladium-catalysts-pdx-rgo-coal-ldh-via-lattice-atomic-confined-in-situ-reduction-for-highly-efficient-heck-coupling-reaction
#1
Yanna Wang, Liguang Dou, Hui Zhang
A series of novel nanosheet array-like catalysts Pdx/rGO@CoAl-LDH (x = 0.0098 - 1.9, refers to Pd loading in wt% on ICP, rGO: reduced graphene oxide, LDH: layered double hydroxide) were first prepared via a simple and green lattice atomic-confined in situ reduction of oxidative Pd precursors by the evenly atomic-dispersed reductive Co2+ sites on LDH layers of a nanohybrid rGO@CoAl-LDH with hexagonal LDH nanoplates (~73 nm × 7 nm) interdigitated vertical to the surfaces of rGO layer in both sides, fabricated through a simple citric acid-assisted aqueous-phase coprecipitation method...
October 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29027990/il6-blockade-potentiates-the-anti-tumor-effects-of-%C3%AE-secretase-inhibitors-in-notch3-expressing-breast-cancer
#2
Dong Wang, Jiahui Xu, Bingjie Liu, Xueyan He, Lei Zhou, Xin Hu, Feng Qiao, Anli Zhang, Xiaojun Xu, Huafeng Zhang, Max S Wicha, Lixing Zhang, Zhi-Ming Shao, Suling Liu
Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma secretase inhibitors (GSIs), have been used in the clinical trials, but the outcomes of these trials have been insufficient and have yielded unclear. In the present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit breast tumor growth, but increase the breast cancer stem cell (BCSC) population in Notch3-expressing breast cancer cells, in a process that is coupled with IL6 induction and is blocked by the IL6R antagonist Tocilizumab (TCZ)...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29025772/impaired-hla-class-i-antigen-processing-and-presentation-as-a-mechanism-of-acquired-resistance-to-immune-checkpoint-inhibitors-in-lung-cancer
#3
Scott Gettinger, Jungmin Choi, Katherine Hastings, Anna Truini, Ila Datar, Ryan Sowell, Anna Wurtz, Weilai Dong, Guoping Cai, Mary Ann Melnick, Victor Y Du, Joseph Schlessinger, Sarah B Goldberg, Anne Chiang, Miguel F Sanmamed, Ignacio Melero, Jackeline Agorreta, Luis M Montuenga, Richard Lifton, Soldano Ferrone, Paula Kavathas, David L Rimm, Susan M Kaech, Kurt A Schalper, Roy S Herbst, Katerina Politi
Mechanisms of acquired resistance to immune checkpoint inhibitors (ICIs) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy number changes were not detected in our cohort. In one case, we found acquired homozygous loss of B2M that caused lack of cell surface HLA class I expression in the tumor and a matched patient-derived xenograft (PDX)...
October 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29017512/metastatic-pathway-and-the-microvascular-and-physicochemical-microenvironments-of-human-melanoma-xenografts
#4
Ruixia Huang, Lise Mari K Andersen, Einar K Rofstad
BACKGROUND: Malignant melanoma of the skin can metastasize through blood vessels and lymphatics. The primary tumor develops a vascular microenvironment characterized by abnormal blood vessels and lymphatics and a physicochemical microenvironment characterized by low oxygen tension, regions with hypoxic tissue, and high interstitial fluid pressure (IFP). This study aimed at identifying relationships between the metastatic route of melanomas and characteristic features of the microvascular and physicochemical microenvironments of the primary tumor...
October 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29016929/trivalent-car-t-cells-overcome-interpatient-antigenic-variability-in-glioblastoma
#5
Kevin Bielamowicz, Kristen Fousek, Tiara T Byrd, Hebatalla Samaha, Malini Mukherjee, Nikita Aware, Meng-Fen Wu, Jordan S Orange, Pavel Sumazin, Tsz-Kwong Man, Sujith K Joseph, Meenakshi Hegde, Nabil Ahmed
Background: Glioblastoma (GBM) is the most common primary malignant brain cancer, and is currently incurable. Chimeric Antigen Receptor (CAR) T-cells have shown promise in GBM treatment. While we have shown that combinatorial targeting of two glioma antigens offsets antigen escape and enhances T-cell effector functions, the inter-patient variability in surface antigen expression between patients hinders the clinical impact of targeting two antigen pairs. This study addresses targeting 3 antigens using a single CAR T-cell product for broader application...
September 16, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28991255/patient-derived-xenografts-undergo-mouse-specific-tumor-evolution
#6
Uri Ben-David, Gavin Ha, Yuen-Yi Tseng, Noah F Greenwald, Coyin Oh, Juliann Shih, James M McFarland, Bang Wong, Jesse S Boehm, Rameen Beroukhim, Todd R Golub
Patient-derived xenografts (PDXs) have become a prominent cancer model system, as they are presumed to faithfully represent the genomic features of primary tumors. Here we monitored the dynamics of copy number alterations (CNAs) in 1,110 PDX samples across 24 cancer types. We observed rapid accumulation of CNAs during PDX passaging, often due to selection of preexisting minor clones. CNA acquisition in PDXs was correlated with the tissue-specific levels of aneuploidy and genetic heterogeneity observed in primary tumors...
October 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28980863/addition-of-exogenous-sodium-palmitate-increases-the-iapp-insulin-mrna-ratio-via-gpr40-in-human-endoc-%C3%AE-h1-cells
#7
Camilla Krizhanovskii, Rikard G Fred, Marie E Oskarsson, Gunilla T Westermark, Nils Welsh
BACKGROUND: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells. METHODS: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms...
October 5, 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/28978722/acquired-resistance-to-fgfr-inhibitor-in-diffuse-type-gastric-cancer-through-an-akt-independent-pkc-mediated-phosphorylation-of-gsk3%C3%AE
#8
Wen Min Lau, Eileen Teng, Kie Kyon Huang, Jin Wei Tan, Kakoli Das, Zhijiang Zang, Tania Chia, Ming Teh, Koji Kono, Wei Peng Yong, Asim Shabbir, Amy Tay, Niam Sin Phua, Patrick Tan, Shing Leng Chan, Jimmy Bok Yan So
Preclinical models of diffuse type gastric cancer (DGC) that reliably predict clinical activity of novel compounds are lacking. To overcome the problem of poor tumor cellularity in DGC, we used cells from malignant ascites to establish diffuse type gastric cancer patient-derived xenograft (PDX) models that recapitulate the primary cancer. Cells in PDX model GAGA6 with FGFR2 amplification were sensitive to AZD4547, a potent FGFR inhibitor that is being clinically evaluated for FGFR-aberrant cancer types. Intermittent in vivo treatment of GAGA6 tumors with AZD4547 gave rise to PDX tumors with acquired resistance to AZD4547, GAGA6-R...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28978636/ezh2-modifies-sunitinib-resistance-in-renal-cell-carcinoma-by-kinome-reprogramming
#9
Remi Adelaiye-Ogala, Justin Budka, Nur P Damayanti, Justine Arrington, Mary W Ferris, Chuan-Chih Hsu, Sreenivasulu Chintala, Ashley R Orillion, Kiersten Marie Miles, Li Shen, May Elbanna, Eric Ciamporcero, Sreevani Arisa, Piergiorgio Pettazzoni, Giulio F Draetta, Mukund Seshadri, Bradley A Hancock, Milan Radovich, Janaiah Kota, Michael Buck, Heike Keilhack, Brian P McCarthy, Scott A Persohn, Paul R Territo, Yong Zang, Joseph Irudayaraj, Andy W Tao, Peter Hollenhorst, Roberto Pili
Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represent a major hurdle in improving the management of clear cell renal cell carcinoma (ccRCC). Recent reports suggest that drug resistance is driven by tumor adaptation via epigenetic mechanisms that activate alternative survival pathways. The histone methyl transferase EZH2 is frequently altered in many cancers including ccRCC. To evaluate its role in ccRCC resistance to RTKi, we established and characterized a spontaneously metastatic, patient-derived xenograft (PDX) model that is intrinsically resistant to the RTKI sunitinib but not to the VEGF therapeutic antibody bevacizumab...
October 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28977728/intraductal-carcinoma-of-the-prostate-can-evade-androgen-deprivation-with-emergence-of-castrate-tolerant-cells
#10
Laura H Porter, Kohei Hashimoto, Mitchell G Lawrence, Carmel Pezaro, David Clouston, Hong Wang, Melissa Papargiris, Heather Thorne, Jason Li, Andrew Ryan, Sam Norden, Daniel Moon, Damien M Bolton, Shomik Sengupta, Mark Frydenberg, Declan G Murphy, Gail P Risbridger, Renea A Taylor
OBJECTIVES: To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer, we first examined whether IDC-P was originally present in patients who later developed advanced prostate cancer and then used patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT). MATERIALS AND METHODS: We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer...
October 4, 2017: BJU International
https://www.readbyqxmd.com/read/28974548/selective-androgen-receptor-modulator-rad140-inhibits-the-growth-of-androgen-estrogen-receptor-positive-breast-cancer-models-with-a-distinct-mechanism-of-action
#11
Ziyang Yu, Suqin He, Dannie Wang, Hitisha K Patel, Chris P Miller, Jeff Brown, Gary Hattersley, Jamal C Saeh
PURPOSE: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+) breast cancer cells and were used to treat breast cancer eliciting favorable response. The present study evaluates the activity and efficacy of the oral selective AR modulator (SARM) RAD140 in in vivo and in vitro models of AR/ER+ breast cancer. EXPERIMENTAL DESIGN: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity...
October 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28971839/simultaneous-k-ras-activation-and-keap1-deletion-cause-atrophy-of-pancreatic-parenchyma
#12
Shin Hamada, Tooru Shimosegawa, Keiko Taguchi, Tatsuhide Nabeshima, Masayuki Yamamoto, Atsushi Masamune
The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response, such as growth promotion and chemoresistance of cancer cells. Nrf2 is constitutively activated in most cancer cells. However, the activation of Nrf2 together with oncogenic mutations does not always result in cancer promotion. K-ras(LSL-G12D/+)::p53(LSL-R172H/+)::Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer, which specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre...
September 28, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28970780/mulberry-branch-bark-powder-significantly-improves-hyperglycemia-and-regulates-insulin-secretion-in-type-ii-diabetic-mice
#13
Xiao-Lu Yin, Hua-Yu Liu, Yu-Qing Zhang
This experiment, based on the previous study on R. mori, introduces whole mulberry branch powder into the diet to treat diabetic mice. Mulberry branch bark powder (MBBP) was administered orally to streptozotocin (STZ)-induced type II diabetic (T2D) mice to investigate hypoglycemic effects. After a 4-week period of diet consumption containing 5%, 10% and 20% MBBP, the fasting blood glucose, body weight and the related western blotting were measured, pathologic and immunohistochemical were observed. The 20% MBBP group showed a significant reduction in hyperglycemia and hyperinsulinemia; fasting blood glucose and insulin decreased from 25...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28967875/combination-curcumin-and-epigallocatechin-3-gallate-inhibits-colorectal-carcinoma-microenvironment-induced-angiogenesis-by-jak-stat3-il-8-pathway
#14
G Jin, Y Yang, K Liu, J Zhao, X Chen, H Liu, R Bai, X Li, Y Jiang, X Zhang, J Lu, Z Dong
Tumor microenvironment has a crucial role in cancer development and progression, whereas the mechanism of how it regulates angiogenesis is unclear. In this study, we simulated the colorectal carcinoma microenvironment by conditioned medium (CM) of colorectal carcinoma cell lines (SW620, HT-29, HCT116) supernatant or colorectal carcinoma tissue homogenate supernatant to induce normal endothelial cells (NECs). We found that colorectal carcinoma CM promoted tumor angiogenesis by coercing NECs toward tumor endothelial cells (TECs) with the activation of the JAK/STAT3 signaling pathway...
October 2, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28966671/pancreatic-islet-regeneration-through-pdx-1-notch-1-ngn3-signaling-after-gastric-bypass-surgery-in-db-db-mice
#15
Tao Huang, Jun Fu, Zhijing Zhang, Yuhao Zhang, Yunjia Liang, Cuicui Ge, Xianju Qin
In view of the compelling anti-diabetic effects of gastric bypass surgery (GBS) in the treatment of morbid obesity, it is important to clarify its enhancing effect on pancreatic islets, which is closely linked with diabetes remission in obese patients, as well as the underlying mechanisms. The present study evaluated the effects of GBS on glycemic control and other pancreatic changes in db/db mice. The db/db mice were divided into Control, Sham and GBS group. A significant improvement in fasting plasma glucose levels and glucose intolerance were observed post-surgery...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28955032/clinical-responses-to-adoptive-t-cell-transfer-can-be-modeled-in-an-autologous-immune-humanized-mouse-model
#16
Henrik Jespersen, Mattias F Lindberg, Marco Donia, Elin M V Söderberg, Rikke Andersen, Ulrich Keller, Lars Ny, Inge Marie Svane, Lisa M Nilsson, Jonas A Nilsson
Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 - a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2)...
September 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28947782/microchamber-cultures-of-bladder-cancer-a-platform-for-characterizing-drug-responsiveness-and-resistance-in-pdx-and-primary-cancer-cells
#17
Pantea Gheibi, Shuxiong Zeng, Kyung Jin Son, Tam Vu, Ai-Hong Ma, Marc A Dall'Era, Stanley Alexander Yap, Ralph W de Vere White, Chong-Xian Pan, Alexander Revzin
Precision cancer medicine seeks to target the underlying genetic alterations of cancer; however, it has been challenging to use genetic profiles of individual patients in identifying the most appropriate anti-cancer drugs. This spurred the development of patient avatars; for example, patient-derived xenografts (PDXs) established in mice and used for drug exposure studies. However, PDXs are associated with high cost, long development time and low efficiency of engraftment. Herein we explored the use of microfluidic devices or microchambers as simple and low-cost means of maintaining bladder cancer cells over extended periods of times in order to study patterns of drug responsiveness and resistance...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28945830/patient-derived-xenografts-effectively-capture-responses-to-oncology-therapy-in-a-heterogeneous-cohort-of-patients-with-solid-tumors
#18
E Izumchenko, K Paz, D Ciznadija, I Sloma, A Katz, D Vasquez-Dunddel, I Ben-Zvi, J Stebbing, W McGuire, W Harris, R Maki, A Gaya, A Bedi, S Zacharoulis, R Ravi, L H Wexler, M O Hoque, C Rodriguez-Galindo, H Pass, N Peled, A Davies, R Morris, M Hidalgo, D Sidransky
Background: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. Patients and methods: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28944003/partial-fusion-of-a-cytochrome-p450-system-by-carboxy-terminal-attachment-of-putidaredoxin-reductase-to-p450cam-cyp101a1
#19
Eachan O Johnson, Luet-Lok Wong
Cytochrome P450 (CYP) enzymes catalyze the insertion of oxygen into carbon-hydrogen bonds and have great potential for enzymatic synthesis. Application development of class I CYPs is hampered by their dependence on two redox partners (a ferredoxin and ferredoxin reductase), slowing catalysis compared to self-sufficient CYPs such as CYP102A1 (P450BM3). Previous attempts to address this have fused all three components in several permutations and geometries, with much reduced activity compared to the native system...
October 21, 2016: Catalysis Science & Technology
https://www.readbyqxmd.com/read/28939655/gpc2-may-be-an-immunotherapeutic-target-in-high-risk-neuroblastoma
#20
(no author information available yet)
A GPC2-targeting antibody-drug conjugate promotes tumor regression in a high-risk neuroblastoma PDX.
September 22, 2017: Cancer Discovery
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