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https://www.readbyqxmd.com/read/28448627/engineering-chimeric-human-and-mouse-major-histocompatibility-complex-mhc-class-i-tetramers-for-the-production-of-t-cell-receptor-tcr-mimic-antibodies
#1
Demin Li, Carol Bentley, Jenna Yates, Maryam Salimi, Jenny Greig, Sarah Wiblin, Tasneem Hassanali, Alison H Banham
Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide...
2017: PloS One
https://www.readbyqxmd.com/read/28448494/integrin-%C3%AE-1-activation-induces-an-anti-melanoma-host-response
#2
Laila Ritsma, Ipsita Dey-Guha, Nilesh Talele, Xavier Sole, Salony, Joeeta Chowdhury, Kenneth N Ross, Sridhar Ramaswamy
TGF-β is a cytokine thought to function as a tumor promoter in advanced malignancies. In this setting, TGF-β increases cancer cell proliferation, survival, and migration, and orchestrates complex, pro-tumorigenic changes in the tumor microenvironment. Here, we find that in melanoma, integrin β1-mediated TGF-β activation may also produce tumor suppression via an altered host response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate that cell surface integrin β1-activation increases TGF-β activity, resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within the tumor microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28447368/optimization-of-aqueous-extraction-and-biological-activity-of-harpagophytum-procumbens-root-on-ex-vivo-rat-colon-inflammatory-model
#3
Marcello Locatelli, Claudio Ferrante, Simone Carradori, Daniela Secci, Lidia Leporini, Annalisa Chiavaroli, Sheila Leone, Lucia Recinella, Giustino Orlando, Sara Martinotti, Luigi Brunetti, Michele Vacca, Luigi Menghini
Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave-assisted aqueous Harpagophytum extract (1-1000 μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis...
April 26, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28446728/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#4
Antonio Cigliano, Chunmei Wang, Maria G Pilo, Marta Szydlowska, Stefania Brozzetti, Gavinella Latte, Giovanni M Pes, Rosa M Pascale, Maria A Seddaiu, Gianpaolo Vidili, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446463/the-national-cancer-institute-almanac-a-comprehensive-screening-resource-for-the-detection-of-anticancer-drug-pairs-with-enhanced-therapeutic-activity
#5
Susan L Holbeck, Richard Camalier, James A Crowell, Jeevan Prasaad Govindharajulu, Melinda G Hollingshead, Lawrence W Anderson, Eric C Polley, Larry Rubinstein, Apurva K Srivastava, Deborah F Wilsker, Jerry M Collins, James H Doroshow
To date, over 100 small molecule oncology drugs have been approved by the US Food and Drug Administration.  Due to the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations.  Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed.  In this study, we performed a systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA-approved cancer drugs against a panel of 60 well-characterized human tumor cell lines (NCI-60) to uncover combinations with greater than additive growth-inhibitory activity...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#6
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445726/sirtuin-1-activation-controls-tumor-growth-by-impeding-th17-differentiation-via-stat3-deacetylation
#7
Emeric Limagne, Marion Thibaudin, Romain Euvrard, Hélène Berger, Pauline Chalons, Frédérique Végan, Etienne Humblin, Romain Boidot, Cédric Rébé, Valentin Derangère, Sylvain Ladoire, Lionel Apetoh, Dominique Delmas, François Ghiringhelli
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445155/retinoblastoma-cells-activate-the-akt-pathway-and-are-vulnerable-to-the-pi3k-mtor-inhibitor-nvp-bez235
#8
Chencheng Xie, Matthew J Freeman, Huarui Lu, Xiaohong Wang, Colleen L Forster, Aaron L Sarver, Timothy C Hallstrom
Retinoblastoma is a pediatric cancer of the retina most often caused by inactivation of the retinoblastoma (RB1) tumor suppressor gene. We previously showed that Rb1 loss cooperates with either co-activating the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, or co-deleting Pten, to initiate retinoblastoma tumors in mice. The objectives of this study were to determine if the AKT pathway is activated in human retinoblastomas and the extent that anti-PI3K therapy induces apoptosis in retinoblastoma cells, alone or in combination with the DNA damaging drugs carboplatin and topotecan...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#9
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444820/casticin-impairs-cell-migration-and-invasion-of-mouse-melanoma-b16f10-cells-via-pi3k-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#10
Yung-Luen Shih, Hsiao-Min Chou, Hsiu-Chen Chou, Hsu-Feng Lu, Yung-Lin Chu, Hung-Sheng Shang, Jing-Gung Chung
Casticin, a polymethoxyflavone, is one of the major active components obtained from Fructus viticis, which have been shown to have anticancer activities including induce cell apoptosis in human cancer cells. The aim of this study was to investigate the molecular mechanisms by which casticin inhibits cell migration and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT assay and the results indicated that casticin decreased the total percentages of viable cells in dose-dependent manners...
April 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28442573/cell-cycle-dependent-degradation-of-the-methyltransferase-setd3-attenuates-cell-proliferation-and-liver-tumorigenesis
#11
Xiaoqing Cheng, Yuan Hao, Wenjie Shu, Mengjie Zhao, Chen Zhao, Yuan Wu, Xiaodan Peng, Pinfang Yao, Daibiao Xiao, Guoliang Qing, Zhengying Pan, Lei Yin, Desheng Hu, Hai-Ning Du
Histone modifications, including lysine methylation, are epigenetic marks that influence many biological pathways. Accordingly, many methyltransferases have critical roles in various biological processes, and their dysregulation is often associated with cancer. However, the biological functions and regulation of many methyltransferases are unclear. Here, we report that a human homolog of the methyltransferase SET domain containing 3 (SETD3) is cell cycle regulated: SETD3 protein levels peaked in S phase and were lowest in M phase...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28441080/color-coded-intravital-imaging-demonstrates-a-transforming-growth-factor-beta-tgf-%C3%AE-antagonist-selectively-targets-stromal-cells-in-a-human-pancreatic-cancer-orthotopic-mouse-model
#12
Takashi Murakami, Yukihiko Hiroshima, Kentaro Miyake, Ho Kyoung Hwang, Tasuku Kiyuna, Jonathan C DeLong, Thinzar M Lwin, Ryusei Matsuyama, Ryutaro Mori, Takafumi Kumamoto, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M Hoffman
Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor-beta (TGF-β) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF-β inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF-β expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP)...
April 25, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28440426/downregulation-of-microrna-30d-promotes-cell-proliferation-and-invasion-by-targeting-lrh-1-in-colorectal-carcinoma
#13
Likun Yan, Jian Qiu, Jianfeng Yao
The aberrant expression of miR-30d has been reported in several types of human malignancies. However, its biological function in colorectal cancer (CRC) remains largely unknown. In this study, we identified that miR‑30d was significantly downregulated in CRC tissues compared to that observed in normal controls as detected by RT‑qPCR analysis. Downregulation of miR‑30d was significantly associated with aggressive clinicopathological parameters including tumor differentiation, invasive depth, TNM stage, lymph node metastasis, distant metastasis, and poor prognosis...
April 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440424/therapeutic-potential-of-the-antidiabetic-drug-metformin-in-small-bowel-adenocarcinoma
#14
Taiga Chiyo, Kiyohito Kato, Hisakazu Iwama, Shintaro Fujihara, Koji Fujita, Tomoko Tadokoro, Kyoko Ohura, Eri Samukawa, Yoshimi Yamana, Nobuya Kobayashi, Tae Matsunaga, Noriko Nishiyama, Maki Ayaki, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Tsutomu Masaki
Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440400/carnosic-acid-and-fisetin-combination-therapy-enhances-inhibition-of-lung-cancer-through-apoptosis-induction
#15
Bin Shi, Li-Fang Wang, Wen-Shu Meng, Liang Chen, Zi-Li Meng
Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440399/%C3%AE-1-antitrypsin-promotes-lung-adenocarcinoma-metastasis-through-upregulating-fibronectin-expression
#16
Yan Li, Liyun Miao, Min Yu, Minke Shi, Yongsheng Wang, Jun Yang, Yonglong Xiao, Hourong Cai
α1-antitrypsin (AAT) has been recognized to be associated with lung adenocarcinoma metastasis. However, the mechanisms by which AAT promotes tumor metastasis remain to be investigated. Herein, we first examined AAT expression in a panel of formalin-fixed paraffin-embedded tumor tissues from 88 lung adenocarcinoma patients undergoing curative resection, using immunohistochemical methods. Lung adenocarcinoma patients with high AAT expression showed a significantly shorter overall survival compared to those with low AAT expression by Kaplan-Meier method (P=0...
April 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#17
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28438626/near-infrared-intraoperative-molecular-imaging-can-identify-metastatic-lymph-nodes-in-prostate-cancer
#18
Leilei Xia, Ryan Zeh, Jack Mizelle, Andrew Newton, Jarrod Predina, Shuming Nie, Sunil Singhal, Thomas J Guzzo
OBJECTIVE: To propose a novel method to perform indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging during pelvic lymph node dissection (PLND) for prostate cancer patients with lymph node metastasis (LNM). MATERIALS AND METHODS: A prostate cancer cell line PC3 was used to establish xenograft model in NOD/SCID mouse. After tumor growth, mice were injected through the tail vein with ICG. Xenografts and surrounding tissues were imaged with NIR camera 24 hours after intravenous ICG and tumor-to-background ratios (TBRs) were calculated...
April 21, 2017: Urology
https://www.readbyqxmd.com/read/28438054/evaluation-of-active-hexose-correlated-compound-ahcc-in-combination-with-anticancer-hormones-in-orthotopic-breast-cancer-models
#19
Lata Mathew, Anjali Gaikwad, Anneliese Gonzalez, Elizabeth K Nugent, Judith A Smith
OBJECTIVE: To determine the impact on antitumor activity when active hexose correlated compound (AHCC) in combination with anticancer hormonal agents in orthotopic mouse models of human estrogen receptor positive breast cancer and evaluate impact of AHCC on aromatase activity. METHODS: The study consisted of 7 treatment arms (n=10) conducted in 2 breast cancer mouse models: MCF-7 and ZR-75. Treatment groups included untreated, vehicle, AHCC 50 mg/kg, AHCC 50 mg/kg + tamoxifen 10 mg/kg, tamoxifen 10 mg/kg, AHCC 50 mg/kg + letrozole 10 µg/mouse, or letrozole 10 µg/mouse...
April 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28434866/lentiviral-vectors-with-cellular-promoters-correct-anemia-and-lethal-bone-marrow-failure-in-a-mouse-model-for-diamond-blackfan-anemia
#20
Shubhranshu Debnath, Pekka Jaako, Kavitha Siva, Michael Rothe, Jun Chen, Maria Dahl, H Bobby Gaspar, Johan Flygare, Axel Schambach, Stefan Karlsson
Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient mice. In our present study, we assessed the efficacy of a clinically relevant promoter, the human elongation factor 1α short promoter, with or without the locus control region of the β-globin gene for treatment of RPS19-deficient Diamond-Blackfan anemia...
April 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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