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https://www.readbyqxmd.com/read/29149649/chk1-inhibitors-overcome-imatinib-resistance-in-chronic-myeloid-leukemia-cells
#1
Hu Lei, Jin Jin, Meng Liu, Xiangyun Li, Hao Luo, Li Yang, Hanzhang Xu, Yingli Wu
Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem of chronic myelogenous leukemia (CML). Bcr-Abl protein depletion is considered as a way to overcome drug resistance to TKIs. In our study, Chk1 inhibitors, AZD7762 and MK-8776, had strong antitumor effects on CML cell line KBM5 and imatinib-resistant form KBM5(T315I). Moreover, Chk1 inhibitors showed a strong cytotoxic effect on leukemia cells from primary CML and imatinib-resistance CML patients, but low cytotoxic effect on normal human mononuclear cells...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#2
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29149451/transcriptional-alterations-in-hereditary-and-sporadic-nonfunctioning-pancreatic-neuroendocrine-tumors-according-to-genotype
#3
Xavier M Keutgen, Suresh Kumar, Sudheer Gara, Myriem Boufraqech, Sunita Agarwal, Ralph H Hruban, Naris Nilubol, Martha Quezado, Richard Finney, Maggie Cam, Electron Kebebew
BACKGROUND: Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype...
November 17, 2017: Cancer
https://www.readbyqxmd.com/read/29149426/relationship-between-lat1-expression-and-resistance-to-chemotherapy-in-pancreatic-ductal-adenocarcinoma
#4
Bolag Altan, Kyoichi Kaira, Akira Watanabe, Norio Kubo, Pinjie Bao, Gantumur Dolgormaa, Erkhem-Ochir Bilguun, Kenichiro Araki, Yoshikatsu Kanai, Takehiko Yokobori, Tetsunari Oyama, Masahiko Nishiyama, Hiroyuki Kuwano, Ken Shirabe
PURPOSE: L-type amino acid transporter 1 (LAT1) is linked to tumor cell proliferation, angiogenesis, and survival in various human cancers. Although the expression of LAT1 was identified as a significant prognostic predictor after surgery in patients with pancreatic ductal adenocarcinoma (PDAC), little is known about the clinical significance of LAT1 as a chemotherapeutic resistance factor in PDAC. METHODS: A total of 110 patients with surgically resected PDAC were retrospectively reviewed as the training set...
November 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29149416/history-of-histamine-releasing-factor-hrf-translationally-controlled-tumor-protein-tctp-including-a-potential-therapeutic-target-in-asthma-and-allergy
#5
Susan M MacDonald
Histamine-releasing factor (HRF) also known as translationally controlled tumor protein (TCTP) is a highly conserved, ubiquitous protein that has both intracellular and extracellular functions. Here we will highlight the subcloning of the molecule, its clinical implications, as well as an inducible-transgenic mouse. Particular attention will be paid to its extracellular functioning and its potential role as a therapeutic target in asthma and allergy. The cells and the cytokines that are produced when stimulated or primed by HRF/TCTP will be detailed as well as the downstream signaling pathway that HRF/TCTP elicits...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149415/targeting-tctp-with-sertraline-and-thioridazine-in-cancer-treatment
#6
Robert Amson, Christian Auclair, Fabrice André, Judith Karp, Adam Telerman
We have initially demonstrated in knocking down experiments that decreasing TCTP in cancer cells leads in some tissues to cell death while in others to a complete reorganization of the tumor into architectural structures reminiscent of normal ones. Based on these experiments and a series of other findings confirming the key role of TCTP in cancer, it became important to find pharmacological compounds to inhibit its function, and this became for us a priority. In the present text, we explain in detail the experiments that were performed and the perspectives of sertraline in cancer treatment, as this became today a reality with a clinical study that started in collaboration with Columbia University and Johns Hopkins University...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#7
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149405/current-understanding-of-the-tctp-interactome
#8
Siting Li, Feng Ge
Evolutionarily conserved and pleiotropic, the translationally controlled tumor protein (TCTP) is a housekeeping protein present in eukaryotic organisms. It plays an important role in regulating many fundamental processes, such as cell proliferation, cell death, immune responses, and apoptosis. As a result of the pioneer work by Adam Telerman and Robert Amson, the critical role of TCTP in tumor reversion was revealed. Moreover, TCTP has emerged as a regulator of cell fate determination and a promising therapeutic target for cancers...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#9
REVIEW
Shailaja Mahajan-Thakur, Sandra Bien-Möller, Sascha Marx, Henry Schroeder, Bernhard H Rauch
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29148898/enhancement-of-invadopodia-activity-in-glioma-cells-by-sublethal-doses-of-irradiation-and-temozolomide
#10
Leon Mao, Clarissa A Whitehead, Lucia Paradiso, Andrew H Kaye, Andrew P Morokoff, Rodney B Luwor, Stanley S Stylli
OBJECTIVE Glioblastoma is the most common primary central nervous system tumor in adults. These tumors are highly invasive and infiltrative and result in tumor recurrence as well as an extremely poor patient prognosis. The current standard of care involves surgery, radiotherapy, and chemotherapy. However, previous studies have suggested that glioblastoma cells that survive treatment are potentially more invasive. The goal of this study was to investigate whether this increased phenotype in surviving cells is facilitated by actin-rich, membrane-based structures known as invadopodia...
November 17, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29148709/nir-emitting-nanoprobes-based-on-cyclic-rgd-motif-conjugated-pbs-quantum-dots-for-integrin-targeted-optical-bioimaging
#11
Nicoletta Depalo, Michela Corricelli, Ivan de Paola, Gianpiero Valente, Rosa M Iacobazzi, Emiliano Altamura, Doriana Debellis, Daniela Comegna, Elisabetta Fanizza, Nunzio Denora, Valentino Laquintana, Fabio Mavelli, Marinella Striccoli, Michele Saviano, Angela Agostiano, Annarita Del Gatto, Laura Zaccaro, Maria Lucia Curri
Here, silica coated PbS quantum dots (QDs) with photoluminesce emission properties in the near-infrared (NIR) region are proposed as potential effective single particle optical nanoprobes for future in vivo imaging of tumors. The dispersibility in aqueous medium of hydrophobic PbS QDs was accomplished by growing a silica shell on their surface by exploiting a base assisted water-in-oil microemulsion method. The silica coated PbS QDs were then conjugated with specifically designed cyclic arginine-glycine-aspartic acid (cRGD) peptide, that are able to specifically recognizes the αvβ3 integrins which is overexpressed in the angiogenic tumor induced vasculatures and on some solid tumours, in order to achieve a tumor-specific targeting...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29148707/versatile-supermolecular-inclusion-complex-based-on-host-guest-interaction-for-targeted-gene-delivery
#12
Yunxia Sun, Jingyi Zhu, Wen-Xiu Qiu, Qi Lei, Si Chen, Xian-Zheng Zhang
A facile and targeted gene delivery system was prepared by conjugating β-cyclodextrin modified polyethylenimine (PEI-CD) and adamantyl peptide (AdGRGDS) based on host-guest interaction. With the rational design between PEI-CD and AdGRGDS, PEI-CD/AdGRGDS gene delivery system showed excellent DNA binding capability, and exhibited good ability to compact DNA into uniform spherical nanoparticles. In vitro luciferase assay showed that gene expression transfected by PEI-CD/AdGRGDS was stronger than that by PEI-CD in HeLa cells, whereas, gene expression transfected by PEI-CD/AdGRGDS and PEI-CD was similar to each other in COS7 cells...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29148570/robust-optimization-in-impt-using-quadratic-objective-functions-to-account-for-the-minimum-mu-constraint
#13
Jie Shan, Yu An, Martin Bues, Steven E Schild, Wei Liu
PURPOSE: Currently, in clinical practice of intensity-modulated proton therapy (IMPT), the influence of the minimum monitor unit (MU) constraint is taken into account through post-processing after the optimization is completed. This may degrade the plan quality and plan robustness. This study aims to mitigate the impact of the minimum MU constraint directly during the plan robust optimization. METHODS AND MATERIALS: Cao et al. have demonstrated a two-stage method to account for the minimum MU constraint using linear programming without the impact of uncertainties considered...
November 17, 2017: Medical Physics
https://www.readbyqxmd.com/read/29148538/molecular-testing-for-braf-mutations-to-inform-melanoma-treatment-decisions-a-move-toward-precision-medicine
#14
Liang Cheng, Antonio Lopez-Beltran, Francesco Massari, Gregory T MacLennan, Rodolfo Montironi
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148169/antitumor-and-anti-metastatic-mechanisms-of-rhizoma-paridis-saponins-in-lewis-mice
#15
Shuli Man, Hongyan Chai, Jingxia Cui, Jingwen Yao, Long Ma, Wenyuan Gao
Lung cancer is one of the most common causes of death in the world. Rhizoma paridis saponins (RPS) have been found to show inhibition of pulmonary adenoma in previous research. However, the detailed mechanisms of RPS from a holistic view have not been established. In this study, Lewis pulmonary adenoma mice were successfully established to analyze the pathways involved in RPS intervening tumor formation and progression. As a result, RPS inhibited levels of cytokines or receptors such as VEGFD, VEGFR3, RAGE, IL6R, IL17BR, and CXCL16 which were regarded as the initiators induced tumor cell proliferation, adhesion, angiogenesis, and invasion...
November 17, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29147911/dj-1-as-a-therapeutic-target-against-cancer
#16
Ji Cao, Xiaobing Chen, Meidan Ying, Qiaojun He, Bo Yang
DJ-1 is a gene involved in various cellular processes, including transcriptional regulation, oxidative stress response, fertilization, mitochondrial regulation, inflammatory and fibrogenic niche formation, and glycation damage prevention. Although a disease-associated genetic study within the past decade has demonstrated that the mutation of DJ-1 is associated with autosomal early-onset Parkinson's disease, increasing evidence suggests that DJ-1 also plays a critical role in tumor development and progression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147881/childhood-cancer-and-brain-tumor-late-effects-relationships-with-family-burden-and-survivor-psychological-outcomes
#17
Melissa K Cousino, Rebecca Hazen, Katherine Leigh Josie, Kelly Laschinger, Peter de Blank, H Gerry Taylor
This study examines illness-specific family burden as a mediator of the association between late effects of childhood cancer and survivors' emotional and behavioral outcomes. Childhood cancer survivors (n = 65; ages 10-17) two or more years off-treatment completed measures assessing internalizing and PTSD symptoms. Parents reported on illness-specific family burden, late effects severity, and survivor internalizing/externalizing problems. Providers documented the number of late effects. Illness-specific family burden was correlated with provider-reported late effects (r = ...
November 16, 2017: Journal of Clinical Psychology in Medical Settings
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#18
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29147764/prospective-evaluation-of-18-f-facbc-pet-ct-and-pet-mri-versus-multiparametric-mri-in-intermediate-to-high-risk-prostate-cancer-patients-flucipro-trial
#19
Ivan Jambor, Anna Kuisma, Esa Kähkönen, Jukka Kemppainen, Harri Merisaari, Olli Eskola, Jarmo Teuho, Ileana Montoya Perez, Marko Pesola, Hannu J Aronen, Peter J Boström, Pekka Taimen, Heikki Minn
PURPOSE: The purpose of this study was to evaluate (18)F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). METHODS: Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq (18)F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUVmax) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans...
November 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29147733/-inhibitors-of-the-androgen-receptor-n%C3%A2-terminal-domain-therapies-targeting-the-achilles-heel-of-various-androgen-receptor-molecules-in-advanced-prostate-cancer
#20
REVIEW
M C Hupe, A Offermann, F Perabo, C Chandhasin, S Perner, A S Merseburger, M V Cronauer
Although prostate cancer responds well to primary endocrine therapies, tumor progression with castration resistant tumor cells almost invariably occurs within a few years. Unfortunately, some CRPC patients do not respond to second-line therapies with abiraterone or enzalutamide. Moreover, patients who initially responded well to second-line hormone therapy develop resistance to abiraterone and/or enzalutamide within a short period of time. Besides an increase of intracellular androgen receptor (AR) levels, the predominant resistance mechanisms include AR aberrations (point mutations, AR splice variants) occurring predominantly at the androgen or ligand binding domain of the AR...
November 16, 2017: Der Urologe. Ausg. A
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