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https://www.readbyqxmd.com/read/29220793/design-synthesis-and-biological-evaluation-of-novel-highly-selective-polo-like-kinase-2-inhibitors-based-on-the-tetrahydropteridin-chemical-scaffold
#1
Mei-Miao Zhan, Yang Yang, Jinfeng Luo, Xing-Xing Zhang, Xuan Xiao, Shiyu Li, Kai Cheng, Zhouling Xie, Zhengchao Tu, Chenzhong Liao
Polo-like kinase 2 (Plk2) is a potential target for the treatment of cancer, which displays an important role in tumor cell proliferation and survival. In this report, according to the analysis of critical amino acid residue differences among Plk1, Plk2 and Plk3, and structure-based drug design strategies, two novel series of selective Plk2 inhibitors based on tetrahydropteridin chemical scaffold were designed and synthesized to target two specific residues, Lys86 and Tyr161 of Plk2. All compounds were evaluated for their inhibitory activity against Plk1-Plk3 and the cellular inhibition activity on six different human cancer cell lines...
November 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29220745/identification-and-characterization-of-six-peroxiredoxin-transcripts-from-mud-crab-scylla-paramamosain-the-first-evidence-of-peroxiredoxin-gene-family-in-crustacean-and-their-expression-profiles-under-biotic-and-abiotic-stresses
#2
Dan-Dan Tu, Yi-Lian Zhou, Wen-Bin Gu, Qi-Hui Zhu, Bin-Peng Xu, Zhong-Kai Zhou, Ze-Peng Liu, Cong Wang, Yu-Yin Chen, Miao-An Shu
The peroxiredoxins (Prxs) define a novel and evolutionarily conserved superfamily of peroxidases able to protect cells from oxidative damage by catalyzing the reduction of a wide range of cellular peroxides. Prxs have been identified in prokaryotes as well as in eukaryotes, however, the composition and number of Prxs family members vary in different species. In this study, six Prxs were firstly identified from the mud crab Scylla paramamosain by RT-PCR and RACE methods. Six SpPrxs can be subdivided into three classes: (a) three typical 2-Cys enzymes denominated as Prx1/2, 3, 4, (b) two atypical 2-Cys enzymes known as Prx5-1 and Prx5-2, and (c) a 1-Cys isoform named Prx6...
December 4, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29220731/quantitative-texture-analysis-in-the-prediction-of-idh-status-in-low-grade-gliomas
#3
Asgeir Store Jakola, Yi-Hua Zhang, Anne J Skjulsvik, Ole Solheim, Hans Kristian Bø, Erik Magnus Berntsen, Ingerid Reinertsen, Sasha Gulati, Petter Förander, Torkel B Brismar
OBJECTIVES: Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI). PATIENTS AND METHODS: All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008-2015 were retrospectively identified...
December 5, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29220723/gold-nanoparticles-enhance-radiation-sensitization-and-suppress-colony-formation-in-a-feline-injection-site-sarcoma-cell-line-in-vitro
#4
J Z Benton, R J Williams, A Patel, K Meichner, J Tarigo, K Nagata, T D Pethel, R M Gogal
Injection Site Sarcomas (ISS) are highly invasive feline malignant tumors that are frequently associated with routine vaccination. Current treatment modalities include chemotherapy, radiation, and radical surgery. ISS have been shown to be one of the most treatment resistant of feline cancers with high rates of recurrence. Previous studies have shown that gold and other high atomic number nanoparticles have the ability to increase the dose of radiation deposited into tissue by generating secondary electrons...
December 2, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/29220700/prognostic-importance-of-aurora-kinases-and-mitotic-spindle-genes-transcript-levels-in-myelodysplastic-syndrome
#5
Daniela de Paula Borges, Antônio Wesley Araújo Dos Santos, Carlos Roberto Koscky Paier, Howard Lopes Ribeiro, Marília Braga Costa, Izabelle Rocha Farias, Roberta Taiane Germano de Oliveira, Ivo Gabriel da Frota França, Gabrielle Melo Cavalcante, Sílvia Maria Meira Magalhães, Ronald Feitosa Pinheiro
Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (p21) are directly related to chromosomal stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients using a real-time PCR methodology...
November 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29220669/modulation-of-dietary-folate-with-age-confers-selective-hepatocellular-epigenetic-imprints-through-dna-methylation
#6
Rauf Ahmad Najar, Nissar Ahmad Wani, Javeed Ahmad Bhat, Nawab John Dar, Beenish Rahat, Ajai Prakash Gupta, Jaspreet Kaur, Jyotdeep Kaur, Abid Hamid
The present study has been designed to determine the effect of folate modulation (deficiency/supplementation) with aging on the promoter methylation of tumor suppressor and proto-oncogenes to understand the underlying mechanism of epigenetic alterations. Folate deficiency was induced for 3 and 5 months in weanling, young and adult groups, and after 3 months of folate deficiency, they were repleted with physiological folate (2 mg/kg diet) and folate oversupplementation (8 mg/kg diet) for another 2 months. The methylation facet in the present study revealed that the combined effect of folate deficiency and aging decreased the methylation index...
November 2, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29220605/nut-midline-carcinoma-of-the-lung-in-a-six-year-old-child
#7
Esra Karakuş, Aylar Poyraz, Ayşe Selcen Oğuz Erdogan, Suna Emir, Derya Özyörük
BACKGROUND: Nuclear protein of the testis (NUT) midline carcinoma is genetically defined by rearrangement of NUT or by immunohistochemical expression of NUT. FINDINGS: A 6-year old child had a NUT midline carcinoma of the lung. Despite aggressive therapy, the child died. CONCLUSION: NUT carcinoma, which can be diagnosed immunohistochemically, remains an aggressive tumor.
December 8, 2017: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/29220578/pd-1-pd-l1-pathway-mediates-the-alleviation-of-pulmonary-fibrosis-by-human-mesenchymal-stem-cells-in-humanized-mice
#8
Ke Ni, Ming Liu, Jian Zheng, Liyan Wen, Qingyun Chen, Zheng Xiang, Kowk-Tai Lam, Yinping Liu, Godfrey Chi-Fung Chan, Yu-Lung Lau, Wenwei Tu
RATIONALE: Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSC) have been shown to be beneficial to pulmonary fibrosis as they have the immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSC in vivo. METHODS: Here, to mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. Based on this model, the benefit of human MSC to pulmonary fibrosis and underlying mechanism were investigated...
December 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29220576/oxygenic-hybrid-semiconducting-nanoparticles-for-enhanced-photodynamic-therapy
#9
Houjuan Zhu, Jingchao Li, Xiaoying Qi, Peng Chen, Kanyi Pu
Photodynamic nanotheranostics has shown great promise for cancer therapy; however, its therapeutic efficacy is limited due to the hypoxia of tumor microenvironment and the unfavorable bioavailability of existing photodynamic agents. We herein develop hybrid core-shell semiconducting nanoparticles (SPN-Ms) that can undergo O2 evolution in hypoxic solid tumor to promote photodynamic process. Such oxygenic nanoparticles are synthesized through a one-pot surface growth reaction and have a unique multilayer structure cored and coated with semiconducting polymer nanoparticles (SPNs) and manganese dioxide (MnO2) nanosheets, respectively...
December 8, 2017: Nano Letters
https://www.readbyqxmd.com/read/29220539/significance-and-mechanism-of-androgen-receptor-ar-overexpression-and-ar-mtor-crosstalk-in-hepatocellular-carcinoma
#10
Hong Zhang, Xiaoxing Li, Yang Yang, Yanjie Zhang, Hui-Yun Wang, X F Steven Zheng
Hepatocellular carcinoma (HCC) is a male-dominant cancer and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous anti-androgen and -AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth and determines therapeutic response to enzalutamide, a second generation of AR antagonist...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29220536/cd36-deficiency-attenuates-immune-mediated-hepatitis-in-mice-by-modulating-the-proapoptotic-effects-of-cxcl10
#11
Che Xu, Chen Zhang, Jie Ji, Chao Wang, Jing Yang, Biao Geng, Ting Zhao, Hong Zhou, Xianmin Mu, Jinshun Pan, Shi Hu, Yuanfang Lv, Xingguo Chen, Hao Wen, Qiang You
The scavenger receptor, CD36, recognizes a diverse set of ligands, and has been implicated in a wide variety of normal and pathological processes, including lipid metabolism, angiogenesis, atherosclerosis, and phagocytosis. In particular, recent findings have demonstrated its crucial functions in sterile inflammation and tumor metastasis. However, the role of CD36 in immune-mediated hepatitis remains unclear. Concanavalin A (Con A)-induced liver injury is a well-established experimental T cell-mediated hepatitis...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29220501/combination-of-247-genome-wide-association-studies-reveals-high-cancer-risk-as-a-result-of-evolutionary-adaptation
#12
Konstantinos Voskarides
Analysis of GLOBOCAN-2012 data shows clearly here that cancer incidence worldwide is highly related with low average annual temperatures and extreme low temperatures. This applies for all cancers together or separately for many frequent or rare cancer types (all cancers P = 9.49 x 10-18). Supporting fact is that Inuit people, living at extreme low temperatures, have the highest cancer rates today. Hypothesizing an evolutionary explanation, 240 cancer genome-wide association studies (GWAS) and seven GWAS for cold and high-altitude adaptation were combined...
December 5, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29220430/postoperative-outcomes-in-ustekinumab-treated-patients-undergoing-abdominal-operations-for-crohn-s-disease
#13
Amy L Lightner, Nicholas P McKenna, Chung Sang Tse, Neil Hyman, Radhika Smith, Gayane Ovsepyan, Phillip Fleshner, Kristen Crowell, Walter Koltun, Marc Ferrante, Andre D'Hoore, Nathalie Lauwers, Bram Verstockt, Antonino Spinelli, Francesca DiCandido, Laura E Raffals, Kellie L Mathis, Edward V Loftus
Introduction: Ustekinumab, a monoclonal antibody targeting interleukins-12 and -23 is used to treat adults with Crohn's disease (CD). We determined the 30-day postoperative infectious complication rate among CD patients who received ustekinumab within 12 weeks prior to an abdominal operation as compared to patients who received anti-tumor necrosis factor (TNF) agents. Methods: A retrospective chart review of adults with CD who underwent an abdominal operation between 1/1/2015 and 5/1/2017 was performed across six sites...
December 6, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29220427/steroid-but-not-biological-therapy-elevates-the-risk-of-venous-thromboembolic-events-in-inflammatory-bowel-disease-a-meta-analysis
#14
Patricia Sarlos, Kata Szemes, Peter Hegyi, Andras Garami, Imre Szabo, Anita Illes, Margit Solymar, Erika Petervari, Aron Vincze, Gabriella Par, Judit Bajor, Jozsef Czimmer, Orsolya Huszar, Peter Varju, Nelli Farkas
Background and aim: Inflammatory bowel disease [IBD] is associated with 1.5- to 3-fold increased risk of venous thromboembolic events [VTE]. The aim of this study was to determine the risk of VTE in IBD as a complication of systemic corticosteroids and anti-tumor necrosis factor alpha [TNFα] therapies. Methods: A systematic review and meta-analysis was conducted, which conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA] statement...
December 6, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29220404/pymt-maclow-a-novel-inducible-murine-model-for-determining-the-role-of-cd68-positive-cells-in-breast-tumor-development
#15
Robin M H Rumney, Seth B Coffelt, Terence A Neale, Sandeep Dhayade, Gillian M Tozer, Gaynor Miller
CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development...
2017: PloS One
https://www.readbyqxmd.com/read/29220395/microrna-93-promotes-proliferation-and-metastasis-of-gastric-cancer-via-targeting-timp2
#16
Hao Guan, Weiming Li, Yuanyuan Li, Jichang Wang, Yan Li, Yanan Tang, Shaoying Lu
MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29220390/maldi-msi-of-melim-melanoma-searching-for-differences-in-protein-profiles
#17
Roman Guran, Lucie Vanickova, Vratislav Horak, Sona Krizkova, Petr Michalek, Zbynek Heger, Ondrej Zitka, Vojtech Adam
BACKGROUND: Treatment of advanced cutaneous melanoma remains challenging, and new data on melanoma biology are required. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional tumor markers is thus of paramount importance. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), an important tool in cancer research, is useful for unraveling the molecular profile of melanoma...
2017: PloS One
https://www.readbyqxmd.com/read/29220380/hexokinase-2-hk2-the-tumor-promoter-in-glioma-is-downregulated-by-mir-218-bmi1-pathway
#18
Hui Liu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Xiaoshan Xu, Zhen Wang, Yanyang Tu
In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29220303/locally-aggressive-connective-tissue-tumors
#19
Mrinal M Gounder, David M Thomas, William D Tap
In this review, we highlight the complexities of the natural history, biology, and clinical management of three intermediate connective tissue tumors: desmoid tumor (DT) or aggressive fibromatosis, tenosynovial giant cell tumor (TGCT) or diffuse-type pigmented villonodular synovitis (dtPVNS), and giant cell tumor of bone (GCTB). Intermediate histologies include tumors of both soft tissue and bone origin and are locally aggressive and rarely metastatic. Some common aspects to these tumors are that they can be locally infiltrative and/or impinge on critical organs, which leads to disfigurement, pain, loss of function and mobility, neurovascular compromise, and occasionally life-threatening consequences, such as mesenteric, bowel, ureteral, and/or bladder obstruction...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29220302/biology-and-management-of-undifferentiated-pleomorphic-sarcoma-myxofibrosarcoma-and-malignant-peripheral-nerve-sheath-tumors-state-of-the-art-and-perspectives
#20
Brigitte C Widemann, Antoine Italiano
Undifferentiated pleomorphic sarcomas, myxofibrosarcomas, and malignant peripheral nerve sheath tumors are characterized by complex genomic characteristics and aggressive clinical behavior. Recent advances in the understanding of the pathogenesis of these tumors may allow for the development of more-effective innovative therapeutic strategies, including immunotherapies. This review describes the current knowledge of the epidemiology, clinical presentation, treatment, and pathogenesis of these tumors and highlights ongoing and future research...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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