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Hany M Hassanin, Rabah A T Serya, Wafaa R Abd Elmoneam, Mai A Mostafa
A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the Discovery Studio 2.5 software, where they showed very interesting ability to intercalate the DNA-topoisomerase complex. Compounds 2a , 2c and 2f showed high docking score values (82...
June 2018: Royal Society Open Science
Angela C Tramontano, Ryan Nipp, Nathaniel D Mercaldo, Chung Yin Kong, Deborah Schrag, Chin Hur
BACKGROUND: Survival outcome disparities among esophageal cancer patients exist, but are not fully understood. AIMS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine whether survival differences among racial/ethnic patient populations persist after adjusting for demographic and clinical characteristics. METHODS: Our study included T1-3N0M0 adenocarcinoma and squamous cell cancer patients diagnosed between 2003 and 2011...
August 14, 2018: Digestive Diseases and Sciences
Anna L Means, Tanner J Freeman, Jing Zhu, Luke G Woodbury, Paula Marincola-Smith, Chao Wu, Anne R Meyer, Connie J Weaver, Chandrasekhar Padmanabhan, Hanbing An, Jinghuan Zi, Bronson C Wessinger, Rupesh Chaturvedi, Tasia D Brown, Natasha G Deane, Robert J Coffey, Keith T Wilson, J Joshua Smith, Charles L Sawyers, James R Goldenring, Sergey V Novitskiy, M Kay Washington, Chanjuan Shi, R Daniel Beauchamp
Background & Aims: Chronic inflammation is a predisposing condition for colorectal cancer. Many studies to date have focused on proinflammatory signaling pathways in the colon. Understanding the mechanisms that suppress inflammation, particularly in epithelial cells, is critical for developing therapeutic interventions. Here, we explored the roles of transforming growth factor β (TGFβ) family signaling through SMAD4 in colonic epithelial cells. Methods: The Smad4 gene was deleted specifically in adult murine intestinal epithelium...
2018: Cellular and Molecular Gastroenterology and Hepatology
Zijun Zhao, Yu Chen, Ngiambudulu M Francisco, Yuanqing Zhang, Minhao Wu
Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma...
July 2018: Acta Pharmaceutica Sinica. B
Marina P Savić, Jovana J Ajduković, Jovana J Plavša, Sofija S Bekić, Andjelka S Ćelić, Olivera R Klisurić, Dimitar S Jakimov, Edward T Petri, Evgenija A Djurendić
New A-ring pyridine fused androstanes in 17a-homo-17-oxa (d-homo lactone), 17α-picolyl or 17( E )-picolinylidene series were synthesized and validated by X-ray crystallography, HRMS, IR and NMR spectroscopy. Novel compounds 3 , 5 , 8 and 12 were prepared by treatment of 4-en-3-one or 4-ene-3,6-dione d-modified androstane derivatives with propargylamine catalyzed by Cu(ii), and evaluated for potential anticancer activity in vitro using human cancer cell lines and recombinant targets of steroidal anti-cancer drugs...
June 1, 2018: MedChemComm
H M Manukumar, B Chandrasekhar, K P Rakesh, A P Ananda, M Nandhini, P Lalitha, S Sumathi, Hua-Li Qin, S Umesha
Staphylococcus aureus is a commonly found pathogen that can cause food-spoilage and life threatening infections. However, the potential molecular effects of natural active thymol molecules and chitosan silver nanoparticles (C@AgNPs) in bacteria remain unclear. This gap in the literature has prompted us to study the effects of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) against biofilm associated proteins in methicillin-resistant S. aureus (Bap-MRSA) 090 and also their toxicity, anti-cancer activity, and validation of their in silico molecular docking...
December 1, 2017: MedChemComm
XiXi Xu, Tristan Rawling, Ariane Roseblade, Roger Bishop, Alison T Ung
Tricyclic alkaloid-like compounds were synthesised in a few steps, via the bridging Ritter reaction. The compounds were evaluated for their antiproliferative activity against the MCF-7 and the aggressive MDA-MB-231 breast cancer cells. The anti-cancer activities of 2c were found to be selective towards the aggressive and more challenging to treat triple negative (MDA-MB-231) cell line while exhibiting no antiproliferative activities towards the MCF-7 cells at the highest concentration tested (50 μM). The IC50 of compound 2c was determined to be 7...
November 1, 2017: MedChemComm
Angela Rita Elia, Sara Caputo, Matteo Bellone
Prostate adenocarcinoma (PCa) and melanoma are paradigmatic examples of tumors that are either poorly or highly sensitive to therapies based on monoclonal antibodies directed against regulatory pathways in T lymphocytes [i.e., immune checkpoint blockade (ICB)]. Yet, approximately 40% of melanoma patients are resistant or acquire resistance to ICB. What characterize the microenvironment of PCa and ICB-resistant melanoma are a scanty cytotoxic T cell infiltrate and a strong immune suppression, respectively. Here, we compare the tumor microenvironment in these two subgroups of cancer patients, focusing on some among the most represented immune checkpoint molecules: cytotoxic T lymphocyte-associated antigen-4, programmed death-1, lymphocyte activation gene-3, and T cell immunoglobulin and mucin-domain containing-3...
2018: Frontiers in Immunology
Maysaloun Merhi, Afsheen Raza, Varghese Philipose Inchakalody, Abdulqadir Jeprel Japer Nashwan, Niloofar Allahverdi, Roopesh Krishnankutty, Shahab Uddin, Abdul Rehman Zar Gul, Mohammed Ussama Al Homsi, Said Dermime
Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention. The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses...
2018: Frontiers in Immunology
Jiyan Su, Lu Su, Dan Li, Ou Shuai, Yifan Zhang, Huijia Liang, Chunwei Jiao, Zhanchi Xu, Yong Lai, Yizhen Xie
As breast cancer is the leading cause of cancer-related deaths in women population worldwide, ongoing endeavor has been made for alternative regimens with improved efficacy but fewer adverse effects. Recently, active components from the spores of Ganoderma lucidum have attracted much attention for their versatile biological activities owing to the advance in sporoderm-breaking technology. Here, anticancer potential of an extract derived from the sporoderm-breaking spores of G. lucidum (ESG) was explored in a 4T1-breast cancer xenograft mice model...
2018: Frontiers in Immunology
Reza Elahi, Elnaz Khosh, Safa Tahmasebi, Abdolreza Esmaeilzadeh
T cells equipped with chimeric antigen receptors (CAR T cells) have recently provided promising advances as a novel immunotherapeutic approach for cancer treatment. CAR T cell therapy has shown stunning results especially in B-cell malignancies; however, it has shown less success against solid tumors, which is more supposed to be related to the specific characteristics of the tumor microenvironment. In this review, we discuss the structure of the CAR, current clinical advantages from finished and ongoing trials, adverse effects, challenges and controversies, new engineering methods of CAR, and clinical considerations that are associated with CAR T cell therapy both in hematological malignancies and solid tumors...
2018: Frontiers in Immunology
Michael Hubberten, Gregor Bochenek, Hong Chen, Robert Häsler, Ricarda Wiehe, Philip Rosenstiel, Søren Jepsen, Henrik Dommisch, Arne S Schaefer
Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA 1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis, and several forms of cancer. However, it is currently not understood how CDKN2B-AS1 transcripts translate into diabetes. We previously demonstrated trans-regulation of the proximal polyadenylated transcripts on several genes with functions in glucose and lipid metabolism. However, information on specific genes that are regulated at physiological concentrations by the distal polyadenylated CDKN2B-AS1 transcripts is lacking...
August 14, 2018: European Journal of Human Genetics: EJHG
Dushan N Wadduwage, Jennifer Kay, Vijay Raj Singh, Orsolya Kiraly, Michelle R Sukup-Jackson, Jagath Rajapakse, Bevin P Engelward, Peter T C So
Homologous recombination (HR) events are key drivers of cancer-promoting mutations, and the ability to visualize these events in situ provides important information regarding mutant cell type, location, and clonal expansion. We have previously created the Rosa26 Direct Repeat (RaDR) mouse model wherein HR at an integrated substrate gives rise to a fluorescent cell. To fully leverage this in situ approach, we need better ways to quantify rare fluorescent cells deep within tissues. Here, we present a robust, automated event quantification algorithm that uses image intensity and gradient features to detect fluorescent cells in deep tissue specimens...
August 14, 2018: Scientific Reports
Snigdha Majumder, Rakshit Shah, Jisha Elias, Malini Manoharan, Priyanka Shah, Anjali Kumari, Papia Chakraborty, Vasumathi Kode, Yogesh Mistry, Karunakaran Coral, Bharti Mittal, Sakthivel Murugan Sm, Lakshmi Mahadevan, Ravi Gupta, Amitabha Chaudhuri, Arati Khanna-Gupta
Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70-80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families. Since defects in DNA mismatch repair genes generate frame-shift mutations giving rise to highly immunogenic neoepitopes, we postulated that vaccination with these mutant peptide antigens could offer promising treatment options to LS patients...
August 14, 2018: Scientific Reports
Mohamed Y Elsaid, Ankita Shahi, Albert R Wang, Dana C Baiu, Chunrong Li, Lauryn R Werner, Sorabh Singhal, Lance T Hall, Jamey P Weichert, Eric A Armstrong, Bryan P Bednarz, Paul M Harari, Gopal Iyer, Mario Otto
Anti-tumor alkyl phospholipid analogs comprise a group of structurally related molecules with remarkable tumor selectivity. Some of these compounds have shown radiosensitizing capabilities. CLR127 is a novel, clinical-grade anti-tumor alkyl phospholipid ether analog, a subtype of synthetic alkyl phospholipids broadly targeting cancer cells with limited uptake in normal tissues. The purpose of this study was to investigate the effect of CLR127 to modulate radiation response across several adult and pediatric cancer types in vitro as well as in murine xenograft models of human prostate adenocarcinoma, neuroblastoma, Ewing sarcoma and rhabdomyosarcoma...
August 14, 2018: Molecular Cancer Therapeutics
X Lu, C Zhou, R F Li, J W Ye, W L Zhai
Objective: To investigate the effects of Kindlin-2 on malignant phenotypes of human gallbladder cancer cells and discuss the mechanisms. Methods: The expression level of Kindlin-2 in 30 cases of gallbladder cancer tissues and adjacent non-tumoral tissues collected from the First Affiliated Hospital of Zhengzhou University between September 2012 and May 2013 was assessed by real-time PCR and immunohistochemistry.Lentivirus-mediated Kindlin-2 overexpression was used in gallbladder cancer cell lines GBC-SD and SGC-996...
August 1, 2018: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
Feng Qiu, Kyle W Becker, Frances C Knight, Jessalyn J Baljon, Sema Sevimli, Daniel Shae, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Cancer vaccines targeting patient-specific tumor neoantigens have recently emerged as a promising component of the rapidly expanding immunotherapeutic armamentarium. However, neoantigenic peptides typically elicit weak CD8+ T cell responses, and so there is a need for universally applicable vaccine delivery strategies to enhance the immunogenicity of these peptides. Ideally, such vaccines could also be rapidly fabricated using chemically synthesized peptide antigens customized to an individual patient. Here, we describe a strategy for simple and rapid packaging of peptide antigens into pH-responsive nanoparticles with endosomal escape activity...
July 30, 2018: Biomaterials
Ian Ganly, Vladimir Makarov, Shyamprasad Deraje, YiYu Dong, Ed Reznik, Venkatraman Seshan, Gouri Nanjangud, Stephanie Eng, Promita Bose, Fengshen Kuo, Luc G T Morris, Inigo Landa, Pedro Blecua Carrillo Albornoz, Nadeem Riaz, Yuri E Nikiforov, Kepal Patel, Christopher Umbricht, Martha Zeiger, Electron Kebebew, Eric Sherman, Ronald Ghossein, James A Fagin, Timothy A Chan
The molecular foundations of Hürthle cell carcinoma (HCC) are poorly understood. Here we describe a comprehensive genomic characterization of 56 primary HCC tumors that span the spectrum of tumor behavior. We elucidate the mutational profile and driver mutations and show that these tumors exhibit a wide range of recurrent mutations. Notably, we report a high number of disruptive mutations to both protein-coding and tRNA-encoding regions of the mitochondrial genome. We reveal unique chromosomal landscapes that involve whole-chromosomal duplications of chromosomes 5 and 7 and widespread loss of heterozygosity arising from haploidization and copy-number-neutral uniparental disomy...
August 13, 2018: Cancer Cell
Adi Sharbi-Yunger, Mareike Grees, Cafri Gal, David Bassan, Stefan B Eichmüller, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach
For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen...
August 14, 2018: International Journal of Cancer. Journal International du Cancer
Yangyang Wang, Enhao Zhao, Zizhen Zhang, Gang Zhao, Hui Cao
The T‑cell immunoglobulin and mucin domain‑containing protein 3 (Tim‑3)/galectin 9 (Gal‑9) pathway, which serves a pivotal role in immune regulation, is similar to the programmed death (PD)‑1/PD‑ligand 1 pathway. Recent evidence has suggested that Tim‑3 is differentially regulated in a variety of tumors and is a potential therapeutic target. The aim of the present study was to evaluate Tim‑3 and Gal‑9 expression and cluster of differentiation (CD)3+, CD8+ and forkhead box (FOX)p3+ T cell tumor‑infiltration in gastric cancer, as well as their impact on prognosis...
August 6, 2018: Oncology Reports
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