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Tomoyuki Moriyama, Dai Kakiuchi, Luigi Grasso, David L Hutto, Danielle Fernando, Charles Schweizer
Farletuzumab is a humanized monoclonal antibody targeting human folate receptor alpha, which is being developed as an anti-cancer drug. A non-human primate reproductive study was conducted to evaluate whether it could cause any embryonic or fetal abnormalities. Farletuzumab was administered intravenously to pregnant cynomolgus monkeys (n = 16/group) at doses of 0 or 67.5 mg/kg once weekly during gestation day (GD) 20 through 97. C-section was performed on GD100 ± 2, and fetuses were evaluated for morphologic (external, visceral and skeletal) effects...
June 18, 2018: Reproductive Toxicology
Mehdi Dehghani, Reynolds K Brobey, Yue Wang, Glauco Souza, Robert J Amato, Kevin P Rosenblatt
Klotho is a single-pass transmembrane protein with documented anti-cancer properties. Recent reports have implicated Klotho as an inhibitor of transforming growth factor β1 induced cell migration in renal fibrosis. Overexpression of epidermal growth factor receptor (EGFR) is known to promote tumor initiation and progression in clear-cell renal cell carcinoma (cRCC). We tested our hypothesis that Klotho inhibits EGF-mediated cell migration in cRCC by interfering with the EGFR signaling complex and mitogen-activated protein kinase (MAPK) pathways...
June 1, 2018: Oncotarget
Huan Liu, Zhouping Yang, Linquan Zang, Guixiang Wang, Sigui Zhou, Guifang Jin, Zhicheng Yang, Xuediao Pan
Glutathione S-transferase A1 (GSTA1) is a phase II detoxification enzyme and serves a crucial role in anti-cancer drug resistance. In our previous study, GSTA1 was identified to be highly expressed in various subtypes of non-small-cell lung cancer cell lines compared with human embryonic lung fibroblast cell line MRC-5. The aim of the present study was to investigate the effect of GSTA1 expression on the proliferation and apoptosis of A549 cells. GSTA1 expression was knocked down or with overexpressed using lentivirus particles...
July 2018: Oncology Letters
Yi-Shih Ma, Chien-Ning Yao, Hsin-Chung Liu, Fu-Shun Yu, Jen-Jyh Lin, Kung-Wen Lu, Ching-Lung Liao, Fu-Shin Chueh, Jing-Gung Chung
Oral cancer is a cause of cancer-associated mortality worldwide and the treatment of oral cancer includes radiation, surgery and chemotherapy. Quercetin is a component from natural plant products and it has been demonstrated that quercetin is able to induce cytotoxic effects through induction of cell apoptosis in a number of human cancer cell lines. However, there is no available information to demonstrate that quercetin is able to induce apoptosis in human oral cancer cells. In the present study, the effect of quercetin on the cell death via the induction of apoptosis in human oral cancer SAS cells was investigated using flow cytometry, Annexin V/propidium iodide (PI) double staining, western blotting and confocal laser microscopy examination, to test for cytotoxic effects at 6-48 h after treatment with quercetin...
June 2018: Oncology Letters
Min Liu, Jie Ran, Jun Zhou
Kinesins are widely expressed, microtubule-dependent motors that play vital roles in microtubule-associated cellular activities, such as cell division and intracellular transport. Eg5, also known as kinesin-5 or kinesin spindle protein, is a member of the kinesin family that contributes to the formation and maintenance of the bipolar mitotic spindle during cell division. Small-molecule compounds that inhibit Eg5 activity have been shown to impair spindle assembly, block mitotic progression, and possess anti-cancer activity...
June 21, 2018: Thoracic Cancer
Jin Wang, Lu Qi, Zejuan Wang, Gang Chen, Chen Liu, Ying Liu, Xiaona Liu, Yu Wang, Chunpu Lei, Xinghe Wang
OBJECTIVE: Lenalidomide is a 4-amino-glutaryl derivative of thalidomide and belongs to a new generation of immunomodulatory agents for the treatment of patients with myelodysplastic syndrome and multiple myeloma. The aim of this study is to evaluate the bioequivalence and safety of a capsule containing 25 mg of a test formulation of lenalidomide and a 25 mg Revlimid® capsule in healthy, Chinese adult males for good quality anti-cancer medicine with lower costs. METHODS: This was a single-center, randomized, open-label, single-dose, two-period, crossover pharmacokinetic study...
July 2018: Cancer Chemotherapy and Pharmacology
Ryota Kanemaru, Fumiyuki Takahashi, Motoyasu Kato, Yoichiro Mitsuishi, Ken Tajima, Hiroaki Ihara, Moulid Hidayat, Aditya Wirawan, Yoshika Koinuma, Daisuke Hayakawa, Shigehiro Yagishita, Ryo Ko, Tadashi Sato, Norihiro Harada, Yuzo Kodama, Fariz Nurwidya, Shinichi Sasaki, Shin-Ichiro Niwa, Kazuhisa Takahashi
PURPOSE: Transforming growth factor β (TGFβ)-mediated epithelial-mesenchymal transition (EMT) of alveolar epithelial cells contributes to pulmonary fibrosis. Dasatinib (DAS), a potent and broad-spectrum tyrosine kinase inhibitor, has been widely studied as an anti-cancer agent. However, the therapeutic application of DAS for pulmonary fibrosis has not been clarified. Our purpose here is to investigate the effect of DAS on TGFβ1-induced EMT in human alveolar and bronchial epithelial cells in vitro and to evaluate the efficacy of DAS on lung fibrosis in vivo...
June 20, 2018: Lung
Mohammad Norouzi, Zahra Abdali, Song Liu, Donald W Miller
Salinomycin is an antibiotic that has recently been introduced as a novel and effective anti-cancer drug. In this study, PLGA nanofibers (NFs) containing salinomycin (Sali) were fabricated by electrospinning for the first time. The biodegradable PLGA NFs had stability for approximately 30 days and exhibited a sustained release of the drug for at least a 2-week period. Cytotoxicity of the NFs + Sali was evaluated on human glioblastoma U-251 cells and more than 50% of the treated cells showed apoptosis in 48 h...
June 20, 2018: Scientific Reports
Ashley Leak Bryant, Sarah W Drier, Sejin Lee, Antonia V Bennett
The purpose of this systematic literature review was to identify clinical trials of MDS and AML that included patient-reported outcome (PRO) instruments, and to summarize the symptom and other health related quality of life (HRQOL) concepts most frequently assessed and the PRO instruments that were used. Sixteen manuscripts describing 14 distinct trials met all criteria (i.e., phase 2 or 3 clinical trial for MDS or AML which included PRO assessment) and were published between 1996-2017. In trials evaluating anemia, PRO scores showed significant improvement in relevant domains (e...
June 7, 2018: Leukemia Research
Laurence Booth, Jane L Roberts, Rumeesa Rais, Andrew Poklepovic, Paul Dent
PARP1 inhibitors are approved therapeutic agents in ovarian carcinomas, and have clinical activity in some breast cancers. As a single agent, niraparib killed ovarian and mammary tumor cells via an ATM-AMPK-ULK1 pathway which resulted in mTOR inactivation and the formation of autophagosomes, temporally followed by autolysosome formation. In parallel, niraparib activated a CD95-FADD-caspase 8 pathway, and collectively these signals caused tumor cell death that was suppressed by knock down of Beclin1, ATG5, CD95, FADD or AIF; or by expression of c-FLIP-s, BCL-XL or dominant negative caspase 9...
June 20, 2018: Cancer Biology & Therapy
Aroonwan Lam-Ubol, Alison Lea Fitzgerald, Arnat Ritdej, Tawaree Phonyiam, Hui Zhang, Jeffrey N Myers, Peng Huang, Dunyaporn Trachootham
High doses of β-phenylethyl isothiocyanate (PEITC), a phytochemical in cruciferous vegetables, are not feasible for consumption due to a strong mouth-tingling effect. This study investigated the anti-cancer effect of PEITC at sensory acceptable doses. In vitro, PEITC was selectively toxic to oral cancer cells (CAL-27, FaDu, SCC4, SCC 9, SCC15, SCC25 and TU138), compared to oral keratinocytes (OKF6/TERT2 and NOK/Si). In vivo, 5 and 10 mg kg-1 PEITC, equivalent to human organoleptically acceptable doses, retarded tumor growth and prolonged the survival of mice bearing p53-mutated oral cancer cells - TU138 xenograft...
June 20, 2018: Food & Function
Yinping Tong, Gongye Zhang, Yang Li, Jiajia Xu, Jiahui Yuan, Bing Zhang, Tianhui Hu, Gang Song
Corilagin is a component of Phyllanthus urinaria extract and has been found of possessing anti-inflammatory, anti-oxidative, and anti-tumour properties in clinic treatments. However, the underlying mechanisms in anti-cancer particularly of its induction of cell death in human breast cancer remain undefined. Our research found that corilagin-induced apoptotic and autophagic cell death depending on reactive oxygen species (ROS) in human breast cancer cell, and it occurred in human breast cancer cell (MCF-7) only comparing with normal cells...
June 19, 2018: Journal of Cellular and Molecular Medicine
Signe Borgquist, Olöf Bjarnadottir, Siker Kimbung, Thomas P Ahern
Statin drugs have been used for more than two decades to treat hypercholesterolemia and as cardio-preventive drugs, resulting in a marked decrease in cardiovascular morbidity and mortality worldwide. Statins halt hepatic cholesterol biosynthesis by inhibiting the rate-limiting enzyme in the mevalonate pathway, hydroxymethylglutaryl-coenzyme A reductase (HMGCR). The mevalonate pathway regulates a host of biochemical processes in addition to cholesterol production. Attenuation of these pathways is likely responsible for the myriad benefits of statin therapy beyond cholesterol reduction-the so-called pleiotropic effects of statins...
June 20, 2018: Journal of Internal Medicine
AmirReza Hesari, Faezeh Ghasemi, Reza Salarinia, Hamed Biglari, Agheel Tabar Molla Hassan, Vali Abdoli, Hamed Mirzaei
Curcumin is a yellow-orange powder derived from the Curcuma longa plant. Curcumin has been used extensively in traditional medicine for centuries. This component is non-toxic and shown different therapeutic properties such as anti-inflammatory, anti-cancer, antiviral, anti-bacterial, anti-fungal, anti-parasites, and anti-oxidant. Hepatitis B virus (HBV) is a small DNA member of the genus Orthohepadnavirus (Hepadnaviridae family) which is a highly contagious blood-borne viral pathogen. HBV infection is a major public health problem with 2 billion people infected throughout the world and 350 million suffering from chronic HBV infection...
June 19, 2018: Journal of Cellular Biochemistry
Bassam Janji, Guy Berchem, Salem Chouaib
Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the "tumor ecosystem" and the diversity of the stromal cell types that constitute the tumor microenvironment...
2018: Frontiers in Immunology
Kevin Pruitt, Deborah Molehin, Isabel Castro-Piedras, Monica Sharma, Souad R Sennoune, Daphne Arena, Pulak R Manna
Aromatase, a cytochrome P450 member, is a key enzyme involved in estrogen biosynthesis and is dysregulated in the majority of breast cancers. Studies have shown that lysine deacetylase inhibitors (KDI) decrease aromatase expression in cancer cells, yet many unknowns remain regarding the mechanism by which this occurs. While advances have been made to clarify factors involved in the transcriptional regulation of the aromatase gene (CYP19A1). Yet, despite aromatase being a primary target for breast cancer therapy, its post-translational regulation has been virtually unexplored...
June 19, 2018: Molecular Cancer Research: MCR
Liu-Jun He, Dong-Lin Yang, Shi-Qiang Li, Ya-Jun Zhang, Yan Tang, Jie Lei, Brendan Frett, Hui-Kuan Lin, Hong-Yu Li, Zhong-Zhu Chen, Zhi-Gang Xu
Colorectal cancer (CRC) is one of the most frequent, malignant gastrointestinal tumors, and strategies and effectiveness of current therapy are limited. A series of benzimidazole-isoquinolinone derivatives (BIDs) was synthesized and screened to identify novel scaffolds for CRC. Of the compounds evaluated, 7g exhibited the most promising anti-cancer properties. Employing two CRC cell lines, SW620 and HT29, 7g was found to suppress growth and proliferation of the cell lines at a concentration of ∼20 µM. Treatment followed an increase in G2 /M cell cycle arrest, which was attributed to cyclin B1 and cyclin-dependent kinase 1 (CDK1) signaling deficiencies with simultaneous enhancement in p21 and p53 activity...
June 12, 2018: Bioorganic & Medicinal Chemistry
Paula Nunes-Hasler
In a recent publication in Nature Communications the group of Dr. Dmitry Gabrilovich takes us one step closer to understanding why lipid accumulation impairs the function of tumour-associated dendritic cells (DCs). In this study, the authors present two surprising and significant findings. First, they show that in mouse DCs oxidized lipids function as a sink that traps the heat shock chaperone HSP70, a molecular target of emerging anti-cancer strategies. Secondly, they find that HSP70 in turn regulates the trafficking of peptide-loaded major histocompatibility complex class I (pMHC-I) molecules, a complex that triggers the proliferation of cancer-killing T cells...
June 20, 2018: Journal for Immunotherapy of Cancer
Bushra Uzair, Sarah Bint-E-Irshad, Barkat Ali Khan, Beenish Azad, Tariq Mahmood, Mujaddad Ur Rehman, Valdir A Braga
BACKGROUND: Scorpion venom is the most expensive and deadly venom with exciting medical prospects and having a potential as a source of drug candidates. A number of scorpion venom peptides have shown promising site specificity and are involved in the regulation of biological mechanisms. Due to the structural and functional specificity, the scorpion peptides are widely used for the development of specific drugs especially for the cardiovascular and other immune diseases. In this review, we summarize scorpion venom's biological activities such as antimicrobial, antiviral, anti-cancerous and in immune diseases...
June 13, 2018: Protein and Peptide Letters
Włodzimierz Opoka, Joanna Piotrowska, Adam Krakowski, Agata Kryczyk, Kinga Sałat, Małgorzata Zygmunt, Tadeusz Librowski, Bożena Muszyńska
BACKGROUND: Zinc (Zn) is a micronutrient and essential element of life and its deficiency causes severe disorders of numerous body systems, such as immune, reproductive and central nervous system. Zinc supplementation affects wound healing and sexual development. The interactions between drugs administration and Zn level in tissues are not fully understood. The aim of the study was to demonstrate differences in Zn content in teeth of laboratory animals that have undergone pharmacological tests...
February 5, 2018: Pharmacological Reports: PR
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