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Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Tao Lin, Jae Eun Lee, Reza K Oqani, So Yeon Kim, Eun Seok Cho, Yong Dae Jeong, Jun Jong Baek, Dong Il Jin
The aim of this study is to investigate whether endoplasmic reticulum (ER) stress attenuation could improve porcine somatic cell nuclear transfer (SCNT) embryo developmental competence. We treated porcine SCNT embryos with TUDCA (tauroursodeoxycholic acid, an inhibitor of ER stress) and/or TM (tunicamycin, an ER stress inducer), and examined embryonic developmental potential, embryo quality, the levels of ER stress markers (XBP1 protein and mRNA) and apoptosis-related-genes (BAX and BCL2 mRNA). Immunostaining detected X-box-binding protein (XBP1), a key gene regulator during ER stress, at all stages of SCNT embryo development...
October 17, 2016: Reproductive Biology
Alexander N Shikov, Olga N Pozharitskaya, Valery G Makarov
PURPOSE: Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen syn. A. mandshurica Rupr. & Maxim is evaluated for its medicinal application. The aim of this study is to analyze pharmacological studies on A. elata var. mandshurica published until December 2015. METHODS: The information regarding the chemistry, safety, effectiveness, and pharmacological and clinical effects of A. elata was systematically collected from the scientific literature through library catalogs; online services such as E-library...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Guangxian Zhang, Xiancheng Zeng, Ren Zhang, Juan Liu, Weici Zhang, Yujun Zhao, Xiaoyuan Zhang, Zhixue Wu, Yuhui Tan, Yingya Wu, Biaoyan Du
BACKGROUND: Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, occurs frequently in the setting of chronic liver injury. Although multiple therapeutic approaches are available, the prognosis of patients with HCC remains poor. Dioscin is a natural steroid saponin that presents in various plants. The anti-cancer and anti-fibrotic effects have been extensively reported. However, the effect of dioscin on HCC remains unclear. We aimed to investigate the anti-HCC properties of dioscin in vitro and in vivo...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Maria Prokofjeva, Vladimir Tsvetkov, Dmitry Basmanov, Anna Varizhuk, Maria Lagarkova, Igor Smirnov, Kirill Prusakov, Dmitry Klinov, Vladimir Prassolov, Galina Pozmogova, Sergey N Mikhailov
New natural and chemically modified DNA aptamers that inhibit HIV-1 activity at submicromolar concentrations (presumably via preventing viral entry into target cells) are reported. The new DNA aptamers were developed based on known intramolecular G-quadruplexes (G4s) that were functionally unrelated to HIV inhibition [the thrombin-binding aptamer and the fragment of the human oncogene promoter (Bcl2)]. The majority of previously described DNA inhibitors of HIV infection adopt intermolecular structures, and thus their folding variability represents an obvious disadvantage...
October 20, 2016: Nucleic Acid Therapeutics
Albino Carrizzo, Antonio Damato, Mariateresa Ambrosio, Antonia Falco, Alessandra Rosati, Mario Capunzo, Michele Madonna, Maria C Turco, James L Januzzi, Vincenzo De Laurenzi, Carmine Vecchione
Bcl2-associated athanogene 3 (BAG3), is constitutively expressed in a few normal cell types, including myocytes, peripheral nerves and in the brain, and is also expressed in certain tumors. To date, the main studies about the role of BAG3 are focused on its pro-survival effect in tumors through various mechanisms that vary according to cellular type. Recently, elevated concentrations of a soluble form of BAG3 were described in patients affected by advanced stage of heart failure (HF), identifying BAG3 as a potentially useful biomarker in monitoring HF progression...
October 20, 2016: Cell Death & Disease
Feng Zhang, Bo Yang, Kailiang Zhang, Mei-Ling Hou, Xue-Chun Lu, Yu-Xin Li
Amifostine (AMF), 2-(3-Aminopropyl) aminoethyl phosphorothioate is a broad-spectrum cytoprotective agent used to treat nuclear radiation and chemical weapon injuries. Recently, amifostine has been shown to have a profound biological influence on tumor cells. In order to examine the effects and mechanisms underlying the effects of amifostine on human acute megakaryocytic leukemia, we evaluated the efficacy of amifostine against Dami cells and observed a cell cycle arrest in G2 /M phase. Amifostine treatment also induced cell apoptosis of Dami cells which corresponds to formal studies...
October 19, 2016: Chemical Biology & Drug Design
Xinhui Wu, Yao Fu, Xulei Sun, Chang Liu, Menglong Chai, Chengzhen Chen, Lisheng Dai, Yan Gao, Hao Jiang, Jiabao Zhang
Porcine cumulus cells are localized around oocytes and act as a specific type of granulosa that plays essential roles in the development and maturation of oocytes, the development and atresia of follicles and the development of embryos. Studies of FAT1 have demonstrated its functions in cell-cell contact, actin dynamics, and cell growth suppression. To understand whether the FAT1 gene affects the apoptosis of porcine cumulus cells and to elucidate the mechanism of this potential action, FAT1 was knocked down using RNA interference...
October 20, 2016: Cell Biology International
Konstantinos Tzelepis, Hiroko Koike-Yusa, Etienne De Braekeleer, Yilong Li, Emmanouil Metzakopian, Oliver M Dovey, Annalisa Mupo, Vera Grinkevich, Meng Li, Milena Mazan, Malgorzata Gozdecka, Shuhei Ohnishi, Jonathan Cooper, Miten Patel, Thomas McKerrell, Bin Chen, Ana Filipa Domingues, Paolo Gallipoli, Sarah Teichmann, Hannes Ponstingl, Ultan McDermott, Julio Saez-Rodriguez, Brian J P Huntly, Francesco Iorio, Cristina Pina, George S Vassiliou, Kosuke Yusa
Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates...
October 18, 2016: Cell Reports
Yuan-Chin Lee, Ying-Jung Chen, Chia-Hui Huang, Long-Sen Chang
Previous studies have attributed the anticancer activity of amsacrine to its inhibitory effect on topoisomerase II. However, 9-aminoacridine derivatives, which have the same structural scaffold as amsacrine, induce cancer cell apoptosis by altering the expression of BCL2 family proteins. Therefore, in the present study, we assessed whether BCL2 family proteins mediated the cytotoxic effects of amsacrine on human leukemia U937 cells. Amsacrine-induced apoptosis of U937 cells was characterized by caspase-9 and caspase-3 activation, increased intracellular Ca(2+) concentration, mitochondrial depolarization, and MCL1 down-regulation...
October 19, 2016: Apoptosis: An International Journal on Programmed Cell Death
Manish Kumar Pal, Shyama Pyari Jaiswar, Ajeet Kumar Srivastav, Shruti Goyal, Ashish Dwivedi, Ankit Verma, Jyoti Singh, Anumesh Kumar Pathak, Pushpa Lata Sankhwar, Ratan Singh Ray
Ovarian cancer is fourth most common and lethal among all gynecologic malignancies. The chemotherapy usually requires in all stages of ovarian cancer but drugs have several side effects. We hypothesized that use of combination therapy of paclitaxel (PTX) and phytochemical piperine (PIP) may reduce the PTX dose as well as toxicity.The human ovarian adenocarcinomas SKOV3 cell treated with PTX-5nM and PIP-10µM after determination of IC50 by MTT assay. Reactive oxygen species generation, mitochondrial membrane potential (MMP), DNA damage, cell death pathway markers as release of cyt-c, Bax/Bcl2-caspase-3 and cell cycle arrest were analyzed...
October 15, 2016: European Journal of Pharmacology
Liza J Burton, Mariela Rivera, Ohuod Hawsawi, Jin Zou, Tamaro Hudson, Guangdi Wang, Qiang Zhang, Luis Cubano, Nawal Boukli, Valerie Odero-Marah
Muscadine grape skin extract (MSKE) is derived from muscadine grape (Vitis rotundifolia), a common red grape used to produce red wine. Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy...
2016: PloS One
Xueyan Zhang, Katsuyoshi Takata, Wei Cui, Tomoko Miyata-Takata, Yasuharu Sato, Mai Noujima-Harada, Tadashi Yoshino
Protocadherin genes (PCDHs) have been suggested to act as tumor suppressor genes in various tumor types. Previous studies have demonstrated the upregulation of certain PCDH‑γ subfamily genes in nodal and duodenal follicular lymphoma (FL) using gene expression analyses. However, the mechanisms and associated molecular function of PCDH‑γ subfamily gene upregulation in FL remain to be elucidated. The present study examined the expression of PCDHGA3, an upregulated PCDH‑γ gene subfamily member, in B‑cell lymphoma 2 (BCL2)‑positive and ‑negative FL, and evaluated its association with tumor cell proliferation in an FL‑derived cell line...
October 5, 2016: Molecular Medicine Reports
Jianheng Wu, Linfan Li, Guangyuan Jiang, Hui Zhan, Nannan Wang
Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues...
October 12, 2016: International Journal of Oncology
Khairy M A Zoheir, Gamaleldin I Harisa, Ahmed A Allam, Ligu Yang, Xiang Li, Aixin Liang, Ahmed A Abd-Rabou, Abdel Halim Harrath
The present study aimed to evaluate the in vitro effect of alpha lipoic acid (ALA) addition to the culture medium on the development of the bovine secondary preantral follicles. Bovine secondary preantral follicles were collected and divided into two groups depending on their size (80-100 μm and 100-110 μm). They were cultured in vitro for 15 days (D) using different media including at three different doses of ALA. The genes expression levels of follicle-stimulating hormone beta-subunit (FSHR), insulin-like growth factor (IGF-1), Activin, luteinizing hormone/choriogonadotropin receptor, bone morphogenetic protein receptor type IA, transforming growth factor beta receptor 1, growth differentiation factor 9, BCL2-associated X protein (BAX), and C-Myc were studied using real-time polymerase chain reaction...
September 13, 2016: Theriogenology
Emili Montserrat, Tycho Bauman, Julio Delgado
Medicine has been 'personalized' (i.e. centred in persons) since its foundation. Recently, however, the term 'personalized medicine' (or, better, 'precision medicine') has been introduced to define 'a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease'. This concept has gained momentum thanks to next-generation-sequencing (NGS) techniques that allow identification of molecular characteristics unique to the patient and to the tumour...
March 2016: Best Practice & Research. Clinical Haematology
Xuan J Wang, L Jeffrey Medeiros, Carlos E Bueso-Ramos, Guilin Tang, Sa Wang, Yasuhiro Oki, Parth Desai, Joseph D Khoury, Roberto N Miranda, Zhenya Tang, Nishitha Reddy, Shaoying Li
In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Yaming Du, Peng Wang, Hongzhi Sun, Jing Yang, Xianping Lang, Zhongbin Wang, Sheng Zang, Lei Chen, Junjun Ma, Daohan Sun
HCRP1 has been reported to have tumor suppressive function. However, its expression pattern and function in human non-small cell lung cancer (NSCLC) remain obscure. This study aims to explore clinical significance of HCRP1 in NSCLC. Immunohistochemical results showed high HCRP1 protein in normal bronchial epithelial tissue and downregulated HCRP1 expression in 47/98 lung cancer specimens. HCRP1 downregulation correlated with clinical stage (p = 0.0203), nodal status (p = 0.0168), and poor patient prognosis (log-rank, p = 0...
October 13, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
Shuvasree Sarkar, Sandip Mukherjee, Ansuman Chattopadhyay, Shelley Bhattacharya
Zebrafish were exposed to a nonlethal dose (1/350LC50; 50µg/L) of As2O3 and sampled at 7, 15, 30, 60 and 90 days of treatment. The oxidative stress response was assessed in terms of time-dependent histopathological changes, lipid peroxidation, GSH status, activities of detoxification enzymes and expression of antioxidant genes in liver and kidney. As2O3 treatment enhanced lipid peroxidation except at day 90 in liver and day 30 in kidney. Glutathione depleted significantly in the liver except on day 30; whereas in kidney, it increased initially but thereafter depleted significantly...
October 10, 2016: Ecotoxicology and Environmental Safety
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