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Lea Bayer, Jessica Gümpel, Gerd Hause, Martin Müller, Thomas Grunwald
Papillomavirus capsids are known to have the ability to package DNA plasmids and deliver them both in vitro and in vivo. Of all known papillomavirus types, human papillomaviruses (HPVs) are by far the most intensely studied. Although HPVs work well as gene transfer vectors, their use is limited as most individuals are exposed to this virus either through a HPV vaccination or natural infection. To circumvent these constraints, we produced pseudovirions (PsVs) of ten non-human papillomavirus types and tested their transduction efficiencies in vitro...
2018: PloS One
J Scott Lee, Andrew Roberts, Dennis Juarez, Thanh-Trang T Vo, Shruti Bhatt, Lee-Or Herzog, Sharmila Mallya, Richard J Bellin, Suresh K Agarwal, Ahmed Hamed Salem, Tu Xu, Jia Jia, Lingxiao Li, John R Hanna, Matthew S Davids, Angela G Fleischman, Susan O'Brien, Lloyd T Lam, Joel D Leverson, Anthony Letai, Jonathan H Schatz, David A Fruman
Statins have shown promise as anticancer agents in experimental and epidemiologic research. However, any benefit that they provide is likely context-dependent, for example, applicable only to certain cancers or in combination with specific anticancer drugs. We report that inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) using statins enhances the proapoptotic activity of the B cell lymphoma-2 (BCL2) inhibitor venetoclax (ABT-199) in primary leukemia and lymphoma cells but not in normal human peripheral blood mononuclear cells...
June 13, 2018: Science Translational Medicine
Xiangrong Liu, Shaohong Wen, Shunying Zhao, Feng Yan, Shangfeng Zhao, Di Wu, Xunming Ji
Mild therapeutic hypothermia, a robust neuroprotectant, reduces neuronal apoptosis, but the precise mechanism is not well understood. Our previous study showed that a novel inhibitor of an apoptosis-stimulating protein of p53 (iASPP) might be involved in neuronal death after stroke. The aim of this study was to confirm the role of iASPP after stroke treated with mild therapeutic hypothermia. To address this, we mimicked ischemia/reperfusion injury in vitro by using oxygen-glucose deprivation/reperfusion (OGD/R) in primary rat neurons...
June 2018: Aging and Disease
Jingshan Tong, Xingnan Zheng, Xiao Tan, Rochelle Fletcher, Zaneta Nikolovska-Coleska, Jian Yu, Lin Zhang
Mcl-1, a pro-survival Bcl-2 family protein, is frequently overexpressed in cancer cells and plays a critical role in therapeutic resistance. It is well known that anti-cancer agents induce phosphorylation of Mcl-1, which promotes its binding to E3 ubiquitin ligases and subsequent proteasomal degradation and apoptosis. However, other functions of Mcl-1 phosphorylation in cancer cell death have not been well characterized. In this study, we show in colon cancer cells that histone deacetylase inhibitors (HDACi) induce GSK3β-dependent Mcl-1 phosphorylation, but not degradation or downregulation...
June 12, 2018: Cancer Research
Ana Janic, Liz J Valente, Matthew J Wakefield, Leon Di Stefano, Liz Milla, Stephen Wilcox, Haoyu Yang, Lin Tai, Cassandra J Vandenberg, Andrew J Kueh, Shinsuke Mizutani, Margs S Brennan, Robyn L Schenk, Lisa M Lindqvist, Anthony T Papenfuss, Liam O'Connor, Andreas Strasser, Marco J Herold
It has long been assumed that p53 suppresses tumor development through induction of apoptosis, possibly with contributions by cell cycle arrest and cell senescence1,2 . However, combined deficiency in these three processes does not result in spontaneous tumor formation as observed upon loss of p53, suggesting the existence of additional mechanisms that are critical mediators of p53-dependent tumor suppression function3-5 . To define such mechanisms, we performed in vivo shRNA screens targeting p53-regulated genes in sensitized genetic backgrounds...
June 11, 2018: Nature Medicine
Piero Procacci
In this paper, we compute, by means of a non equilibrium alchemical technique (Fast Switching Double Annihilation Methods, FSDAM), the dissociation free energy for five recently discovered micromolar to subnanomolar inhibitors of the Myeloid cell leukemia 1 protein, a key regulator in cell survival and death, providing valuable clues in the chemical-physical determinants of Mcl-1 inhibition. Using the same methodology, we attempt the calculation of the dissociation free energy of the BH3 domain from PUMA protein, binding Mcl-1 in the α-helical state...
June 6, 2018: Journal of Chemical Theory and Computation
Se Hoon Hong, Dae-Hee Lee, Young-Sun Lee, Min Jee Jo, Yoon A Jeong, William T Kwon, Haroon A Choudry, David L Bartlett, Yong J Lee
[This corrects the article DOI: 10.18632/oncotarget.23046.].
May 15, 2018: Oncotarget
Joe Jabbour, Haryana M Dhillon, Heather L Shepherd, Puma Sundaresan, Chris Milross, Jonathan R Clark
OBJECTIVE: Is there a relationship between decision-making preferences and psychological distress? METHODS: Patients who had received treatment for head and neck cancer (HNC) at four institutions within NSW, Australia were invited to complete a single questionnaire. RESULTS: Five hundred and ninety-seven patients completed the questionnaire. The majority of patients (308, 54%) preferred shared decision making. Significant predictors of a preference towards active decision making were education level (OR 2...
May 28, 2018: Patient Education and Counseling
Tian Feng, Jiyuan Liu, Nan Zhou, Libin Wang, Xueying Liu, Shengyong Zhang, Siwang Wang, Hui Chen
PUMA (p53 up-regulated mediator of apoptosis) is particularly important in initiating radiation-induced damage and apoptosis. It has been shown that inhibition of PUMA can provide a profound benefit for the long-term survival of the mice, without an increased risk of malignancies after irradiation. It becomes to be a potential target for developing an effective treatment aimed to protect cells from lethal radiation. CLZ-8, a novel small-molecular inhibition targeting PUMA, could have considerable protection against cell apoptosis and DNA damage...
May 12, 2018: Environmental Toxicology and Pharmacology
Laís Verdan Dib, Cecília Cronemberger, Fabiane de Aguiar Pereira, Paula Forain Bolais, Claudia Maria Antunes Uchôa, Otilio Machado Pereira Bastos, Maria Regina Reis Amendoeira, Alynne da Silva Barbosa
This study aimed to investigate the species of felids that inhabit the Serra dos Órgãos National Park (Parnaso) and gastrointestinal parasites at various stages of their life cycles in the feces of these animals. Between 2013 and 2015, felid feces were collected from trails in Parnaso. The sampling points were georeferenced. A total of 82 fecal samples were processed, of which 79 were collected on the ground, two from captured felids and one from a necropsied animal. All samples underwent coproparasitological techniques...
May 24, 2018: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
Eun-Seok Choi, Hanna Lee, Jee Young Sung, Chang-Hun Lee, Hyonchol Jang, Kyung Tae Kim, Yong-Nyun Kim, Hyoung-Pyo Kim, Sung-Ho Goh
We have previously reported that FAM188B showed significant differential exon usage in cancers (NCBI GEO GSE30727), but the expression and function of FAM188B is not well characterized. In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer...
May 24, 2018: Cell Death & Disease
Quynh-Nhu Nguyen, Nadeen Zerafa, Seng H Liew, F Hamish Morgan, Andreas Strasser, Clare L Scott, Jock K Findlay, Martha Hickey, Karla J Hutt
Female gametes are stored in the ovary in structures called primordial follicles, the supply of which is non-renewable. It is well established that DNA-damaging cancer treatments can deplete the ovarian reserve of primordial follicles, causing premature ovarian failure and infertility. The precise mechanisms underlying this chemotherapy-driven follicle loss are unclear, and this has limited the development of targeted ovarian-protective agents. To address this fundamental knowledge gap, we used gene deletion mouse models to examine the role of the DNA damage-induced pro-apoptotic protein, PUMA, and its transcriptional activator TAp63, in primordial follicle depletion caused by treatment with cyclophosphamide or cisplatin...
May 23, 2018: Cell Death & Disease
Faiha A Suliman, Dina M Khodeer, Afaf Ibrahiem, Eman T Mehanna, Mohamed K El-Kherbetawy, Hala M F Mohammad, Sawsan A Zaitone, Yasser M Moustafa
Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40 mg/kg) in mice treated with a single injection of cisplatin (10 mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen...
May 21, 2018: International Immunopharmacology
Chaojin Chen, Yao Weifeng, Wu Shan, Zhou Shaoli, Gu Yu, Ge Mian, Li Xiang, Guihua Chen, Joseph A Bellanti, Songguo Zheng, Dongdong Yuan, Ziqing Hei
AIMS: Perioperative acute kidney injury (AKI) resulting from renal ischemia reperfusion (IR) is not conducive to the postoperative surgical recovery. Our previous study demonstrated that reactive oxygen species (ROS) transmitted by gap junction (GJ) composed of connexin32 (Cx32) contributed to AKI. However, the precise pathophysiologic mechanisms were unknown. The present study focuses on the underlying mechanisms related to ROS transmitted by Cx32 responsible for AKI aggravation. RESULTS: In a set of vivo studies, renal IR was found to cause severe impairment in renal tissues with massive ROS generation, and occurred contemporaneously with activation of NF-κB/p53/PUMA-mediated mitochondrial apoptosis pathways...
May 23, 2018: Antioxidants & Redox Signaling
Caroline Szpalski, Parag Butala, Meredith T Vandegrift, Denis Knobel, Robert J Allen, Pierre B Saadeh, Stephen M Warren
The population is aging, and the prevalence of chronic wounds is increasing. Because neovascularization is essential for tissue repair and both local and systemic factors affect new blood vessel formation, we hypothesize that altering either pathway would reciprocally enhance wound healing in the aged. To test this hypothesis, p53 was locally suppressed and endothelial progenitor cells (EPCs) were systemically mobilized in a murine model of senescent wound healing.Bilateral 6-mm full-thickness stented wounds were made on the dorsum of Zmpste24 mice...
May 17, 2018: Annals of Plastic Surgery
Boris Sabirzhanov, Alan Faden, Taryn Aubrecht, Rebecca Henry, Ethan Glaser, Bogdan A Stoica
Angiopoietin-1 (Ang-1) is a well-known endothelial growth factor but its effects on neurons have yet to be elucidated. We show that Ang-1 is rapidly down-regulated in the injured brain after controlled cortical impact (CCI), a mouse experimental TBI model and in etoposide-induced neuronal apoptosis in vitro. Ang-1 treatment inhibits etoposide-induced up-regulation of pro-apoptotic Bcl-2 family members Noxa, Puma, Bim, and Bax; reduces markers of caspase-dependent (cytochrome c release/caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways; and limits neuronal cell death...
May 18, 2018: Journal of Neurotrauma
Saraschandra Naraginti, Yi Li, Gianluca Li Puma
The photodegradation and phytotoxicity of the pharmaceutical antibiotic, sulphamethoxazole (SMX) and the azo-dye reactive-red-194 (RR194) under visible-light irradiation of TiO2 nanoparticles modified by silver and zirconium was investigated. The results indicated that sulphamethoxazole and its toxic degradation by product, 3-amino-5-methylisoxazole and RR-194 could be degraded efficiently by the co-doped Zr/Ag-TiO2 catalyst. PL studies and ROS generation results suggested that the effective charge separation was carried out while irradiation of the modified TiO2 nanoparticles...
May 14, 2018: Ecotoxicology and Environmental Safety
Timothy L Lochmann, Krista M Powell, Jungoh Ham, Konstantinos V Floros, Daniel A R Heisey, Richard I J Kurupi, Marissa L Calbert, Maninderjit S Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J Souers, C Patrick Reynolds, Cyril H Benes, Anthony C Faber
High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death...
May 16, 2018: Science Translational Medicine
Kazutoshi Isobe, Atsushi Kakimoto, Tetuo Mikami, Kyohei Kaburaki, Hiroshi Kobayashi, Takahiro Yoshizawa, Yuta Nakano, Takashi Makino, Hajime Otsuka, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Naobumi Tochigi, Akira Iyoda, Sakae Homma
Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined...
May 16, 2018: Oncology Reports
Tian-Hua Yao, Parekejiang Pataer, Krishna Prasad Regmi, Xi-Wen Gu, Quan-Yan Li, Jing-Ting Du, Su-Meng Ge, Jun-Bo Tu
The use of propranolol for the treatment of infantile hemangioma (IH) has been widely investigated in recent years. However, the underlying therapeutic mechanism of propranolol for the treatment of IH remains poorly understood. The aim of the present study was to investigate the expression of proteins regulated by cellular tumor antigen p53 (p53) in associated apoptosis pathways in IH endothelial cells (HemECs) treated with propranolol. Furthermore, the present study aimed to investigate the exact apoptotic pathway underlying the therapeutic effect of propranolol against IH...
May 14, 2018: Molecular Medicine Reports
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