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Barbara Altieri, Silviu Sbiera, Silvia Della Casa, Isabel Weigand, Vanessa Wild, Sonja Steinhauer, Guido Fadda, Arkadius Kocot, Michaela Bekteshi, Egle M Mambretti, Andreas Rosenwald, Alfredo Pontecorvi, Martin Fassnacht, Cristina L Ronchi
Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG)...
December 21, 2016: Oncotarget
Bianca de Cássia Troncarelli de Campos Parra Flores, Silvia Vanessa Lourenço, Aline Santos Damascena, Luiz Paulo Kowaslki, Fernando Augusto Soares, Cláudia Malheiros Coutinho-Camillo
Salivary gland tumors comprise a heterogeneous group of lesions with different histological features and diverse clinical pathophysiology. They account for about 3% of all head and neck tumors. Apoptosis plays an important role during morphogenesis of glandular structures, including that of the salivary gland. Recent studies have demonstrated that several microRNAs (miRNAs) are involved in the control of apoptosis. The aim of the present study was to determine the expression of apoptosis-related miRNAs (miR-15a, miR-16, miR-17-5p, miR-20a, miR-21, miR-29, and miR-34) and their target mRNAs in 25 pleomorphic adenomas, 23 mucoepidermoid carcinomas, and 10 non-neoplastic salivary gland samples by real-time RT-PCR...
December 15, 2016: Virchows Archiv: An International Journal of Pathology
Thomas B Shiell, Dougal G McCulloch, Jodie E Bradby, Bianca Haberl, Reinhard Boehler, David R McKenzie
Carbon exhibits a large number of allotropes and its phase behaviour is still subject to significant uncertainty and intensive research. The hexagonal form of diamond, also known as lonsdaleite, was discovered in the Canyon Diablo meteorite where its formation was attributed to the extreme conditions experienced during the impact. However, it has recently been claimed that lonsdaleite does not exist as a well-defined material but is instead defective cubic diamond formed under high pressure and high temperature conditions...
November 29, 2016: Scientific Reports
Hongrui Guo, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Xun Wang, Ling Zhao, Bangyuan Wu, Kejie Chen, Jie Deng
Ni, a metal with industrial and commercial uses, poses a serious hazard to human and animal health. In the present study, we used flow cytometry, immunohistochemistry and qRT-PCR to investigate the mechanisms of NiCl2-induced apoptosis in kidney cells. After treating 280 broiler chickens with 0, 300, 600 or 900 mg/kg NiCl2 for 42 days, we found that two caspase-dependent pathways were involved in the induced renal tubular cell apoptosis. In the mitochondria-mediated caspase-dependent apoptotic pathway, cyt-c, HtrA2/Omi, Smac/Diablo, apaf-1, PARP, and caspase-9, 3, 6 and 7 were all increased, while...
October 27, 2016: Oncotarget
Esther P Jane, Daniel R Premkumar, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
Because the anti-apoptotic protein Bcl-xL is overexpressed in glioma, one might expect that inhibiting or silencing this gene would promote tumor cell killing. However, our studies have shown that this approach has limited independent activity, but may tip the balance in favor of apoptosis induction in response to other therapeutic interventions. To address this issue, we performed a pharmacological screen using a panel of signaling inhibitors and chemotherapeutic agents in Bcl-xL silenced cells. Although limited apoptosis induction was observed with a series of inhibitors for receptor tyrosine kinases, PKC inhibitors, Src family members, JAK/STAT, histone deacetylase, the PI3K/Akt/mTOR pathway, MAP kinase, CDK, heat shock proteins, proteasomal processing, and various conventional chemotherapeutic agents, we observed a dramatic potentiation of apoptosis in Bcl-xL silenced cells with the survivin inhibitor, YM155...
November 2, 2016: Molecular Carcinogenesis
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
Renato José Mendonça Natalino, Célia Beatriz Gianotti Antoneli, Karina de Cássia Braga Ribeiro, Antônio Hugo José Fróes Marques Campos, Fernando Augusto Soares
Retinoblastoma is the most common intraocular malignant neoplasia during childhood and results from the partial or total inactivity of the retinoblastoma protein (pRb). In the absence of pRb, the E2F transcription factors increase the levels of cell cycle proteins as well as some pro-apoptotic proteins. We intended to study the immunohistochemistry profile of apoptotic-related proteins in retinoblastoma. We also evaluated the association between the expression of apoptotic protein and stage of tumor or survivor after a 5year follow up...
December 2016: Pathology, Research and Practice
Hanna Kędzierska, Piotr Popławski, Grażyna Hoser, Beata Rybicka, Katarzyna Rodzik, Elżbieta Sokół, Joanna Bogusławska, Zbigniew Tański, Anna Fogtman, Marta Koblowska, Agnieszka Piekiełko-Witkowska
Serine and arginine rich splicing factor 2(SRSF2) belongs to the serine/arginine (SR)-rich family of proteins that regulate alternative splicing. Previous studies suggested that SRSF2 can contribute to carcinogenic processes. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, highly aggressive and difficult to treat, mainly due to resistance to apoptosis. In this study we hypothesized that SRSF2 contributes to the regulation of apoptosis in ccRCC. Using tissue samples obtained from ccRCC patients, as well as independent validation on The Cancer Genome Atlas (TCGA) data, we demonstrate for the first time that expression of SRSF2 is decreased in ccRCC tumours when compared to non-tumorous control tissues...
2016: International Journal of Molecular Sciences
Yangbai Sun, Nengbin He, Yang Dong, Chaoyin Jiang
Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients' serum, tumor tissues and OS cell lines. Furthermore, we found that knockdown of miR-24 by its specific inhibitors significantly increased the therapeutic effect of doxorubicin (DOX) on OS cell lines (MG-63 and HOS). Moreover, miR-24 inhibitors resensitized the doxorubicin-resistant MG-63 cells (MG-63/R) and HOS cells (HOS/R) to DOX...
September 29, 2016: Scientific Reports
Silvia Grancara, Shinji Ohkubo, Marco Artico, Mauro Ciccariello, Sabrina Manente, Marcantonio Bragadin, Antonio Toninello, Enzo Agostinelli
Mitochondria represent cell "powerhouses," being involved in energy transduction from the electrochemical gradient to ATP synthesis. The morphology of their cell types may change, according to various metabolic processes or osmotic pressure. A new morphology of the inner membrane and mitochondrial cristae, significantly different from the previous one, has been proposed for the inner membrane and mitochondrial cristae, based on the technique of electron tomography. Mitochondrial Ca(2+) transport (the transporter has been isolated) generates reactive oxygen species and induces the mitochondrial permeability transition of both inner and outer mitochondrial membranes, leading to induction of necrosis and apoptosis...
October 2016: Amino Acids
Mohamed El-Mesery, Mohamed E Shaker, Abdelaziz Elgaml
The inhibitors of apoptosis proteins are implicated in promoting cancer cells survival and resistance toward immune surveillance and chemotherapy. Second mitochondria-derived activator of caspases (SMAC) mimetics are novel compounds developed to mimic the inhibitory effect of the endogenous SMAC/DIABLO on these IAPs. Here, we examined the potential effects of the novel SMAC mimetic BV6 on different human cancer cell lines. Our results indicated that BV6 was able to induce cell death in different human cancer cell lines...
July 27, 2016: Experimental Biology and Medicine
N J O'Farrell, R Feighery, S L Picardo, N Lynam-Lennon, M Biniecka, S A McGarrigle, J J Phelan, F MacCarthy, D O'Toole, E J Fox, N Ravi, J V Reynolds, J O'Sullivan
BACKGROUND: Barrett's esophagus follows the classic step-wise progression of metaplasia-dysplasia-adenocarcinoma. While Barrett's esophagus is a leading known risk factor for esophageal adenocarcinoma, the pathogenesis of this disease sequence is poorly understood. Mitochondria are highly susceptible to mutations due to high levels of reactive oxygen species (ROS) coupled with low levels of DNA repair. The timing and levels of mitochondria instability and dysfunction across the Barrett's disease progression is under studied...
2016: BMC Cancer
Julie Grasset, Élodie Ollivier, Bérénice Bougas, Glenn Yannic, Peter G C Campbell, Louis Bernatchez, Patrice Couture
In this study, we measured the effects of temperature (9°C, 20°C, and 28°C), metal contamination (cadmium and nickel) and their interaction on yellow perch (Perca flavescens) using liver enzymatic and transcriptomic endpoints and biometric indices. Kidney metal concentrations increased with a rise of temperature. The biometric indices analysed (Fulton condition factor, pyloric cæca, hepatosomatic and gonadosomatic indices) generally decreased with an increase of temperature but not with metal contamination...
August 2016: Aquatic Toxicology
Kyoung Jin Nho, Jin Mi Chun, Ho Kyoung Kim
Timosaponin A-III (TSA-III), a saponin isolated from the rhizome of Anemarrhena asphodeloides, exhibits potent cytotoxicity and has the potential to be developed as an anticancer agent. However, the molecular mechanism underlying the anticancer activity of TSA-III has not been fully elucidated. In this study, the apoptotic effects of TSA-III were investigated in HepG2 cells. Treatment with TSA-III significantly inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis in HepG2 cells...
July 2016: Environmental Toxicology and Pharmacology
Niveen Madi, Mohammed Dany, Salah Abdoun, Julnar Usta
INTRODUCTION: Moringa oleifera (MO) is an important dietary component for many populations in West Africa and the Indian subcontinent. In addition to its highly nutritious value, almost all parts of this plant have been widely used in folk medicine in curing infectious, cardiovascular, gastrointestinal, hepatic, and other diseases. Evidence-based research supported its versatile medicinal properties; however, more rigorous research is required to establish it in cancer therapy. As such, in this study we aim to investigate the in vitro anticancerous effect of Moringa oleifera's aqueous leaf extract...
June 17, 2016: Journal of the American College of Nutrition
Federica Frezzato, Benedetta Accordi, Valentina Trimarco, Cristina Gattazzo, Veronica Martini, Gloria Milani, Silvia Bresolin, Filippo Severin, Andrea Visentin, Giuseppe Basso, Gianpietro Semenzato, Livio Trentin
B cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B lymphocytes from proliferative activity and apoptosis resistance. The increased awareness of the importance of B cell receptor signaling in CLL has raised new opportunities for targeted intervention. Herein, we describe a study performed with the high-throughput RPPA (reverse phase protein array) technique, which allowed us to simultaneously study different molecules in a large series of patients. We analyzed B lymphocytes from 57 patients with CLL and 11 healthy subjects...
June 16, 2016: Journal of Leukocyte Biology
Julien Broséus, Gaili Chen, Sébastien Hergalant, Gérard Ramstein, Nicolas Mounier, Jean-Louis Guéant, Pierre Feugier, Christian Gisselbrecht, Catherine Thieblemont, Rémi Houlgatte
Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Prognosis is particularly poor for relapses occurring less than one year after the end of first-line treatment (early relapses/ER) compared to those occurring more than one year after (late relapses/LR). To better understand genomic alterations underlying the delay of relapse, we identified copy number variations (CNVs) on 39 tumor samples from a homogeneous series of patients included in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) prospective study...
June 2, 2016: Oncotarget
Hanna Mandel, Shotaro Saita, Simon Edvardson, Chaim Jalas, Avraham Shaag, Dorit Goldsher, Euvgeni Vlodavsky, Thomas Langer, Orly Elpeleg
BACKGROUND: Cell survival critically depends on the integrity of mitochondria, which play a pivotal role during apoptosis. Extensive mitochondrial damage promotes release of pro-apoptotic factors from the intermembrane space of mitochondria. Released mitochondrial proteins include Smac/DIABLO and HTRA2/Omi, which inhibit the cytosolic E3 ubiquitin ligase XIAP and other inhibitors of apoptosis proteins. AIMS: Here we investigated the cause of extreme hypertonia at birth, alternating with hypotonia, with the subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, intractable seizures and early death in four patients from two unrelated families...
October 2016: Journal of Medical Genetics
Gabriela Brumatti, Chunyan Ma, Najoua Lalaoui, Nhu-Y Nguyen, Mario Navarro, Maria C Tanzer, Jennifer Richmond, Margherita Ghisi, Jessica M Salmon, Natasha Silke, Giovanna Pomilio, Stefan P Glaser, Elisha de Valle, Raffi Gugasyan, Mark A Gurthridge, Stephen M Condon, Ricky W Johnstone, Richard Lock, Guy Salvesen, Andrew Wei, David L Vaux, Paul G Ekert, John Silke
Resistance to chemotherapy is a major problem in cancer treatment, and it is frequently associated with failure of tumor cells to undergo apoptosis. Birinapant, a clinical SMAC mimetic, had been designed to mimic the interaction between inhibitor of apoptosis proteins (IAPs) and SMAC/Diablo, thereby relieving IAP-mediated caspase inhibition and promoting apoptosis of cancer cells. We show that acute myeloid leukemia (AML) cells are sensitive to birinapant-induced death and that the clinical caspase inhibitor emricasan/IDN-6556 augments, rather than prevents, killing by birinapant...
May 18, 2016: Science Translational Medicine
Johanna Falkenhorst, Susanne Grunewald, Thomas Mühlenberg, Adrian Marino-Enriquez, Anna-Carina Reis, Christopher Corless, Michael Heinrich, Jürgen Treckmann, Lars Erik Podleska, Martin Schuler, Jonathan Alfred Fletcher, Sebastian Bauer
Gastrointestinal stromal tumors (GIST) exhibit a strong oncogenic dependency on KIT and KIT inhibitors confer long lasting disease stabilization in the majority of patients. Nonetheless, KIT inhibition alone does not cure GIST as a subset of GIST cells evade apoptosis and eventually develop resistance. Inhibitors of Apoptosis Proteins (IAPs) may confer resistance to drug-induced apoptosis. We observed that the mRNA and protein of IAPs XIAP (BIRC4) and survivin (BIRC5) were highly expressed in primary GIST tumors and cell line models...
July 5, 2016: Oncotarget
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