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Mauro Ravera, Elisabetta Gabano, Ilaria Zanellato, Elena Perin, Aldo Arrais, Domenico Osella
Phenanthriplatin, that is, (SP-4-3)-diamminechlorido(phenanthridine)platinum(II) nitrate, an effective antitumor cationic Pt(II) complex, was loaded on negatively charged dextran sulfate (DS) as a model vector for drug delivery via electrostatic interactions. The free complex and the corresponding conjugate with DS were tested on two standard human tumor cell lines, namely, ovarian A2780 and colon HCT 116, and on several malignant pleural mesothelioma cell lines (namely, epithelioid BR95, mixed/biphasic MG06, sarcomatoid MM98, and sarcomatoid cisplatin-resistant MM98R)...
2016: Bioinorganic Chemistry and Applications
Kosuke Tanaka, Hirotaka Osada, Yuko Murakami-Tonami, Yoshitsugu Horio, Toyoaki Hida, Yoshitaka Sekido
Malignant mesothelioma (MM) frequently exhibits Hippo signaling pathway inactivation (HPI) mainly due to NF2 and/or LATS2 mutations, which leads to the activation of YAP transcriptional co-activator. Here, we show antitumor effects of statin on MM cells with HPI, through the interplay of the mevalonate and Hippo signaling pathways. Statin attenuated proliferation and migration of MM cells harboring NF2 mutation by accelerating YAP phosphorylation/inactivation. CD44 expression was decreased by statin, in parallel with YAP phosphorylation/inactivation...
October 20, 2016: Cancer Letters
Adeline Tan, Paul Cohen, Mooska Raoofi, Jason Tan, Nima Mesbah Ardakani, Greg Sterrett
No abstract text is available yet for this article.
February 2016: Pathology
Nima Mesbah Ardakani, Benjamin A Wood
No abstract text is available yet for this article.
February 2016: Pathology
Lam Nguyen Son, Thanh Tran Dinh, Dung Nguyen Huy
No abstract text is available yet for this article.
February 2016: Pathology
Stephanie McGregor, James McElherne, Agata Minor, Jennifer Keller-Ramey, Ryan Dunning, Aliya N Husain, Wickii Vigneswaran, Carrie Fitzpatrick, Thomas Krausz
BRCA-associated protein 1 (BAP1) immunohistochemistry (IHC) and CDKN2A (p16) fluorescence in situ hybridization (FISH) have shown clinical utility in confirming the diagnosis of malignant pleural mesothelioma (MPM), but the role for using these two markers to guide clinical management is not yet clear. While p16 loss is predictive of poor prognosis, there is controversy as to whether BAP1 loss is predictive of a more favorable prognosis; how these results interact with one another has not been explored. We performed CDKN2A FISH on a previously published tissue microarray on which we had performed BAP1 IHC, revealing combined BAP1/p16 status for 93 MPM cases...
October 19, 2016: Human Pathology
Lin Cheng, Matthew D Blackledge, David J Collins, Matthew R Orton, Neil P Jerome, Thorsten Feiweier, Mihaela Rata, Veronica Morgan, Nina Tunariu, Martin O Leach, Dow-Mu Koh
PURPOSE: To introduce T2-adjusted computed DWI (T2-cDWI), a method that provides synthetic images at arbitrary b-values and echo times (TEs) that improve tissue contrast by removing or increasing T2 contrast in diffusion-weighted images. MATERIALS AND METHODS: In addition to the standard DWI acquisition protocol T2-weighted echo-planar images at multiple (≥2) echo times were acquired. This allows voxelwise estimation of apparent diffusion coefficient (ADC) and T2 values, permitting synthetic images to be generated at any chosen b-value and echo time...
October 1, 2016: Computers in Biology and Medicine
Ran Ren, Pengpeng Yin, Yan Zhang, Jianyun Zhou, Yixing Zhou, Rufu Xu, Hai Lin, Chunji Huang
BACKGROUND: Several studies have investigated the diagnostic value of fibulin-3 for malignant pleural mesothelioma (MPM), but the results were various. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic value of fibulin-3 for MPM. RESULTS: Eight studies were included in this work. The overall sensitivity of blood fibulin-3 were 0.87 (95% CI, 0.58 - 0.97) and 0.89 (95% CI, 0.77 - 0.95), respectively. The overall sensitivity and specificity of PF fibulin-3 for MPM were 0...
October 17, 2016: Oncotarget
Berna Akıncı Özyürek, Özlem Özmen, Tuğçe Şahin Özdemirel, Yurdanur Erdoğan, Bekir Kaplan, Tuğba Kaplan
The aim of this study was to evaluate the relationship of the pre-treatment blood neutrophil/lymphocyte count ratio (NLR) with the maximum standard uptake value (SUVmax) of primary masses on positron emission tomography/computed tomography (PET/CT) taken before treatment in patients diagnosed with malignant pleural mesothelioma (MPM) and to evaluate the contribution to prognosis. A retrospective evaluation was made of 73 patients diagnosed with MPM in our hospital between January 2006 and January 2014. The SUVmax value of the primary mass on pre-treatment PET/CT, the haemogram parameters (Hb, Hct, NLR, MPV, PLT) at the time of diagnosis, the progression history, the date of the final visit and the date of death of exitus patients was recorted from patient files PET/CT...
October 21, 2016: Clinical Respiratory Journal
Wickii T Vigneswaran, Diana Y Kircheva, Vijayalakshimi Ananthanarayanan, Sydeaka Watson, Qudsia Arif, Amy Durkin Celauro, Hedy L Kindler, Aliya N Husain
BACKGROUND: Macroscopic complete surgical resection with adjuvant chemotherapy can provide a survival advantage in patients with malignant pleural mesothelioma (MPM). Patients with nonepithelioid histology are largely excluded from such radical operations even though they might benefit. The degree of epithelioid differentiation varies in biphasic histology. We report the outcomes of pleurectomy and decortication and the effect of epithelioid differentiation on overall survival of patients with MPM...
October 17, 2016: Annals of Thoracic Surgery
Pierpaolo Ferrante, Alessandra Binazzi, Claudia Branchi, Alessandro Marinaccio
: INTRODUZIONE: sebbene la relazione causale tra esposizione ad amianto e malattie neoplastiche sia ben nota, in molti Paesi il consumo del materiale è ancora rilevante e crescente. A causa della lunga latenza, nei Paesi dove è stato bandito (come in Italia) è oggi in corso un'epidemia di malattie correlate ad amianto. OBIETTIVI: descrivere i sistemi di sorveglianza dei mesoteliomi attivi nel mondo mediante un'analisi comparativa. METODI: è stata condotta una revisione bibliografica della letteratura disponibile sui sistemi di sorveglianza epidemiologica dei mesoteliomi attivi nel mondo, comparando metodi e risultati disponibili...
September 2016: Epidemiologia e Prevenzione
Nurhan Sahin, Ayse Nur Akatli, Muhammet Reha Celik, Hakkı Ulutas, Emine Turkmen Samdanci, Cemil Colak
Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study...
October 19, 2016: Pathology Oncology Research: POR
Anton G T Terwisscha van Scheltinga, Annie Ogasawara, Glenn Pacheco, Alexander Vanderbilt, Jeff Tinianow, Nidhi Gupta, Dongwei Li, Ron Firestein, Jan Marik, Suzie J Scales, Simon-Peter Williams
Antibody-drug conjugates (ADCs) use monoclonal antibodies (mAb) as vehicles to deliver potent cytotoxic drugs selectively to tumor cells expressing the target. Molecular imaging with zirconium-89 (89Zr) labeled mAbs recapitulates similar targeting biology and might help predict the efficacy of these ADCs. An anti-mesothelin antibody (AMA, MMOT0530A) was used to make comparisons between its efficacy as an ADC and its tumor uptake as measured by 89Zr immunoPET imaging. Mesothelin-targeted tumor growth inhibition by monomethyl auristatin E (MMAE), ADC AMA-MMAE (DMOT4039A), was measured in mice bearing xenografts of ovarian cancer OVCAR-3 X2...
October 19, 2016: Molecular Cancer Therapeutics
Valeria Ascoli, Ilaria Cozzi, Simona Vatrano, Stefania Izzo, Jessica Giorcelli, Elisa Romeo, Caterina Carnovale-Scalzo, Lucia Rosalba Grillo, Francesco Facciolo, Paolo Visca, Mauro Papotti, Luisella Righi
Familial malignant mesothelioma clusters are ideal candidates to explore BAP1 genomic status as a predisposing risk factor. We report data on BAP1 analysis in four families with multiple mesothelioma cases to investigate possible BAP1 alterations associated with an inherited cancer syndrome. We also recorded family history of cancer and assessed asbestos exposure. By genomic direct sequencing, we found no evidence of a BAP1 germline mutation in tumor DNA samples (one mesothelioma per family: n = 3 epithelioid; n = 1 biphasic)...
September 2016: Cancer Genetics
Amr S Abu Lila, Masakazu Fukushima, Cheng-Long Huang, Hiromi Wada, Tatsuhiro Ishida
Pemetrexed (PMX) is a key drug for the treatment of malignant pleural mesothelioma (MPM). However, its therapeutic efficacy is cruelly restricted in many clinical settings by the over-expression of thymidylate synthase (TS) gene. Recently, we emphasized the efficacy of locally administered shRNA designed against TS gene in enhancing the cytotoxic effect of PMX against orthotopically implanted MPM cells in tumor xenograft tumor model. In the present study, we investigated the efficacy of systemic, rather than local, delivery of TS RNAi molecule in sensitizing MPM cells to the cytotoxic effect of PMX...
October 14, 2016: Molecular Pharmaceutics
B Mrinakova, K Kajo, M Ondrusova, J Simo, D Ondrus
Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Tatsuya Kasai, Yumi Umeda, Makoto Ohnishi, Takashi Mine, Hitomi Kondo, Tetsuya Takeuchi, Michiharu Matsumoto, Shoji Fukushima
BACKGROUND: Multi-walled carbon nanotubes (MWCNTs) constitute one of the most promising types of nanomaterials in industry today. With their increasing use, the potential toxicity and carcinogenicity of MWCNT needs to be evaluated in bioassay studies using rodents. Since humans are mainly exposed to MWCNT by inhalation, we performed a 104-week carcinogenicity study using whole-body inhalation exposure chambers with a fibrous straight type of MWCNT at concentrations of 0, 0.02, 0.2, and 2 mg/m(3) using male and female F344 rats...
October 13, 2016: Particle and Fibre Toxicology
Wen-Bin Ou, Minmin Lu, Grant Eilers, Hailong Li, Jiongyan Ding, Xuli Meng, Yuehong Wu, Quan He, Qing Sheng, Hai-Meng Zhou, Jonathan A Fletcher
BACKGROUND: Improved mesothelioma patient survival will require development of novel and more effective pharmacological interventions. TP53 genomic mutations are uncommon in mesothelioma, and recent data indicate that p53 remains functional, and therefore is a potential therapeutic target in these cancers. In addition, the tumour suppressor NF2 is inactivated by genomic mechanisms in more than 80% of mesothelioma, causing upregulation of FAK activity. Because FAK is a negative regulator of p53, NF2 regulation of FAK-p53-MDM2 signalling loops were evaluated...
October 13, 2016: British Journal of Cancer
Bruce Armstrong, Tim Driscoll
There has been much recent commentary about the 'third wave' of asbestos-related disease, arising particularly from exposures of people repairing, renovating or demolishing buildings that contain asbestos. The presence and extent of a third wave, however, are difficult to assess, and the extent and risk of both occupational and nonoccupational third-wave exposures are largely unmeasured. Moreover, we lack information on the extent of deterioration of in situ asbestos, and its significance for ambient and third-wave exposures...
April 15, 2016: Public Health Research & Practice
J C Soria, H K Gan, S P Blagden, R Plummer, H T Arkenau, M Ranson, T R J Evans, G Zalcman, R Bahleda, A Hollebecque, C Lemech, E Dean, J Brown, D Gibson, V Peddareddigari, S Murray, N Nebot, J Mazumdar, L Swartz, K R Auger, R A Fleming, R Singh, M Millward
BACKGROUND: Focal adhesion kinase (FAK) is important in cancer growth, survival, invasion, and migration. The purpose of this study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the FAK inhibitor, GSK2256098, in cancer patients. PATIENTS AND METHODS: The dose of GSK2256098 was escalated, in cohorts of patients with advanced cancer, from 80 to 1500 mg, oral twice daily (BID), until the MTD was determined...
October 11, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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