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https://www.readbyqxmd.com/read/28637328/diesel-engine-exhaust-basis-for-occupational-exposure-limit-value
#1
Piia Taxell, Tiina Santonen
Diesel engines are widely used in transport and power supply, making occupational exposure to diesel exhaust common. Both human and animal studies associate exposure to diesel exhaust with inflammatory lung effects, cardiovascular effects, and an increased risk of lung cancer. The International Agency for Research on Cancer (IARC) has evaluated diesel exhaust as carcinogenic to humans. Yet national or regional limit values for controlling occupational exposure to diesel exhaust are rare. In recent decades, stricter emission regulations have led to diesel technologies evolving significantly, resulting in changes in exhaust emissions and composition...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28637221/digital-direct-detection-of-micrornas-using-single-molecule-arrays
#2
Limor Cohen, Mark R Hartman, Aaron Amardey-Wellington, David R Walt
MicroRNAs (miRNAs) are involved in many biological pathways, and detecting miRNAs accurately is critical for diagnosing a variety of diseases including cancer. However, most current methods for miRNA detection require lengthy sample preparation and amplification steps that can bias the results. In addition, lack of specificity and reproducibility give rise to various challenges in detection of circulating miRNAs in biological samples. In this work, we applied the Single Molecule Array (Simoa) technique to develop an ultra-sensitive sandwich assay for direct detection of multiple miRNAs without pre-amplification...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637024/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#3
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637023/cationic-liquid-crystalline-nanoparticles-for-the-delivery-of-synthetic-rnai-based-therapeutics
#4
Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A Roth, Lin Ji
RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637022/cdkn2a-methylation-in-esophageal-cancer-a-meta-analysis
#5
Chongchang Zhou, Jinyun Li, Qun Li
CDKN2A is a tumor suppressor gene and is frequently inactivated in human cancers by hypermethylation of its promoter. However, the role and diagnostic value of CDKN2A methylation in esophageal cancer (EC) remains controversial. Therefore, we performed a meta-analysis, including data from 42 articles (2656 ECs, 612 precancerous lesions, and 2367 controls). A significant increase in the frequency of CDKN2A methylation was identified during EC carcinogenesis: cancer vs. controls, odds ratio (OR) = 12.60 (95 % CI, 8...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#6
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637009/jagged-2-jag2-enhances-tumorigenicity-and-chemoresistance-of-colorectal-cancer-cells
#7
Vivek Vaish, Joohwee Kim, Minsub Shim
Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Recent studies have stated that NOTCH signaling plays an important role in the development and progression of CRC. However, the role of Jagged-2 (JAG2), one of the NOTCH ligands, has not been delineated in colorectal tumorigenesis and drug resistance. In the present study, we have examined the impact of targeting JAG2 on CRC cells. Among all the members of NOTCH ligands, only the expression of JAG2 was found up-regulated in the intestinal tumors of ApcMin/+ mice as compared to the nearby normal mucosa...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#8
Annemarie Ackermann, Aysun Çapcı Karagöz, Ali Ghoochani, Michael Buchfelder, Ilker Eyüpoglu, Svetlana B Tsogoeva, Nicolai Savaskan
Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#9
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637003/structural-recognition-of-tubulysin-b-derivatives-by-multidrug-resistance-efflux-transporters-in-human-cancer-cells
#10
Michal Stark, Yehuda G Assaraf
Multidrug resistance (MDR) is a major hindrance to curative chemotherapy of various human malignancies. Hence, novel chemotherapeutics must be evaluated for their recognition by MDR efflux transporters. Herein we explored the cytotoxic activity of synthetic tubulysin B (Tub-B, EC1009) derivatives (Tub-B-hydrazide/EC0347 and Tub-B bis-ether/EC1820), and their recognition by the MDR efflux transporters P-glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636998/physiologically-based-pharmacokinetic-modeling-for-predicting-irinotecan-exposure-in-human-body
#11
Yingfang Fan, Najia Mansoor, Tasneem Ahmad, Rafeeq Alam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang, Mansoor Ahmed
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#12
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636989/satb1-overexpression-correlates-with-gastrointestinal-neoplasms-invasion-and-metastasis-a-meta-analysis-for-chinese-population
#13
Tao Xiao, Lei Fu, Zhigang Jie
BACKGROUND: Gastrointestinal neoplasm (GIN) is the most common neoplasm in China. The global chromatin organizer SATB1 (special AT-rich sequence binding protein 1) is aberrantly expressed in multiple human neoplasms. We conducted this meta-analysis to investigate whether the invasion and metastasis of GIN correlates with SATB1 levels in tumor tissues in Chinese patients. MATERIALS AND METHODS: Eligible studies were identified through multiple search strategies in the databases PubMed, Embase, Medline, CNKI, and WANFANG, and the relevant clinicopathological data were extracted...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#14
Theodosia Maina, Aikaterini Kaloudi, Ibai E Valverde, Thomas L Mindt, Berthold A Nock
INTRODUCTION: Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG4-[Nle(14)]BBN(7-14) (1) was reported to improve the in vitro stability of resulting (177)Lu-radioligands...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#15
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636931/p53-prohibits-propagation-of-chromosome-segregation-errors-that-produce-structural-aneuploidies
#16
Mar Soto, Jonne A Raaijmakers, Bjorn Bakker, Diana C J Spierings, Peter M Lansdorp, Floris Foijer, René H Medema
The presence of an abnormal karyotype has been shown to be profoundly detrimental at the cellular and organismal levels but is an overt hallmark of cancer. Aneuploidy can lead to p53 activation and thereby prevents proliferation, but the exact trigger for p53 activation has remained controversial. Here, we have used a system to induce aneuploidy in untransformed human cells to explore how cells deal with different segregation errors. We show that p53 is activated only in a subset of the cells with altered chromosome content...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#17
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28636844/clonal-hematopoiesis-and-risk-of-atherosclerotic-cardiovascular-disease
#18
Siddhartha Jaiswal, Pradeep Natarajan, Alexander J Silver, Christopher J Gibson, Alexander G Bick, Eugenia Shvartz, Marie McConkey, Namrata Gupta, Stacey Gabriel, Diego Ardissino, Usman Baber, Roxana Mehran, Valentin Fuster, John Danesh, Philippe Frossard, Danish Saleheen, Olle Melander, Galina K Sukhova, Donna Neuberg, Peter Libby, Sekar Kathiresan, Benjamin L Ebert
Background Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. Methods We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls...
June 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636807/targeting-protein-for-xenopus-kinesin-like-protein-2-knockdown-enhances-radiation-sensitivity-of-human-lung-squamous-carcinoma-cell
#19
Jie Yang, Feng Gao, Xinjian Xu, Yuxiang Wang, Shuchai Zhu
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been demonstrated to be associated with the tumorigenesis of many cancers. In the present study, we investigated the role and preliminary mechanism of TPX2 in the resistance of lung squamous carcinoma to radiation therapy. The results showed that SK-MES-1R and NCI-H226R cells were more resistant to X-ray irradiation than the parental cells (SK-MES-1 and NCI-H226). Moreover, TPX2 was upregulated in the radioresistant cells compared with the parental cells...
June 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28636767/aberrant-expression-of-kallikrein-related-peptidase-7-is-correlated-to-human-melanoma-aggressiveness-by-stimulating-cell-migration-and-invasion
#20
Tiphaine Delaunay, Lydia Deschamps, Meriem Haddada, Francine Walker, Antoninus Soosaipillai, Feryel Soualmia, Chahrazade El Amri, Eleftherios P Diamandis, Maria Brattsand, Viktor Magdolen, Dalila Darmoul
Members of the tissue kallikrein-related peptidase (KLK) family not only regulate several important physiological functions, but aberrant expression has also been associated with various malignancies. Clinically, KLKs have been suggested as promising biomarkers for diagnosis and prognosis in many types of cancer. As of yet, expression of KLKs and their role in skin cancers are, however, poorly addressed. Malignant melanoma is an aggressive disease associated with poor prognosis. Hence, diagnostic biomarkers to monitor melanoma progression are needed...
June 21, 2017: Molecular Oncology
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