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cancer proteomics

Varsha G Desai, Taewon Lee, Carrie L Moland, Vikrant Vijay, Tao Han, Sherry M Lewis, Eugene H Herman, James C Fuscoe
Cardiotoxicity is a serious adverse effect of doxorubicin (DOX) treatment in cancer patients. Currently, there is a lack of sensitive biomarkers to predict the risk of DOX-induced cardiotoxicity. Using SOMAmer-based proteomic technology, 1129 proteins were profiled to identify potential early biomarkers of cardiotoxicity in plasma from male B6C3F1 mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively)...
December 2, 2018: Toxicology and Applied Pharmacology
Tz-Wen Yang, Divya Sahu, Yi-Wen Chang, Chia-Lang Hsu, Chiao-Hui Hsieh, Hsuan-Cheng Huang, Hsueh-Fen Juan
The interaction of long noncoding RNAs (lncRNAs) with one or more RNA-binding proteins (RBPs) are important to a plethora of cellular and physiological processes. The lncRNA SNHG1 was reported to be aberrantly expressed and associated with poor patient prognosis in several cancers, including neuroblastoma. However, the interacting RBPs and biological functions associated with SNHG1 in neuroblastoma remains unknown. In this study, we identified 283, 31, and 164 SNHG1-interacting proteins in SK-N-BE(2)C, SK-N-DZ and SK-N-AS neuroblastoma cells, respectively, using a RNA-protein pull-down assay coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
December 5, 2018: Journal of Proteome Research
Roger Davies, Kieran O'Dea, Anthony Gordon
Immune therapy to ease the burden of sepsis has thus far failed to consistently improve patient outcomes. Advances in cancer immune therapy and awareness that prolonged immune-suppression in sepsis can leave patients vulnerable to secondary infection and death have driven resurgence in the field of sepsis immune-therapy investigation. As we develop and evaluate these novel therapies, we must learn from past experiences where single-mediator targeted immune therapies were blindly delivered to heterogeneous patient cohorts with complex and evolving immune responses...
November 2018: Journal of the Intensive Care Society
Elisa Caiola, Francesca Falcetta, Silvia Giordano, Mirko Marabese, Marina C Garassino, Massimo Broggini, Roberta Pastorelli, Laura Brunelli
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with multiple different oncogenic mutations. Approximately 25-30% of NSCLC patients present KRAS mutations, which confer poor prognosis and high risk of tumor recurrence. About half of NSCLCs with activating KRAS lesions also have deletions or inactivating mutations in the serine/threonine kinase 11 (LKB1) gene. Loss of LKB1 on a KRAS-mutant background may represent a significant source of heterogeneity contributing to poor response to therapy...
December 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Anaïs Chauvin, François-Michel Boisvert
Colorectal cancer is the third most common and the fourth most lethal cancer worldwide. In most of cases, patients are diagnosed at an advanced or even metastatic stage, thus explaining the high mortality. The lack of proper clinical tests and the complicated procedures currently used for detecting this cancer, as well as for predicting the response to treatment and the outcome of a patient's resistance in guiding clinical practice, are key elements driving the search for biomarkers. In the present overview, the different biomarkers (diagnostic, prognostic, treatment resistance) discovered through proteomics studies in various colorectal cancer study models (blood, stool, biopsies), including the different proteomic techniques used for the discovery of these biomarkers, are reviewed, as well as the various tests used in clinical practice and those currently in clinical phase...
December 2, 2018: Proteomes
Russell Emmons, Guanying Xu, Diego Hernandez-Saavedra, Adam Kriska, Yuan-Xiang Pan, Hong Chen, Michael De Lisio
Obesity-induced inflammation associated with increased risk for colorectal cancer (CRC). The role of diet and exercise in modulating increased CRC risk in obesity, and the potential role of altered hematopoiesis as a contributor to these effects remain unknown. The purpose of this study was to examine how weight loss induced during CRC induction with or without exercise alter CRC initiation and their relationship to altered hematopoiesis. Mice consumed either a control (CON) or high fat diet to induce obesity...
December 4, 2018: American Journal of Physiology. Endocrinology and Metabolism
Linus Aronsson, Roland Andersson, Monika Bauden, Bodil Andersson, Thomas Bygott, Daniel Ansari
OBJECTIVE: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). MATERIAL AND METHODS: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls...
December 3, 2018: Scandinavian Journal of Gastroenterology
Sneha P Couvillion, Ying Zhu, Gabe Nagy, Joshua N Adkins, Charles Ansong, Ryan S Renslow, Paul D Piehowski, Yehia M Ibrahim, Ryan T Kelly, Thomas O Metz
Mass-spectrometry based omics technologies - namely proteomics, metabolomics and lipidomics - have enabled the molecular level systems biology investigation of organisms in unprecedented detail. There has been increasing interest for gaining a thorough, functional understanding of the biological consequences associated with cellular heterogeneity in a wide variety of research areas such as developmental biology, precision medicine, cancer research and microbiome science. Recent advances in mass spectrometry (MS) instrumentation and sample handling strategies are quickly making comprehensive omics analyses of single cells feasible, but key breakthroughs are still required to push through remaining bottlenecks...
December 3, 2018: Analyst
Katri Aro, Karolina Kaczor-Urbanowicz, Carmen Martín Carreras-Presas
PURPOSE OF REVIEW: The goal of cancer screening is to detect tumor at an early stage, and early cancer detection is the hallmark of successful treatment. In addition to traditional tissue biopsy-based diagnostics, more reliable, inexpensive, and noninvasive methods are required for early diagnosis of cancer. In this review, we highlight some of the recent advancements in the field of salivary diagnostics in oral cancer. RECENT FINDINGS: 'Salivaomics' is a broad collection of technologies used to explore different types of molecules contained in saliva...
November 30, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
José A Fernández Robledo, Raghavendra Yadavalli, Bassem Allam, Emmanuelle Pales-Espinosa, Marco Gerdol, Samuele Greco, Rebecca J Stevick, Marta Gómez-Chiarri, Ying Zhang, Cynthia A Heil, Adrienne N Tracy, David Bishop-Bailey, Michael J Metzger
Bivalves, from raw oysters to steamed clams, are popular choices among seafood lovers and once limited to the coastal areas. The rapid growth of the aquaculture industry and improvement in the preservation and transport of seafood have enabled them to be readily available anywhere in the world. Over the years, oysters, mussels, scallops, and clams have been the focus of research for improving the production, managing resources, and investigating basic biological and ecological questions. During this decade, an impressive amount of information using high-throughput genomic, transcriptomic and proteomic technologies has been produced in various classes of the Mollusca group, and it is anticipated that basic and applied research will significantly benefit from this resource...
November 29, 2018: Developmental and Comparative Immunology
Wittaya Suwakulsiri, Alin Rai, Rong Xu, Maoshan Chen, David W Greening, Richard J Simpson
Extracellular vesicles can be classified into two main classes - exosomes and shed microvesicles (sMVs). Whilst much is known about exosome cargo and functionality, sMVs are poorly understood. Here, we describe the large-scale purification of sMVs released from primary (SW480) and metastatic (SW620) human isogenic colorectal cancer (CRC) cell lines using a combination of differential ultracentrifugation and isopycnic iodixanol density centrifugation. The yield of SW480-sMVs and SW620-sMVs was 0.75 mg and 0...
November 28, 2018: Biochimica et biophysica acta. Proteins and proteomics
Ting Yang, Pengfei Xu, Lize Gu, Zhiyuan Xu, Weihong Ge, Qing Li, Feifei Xu
BACKGROUND: Heat shock protein 27 (HSP27) may take part in the epithelial ovarian cancer (EOC) malignant process because it is elevated in the serum of EOC patients, suggesting that HSP27 may serve as an EOC biomarker to complement the standard serum carbohydrate antigen 125 (CA125) test. Thus, accurate quantification of serum HSP27 would assist the diagnosis of EOC. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics coupled with an immunoaffinity enrichment assay was developed and validated to monitor HSP27 concentrations in serum...
November 28, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Wei Tang, Ming Zhou, Tiffany H Dorsey, DaRue A Prieto, Xin W Wang, Eytan Ruppin, Timothy D Veenstra, Stefan Ambs
BACKGROUND: Transcriptome analysis of breast cancer discovered distinct disease subtypes of clinical significance. However, it remains a challenge to define disease biology solely based on gene expression because tumor biology is often the result of protein function. Here, we measured global proteome and transcriptome expression in human breast tumors and adjacent non-cancerous tissue and performed an integrated proteotranscriptomic analysis. METHODS: We applied a quantitative liquid chromatography/mass spectrometry-based proteome analysis using an untargeted approach and analyzed protein extracts from 65 breast tumors and 53 adjacent non-cancerous tissues...
December 3, 2018: Genome Medicine
Martin C H Gruhlke, Haike Antelmann, Jörg Bernhardt, Veronika Kloubert, Lothar Rink, Alan J Slusarenko
A single clove of edible garlic (Allium sativum L.) of about 10g produces up to 5mg of allicin (diallylthiosulfinate), a thiol-reactive sulfur-containing defence substance that gives injured garlic tissue its characteristic smell. Allicin induces apoptosis or necrosis in a dose-dependent manner but biocompatible doses influence cellular metabolism and signalling cascades. Oxidation of protein thiols and depletion of the glutathione pool are thought to be responsible for allicin's physiological effects. Here, we studied the effect of allicin on post-translational thiol-modification in human Jurkat T-cells using shotgun LC-MS/MS analyses...
November 27, 2018: Free Radical Biology & Medicine
Venkatesh Chanukuppa, Ravindra Taware, Tathagat Chatterjee, Sanjeevan Sharma, Tushar H More, Khushman Taunk, Saravanan Kumar, Manas K Santra, Srikanth Rapole
Chemoresistance is one of the major hurdles in cancer treatment leading to recurrence of cancer and affects overall survival of patients. Cancer chemoresistance can be associated with various phenomena including modulation of vital cellular pathways. Unrevealing these alterations could provide better understanding of chemoresistance and assist in identification of new targets to overcome it. Recent advances in the field of proteomics and metabolomics have substantially helped in identification of potential targets for chemoresistance in various cancers...
November 29, 2018: Current Topics in Medicinal Chemistry
Anna Roth, Karine Boulay, Matthias Groß, Maria Polycarpou-Schwarz, Frédérick A Mallette, Marine Regnier, Or Bida, Doron Ginsberg, Arne Warth, Philipp A Schnabel, Thomas Muley, Michael Meister, Heike Zabeck, Hans Hoffmann, Sven Diederichs
Aberrant expression of noncoding RNAs plays a critical role during tumorigenesis. To uncover novel functions of long non-coding RNA (lncRNA) in lung adenocarcinoma, we used a microarray-based screen identifying LINC00673 with elevated expression in matched tumor versus normal tissue. We report that loss of LINC00673 is sufficient to trigger cellular senescence, a tumor suppressive mechanism associated with permanent cell cycle arrest, both in lung cancer and normal cells in a p53-dependent manner. LINC00673-depleted cells fail to efficiently transit from G1- to S-phase...
November 30, 2018: RNA Biology
Ryoichi Matsunuma, Doug W Chan, Beom-Jun Kim, Purba Singh, Airi Han, Alexander B Saltzman, Chonghui Cheng, Jonathan T Lei, Junkai Wang, Leonardo Roberto da Silva, Ergun Sahin, Mei Leng, Cheng Fan, Charles M Perou, Anna Malovannaya, Matthew J Ellis
A Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomic analysis prioritized dihydropyrimidinase-like-3 (DPYSL3) as a multilevel (RNA/protein/phosphoprotein) expression outlier specific to the claudin-low (CLOW) subset of triple-negative breast cancers. A PubMed informatics tool indicated a paucity of data in the context of breast cancer, which further prioritized DPYSL3 for study. DPYSL3 knockdown in DPYSL3-positive ([Formula: see text]) CLOW cell lines demonstrated reduced proliferation, yet enhanced motility and increased expression of epithelial-to-mesenchymal transition (EMT) markers, suggesting that DPYSL3 is a multifunctional signaling modulator...
November 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
Maya Cohen, Sharon Amir, Maya Golan, Yinon Ben-Neriah, Nicola J Mabjeesh
The substantial availability of hypoxia-inducible factor 1 (HIF-1) for pathophysiological states, such as malignancies and ischemia, is primarily regulated post-translationally through the ubiquitin proteolytic system. The balance between degradation and stabilization of HIF-1α protein is determined by specific E3 ligases. In our search for new E3 ligases that might affect HIF-1α protein expression, we studied the effects of beta-transducin repeat-containing protein (β-TrCP) on the hypoxic pathway in cancer cells...
November 28, 2018: Prostate
Bing Zhang, Jeffrey R Whiteaker, Andrew N Hoofnagle, Geoffrey S Baird, Karin D Rodland, Amanda G Paulovich
Cancer genomics research aims to advance personalized oncology by finding and targeting specific genetic alterations associated with cancers. In genome-driven oncology, treatments are selected for individual patients on the basis of the findings of tumour genome sequencing. This personalized approach has prolonged the survival of subsets of patients with cancer. However, many patients do not respond to the predicted therapies based on the genomic profiles of their tumours. Furthermore, studies pairing genomic and proteomic analyses of samples from the same tumours have shown that the proteome contains novel information that cannot be discerned through genomic analysis alone...
November 28, 2018: Nature Reviews. Clinical Oncology
Lin Li, Weili Miao, Ming Huang, Preston Williams, Yinsheng Wang
Clear cell renal cell carcinoma (ccRCC) is the most common type of RCC in humans. SET domain-containing 2 (SETD2), a lysine methyltransferase for histone and other proteins, has been found to be frequently lost in ccRCC. However, the mechanisms through which deficiency in SETD2 contributes to ccRCC development remain largely unknown. Here, we used a human embryonic kidney epithelial cell line with the SETD2 gene knocked out using CRISPR/Cas9 technology. Using ChIP-seq analysis, we showed that SETD2 loss leads to diminished occupancy of histone H3K36me3 and H4K16ac on actively transcribed genes...
November 28, 2018: Molecular & Cellular Proteomics: MCP
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