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cancer proteomics

Diptiman Chanda, Eva Otoupalova, Kenneth P Hough, Morgan L Locy, Karen Bernard, Jessy S Deshane, Ralph D Sanderson, James A Mobley, Victor J Thannickal
Extracellular vesicles (EVs) are endosome and plasma membrane-derived nanosized vesicles that participate in intercellular signaling. Although EV cargo may signal via multiple mechanisms, how signaling components on the surface of EVs mediate cellular signaling is less well understood. In this study, we show that fibroblast-derived EVs carry fibronectin on the vesicular surface, as evidenced by mass spectrometry-based proteomics (sequential windowed acquisition of all theoretical peptides; SWATH) and flow cytometric analyses...
October 15, 2018: American Journal of Respiratory Cell and Molecular Biology
Guangxia Chen, Chenxiao Yu, Zhicheng Tang, Shiyu Liu, Fangmei An, Junjia Zhu, Qianqian Wu, Jianping Cao, Qiang Zhan, Shuyu Zhang
Gastric cancer is one of the most common malignant tumor types worldwide, with a high morbidity and associated mortality. The interaction between gastric cancer cells and their microenvironment has a significant role in their maintenance and progression. Gastric tumor‑associated fibroblasts (TAFs) are among the major regulators of the gastric cancer microenvironment. Metformin, a classical anti‑diabetic drug, is known to prevent cancer progression. However, the effect of metformin on gastric TAFs and TAF‑associated cancer progression has remained to be elucidated...
October 11, 2018: Oncology Reports
Jonathan D Mortison, Monica Schenone, Jacob A Myers, Ziyang Zhang, Linfeng Chen, Christie Ciarlo, Eamon Comer, S Kundhavai Natchiar, Steven A Carr, Bruno P Klaholz, Andrew G Myers
Apart from their antimicrobial properties, tetracyclines demonstrate clinically validated effects in the amelioration of pathological inflammation and human cancer. Delineation of the target(s) and mechanism(s) responsible for these effects, however, has remained elusive. Here, employing quantitative mass spectrometry-based proteomics, we identified human 80S ribosomes as targets of the tetracyclines Col-3 and doxycycline. We then developed in-cell click selective crosslinking with RNA sequence profiling (icCL-seq) to map binding sites for these tetracyclines on key human rRNA substructures at nucleotide resolution...
October 5, 2018: Cell Chemical Biology
Nuzhat Ahmed, Ruth Escalona, Dilys Leung, Emily Chan, George Kannourakis
Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions...
October 11, 2018: Seminars in Cancer Biology
Laura M Snell, Bethany L MacLeod, Jaclyn C Law, Ivan Osokine, Heidi J Elsaesser, Kebria Hezaveh, Russell J Dickson, Marc A Gavin, Cynthia J Guidos, Tracy L McGaha, David G Brooks
CD8+ T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8+ T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1+ cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy...
October 1, 2018: Immunity
Juan Ma, Bei-Bei Wang, Xiao-Yan Ma, Wei-Ping Deng, Li-Shu Xu, Wei-Hong Sha
AIM: To identify functional proteins involved in pancreatic-duodenal homeobox-1 (PDX1)-mediated effects on gastric carcinogenesis. METHODS: A PDX1-overexpressed model was established by transfecting gastric cancer cell line SGC7901 with pcDNA3.1(+)-PDX1 vector (SGC-PDX1). Transfection with empty pcDNA3.1 vector (SGC-pcDNA) served as control. Comparative protein profiles of the two groups were analyzed by two-dimensional electrophoresis based-proteomics (2DE gel-based proteomics)...
October 7, 2018: World Journal of Gastroenterology: WJG
Asif Ali, Anindya Biswas, Mahadeb Pal
The proteotoxic stress response that safeguards the cellular proteome from various stressors was shown to activate NF-κB signaling pathways (NκBS) with an underlying mechanism that is poorly understood. We show here that the TNF-α gene, a pleiotropic NκBS inducer, is a direct target of heat shock factor 1 (HSF1). Human HSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 3'-UTR of the TNF-α gene (HSE5). HSF1 associated with the HSE5 at the TNF-α 3'-UTR communicates with the promoter through chromatin looping by recruiting lymphoid enhancer-binding factor 1 at an adjacent Wnt-responsive element through its transactivation domain...
October 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
H Rudolf de Boer, Martin Pool, Esméé Joosten, Marieke Everts, Douwe F Samplonius, Wijnand Helfrich, Harry J M Groen, Suzanne van Cooten, Fabrizia Fusetti, Rudolf S N Fehrmann, Elisabeth G E de Vries, Marcel A T M van Vugt
Tumor responses to cancer therapeutics are generally monitored every 2-3 months based on changes in tumor size. Dynamic biomarkers that reflect effective engagement of targeted therapeutics to the targeted pathway, so-called "effect sensors", would fulfill a need for non-invasive, drug-specific indicators of early treatment effect. Using a proteomics approach to identify effect sensors, we demonstrated MUC1 upregulation in response to epidermal growth factor receptor (EGFR)-targeting treatments in breast and lung cancer models...
October 10, 2018: Oncogene
Prajish Iyer, Shailesh V Shrikhande, Malika Ranjan, Asim Joshi, Nilesh Gardi, Ratnam Prasad, Bhasker Dharavath, Rahul Thorat, Sameer Salunkhe, Bikram Sahoo, Pratik Chandrani, Hitesh Kore, Bhabani Mohanty, Vikram Chaudhari, Anuradha Choughule, Dhananjay Kawle, Pradip Chaudhari, Arvind Ingle, Shripad Banavali, Poonam Gera, Mukta R Ramadwar, Kumar Prabhash, Savio George Barreto, Shilpee Dutt, Amit Dutt
The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n=25) and recurrent mutations in 14% tumors (n=44); along with co-occurring KRAS mutation in 7% tumors (n=44)...
October 10, 2018: International Journal of Cancer. Journal International du Cancer
Shuangshuang Mao, Yuan Li, Zhiliang Lu, Yun Che, Shouguo Sun, Jianbing Huang, Yuanyuan Lei, Xinfeng Wang, Chengming Liu, Sufei Zheng, Ruochuan Zang, Ning Li, Jiagen Li, Nan Sun, Jie He
Alternative splicing (AS), a major mechanism for the enhancement of transcriptome and proteome diversity, has been widely demonstrated to be involved in the full spectrum of oncogenic processes. High-throughput sequencing technology and the rapid accumulation of clinical data sets have provided an opportunity to systemically analyze the association between messenger RNA AS variants and patient clinical outcomes. Here, we compared differentially spliced AS transcripts between esophageal carcinoma (ESCA) and non-tumor tissues, profiled genome-wide survival-associated AS events in 87 patients with esophageal adenocarcinoma (EAC) and 79 patients with esophageal squamous cell carcinoma (ESCC) using The Cancer Genome Atlas (TCGA) RNA-seq data set, and constructed predictive models as well as splicing regulation networks by integrated bioinformatic analysis...
October 9, 2018: Carcinogenesis
J Almeida, J Costa, P Coelho, V Cea, M Galesio, J P Noronha, M S Diniz, C Prudêncio, R Soares, C Sala, Rúben Fernandes
Gliomas represent the most common primary malignant brain tumors in adults, with an extremely poor prognosis. Among several risk factors, lifestyle was also recently identified as a major risk factor for the development of primary glioma. In the present study, we explore the relationship between obesity and glioma in a cellular model. Thus, we have study the influence of adipocytes secretome on glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned medium (adipokines-enriched medium), we showed that adipocyte-released factors relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI-TOF-MS and proteomic array analysis...
October 9, 2018: Metabolic Brain Disease
Wei Liang, Qin Li, Napoleone Ferrara
The tumor-promoting functions of neutrophils have been mainly attributed to induction of tumor angiogenesis or suppression of anticancer immunity. However, a direct impact of neutrophils on tumor cell growth and metastasis remains largely uncharacterized. Here, we coupled a proteomic approach with a functional screen to interrogate the secretome of tumor-associated neutrophils. Surprisingly, the iron-transporting protein transferrin was identified as the major mitogen for tumor cells secreted by neutrophils...
October 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Min Jin Ha, Sayantan Banerjee, Rehan Akbani, Han Liang, Gordon B Mills, Kim-Anh Do, Veerabhadran Baladandayuthapani
Personalized (patient-specific) approaches have recently emerged with a precision medicine paradigm that acknowledges the fact that molecular pathway structures and activity might be considerably different within and across tumors. The functional cancer genome and proteome provide rich sources of information to identify patient-specific variations in signaling pathways and activities within and across tumors; however, current analytic methods lack the ability to exploit the diverse and multi-layered architecture of these complex biological networks...
October 8, 2018: Scientific Reports
Hong Zhang, Yirong Wang, Jun Li, Han Chen, Xionglei He, Huiwen Zhang, Han Liang, Jian Lu
Rapidly proliferating cancer cells have much higher demand for proteinogenic amino acids than normal cells. The use of amino acids in human proteomes is largely affected by their bioavailability, which is constrained by the biosynthetic energy cost in living organisms. Conceptually distinct from gene-based analyses, we introduce the energy cost per amino acid (ECPA) to quantitatively characterize the use of 20 amino acids during protein synthesis in human cells. By analyzing gene expression data from The Cancer Genome Atlas, we find that cancer cells evolve to utilize amino acids more economically by optimizing gene expression profile and ECPA shows robust prognostic power across many cancer types...
October 8, 2018: Nature Communications
Dinoop Ravindran Menon, Yuchun Luo, John J Arcaroli, Sucai Liu, Lekha Nair KrishnanKutty, Douglas G Osborne, Yang Li, Jenny Mae Samson, Stacey Bagby, Aik-Choon Tan, William A Robinson, Wells A Messersmith, Mayumi Fujita
Cancers are comprised of heterogeneous subpopulations with various tumor-initiating capacities, yet key stem cell genes associated with enhanced tumor initiating capacities and their regulatory mechanisms remain elusive. Here we analyzed patient-derived xenografts from melanoma, colon, and pancreatic cancer tissues and identified enrichment of tumor-initiating cells in MHC class I-hi cells, where CDK1, a master regulator of the cell cycle, was upregulated. Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells increased their spheroid forming ability, tumorigenic potential, and tumor-initiating capacity; inhibition of CDK1 with pharmacological agents reduced these characteristics, which was unexplained by the role of CDK1 in regulating the cell cycle...
October 8, 2018: Cancer Research
Jun Dong, Zeyu Wu, Dan Wang, Laura E Pascal, Joel B Nelson, Peter Wipf, Zhou Wang
The androgen receptor (AR) is a key driver and therapeutic target in androgen-sensitive prostate cancer, castration resistant prostate cancer (CRPC), and CRPC resistant to abiraterone and enzalutamide, two second generation inhibitors of AR signaling. Since current AR inhibitors target a functioning C-terminal ligand binding domain (LBD), the identification and characterization of co-factors interacting with the N-terminal domain (NTD) of AR may lead to new approaches to target AR signaling in CRPC. Using a pulldown approach coupled with proteomics, we have identified Hsp70 as a co-factor for the NTD of AR in prostate cancer cells...
October 8, 2018: Molecular Cancer Therapeutics
Osamu Ichiyanagi, Sei Naito, Hiromi Ito, Takanobu Kabasawa, Takafumi Narisawa, Hidenori Kanno, Yuta Kurota, Masayuki Kurokawa, Hiroki Fukuhara, Toshihiko Sakurai, Hayato Nishida, Tomoyuki Kato, Mitsunori Yamakawa, Norihiko Tsuchiya
BACKGROUND: The objective was to explore the predictive markers of late recurrence (LR) > 5 years after curative nephrectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS: We retrospectively examined the data from 303 patients with localized clear cell RCC treated surgically at our institution from 1993 to 2011. Activation of the eukaryotic initiation factor (eIF)4E-binding protein 1 (4EBP1)/eIF4E axis at the mammalian target of rapamycin complex 1 (mTORC1) was evaluated in the tumor specimens...
October 2018: Clinical Genitourinary Cancer
Katrin Tiemann, Carolina Garri, Jeffrey Wang, Lauren Clarke, Kian Kani
Cancer patients with an aberrant regulation of the protein phosphorylation networks are often treated with the tyrosine kinase inhibitors. Response rates approaching 85% are common. Unfortunately, patients often become refractory to the treatment by altering their signal transduction pathways. An implementation of the expression profiling with microarrays can identify the overall mRNA-level changes, and proteomics can identify the overall changes in protein levels or can identify the proteins involved, but the activity of the signal transduction pathways can only be established by interrogating post-translational modifications of the proteins...
September 19, 2018: Journal of Visualized Experiments: JoVE
Zsuzsanna Kovacs, Andras Guttman
Multiple myeloma (MM) is characterized as the clonal proliferation of malignant plasma B-lymphocytes and even as of today, it is an incurable disease. MM accounts for approximately 10% of all hematologic cancers. Its molecular pathogenesis is poorly understood, but the bone marrow microenvironment of tumor cells and genetic factors have apparent roles in the process. Accurate diagnosis is important to properly identify and stratify the disease, however, MM identification steps are time-consuming and expensive...
October 8, 2018: Current Molecular Medicine
Katrin Erich, Kevin Reinle, Torsten Müller, Bogdan Munteanu, Denis A Sammour, Isabel Hinsenkamp, Tobias Gutting, Elke Burgermeister, Peter Findeisen, Matthias P Ebert, Jeroen Krijgsveld, Carsten Hopf
Aberrant protease activity has been implicated in the etiology of various prevalent diseases including neurodegeneration and cancer, in particular metastasis. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has recently been established as a key technology for bioanalysis of multiple biomolecular classes such as proteins, lipids, and glycans. However, it has not yet been systematically explored for investigation of a tissue's endogenous protease activity. In this study, we demonstrate that different tissues, spray-coated with substance P as a tracer, digest this peptide with different time-course profiles...
October 7, 2018: Molecular & Cellular Proteomics: MCP
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