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https://www.readbyqxmd.com/read/30439456/altered-cancer-metabolism-in-mechanisms-of-immunotherapy-resistance
#1
REVIEW
Rishab Ramapriyan, Mauricio da Silva Caetano, Hampartsoum B Barsoumian, Ana Carolina P Mafra, Erika Pereira Zambalde, Hari Menon, Efrosini Tsouko, James W Welsh, Maria Angelica Cortez
Many metabolic alterations, including the Warburg effect, occur in cancer cells that influence the tumor microenvironment, including switching to glycolysis from oxidative phosphorylation, using opportunistic modes of nutrient acquisition, and increasing lipid biosynthesis. The altered metabolic landscape of the tumor microenvironment can suppress the infiltration of immune cells and other functions of antitumor immunity through the production of immune-suppressive metabolites. Metabolic dysregulation in cancer cells further affects the expression of cell surface markers, which interferes with immune surveillance...
November 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30431206/an-amino-acid-metabolism-related-gene-expression-based-risk-signature-can-better-predict-overall-survival-for-glioma
#2
Yu-Qing Liu, Rui-Chao Chai, Yong-Zhi Wang, Zheng Wang, Xing Liu, Fan Wu, Tao Jiang
Metabolic reprogramming has been proposed to be a hallmark of cancer. Aside from glycolytic pathway, the metabolic changes of cancer cells primarily involve amino acid metabolism. However, the characteristic of amino acid metabolism-related gene set has not been systematically profiled in glioma. In this study, RNA sequencing expression data from 309 patients in the Chinese Glioma Genome Atlas database were included as training set, while another 550 patients with the Cancer Genome Atlas database were used to validate...
November 15, 2018: Cancer Science
https://www.readbyqxmd.com/read/30431179/3d-gradient-echo-snapshot-cest-mri-with-low-power-saturation-for-human-studies-at-3t
#3
Anagha Deshmane, Moritz Zaiss, Tobias Lindig, Kai Herz, Mark Schuppert, Chirayu Gandhi, Benjamin Bender, Ulrike Ernemann, Klaus Scheffler
PURPOSE: For clinical implementation, a chemical exchange saturation transfer (CEST) imaging sequence must be fast, with high signal-to-noise ratio (SNR), 3D coverage, and produce robust contrast. However, spectrally selective CEST contrast requires dense sampling of the Z-spectrum, which increases scan duration. This article proposes a compromise: using a 3D snapshot gradient echo (GRE) readout with optimized CEST presaturation, sampling, and postprocessing, highly resolved Z-spectroscopy at 3T is made possible with 3D coverage at almost no extra time cost...
November 15, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/30430946/the-development-of-epigenetics-and-related-inhibitors-for-targeted-drug-design-in-cancer-therapy
#4
Na Liu, Rongtong Zhao, Yue Ma, Dongyuan Wang, Chen Yan, Dongxian Zhou, Feng Yin, Zigang Li
Epigenetics process is the heritable change in gene function that does not involve changes in the DNA sequence. Until now, several types of epigenetic mechanisms have been characterized, including DNA methylation, histone modification (acetylation, methylation, etc.), nucleosome remodeling, and noncoding RNAs. With the biological investigations of these modifiers, some of them are identified as promoters in the process of various diseases, such as cancer, cardiovascular disease and virus infection. Epigenetic changes may serve as potential "first hits" for tumorigenesis...
November 14, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/30430578/single-cell-sequencing-defines-genetic-heterogeneity-in-pancreatic-cancer-precursor-lesions
#5
Yuko Kuboki, Catherine G Fischer, Violeta Beleva Guthrie, Wenjie Huang, Jun Yu, Peter Chianchiano, Waki Hosoda, Hao Zhang, Lily Zheng, Xiaoshan Shao, Elizabeth D Thompson, Kevin Waters, Justin Poling, Jin He, Matthew J Weiss, Christopher L Wolfgang, Michael G Goggins, Ralph H Hruban, Nicholas J Roberts, Rachel Karchin, Laura D Wood
Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer; however, little is known about genetic heterogeneity in these lesions. The objective of this study was to characterize genetic heterogeneity in IPMNs at the single-cell level. We isolated single cells from fresh tissue from ten IPMNs, followed by whole genome amplification and targeted next generation sequencing of pancreatic driver genes. We then determined single-cell genotypes using a novel multi-sample mutation calling algorithm...
November 14, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/30430365/characterization-of-circulating-tumor-cells-in-breast-cancer-patients-by-spiral-microfluidics
#6
Jianhua Yin, Zhifeng Wang, Guibo Li, Feng Lin, Kang Shao, Boyang Cao, Yong Hou
Circulating tumor cells (CTCs) have important application prospects in the early diagnosis, treatment evaluation, and prognostic prediction of tumors. In this study, we enrolled a total of 65 patients with different stages and molecular subtypes of breast cancer and isolated and enriched for CTCs from peripheral blood using the ClearCell FX1 platform, which is based on a label-free spiral microfluidic method. The ClearCell platform can successfully isolate CTCs from peripheral blood with different detection rates in breast cancer patients...
November 14, 2018: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/30430107/ctdna-detection-based-on-dna-clutch-probes-and-strand-exchange-mechanism
#7
Huan Chang, Yiyi Zhang, Fan Yang, Changtao Wang, Haifeng Dong
Circulating tumor DNA (ctDNA), originating directly from the tumor or circulating tumor cells, may reflect the entire tumor genom and has gained considerable attention for its potential clinical diagnosis and prognosis throughout the treatment regimen. However, the reliable and robust ctDNA detection remains a key challenge. Here, this work designs a pair of DNA clutch separation probes and an ideal discrimination probes based on toehold-mediated strand displacement reaction (TSDR) to specifically recognize ctDNA...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/30429889/theranostic-pretargeted-radioimmunotherapy-of-internalizing-solid-tumor-antigens-in-human-tumor-xenografts-in-mice-curative-treatment-of-her2-positive-breast-carcinoma
#8
Sarah M Cheal, Hong Xu, Hong-Fen Guo, Mitesh Patel, Blesida Punzalan, Edward K Fung, Sang-Gyu Lee, Meghan Bell, Manisha Singh, Achim A Jungbluth, Pat B Zanzonico, Alessandra Piersigilli, Steven M Larson, Nai-Kong V Cheung
In recent reports, we have shown that optimized pretargeted radioimmunotherapy (PRIT) based on molecularly engineered antibody conjugates and 177 Lu-DOTA chelate (DOTA-PRIT) can be used to cure mice bearing human solid tumor xenografts using antitumor antibodies to minimally internalizing membrane antigens, GPA33 (colon) and GD2 (neuroblastoma). However, many solid tumor membrane antigens are internalized after antibody binding and it is generally believed that internalizing tumor membrane antigens are not suitable targets for PRIT...
2018: Theranostics
https://www.readbyqxmd.com/read/30429477/whole-genome-sequencing-puts-forward-hypotheses-on-metastasis-evolution-and-therapy-in-colorectal-cancer
#9
Naveed Ishaque, Mohammed L Abba, Christine Hauser, Nitin Patil, Nagarajan Paramasivam, Daniel Huebschmann, Jörg Hendrik Leupold, Gnana Prakash Balasubramanian, Kortine Kleinheinz, Umut H Toprak, Barbara Hutter, Axel Benner, Anna Shavinskaya, Chan Zhou, Zuguang Gu, Jules Kerssemakers, Alexander Marx, Marcin Moniuszko, Miroslaw Kozlowski, Joanna Reszec, Jacek Niklinski, Jürgen Eils, Matthias Schlesner, Roland Eils, Benedikt Brors, Heike Allgayer
Incomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33. Recurrently mutated non-coding elements include ncRNAs RP11-594N15...
November 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/30429351/infection-of-cell-lines-derived-from-diffuse-large-b-cell-lymphoma-dlbcl-with-the-epstein-barr-virus-ebv-alters-the-mirna-loading-of-the-ago2-complex
#10
Hiresh Ayoubian, Nicole Ludwig, Tobias Fehlmann, Jennifer Menegatti, Laura Gröger, Eleni Anastasiadou, Pankaj Trivedi, Andreas Keller, Eckart Meese, Friedrich A Grässer
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoid tumor which is occasionally Epstein-Barr virus (EBV)-positive and is further subtyped as activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL, which has implications for prognosis and treatment.We performed Ago2-RNA immunoprecipitation followed by high throughput RNA sequencing (Ago2-RIP-Seq) to capture functionally active miRNAs in EBV-negative ABC-DLBCL and GC-DLBCL cell lines and their EBV-infected counterparts. In parallel, total miRNomes of these cells were sequenced to capture the cellular miRNA profile for comparison with the functionally active profile...
November 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30429336/rna-sequencing-of-the-i-n-vivo-human-herpesvirus-6b-transcriptome-to-identify-targets-for-clinical-assays-distinguishing-between-latent-and-active-infections
#11
Joshua A Hill, Minako Ikoma, Danielle M Zerr, Ryan S Basom, Vikas Peddu, Meei-Li Huang, Ruth Hall Sedlak, Keith R Jerome, Michael Boeckh, Serge Barcy
Human herpesvirus 6B (HHV-6B) DNA is frequently detected in human samples. Diagnostic assays distinguishing HHV-6B reactivation from latency are limited. This has impaired strategies to diagnose and treat HHV-6B-associated diseases. We used RNA sequencing to characterize and compare the HHV-6B transcriptome in multiple sample types, including 1) whole blood from hematopoietic cell transplant (HCT) recipients with and without HHV-6B plasma viremia; 2) tumor tissue samples from subjects with large B cell lymphoma infected with HHV-6B; 3) lymphoblastoid cell lines (LCLs) from subjects with inherited chromosomally integrated HHV-6B or latent infection with HHV-6B; and 4) HHV-6B Z29 infected SupT1 CD4+ T cells...
November 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30429033/clinicopathological-and-genomic-comparisons-between-different-histologic-components-in-combined-small-cell-lung-cancer-and-non-small-cell-lung-cancer
#12
Mong-Wei Lin, Kang-Yi Su, Te-Jen Su, Chia-Ching Chang, Jing-Wei Lin, Yi-Hsuan Lee, Sung-Liang Yu, Jin-Shing Chen, Min-Shu Hsieh
OBJECTIVE: Histologic transformation from adenocarcinoma to small cell lung cancer (SCLC) is one of the mechanisms of acquired resistance after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. Furthermore, de novo combined SCLC/non-small cell lung cancer (NSCLC) have occasionally been reported; however, their mutational statuses and clinicopathological features have not yet been elucidated. In this study, we aimed to profile the genetic backgrounds of these 2 different histologic components by investigating patients with de novo combined SCLC/NSCLC as well as those with lung adenocarcinoma who experienced SCLC transformation after TKI treatment...
November 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/30428910/downregulation-of-cldn7-due-to-promoter-hypermethylation-is-associated-with-human-clear-cell-renal-cell-carcinoma-progression-and-poor-prognosis
#13
Yifan Li, Yanqing Gong, Xianghui Ning, Ding Peng, Libo Liu, Shiming He, Kan Gong, Cuijian Zhang, Xuesong Li, Liqun Zhou
BACKGROUND: Metastasis is the primary cause of death in renal cell carcinoma (RCC). Loss of cell-to-cell adhesion, including tight junctions (TJs) is the initial step in the process of metastasis. Claudin-7 (CLDN7) is a major component of TJs. However, the clinical significance and its regulation of kidney tumorigenesis remain poorly understood. METHODS: A total of 120 fresh clear cell RCC (ccRCC) specimens and 144 primary RCC and adjacent nonmalignant renal paraffin specimens were obtained from Department of Urology, Peking University First Hospital...
November 14, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30428830/hseghmm-hidden-markov-model-based-allele-specific-copy-number-alteration-analysis-accounting-for-hypersegmentation
#14
Hyoyoung Choo-Wosoba, Paul S Albert, Bin Zhu
BACKGROUND: Somatic copy number alternation (SCNA) is a common feature of the cancer genome and is associated with cancer etiology and prognosis. The allele-specific SCNA analysis of a tumor sample aims to identify the allele-specific copy numbers of both alleles, adjusting for the ploidy and the tumor purity. Next generation sequencing platforms produce abundant read counts at the base-pair resolution across the exome or whole genome which is susceptible to hypersegmentation, a phenomenon where numerous regions with very short length are falsely identified as SCNA...
November 14, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/30428773/farnesoid-x-receptor-agonist-gw4064-inhibits-aromatase-and-er%C3%AE-expression-in-human-endometriotic-stromal-cells
#15
Pei-Li Wu, Cheng Zeng, Ying-Fang Zhou, Ling Yin, Xiao-Lan Yu, Qing Xue
Endometriosis is an estrogen-dependent disease. Farnesoid X receptor (FXR) activation has been shown to inhibit estrogen signaling in breast cancer and testicular tumors. However, the role of FXR in endometriosis is still poorly understood. Here, we aimed to investigate whether FXR activation by its synthetic agonist GW4064 has a therapeutic effect on endometriosis and the underlying molecular mechanisms. We found that the expression of FXR (encoded by the NR1H4 gene) in endometriotic tissues and stromal cells (ESCs) was higher than that in eutopic endometrial tissues and stromal cells...
November 14, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/30428638/genetic-profiles-associated-with-chemoresistance-in-patient-derived-xenograft-models-of-ovarian-cancer
#16
Lan Ying Li, Hee Jung Kim, Sun Ae Park, So Hyun Lee, Lee Kyung Kim, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim, Eun Ji Nam
Purpose: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. Materials and Methods: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes...
November 6, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/30427722/revising-the-plac8-gene-family-from-a-central-role-in-differentiation-proliferation-and-apoptosis-in-mammals-to-a-multifunctional-role-in-plants
#17
Caroline Cabreira-Cagliari, Nathalia de Cassia Dias, Bianca Bohn, David Gabriel Dos Santos Fagundes, Marcia Margis-Pinheiro, Maria Helena Bodanese Zanettini, Alexandro Cagliari
PLAC8 is a cysteine-rich protein described as a central mediator of tumor evolution in mammals, being a promising candidate for diagnostic and therapeutic targeting. The PLAC8 gene also acts in the contact hypersensitivity response and serves a role in psoriatic skin. In plants, PLAC8 motif-containing proteins are involved in determination of organ size, growth, response to infection, Ca2+ influx, Cd resistance, and zinc detoxification. In general, the PLAC8 motif-containing proteins present the conserved CCXXXXCPC or CLXXXXCPC region...
November 14, 2018: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/30427539/regional-differences-in-gallbladder-cancer-pathogenesis-insights-from-a-multi-institutional-comparison-of-tumor-mutations
#18
Raja R Narayan, John M Creasy, Debra A Goldman, Mithat Gönen, Cyriac Kandoth, Ritika Kundra, David B Solit, Gokce Askan, David S Klimstra, Olca Basturk, Peter J Allen, Vinod P Balachandran, Michael I D'Angelica, Ronald P DeMatteo, Jeffrey A Drebin, T Peter Kingham, Amber L Simpson, Ghassan K Abou-Alfa, James J Harding, Eileen M O'Reilly, Jean M Butte, Ryusei Matsuyama, Itaru Endo, William R Jarnagin
BACKGROUND: Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens. METHODS: Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer-associated genes. Fisher exact and Kruskal-Wallis tests assessed differences in clinicopathologic and genetic factors...
November 14, 2018: Cancer
https://www.readbyqxmd.com/read/30426614/t-cell-receptor-%C3%AE-chain-repertoire-analysis-of-tumor-infiltrating-lymphocytes-in-pancreatic-cancer
#19
Can Cui, Xiuyun Tian, Jianhui Wu, Chaoting Zhang, Qin Tan, Xiaoya Guan, Bin Dong, Min Zhao, Zheming Lu, Chunyi Hao
Pancreatic cancer is lethal due to lack of perceptible symptoms and effective treatment methods. Immunotherapy may provide promising therapeutic choices for malignant tumors like pancreatic cancer. Tumor infiltrating lymphocytes (TILs) in tumor mesenchyme could recognize peptide antigens presented on the surface of tumor cells. This study aimed to test the relationship between the TCR β repertoire of the tumor and peripheral blood, and also to investigate the intra-tumor spatial heterogeneity of the TCR β repertoire in pancreatic cancer...
November 13, 2018: Cancer Science
https://www.readbyqxmd.com/read/30425968/high-sensitive-and-non-invasive-ctdnas-sequencing-facilitate-clinical-diagnosis-and-clinical-guidance-of-non-small-cell-lung-cancer-patient-a-time-course-study
#20
Yongqiang Li, Jiajia Lv, Shaogui Wan, Junfang Xin, Tiantian Xie, Tao Li, Wan Zhu, Guosen Zhang, Yunlong Wang, Yitai Tang, Ao Li, Xiangqian Guo
Lung cancer is one of leading causes of cancer death all over the world. Non-small cell lung cancer (NSCLC) is the most predominant subtype of lung cancer. Molecular targeting therapy has been shown great success in the treatment of advanced NSCLC. Thus, an easy, sensitive, and specific way of recognizing therapeutic gene targets would help to select effective treatments, to improve physical condition and increase patient survival. In this study, we recruited and followed up a female NSCLC patient, whose plasma ctDNAs (circulating tumor DNAs), blood cell DNAs, psDNAs (pleural effusion supernatant DNAs), and ppDNAs (pleural effusion pellet DNAs), were collected and analyzed over periodic time points by methods of next generation sequencing (NGS), droplet digital PCR (ddPCR), and Amplification Refractory Mutation System (ARMS)...
2018: Frontiers in Oncology
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