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https://www.readbyqxmd.com/read/29456552/identification-of-single-nucleotide-non-coding-driver-mutations-in-cancer
#1
REVIEW
Kok A Gan, Sebastian Carrasco Pro, Jared A Sewell, Juan I Fuxman Bass
Recent whole-genome sequencing studies have identified millions of somatic variants present in tumor samples. Most of these variants reside in non-coding regions of the genome potentially affecting transcriptional and post-transcriptional gene regulation. Although a few hallmark examples of driver mutations in non-coding regions have been reported, the functional role of the vast majority of somatic non-coding variants remains to be determined. This is because the few driver variants in each sample must be distinguished from the thousands of passenger variants and because the logic of regulatory element function has not yet been fully elucidated...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29455885/vincristine-resistance-in-relapsed-neuroblastoma-can-be-efficiently-overcome-by-smac-mimetic-lcl161-treatment
#2
Kristin Frommann, Birgit Appl, Patrick Hundsdoerfer, Konrad Reinshagen, Georg Eschenburg
PURPOSE: In spite of good initial therapy response neuroblastomas often spread to distant organs or relapse after periods of remission. Dysregulation of apoptosis, a hallmark of cancer, is often effected by elevated levels of antiapoptotic signals leading to resistance against chemotherapeutic drugs. Inhibitors of apoptosis proteins (IAPs) are crucial cellular apoptosis regulators. Targeting IAPs with Smac mimetics has been demonstrated as a promising strategy for treatment of neuroblastoma and other tumors...
January 31, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29455351/lead-facilitates-foci-formation-in-a-balb-c-3t3-two-step-cell-transformation-model-role-of-ape1-function
#3
Pablo Hernández-Franco, Martín Silva, Rodrigo Franco, Mahara Valverde, Emilio Rojas
Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 μM induced APE1 mRNA and upregulation of protein expression...
February 17, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29454048/new-insights-into-the-molecular-characteristics-of-pulmonary-carcinoids-and-large-cell-neuroendocrine-carcinomas-and-the-impact-on-their-clinical-management
#4
REVIEW
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29449774/reactive-oxygen-species-a-key-constituent-in-cancer-survival
#5
REVIEW
Seema Kumari, Anil Kumar Badana, Murali Mohan G, Shailender G, RamaRao Malla
Background: Cancer is one of the major heterogeneous disease with high morbidity and mortality with poor prognosis. Elevated levels of reactive oxygen species (ROS), alteration in redox balance, and deregulated redox signaling are common hallmarks of cancer progression and resistance to treatment. Mitochondria contribute mainly in the generation of ROS during oxidative phosphorylation. Elevated levels of ROS have been detected in cancers cells due to high metabolic activity, cellular signaling, peroxisomal activity, mitochondrial dysfunction, activation of oncogene, and increased enzymatic activity of oxidases, cyclooxygenases, lipoxygenases, and thymidine phosphorylases...
2018: Biomarker Insights
https://www.readbyqxmd.com/read/29449531/car-t-cells-the-long-and-winding-road-to-solid-tumors
#6
REVIEW
Maria Michela D'Aloia, Ilaria Grazia Zizzari, Benedetto Sacchetti, Luca Pierelli, Maurizio Alimandi
Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449326/fatty-acid-synthase-mediates-egfr-palmitoylation-in-egfr-mutated-non-small-cell-lung-cancer
#7
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29445137/metabolic-features-of-cancer-stem-cells-the-emerging-role-of-lipid-metabolism
#8
REVIEW
Rita Mancini, Alessia Noto, Maria Elena Pisanu, Claudia De Vitis, Marcello Maugeri-Saccà, Gennaro Ciliberto
Cancer stem cells (CSCs) are an uncommon subset of tumor cells capable of self-renewal, differentiating, and recreating the parental tumor when transplanted into the murine background. Over the past two decades, efforts toward understanding CSC biology culminated into identifying a set of signaling pathways sustaining "stemness". Nevertheless, while metabolic rewiring is nowadays considered a hallmark of cancer, no consensus has been reached on the metabolic features underlying the plastic nature of CSCs, which are capable of residing in a dormant state, and able to rapidly proliferate when the need to repopulate the tumor mass arises...
February 15, 2018: Oncogene
https://www.readbyqxmd.com/read/29445084/the-carnitine-system-and-cancer-metabolic-plasticity
#9
REVIEW
Melone Mariarosa Anna Beatrice, Valentino Anna, Margarucci Sabrina, Galderisi Umberto, Giordano Antonio, Peluso Gianfranco
Metabolic flexibility describes the ability of cells to respond or adapt its metabolism to support and enable rapid proliferation, continuous growth, and survival in hostile conditions. This dynamic character of the cellular metabolic network appears enhanced in cancer cells, in order to increase the adaptive phenotype and to maintain both viability and uncontrolled proliferation. Cancer cells can reprogram their metabolism to satisfy the energy as well as the biosynthetic intermediate request and to preserve their integrity from the harsh and hypoxic environment...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444517/acetyl-coa-synthetase-2-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-upregulating-lysosomal-associated-membrane-protein-1-expression
#10
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
February 8, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29443051/detecting-anastasis-in-vivo-by-caspasetracker-biosensor
#11
Ho Man Tang, Ming Chiu Fung, Ho Lam Tang
Anastasis (Greek for "rising to life") is a recently discovered cell recovery phenomenon whereby dying cells can reverse late-stage cell death processes that are generally assumed to be intrinsically irreversible. Promoting anastasis could in principle rescue or preserve injured cells that are difficult to replace such as cardiomyocytes or neurons, thereby facilitating tissue recovery. Conversely, suppressing anastasis in cancer cells, undergoing apoptosis after anti-cancer therapies, may ensure cancer cell death and reduce the chances of recurrence...
February 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29440170/rsk-regulates-pfk-2-activity-to-promote-metabolic-rewiring-in-melanoma
#12
Thibault Houles, Simon-Pierre Gravel, Geneviève Lavoie, Sejeong Shin, Mathilde Savall, Antoine Méant, Benoit Grondin, Louis Gaboury, Sang-Oh Yoon, Julie St-Pierre, Philippe P Roux
Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype is required to fulfill anabolic demands associated with aberrant cell proliferation and is often mediated by oncogenic drivers such as activated BRAF. In this study, we show that the MAPK-activated p90 ribosomal S6 kinase (RSK) is necessary to maintain glycolytic metabolism in BRAF-mutated melanoma cells. RSK directly phosphorylated the regulatory domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), an enzyme that catalyzes the synthesis of fructose-2,6-bisphosphate during glycolysis...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439487/alternative-splicing-as-a-target-for-cancer-treatment
#13
REVIEW
Nancy Martinez-Montiel, Nora Hilda Rosas-Murrieta, Maricruz Anaya Ruiz, Eduardo Monjaraz-Guzman, Rebeca Martinez-Contreras
Alternative splicing is a key mechanism determinant for gene expression in metazoan. During alternative splicing, non-coding sequences are removed to generate different mature messenger RNAs due to a combination of sequence elements and cellular factors that contribute to splicing regulation. A different combination of splicing sites, exonic or intronic sequences, mutually exclusive exons or retained introns could be selected during alternative splicing to generate different mature mRNAs that could in turn produce distinct protein products...
February 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29438696/the-integrated-genomic-landscape-of-thymic-epithelial-tumors
#14
Milan Radovich, Curtis R Pickering, Ina Felau, Gavin Ha, Hailei Zhang, Heejoon Jo, Katherine A Hoadley, Pavana Anur, Jiexin Zhang, Mike McLellan, Reanne Bowlby, Thomas Matthew, Ludmila Danilova, Apurva M Hegde, Jaegil Kim, Mark D M Leiserson, Geetika Sethi, Charles Lu, Michael Ryan, Xiaoping Su, Andrew D Cherniack, Gordon Robertson, Rehan Akbani, Paul Spellman, John N Weinstein, D Neil Hayes, Ben Raphael, Tara Lichtenberg, Kristen Leraas, Jean Claude Zenklusen, Junya Fujimoto, Cristovam Scapulatempo-Neto, Andre L Moreira, David Hwang, James Huang, Mirella Marino, Robert Korst, Giuseppe Giaccone, Yesim Gokmen-Polar, Sunil Badve, Arun Rajan, Philipp Ströbel, Nicolas Girard, Ming S Tsao, Alexander Marx, Anne S Tsao, Patrick J Loehrer
Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29438108/stat3-enhancing-germline-mutations-contribute-to-tumor-extrinsic-immune-evasion
#15
Daniel Kogan, Alexander Grabner, Christopher Yanucil, Christian Faul, Vijay Kumar Ulaganathan
Immune evasion and the suppression of anti-tumor responses during cancer progression are considered hallmarks of cancer and are typically attributed to tumor-derived factors. Although the molecular basis for the crosstalk between tumor and immune cells is an area of active investigation, whether host-specific germline variants can dictate immunosuppressive mechanisms has remained a challenge to address. A commonly occurring germline mutation (c.1162G>A/rs351855 G/A) in the FGFR4 (CD334) gene enhances STAT3 signaling and is associated with poor prognosis and accelerated progression of multiple cancer types...
February 13, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29437870/cpt2-downregulation-adapts-hcc-to-lipid-rich-environment-and-promotes-carcinogenesis-via-acylcarnitine-accumulation-in-obesity
#16
Naoto Fujiwara, Hayato Nakagawa, Kenichiro Enooku, Yotaro Kudo, Yuki Hayata, Takuma Nakatsuka, Yasuo Tanaka, Ryosuke Tateishi, Yohko Hikiba, Kento Misumi, Mariko Tanaka, Akimasa Hayashi, Junji Shibahara, Masashi Fukayama, Junichi Arita, Kiyoshi Hasegawa, Hadassa Hirschfield, Yujin Hoshida, Yoshihiro Hirata, Motoyuki Otsuka, Keisuke Tateishi, Kazuhiko Koike
OBJECTIVE: Metabolic reprogramming of tumour cells that allows for adaptation to their local environment is a hallmark of cancer. Interestingly, obesity-driven and non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) mouse models commonly exhibit strong steatosis in tumour cells as seen in human steatohepatitic HCC (SH-HCC), which may reflect a characteristic metabolic alteration. DESIGN: Non-tumour and HCC tissues obtained from diethylnitrosamine-injected mice fed either a normal or a high-fat diet (HFD) were subjected to comprehensive metabolome analysis, and the significance of obesity-mediated metabolic alteration in hepatocarcinogenesis was evaluated...
February 6, 2018: Gut
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#17
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436661/transdifferentiation-of-type-ii-alveolar-epithelial-cells-induces-reactivation-of-dormant-tumor-cells-by-enhancing-tgf-%C3%AE-1-snai2-signaling
#18
Yuanhong Zhou, Qiang Liu, Xiangchen Dai, Yuling Yan, Ying Yang, Hua Li, Xiaoling Zhou, Wenqi Gao, Xiaolan Li, Zuyang Xi
Dormant tumor cells (DTCs) serve a crucial role in the pathogenesis of metastasis and may compromise the efficacy of existing therapeutic modalities aimed at fully eradicating cancer. However, the mechanisms underlying the dormant-to-proliferating switch of DTCs remain largely unknown. The lung is one of the most common sites of metastatic recurrence. The transdifferentiation of alveolar epithelial cells II (AEC IIs) to AEC Is is a hallmark of alveolar epithelial stimulation. However, the role of AEC II transdifferentiation during the reactivation of DTCs has not been fully elucidated...
February 6, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29435270/roles-of-toll-like-receptors-from-inflammation-to-lung-cancer-progression
#19
Jinjing Gu, Yi Liu, Bin Xie, Pingping Ye, Jiefan Huang, Zhe Lu
Lung cancer is among the most common malignant tumors worldwide, and is characterized by a low survival rate compared with other cancers. Toll-like receptors (TLRs) are highly conserved in evolution and widely expressed on immune cells, where they serve an important role in the innate immune system by evoking inflammatory responses. Evasion of immune destruction is an important hallmark in the development of cancer. There is an established association between chronic inflammation and cancer, with TLRs serving important roles in the immune response against tumor cells...
February 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29434845/all-trans-retinoic-acid-inhibits-the-proliferation-of-sgc7901-cells-by-regulating-caveolin-1-localization-via-the-erk-mapk-signaling-pathway
#20
Sumei Zhang, Rui Shi, Shaolong Chen, Xiang Wei, Qing Zhou, Yuan Wang
Caveolin-1 is a scaffold protein of caveolae in the mucosa of the gastrointestinal tract and acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. Caveolin-1 stabilizes cell-cell and cell-matrix contacts and is a hallmark of a number of different types of human cancer, including gastric cancer. All-trans retinoic acid (ATRA), a derivative of vitamin A, has been demonstrated to exhibit tumor inhibitory effects in acute leukemia and certain types of solid tumor. In the present study, treatment with ATRA was demonstrated to inhibit the proliferation of gastric cancer cell line SGC7901, in a time- and dose-dependent manner...
February 2018: Oncology Letters
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