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https://www.readbyqxmd.com/read/28636991/non-invasive-detection-of-somatic-mutations-using-next-generation-sequencing-in-primary-central-nervous-system-lymphoma
#1
Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Sydney Dubois, Philippe Bertrand, Vincent Camus, Sylvain Mareschal, Philippe Ruminy, Catherine Maingonnat, Stéphane Lepretre, Elena-Liana Veresezan, Stéphane Derrey, Hervé Tilly, Jean-Michel Picquenot, Annie Laquerrière, Fabrice Jardin
PURPOSE: Primary central nervous system lymphomas (PCNSL) have recurrent genomic alterations. The main objective of our study was to demonstrate that targeted sequencing of circulating cell-free DNA (cfDNA) released by PCNSL at the time of diagnosis could identify somatic mutations by next-generation sequencing (NGS). PATIENTS AND METHODS: PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®)...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636544/analysis-of-esr1-and-pik3ca-mutations-in-plasma-cell-free-dna-from-er-positive-breast-cancer-patients
#2
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Aiko Sueta, Keiichi Murakami, Yoko Omoto, Hirotaka Iwase
BACKGROUND: The measurement of ESR1 and PIK3CA mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive method to quickly assess and monitor endocrine therapy (ET) resistant metastatic breast cancer (MBC) patients. METHODS: The subjects of this retrospective study were a total of 185 plasma samples from 86 estrogen receptor-positive BC patients, of which 151 plasma samples were from 69 MBC patients and 34 plasma samples were from 17 primary BC (PBC) patients...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636317/downsizing-proto-oncogene-cfos-to-short-helix-constrained-peptides-that-bind-jun
#3
Daniel Baxter, Samuel R Perry, Timothy A Hill, W Mei Kok, Nathan R Zaccai, R Leo Brady, David P Fairlie, Jody M Mason
The oncogenic transcription factor activator protein-1 (AP-1) is a DNA-binding protein that assembles through dimerization of Fos and Jun protein subunits, their leucine-rich helical sequences entwining into a coiled-coil structure. This study reports on downsizing the proto-oncogene cFos protein (380 residues) to shorter peptides (37-25 residues) modified with helix-inducing constraints to enhance binding to Jun. A crystal structure is reported for a 37-residue Fos-derived peptide (FosW) bound to Jun. This guided iterative downsizing of FosW to shorter peptide sequences that were constrained into stable water-soluble α-helices by connecting amino acid side chains to form cyclic pentapeptide components...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28632936/peritumoral-cuffing-by-t-cell-tumor-infiltrating-lymphocytes-distinguishes-hpv-related-oropharyngeal-squamous-cell-carcinoma-from-oral-cavity-squamous-cell-carcinoma
#4
Kate Poropatich, David Hernandez, Joel Fontanarosa, Koshonna Brown, Gayle Woloschak, Ajit Paintal, Kirtee Raparia, Sandeep Samant
BACKGROUND: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and -negative tumors. METHODS: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n= 21 HPV DNA-positive, n= 19 HPV DNA-negative)...
June 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28629450/interaction-with-adipocyte-stromal-cells-induces-breast-cancer-malignancy-via-s100a7-upregulation-in-breast-cancer-microenvironment
#5
Minako Sakurai, Yasuhiro Miki, Kiyoshi Takagi, Takashi Suzuki, Takanori Ishida, Noriaki Ohuchi, Hironobu Sasano
BACKGROUND: Breast adipocytes play important roles in both the development and function of mammary epithelial cells. Therefore, carcinoma-adipose stromal cell (ASC) interactions have been considered pivotal in supporting tumor growth in breast cancer. In addition, it has been demonstrated that the biological features of cancer-associated adipocytes differ from those of normal ASCs. Therefore, we investigated an interaction between ASCs and carcinoma cell lines to identify genes associated with ASC invasion of carcinoma cells...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28629339/droplet-digital-pcr-for-detection-and-quantification-of-circulating-tumor-dna-in-plasma-of-head-and-neck-cancer-patients
#6
Joost H van Ginkel, Manon M H Huibers, Robert J J van Es, Remco de Bree, Stefan M Willems
BACKGROUND: During posttreatment surveillance of head and neck cancer patients, imaging is insufficiently accurate for the early detection of relapsing disease. Free circulating tumor DNA (ctDNA) may serve as a novel biomarker for monitoring tumor burden during posttreatment surveillance of these patients. In this exploratory study, we investigated whether low level ctDNA in plasma of head and neck cancer patients can be detected using Droplet Digital PCR (ddPCR). METHODS: TP53 mutations were determined in surgically resected primary tumor samples from six patients with high stage (II-IV), moderate to poorly differentiated head and neck squamous cell carcinoma (HNSCC)...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28629197/reply-to-the-letter-to-the-editor-by-c-nicolazzo-et-al-circulating-cell-free-dna-and-circulating-tumor-cells-as-prognostic-and-predictive-biomarkers-in-advanced-non-small-cell-lung-cancer-patients-treated-with-first-line-chemotherapy
#7
https://www.readbyqxmd.com/read/28624783/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#8
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198+ pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623396/assessment-of-the-circulating-cell-free-dna-marker-association-with-diagnosis-and-prognostic-prediction-in-patients-with-lymphoma-a-single-center-experience
#9
Mao Li, Yongqian Jia, Juan Xu, Xiaomin Cheng, Caigang Xu
Circulating cell-free DNA (ccfDNA) has been shown to be associated with the clinical characteristics and prognosis of cancer patients. Our objective was to assess whether the concentration and integrity index of ccfDNA in plasma may be useful for diagnosing and monitoring the progression of patients with lymphoma. We included plasma samples from 174 lymphoma patients and 80 healthy individuals. The total concentration of ccfDNA was determined using a fluorometry method, and the DNA integrity index (DII), which is the ratio of longer to shorter DNA fragments, for the APP gene was detected using real-time quantitative PCR...
June 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28623355/epigenetic-and-antitumor-effects-of-platinum-iv-octanoato-conjugates
#10
Vojtech Novohradsky, Ilaria Zanellato, Cristina Marzano, Jitka Pracharova, Jana Kasparkova, Dan Gibson, Valentina Gandin, Domenico Osella, Viktor Brabec
We present the anticancer properties of cis, cis, trans-[Pt(IV)(NH3)2Cl2(OA)2] [Pt(IV)diOA] (OA = octanoato), Pt(IV) derivative of cisplatin containing two OA units appended to the axial positions of a six-coordinate Pt(IV) center. Our results demonstrate that Pt(IV)diOA is a potent cytotoxic agent against many cancer cell lines (the IC50 values are approximately two orders of magnitude lower than those of clinically used cisplatin or Pt(IV) derivatives with biologically inactive axial ligands). Importantly, Pt(IV)diOA overcomes resistance to cisplatin, is significantly more potent than its branched Pt(IV) valproato isomer and exhibits promising in vivo antitumor activity...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622697/vitamin-c-and-doxycycline-a-synthetic-lethal-combination-therapy-targeting-metabolic-flexibility-in-cancer-stem-cells-cscs
#11
Ernestina Marianna De Francesco, Gloria Bonuccelli, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti
Here, we developed a new synthetic lethal strategy for further optimizing the eradication of cancer stem cells (CSCs). Briefly, we show that chronic treatment with the FDA-approved antibiotic Doxycycline effectively reduces cellular respiration, by targeting mitochondrial protein translation. The expression of four mitochondrial DNA encoded proteins (MT-ND3, MT-CO2, MT-ATP6 and MT-ATP8) is suppressed, by up to 35-fold. This high selection pressure metabolically synchronizes the surviving cancer cell sub-population towards a predominantly glycolytic phenotype, resulting in metabolic inflexibility...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614831/liquid-biopsies-for-monitoring-temporal-genomic-heterogeneity-in-breast-and-colon-cancers
#12
Tiziana Venesio, Giulia Siravegna, Alberto Bardelli, Anna Sapino
Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the "liquid biopsy" was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term "liquid biopsy" generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28611200/dendritic-cell-cytokine-induced-killer-cell-immunotherapy-combined-with-s-1-in-patients-with-advanced-pancreatic-cancer-a-prospective-study
#13
Ni Jiang, Guoliang Qiao, Xiao-Li Wang, Michael A Morse, William R Gwin, Lei Zhou, Yuguang Song, Yanjie Zhao, Feng Chen, Xin-Na Zhou, Lefu Huang, Amy Hobeika, Xin Yi, Xuefeng Xia, Yanfang Guan, Jin Song, Jun Ren, H Kim Lyerly
Purpose: Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine induced killer cells (DC-CIK) administered with the chemotherapy (CT) S-1 in this malignancy. <p> Experimental Design: Consecutive patients (n=47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care.</p> <p> Results: DC-CIK plus S-1 produced significantly longer median OS and PFS (212 and 136 days) compared with DC-CIK (128 and 85 days), CT (141 and 92 days) or supportive care only (52 and 43 days) (P<0...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28611011/application-of-plasma-genotyping-technologies-in-non-small-cell-lung-cancer-a-practical-review
#14
REVIEW
Adrian G Sacher, Kimberly M Komatsubara, Geoffrey R Oxnard
The rational treatment of metastatic NSCLC hinges upon the timely detection of potentially targetable genomic alterations in order to guide therapy. Recent advances in highly sensitive genotyping technologies have allowed for the development of novel plasma genotyping assays which are capable of noninvasively detecting targetable alterations in plasma cell-free DNA without reliance on traditional tissue genotyping. The rapid development of plasma genotyping has led to an explosion in the number of assay platforms available from both commercial and laboratory sources...
June 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28609132/antioxidant-and-anticancer-properties-of-berries
#15
Bincy Baby, Priya Antony, Ranjit Vijayan
The enduring relationship between dietary patterns and human health has led us to investigate the bioactive components present in fruits and vegetables for a very long time. Berries, notably the popular ones such as strawberry, raspberry, blueberry, blackberry and the Indian gooseberry, are among the best known dietary sources due to the presence of a wide range of bioactive nutritive components. Bioactive components in berries include phenolic compounds, flavonoids and tannins apart from vitamins, minerals, sugars and fibers...
June 13, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28608976/tp53-mutation-does-not-confer-a-poor-outcome-in-adult-patients-with-acute-lymphoblastic-leukemia-who-are-treated-with-frontline-hyper-cvad-based-regimens
#16
Rashmi Kanagal-Shamanna, Preetesh Jain, Koichi Takahashi, Nicholas J Short, Guilin Tang, Ghayas C Issa, Farhad Ravandi, Guillermo Garcia-Manero, Cameron C Yin, Rajyalakshmi Luthra, Keyur P Patel, Joseph D Khoury, Guillermo Montalban-Bravo, Koji Sasaki, Tapan M Kadia, Gautam Borthakur, Marina Konopleva, Nitin Jain, Rebecca Garris, Sherry Pierce, William Wierda, Zeev Estrov, Jorge Cortes, Susan O'Brien, Hagop Kantarjian, Elias Jabbour
BACKGROUND: Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome. METHODS: TP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon-based next-generation sequencing and Sanger sequencing. RESULTS: TP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.2% (range, 5...
June 13, 2017: Cancer
https://www.readbyqxmd.com/read/28607924/hipk2-overexpression-and-its-prognostic-role-in-human-papillomavirus-positive-tonsillar-squamous-cell-carcinoma
#17
Mi Jung Kwon, So Young Kang, Eun Sook Nam, Seong Jin Cho, Young-Soo Rho
Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28602964/droplet-digital-pcr-improved-the-egfr-mutation-diagnosis-with-pleural-fluid-samples-in-non-small-cell-lung-cancer-patients
#18
Xiaoyan Li, Yi Liu, Weiwei Shi, Huayan Xu, Haixu Hu, Zhengwei Dong, Guanshan Zhu, Yun Sun, Bing Liu, Hongjun Gao, Chuanhao Tang, Xiaoqing Liu
BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is a promising method for analyzing minor amounts of nucleic acid. However, its application has not been reported in pleural fluid, which is an ideal sample source for epidermal growth factor receptor (EGFR) mutation analysis in non-small-cell lung cancer (NSCLC) patients. METHODS: The extracted DNA from supernatants of pleural fluid was selected from our sample bank and re-analyzed by our previously established ddPCR assay...
June 8, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28601386/detection-of-alk-and-kras-mutations-in-circulating-tumor-dna-of-patients-with-advanced-alk-positive-nsclc-with-disease-progression-during-crizotinib-treatment
#19
Paola Bordi, Marcello Tiseo, Eleonora Rofi, Iacopo Petrini, Giuliana Restante, Romano Danesi, Marzia Del Re
BACKGROUND: In patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), disease progression occurs after a median of 9 to 10 months of crizotinib treatment. Several mechanisms of resistance have been identified and include ALK mutations and amplification or the activation of bypassing signaling pathways. Rebiopsy in NSCLC patients represents a critical issue and the analysis of circulating cell-free DNA (cfDNA) has a promising role for the identification of resistance mechanisms...
May 18, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28600783/kinetochore-malfunction-in-human-pathologies
#20
Bas de Wolf, Geert J P L Kops
The cell cycle culminates in mitosis with the purpose of dividing the cell's DNA content equally over two daughter cells. Error-free segregation relies on correct connections between chromosomes and spindle microtubules. Kinetochores are complex multi-protein assemblies that mediate these connections and are the platforms for attachment-error-correction and spindle assembly checkpoint signaling. Proper kinetochore function is therefore key in preventing aneuploidization. Mutations in genes encoding kinetochore proteins are associated with several severe developmental disorders associated with microcephaly, and kinetochore defects contribute to chromosomal instability in certain cancers...
2017: Advances in Experimental Medicine and Biology
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