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https://www.readbyqxmd.com/read/30222105/a-novel-ph-dependent-membrane-peptide-that-binds-to-epha2-and-inhibits-cell-migration
#1
Daiane Santana Alves, Justin M Westerfield, Xiaojun Shi, Vanessa P Nguyen, Katherine M Stefanski, Kristen R Booth, Soyeon Kim, Jennifer Morrell-Falvey, Bing-Cheng Wang, Steven M Abel, Adam W Smith, Francisco N Barrera
Misregulation of the signaling axis formed by the receptor tyrosine kinase (RTK) EphA2 and its ligand, ephrinA1, causes aberrant cell-cell contacts that contribute to metastasis. Solid tumors are characterized by an acidic extracellular medium. We intend to take advantage of this tumor feature to design new molecules that specifically target tumors. We created a novel pH-dependent transmembrane peptide, TYPE7, by altering the sequence of the transmembrane domain of EphA2. TYPE7 is highly soluble and interacts with the surface of lipid membranes at neutral pH, while acidity triggers transmembrane insertion...
September 17, 2018: ELife
https://www.readbyqxmd.com/read/30221068/clinical-implication-of-tumor-mutational-burden-in-patients-with-her2-positive-refractory-metastatic-breast-cancer
#2
Song Ee Park, Kyunghee Park, Eunjin Lee, Ji-Yeon Kim, Jin Seok Ahn, Young-Hyuck Im, Choonghoon Lee, Hun Jung, Soo Youn Cho, Woong-Yang Park, Razvan Cristescu, Yeon Hee Park
This study explored the clinical implications of tumor mutational burden (TMB) in a well-defined HER2-positive metastatic breast cancer (MBC) patient population who had been previously treated but had subsequent disease progression. Whole exome sequencing was performed on formalin-fixed paraffin-embedded tumor samples and matched normal tissue. Among the 46 patients, 13 (28.3%) were estrogen receptor-positive and nine (19.6%) were progesterone receptor-positive by immunohistochemistry analysis. Twenty patients (43...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/30221045/detailed-analysis-of-adenosine-a2a-receptor-adora2a-and-cd73-5-nucleotidase-ecto-nt5e-methylation-and-gene-expression-in-head-and-neck-squamous-cell-carcinoma-patients
#3
Timo J Vogt, Heidrun Gevensleben, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Jennifer Landsberg, Diane Goltz, Dimo Dietrich
Background : The adenosine A2a receptor (A2aR) and the adenosine synthesizing enzyme CD73 have recently evolved as a novel immunotherapeutic target. However, little is known about epigenetic modification of the encoding genes ADORA2A and NT5E . Methods : In the present study, we evaluated methylation at 23 loci of ADORA2A and 17 loci of NT5E with regard to transcriptional activity, human papilloma virus (HPV) status, immune cell infiltration, and outcome in a cohort of 279 head and neck squamous carcinoma (HNSCC) patients obtained from The Cancer Genome Atlas (TCGA)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/30220977/a-patient-derived-orthotopic-xenograft-model-enabling-human-high-grade-urothelial-cell-carcinoma-of-the-bladder-tumor-implantation-growth-angiogenesis-and-metastasis
#4
Jessie Gills, Ravan Moret, Xin Zhang, John Nelson, Grace Maresh, Linh Hellmers, Daniel Canter, M'Liss Hudson, Shams Halat, Marc Matrana, Michael P Marino, Jakob Reiser, Maureen Shuh, Eric Laborde, Maria Latsis, Sunil Talwar, Stephen Bardot, Li Li
High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph node stromal cells (HK cells)...
August 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/30220971/mutational-analysis-of-uterine-cervical-cancer-that-survived-multiple-rounds-of-radiotherapy
#5
Endang Nuryadi, Yasushi Sasaki, Yoshihiko Hagiwara, Tiara Bunga Mayang Permata, Hiro Sato, Shuichiro Komatsu, Yuya Yoshimoto, Kazutoshi Murata, Ken Ando, Nobuteru Kubo, Noriyuki Okonogi, Yosuke Takakusagi, Akiko Adachi, Mototaro Iwanaga, Keisuke Tsuchida, Tomoaki Tamaki, Shin-Ei Noda, Yuka Hirota, Atsushi Shibata, Tatsuya Ohno, Takashi Tokino, Takahiro Oike, Takashi Nakano
Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer-related genes in the treatment-naïve tumor and the tumors that recurred after initial and secondary radiotherapy identified (i) activating mutations in PIK3CA and KRAS , and putative inactivating mutations in SMAD4 , as trunk mutation signatures that persisted over the clinical course; and (ii) mutations in KMT2A , TET1 , and NLRP1 as acquired mutation signatures observed only in recurrent tumors after radiotherapy...
August 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/30220966/circulating-tumor-dna-as-a-marker-of-treatment-response-in-braf-v600e-mutated-non-melanoma-solid-tumors
#6
Lise Barlebo Ahlborn, Ida Viller Tuxen, Florent Mouliere, Savvas Kinalis, Ane Y Schmidt, Kristoffer Staal Rohrberg, Eric Santoni-Rugiu, Finn Cilius Nielsen, Ulrik Lassen, Christina Westmose Yde, Olga Oestrup, Morten Mau-Sorensen
Purpose: We evaluated longitudinal tracking of BRAF V600E in circulating cell-free DNA (cfDNA) as a marker of treatment response to BRAF inhibitor (BRAFi) combination therapies in non-melanoma solid tumors included in the Copenhagen Prospective Personalized Oncology (CoPPO) program. Experimental design: Patients with BRAF V600E-mutated tumors were treated with combination therapies including BRAFi. Quantification of mutant cfDNA from plasma was determined and correlated to clinical outcomes...
August 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/30220882/bc094916-suppressed-sp-2-0-xenograft-tumor-by-down-regulating-creb1-and-bcl2-transcription
#7
Ruonan Xu, Ying Fang, Chunmei Hou, Bing Zhai, Zhenyu Jiang, Ning Ma, Liang Wang, Gencheng Han, Renxi Wang
Background: Both multiple myeloma (MM) and systemic lupus erythematosus (SLE) are associated with abnormal production of plasma cells, although their pathological mechanism of each disease is different. The main characteristic of both diseases is uncontrolled differentiation of B cells into plasmablast/plasma cells. Despite continuous research on prognostic factors and the introduction of new agents for MM and SLE, treatments still do not exist for controlling plasmablast/plasma cells...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/30220274/-protective-effect-of-microrna-155-antisense-oligonucleotid-on-lipopolysaccharide-induced-acute-lung-injury-in-mice
#8
Jin Tang, Wang Xie, Tingting Cheng, Kailing Wang, Xia Gu, Qian Zhang, Zhongliang Guo
OBJECTIVE: To investigate the protective effect of microRNA-155 (miR-155) antisense oligonucleotid (ASO) on acute lung injury (ALI) mice by establishing a lentiviral expression vector of ASO of miRNA. METHODS: miR-155 antisense oligonucleotides amplified by polymerase chain reaction (PCR) from genomic, using BamH I and Nhe I double digestion, ligated into lentiviral expression vector. Sequence and virus titer were measured. According to the random number table method, 54 male BALB/c mice of 4-6 weeks old were divided into three groups...
August 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/30220117/-prognostic-significance-of-combined-tert-and-idh-gene-mutation-analysis-in-diffusely-infiltrating-gliomas
#9
Q Q Liu, X X Yin, Y Zou, T P Yu, J Gong, X Q Chen, L Nie, M Xu, M N Zhang, Q Zhou, N Chen
Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases)...
September 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/30219970/mutational-and-copy-number-asset-of-primary-sporadic-neuroendocrine-tumors-of-the-small-intestine
#10
Michele Simbolo, Caterina Vicentini, Andrea Mafficini, Matteo Fassan, Serena Pedron, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Corrado Pedrazzani, Luca Landoni, Federica Grillo, Sara Cingarlini, Guido Rindi, Claudio Luchini, Aldo Scarpa, Rita T Lawlor
Small intestine neuroendocrine tumors (SI-NETs) represent the most common histotype among small intestine neoplasms, and metastatic disease is usually present at diagnosis. A retrospective series of 52 sporadic primary surgically resected SI-NETs, which were metastatic at diagnosis, was analyzed by high-coverage target sequencing (HCTS) for the mutational status of 57 genes and copy number status of 40 genes selected from recently published genome sequencing data. Seven genes were found to be recurrently mutated: CDKN1B (9...
September 16, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/30219675/the-influence-of-gut-microbiota-dysbiosis-to-the-efficacy-of-5-fluorouracil-treatment-on-colorectal-cancer
#11
Lu Yuan, Siruo Zhang, Huan Li, Fan Yang, Noosheen Mushtaq, Shakir Ullah, Yi Shi, Cuihong An, Jiru Xu
Colorectal cancer is one of the most frequently diagnosed cancers worldwide. Gut flora can modulate the host response to chemotherapeutic drugs. However, the understanding regarding the relationship between the gut microbiota and the antitumor efficacy of 5- Fluorouracil (5-FU) treatment is limited. Therefore, we compared the tumor size and profiled the gut microbiota of mice treated with 5-FU, combined with probiotics or ABX (an antibiotic cocktail of antibiotics) by using the Colorectal Cancer (CRC) mouse model and high-throughput sequencing...
September 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30219508/upregulated-circular-rna-circ-102004-that-promotes-cell-proliferation-in-prostate-cancer
#12
Jie Si-Tu, Yi Cai, Ting Feng, Delin Yang, Shunhui Yuan, Xiaofang Yang, Shuchen He, Zhuoheng Li, Yanwen Wang, Yasi Tang, Chunwei Ye, Zhipeng Li
OBJECTIVE: Prostate cancer (PCa) is one of the most prevalent cancers affecting men worldwide. However, the biological functions of circRNAs in PCa are still largely unknown. METHODS: Real-time PCR (RT-PCR) and immunohistochemistry were performed to characterize the circ-102004 expression in both human PCa tissues and cell lines. The apoptosis and cell cycle status of prostate immortalized cell lines that were overexpressed with circ-102004 by transfection was analyzed using flow cytometry...
September 13, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/30219185/whole-body-mr-imaging-the-novel-intrinsically-hybrid-approach-to-metastases-myeloma-lymphoma-in-bones-and-beyond
#13
REVIEW
Frederic E Lecouvet, Sandy Van Nieuwenhove, François Jamar, Renaud Lhommel, Ali Guermazi, Vassiliki P Pasoglou
Whole-body MR imaging (WB-MR imaging) has become a modality of choice for detecting bone metastases in multiple cancers, and bone marrow involvement by multiple myeloma or lymphoma. Combination of anatomic and functional sequences imparts an inherently hybrid dimension to this nonirradiating tool and extends the screening of malignancies outside the skeleton. WB-MR imaging outperforms bone scintigraphy and CT and offers an alternative to PET in many tumors by time of lesion detection and assessment of treatment response...
October 2018: PET Clinics
https://www.readbyqxmd.com/read/30219179/a-multiplex-homology-directed-dna-repair-assay-reveals-the-impact-of-more-than-1-000-brca1-missense-substitution-variants-on-protein-function
#14
Lea M Starita, Muhtadi M Islam, Tapahsama Banerjee, Aleksandra I Adamovich, Justin Gullingsrud, Stanley Fields, Jay Shendure, Jeffrey D Parvin
Loss-of-function pathogenic variants in BRCA1 confer a predisposition to breast and ovarian cancer. Genetic testing for sequence changes in BRCA1 frequently reveals a missense variant for which the impact on cancer risk and on the molecular function of BRCA1 is unknown. Functional BRCA1 is required for the homology-directed repair (HDR) of double-strand DNA breaks, a critical activity for maintaining genome integrity and tumor suppression. Here, we describe a multiplex HDR reporter assay for concurrently measuring the effects of hundreds of variants of BRCA1 for their role in DNA repair...
August 24, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/30218772/an-intronic-single-nucleotide-polymorphism-in-the-mutyh-gene-is-associated-with-increased-risk-for-hcv-induced-hepatocellular-carcinoma
#15
Akira Sakurada, Koji Miyanishi, Shingo Tanaka, Masanori Sato, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato
BACKGROUND & AIMS: The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants of these genes and the risk of developing hepatocellular carcinoma (HCC). METHODS: Nineteen tagging SNPs in base excision repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays; one significant SNP was found and confirmed in Japanese patients with chronic hepatitis C (CHC) (n=38 HCC and 55 controls)...
September 12, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30218756/usefulness-of-complementary-next-generation-sequencing-and-quantitative-immunohistochemistry-panels-for-predicting-brain-metastases-and-selecting-a-treatment-outcomes-of-non-small-cell-lung-cancer
#16
Juliana Machado-Rugolo, Alexandre Todorovic Fabro, Daniel Ascheri, Cecília Farhat, Alexandre Muxfeldt Ab'Saber, Vanessa Karen de Sá, Maria Aparecida Nagai, Teresa Takagaki, Ricardo Terra, Edwin Roger Parra, Vera Luiza Capelozzi
To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small cell lung cancer (NSCLC) who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and large-cell carcinoma (LCC) were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors (VEGFs)...
September 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/30218497/molecular-cytogenetics-and-quality-control-clinical-guardians-for-pluripotent-stem-cells
#17
REVIEW
Leili Rohani, Adiv A Johnson, Pooyan Naghsh, Derrick E Rancourt, Henning Ulrich, Heidrun Holland
Now that induced pluripotent stem cell (iPSC)-based transplants have been performed in humans and organizations have begun producing clinical-grade iPSCs, it is imperative that strict quality control standards are agreed upon. This is essential as both ESCs and iPSCs have been shown to accumulate genomic aberrations during long-term culturing. These aberrations can include copy number variations, trisomy, amplifications of chromosomal regions, deletions of chromosomal regions, loss of heterozygosity, and epigenetic abnormalities...
September 14, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/30217929/whole-genome-sequencing-reveals-elevated-tumor-mutational-burden-and-initiating-driver-mutations-in-african-men-with-treatment-naive-high-risk-prostate-cancer
#18
Weerachai Jaratlerdsiri, Eva K F Chan, Tingting Gong, Desiree C Petersen, Anton M F Kalsbeek, Philip A Venter, Phillip D Stricker, Ms Riana Bornman, Vanessa M Hayes
African American men are more likely than any other racial group to die from prostate cancer. The contribution of acquired genomic variation to this racial disparity is largely unknown, as genomic from Africa is lacking. Here we performed the first tumor-normal paired deep whole-genome sequencing for Africa. A direct study-matched comparison between African- and European-derived, treatment-naïve, high-risk prostate tumors for 15 cases allowed for further comparative analyses of existing data. Excluding a single hyper-mutated tumor with 55 mutations per megabase, we observed a 1...
September 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/30217218/overexpression-of-clc-3-is-regulated-by-xrcc5-and-is-a-poor-prognostic-biomarker-for-gastric-cancer
#19
Zhuoyu Gu, Yixin Li, Xiaoya Yang, Meisheng Yu, Zhanru Chen, Chan Zhao, Lixin Chen, Liwei Wang
BACKGROUND: Recently, many potential prognostic biomarkers for gastric cancer (GC) have been identified, but the prognosis of advanced GC patients remains poor. Chloride channels are promising cancer biomarkers, and their family member chloride channel-3 (CLC-3) is involved in multiple biological behaviors. However, whether CLC-3 is a prognostic biomarker for GC patients is rarely reported. The molecular mechanisms by which CLC-3 is regulated in GC are unclear. METHODS: The expression of CLC-3 and XRCC5 in human specimens was analyzed using immunohistochemistry...
September 14, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/30216764/clinical-relevance-of-genomic-changes-in-recurrent-pediatric-solid-tumors
#20
Boram Lee, Ji Won Lee, Joon Ho Shim, Je-Gun Joung, Jae Won Yun, Joon Seol Bae, Hyun-Tae Shin, Ki Woong Sung, Woong-Yang Park
PURPOSE: Relapsed/refractory pediatric cancers show poor prognosis; however, their genomic patterns remain unknown. To investigate the genetic mechanisms of tumor relapse and therapy resistance, we characterized genomic alterations in diagnostic and relapsed lesions in patients with relapsed/refractory pediatric solid tumors using targeted deep sequencing. PATIENTS AND METHODS: A targeted sequencing panel covering the exons of 381 cancer genes was used to characterize 19 paired diagnostic and relapsed samples from patients with relapsed/refractory pediatric solid tumors...
September 11, 2018: Translational Oncology
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