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https://www.readbyqxmd.com/read/28732214/crispr-cas9-technology-based-xenograft-tumors-as-candidate-reference-materials-for-multiple-eml4-alk-rearrangements-testing
#1
Rongxue Peng, Rui Zhang, Guigao Lin, Xin Yang, Ziyang Li, Kuo Zhang, Jiawei Zhang, Jinming Li
The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (EML4-ALK) rearrangement is an important biomarker that plays a pivotal role in therapeutic decision making for non-small-cell lung cancer (NSCLC) patients. Ensuring accuracy and reproducibility of EML4-ALK testing by fluorescence in situ hybridization, immunohistochemistry, RT-PCR, and next-generation sequencing requires reliable reference materials for monitoring assay sensitivity and specificity...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28728506/microsatellite-instability-and-promoter-hypermethylation-of-dna-repair-genes-in-hematologic-malignancies-a-forthcoming-direction-toward-diagnostics
#2
Priyanjali Bhattacharya, Trupti N Patel
OBJECTIVE: The objective of our review is to highlight the significance of microsatellite hypervariation in diagnostics of hematologic malignancies. METHODS: For the past few decades, extensive experiments in cancer research have explored all the possible pathways and a number of deleterious mutations that either make the tumor suppressor genes (TSGs) dysfunctional or cause the proto-oncogenes to behave abnormally by changing the cellular phenotype hence rendering disease...
July 20, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28725161/ep300-single-nucleotide-polymorphism-rs20551-correlates-with-prolonged-overall-survival-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#3
Jiao Li, Ning Ding, Xiaogan Wang, Lan Mi, Lingyan Ping, Xuan Jin, Yalu Liu, Zhitao Ying, Yan Xie, Weiping Liu, Yuqin Song, Jun Zhu
BACKGROUND: Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28724971/computational-design-of-a-symmetrical-%C3%AE-trefoil-lectin-with-cancer-cell-binding-activity
#4
Daiki Terada, Arnout R D Voet, Hiroki Noguchi, Kenichi Kamata, Mio Ohki, Christine Addy, Yuki Fujii, Daiki Yamamoto, Yasuhiro Ozeki, Jeremy R H Tame, Kam Y J Zhang
Computational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificial β-trefoil lectin that recognises Burkitt's lymphoma cells, and which was designed with the intention of finding a basis for novel cancer treatments or diagnostics. The new protein, called "Mitsuba", is based on the structure of the natural shellfish lectin MytiLec-1, a member of a small lectin family that uses unique sequence motifs to bind α-D-galactose...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#5
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#6
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28716242/a-novel-pathogenic-variant-in-an-iranian-ataxia-telangiectasia-family-revealed-by-next-generation-sequencing-followed-by-in-silico-analysis
#7
Mohammad Amin Tabatabaiefar, Paria Alipour, Azam Pourahmadiyan, Najmeh Fattahi, Laleh Shariati, Neda Golchin, Javad Mohammadi-Asl
Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28715472/a-novel-isoform-of-il-33-revealed-by-screening-for-transposable-element-promoted-genes-in-human-colorectal-cancer
#8
Frances E Lock, Artem Babaian, Ying Zhang, Liane Gagnier, Sabrina Kuah, Antonia Weberling, Mohammad M Karimi, Dixie L Mager
Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences contain multiple regulatory motifs and hence are capable of influencing expression of host genes. TEs are known to be released from epigenetic repression and can become transcriptionally active in cancer. Such activation could also lead to lineage-inappropriate activation of oncogenes, as previously described in lymphomas. However, there are few reports of this mechanism occurring in non-blood cancers. Here, we re-analyzed whole transcriptome data from a large cohort of patients with colon cancer, compared to matched normal colon control samples, to detect genes or transcripts ectopically expressed through activation of TE promoters...
2017: PloS One
https://www.readbyqxmd.com/read/28707270/profiling-of-cellular-microrna-responses-during-the-early-stages-of-kshv-infection
#9
Hosni A M Hussein, Shaw M Akula
Kaposi's sarcoma-associated herpesvirus (KSHV) causes a variety of cancers, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Host cellular microRNAs (miRNAs) play important post-transcriptional regulatory roles in gene expression and can greatly influence virus-host cell interactions. This study investigated cellular miRNA expression profiles operating in response to early stages of KSHV infection of human Burkitt lymphoma B cells (BJAB). We employed deep sequencing to analyze miRNA expression in KSHV-infected BJAB cells 15 min post infection (PI) and compared this to uninfected BJAB cells...
July 13, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28705173/conserved-sequences-of-bart-and-bhrf-regions-encoding-viral-micrornas-in-epstein-barr-virus-associated-lymphoma
#10
Keishin Sunagawa, Tsunekazu Hishima, Hitomi Fukumoto, Hideki Hasegawa, Harutaka Katano
OBJECTIVE: Epstein-Barr virus (EBV) encodes at least 25 pri-microRNAs (miRNAs) in two regions of its DNA genome, BART and BHRF. B95-8, an EBV reference strain, has a deletion in the BART region. However, no information is available on the deletions or mutations in the BART and BHRF regions in clinical samples of EBV-associated lymphoma. RESULTS: Nine DNA fragments encoding miR-BARTs and two coding miR-BHRF1s were amplified by PCR from DNA samples extracted from 16 cases of EBV-associated lymphoma...
July 14, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28697001/the-genetics-of-hodgkin-lymphoma-an-overview-and-clinical-implications
#11
Sven Borchmann, Andreas Engert
PURPOSE OF REVIEW: The goal of this review is to give an overview of the genetics of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome-wide association studies, changes in gene expression, familial classical Hodgkin lymphoma and epigenetic changes will be reviewed. In doing so, special focus is placed on the way recent discoveries have influenced clinical research, diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on how these advances can help to advance the treatment of elderly patients who have a markedly worse prognosis than younger patients...
July 10, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28695659/epstein-barr-virus-negative-extranodal-true-natural-killer-cell-lymphoma-harbouring-a-kdm6a-mutation
#12
Naoko Tsuyama, Reimi Asaka, Akito Dobashi, Satoko Baba, Yuko Mishima, Kyoko Ueda, Masahiko Oguchi, Hideki Tsuji, Kiyohiko Hatake, Kengo Takeuchi
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an extranodal aggressive T or NK-cell lymphoma that is characteristically associated with Epstein-Barr virus (EBV) infection and cytotoxic tissue-destructive features. Although ENKTL is described as a distinct entity according to the 2008 WHO classification, a considerable complexity is associated with the differential diagnosis of other T-cell lymphomas with respect to tumour cell origins, locations, and the presence of EBV infection, as well as molecular and cytogenetic abnormalities...
July 10, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28694799/a-tiny-rna-that-packs-a-big-punch-the-critical-role-of-a-viral-mir-155-ortholog-in-lymphomagenesis-in-marek-s-disease
#13
REVIEW
Guoqing Zhuang, Aijun Sun, Man Teng, Jun Luo
MicroRNAs (miRNAs) are small non-coding RNAs that have been identified in animals, plants, and viruses. These small RNAs play important roles in post-transcriptional regulation of various cellular processes, including development, differentiation, and all aspects of cancer biology. Rapid-onset T-cell lymphoma of chickens, namely Marek's disease (MD), induced by Gallid alphaherpesvirus 2 (GaHV2), could provide an ideal natural animal model for herpesvirus-related cancer research. GaHV2 encodes 26 mature miRNAs derived from 14 precursors assembled in three distinct gene clusters in the viral genome...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28691928/mutations-in-5-methylcytosine-oxidase-tet2-and-rhoa-cooperatively-disrupt-t-cell-homeostasis
#14
Shengbing Zang, Jia Li, Haiyan Yang, Hongxiang Zeng, Wei Han, Jixiang Zhang, Minjung Lee, Margie Moczygemba, Sevinj Isgandarova, Yaling Yang, Yubin Zhou, Anjana Rao, M James You, Deqiang Sun, Yun Huang
Angioimmunoblastic T cell lymphoma (AITL) represents a distinct, aggressive form of peripheral T cell lymphoma with a dismal prognosis. Recent exome sequencing in patients with AITL has revealed the frequent coexistence of somatic mutations in the Rho GTPase RhoA (RhoAG17V) and loss-of-function mutations in the 5-methylcytosine oxidase TET2. Here, we have demonstrated that TET2 loss and RhoAG17V expression in mature murine T cells cooperatively cause abnormal CD4+ T cell proliferation and differentiation by perturbing FoxO1 gene expression, phosphorylation, and subcellular localization, an abnormality that is also detected in human primary AITL tumor samples...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28680000/genetic-heterogeneity-of-dlbcl-not-otherwise-specified
#15
Kennosuke Karube
Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, is the most common malignant lymphoma in the world. The recent progress of molecular techniques has proved its heterogeneity. Gene expression profiling for DLBCL, recently achieved using formalin-fixed paraffin-embedded samples, has identified two molecular subtypes, according to their cell of origin correlated with prognosis. Genomic abnormalities are roughly divided into translocations, amplifications/deletions, and mutations. Translocations involving MYC and BCL2 frequently co-occur in 5%-10% of DLBCL and are associated with aggressive clinical behavior with poor outcomes...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28677789/mirna%C3%A2-504-inhibits-p53%C3%A2-dependent-vascular-smooth-muscle-cell-apoptosis-and-may-prevent-aneurysm-formation
#16
Xue Cao, Zhenguo Cai, Junyan Liu, Yanru Zhao, Xin Wang, Xueqi Li, Hongyuan Xia
Abdominal aortic aneurysm (AAA) is a common disease that is associated with the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). VSMCs are regulated by microRNAs (miRNA). The aim of the present study was to identify miRNA sequences that regulate aortic SMCs during AAA. miRNA‑504 was identified using a miRNA PCR array and by reverse transcription‑quantitative polymerase chain reaction analysis, and its expression levels were observed to be downregulated in the aortic cells derived from patients with AAA when compared with controls...
June 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28676342/tumor-antigen-and-receptor-densities-regulate-efficacy-of-a-chimeric-antigen-receptor-targeting-anaplastic-lymphoma-kinase
#17
Alec J Walker, Robbie G Majzner, Ling Zhang, Kelsey Wanhainen, Adrienne H Long, Sang M Nguyen, Paola Lopomo, Marc Vigny, Terry J Fry, Rimas J Orentas, Crystal L Mackall
We explored the utility of targeting anaplastic lymphoma kinase (ALK), a cell surface receptor overexpressed on pediatric solid tumors, using chimeric antigen receptor (CAR)-based immunotherapy. T cells expressing a CAR incorporating the single-chain variable fragment sequence of the ALK48 mAb linked to a 4-1BB-CD3ζ signaling domain lysed ALK-expressing tumor lines and produced interferon-gamma upon antigen stimulation but had limited anti-tumor efficacy in two xenograft models of human neuroblastoma. Further exploration demonstrated that cytokine production was highly dependent upon ALK target density and that target density of ALK on neuroblastoma cell lines was insufficient for maximal activation of CAR T cells...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28672935/next-generation-sequencing-reveals-lymph-node-metastasis-associated-genetic-markers-in-colorectal-cancer
#18
Ni Xie, Yujiang Yao, Lili Wan, Ting Zhu, Litao Liu, Jianhui Yuan
Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#19
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28665088/a-role-for-susceptibility-weighted-imaging-in-progressive-multifocal-leukoencephalopathy
#20
S M Yap, B Murray, T Lynch, E Kavanagh, P MacMahon
We report a radiologic finding on magnetic resonance imaging (MRI) of the brain of two cases of progressive multifocal leukoencephalopathy (PML) of hypointense signal of subcortical U-fibres on susceptibility weighted (SW) sequence. The first case is a 50-year-old man recently treated with chemotherapy including rituximab for non-Hodgkin's lymphoma. The second case is a 64-year-old woman with human immunodeficiency virus (HIV) infection. Iron deposition is a likely causative factor. We propose that SWI may be especially useful in the assessment of indeterminate cases to reduce the likelihood of a missed diagnosis of PML...
April 10, 2017: Irish Medical Journal
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