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https://www.readbyqxmd.com/read/28454108/telomere-erosion-in-nf1-tumorigenesis
#1
Rhiannon E Jones, Julia W Grimstead, Ashni Sedani, Duncan Baird, Meena Upadhyaya
Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that affects 1 in 3,500 individuals worldwide and is inherited in an autosomal dominant fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a significant cause of morbidity and mortality in NF1 and currently there is no treatment or definite prognostic biomarkers for these tumors. Telomere shortening has been documented in numerous tumor types. Short dysfunctional telomeres are capable of fusion and it is considered that the ensuing genomic instability may facilitate clonal evolution and the progression to malignancy...
April 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453505/breast-cancer-intra-tumor-heterogeneity-one-tumor-different-entities
#2
José Esparza-López, Elizabet Escobar-Arriaga, Santos Soto-Germes, María de Jesús Ibarra-Sánchez
In recent years, it has become evident that intra-tumor heterogeneity of breast cancer is a big challenge for the diagnosis, treatment, and clinical course of tumor-bearing patients. The advances in molecular biology and other technologies have led to the knowledge that a breast cancer tumor is comprised of multiple cellular entities. Here we review the two theories that have been described, trying to explain the origin of intra-tumor heterogeneity: clonal evolution and cancer stem cells. The first one considers that a single cell gives rise to many subpopulations through the accumulation of multiple aberrations, while the cancer stem cells theory foresees a hierarchical tumor evolution where only a few cells with self-renewal capacity give rise to different subpopulations...
March 2017: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/28448707/-joint-replacement-and-giant-cell-tumor-report-of-8-cases
#3
J G Martínez-Estrada, O Santamaría-Bahena
INTRODUCTION: The giant-cell tumor is an aggressive neoplasia, represents approximately from the 5 the 8.6% of primary bone tumors; more of 50% affects the pelvic extremity, being able to affect the totality of the bones. OBJECTIVE: To present the case series of tumors around the knee and hip that we offered a tumoral joint replacement as an alternative to amputation. MATERIAL AND METHODS: We present eight cases of extensive giant cells tumors, we did en bloc resection and tumoral joint replacement...
September 2016: Acta Ortopédica Mexicana
https://www.readbyqxmd.com/read/28448628/determinants-of-formal-care-use-and-expenses-among-in-home-elderly-in-jing-an-district-shanghai-china
#4
Fen Li, Xinye Fang, Jiechun Gao, Hansheng Ding, Changying Wang, Chunyan Xie, Yitong Yang, Chunlin Jin
The need for formal care among the elderly population has been increasing due to their greater longevity and the evolution of family structure. We examined the determinants of the use and expenses of formal care among in-home elderly adults in Shanghai. A two-part model based on the data from the Shanghai Long-Term Care Needs Assessment Questionnaire was applied. A total of 8428 participants responded in 2014 and 7100 were followed up in 2015. The determinants of the probability of using formal care were analyzed in the first part of the model and the determinants of formal care expenses were analyzed in the second part...
2017: PloS One
https://www.readbyqxmd.com/read/28445469/phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#5
Christopher Abbosh, Nicolai J Birkbak, Gareth A Wilson, Mariam Jamal-Hanjani, Tudor Constantin, Raheleh Salari, John Le Quesne, David A Moore, Selvaraju Veeriah, Rachel Rosenthal, Teresa Marafioti, Eser Kirkizlar, Thomas B K Watkins, Nicholas McGranahan, Sophia Ward, Luke Martinson, Joan Riley, Francesco Fraioli, Maise Al Bakir, Eva GrÖnroos, Francisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M Fennessy, Nicole Sponer, Diana Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin Hiley, Siow Ming Lee, Martin D Forster, Tanya Ahmad, Mary Falzon, Elaine Borg, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Dina Hafez, Ashwini Naik, Apratim Ganguly, Stephanie Kareht, Rajesh Shah, Leena Joseph, Anne Marie Quinn, Phil Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Dahmane Oukrif, Ayse U Akarca, John A Hartley, Helen L Lowe, Sara Lock, Natasha Iles, Harriet Bell, Yenting Ngai, Greg Elgar, Zoltan Szallasi, Roland F Schwarz, Javier Herrero, Aengus Stewart, Sergio A Quezada, Peter Van Loo, Caroline Dive, C Jimmy Lin, Matthew Rabinowitz, Hugo Jwl Aerts, Allan Hackshaw, Jacqui A Shaw, Bernhard G Zimmermann, Charles Swanton
The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#6
Mariam Jamal-Hanjani, Gareth A Wilson, Nicholas McGranahan, Nicolai J Birkbak, Thomas B K Watkins, Selvaraju Veeriah, Seema Shafi, Diana H Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D Forster, Tanya Ahmad, Crispin T Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M Quinn, Phil A Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O'Sullivan, Helen L Lowe, John A Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A Shaw, Javier Herrero, Zoltan Szallasi, Roland F Schwarz, Aengus Stewart, Sergio A Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy...
April 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28444372/quantifying-the-number-of-independent-organelle-dna-insertions-in-genome-evolution-and-human-health
#7
Einat Hazkani-Covo, William F Martin
Fragments of organelle genomes are often found as insertions in nuclear DNA. These fragments of mitochondrial DNA (numts) and plastid DNA (nupts) are ubiquitous components of eukaryotic genomes. They are, however, often edited out during the genome assembly process, leading to systematic underestimation of their frequency. Numts and nupts, once inserted, can become further fragmented through subsequent insertion of mobile elements or other recombinational events that disrupt the continuity of the inserted sequence relative to the genuine organelle DNA copy...
April 21, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28442904/anti-fgfr1-aptamer-tagged-superparamagnetic-conjugates-for-anticancer-hyperthermia-therapy
#8
Przemysław M Jurek, Konrad Zabłocki, Urszula Waśko, Maciej P Mazurek, Jacek Otlewski, Filip Jeleń
Compounds that recognize and strongly bind to molecular targets are one of the cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years on the therapeutic use of aptamers, nucleic acid molecules, whose three-dimensional structure is the result of interactions between complementary base pairs. The aptamers selection methods allow the oligonucleotides which bind the molecular target in its native environment to be quickly isolated from a large library of random oligonucleotides. The possibilities presented for aptamers in the field of targeted therapy require the application of effective carriers to counter the renal clearance effect and/or functional cargo to exert therapeutic action if the aptamer is only used as a targeting moiety...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28442585/next-gen-sequencing-analysis-and-algorithms-for-pdx-and-cdx-models
#9
Garima Khandelwal, Maria Romina Girotti, Christopher Smowton, Sam Taylor, Chris Wirth, Marek Dynowski, Kristopher K Frese, Ged Brady, Caroline Dive, Richard Marais, Crispin Miller
Patient-derived xenograft (PDX) and CTC-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions including the study of metastatic progression, genetic evolution and therapeutic drug responses. Since PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing (NGS) in order to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442318/brownian-model-of-transcriptome-evolution-and-phylogenetic-network-visualization-between-tissues
#10
Xun Gu, Hang Ruan, Zhixi Su, Yangyun Zou
While phylogenetic analysis of transcriptomes of the same tissue is usually congruent with the species tree, the controversy emerges when multiple tissues are included, that is, whether species from the same tissue are clustered together, or different tissues from the same species are clustered together. Recent studies have suggested that phylogenetic network approach may shed some lights on our understanding of multi-tissue transcriptome evolution; yet the underlying evolutionary mechanism remains unclear...
April 22, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28442298/how-to-study-and-overcome-tumor-heterogeneity-with-circulating-biomarkers-the-breast-cancer-case
#11
REVIEW
Valentina Appierto, Serena Di Cosimo, Carolina Reduzzi, Valentina Pala, Vera Cappelletti, Maria Grazia Daidone
Breast cancer ranks first among female cancer-related deaths in Western countries. As the primary tumor can often be controlled by surgical resection, the survival of women with breast cancer is closely linked to the incidence of distant metastases. Molecular screening by next generation sequencing highlighted the spatial and temporal heterogeneity of solid tumors as well as the clonal evolution of cancer cells during progression and under treatment pressure. Such findings question whether an optimal assessment of disease progression and a screening for druggable mutations should be based on molecular features of primary or recurrent/metastatic lesions and therefore represent a crucial element for failure or success of personalized medicine...
April 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28440459/hypoxia-induced-mir-210-promoter-demethylation-enhances-proliferation-autophagy-and-angiogenesis-of-schwannoma-cells
#12
Zhengguang Wang, Mingsi Deng, Zhendong Liu, Song Wu
Hypoxia, a dominant feature in cancer occurrence and evolution, exists throughout the progression of most malignant tumors. This study focused on the mechanism of hypoxia-induced miR-210 upregulation, and the miR-210 functions in schwannoma. We detected microvascular density, vascular endothelial growth factor (VEGF) and miR-210 expression levels using schwannoma tissue mciroarray. The results showed that miR-210 expression was significantly associated with VEGF. Moreover, the cytological tests showed that hypoxia induced miR-210 expression, while reduce ephrin-A3 expression...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439490/watch-and-wait-policy-in-advanced-neuroendocrine-tumors-what-does-it-mean
#13
EDITORIAL
Nicola Fazio
Neuroendocrine neoplasms (NENs) are a group of rare and heterogeneous malignancies, which can develop in various organs. The clinical course of NENs is quite heterogeneous, with different spontaneous growth rates after diagnosis, and different degrees of sensitivity to the same therapy even when they have similar characteristics. Watch and wait (W and W), is a term coined to indicate observation being conducted to assess the evolution of the tumor without administering any anti-tumor therapy. It has been applied to NENs since in extremely rare cases they tend to remain stable for a long time...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28438874/partial-cystectomy-for-atypical-isolated-recurrence-of-ovarian-adenocarcinoma-a-case-report-and-literature-review
#14
Nicolae Bacalbasa, Irina Balescu
BACKGROUND: Most cases with advanced-stage epithelial ovarian malignancies will experience recurrent disease at a certain moment of their evolution, even if maximal cytoreductive surgery has been performed at the moment of initial diagnosis. However, it seems that the best therapeutic strategy, in case of relapse, remains aggressive re-resection, with complete cytoreduction being the most efficient way to improve survival. MATERIALS AND METHODS: We present the case of a 55-year-old patient diagnosed with an isolated pelvic recurrence after stage IIIC surgically-treated ovarian cancer three years after primary cytoreduction...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28438297/investigating-a-case-of-possible-field-cancerization-in-oral-squamous-cell-carcinoma-by-the-use-of-next-generation-sequencing
#15
Siavosh Tabatabaeifar, Martin J Larsen, Stine R Larsen, Torben A Kruse, Mads Thomassen, Jens A Sørensen
OBJECTIVES: Local recurrence and the development of second primary tumors (SPT) are important factors that can influence the survival rate of oral squamous cell carcinoma (OSCC) patients. We investigate the concept of field cancerization which proposes that normal tissue adjacent to the primary tumor harbor pre-neoplastic alterations that can lead to the development of local recurrence and SPTs. MATERIALS AND METHODS: To examine the concept of field cancerization, we applied whole-exome and targeted ultra-deep sequencing on 5 freshly frozen samples from a stage III OSCC patient from three tumor sites, lymph node metastasis and blood...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28434690/assessment-of-potential-mirna-biomarkers-of-vero-cell-tumorigenicity-in-a-new-line-agmk1-9t7-of-african-green-monkey-kidney-cells
#16
Belete Teferedegne, Daniel M Rotroff, Juliete Macauley, Gideon Foseh, Gladys Lewis, Alison Motsinger-Rief, Andrew M Lewis
Patterns of microRNA expression appear to delineate the process of spontaneous neoplastic development-transformation (SPNDT) occurring in the African green monkey kidney (AGMK) VERO cell line (Teferedegne et al., 2010). Analysis of microarray data identified 6 microRNAs whose high-level of expression peaked when the World Health Organization 10-87 VERO cells became tumorigenic at passage (p) 190. Six miRNAs were identified as potential biomarkers for the expression of the VERO-cell tumorigenic phenotype (Teferedegne et al...
April 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#17
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#18
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431643/advances-in-circulating-tumor-dna-analysis
#19
Samantha Perakis, Martina Auer, Jelena Belic, Ellen Heitzer
The analysis of cell-free circulating tumor DNA (ctDNA) is a very promising tool and might revolutionize cancer care with respect to early detection, identification of minimal residual disease, assessment of treatment response, and monitoring tumor evolution. ctDNA analysis, often referred to as "liquid biopsy" offers what tissue biopsies cannot-a continuous monitoring of tumor-specific changes during the entire course of the disease. Owing to technological improvements, efforts for the establishment of preanalytical and analytical benchmark, and the inclusion of ctDNA analyses in clinical trial, an actual clinical implementation has come within easy reach...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28431544/strategies-for-monitoring-and-combating-resistance-to-combination-kinase-inhibitors-for-cancer-therapy
#20
REVIEW
Leanne G Ahronian, Ryan B Corcoran
Targeted therapies such as kinase inhibitors and monoclonal antibodies have dramatically altered cancer care in recent decades. Although these targeted therapies have improved patient outcomes in several cancer types, resistance ultimately develops to these agents. One potential strategy proposed to overcome acquired resistance involves taking repeat tumor biopsies at the time of disease progression, to identify the specific molecular mechanism driving resistance in an individual patient and to select a new agent or combination of agents capable of surmounting that specific resistance mechanism...
April 21, 2017: Genome Medicine
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