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https://www.readbyqxmd.com/read/27926932/epsin-family-member-3-and-ribosome-related-genes-are-associated-with-late-metastasis-in-estrogen-receptor-positive-breast-cancer-and-long-term-survival-in-non-small-cell-lung-cancer-using-a-genome-wide-identification-and-validation-strategy
#1
Birte Hellwig, Katrin Madjar, Karolina Edlund, Rosemarie Marchan, Cristina Cadenas, Anne-Sophie Heimes, Katrin Almstedt, Antje Lebrecht, Isabel Sicking, Marco J Battista, Patrick Micke, Marcus Schmidt, Jan G Hengstler, Jörg Rahnenführer
BACKGROUND: In breast cancer, gene signatures that predict the risk of metastasis after surgical tumor resection are mainly indicative of early events. The purpose of this study was to identify genes linked to metastatic recurrence more than three years after surgery. METHODS: Affymetrix HG U133A and Plus 2.0 array datasets with information on metastasis-free, disease-free or overall survival were accessed via public repositories. Time restricted Cox regression models were used to identify genes associated with metastasis during or after the first three years post-surgery (early- and late-type genes)...
2016: PloS One
https://www.readbyqxmd.com/read/27924156/deficiency-of-atp6v1h-causes-bone-loss-by-inhibiting-bone-resorption-and-bone-formation-through-the-tgf-%C3%AE-1-pathway
#2
Xiaohong Duan, Jin Liu, Xueni Zheng, Zhe Wang, Yanli Zhang, Ying Hao, Tielin Yang, Hongwen Deng
Vacuolar-type H (+)-ATPase (V-ATPase) is a highly conserved, ancient enzyme that couples the energy of ATP hydrolysis to proton transport across vesicular and plasma membranes of eukaryotic cells. Previously reported mutations of various V-ATPase subunits are associated with increased bone density. We now show that haploinsufficiency for the H subunit of the V1 domain (ATP6V1H) is associated with osteoporosis in humans and mice. A genome-wide SNP array analysis of 1625 Han Chinese found that 4 of 15 tag SNPs (26...
2016: Theranostics
https://www.readbyqxmd.com/read/27924064/toward-the-use-of-precision-medicine-for-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#3
REVIEW
Wang Gong, Yandi Xiao, Zihao Wei, Yao Yuan, Min Qiu, Chongkui Sun, Xin Zeng, Xinhua Liang, Mingye Feng, Qianming Chen
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923841/biological-and-clinical-relevance-of-associated-genomic-alterations-in-myd88-l265p-and-non-l265p-mutated-diffuse-large-b-cell-lymphoma-analysis-of-361-cases
#4
Sydney Dubois, Pierre-Julien Viailly, Elodie Bohers, Philippe Bertrand, Philippe Ruminy, Vinciane Marchand, Catherine Maingonnat, Sylvain Mareschal, Jean-Michel Picquenot, Dominique Penther, Jean-Philippe Jais, Bruno Tesson, Pauline Peyrouze, Martin Figeac, Fabienne Desmots, Thierry Fest, Corinne Haioun, Thierry Lamy, Christiane Copie-Bergman, Bettina Fabiani, Richard Delarue, Frederic Peyrade, Marc André, Nicolas Ketterer, Karen Leroy, Gilles Salles, Thierry J Molina, Herve Tilly, Fabrice Jardin
PURPOSE: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of Activated B-Cell like (ABC) Diffuse Large B Cell Lymphoma (DLBCL), leading to constitutive NFkB pathway activation. The aim of this study was to examine the distinct genomic profiles of MYD88 mutant DLBCL, notably according to the presence of the L265P or other non-L265P MYD88 variants. EXPERIMENTAL DESIGN: A cohort of 361 DLBCL cases (94 MYD88 mutant and 267 MYD88 wild-type) was submitted to next generation sequencing (NGS) focusing on 34 genes in order to analyze associated mutations and copy number variations, as well as gene expression profiling, and clinical and prognostic analyses...
December 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27923825/rational-selection-of-syngeneic-preclinical-tumor-models-for-immunotherapeutic-drug-discovery
#5
Suzanne I S Mosely, John E Prime, Richard C A Sainson, Jens-Oliver Koopmann, Dennis Y Q Wang, Danielle M Greenawalt, Miika J Ahdesmaki, Rebecca Leyland, Stefanie Mullins, Luciano Pacelli, Danielle Marcus, Judith Anderton, Amanda Watkins, Jane Coates Ulrichsen, Philip Brohawn, Brandon W Higgs, Matthew McCourt, Hazel Jones, James A Harper, Michelle Morrow, Viia Valge-Archer, Ross Stewart, Simon J Dovedi, Robert W Wilkinson
Murine syngeneic tumor models are critical to novel immuno-based therapy development but the molecular and immunological features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly-used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We employed array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#6
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#7
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27921283/choices-have-consequences-the-nexus-between-dna-repair-pathways-and-genomic-instability-in-cancer
#8
REVIEW
Sonali Bhattacharjee, Saikat Nandi
BACKGROUND: The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27920633/lesch-nyhan-syndrome-models-theories-and-therapies
#9
REVIEW
Scott Bell, Ilaria Kolobova, Liam Crapper, Carl Ernst
Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by mutations in HPRT1, an important enzyme in the purine salvage pathway. Symptoms of LNS include dystonia, gout, intellectual disability, and self-mutilation. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in hypoxanthine and guanine recycling can lead to such a profound neurological phenotype. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients, though none have led to a satisfactory explanation of the disease...
November 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27920481/new-real-time-pcr-method-to-identify-single-point-mutations-in-hepatitis-c-virus
#10
Qian Chen, Irene Belmonte, Maria Buti, Leonardo Nieto, Damir Garcia-Cehic, Josep Gregori, Celia Perales, Laura Ordeig, Meritxell Llorens, Maria Eugenia Soria, Rafael Esteban, Juan Ignacio Esteban, Francisco Rodriguez-Frias, Josep Quer
AIM: To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus (HCV). METHODS: In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27919216/topoisomerase-ii-inhibitors-and-poisons-and-the-influence-of-cell-cycle-checkpoints
#11
Nicholas D Arcy, Brian Gabrielli
Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27917795/lytic-activity-of-various-phage-cocktails-on-multidrug-resistant-bacteria
#12
I Ozkan, E Akturk, N Yeshenkulov, S Atmaca, N Rahmanov, H I Atabay
PURPOSE: A bacteriophage is a virus that infects and replicates within a bacterium following the injection of phage genome into the bacterial cytoplasm. They are seen as a possible therapy for multi-drug-resistant strains of many bacteria. The aim of this study is to evaluate the lytic activity of the Pyo, Intesti and Fersisi bacteriophage cocktails on P. aeruginosa and S. aureus. METHODS: Ten different S. aureus and P. aeruginosa strains, which were isolated from hospitalized patients in Turkey, were used in the study...
December 1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27917773/mutations-of-mtdna-polymerase-%C3%AE-and-hyperlactataemia-in-the-hiv-infected-zulu-population-of-south-africa
#13
D B A Ojwach, C Aldous, P Kochleff, B Sartorius
BACKGROUND: Mitochondrial toxicity, particularly symptomatic hyperlactataemia or lactic acidosis (SHL/LA), has been attributed to the use of nucleoside reverse transcriptase inhibitors (NRTIs), possibly because of their capacity to impede human mitochondrial DNA polymerase-γ (POLG), which is responsible for the replication of mitochondrial DNA. OBJECTIVE: To determine whether known monogenic POLG1 polymorphisms could be linked with the unexpectedly high incidence of SHL/LA observed in HIV-infected Zulu-speaking patients exposed to the NRTIs stavudine or zidovudine in their antiretroviral therapy...
December 1, 2016: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/27915991/control-of-inflammatory-bowel-disease-and-colorectal-cancer-by-synthetic-vitamin-d-receptor-ligands
#14
Ichiro Takada, Makoto Makishima
Vitamin D deficiency and insufficiency are associated with an increased risk of cancer, autoimmune disease, inflammation, infection, cardiovascular disease and metabolic disease, as well as bone and mineral disorders. The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, is a receptor for the active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], and mediates vitamin D regulation of specific target gene expression. The secondary bile acid lithocholic acid, which is produced by intestinal bacteria, is another natural VDR ligand...
December 2, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27915478/targeting-the-phosphatidylinositol-3-kinase-pathway-in-gastric-cancer-can-omics-improve-outcomes
#15
REVIEW
Phu Tran, Cham Nguyen, Samuel J Klempner
Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27915083/pharmacodynamic-and-cytogenetic-evaluation-in-cyp2c19-2-and-cyp2c19-3-allelomorphism-in-south-indian-population-with-clopidogrel-therapy
#16
Javeed Ahmad Tantray, K Pratap Reddy, Kaiser Jamil, Y Shiva Kumar
BACKGROUND: Genetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field. METHODS: 150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping...
November 11, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#17
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913567/drug-repositioning-screens-identify-triamterene-as-a-selective-drug-for-the-treatment-of-dna-mismatch-repair-deficient-cells
#18
Delphine Guillotin, Philip Austin, Rumena Begum, Marta O Freitas, Ashirwad Merve, Tim Brend, Susan C Short, Silvia Marino, Sarah A Martin
PURPOSE: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. EXPERIMENTAL DESIGN: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs...
December 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#19
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912827/new-targets-in-non-small-cell-lung-cancer
#20
REVIEW
Soo J Park, Soham More, Ayesha Murtuza, Brian D Woodward, Hatim Husain
With the implementation of genomic technologies into clinical practice, we have examples of the predictive benefit of targeted therapy for oncogene-addicted cancer and identified molecular dependencies in non-small cell lung cancer. The clinical success of tyrosine kinase inhibitors against epidermal growth factor receptor and anaplastic lymphoma kinase activation has shifted treatment emphasize the separation of subsets of lung cancer and genotype-directed therapy. Advances have validated oncogenic driver genes and led to the development of targeted agents...
February 2017: Hematology/oncology Clinics of North America
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