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https://www.readbyqxmd.com/read/29675807/the-prognostic-impact-of-cdx2-correlates-with-the-underlying-mismatch-repair-status-and-braf-mutational-status-but-not-with-distant-metastasis-in-colorectal-cancer
#1
Jens Neumann, Volker Heinemann, Jutta Engel, Thomas Kirchner, Sebastian Stintzing
Loss of CDX2 expression has been proposed to be a prognostic biomarker in colorectal cancer (CRC) correlating with shorter overall (OS) and progression-free survival (PFS). Since metastatic disease, mismatch repair (MMR) deficiency, and the mutational status of BRAF are considered to be important prognostic determinants in CRC, the present study aimed to analyze CDX2 expression in correlation with these parameters. Immunohistochemistry for CDX2, hMLH1, and hMSH2 was applied to a study cohort of 503 CRC specimens (FIRE-3) and a matched case-control collection of 50 right-sided CRC specimens with synchronous distant metastases and 50 right-sided CRCs without distant metastases...
April 19, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29673110/programmed-death-ligand-1-expression-in-gastric-cancer-correlation-with-mismatch-repair-deficiency-and-her2-negative-status
#2
Lei Wang, Qiongyan Zhang, Shujuan Ni, Cong Tan, Xu Cai, Dan Huang, Weiqi Sheng
Gastric cancer (GC) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of PD-L1 and its prognostic value in GC. We aimed to evaluate the expression rates of PD-L1 in GC, and further assess its relationship with mismatch repair (MMR), and human epidermal growth factor receptor 2 (HER2) status...
April 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29672836/pathogenic-and-targetable-genetic-alterations-in-70-urachal-adenocarcinomas
#3
Henning Reis, Kristan E van der Vos, Christian Niedworok, Thomas Herold, Orsolya Módos, Attila Szendrői, Thomas Hager, Marc Ingenwerth, Daniël J Vis, Mark A Behrendt, Jeroen de Jong, Michiel S van der Heijden, Benoit Peyronnet, Romain Mathieu, Marcel Wiesweg, Jason Ablat, Krzysztof Okon, Yuri Tolkach, David Keresztes, Nikolett Nagy, Felix Bremmer, Nadine T Gaisa, Piotr Chlosta, Joerg Kriegsmann, Ilona Kovalszky, József Timar, Glen Kristiansen, Heinz-Joachim Radzun, Ruth Knüchel, Martin Schuler, Peter Black, Herbert Rübben, Boris Hadaschik, Kurt Werner Schmid, Bas W G van Rhijn, Péter Nyirády, Tibor Szarvas
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins (MMR)) and evaluated the microsatellite instability (MSI) status...
April 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29672549/tumor-development-in-japanese-patients-with-lynch-syndrome
#4
Chiaki Saita, Tatsuro Yamaguchi, Shin-Ichiro Horiguchi, Rin Yamada, Misato Takao, Takeru Iijima, Rika Wakaume, Tomoyuki Aruga, Taku Tabata, Koichi Koizumi
BACKGROUND: Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients. METHODS: This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. RESULTS: The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19-65) and 44 (range, 24-66) years, respectively...
2018: PloS One
https://www.readbyqxmd.com/read/29669924/samhd1-enhances-immunoglobulin-hypermutation-by-promoting-transversion-mutation
#5
Eddy Sanchai Thientosapol, Daniel Bosnjak, Timothy Durack, Igor Stevanovski, Michelle van Geldermalsen, Jeff Holst, Zeenat Jahan, Caitlin Shepard, Wolfgang Weninger, Baek Kim, Robert Brink, Christopher J Jolly
Activation-induced deaminase (AID) initiates hypermutation of Ig genes in activated B cells by converting C:G into U:G base pairs. G1 -phase variants of uracil base excision repair (BER) and mismatch repair (MMR) then deploy translesion polymerases including REV1 and Pol η, which exacerbates mutation. dNTP paucity may contribute to hypermutation, because dNTP levels are reduced in G1 phase to inhibit viral replication. To derestrict G1 -phase dNTP supply, we CRISPR-inactivated SAMHD1 (which degrades dNTPs) in germinal center B cells...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29669262/dna-mismatch-repair-in-cancer
#6
REVIEW
Marina Baretti, Dung T Le
Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch Syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although original methods to assess MSI or MMR deficiency have been developed mostly in LS related cancers...
April 15, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29668816/compliance-with-the-vaccination-schedule-in-children-hospitalized-with-pneumonia-and-associated-factors
#7
Amanda Tabosa Pereira da Silva, Eduardo Jorge da Fonseca Lima, Maria de Fátima Costa Caminha, Andresa Tabosa Pereira da Silva, Edil de Albuquerque Rodrigues Filho, Carmina Silva Dos Santos
OBJECTIVE: To verify the adequacy and factors associated with compliance with the immunization schedule (BCG, DTP-Hib, MMR, PCV-10) in children hospitalized with pneumonia at a pediatric referral hospital in Northeast Brazil. METHODS: This is a cross-sectional, descriptive study with an analytical component, with a sample of 452 children hospitalized with pneumonia at the Instituto de Medicina Integral Prof. Fernando Figueira, between 2010 and 2013. The inclusion criterion was children aged from one month to less than five years of age with proof in the immunization record...
2018: Revista de Saúde Pública
https://www.readbyqxmd.com/read/29667044/germline-variants-in-pancreatic-cancer-patients-with-a-personal-or-family-history-of-cancer-fulfilling-the-revised-bethesda-guidelines
#8
Akihiro Ohmoto, Chigusa Morizane, Emi Kubo, Erina Takai, Hiroko Hosoi, Yasunari Sakamoto, Shunsuke Kondo, Hideki Ueno, Kazuaki Shimada, Shinichi Yachida, Takuji Okusaka
BACKGROUND: Pancreatic cancer (PC) is categorized as a neoplasm associated with Lynch syndrome; however, the precise proportion of PC patients harboring DNA mismatch repair genes (MMR genes) remains unclear, especially in the Asian population. METHODS: Among 304 Japanese patients with pathologically proven pancreatic ductal adenocarcinoma, we selected 20 (6.6%) patients with a personal or family history involving first- or second-degree relatives fulfilling the revised Bethesda guidelines (RBG), defined as RBG-compatible cases...
April 17, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29665906/-imatinib-as-second-line-treatment-drug-for-cml-patients-intolerant-to-nilotinib
#9
Jing Qi, You-Hai Xu, He-Sheng He
OBJECTIVE: To explore the individualized treatment for patient with chronic phase chronic myeloid leukemia(CML-CP). METHODS: The clinical data and treatment process of one CML-CP patient which intolerated to nilotinib were analyzed. RESULTS: Nilotinib was given to the patient once the diagnosis of CML-CP was set. Although major molecular remission (MMR) and complete cytogenetic remission (CCyR) were obtained during treatment for 3 months, a grade 3-4 hepatotoxicity appeared in the course of treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665902/-mean-corpuscular-volume-can-be-a-predictor-for-therapeutic-response-of-patients-with-chronic-myeloid-leukemia
#10
Luo Lu, Chun Qiao, Ming Hong, Yan-Ru Li, Liang-Qin Pan, Si-Xuan Qian, Yu Zhu, Jian-Yong Li
OBJECTIVE: The past studies found that the treatment of chronic myeloid leukemia (CML) with imatinib can induce the macrocytic anemia, moreover the incidence of anemia increases along with enhancement of imatinib concentration. This study was aimed to evaluate the potential relation of erythrocyte mean corpuscular volume (MCV) increase after the treatment with tyrosine kinase inhibitors (TKI) with the therapeutic response in patients with CML-chronic phase (CML-CP). METHODS: The clinical and hematologic data including MCV, molecular and cytogenetic response of 119 patients with CML-CP were collected after treatment with TKIs, and the relation of MCV changes after treatment with the clinical characteristics and therapeutic efficacy for patients with CML-CP was analyzed...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29660177/severe-adverse-events-by-tyrosine-kinase-inhibitors-decrease-survival-rates-in-patients-with-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia
#11
Shuichi Ota, Toshihiro Matsukawa, Satoshi Yamamoto, Ito Shinichi, Motohiro Shindo, Kazuya Sato, Takeshi Kondo, Kyuhei Kohda, Hajime Sakai, Akio Mori, Tohru Takahashi, Hiroshi Ikeda, Hiroyuki Kuroda, Yoshihito Haseyama, Masaki Yamamoto, Takeo Sarashina, Makoto Yoshida, Ryoji Kobayashi, Mitsufumi Nishio, Toshimichi Ishihara, Yasuo Hirayama, Yasutaka Kakinoki, Hajime Kobayashi, Takashi Fukuhara, Masahiro Imamura, Mitsutoshi Kurosawa
OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89...
April 16, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29659608/clinical-impact-of-endometrial-cancer-stratified-by-genetic-mutational-profiles-pole-mutation-and-microsatellite-instability
#12
Tomoko Haruma, Takeshi Nagasaka, Keiichiro Nakamura, Junko Haraga, Akihiro Nyuya, Takeshi Nishida, Ajay Goel, Hisashi Masuyama, Yuji Hiramatsu
BACKGROUND: The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. MATERIALS AND METHODS: A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled...
2018: PloS One
https://www.readbyqxmd.com/read/29658188/strategy-to-targeting-the-immune-resistance-and-novel-therapy-in-colorectal-cancer
#13
REVIEW
Wang Gang, Jun-Jie Wang, Rui Guan, Sun Yan, Feng Shi, Jia-Yan Zhang, Zi-Meng Li, Jing Gao, Xing-Li Fu
Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy...
April 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29656536/mmr-deficiency-does-not-sensitize-or-compromise-the-function-of-hematopoietic-stem-cells-to-low-and-high-let-radiation
#14
Rutulkumar Patel, Yulan Qing, Lucy Kennedy, Yan Yan, John Pink, Brittany Aguila, Amar Desai, Stanton L Gerson, Scott M Welford
One of the major health concerns on long-duration space missions will be radiation exposure to the astronauts. Outside the earth's magnetosphere, astronauts will be exposed to galactic cosmic rays (GCR) and solar particle events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe nuclei. Protons are by far the most common species, but the higher atomic number particles are thought to be more damaging to biological systems. Evaluation and amelioration of risks from GCR exposure will be important for deep space travel...
April 14, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29649292/special-immunization-service-a-14-year-experience-in-italy
#15
Daniele Donà, Susanna Masiero, Sara Brisotto, Lorena Gottardello, Rebecca Lundin, Eleonora Borgia, Federica Visentin, Liviana Da Dalt
BACKGROUND: Concerns regarding vaccine safety are increasing along with lack of compliance to vaccination schedules. This study aimed to assess vaccination-related risks and the impact of a Special Immunization Service (SIS) at the Pediatric Emergency Department (PED) of Padua on vaccination compliance among participants. MATERIALS AND METHODS: This retrospective cohort study included all children attending the SIS from January 1st 2002 to December 31st 2015. The Service is divided into a clinic (SIS-C) where all referred children undergo a pre-vaccination visit and an area within the Pediatric Emergency Department (SIS-PED) where children are vaccinated if indicated...
2018: PloS One
https://www.readbyqxmd.com/read/29645364/costs-and-outcomes-of-lynch-syndrome-screening-in-the-australian-colorectal-cancer-population
#16
Dayna R Cenin, Steffie K Naber, Iris Lansdorp-Vogelaar, Mark A Jenkins, Daniel D Buchanan, David B Preen, Hooi C Ee, Peter O'Leary
BACKGROUND AND AIM: Individuals with Lynch syndrome (LS) are at increased risk of LS-related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost-effectiveness has not been assessed. We aim to determine the cost-effectiveness of screening individuals with CRC for LS at different age-at-diagnosis thresholds. METHODS: We developed a decision-analysis model to estimate yield and costs of LS screening...
April 12, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29625543/mechanisms-of-mitochondrial-dna-repair-in-mammals
#17
REVIEW
L A Zinovkina
Accumulation of mutations in mitochondrial DNA leads to the development of severe, currently untreatable diseases. The contribution of these mutations to aging and progress of neurodegenerative diseases is actively studied. Elucidation of DNA repair mechanisms in mitochondria is necessary for both developing approaches to the therapy of diseases caused by mitochondrial mutations and understanding specific features of mitochondrial genome functioning. Mitochondrial DNA repair systems have become a subject of extensive studies only in the last decade due to development of molecular biology methods...
March 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29620877/a-family-of-rhodium-complexes-with-selective-toxicity-towards-mismatch-repair-deficient-cancers
#18
Kelsey M Boyle, Jacqueline K Barton
Rhodium metalloinsertors are a unique set of metal complexes that bind specifically to DNA base pair mismatches in vitro and kill mismatch repair (MMR)-deficient cells at lower concentrations than their MMR-proficient counterparts. A family of metalloinsertors containing rhodium-oxygen ligand coordination, termed "Rh-O" metalloinsertors, has been prepared and shown to have a significant increase in both overall potency and selectivity towards MMR-deficient cells regardless of structural changes in the ancillary ligands...
April 5, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29619485/how-often-do-children-receive-their-vaccinations-late-and-why
#19
Maysaa A Banjari, Ahmed A Alamri, Ahmad Y Algarni, Meral H Abualjadayel, Yahya S Alshardi, Turki S Alahmadi
OBJECTIVES: To assess vaccination timeliness, risk factors associated with delays and the reasons for delayed vaccinations among children below the age of 3 years in Jeddah, Kingdom of Saudi Arabia. METHODS: This is a cross-sectional study conducted in Jeddah, Saudi Arabia during the period of May 2016 to August 2017. Data were obtained from parents of children under the age of 3 years using a structured questionnaire comprised of questions about sociodemographics, physical well-being of the child and the reasons that are used to justify delayed vaccinations...
April 2018: Saudi Medical Journal
https://www.readbyqxmd.com/read/29616365/multi-institutional-quantitative-phantom-study-of-yttrium-90-pet-in-pet-mri-the-mr-quest-study
#20
Nichole M Maughan, Mootaz Eldib, David Faul, Maurizio Conti, Mattijs Elschot, Karin Knešaurek, Francesca Leek, David Townsend, Frank P DiFilippo, Kimberly Jackson, Stephan G Nekolla, Mathias Lukas, Michael Tapner, Parag J Parikh, Richard Laforest
BACKGROUND: Yttrium-90 (90 Y) radioembolization involves the intra-arterial delivery of radioactive microspheres to treat hepatic malignancies. Though this therapy involves careful pre-treatment planning and imaging, little is known about the precise location of the microspheres once they are administered. Recently, there has been growing interest post-radioembolization imaging using positron-emission tomography (PET) for quantitative dosimetry and identifying lesions that may benefit from additional salvage therapy...
April 4, 2018: EJNMMI Physics
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