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https://www.readbyqxmd.com/read/29667146/cost-effectiveness-analysis-of-crohn-s-disease-treatment-with-vedolizumab-and-ustekinumab-after-failure-of-tumor-necrosis-factor-%C3%AE-antagonist
#1
Przemysław Holko, Paweł Kawalec, Andrzej Pilc
OBJECTIVE: The aim was to evaluate the cost-effectiveness of Crohn's disease (CD) treatment with vedolizumab and ustekinumab after failure of therapy with tumor necrosis factor-α antagonists (anti-TNFs). METHODS: The Markov model incorporated the lifetime horizon, synthesis-based estimates of biologics' efficacy in relation to anti-TNF exposure, and administration of biologics reflecting clinical practice (e.g., sequence of biologics, retreatment, 12-month treatment)...
April 17, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29666669/-egfr-amplification-induces-sensitivity-to-anti-egfr-therapy-in-pancreatic-acinar-cell-carcinoma
#2
Corentin Richard, Julie Niogret, Romain Boidot, Francois Ghiringhelli
Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses...
April 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29666303/gallium-67-68-labeled-antibody-fragments-for-immuno-spect-pet-show-low-renal-radioactivity-without-loss-of-tumor-uptake
#3
Tomoya Uehara, Miki Yokoyama, Hiroyuki Suzuki, Hirofumi Hanaoka, Yasushi Arano
PURPOSE: This study was undertaken to evaluate the renal radioactivity levels of a newly designed 67 Ga-labeled antibody fragment with a linkage cleaved by enzymes present on the brush border membrane (BBM) lining the lumen of the renal tubule. EXPERIMENTAL DESIGN: 67 Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) was conjugated with an antibody Fab fragment through a Met-Val-Lys linkage (67 Ga-NOTA-MVK-Fab) considering that a Met-Val sequence is a substrate of enzymes on the renal BBM and 67 Ga-NOTA-Met is excreted from the kidney into the urine...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666243/-o-6-methylguanine-induced-transcriptional-mutagenesis-reduces-p53-tumor-suppressor-function
#4
Monika Ezerskyte, João A Paredes, Stefano Malvezzi, John A Burns, Geoffrey P Margison, Magnus Olsson, David A Scicchitano, Kristian Dreij
Altered protein function due to mutagenesis plays an important role in disease development. This is perhaps most evident in tumorigenesis and the associated loss or gain of function of tumor-suppressor genes and oncogenes. The extent to which lesion-induced transcriptional mutagenesis (TM) influences protein function and its contribution to the development of disease is not well understood. In this study, the impact of O 6 -methylguanine on the transcription fidelity of p53 and the subsequent effects on the protein's function as a regulator of cell death and cell-cycle arrest were examined in human cells...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666187/a-putative-g-quadruplex-structure-in-the-proximal-promoter-of-vegfr-2-has-implications-for-drug-design-to-inhibit-tumor-angiogenesis
#5
Yaping Liu, Wenxian Lan, Chunxi Wang, Chunyang Cao
Tumor angiogenesis is mainly regulated by vascular endothelial growth factor (VEGF), produced by cancer cells. It is active on the endothelium via VEGF receptor 2 (VEGFR-2). G-quadruplexes are DNA secondary structures formed by guanine-rich sequences, for example, within gene promoters where they may contribute to transcriptional activity. The proximal promoter of vegfr-2 contains a G-quadruplex, which has been suggested to interact with small molecules that inhibit VEGFR-2 expression and thereby tumor angiogenesis...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29666142/tumor-xenograft-modeling-identifies-tcf4-itf2-loss-associated-with-breast-cancer-chemoresistance
#6
Gorka Ruiz de Garibay, Francesca Mateo, Agostina Stradella, Rafael Valdés-Mas, Luis Palomero, Jordi Serra-Musach, Diana A Puente, Ander Díaz-Navarro, Gardenia Vargas-Parra, Eva Tornero, Idoia Morilla, Lourdes Farré, María Martinez-Iniesta, Carmen Herranz, Emmet McCormack, August Vidal, Anna Petit, Teresa Soler, Conxi Lázaro, Xose S Puente, Alberto Villanueva, Miguel Angel Pujana
Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify loss of transcription factor 4 (TCF4) associated with this process. A triple-negative BRCA1 -mutated PDX was used to study the genetics of chemoresistance...
April 13, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29665942/-research-progress-of-histone-modification-in-b-cell-lymphoma-pathogenesis-review
#7
Jiao Zhang, Yun Pan, Yan Li
It has been increasingly recognized that the pathogenesis of B-cell lymphoma closely relates to the epigenetic disregulations. Epigenetics is a subdiscipline, which means heritable changes in gene expressions without alterations in the DNA sequence, and the DNA methylation, histone modification and miRNA maily were involved. Histone modification is the most important epigenetic modification, the researches showed that the aberrant histone modification is the important pathogenesis in B-cell lymphoma, especially the aberrant histone methylation and acetylation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665853/microsatellite-instability-in-prostate-cancer-by-pcr-or-next-generation-sequencing
#8
Jennifer A Hempelmann, Christina M Lockwood, Eric Q Konnick, Michael T Schweizer, Emmanuel S Antonarakis, Tamara L Lotan, Bruce Montgomery, Peter S Nelson, Nola Klemfuss, Stephen J Salipante, Colin C Pritchard
BACKGROUND: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer. METHODS: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (> 60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system...
April 17, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29665790/the-oncogenic-effects-of-hes1-on-salivary-adenoid-cystic-carcinoma-cell-growth-and-metastasis
#9
Xiao-Yu Huang, Rui-Huan Gan, Jian Xie, Lin She, Yong Zhao, Lin-Can Ding, Bo-Hua Su, Da-Li Zheng, You-Guang Lu
BACKGROUND: Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC. METHODS: Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples...
April 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29665370/conservation-and-polymorphism-of-ebv-rpms1-gene-in-ebv-associated-tumors-and-healthy-individuals-from-endemic-and-non-endemic-nasopharyngeal-carcinoma-areas-in-china
#10
Shuo Wu, Wen Liu, Hong Li, Zhenzhen Zhao, Yang Yang, Hua Xiao, Yingying Song, Bing Luo
As a member of the BamHI-A rightward transcripts family of the Epstein-Barr virus (EBV), RPMS1 expression has been confirmed in all EBV-associated tumors. However, few studies have investigated the single-nucleotide polymorphisms (SNPs) of RPMS1, and only one SNP site (g155391a) has been reported to be associated with nasopharyngeal carcinoma occurrence. The objective of this study was to investigate the polymorphism of RPMS1 in EBV-associated tumors (gastric carcinoma, nasopharyngeal carcinoma, and lymphoma)...
April 14, 2018: Virus Research
https://www.readbyqxmd.com/read/29665239/fbxw7-regulates-a-mitochondrial-transcription-program-by-modulating-mitf
#11
Franco Abbate, Brateil Badal, Karen Mendelson, Iraz Toprak Aydin, Madhavika N Serasinghe, Ramiz Iqbal, Jarvier Mohammed, Alexander Solovyov, Benjamin D Greenbaum, Jerry E Chipuk, Julide Tok Celebi
FBXW7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor suppressive function have not been fully elucidated. We leveraged two distinct RNA sequencing datasets: human melanoma cell lines (n=10) with control versus silenced FBXW7 and a cohort of human melanoma tumor samples (n=51) in order to define the transcriptomic fingerprint regulated by FBXW7. Here, we report that loss of FBXW7 enhances a mitochondrial gene transcriptional program that is dependent on MITF in human melanoma and confers poor patient outcomes...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29663419/accelerated-3d-bssfp-imaging-for-treatment-planning-on-an-mri-guided-radiotherapy-system
#12
Yu Gao, Ziwu Zhou, Fei Han, Minsong Cao, Narek Shaverdian, John V Hegde, Biraj B Bista, Michael Steinberg, Percy Lee, Ann Raldow, Daniel A Low, Yingli Yang, Peng Hu
PURPOSE: To introduce a compressed sensing and parallel imaging combined technique to reduce the acquisition time of planning MRI for MR-guided radiotherapy (MRgRT) systems. METHODS AND MATERIALS: A variable-density Poisson-Disk (VDPD) under-sampling acquisition along with compressed sensing reconstruction technique was developed and compared with the current planning MR protocol, which uses an optimized balanced-steady-state-free-precession sequence with 7.5-fold (7...
April 16, 2018: Medical Physics
https://www.readbyqxmd.com/read/29662633/tracking-cellular-and-molecular-changes-in-a-species-specific-manner-during-experimental-tumor-progression-in-vivo
#13
Emilie Indersie, Katarzyna B Hooks, Caroline Capdevielle, Monique Fabre, Nathalie Dugot-Senant, Angélique Desplat, Sébastien Lepreux, Aksam Merched, Christophe F Grosset, Martin Hagedorn
Hepatoblastoma (HBL) is a pediatric liver cancer with defined molecular alterations driving its progression. Here, we describe an animal model for HBL on the chick chorioallantoic membrane (CAM), which recapitulates relevant features of HBL in patients. Expression of classic tumor-associated proteins such as β-catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as was synthesis of AFP, a tumor marker used for monitoring patient response. RNA sequencing revealed an unexpected molecular evolution of HBL cells on the CAM, with significant deregulation of more than 6,000 genes including more than half of all HOX genes...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662615/transcriptome-and-proteome-profiling-reveals-stress-induced-expression-signatures-of-imiquimod-treated-tasmanian-devil-facial-tumor-disease-dftd-cells
#14
Amanda L Patchett, Richard Wilson, Jac C Charlesworth, Lynn M Corcoran, Anthony T Papenfuss, Bruce A Lyons, Gregory M Woods, Cesar Tovar
As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro , but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil ( Sarcophilus harrisii ), are sensitive to imiquimod-induced apoptosis...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662195/ngr-asn-gly-arg-targeted-delivery-of-coagulase-to-tumor-vasculature-arrests-cancer-cell-growth
#15
Khaled Seidi, Rana Jahanban-Esfahlan, Hassan Monhemi, Peyman Zare, Babak Minofar, Amir Daei Farshchi Adli, Davoud Farajzadeh, Ramezan Behzadi, Mehran Mesgari Abbasi, Heidi A Neubauer, Richard Moriggl, Nosratollah Zarghami, Tahereh Javaheri
Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Here we took advantage of the unique coagulation properties of staphylocoagulase and genetically engineered it to generate a new fusion protein with novel anti-cancer properties. This novel bi-functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA) motif that recognizes CD13 and αv β3 integrin receptors, targeting it to tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to an NGR sequence retained its normal binding activity with prothrombin and av β3 integrins, as confirmed in silico and in vitro...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29661850/distinct-3-utrs-regulate-the-life-cycle-specific-expression-of-two-tctp-paralogs-in-trypanosoma-brucei
#16
Borka Jojic, Simona Amodeo, Irina Bregy, Torsten Ochsenreiter
The translationally controlled tumor protein (TCTP) is highly conserved and ubiquitously expressed in eukaryotes. It is involved in growth and development, cell cycle progression, protection against cellular stresses and apoptosis, indicating the multifunctional role of the protein. Here, for the first time we characterize the expression and function of TCTP in the human and animal pathogen, Trypanosoma brucei We identified two paralogs ( TCTP1 and TCTP2 ) that are differentially expressed in the life cycle of the parasite...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29661793/cell-free-plasma-dna-for-disease-stratification-and-prognosis-in-head-and-neck-cancer
#17
Markus A Schirmer, Julia Beck, Martin Leu, Michael Oellerich, Margret Rave-Fränk, Philip D Walson, Ekkehard Schütz, Martin Canis
BACKGROUND: Clinicians face many challenges in disease stratification and outcome prediction in head and neck squamous cancer cell (HNSCC) patients. Given the limitations of currently used clinical scoring, repetitive biopsies, and imaging techniques, liquid biopsy approaches may provide valuable additional diagnostic and prognostic information. METHODS: A noninterventional, single-center observational study was performed with clinical data and plasma samples from HNSCC patients...
April 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29661777/interferon-stimulated-genes-are-involved-in-cross-resistance-to-radiotherapy-in-tamoxifen-resistant-breast-cancer
#18
Annemarie E M Post, Marcel Smid, Anika Nagelkerke, John W M Martens, Johan Bussink, Fred Cjg Sweep, Paul N Span
PURPOSE: Treatment resistance is a main cause of adverse disease outcome in breast cancer patients. Here we aimed to investigate common features in tamoxifen-resistant and radioresistant breast cancer, since tamoxifen-resistant breast cancer cells are cross-resistant to irradiation in vitro. EXPERIMENTAL DESIGN: RNA sequencing of tamoxifen-resistant and radioresistant breast cancer cells was performed and validated by quantitative PCR. Pathways were further investigated in vitro and in breast cancer patient cohorts to establish their relation with treatment resistance...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#19
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661726/detection-of-synchronous-primary-lung-adenocarcinomas-with-genomic-sequencing
#20
Debra Berry, Mani Mahadevan, Mark R Wick
In the setting of synchronous pulmonary carcinomas, distinguishing between a monoclonal process with intrapulmonary metastasis and two independent tumors has significant therapeutic and prognostic implications. We describe two cases in which molecular profiling was used to characterize synchronous, primary pulmonary tumors and guide clinical management. In both cases, the patients underwent surgical resection without adjuvant chemotherapy or radiation and remain free of disease.
January 11, 2018: Annals of Diagnostic Pathology
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