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https://www.readbyqxmd.com/read/29460642/novel-targeted-therapy-strategies-for-biliary-tract-cancers-and-hepatocellular-carcinoma
#1
Thomas T DeLeon, Daniel H Ahn, James M Bogenberger, Panos Z Anastasiadis, Mansi Arora, Ramesh K Ramanathan, Bashar A Aqel, George Vasmatzis, Mark J Truty, Rahmi Oklu, Tanios S Bekaii-Saab, Mitesh J Borad
Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement...
February 20, 2018: Future Oncology
https://www.readbyqxmd.com/read/29458881/prenatal-diagnosis-of-short-rib-polydactyly-syndrome-type-iii-or-short-rib-thoracic-dysplasia-3-with-or-without-polydactyly-srtd3-associated-with-compound-heterozygous-mutations-in-dync2h1-in-a-fetus
#2
Chih-Ping Chen, Tsang-Ming Ko, Tung-Yao Chang, Schu-Rern Chern, Shin-Wen Chen, Shih-Ting Lai, Tzu-Yun Chuang, Wayseen Wang
OBJECTIVE: We present the perinatal imaging findings and molecular genetic analysis in a fetus with short-rib polydactyly syndrome (SRPS) type III or short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3). CASE REPORT: A 29-year-old, primigravid woman was referred for genetic counseling at 15 weeks of gestation because of abnormal ultrasound findings of short limbs, a narrow chest and bilateral polydactyly of the hands and feet, consistent with a diagnosis of SRPS type III...
February 2018: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29446487/tm2d3-rs675436-or-fgfr2-rs755793-polymorphisms-and-susceptibility-to-epstein-barr-virus-associated-tumors-in-chinese-han-population
#3
Qianqian Zhang, Wen Liu, Yang Yang, Zhenzhen Zhao, Bing Luo
BACKGROUND: Epstein-Barr virus (EBV) is etiologically linked to nasopharyngeal carcinoma, lymphoma and gastric carcinoma. The aim of this study was to assess the association of TM2 domain containing 3 (TM2D3) and fibroblast growth factor receptor 2 (FGFR2) SNPs rs675436 and rs755793 with susceptibility to EBV-associated tumors in Chinese Han population. MATERIALS AND METHODS: Genomic DNA of 415 patients with cancer and 99 healthy controls was assessed using a MALDI-TOF mass spectrometer, and was genotyped in EBV-associated/-negative gastric cancer (EBVa/nGC), EBV-associated/-negative nasopharyngeal carcinoma (EBVa/nNPC), EBV-associated/ -negative lymphoma (EBVa/nL) and normal controls (NC)...
February 15, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29444487/paracrine-fibroblast-growth-factor-initiates-oncogenic-synergy-with-epithelial-fgfr-src-transformation-in-prostate-tumor-progression
#4
Qianjin Li, Lishann Ingram, Sungjin Kim, Zanna Beharry, Jonathan A Cooper, Houjian Cai
Cross talk of stromal-epithelial cells plays an essential role in both normal development and tumor initiation and progression. Fibroblast growth factor (FGF)-FGF receptor (FGFR)-Src kinase axis is one of the major signal transduction pathways to mediate this cross talk. Numerous genomic studies have demonstrated that expression levels of FGFR/Src are deregulated in a variety of cancers including prostate cancer; however, the role that paracrine FGF (from stromal cells) plays in dysregulated expression of epithelial FGFRs/Src and tumor progression in vivo is not well evaluated...
February 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29436723/variable-prenatal-presentation-of-pfeiffer-syndrome-suggested-aids-to-prenatal-sonographic-diagnosis
#5
Souha Saliba, Baptiste Morel, Marie Gonzales, Marie-Victoire Sénat, Lucie Guilbaud, Jean-Marie Jouannic, Marie Cassart, Catherine Garel, Eléonore Blondiaux
BACKGROUND: Our purpose was to describe and compare the cranial and extracranial abnormalities of Pfeiffer syndrome on prenatal imaging with postnatal or postmortem findings, which may help in prenatal diagnosis of Pfeiffer syndrome (PS). METHODS: Cases of fetuses with a confirmed diagnosis of PS over a 4-year period (2012-2016) were retrospectively reviewed. Prenatal imaging findings, postnatal or postmortem investigations and genetic test results were analyzed...
February 13, 2018: Prenatal Diagnosis
https://www.readbyqxmd.com/read/29434882/prognostic-relevance-of-fgfr2-expression-in-stage-ii-iii-gastric-cancer-with-curative-resection-and-s-1-chemotherapy
#6
Kei Hosoda, Keishi Yamashita, Hideki Ushiku, Akira Ema, Hiromitsu Moriya, Hiroaki Mieno, Marie Washio, Masahiko Watanabe
Curative gastrectomy and adjuvant chemotherapy using S-1 is a standard treatment for stage II/III gastric cancer in Japan. The purpose of the present study was to evaluate the prognostic relevance of fibroblast growth factor receptor (FGFR)2 expression in patients with stage II/III gastric cancer that underwent postoperative adjuvant chemotherapy with S-1. Formalin-fixed paraffin-embedded surgical specimens were retrospectively examined in 167 patients with stage II/III gastric cancer that underwent curative gastrectomy followed by adjuvant S1 chemotherapy...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29423271/dual-roles-of-endothelial-fgf-2-fgfr1-pdgf-bb-and-perivascular-fgf-2-fgfr2-pdgfr%C3%AE-signaling-pathways-in-tumor-vascular-remodeling
#7
Kayoko Hosaka, Yunlong Yang, Masaki Nakamura, Patrik Andersson, Xiaojuan Yang, Yin Zhang, Takahiro Seki, Martin Scherzer, Olivier Dubey, Xinsheng Wang, Yihai Cao
Perivascular cells are important cellular components in the tumor microenvironment (TME) and they modulate vascular integrity, remodeling, stability, and functions. Here we show using mice models that FGF-2 is a potent pericyte-stimulating factor in tumors. Mechanistically, FGF-2 binds to FGFR2 to stimulate pericyte proliferation and orchestrates the PDGFRβ signaling for vascular recruitment. FGF-2 sensitizes the PDGFRβ signaling through increasing PDGFRβ levels in pericytes. To ensure activation of PDGFRβ, the FGF-2-FGFR1-siganling induces PDGF-BB and PDGF-DD, two ligands for PDGFRβ, in angiogenic endothelial cells...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29420662/generation-of-high-affinity-internalizing-anti-fgfr2-single-chain-variable-antibody-fragment-fused-with-fc-for-targeting-gastrointestinal-cancers
#8
Aleksandra Borek, Aleksandra Sokolowska-Wedzina, Grzegorz Chodaczek, Jacek Otlewski
Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2)...
2018: PloS One
https://www.readbyqxmd.com/read/29410024/dna-methylation-profiling-in-nonfunctioning-pituitary-adenomas
#9
Paulina Kober, Joanna Boresowicz, Nataliia Rusetska, Maria Maksymowicz, Krzysztof Goryca, Jacek Kunicki, Wiesław Bonicki, Janusz Aleksander Siedlecki, Mateusz Bujko
Nonfunctioning pituitary adenomas (NFPAs) are among the most frequent intracranial tumors but their molecular background, including changes in epigenetic regulation, remains poorly understood. We performed genome-wide DNA methylation profiling of 34 NFPAs and normal pituitary samples. Methylation status of the selected genomic regions and expression level of corresponding genes were assessed in a group of 75 patients. NFPAs exhibited distinct global methylation profile as compared to normal pituitary. Aberrant DNA methylation appears to contribute to deregulation of the cancer-related pathways as shown by preliminary functional analysis...
February 1, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29409051/impact-of-genomic-alterations-on-lapatinib-treatment-outcome-and-cell-free-genomic-landscape-during-her2-therapy-in-her2-positive-gastric-cancer-patients
#10
S T Kim, K C Banks, E Pectasides, S Y Kim, K Kim, R B Lanman, A Talasaz, J An, M G Choi, J H Lee, T S Sohn, J M Bae, S Kim, S H Park, J O Park, Y S Park, H Y Lim, N K D Kim, W Park, H Lee, A J Bass, K Kim, W K Kang, J Lee
Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and Methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer (AGC). A parallel biomarker study was conducted by simultaneously performing immunohistochemistry (IHC) and next-generation sequencing with tumor and blood samples...
February 2, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29408236/the-strength-of-mechanical-forces-determines-the-differentiation-of-alveolar-epithelial-cells
#11
Jiao Li, Zheng Wang, Qiqi Chu, Kewu Jiang, Juan Li, Nan Tang
The differentiation of alveolar epithelial type I (AT1) and type II (AT2) cells is essential for the lung gas exchange function. Disruption of this process results in neonatal death or in severe lung diseases that last into adulthood. We developed live imaging techniques to characterize the mechanisms that control alveolar epithelial cell differentiation. We discovered that mechanical forces generated from the inhalation of amniotic fluid by fetal breathing movements are essential for AT1 cell differentiation...
February 5, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29392781/activated-receptor-tyrosine-kinases-in-granulosa-cells-of-ovulating-follicles-in-mice
#12
Yasmin Schuermann, Dayananda Siddappa, Melissa Pansera, Raj Duggavathi
Successful ovulation requires the actions of gonadotropins along with those mediated by growth factors binding to their receptor tyrosine kinases (RTKs). There are several growth factors such as epidermal growth factor family ligands and interleukins that play a role during ovulation initiated by the preovulatory surge of luteinizing hormone (LH). The aim of this project was to analyze growth factor signaling pathways induced by LH in mouse granulosa cells. Immature female mice were treated with equine chorionic gonadotropin (eCG) followed 48h later by human chorionic gonadotropin (hCG) to induce follicular growth and ovulation...
February 2, 2018: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29392564/craniosynostosis-as-a-clinical-and-diagnostic-problem-molecular-pathology-and-genetic-counseling
#13
REVIEW
Anna Kutkowska-Kaźmierczak, Monika Gos, Ewa Obersztyn
Craniosynostosis (occurrence: 1/2500 live births) is a result of premature fusion of cranial sutures, leading to alterations of the pattern of cranial growth, resulting in abnormal shape of the head and dysmorphic facial features. In approximately 85% of cases, the disease is isolated and nonsyndromic and mainly involves only one suture. Syndromic craniosynostoses such as Crouzon, Apert, Pfeiffer, Muenke, and Saethre-Chotzen syndromes not only affect multiple sutures, but are also associated with the presence of additional clinical symptoms, including hand and feet malformations, skeletal and cardiac defects, developmental delay, and others...
February 1, 2018: Journal of Applied Genetics
https://www.readbyqxmd.com/read/29390357/association-between-rs11200014-rs2981579-and-rs1219648-polymorphism-and-breast-cancer-susceptibility-a-meta-analysis
#14
Yafei Zhang, Hongwei Lu, Hong Ji, Le Lu, Pengdi Liu, Ruofeng Hong, Yiming Li
BACKGROUND: Research on the polymorphism of breast cancer (BC) helps to search the BC susceptibility gene for mass screening, early diagnosis, and gene therapy, which has become a hotspot in BC research field. Previous studies have suggested associations between rs11200014, rs2981579, and rs1219648 polymorphisms and cancer risk. The aim of this study was to evaluate the relationship between rs11200014, rs2981579, and rs1219648 polymorphism and BC risk. METHODS: PubMed, Web of science, and the Cochrane Library databases were searched before October 11, 2015, to identify relevant studies...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29372690/association-of-single-nucleotide-polymorphisms-in-fgf-ras-map-signalling-cascade-with-breast-cancer-susceptibility
#15
Zuzana Dankova, Pavol Zubor, Marian Grendar, Andrea Kapinova, Katarina Zelinova, Mariana Jagelkova, Alexandra Gondova, Karol Dokus, Michal Kalman, Zora Lasabova, Jan Danko
The fibroblast growth factor receptors (FGFRs) and Ras/mitogen activated protein (RAS/MAP) signalling cascades are the main molecular pathways involved in breast carcinogenesis. This study aims to determine the association between FGF10 (rs4415084 C>T), FGFR2 (rs2981582 C>T) and MAP3K1 (rs889312 A>C) gene polymorphisms and breast cancer, to analyse the discriminative ability of each SNP and to test the accuracy of the predictive breast cancer risk model which includes all SNPs. We conducted a case-control study of 170 women (57...
December 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29356025/identification-and-therapeutic-intervention-of-co-activated-alk-fgfr2-and-epha5-kinases-in-hepatocellular-carcinoma
#16
Xin Wang, Minmin Zhang, Fangfang Ping, Hongchun Liu, Jingya Sun, Yueqin Wang, Aijun Shen, Jian Ding, Meiyu Geng
Though kinase inhibitors are heavily investigated in clinic to combat advanced hepatocellular carcinoma (HCC), clinical outcomes are overall disappointing, which may result from the absence of kinase-addicted subsets in HCC. Recently, a combination strategy that simultaneously inhibits multiple kinases are increasingly appreciated in HCC treatment, yet it is challenged by the dynamic nature of kinase network. This study aims to identify kinase clusters that may cooperate to drive the malignant growth of HCC...
January 21, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29352310/leishmania-proteophosphoglycans-regurgitated-from-infected-sand-flies-accelerate-dermal-wound-repair-and-exacerbate-leishmaniasis-via-insulin-like-growth-factor-1-dependent-signalling
#17
Emilie Giraud, Tereza Lěstinová, Tamsyn Derrick, Oihane Martin, Rod J Dillon, Petr Volf, Ingrid Műller, Paul A Bates, Matthew E Rogers
Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29344510/ablation-of-fgfr2-in-fibroblasts-ameliorates-kidney-fibrosis-after-ischemia-reperfusion-injury-in-mice
#18
Zhuo Xu, Chunsun Dai
Background: Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation. Methods: In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#19
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29316748/-preliminary-study-of-exon-sequence-in-pneumoconiosis-and-pneumoconiosis-complicated-with-lung-cancer-using-high-throughput-sequencing-technology
#20
M F Jiang, L Li, Z Wang, C L Zhang, H Zhang
Objective: The detection and analysis of exon mutations of pneumoconiosis and pneumoco-niosis complicated with lung cancer provide reference evidence for screening, clinical diagnosis and treatment and prognosis in pneumoconiosis and pneumoconiosis complicated with lung cancer. Methods: The pathologi-cal tissue samples from 3 pneumoconiosis patients and 3 pneumoconiosis complicated with lung cancer pa-tients were collected. Genomic DNA was extracted and library was prepared. Exomes of the pathological tissue samples in pneumoconiosis patients and pneumoconiosis complicated with lung cancer patients were se-quenced using Ion Torrent PGM platform...
November 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
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