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https://www.readbyqxmd.com/read/27911727/role-of-the-bone-morphogenic-protein-pathway-in-developmental-haemopoiesis-and-leukaemogenesis
#1
REVIEW
Parto Toofan, Helen Wheadon
Myeloid leukaemias share the common characteristics of being stem cell-derived clonal diseases, characterised by excessive proliferation of one or more myeloid lineage. Chronic myeloid leukaemia (CML) arises from a genetic alteration in a normal haemopoietic stem cell (HSC) giving rise to a leukaemic stem cell (LSC) within the bone marrow (BM) 'niche'. CML is characterised by the presence of the oncogenic tyrosine kinase fusion protein breakpoint cluster region-abelson murine leukaemia viral oncogene homolog 1 (BCR-ABL), which is responsible for driving the disease through activation of downstream signal transduction pathways...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27907819/giant-primary-malignant-mesothelioma-of-the-liver-a-case-report
#2
Ruba Haji Ali, Mohamad Khalife, Ghina El Nounou, Ruba Zuhri Yafi, Hussein Nassar, Zeinab Aidibe, Randa Raad, Rania Abou Eid, Walid Faraj
INTRODUCTION: Malignant mesothelioma is a rare neoplasm of mesothelial cells arising most frequently in the pleura or peritoneum and less frequently in the liver. CASE PRESENTATION: We present a case of primary hepatic mesothelioma of 41year old woman. She had no history of asbestos exposure or cancer. Abdominal computed tomography (CT) showed 21cm intrahepatic mass in the right lobe with many cystic lesions and few small calcifications. Pathology showed a biphasic cellular pattern...
November 11, 2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/27827359/vasculogenic-mimicry-in-small-cell-lung-cancer
#3
Stuart C Williamson, Robert L Metcalf, Francesca Trapani, Sumitra Mohan, Jenny Antonello, Benjamin Abbott, Hui Sun Leong, Christopher P E Chester, Nicole Simms, Radoslaw Polanski, Daisuke Nonaka, Lynsey Priest, Alberto Fusi, Fredrika Carlsson, Anders Carlsson, Mary J C Hendrix, Richard E B Seftor, Elisabeth A Seftor, Dominic G Rothwell, Andrew Hughes, James Hicks, Crispin Miller, Peter Kuhn, Ged Brady, Kathryn L Simpson, Fiona H Blackhall, Caroline Dive
Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27814611/targeted-drugs-and-diagnostic-assays-companions-in-the-race-to-combat-ethnic-disparity
#4
Nikita Wright, Padmashree Rida, Uma Krishnamurti, Xiaoxian Li, Ritu Aneja
African Americans (AAs) are more likely than European Americans to develop aggressive breast cancer subtypes, and have higher recurrence and mortality rates; this results in a stark breast-cancer related ethnic disparity in clinical outcomes. In this era of personalized oncology, companion diagnostics (CDx) are transforming the cancer treatment narrative slowly but steadily, by enabling the use of safety and/or efficacy biomarkers to stratify patient populations, and thus ensuring more effective deployment of targeted therapeutics...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27797175/liposome-based-systemic-glioma-targeted-drug-delivery-enabled-by-all-d-peptides
#5
Man Ying, Changyou Zhan, Songli Wang, Bingxin Yao, Xuefeng Hu, Xianfei Song, Mingfei Zhang, Xiaoli Wei, Yan Xiong, Weiyue Lu
As the most aggressive brain tumor, chemotherapy of malignant glioma remains to be extremely challenging in clinic. The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) are physiological and pathological barriers preventing therapeutic drugs from reaching the glioma region. In addition, vasculogenic mimicry (VM) formed by invasive glioma cells instead of endothelial cells and angiogenesis are very common in glioma, leading to the poor prognosis and recurrence of glioma. An ideal drug delivery system for glioma chemotherapy needs to traverse the BBB and BBTB and then target VM, angiogenesis, and glioma cells...
October 31, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27789023/the-evolution-of-oncology-companion-diagnostics-from-signal-transduction-to-immuno-oncology
#6
REVIEW
Nicholas C Dracopoli, Mark S Boguski
Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II...
October 24, 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27753661/pulmonary-adenocarcinoma-with-enteric-differentiation-immunohistochemistry-and-molecular-morphology
#7
Alessia Nottegar, Fabrizio Tabbò, Claudio Luchini, Matteo Brunelli, Emilio Bria, Nicola Veronese, Antonio Santo, Sara Cingarlini, Eliana Gilioli, Chiara Ogliosi, Albino Eccher, Licia Montagna, Serena Pedron, Claudio Doglioni, Maria G Cangi, Giorgio Inghirami, Marco Chilosi
Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27671527/development-of-a-novel-antibody-drug-conjugate-for-the-potential-treatment-of-ovarian-lung-and-renal-cell-carcinoma-expressing-tim-1
#8
Lawrence J Thomas, Laura Vitale, Thomas O'Neill, Ree Y Dolnick, Paul K Wallace, Hans Minderman, Lauren E Gergel, Eric M Forsberg, James M Boyer, James R Storey, Catherine D Pilsmaker, Russell A Hammond, Jenifer Widger, Karuna Sundarapandiyan, Andrea Crocker, Henry C Marsh, Tibor Keler
T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27661101/the-new-eu-regulation-on-in-vitro-diagnostics-potential-issues-at-the-interface-of-medicines-and-companion-diagnostics
#9
Harald Enzmann, Ralf Meyer, Karl Broich
The new European regulation for in vitro diagnostics (IVD) divides the certification of IVD including companion diagnostics (CDx) by notified bodies (NB) from the market authorization of medicines. With the new regulation, CDx will require conformity assessment which is expected to include clinical evidence by NB. This is a significant change from the current situation: until now most IVD have been certified based on their manufacturers' assessment. For one medicine assessed by the EMA, certification of several different CDx by different NB is possible...
September 23, 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27649095/statistical-evaluation-of-drug-efficacy-for-bridging-study-in-companion-diagnostic-test-trials
#10
Yunqi Bu, Xiao-Hua Zhou
Personalized medicine is an area of growing attention in medical research and practice. A market-ready companion diagnostic test (CDx) is used in personalized medicine for identifying the best treatment for an individual patient. Unfortunately, development of CDx may lag behind the development of the drug, and consequently we use a clinical trial assay (CTA) to enroll patients into the drug pivotal clinical trial instead. Thus, when CDx becomes available, a bridging study will be required to assess the drug efficacy in the CDx intended use (CDx IU) population...
September 20, 2016: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/27629260/metastatic-signet-ring-cell-carcinoma-of-the-bladder-in-cerebrospinal-fluid
#11
Diana Murro Lin, Ji-Weon Park, Paolo Gattuso
Primary bladder signet-ring cell carcinoma (SRCC) is extremely rare and associated with an aggressive course. To our knowledge, we describe the first metastatic bladder SRCC identified in cerebrospinal fluid (CSF). A 68-year-old male with 1 year history of primary bladder SRCC with spinal metastasis presented with multiple falls and loss of consciousness. Brain imaging showed high signal in the frontoparietal sulci and superior cerebellum. CSF analysis was significant for increased leukocytes with monocyte predominance while protein and glucose values were within normal range...
September 15, 2016: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/27583877/urachal-adenocarcinoma-that-metastasized-to-breast-was-misinterpreted-as-primary-breast-mucinous-carcinoma-a-rare-case-report-and-literature-review
#12
Xiang-Rong Zhao, Chao Gao, Yong Zhang, Lei Kong, Wei Qu, Jia Li, Yong-Sheng Gao, Yong-Hua Yu
BACKGROUND: The urachus is a vestigial tubular structure that connects the urinary bladder to the allantois during early embryonic development. Urachal carcinoma develops in the urachus, which is an embryological remnant of the urogenital sinus and allantois. The estimated annual incidence of urachal carcinoma in the general population is 0.01% of all cancers in adults. Moreover, urachal carcinoma accounts for 0.34% to 0.7% of all bladder carcinoma cases. And breast metastasis is extremely rarer...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27565907/validation-of-a-new-algorithm-for-a-quick-and-easy-rt-pcr-based-alk-test-in-a-large-series-of-lung-adenocarcinomas-comparison-with-fish-immunohistochemistry-and-next-generation-sequencing-assays
#13
Antonio Marchetti, Maria Vittoria Pace, Alessia Di Lorito, Sara Canarecci, Lara Felicioni, Tommaso D'Antuono, Marcella Liberatore, Giampaolo Filice, Luigi Guetti, Felice Mucilli, Fiamma Buttitta
OBJECTIVES: Anaplastic Lymphoma Kinase (ALK) gene rearrangements have been described in 3-5% of lung adenocarcinomas (ADC) and their identification is essential to select patients for treatment with ALK tyrosine kinase inhibitors. For several years, fluorescent in situ hybridization (FISH) has been considered as the only validated diagnostic assay. Currently, alternative methods are commercially available as diagnostic tests. MATERIAL AND METHODS: A series of 217 ADC comprising 196 consecutive resected tumors and 21 ALK FISH-positive cases from an independent series of 702 ADC were investigated...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27515385/absorption-enhancement-in-giant-core-alloyed-shell-quantum-dots-for-luminescent-solar-concentrator
#14
Haiguang Zhao, Daniele Benetti, Lei Jin, Yufeng Zhou, Federico Rosei, Alberto Vomiero
Luminescent solar concentrators (LSCs) can potentially reduce the cost of solar cells by decreasing the photoactive area of the device and boosting the photoconversion efficiency (PCE). This study demonstrates the application of "giant" CdSe/Cdx Pb1-x S core/shell quantum dots (QDs) as light harvesters in high performance LSCs with over 1.15% PCE. Pb addition is critical to maximize PCE. First, this study synthesizes "giant" CdSe/Cdx Pb1-x S QDs with high quantum yield (40%), narrow size distribution (<10%), and stable photoluminescence in a wide temperature range (100-300 K)...
October 2016: Small
https://www.readbyqxmd.com/read/27515299/mapk-pathway-inhibitors-sensitize-braf-mutant-melanoma-to-an-antibody-drug-conjugate-targeting-gpnmb
#15
April A N Rose, Matthew G Annis, Dennie T Frederick, Marco Biondini, Zhifeng Dong, Lawrence N Kwong, Lynda Chin, Tibor Keler, Thomas Hawthorne, Ian R Watson, Keith T Flaherty, Peter M Siegel
PURPOSE: To determine if BRAF and/or MEK inhibitor-induced GPNMB expression renders melanomas sensitive to CDX-011, an antibody-drug conjugate targeting GPNMB. EXPERIMENTAL DESIGN: The TCGA melanoma dataset was interrogated for a panel of MITF-regulated melanosomal differentiation antigens, including GPNMB. BRAF mutant melanoma cell lines treated with BRAF or MEK inhibitors were assessed for GPNMB expression by RT-qPCR, immunoblot and FACs analyses. Transient siRNA-mediated knockdown approaches were used to determine if MITF is requirement for treatment-induced GPNMB upregulation...
August 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27495736/inconsistent-results-in-the-analysis-of-alk-rearrangements-in-non-small-cell-lung-cancer
#16
Johanna S M Mattsson, Hans Brunnström, Verena Jabs, Karolina Edlund, Karin Jirström, Stephanie Mindus, Linnéa la Fleur, Fredrik Pontén, Mats G Karlsson, Christina Karlsson, Hirsh Koyi, Eva Brandén, Johan Botling, Gisela Helenius, Patrick Micke, Maria A Svensson
BACKGROUND: Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27470268/ubiquitin-ligase-fbw7-targets-cdx2-for-degradation-via-two-phosphodegron-motifs-in-a-gsk3beta-dependent-manner
#17
Yogesh Kumar, Nidhi Shukla, Gatha Thacker, Isha Kapoor, Savita Lochab, Madam Lal Brahma Bhatt, Naibedya Chattopadhyay, Sabyasachi Sanyal, Arun Kumar Trivedi
: Drosophila caudal-related homeobox transcription factor 2 (CDX2) drives differentiation of the intestinal epithelium. Loss of CDX2 expression has been reported in several colorectal cancers and cancer cell lines with a potential inverse correlation between CDX2 levels and tumor stage. Ubiquitination of CDX2 leading to its down-regulation has been implicated in several studies; however, the E3 ubiquitin ligases involved in CDX2 ubiquitination have largely remained unknown. Here, it is mechanistically determined that the E3 ubiquitin ligase Fbw7 promotes CDX2 ubiquitination and degradation through two phosphodegron motifs present within CDX2 in a GSK3beta-dependent manner leading to its reduced expression and function in colon cancer cells...
July 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27443976/on-the-synthesis-of-cyclodextrin-peptide-conjugates-by-the-huisgen-reaction
#18
Rémy Lartia, Christopher K Jankowski, Sébastien Arseneau
A,D-substituted cyclodextrin (CDX) substituted on their primary rim side are ideal scaffolds for the macromolecular assembly and formation of templated structures. Their substitution can be achieved through various reactions. However, the use of the well-known Huisgen reaction in this context is under-reported. We present here results of the synthesis of model conjugates formed between CDX and representative peptides by click chemistry. Notably, bis-conjugation of peptides onto a unique scaffold promotes α-helix formation...
August 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/27435453/associations-of-vitamin-d-deficiency-and-vitamin-d-receptor-cdx-2-fok-i-bsm-i-and-taq-i-polymorphisms-with-the-risk-of-primary-open-angle-glaucoma
#19
Yingjuan Lv, Qingbin Yao, Wenjiang Ma, Hua Liu, Jian Ji, Xiaorong Li
BACKGROUND: Vitamin D deficiency and vitamin D receptor gene polymorphisms are known to be significantly associated with high myopia. Whether this genetic variant may impact primary open-angle glaucoma is largely unknown. This study investigated whether vitamin D receptor gene polymorphisms are altered in primary open-angle glaucoma subjects carrying the risk allele, and whether vitamin D deficiency is an important factor in the development of glaucoma. METHODS: Seventy-three POAG patients and 71 age-matched controls from the Han population were enrolled...
2016: BMC Ophthalmology
https://www.readbyqxmd.com/read/27412703/plasma-membrane-cholesterol-level-and-agonist-induced-internalization-of-%C3%AE-opioid-receptors-colocalization-study-with-intracellular-membrane-markers-of-rab-family
#20
Jana Brejchova, Miroslava Vosahlikova, Lenka Roubalova, Marco Parenti, Mario Mauri, Oleksandr Chernyavskiy, Petr Svoboda
Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4)...
August 2016: Journal of Bioenergetics and Biomembranes
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