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https://www.readbyqxmd.com/read/29777957/dual-ph-reduction-responsive-hybrid-polymeric-micelles-for-targeted-chemo-photothermal-combination-therapy
#1
Linhua Zhang, Yu Qin, Zhiming Zhang, Fan Fan, Chenlu Huang, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Deling Kong, Chun Wang, Hongfan Sun, Xigang Leng, Dunwan Zhu
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation...
May 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29777586/platelets-autotaxin-and-lysophosphatidic-acid-signaling-win-win-factors-for-cancer-metastasis
#2
REVIEW
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#3
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29776293/analysis-of-circulating-tumor-dna-the-next-paradigm-shift-in-detection-and-treatment-of-lung-cancer
#4
EDITORIAL
David S Schrump, Julie A Hong
No abstract text is available yet for this article.
June 2018: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29775808/phase-ii-study-of-maintenance-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-sclc
#5
Shirish M Gadgeel, Nathan A Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P Kalemkerian
PURPOSE: To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. PATIENTS AND METHODS: Extensive-stage SCLC patients with a response or stable disease following induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg IV every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary endpoint...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775625/reduction-sensitive-polymeric-nanomedicines-an-emerging-multifunctional-platform-for-targeted-cancer-therapy
#6
Huanli Sun, Yifan Zhang, Zhiyuan Zhong
The development of smart delivery systems that are robust in circulation and quickly release drugs following selective internalization into target cancer cells is a key to precision cancer therapy. Interestingly, reduction-sensitive polymeric nanomedicines showing high plasma stability and triggered cytoplasmic drug release behavior have recently emerged as one of the most exciting platforms for targeted delivery of various anticancer drugs including small chemical drugs, proteins, and nucleic acids. In vivo studies in varying tumor models reveal that these reduction-sensitive multifunctional nanomedicines outperform the currently used clinical formulations and reduction-insensitive counterparts, bringing about not only significantly enhanced tumor selectivity, accumulation and inhibition efficacy but also markedly reduced systemic toxicity and improved therapeutic index...
May 15, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29775621/methylation-of-nbpf1-as-a-novel-marker-for-the-detection-of-plasma-cell-free-dna-of-breast-cancer-patients
#7
REVIEW
Dandan Li, Pengchang Li, Jie Yi, Yaling Dou, Xiuzhi Guo, Yicong Yin, Danchen Wang, Chaochao Ma, Jie Wu, Ling Qiu
BACKGROUND: Recent studies revealed that tumor-specific gene methylation can be detected in the circulating cell-free DNA (cfDNA) of cancer patients; therefore, methylated cfDNA is considered a promising biomarker. Human neuroblastoma breakpoint family member 1 (NBPF1) was originally identified in a neuroblastoma (NB) patient. The present study is the first to evaluate the presence of NBPF1 gene methylation in cell-free DNA (cfDNA) in plasma of breast cancer patients. METHODS: Differentially methylated cfDNA was screened using bisulfite sequencing with a next-generation sequencer (BS-seq) among 25 breast cancer patients, 25 patients with a benign breast disease and 25 healthy female volunteers...
May 15, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29775614/tumor-dependent-secretion-of-close-homolog-of-l1-results-in-elevation-of-its-circulating-level-in-mouse-model-for-human-lung-tumor
#8
Norihiro Kotani, Yui Ida, Takanari Nakano, Izumi Sato, Ryusuke Kuwahara, Arisa Yamaguchi, Masahiro Tomita, Koichi Honke, Takayuki Murakoshi
Close homolog of L1 (CHL1) and its truncated form mainly play crucial roles in mouse brain development and neural functions. Herein, we newly identified that truncated form of CHL1 is produced and released from lung tumor tissue in a mouse model expressing human EML4-ALK fusion gene. Both western blot and direct ELISA analysis revealed that mouse CHL1 level in serum (including serum extracellular vesicles) was significantly elevated in EML4-ALK transgenic mice. The correlation between the tumor size and the amount of CHL1 secretion could be examined in this study, and showed a significant positive correlation in a tumor size-dependent manner...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775284/multifunctional-tumor-targeting-cathepsin-b-sensitive-gemcitabine-prodrug-covalently-targets-albumin-in-situ-and-improves-cancer-therapy
#9
Huicong Zhang, Zhisu Sun, Kuanglei Wang, Na Li, Hongxiang Chen, Xiao Tan, Lingxiao Li, Zhonggui He, Jin Sun
We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting and site-specific drug release are achieved and such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.
May 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29775157/blood-based-biomarkers-in-breast-cancer-from-proteins-to-circulating-tumor-cells-to-circulating-tumor-dna
#10
Michael J Duffy, Enda W McDermott, John Crown
Biomarkers are the key to personalized treatment in patients with breast cancer. While tissue biomarkers are most useful in determining prognosis and upfront predicting response to therapy, circulating protein biomarkers such as CA 15-3 and carcinoembryonic antigen are mainly used in monitoring response to endocrine or chemotherapy in patients with advanced disease. Although several centers measure biomarkers in asymptomatic patients following curative surgery for primary breast cancer, the clinical utility of this practice is unclear...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29774608/virion-like-membrane-breaking-nanoparticles-with-tumor-activated-cell-and-tissue-dual-penetration-conquer-impermeable-cancer
#11
Xiao Zhang, Xianghui Xu, Yachao Li, Cheng Hu, Zhijun Zhang, Zhongwei Gu
Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion-like membrane-breaking nanoparticles (MBNs) to smoothly accomplish tumor-activated cell-and-tissue dual-penetration for surmounting impermeable drug-resistant cancer. Tailor-made dendritic arginine-rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self-assemble into virion-like nanoparticles in aqueous solution, having highly ordered secondary structure...
May 17, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29774603/programmed-nanoparticle-loaded-nanoparticles-for-deep-penetrating-3d-cancer-therapy
#12
Jinhwan Kim, Changshin Jo, Won-Gwang Lim, Sungjin Jung, Yeong Mi Lee, Jun Lim, Haeshin Lee, Jinwoo Lee, Won Jong Kim
Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting "nanoparticle-loaded nanoparticles" to address the long-lasting problem is reported for effective surface-to-core drug delivery in entire 3D tumors...
May 18, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29773101/-microvesicles-derived-from-lps-induced-microglia-aggravate-the-injury-of-tight-junction-in-rat-brain-microvascular-endothelial-cells-under-oxygen-glucose-deprivation
#13
Yanni Lyu, Longsheng Fu, Yanming Li, Jinhua Wen, Xiaohua Wei, Yisong Qian
Objective To study the effect of the administration of the circulating microvesicles (MV) obtained from lipopolysaccharide (LPS)-stimulated microglia supernatant into rat brain endothelial cells (RBECs) on the injury of tight junction in RBECs under the condition of oxygen-glucose deprivation (OGD) as well as the underlying mechanism. Methods The circulating MV was isolated from the supernatant of microglia stimulated with LPS 1 mg/L for 24 hours and subjected to morphological identification. The expression of miR-27a in MV was detected by real-time PCR...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29772843/the-role-of-trp-channels-in-the-metastatic-cascade
#14
REVIEW
Benedikt Fels, Etmar Bulk, Zoltán Pethő, Albrecht Schwab
A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues...
May 17, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29770688/frosted-slides-decorated-with-silica-nanowires-for-detecting-circulating-tumor-cells-from-prostate-cancer-patients
#15
Haijun Cui, Binshuai Wang, Wenshuo Wang, Yuwei Hao, Chuanyong Liu, Kai Song, Shudong Zhang, Shutao Wang
Developing low-cost and highly efficient nano-biochips are important for liquid biopsies, real-time monitoring, and precision medicine. By in situ growth of silica nanowires on a commercial frosted slide, we develop a biochip for effective circulating tumor cells (CTCs) detection after modifying epithelial cell adhesion molecule antibody (anti-EpCAM). The biochip shows the specificity and high capture efficiency of 85.4 ± 8.3% for prostate cancer cell line (PC-3). The micro-sized frosted slides and silica nanowires allow enhanced efficiency in capture EpCAM positive cells by synergistic topographic interactions...
May 17, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29769179/rna-profiles-of-circulating-tumor-cells-and-extracellular-vesicles-for-therapy-stratification-of-metastatic-breast-cancer-patients
#16
Corinna Keup, Pawel Mach, Bahriye Aktas, Mitra Tewes, Hans-Christian Kolberg, Siegfried Hauch, Markus Sprenger-Haussels, Rainer Kimmig, Sabine Kasimir-Bauer
BACKGROUND: Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS: Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points...
May 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29768879/a-novel-assay-coupling-dephosphorylation-and-blue-white-colony-screening-for-the-g-a-hotspot-mutation-at-codon-13-of-kras-gene
#17
Cuilan Zhou, Wangyang Pu, Yu-Fang Yin, Li Xiao, Dixian Luo, Fenjiao Wang, Cuiying Peng, Zifen Guo, Xuan Liu, Huifen Xu, Chungen Xing, Nongyue He, Wanping Sun, Weijun Cai, Duanfang Liao, Kai Li
Development of sensitive assay for detection of hotspot mutations of cancer driving gene is crucial for circulating tumor DNA analysis. This study tested the possibilities of applying restriction enzyme digestion and dephosphorylation coupled with blue/white screening technology for analyzing a hotspot point mutation in codon 13 of KRAS gene. The present study has documented that the combination of PCR with restriction digestion, dephosphorylation, blue/white screening and Sanger's sequencing can identify rare mutations with sensitivities at 0...
January 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29768008/striking-a-balance-between-carbonate-carbamate-linkage-bond-and-reduction-sensitive-disulfide-bond-bearing-linker-for-tailored-controlled-release-in-situ-covalently-albumin-binding-gemcitabine-prodrugs-promote-bioavailability-and-tumor-accumulation
#18
Huicong Zhang, Kuanglei Wang, Kexin Na, Dan Li, Zhenbao Li, Dongyang Zhao, Lu Zhong, Menglin Wang, Longfa Kou, Cong Luo, Haotian Zhang, Qiming Kan, Huaiwei Ding, Zhonggui He, Jin Sun
To address the challenge of rapid enzyme inactivation, poor tumor targeting, acquired drug resistance in gemcitabine (GEM) application, we report two groups of maleimide-functionalised GEM prodrugs conjugating covalently in situ with cys-34 of blood-circulating albumin, resulting in macromolecular prodrugs after intravenous administration. Specially, tailored and accurate controlled release was achieved through different combinations of linkage bonds relatively stable and labile (carbamate and carbonate, respectively) and linkers with or without insertion of a disulfide bond...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767422/reduction-triggered-transformation-of-crosslinking-modules-of-disulfide-containing-micelles-with-chemically-tunable-rates
#19
Zhengyu Deng, Shuai Yuan, Ronald X Xu, Haojun Liang, Shiyong Liu
A dilemma exists between the circulation stability and cargo release/mass diffusion at desired sites for designing delivery nanocarriers and in vivo nanoreactors. We herein report disulfide-crosslinked (DCL) micelles exhibiting reduction-triggered switching of crosslinking modules and synchronized hydrophobic-to-hydrophilic transition. Tumor cell-targeted DCL micelles undergo cytoplasmic milieu-triggered disulfide cleavage and cascade self-immolative decaging reactions at chemically adjustable rates, generating primary amine moieties...
May 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29766637/subtype-specific-clinical-and-prognostic-relevance-of-tumor-expressed-f5-and-regulatory-f5-variants-in-breast-cancer-the-cocav-study
#20
Mari Tinholt, Øystein Garred, Elin Borgen, Elsa Beraki, Ellen Schlichting, Vessela Kristensen, Kristine Kleivi Sahlberg, Nina Iversen
BACKGROUND: Tumor expression of certain coagulation factors have been linked to cancer progression. Single nucleotide polymorphisms (SNPs) in F5 (encoding the FV protein) have been found associated with breast cancer, however, the role of coagulation factor V (FV) in cancer pathogenesis remains undiscovered. OBJECTIVES: We aimed to investigate the clinical significance of FV and the regulatory role of F5 gene variants in breast cancer. PATIENTS/METHODS: A Scandinavian 503-sample breast cancer cohort and three public breast cancer data sets (GOBO, TCGA, and KM plotter) were used to determine associations between F5 gene expression (tumor-specific), circulating FV, F5 SNPs, clinical characteristics, and breast cancer survival...
May 16, 2018: Journal of Thrombosis and Haemostasis: JTH
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