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https://www.readbyqxmd.com/read/28548843/zwitterionic-nanocarrier-surface-chemistry-improves-sirna-tumor-delivery-and-silencing-activity-relative-to-polyethylene-glycol
#1
Meredith A Jackson, Thomas A Werfel, Elizabeth J Curvino, Fang Yu, Taylor Elizabeth Kavanaugh, Samantha M Sarett, Mary D Dockery, Kameron V Kilchrist, Ayisha N Jackson, Todd D Giorgio, Craig L Duvall
Although siRNA-based nanomedicines hold promise for cancer treatment, conventional siRNA-polymer complex (polyplex) nanocarrier systems have poor pharmacokinetics following intravenous delivery, hindering tumor accumulation. Here, we determined the impact of surface chemistry on the in vivo pharmacokinetics and tumor delivery of siRNA polyplexes. A library of diblock polymers was synthesized, all containing the same pH-responsive, endosomolytic polyplex core-forming block but different corona blocks: 5 kDa (benchmark) and 20 kDa linear PEG, 10 kDa and 20 kDa brush-like poly(oligo ethylene glycol) (POEGMA), and 10 kDa and 20 kDa zwitterionic phosphorylcholine-based polymers (PMPC)...
May 26, 2017: ACS Nano
https://www.readbyqxmd.com/read/28548481/isolation-of-phenotypically-distinct-cancer-cells-using-nanoparticle-mediated-sorting
#2
Brenda Green, Leyla Kermanshah, Mahmoud Labib, Sharif Ahmed, Pamuditha Silva, Laili Mahmoudian, I-Hsin Chang, Reza M Mohamadi, Jonathan V Rocheleau, Shana O Kelley
Isolating subpopulations of heterogeneous cancer cells is an important capability for the meaningful characterization of circulating tumor cells at different stages of tumor progression and during epithelial to mesenchymal transition (EMT). Here, we describe a two-dimensional separation approach that yields phenotypically-distinct subpopulations of cancer cells. Magnetic nanoparticles coated with antibodies against the epithelial cell adhesion molecule (EpCAM) are used to enrich cancer cells in a microfluidic platform...
May 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28546516/re-evaluating-the-role-of-epithelial-mesenchymal-transition-in-cancer-progression
#3
Andrew Sulaiman, Zemin Yao, Lisheng Wang
Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are essential for embryonic development and also important in cancer progression. In a conventional model, epithelial-like cancer cells transit to mesenchymal-like tumor cells with great motility via EMT transcription factors; these mesenchymal-like cells migrate through the circulation system, relocate to a suitable site and then convert back to an epithelial-like phenotype to regenerate the tumor. However, recent findings challenge this conventional model and support the existence of a stable hybrid epithelial/mesenchymal (E/M) tumor population...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28544498/cancer-metastasis-through-the-prism-of-epithelial-to-mesenchymal-transition-in-circulating-tumor-cells
#4
REVIEW
Douglas S Micalizzi, Daniel A Haber, Shyamala Maheswaran
Metastasis of epithelial cancer cells to distal sites is a particularly critical stage of cancer progression that typically marks the incurability of the disease. It is governed by a complex series of events including invasion and intravasation of tumor cells into the stroma and blood, respectively. Epithelial to mesenchymal transition (EMT), a phenotypic change marked by the loss of epithelial characteristics and the acquisition of invasive mesenchymal properties, is implicated in the dissemination of tumor cells...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544324/albumin-templated-manganese-dioxide-nanoparticles-for-enhanced-radioisotope-therapy
#5
Longlong Tian, Qian Chen, Xuan Yi, Jiawen Chen, Chao Liang, Yu Chao, Kai Yang, Zhuang Liu
Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide (131) I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles ((131) I-HSA-MnO2 ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME)...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28543104/circulating-tumor-dna-profiling-reveals-clonal-evolution-and-real-time-disease-progression-in-advanced-hepatocellular-carcinoma
#6
Zhi-Xiong Cai, Geng Chen, Yong-Yi Zeng, Xiu-Qing Dong, Min-Jie Lin, Xin-Hui Huang, Da Zhang, Xiao-Long Liu, Jing-Feng Liu
Circulating tumor DNA (ctDNA) provides a potential non-invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis...
May 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28542880/suicidal-death-of-erythrocytes-in-cancer-and-its-chemotherapy-a-potential-target-in-the-treatment-of-tumor-associated-anemia
#7
REVIEW
Elisabeth Lang, Rosi Bissinger, Syed M Qadri, Florian Lang
In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca(2+) -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4...
May 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28542798/glut-1-receptor-expression-and-circulating-levels-of-fasting-glucose-in-high-grade-serous-ovarian-cancer
#8
L Pizzuti, D Sergi, Chiara Mandoj, B Antoniani, Francesca Sperati, Andrea Chirico, Luigi Di Lauro, Mario Valle, Alfredo Garofalo, Enrico Vizza, Gabriele Corrado, Federica Tomao, Massimo Rinaldi, Silvia Carpano, M Maugeri-Saccà, Laura Conti, Giovanna Digiesi, Paolo Marchetti, Ruggero De Maria, A Giordano, Maddalena Barba, Maria Antonietta Carosi, Patrizia Vici
In recent years, the poorly remarkable goals achieved in terms of patients' important outcomes for ovarian cancer have fueled our interest towards the study of its metabolic roots. Within this research pipeline, we assessed the association between the expression of the glucose transporter GLUT1, as expressed at the tumor tissue level, and circulating pre-surgical levels of fasting glucose in a case series including data from 40 patients with high FIGO stage serous ovarian cancer. Patients who provided data to the current analysis were randomly selected from a larger cohort...
May 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28539838/andrographolide-inhibits-angiogenesis-by-inhibiting-the-mir-21-5p-timp3-signaling-pathway
#9
Jianwei Dai, Yuyin Lin, Youfa Duan, Zixuan Li, Dalei Zhou, Wensheng Chen, Lijing Wang, Qian-Qian Zhang
Angiogenesis provides nutrients and oxygen to promote tumor growth and affords a channel that facilitates tumor cell entry into the circulation. Andrographolide (Andro) possess anti-tumor activity; however, its direct effect on angiogenesis still needs to be clarified. In this study, our experiments revealed that Andro significantly inhibited vascular growth in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumor angiogenesis was also suppressed by Andro. Additionally, we found that cell proliferation, migration and tube formation of vascular endothelial cells was inhibited by Andro treatment in vitro...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28539465/utility-of-genomic-assessment-of-blood-derived-circulating-tumor-dna-ctdna-in-patients-with-advanced-lung-adenocarcinoma
#10
Maria Schwaederle, Sandip P Patel, Hatim Husain, Megumi Ikeda, Richard Lanman, Kimberly C Banks, AmirAli Talasaz, Lyudmila Bazhenova, Razelle Kurzrock
<p>Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes.</p> <br /><br />Experimental Design: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28539031/-micrometastasis-in-gastric-cancer
#11
REVIEW
Gun Jung Youn, Woo Chul Chung
Although the incidence and mortality rate of gastric cancer have been steadily declining, gastric cancer is still the fourth most common cancer in the world and more than 50% of cases occur in Eastern Asia. In Korea, gastric cancer is the second most common cancer and third cause of cancer related death. The standard surgical procedure for resectable advanced gastric cancer is D2 lymphadenectomy with radical gastrectomy. Even though R0 resection was completed, recurrence is relatively common, and contributes to the limited survival of the patients in gastric cancer...
May 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#12
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537901/inflammatory-cytokines-are-associated-with-response-and-prognosis-in-patients-with-esophageal-cancer
#13
Susanne Blank, Henrik Nienhüser, Lena Dreikhausen, Leila Sisic, Ulrike Heger, Katja Ott, Thomas Schmidt
BACKGROUND: Esophageal cancer is often marked by aggressive tumor growth and poor prognosis. Patient groups who benefit from perioperative therapy are not yet defined. The tumor microenvironment and circulating factors as possible predictors of response and prognosis gain interest. This study aimed to investigate cytokines in patients' serum and tumor tissue with regard to response and prognosis. RESULTS: Median survival between SCC and AC was not different (published previously)...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536706/plasma-levels-of-high-mobility-group-box-1-during-peptide-vaccination-in-patients-with-recurrent-ovarian-cancer
#14
Kayoko Waki, Kouichiro Kawano, Naotake Tsuda, Kimio Ushijima, Kyogo Itoh, Akira Yamada
High-mobility group box 1 (HMGB1) is a nuclear protein that is known to be secreted into extracellular fluids from injured cells, activated macrophages, and tumor cells. The clinical correlation of circulating HMGB1 levels with various diseases including cancer has been reported. However, there is no information on HMGB1 levels in cancer patients treated with peptide vaccination. In the present study, we investigated the plasma levels of HMGB1 during personalized peptide vaccination in patients with recurrent ovarian cancer...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28536426/toll-like-receptor-4-mediates-lewis-lung-carcinoma-induced-muscle-wasting-via-coordinate-activation-of-protein-degradation-pathways
#15
Guohua Zhang, Zhelong Liu, Hui Ding, Hongyu Miao, Jose M Garcia, Yi-Ping Li
Cancer-induced cachexia, characterized by muscle wasting, is a lethal metabolic syndrome with undefined etiology. Current consensus is that multiple factors contribute to cancer-induced muscle wasting, and therefore therapy requires combinational strategies. Here, we show that Toll-like receptor 4 (TLR4) mediates cancer-induced muscle wasting by directly activating muscle catabolism as well as stimulating an innate immune response in mice bearing Lewis lung carcinoma (LLC), and targeting TLR4 alone effectively abrogate muscle wasting...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536328/-microrna-in-various-aspects-of-cancer-development
#16
Sho Nambara, Koshi Mimori
MicroRNAs(miRNAs)are small(18-25 nucleotides)noncoding RNA molecules that bind to partially complementary mRNA sequences, resulting in target degradation or translation inhibition. A single miRNA can influence the expression of hundreds of target genes, and miRNAs have been implicated as key molecules in various diseases, including cancer. Many studies have shown that the miRNAs play an important role in cancer cells and tumor microenvironment and may be biomarkers for early detection and therapeutic targets for various cancers...
May 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28536280/liver-metastasis-is-facilitated-by-the-adherence-of-circulating-tumor-cells-to-vascular-fibronectin-deposits
#17
Jorge Barbazan, Lorena Alonso-Alconada, Nadia Elkhatib, Sara Geraldo, Vasily Gurchenkov, Alexandros Glentis, Guillaume van Niel, Roberta Palmulli, Beatriz Fernandez, Patricia Viaño, Tomás García-Caballero, Rafael López López, Miguel Abal, Danijela Matic Vignjevic
The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are enriched in mice bearing primary tumors and are also present in vessels from human livers affected with metastases. Cancer cells attached to endothelial fibronectin deposits via talin1, a major component of focal adhesions...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28536100/depletion-of-tumor-associated-macrophages-with-a-csf-1r-kinase-inhibitor-enhances-antitumor-immunity-and-survival-induced-by-dc-immunotherapy
#18
Floris Dammeijer, Lysanne A Lievense, Margaretha E H Kaijen-Lambers, Menno van Nimwegen, Koen Bezemer, Joost P Hegmans, Thorbald van Hall, Rudi W Hendriks, Joachim G Aerts
New immunotherapeutic strategies are needed to induce effective anti-tumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppression, angiogenesis and tumor aggressiveness. Therefore, TAM depletion could potentially reactivate anti-tumor immunity. We show that M-CSFR-inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of TAMs, circulating nonclassical monocytes, as well as amount of neo-angiogenesis and ascites in mesothelioma mouse models, but did not improve survival...
May 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28536023/development-of-long-circulating-docetaxel-loaded-poly-3-hydroxybutyrate-co-3-hydroxyvalerate-nanoparticles-optimization-pharmacokinetic-cytotoxicity-and-in-vivo-assessments
#19
Harsh Vardhan, Pooja Mittal, Sandeep K Reddy Adena, Mansi Upadhyay, Brahmeshwar Mishra
Long-circulating Nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett-Burman (PBD) and Box-Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39±0...
May 20, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28535990/intravenous-and-intratumoral-injection-of-pluronic-p94-the-effect-of-administration-route-on-biodistribution-and-tumor-retention
#20
C Santini, A Arranja, A G Denkova, F Schosseler, K Morawska, P Dubruel, E Mendes, M de Jong, M Bernsen
Pluronics P94 are block-copolymer showing prolonged circulation time and tumor-cell internalization in vitro, suggesting a potential for tumor accumulation and as a drug carrier. Here we report the results of the radiolabeled-P94 unimers (P94-(111)In-DTPA) on tumor uptake/retention and biodistribution after intravenous and intratumoral administration injection to tumor-bearing mice. Intravenous administration results in a high radioactive signal in the liver; while in tumor and other healthy tissues only little levels of radioactivity could be measured...
May 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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