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https://www.readbyqxmd.com/read/27911475/carboplatin-complexed-and-crgd-conjugated-unimolecular-nanoparticles-for-targeted-ovarian-cancer-therapy
#1
Yuyuan Wang, Liwei Wang, Guojun Chen, Shaoqin Gong
Platinum-based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose-limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum-based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water-soluble unimolecular nanoparticle constructed from a hydrophilic multi-arm star block copolymer poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol) (PAMAM-PAsp-PEG) conjugated with both cRGD (cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum-based drug nanocarrier for targeted ovarian cancer therapy...
December 1, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27911279/microrna-101-inhibits-proliferation-migration-and-invasion-of-human-glioblastoma-by-targeting-sox9
#2
Nan Liu, Lei Zhang, Zhen Wang, Yingduan Cheng, Pengxing Zhang, Xin Wang, Weihong Wen, Hongwei Yang, Hui Liu, Weilin Jin, Yongsheng Zhang, Yanyang Tu
Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#3
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911269/the-matricellular-protein-cyr61-promotes-breast-cancer-lung-metastasis-by-facilitating-tumor-cell-extravasation-and-suppressing-anoikis
#4
Yu-Ting Huang, Qiang Lan, Girieca Lorusso, Nathalie Duffey, Curzio Rüegg
Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911267/oncogenic-secretory-clusterin-in-hepatocellular-carcinoma-expression-at-early-staging-and-emerging-molecular-target
#5
Wenjie Zheng, Min Yao, Qi Qian, Wenli Sai, Liwei Qiu, Junling Yang, Wei Wu, Zhizhen Dong, Dengfu Yao
Secretory clusterin (sCLU) is associated with hepatocellular carcinoma (HCC) progression by contributing to angiogenesis, chemoresistance, cell survival, and metastasis. However, the sCLU expression at early stage of HCC progression remains to be clarified. In this study, the alteration of sCLU oncogenicity was firstly evaluated in HCC- and their para-cancerous- tissues. The incidence of sCLU expression in HCC was significantly higher than that in their non-tumorous tissues at message RNA (mRNA) or protein level, gradually increasing with tumor-node-metastasis (TNM) staging...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911266/down-regulation-of-salt-inducible-kinase-1-sik1-is-mediated-by-rnf2-in-hepatocarcinogenesis
#6
Chao Qu, Yaqin Qu
Our previous study reported that down-regulation of SIK1 accelerates the growth and invasion of hepatocellular carcinoma (HCC). However, the underlying mechanism leading to SIK1 down-regulation in HCC largely remains to be determined. Herein, we demonstrated that RNF2 expression is negatively correlated with SIK1 levels in HCC tissues. Kaplan-Meier analysis of tumor samples revealed that high RNF2 expression with concurrent low SIK1 expression is associated with poor overall survival. The down-regulation of RNF2 expression in HCC cells significantly reduces tumor cell growth and metastasis, while the simultaneous down-regulation of both RNF2 and SIK1 restores tumor cell growth in vitro and in tumor xenograft models...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911265/mirna-543-promotes-osteosarcoma-cell-proliferation-and-glycolysis-by-partially-suppressing-prmt9-and-stabilizing-hif-1%C3%AE-protein
#7
Heng Zhang, Xiaofeng Guo, Xing Feng, Tingting Wang, Zhaohua Hu, Xiangyong Que, Qingsong Tian, Tianbo Zhu, Guixian Guo, Wei Huang, Xinzhi Li
Osteosarcoma (OS) is the most common primary bone tumor, occurring frequently in adolescents and possessing a high malignant severity. MicroRNAs play critical roles during OS development. Thus, elucidation of the involvement of specific microRNAs in the development of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-543 were significantly increased whereas the levels of PRMT9 were significantly decreased, compared to the paired normal bone tissue...
November 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911045/anti-cancer-potential-of-ionic-liquids
#8
Ana Rita Dias, João Costa-Rodrigues, Maria Helena Fernandes, Ricardo Ferraz, Cristina Prudêncio
Nowadays, many of the challenges that pharmaceutical industry faces impose the need to innovative and effective therapies. The investigation of alternative and effective therapies at the level of cancer is an actual goal of pharmaceutical industry. Ionic Liquids (ILs) appear recently as potential target of study by pharmaceutical industry on search of new therapeutic agents. They are, by definition, organic salts with melting point below 100°C only composed by ions. Their man advantage, is the numerous combinations made between the cation and the anion, which allow adjustments in their physicochemical properties...
December 2, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27910990/a-ph-responsive-sequential-disassembly-nanohybrid-for-mitochondrial-targeting
#9
Lijia Li, Wei Sun, Lian Li, Yuanyuan Liu, Lei Wu, Fengling Wang, Zhou Zhou, Zhirong Zhang, Yuan Huang
Cationic materials have been reported as promising tools for targeting to mitochondria which are the "power houses" and "metabolic garbage keepers" of cells. However, their positive nature also restricts their in vivo application due to the quick clearance. Herein, we fabricated a nanohybrid consisting of the pH-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) co-polymer (R-P) shells and positive mesoporous silica nanoparticle cores via electrostatic interaction. The anticancer drug, docetaxel (DTX), was encapsulated in the positive MSN cores (MSN-DTX)...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910972/a-liver-microphysiological-system-of-tumor-cell-dormancy-and-inflammatory-responsiveness-is-affected-by-scaffold-properties
#10
A M Clark, S E Wheeler, C L Young, L Stockdale, J Shepard Neiman, W Zhao, D B Stolz, R Venkataramanan, D Lauffenburger, L Griffith, A Wells
Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells...
December 2, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27910964/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-targeting-non-small-cell-lung-cancer-with-egfr-t790m-mutations
#11
C E McCoach, A Jimeno
Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#12
Hee Dong Han, Yeongseon Byeon, Jong-Hwa Jang, Hat Nim Jeon, Ga Hee Kim, Min Gi Kim, Chan-Gi Pack, Tae Heung Kang, In Duk Jung, Yong Taik Lim, Young Joo Lee, Jeong-Won Lee, Byung Cheol Shin, Hyung Jun Ahn, Anil K Sood, Yeong-Min Park
Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#13
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910912/bhx-inhibits-the-wnt-signaling-pathway-by-suppressing-%C3%AE-catenin-transcription-in-the-nucleus
#14
Fengxia Ding, Meisa Wang, Yibo Du, Shuangshuang Du, Zhongling Zhu, Zhao Yan
BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#15
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910858/immunosuppression-in-liver-tumors-opening-the-portal-to-effective-immunotherapy
#16
REVIEW
P Guha, J Reha, S C Katz
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910782/chemoprevention-of-colon-cancer-through-inhibition-of-angiogenesis-and-induction-of-apoptosis-by-nonsteroidal-anti-inflammatory-drugs
#17
Preety Ghanghas, Shelly Jain, Chandan Rana, Sankar Nath Sanyal
Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910777/gastric-adenocarcinoma-biomarker-expression-profiles-and-their-prognostic-value
#18
Serkan Senol, Abdullah Aydin, Duygu Kosemetin, Dilek Ece, Ibrahim Akalin, Hasan Abuoglu, Esra Akdeniz Duran, Dincer Aydin, Burcak Erkol
Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910734/targeting-the-akt-cyclin-d1-pathway-to-overcome-intrinsic-and-acquired-radioresistance-of-tumors-for-effective-radiotherapy
#19
Tsutomu Shimura
PURPOSE: Radiotherapy (RT) is a powerful tool in the treatment of cancer, having the advantage of preserving normal tissues. Clinical outcomes of RT are significantly improved by technological advances, enabling increased radiation doses directed very specifically to a tumor. However, tumor radioresistance remains a major impediment to effective RT. We have shown that human tumor cells surviving after repeated exposure to fractionated radiation (FR) of X-rays for 1 month have acquired radioresistance through constitutive activation of AKT and downstream cyclin D1 nuclear retention...
December 2, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27910713/sn-38-loading-capacity-of-hydrophobic-polymer-blend-nanoparticles-formulation-optimization-and-efficacy-evaluation
#20
Simona Dimchevska, Nikola Geskovski, Gjorgji Petruševski, Marina Chacorovska, Riste Popeski-Dimovski, Sonja Ugarkovic, Katerina Goracinova
One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to nanoparticles prepared using individual polymers...
December 2, 2016: Drug Development and Industrial Pharmacy
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