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Yuanyuan Liu, Lian Li, Lijia Li, Zhou Zhou, Fengling Wang, Xiaofeng Xiong, Rui Zhou, Yuan Huang
Requirements on drug delivery systems to surmount a complex series of pathophysiological barriers bear "cascading contradictions", especially size and hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery system (GNPs-Dox-Lac) based on optimized "size decrease and hydrophilicity/hydrophobicity transformation" was developed by combination the gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood circulation and inclined to accumulate at the tumor site...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Joseph X DiMario
Dystrophic skeletal muscle is characterized by fibrotic accumulation of extracellular matrix components that compromise muscle structure, function, and capacity for regeneration. Tissue fibrosis is often initiated and sustained through transforming growth factor β (TGFβ) signaling, and KLF10 is an immediate early gene that is transcriptionally activated in response to TGFβ signaling. It encodes a transcriptional regulator that mediates the effects of TGFβ signaling in a variety of cell types. This report presents results of investigation of the effects of loss of KLF10 gene expression in wild-type and dystrophic (mdx) skeletal muscle...
February 16, 2018: American Journal of Pathology
Jinyu Pan, Lu Lu, Xuyang Wang, Dian Liu, Jingjing Tian, Hui Liu, Mingjun Zhang, Fengqin Xu, Fengshuang An
BACKGROUND: Atherosclerosis (AS) is a common pathological basis of various cardiovascular and cerebrovascular diseases. Plaque formation is initiated and triggered by vascular smooth musclecells (VSMCs) migration in vascular wall, which gradually aggravates atherosclerosis progression. Absent in melanoma 2 (AIM2), a member of HIN-200 family, plays an important role in activating inflammasome. However, the role of AIM2 in atherosclerotic plaque progression outside of the inflammasome has not yet been reported...
February 12, 2018: Biochemical and Biophysical Research Communications
Sharad Purohit, Ashok Sharma, Wenbo Zhi, Shan Bai, Diane Hopkins, Leigh Steed, Bruce Bode, Stephen W Anderson, John Chip Reed, R Dennis Steed, Jin-Xiong She
Soluble cytokine receptors may play an important role in development of microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA ( n = 89) and T1D patients without MA ( n = 483) participating in the PAGODA study. Twelve proteins in the sera from T1D patients with and without MA were measured using multiplex Luminex assays. Ten serum proteins (sTNFR1, sTNFR2, sIL2Rα, MMP2, sgp130, sVCAM1, sIL6R, SAA, CRP, and sICAM1) were significantly elevated in T1D patients with MA...
2018: Frontiers in Immunology
Shichao Han, Jinming Zhu, Yilei Zhang
BACKGROUND Ovarian cancer (OC) is one of the most common malignant diseases of the female reproductive system worldwide. Evidence has shown that microRNAs are involved in the development of ovarian cancer. miR-144, one of these microRNAs, has been found have upregulated expression in various human malignancies. The present study aimed to investigate the role miR-144 in ovarian cancer cell lines and to elucidate the mechanism involved. MATERIAL AND METHODS Human ovarian cancer cell lines (SKOV3/OVCAR3) and a normal ovarian cell line (IOSE80) were used to identify the miR-144 expression though qRT-PCR method...
February 15, 2018: Medical Science Monitor Basic Research
Nagore I Marín-Ramos, Thu Zan Thein, Hee-Yeon Cho, Stephen D Swenson, Weijun Wang, Axel H Schönthal, Thomas C Chen, Florence M Hofman
Glioblastoma multiforme is a malignant brain tumor noted for its extensive vascularity, aggressiveness, and highly invasive nature, suggesting that cell migration plays an important role in tumor progression. The poor prognosis in GBM is associated with a high rate of tumor recurrence, and resistance to the standard of care chemotherapy, temozolomide (TMZ). The novel compound NEO212, a conjugate of TMZ and perillyl alcohol (POH), has proven to be 10 fold more cytotoxic to glioma stem cells (GSCs) than TMZ, and is active against TMZ-resistant tumor cells...
February 13, 2018: Molecular Cancer Therapeutics
Qiao-Li Lv, Hui-Ting Zhu, Xiao-Hua Cheng, Hong-Mi Li, Hong-Hao Zhou, Shu-Hui Chen
Emerging studies show that dysregulated miRNAs are implicated in tumorigenesis and progression of various cancers. MiRNA-320c, an important member of miRNA-320 family, was characterized as a new candidate miRNA that suppressed the development of colorectal cancer and bladder cancer. However, the function of miRNA-320c in human glioma remained unclear. Here, we found that miRNA-320c was significantly down-regulated in glioma tissues and cell lines in contrast with normal brain tissues, being tightly related to clinical stage of glioma by qRT-PCR...
February 10, 2018: Brain Research Bulletin
Kim E Schmidt, Janina M Kuepper, Beatrix Schumak, Judith Alferink, Andrea Hofmann, Shanshan W Howland, Laurent Rénia, Andreas Limmer, Sabine Specht, Achim Hoerauf
Malaria ranks among the most important infectious diseases worldwide and affects mostly people living in tropical countries. Mechanisms involved in disease progression are still not fully understood and specific treatments that might interfere with cerebral malaria (CM) are limited. Here we show that administration of doxycycline (DOX) prevented experimental CM (ECM) in Plasmodium berghei ANKA (PbA)-infected C57BL/6 wildtype (WT) mice in an IL-10-independent manner. DOX-treated mice showed an intact blood-brain barrier (BBB) and attenuated brain inflammation...
2018: PloS One
Yuichiro Miki, Masakazu Yashiro, Tomohisa Okuno, Kishu Kitayama, Go Masuda, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Crosstalk between cancer cells and fibroblasts is crucial for tumour progression. It has been reported that exosomes derived from cancer cells play an important role in the intracellular communications involved in the development of carcinoma. However, the role of exosomes from fibroblasts remains unclear. This study aimed to clarify the effect of exosomes from fibroblasts on the motility of gastric cancer cells. METHODS: 5 gastric cancer cell lines were used: OCUM-12, NUGC-3, MKN45, FU97 and MKN74...
February 13, 2018: British Journal of Cancer
Siriporn Keeratichamroen, Kriengsak Lirdprapamongkol, Jisnuson Svasti
It is now widely accepted that the tumor microenvironment influences the fate of cancer cells and plays crucial roles in regulating tumor dormancy and chemoresistance. The standard cell culture system on plastic surfaces does not account for cell interactions with the extracellular matrix (ECM), and is thus a less reliable approach to analyze cellular activity ex vivo. In the present study, A549 lung cancer cells were cultured in a semi-solid growth substrate (Matrigel) to mimic the tumor microenvironment and to investigate the role played by ECM proteins, as well as to evaluate the mechanism of cell-ECM communication...
February 12, 2018: Oncology Reports
Kun Han, Yan Zhou, Kuo-Fu Tseng, Haiyan Hu, Kunpeng Li, Yaling Wang, Zhihua Gan, Shuchen Lin, Yongning Sun, Daliu Min
p21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases, which are associated with cytoskeletal organization, cellular morphogenesis, migration and survival. PAKs are overactive in a number of tumor tissues and have attracted attention as a potential target for cancer therapy. In the present study, PAK5 levels were analyzed in primary osteosarcoma (OS) samples (n=65) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) methods. In the primary OS tissue, increased PAK5 expression (IHC score >2, n=37) was associated with significantly decreased overall survival (P=0...
February 2018: Oncology Letters
Christian Bolenz, Daniel Knauf, Axel John, Philipp Erben, Annette Steidler, Stefan W Schneider, Cagatay Günes, Christian Gorzelanny
Objectives: To measure and to modulate the invasive potential of urothelial carcinoma of the bladder (UCB) cells in a standardized preclinical setting using broad-spectrum matrix-metalloproteinase (MMPs) inhibitors and specific targeting of MMP7. Materials and Methods: MMP expression levels in UCB cells were determined by quantitative real-time PCR (qRT-PCR) and gel zymographies of cell supernatants (MMP9, MMP2 and MMP1) and cell lysates (MMP7). The invasiveness of human UCB cells (HT1197 and T24/83) and human benign urothelial cells (UROtsa) was modulated by a broad-spectrum MMP inhibitor (4-Aminobenzoyl-Gly-Pro-D-Leu-D-Ala hydroxamic acid; AHA) and by MMP7 specific siRNAs...
January 20, 2018: Bladder Cancer
Xue Guan, Shuo Chen, Yao Liu, Li-Li Wang, Yang Zhao, Zhi-Hong Zong
BACKGROUND: Abnormal expression of the PUM1 gene (pumilio RNA binding family member 1) is closely related to chromosomal mutations and carcinogenesis. However, there is no report about expression or function of PUM1 in ovarian cancer. The present study explored the role of PUM1 in the development and progression of ovarian cancer. METHODS: Immunohistochemistry was used to detect the expression of PUM1 in normal ovarian tissues and ovarian cancer tissues. The PUM1 gene was silenced using small interfering RNAs in ovarian cancer cell line A2780...
February 8, 2018: Biochemical and Biophysical Research Communications
Kanae Echizen, Hiroko Oshima, Mizuho Nakayama, Masanobu Oshima
Accumulating evidence has indicated that the inflammatory response is important for tumor promotion. However, the mechanisms underlying the induction of the inflammatory response in cancer tissues and how it promotes tumorigenesis remain poorly understood. We constructed several mouse models that develop inflammation-associated gastric and intestinal tumors and examined the in vivo mechanisms of tumorigenesis. Of note, the activation of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway and Toll-like receptor (TLR)/MyD88 signaling cooperatively induced the generation of an inflammatory microenvironment, which is required for early-stage tumorigenesis...
February 5, 2018: Advances in Biological Regulation
Dan Zhao, Qianshun Li, Mengting Liu, Wenjuan Ma, Tengfei Zhou, Changyue Xue, Xiaoxiao Cai
OBJECTIVES: Human salivary adenoid cystic carcinoma (SACC) is one of the most common malignant tumours of the salivary gland and has strong migratory and invasive ability, which often lead to poor prognosis and lower survival rate. Tumour tissue tends to stiffen during solid tumour progression. This study aimed to investigate the influence of various substrate stiffness on the migration and invasion of SACC. METHODS: Salivary adenoid cystic carcinoma cell line ACC2 cells were cultured on polydimethylsiloxane substrates (PDMS) with varying stiffness for investigating the effects of substrate stiffness on the activities of MMPs and TIMPs...
February 8, 2018: Cell Proliferation
Zhaotao Wang, Zhi Liu, Guoyong Yu, Xiaohu Nie, Weiqiang Jia, Ru-En Liu, Ruxiang Xu
Paeoniflorin (PF) is a polyphenolic compound derived from Radix Paeoniae Alba thathas anti-cancer activities in a variety of human malignancies including glioblastoma. However, the underlying mechanisms have not been fully elucidated. Epithelial to mesenchymal transition (EMT), characterized as losing cell polarity, plays an essential role in tumor invasion and metastasis. TGFβ, a key member of transforming growth factors, has been demonstrated to contribute to glioblastoma aggressiveness through inducing EMT...
February 8, 2018: Neurochemical Research
Caojian Zuo, Xiaodong Li, Jun Huang, Dongrui Chen, Kaida Ji, Yan Yang, Tingyan Xu, Ding-Liang Zhu, Chen Yan, Pingjin Gao
Aims: Cardiac myofibroblasts (CMFs) play a crucial role in the progression of pathological fibrotic cardiac remodeling. The expression of osteoglycin (OGN) is increased in diseased hearts; however, the role of OGN in pathological cardiac remodeling is not understood. Here we sought to determine the effect of OGN on cardiac interstitial fibrosis and investigated the molecular mechanisms of OGN in CMF activation and matrix production. Methods and results: We found that OGN expression was significantly upregulated in mouse hearts in response to chronic 14-day angiotensin II (Ang II) infusion...
February 5, 2018: Cardiovascular Research
Jinfeng Zhang, Jian Zhang, Shouping Xu, Xianyu Zhang, Peiyuan Wang, Hao Wu, Bingshu Xia, Guangwen Zhang, Bo Lei, Lin Wan, Dekai Zhang, Da Pang
BACKGROUND/AIMS: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. METHODS: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer...
January 31, 2018: Cellular Physiology and Biochemistry
Nehal Aly Afifi, Marwa Ibrahim, Mona Galal
Despite all the studies performed up to now, therapy choices for liver injuries are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. The Quercetin (QR) and ellagic acid (EA) had a potent antioxidant and anti-inflammatory activities. The current study aimed at evaluating the potential hepatoprotective influence of QR and EA against thioacetamide (TAA)-induced liver toxicity in rats and the underlying mechanism using silymarin as a reference drug...
February 7, 2018: Canadian Journal of Physiology and Pharmacology
Fu-Hua Liu, Chun-Yuan Hou, Di Zhang, Wen-Jing Zhao, Yong Cong, Zhong-Yu Duan, Zeng-Ying Qiao, Hao Wang
Peptide nanodrugs have been developed as promising antitumor chemotherapeutics because they partially overcome the drawbacks of free peptide drugs, but insufficient tumor penetration and interference of peptide function limit their further application. In this work, we have developed multifunctional peptide conjugated dendrimers for improving tumor penetration, cancer cell-specific peptide delivery and anticancer ability. The cytotoxic peptide KLAK, cell-penetrating peptide TAT and matrix metalloproteinase 2 (MMP2)-sensitive peptide-poly(ethylene glycol) (PEG) were conjugated onto dendrimers by one-pot synthesis to gain PKT-S-PEG...
February 6, 2018: Biomaterials Science
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