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Laurence Booth, Jane Roberts, Andrew Poklepovic, Paul Dent
Inhibitors of PARP1 are approved therapeutic agents in ovarian carcinomas. We determined whether the novel clinically relevant CHK1 inhibitor SRA737 interacted with PARP1 inhibitors to kill carcinoma cells. In multiple mammary and ovarian cancer lines SRA737 synergized with the PARP1 inhibitors olaparib and niraparib to cause cell death. The [SRA737 + niraparib] drug combination activated an ATM-AMPK-ULK1-mTOR pathway which resulted in the formation of autophagosomes, temporally followed by autolysosome formation...
July 19, 2018: Cancer Biology & Therapy
Zining Jin, Lu Xu, Lei Zhang, Min Zhao, Dongbao Li, Lijun Ye, Ying Ma, Siyu Ren, Hailan Yu, Danyu Wang, Chunyan Liang, Bo Chen
Interleukin enhancer binding factor 2 (ILF2) participates in several aspects of DNA and RNA metabolism and regulates gene expression at multiple levels; however, its role in breast cancer remains undefined. The variant statuses of ILF2 in human breast cancer were evaluated using the COSMIC database. Altered ILF2 expression in normal breast tissue relative to cancer tissue and in breast cancer patients with different clinicopathological characteristics, molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO, Kaplan-Meier plotter and GEO datasets...
2018: American Journal of Translational Research
Jian Chen, Zijun Zhou, Yuying Yao, Jianwei Dai, Dalei Zhou, Lijing Wang, Qian-Qian Zhang
Tumour growth depends on a continual supply of the nutrients and oxygen, which are offered by tumour angiogenesis. Our previous study showed that dipalmitoylphosphatidic acid (DPPA), a bioactive phospholipid, inhibits the growth of triple-negative breast cancer cells. However, its direct effect on angiogenesis remains unknown. Our work showed that DPPA significantly suppressed vascular growth in the chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumour angiogenesis and tumour growth were inhibited by DPPA in the tumour tissues of an experimental breast cancer model, a subcutaneous xenograft mouse model and a genetically engineered spontaneous breast cancer mouse model (MMTV-PyMT)...
July 16, 2018: Journal of Cellular and Molecular Medicine
Arash Chitsazan, Pamela Mukhopadhyay, Blake Ferguson, Herlina Y Handoko, Graeme J Walker
Melanocytes can group together in nevi, commonly thought to form due to intrinsic somatic mutations involving MAPK pathway activation. However, the role of the microenvironment, in particular keratinocytes, in nevogenesis, is rarely studied. Melanocytes proliferate during the hair follicle growth phase and in some basal cell carcinomas, allowing us to construct keratinocyte gene expression clusters correlated with melanocyte activation. We asked whether such correlations are evident in the more subtle context of regulation of melanocyte behaviour in normal skin...
July 13, 2018: Journal of Investigative Dermatology
Mengmeng Wang, Lili Song, Charlie Strange, Xiao Dong, Hongjun Wang
To assess the potential therapeutic effects of adipose tissue-derived mesenchymal stem cells (ASCs) for the treatment of type 2 diabetes (T2D), we compared the phenotype and functionality of ASCs isolated from high-fat diet and streptozotocin (STZ)-induced T2D and the leptin receptor-deficient (db/db) mice with cells from healthy C57BL/6 mice. ASCs from T2D or db/db mice showed similar expression patterns of cellular markers and abilities to differentiate into adipocytes, osteoblasts, and chondrocytes. However, the rate of proliferation was reduced...
June 19, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Christian Breunig, Nese Erdem, Alexander Bott, Julia Franziska Greiwe, Eileen Reinz, Stephan Bernhardt, Chiara Giacomelli, Astrid Wachter, Eva Johanna Kanthelhardt, Tim Beißbarth, Martina Vetter, Stefan Wiemann
Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer. In this study, we performed genome-wide correlation analysis of TGFBR2 expression in a panel of 51 breast cancer cell lines and identified that MET is co-regulated with TGFBR2...
July 13, 2018: Molecular Oncology
L van der Merwe, Y Wan, H J Cheong, C Perry, C Punyadeera
BACKGROUND: Early diagnosis of head and neck squamous cell carcinoma (HNSCCs) is an appealing way to increase survival rates in these patients as well as to improve quality of life post-surgery. Angiogenesis is a hallmark of tumor initiation and progression. We have investigated a panel of angiogenic factors in saliva samples collected from HNSCC patients and controls using the Bio-Plex ProTM assays. METHODS: We have identified a panel of five angiogenic proteins (sEGFR, HGF, sHER2, sIL-6Ra and PECAM-1) to be elevated in the saliva samples collected from HNSCC patients (n = 58) compared to a control cohort (n = 8 smokers and n = 30 non-smokers)...
July 13, 2018: BMC Cancer
Hong Li, Qiang Liu, Ningfu Wang, Yizhou Xu, Lan Kang, Yaqi Ren, Gangjie Zhu
BACKGROUND: In a previous study, a low level of miR-126-3p in endothelial progenitor cells (EPCs) was linked to the outcome of ischemic cardiomyopathy (ICM) patients. However, it remains unclear whether transplantation with miR-126-3p-overexpressing EPCs (MO-EPCs) can improve the cardiac function of ICM animal models.Methods and Results:miR-126-3p overexpression by lentiviral vector significantly increased migration and tube-like structures of EPCs from ICM patients. MO-EPCs or non-modified EPCs (NM-EPCs) were transplanted into nude rats with ICM induced by coronary artery ligation...
July 10, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
Yingmiao Liu, Mark D Starr, John C Brady, Christel Rushing, Herbert Pang, Bonne Adams, Delia Alvarez, Charles P Theuer, Herbert I Hurwitz, Andrew B Nixon
TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV) and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy...
July 11, 2018: Molecular Cancer Therapeutics
Siyeon Kim, Kyo Eun Kook, Changhee Kim, Jae-Kwan Hwang
Periodontal disease is triggered by the host immune response to pathogens in the microbial biofilm. Worsening of periodontal disease destroys the tooth-supporting tissues and alveolar bone. As oral inflammation can induce systemic diseases in humans, it is important to prevent periodontal disease. In this study, we demonstrated that Curcuma xanthorrhiza supercritical extract(CXS) and its active compound, xanthorrhizol (XAN), exhibit anti-inflammatory effects on lipopolysaccharide (LPS)-treated HGF-1 cells and anti-osteoclastic effects on receptor activator of nuclear factor kappa B ligand (RANKL)-treated RAW264...
June 6, 2018: Journal of Microbiology and Biotechnology
Phuc Anh Nguyen, Thuy Anh Vu Pham
OBJECTIVE: This study evaluated the influence of platelet-rich plasma (PRP) on the behaviour of human gingival fibroblasts (hGFs), including fibroblast proliferation, migration and colony formation. METHODS: PRP was obtained from the human peripheral blood of a healthy volunteer and then was diluted into platelet concentrations of 1%, 2% and 5%. The proliferation of hGFs was determined by two methods: (1) Cell-number counting with a haemocytometer method at days 1, 3, 5 and 7; (2) Colony-forming unit-fibroblast (CFU-F) assay at 2 weeks...
July 10, 2018: Journal of Applied Oral Science: Revista FOB
Syue-Ting Chen, Ting-Chun Kuo, Ying-Yu Liao, Mei-Chun Lin, Yu-Wen Tien, Min-Chuan Huang
Mucins are heavily glycosylated proteins that play critical roles in the pathogenesis of tumour malignancies. Pancreatic ductal adenocarcinoma (PDAC) is characterised by the aberrant expression of mucins. However, the role of mucin (MUC) 20 in PDAC remains unclear. PDAC is usually surrounded by a dense fibrotic stroma consisting of an extracellular matrix and pancreatic stellate cells (PSCs). The stroma creates a nutrient-deprived, hypoxic, and acidic microenvironment, and promotes the malignant behaviours of PDAC cells...
July 11, 2018: Oncogene
Jeffrey A Knauf, Kathleen A Luckett, Kuen-Yuan Chen, Francesca Voza, Nicholas D Socci, Ronald Ghossein, James A Fagin
Anaplastic thyroid carcinomas (ATC) have a high prevalence of BRAF and TP53 mutations. A trial of vemurafenib in non-melanoma BRAFV600E-mutant cancers showed significant, although short-lived, responses in ATCs, indicating that these virulent tumors remain addicted to BRAF despite their high mutation burden. To explore the mechanisms mediating acquired resistance to BRAF blockade we generated mice with thyroid-specific deletion of p53 and dox-dependent expression of BRAFV600E, 50% of which developed ATCs after dox treatment...
July 10, 2018: Journal of Clinical Investigation
Katarzyna Gawron, Anna Ochała-Kłos, Zuzanna Nowakowska, Grzegorz Bereta, Katarzyna Łazarz-Bartyzel, Aleksander M Grabiec, Paweł Plakwicz, Renata Górska, Andrzej Fertala, Maria Chomyszyn-Gajewska, Jan Potempa
OBJECTIVES: To investigate the processes associated with the excessive production of collagen I in hereditary gingival fibromatosis (HGF). MATERIALS AND METHODS: Three HGF subjects and five controls were enrolled in the study. Histomorphological and immunohistological analyses were performed on gingival tissues. The expression of heat shock protein 47 (HSP47), collagen I, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) by gingival fibroblasts isolated from HGF and controls was analysed using qRT-PCR, Western blotting and ELISA...
July 10, 2018: Oral Diseases
Jun Chen, Lin Ma, Nianzhao Zhang, Yaofeng Zhu, Keqin Zhang, Zhishun Xu, Qian Wang
Background and aim: Mesenchymal stem cells (MSCs) are capable of impacting tumor progression but its role in tumor stroma remodeling still remains unclear. This present study was aimed to evaluate the potential function of MSCs on tumor stroma remodeling using rabbits VX2 bladder tumor model. Methods: The VX2 bladder tumor models were established by injecting mixed cell suspensions (106 of VX2 tumor cells and 0/106 /107 of autologous MSCs in group A, B, C, respectively) into the bladder mucosa using thirty male New Zealand white rabbits...
2018: International Journal of Biological Sciences
Tsuyoshi Fukushima, Makiko Kawaguchi, Koji Yamamoto, Fumiki Yamashita, Aya Izumi, Takashi Kaieda, Yuka Takezaki, Hiroshi Itoh, Hideo Takeshima, Hiroaki Kataoka
Hepatocyte growth factor activator inhibitor type 2 (HAI-2), encoded by the SPINT2 gene, is a membrane-anchored protein that inhibits proteases involved in the activation of hepatocyte growth factor (HGF), a ligand of MET receptor. Epigenetic silencing of the SPINT2 gene has been reported in a human glioblastoma cell line (U87) and glioblastoma-derived cancer stem cells. However, the incidence of SPINT2 methylation in tumor tissues obtained from glioma patients is unknown. In this study, we analyzed the methylation status of the SPINT2 gene of eight human glioblastoma cell lines and surgically resected glioma tissues of different grades (II, III and IV) by bisulfite sequence analysis and methylation-specific PCR (MSP)...
July 10, 2018: Cancer Science
Yongwen Li, Hongbing Zhang, Hao Gong, Yin Yuan, Ying Li, Cong Wang, Weiting Li, Zihe Zhang, Minghui Liu, Hongyu Liu, Jun Chen
BACKGROUND: Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma. Cortactin, a critical component of invadopodia, frequently used as an invadopodia marker, a universally important player in invadopodia function, and is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood...
July 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
Shuangzhu Liu, Jingjing Han, Huanle Gong, Yongsheng Li, Xiebing Bao, Jiaqian Qi, Hong Liu, Jia Chen, Xiaojin Wu, Yang Xu, Shoubao Ma, Depei Wu
Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after allogeneic haematopoietic stem cell transplantation. Interleukin-27 receptor alpha (IL-27Rα) is a co-receptor of IL-27, an inflammatory cytokine that possesses extensive immunological functions. It has been reported that IL-27Rα can exist in its soluble form (sIL-27Rα) in human serum and can function as a natural IL-27 antagonist. In this study, we examined serum sIL-27Rα levels and evaluated their prognostic value in aGVHD...
July 9, 2018: Scientific Reports
Soumaya Souid, Heba E Elsayed, Hassan Y Ebrahim, Mohamed M Mohyeldin, Abu Bakar Siddique, Habib Karoui, Khalid A El Sayed, Khadija Essafi-Benkhadir
The failure of chemotherapy especially in triple negative breast cancer (TNBC) patients has been correlated with the overexpression of the mesenchymal-epithelial transition factor (c-Met) receptor. Thus, the hepatocyte growth factor (HGF)/c-Met signaling axis has gained considerable attention as a valid molecular target for breast cancer therapy. This study reports for the first time the discovery of the 131 -oxophorbines pheophorbide A and protopheophorbide A along with chlorophyllide A from Ziziphus lotus, an edible typical Tunisian plant, as the potent antiproliferative compounds against the human breast cancer cells MDA-MB-231 and MCF-7...
July 6, 2018: Molecular Carcinogenesis
Takeo Mukai, Arinobu Tojo, Tokiko Nagamura-Inoue
Several studies have reported that human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) restore neurological damage in vivo through their secretion of paracrine factors. We previously found that UC-MSCs attenuate brain injury by secreting neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and hepatocyte growth factor (HGF). However, how these factors contribute to neuroprotection remains unknown. In this study, we aimed to investigate to what extent UC-MSC-derived HGF and BDNF contribute to neuroprotection using a Transwell co-culture system of neonatal cortical neurons damaged by oxygen-glucose deprivation...
2018: Frontiers in Neurology
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