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https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#1
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534824/isorhynchophylline-a-potent-plant-alkaloid-induces-apoptotic-and-anti-metastatic-effects-in-human-hepatocellular-carcinoma-cells-through-the-modulation-of-diverse-cell-signaling-cascades
#2
Hanwool Lee, Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534212/breast-cancer-metastasis-putative-therapeutic-role-of-vascular-cell-adhesion-molecule-1
#3
REVIEW
Rohit Sharma, Rohini Sharma, Tejinder Pal Khaket, Chanchala Dutta, Bornisha Chakraborty, Tapan Kumar Mukherjee
BACKGROUND: Breast cancer is a notable cause of cancer-related death in women worldwide. Metastasis to distant organs is responsible for ~90% of this death. Breast cells convert to malignant cancer cells after acquiring the capacity of invasion/intravasation into surrounding tissues and, finally, extravasation/metastasis to distant organs (i.e., lymph nodes, lungs, bone, brain). Metastasis to distant organs depends on interactions between disseminated tumor cells (DTCs) and the endothelium of blood vessels present in the tumor microenvironment...
May 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28533486/galectin-3-acts-as-an-angiogenic-switch-to-induce-tumor-angiogenesis-via-jagged-1-notch-activation
#4
Sofia Nascimento Dos Santos, Helen Sheldon, Jonathas Xavier Pereira, Christopher Paluch, Esther M Bridges, Márcia Curry El-Cheikh, Adrian L Harris, Emerson Soares Bernardes
Angiogenesis is a coordinated process tightly regulated by the balance between Delta-like-4 (DLL4) and Jagged-1 (JAG1) in endothelial cells. Here we show that galectin-3 (gal-3), a glycan-binding protein secreted by cancer cells under hypoxic conditions, triggers sprouting angiogenesis, assisted by hypoxic changes in the glycosylation status of endothelial cells that enhance binding to gal-3. Galectin-3's proangiogenic functions were found to be predominantly dependent on the Notch ligand JAG1. Differential direct binding to JAG1 was shown by surface plasmon resonance assay...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#5
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28525947/dianhydrogalactitol-a-potential-multitarget-agent-inhibits-glioblastoma-migration-invasion-and-angiogenesis
#6
Xia Jiang, Yinmei Huang, Xiaojie Wang, Qiaofang Liang, Yingjie Li, Fuji Li, Xuanhao Fu, Chonghuan Huang, Huagang Liu
The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28525888/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#7
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514746/diagnostic-and-prognostic-values-of-endothelial-cell-specific-molecule-1-with-malignant-pleural-effusions-in-patients-with-non-small-cell-lung-cancer
#8
Guo-Jun Lu, Cheng-Jie Shao, Yu Zhang, Yong-Yue Wei, Wei-Ping Xie, Hui Kong
Over-expressed endothelial-cell-specific molecule-1 (ESM-1) in tumor vascular endothelium contributes to tumor angiogenesis, metastasis, and poor prognosis. However, the content of ESM-1 in pleural effusion is unclear. A retrospective study was carried out to investigate the diagnostic and prognostic values of ESM-1 with malignant pleural effusions in patients with non-small cell lung cancer (NSCLC). ESM-1 levels in malignant pleural effusion (MPE) from 70 patients with NSCLC and 50 cases of benign pleural effusion (BPE) were measured using enzyme-linked immunosorbent assay...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514740/differential-expression-of-circulating-biomarkers-of-tumor-phenotype-and-outcomes-in-previously-treated-non-small-cell-lung-cancer-patients-receiving-erlotinib-vs-cytotoxic-chemotherapy
#9
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498425/gene-silencing-of-indoleamine-2-3-dioxygenase-hinders-tumor-growth-through-angiogenesis-inhibition
#10
Jinfeng Pan, Keng Yuan, Shanshan Peng, Yanqin Huang, Yujuan Zhang, Yinying Hu, Yuanyuan Feng, Yanmei Shi, Yanling Liu, Hongmei Wang, Nanjin Zhou, Weiping Min
The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in various types of tumors, but the relationship between IDO1 and tumor angiogenesis needs further delineation. We aimed to clarify the relationship between tumor angiogenesis and IDO1 expression, and to explore the possibility of IDO1-targeting molecular therapy for lung cancer. For the first time, we found that silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro cancer cell invasion and migration. We further demonstrated that knockdown of IDO1 decreased the formation of vasculogenic mimicry...
April 25, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28469956/targeting-nras-q61k-mutant-delays-tumor-growth-and-angiogenesis-in-non-small-cell-lung-cancer
#11
Zhaowei Song, Fenghai Liu, Jie Zhang
Tumor cells require vascular supply for their growth, and they express proangiogenic growth factors that promote the formation of vascular networks. Many oncogenic mutations that may potentially lead to tumor angiogenesis have been identified. Somatic mutations in the small GTPase NRAS are the most common activating lesions found in human cancer and are generally associated with poor response to standard therapies. However, the mechanisms by which NRAS mutations affect tumor angiogenesis are largely unknown...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28469955/molecular-mechanism-underlying-the-pharmacological-interactions-of-the-protein-kinase-c-%C3%AE-inhibitor-enzastaurin-and-erlotinib-in-non-small-cell-lung-cancer-cells
#12
Nele Van Der Steen, Lisette Potze, Elisa Giovannetti, Andrea Cavazzoni, Rob Ruijtenbeek, Christian Rolfo, Patrick Pauwels, Godefridus J Peters
Erlotinib is commonly used as a second line treatment in non-small cell lung cancer patients with sensitizing EGFR mutations. In EGFR-wild type patients, however the results are limited. Therefore we evaluated whether the combination of the Protein kinase C-β inhibitor enzastaurin with erlotinib could enhance the effect in the A549 and H1650 cell lines. Cytotoxicity of erlotinib, enzastaurin and their 72-h simultaneous combination was assessed with the MTT assay. The pharmacologic interaction was studied using the method of Chou and Talalay, cell cycle perturbations were assessed by flow cytometry and modulation of ERK1/2 and AKT phosphorylation was determined with ELISA...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28462515/tab3-defect-induces-augmented-cardioprotection-loss-from-ischemic-injury
#13
Yang Sheng, Changfu Xu, Wenping Zeng
The transforming growth factor β-activated kinase-binding protein 3 (TAB3) plays a crucial role in modulating cell apoptosis and proliferation in many diseases, including hepatocellular carcinoma, lung cancer and intracerebral hemorrhage. However, the functional role of TAB3 in the heart is not well reported. In our study, we first investigated the role of TAB3 in ischaemia heart diseases. For in vitro studies, cardiomyocytes were isolated from both TAB3 knockout (KO) and WT mice, and the apoptosis ratios were tested after a 48-h ischaemic stimulation...
April 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28458672/group-v-secreted-phospholipase-a2-induces-the-release-of-proangiogenic-and-antiangiogenic-factors-by-human-neutrophils
#14
Stefania Loffredo, Francesco Borriello, Raffaella Iannone, Anne L Ferrara, Maria R Galdiero, Vincenzo Gigantino, Pasquale Esposito, Gilda Varricchi, Gerard Lambeau, Marco A Cassatella, Francescopaolo Granata, Gianni Marone
Secreted phospholipases A2 (sPLA2s) are extracellular enzymes that catalyze the release of free fatty acids and lysophospholipids from membrane phospholipids and also bind to different receptors (e.g., PLA2R1 or integrins). To date, 12 mammalian sPLA2s have been identified, which play a critical role in pathophysiological processes including inflammation and cancer. sPLA2s activate immune cells such as human neutrophils (PMNs) by enzymatic activity- or receptor-mediated mechanisms. In addition, human PMNs synthesize and store human group V (hGV) and human group X (hGX) sPLA2s in their granules, but only the former is released upon cellular activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28448232/dynamic-contrast-enhanced-mr-imaging-parameters-in-bone-metastases-from-non-small-cell-lung-cancer-comparison-between-lesions-with-and-lesions-without-epidermal-growth-factor-receptor-mutation-in-primary-lung-cancer
#15
Hyun Su Kim, Young Cheol Yoon, Soyi Kwon, Ji Hyun Lee, Soohyun Ahn, Hyeon Seon Ahn
Purpose To compare dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging parameters between metastatic bone lesions with and without the epidermal growth factor receptor (EGFR) mutation in consecutive patients with primary non-small cell lung cancer (NSCLC). Materials and Methods This study was approved by the institutional review board. Forty-seven patients with NSCLC and a confirmed EGFR mutation status (27 patients were positive and 26 were negative for EGFR mutation), who underwent DCE MR imaging for bone metastases between November 2012 and March 2016, were included in this study...
April 27, 2017: Radiology
https://www.readbyqxmd.com/read/28446465/deletion-of-lactate-dehydrogenase-a-in-myeloid-cells-triggers-antitumor-immunity
#16
Pankaj Seth, Eva Csizmadia, Andreas Hedblom, Marta Vuerich, Han Xie, Mailin Li, Maria Serena Longhi, Barbara Wegiel
Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis; diminished numbers of PD-L1+ cancer cells; increased numbers of CD3+ T cells and activation status of CD8+ T cells...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28442015/-expression-and-clinical-significance-of-progesterone-and-adiponectin-receptor-family-member-3-in-lung-cancer
#17
Xiaohui Liang, Baocun Sun, Jiyuan Han, Xiulan Zhao, Zenghui Liu
BACKGROUND: Progesterone and adiponectin receptor family member 3 (PAQR3) is a recently discovered tumor suppressor gene, which affects the development of a tumor by inhibiting cell proliferation, cell malignant transformation, angiogenesis, and tumor metastasis. This study investigates the expression of PAQR3 in lung cancer and its clinical significance. METHODS: A total of 106 patients with lung cancer received surgical treatment in hospital, and adjacent normal tissues of these patients were utilized as control group...
April 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28440474/kallistatin-exerts-anti-lymphangiogenic-effects-by-inhibiting-lymphatic-endothelial-cell-proliferation-migration-and-tube-formation
#18
Caiqi Ma, Haofan Yin, Jun Zhong, Yang Zhang, Chuanghua Luo, Di Che, Zhenzhen Fang, Lei Li, Shuxing Qin, Jieying Liang, Weiwei Qi, Zhonghan Yang, Ti Zhou, Jianxing Ma, Xia Yang, Guoquan Gao
Kallistatin has been recognized as an endogenous angiogenic inhibitor. However, its effects on lymphatic endothelial cells and lymphangiogenesis remain poorly understood. Lymphangiogenesis is involved in tumor metastasis via the lymphatic vasculature in various types of tumors. The aim of this study was to investigate the effects of kallistatin on lymphangiogenesis and the mechanism of action involved. Treatment with kallistatin recombinant protein or overexpression of kallistatin inhibited the proliferation, migration and tube formation of human lymphatic endothelial cells (hLECs), and induced apoptosis of hLECs...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440285/ionizing-radiation-abrogates-the-pro-tumorigenic-capacity-of-cancer-associated-fibroblasts-co-implanted-in-xenografts
#19
Maria Tunset Grinde, Jørg Vik, Ketil André Camilio, Inigo Martinez-Zubiaurre, Turid Hellevik
Cancer-associated fibroblasts (CAFs) are abundantly present in solid tumors and affect tumorigenesis and therapeutic responses. In the context of clinical radiotherapy, the impact of irradiated CAFs to treatment outcomes is largely unexplored. Aiming at improving radiotherapy efficacy, we have here explored the effect of radiation on the inherent pro-tumorigenic capacity of CAFs in animals. Ionizing radiation was delivered to cultured CAFs as single-high or fractionated doses. Tumor development was compared in mice receiving A549 lung tumor cells admixed with irradiated or control CAFs...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#20
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
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