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https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#1
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28433772/mesenchymal-stem-cells-induce-epithelial-to-mesenchymal-transition-in-colon-cancer-cells-through-direct-cell-to-cell-contact
#2
Hidehiko Takigawa, Yasuhiko Kitadai, Kei Shinagawa, Ryo Yuge, Yukihito Higashi, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow-derived mesenchymal stem cells (MSCs) migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important...
April 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28433697/rab22a-enhances-cd147-recycling-and-is-required-for-lung-cancer-cell-migration-and-invasion
#3
Yang Zhou, Bo Wu, Jiang-Hua Li, Gang Nan, Jian-Li Jiang, Zhi-Nan Chen
Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28433634/dual-sphingosine-kinase-inhibitor-ski-ii-enhances-sensitivity-to-5-fluorouracil-in-hepatocellular-carcinoma-cells-via-suppression-of-osteopontin-and-fak-igf-1r-signalling
#4
Petra Grbčić, Ivana Tomljanović, Marko Klobučar, Sandra Kraljević Pavelić, Ksenija Lučin, Mirela Sedić
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433392/quantifying-rates-of-cell-migration-and-cell-proliferation-in-co-culture-barrier-assays-reveals-how-skin-and-melanoma-cells-interact-during-melanoma-spreading-and-invasion
#5
Parvathi Haridas, Catherine J Penington, Jacqui A McGovern, D L Sean McElwain, Matthew J Simpson
Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro. We perform a suite of circular barrier assays that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast cells...
April 19, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28433158/characterization-of-a-sulfated-galactoglucan-from-antrodia-cinnamomea-and-its-anticancer-mechanism-via-tgf%C3%AE-fak-slug-axis-suppression
#6
Mei-Kuang Lu, Tung-Yi Lin, Chun-Hao Hu, Chi-Hsein Chao, Chia-Chuan Chang, Hsien-Yeh Hsu
A sulfated 1,4-β-d-galactoglucan (B86-III) with 1,6-branches was isolated and identified from Antrodia cinnamomea. The repeating unit of B86-III was proposed based on one-dimensional 1D ((1)H, (13)C and DEPT-135) and 2D (DQF-COSY, TOCSY, HSQC and HMBC) NMR spectra. The conformation of the sugars was hypothesized to be a rare boat form instead of a (4)C1 chair form. The sulfate substitutions were suggested to be on the C-2 and C-3 positions, resulting in the following structure: B86-III inhibited the viability of H1975 lung cancer cells via cell apoptosis, including the activation of caspase 3 and PARP...
July 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28432618/the-identification-of-key-genes-and-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis-of-high-throughput-data
#7
Chaoyang Zhang, Li Peng, Yaqin Zhang, Zhaoyang Liu, Wenling Li, Shilian Chen, Guancheng Li
Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28432273/mir-509-3-5p-inhibits-the-invasion-and-lymphatic-metastasis-by-targeting-podxl-and-serves-as-a-novel-prognostic-indicator-for-gastric-cancer
#8
Jing Zhang, Zhonglin Zhu, Jinxin Sheng, Zhilong Yu, Bin Yao, Kejian Huang, Lisheng Zhou, Zhengjun Qiu, Chen Huang
BACKGROUND: Our study aimed to investigate the clinicopathological feature and prognostic role of miR-509-3-5P in gastric cancer, to determine the invasive and metastatic role of miR-509-3-5P in vitro and in vivo and to explore the molecular mechanism between miR-509-3-5P and PODXL. RESULTS: Strikingly lower miR-509-3-5P expression was detected in gastric cancer tissues with advanced tumor stage, poor differentiation and advanced pT stage, and was regarded as an independent prognostic role for poor prognosis...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#9
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28432002/mir-429-inhibits-metastasis-by-targeting-kiaa0101-in-soft-tissue-sarcoma
#10
Devyani Samantarrai, Bibekanand Mallick
Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors with high metastatic potential. There being only a handful of publication on metastasis of STS, we investigated the miRNA mediated target gene regulations in modulating the metastatic processes in this cancer. In this study, we amalgamated gene and miRNA expression profiles of high-grade STS samples with miRNA target predictions and identified miR-429 targeting KIAA0101 as a novel pair, which remain unexplored in STS metastasis. We validated their expression in metastatic fibrosarcoma cell line, HT1080 and performed several functional assays using miRNA mimics and KIAA0101 over-expression vector to confirm their role in metastasis...
April 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28431931/peroxiredoxin-5-promotes-the-epithelial-mesenchymal-transition-in-colon-cancer
#11
Hye-Mi Ahn, Jin-Woo Yoo, Seunghoon Lee, Hong Jun Lee, Hyun-Shik Lee, Dong-Seok Lee
Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431928/cisplatin-and-photodynamic-therapy-exert-synergistic-inhibitory-effects-on-small-cell-lung-cancer-cell-viability-and-xenograft-tumor-growth
#12
You-Shuang Chen, Yin-Bo Peng, Min Yao, Ji-Ping Teng, Da Ni, Zhi-Jun Zhu, Bu-Feng Zhuang, Zhi-Yin Yang
Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431580/cripto-1-acts-as-a-functional-marker-of-cancer-stem-like-cells-and-predicts-prognosis-of-the-patients-in-esophageal-squamous-cell-carcinoma
#13
Qiang Liu, Xiang Cui, Xi Yu, Bai-Shi-Jiao Bian, Feng Qian, Xu-Gang Hu, Cheng-Dong Ji, Lang Yang, Yong Ren, Wei Cui, Xia Zhang, Peng Zhang, Ji Ming Wang, You-Hong Cui, Xiu-Wu Bian
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is highly malignant with highly invasive and metastatic capabilities and poor prognosis. It is believed that the ESCC cancer stem-like cells (ECSLCs) are critical for tumorigenicity, invasion and metastasis of ESCC. However, the properties of ECSLCs vary with different markers used in isolation, so that new and more effective markers of ECSLCs need to be identified. This study aimed to estimate the potentiality of Cripto-1 (CR-1) as an ECSLC surface marker and investigate the clinical significance of CR-1 expression in ESCC...
April 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28431404/upregulation-of-microrna-125b-by-g-csf-promotes-metastasis-in-colorectal-cancer
#14
Xinghua Zhang, Xiao Ma, Huaying An, Changqing Xu, Wenjo Cao, Wei Yuan, Jie Ma
Although there are reports of miR-125b being dysregulated in colorectal cancer (CRC) and associated with CRC progression, little is known about its intrinsic regulatory mechanisms. Here we detected the expression of miR-125b in CRC tissues, subsequently investigated the effect of miR-125b on the proliferation, apoptosis, cell cycle and metastasis on CRC cells. Our results showed that the expression of miR-125b was significantly decreased in CRC tissues comparing to adjacent tissues. However, with the stimulation of Granulocyte colony-stimulating factor (G-CSF), which was highly expressed in CRC tissues, the expression of miR-125b could be improved...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431393/loss-of-tpm4-1-leads-to-disruption-of-cell-cell-adhesions-and-invasive-behavior-in-breast-epithelial-cells-via-increased-rac1-signaling
#15
SukYeong Jeong, SunYoung Lim, Galina Schevzov, Peter W Gunning, David M Helfman
Here we report the identification and characterization of a novel high molecular weight isoform of tropomyosin, Tpm4.1, expressed from the human TPM4 gene. Tpm4.1 expression is down-regulated in a subset of breast cancer cells compared with untransformed MCF10A breast epithelial cells and in highly metastatic breast cancer cell lines derived from poorly metastatic MDA-MD-231 cells. In addition, patients with invasive ductal breast carcinoma show decreased TPM4 expression compared with patients with ductal breast carcinoma in situ, and low TPM4 expression is associated with poor prognosis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#16
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430582/lncrna-chrf-induced-mir-489-loss-promotes-metastasis-of-colorectal-cancer-via-twist1-emt-signaling-pathway
#17
Youmao Tao, Tao Han, Tao Zhang, Chong Ma, Caixia Sun
microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor suppressor in human cancers. While, the clinical significance of miR-489 and its role in colorectal cancer (CRC) remain rarely known. Here, we found that the levels of miR-489 in CRC tissues were significantly lower than those in matched tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that miR-489 underexpression was positively correlated with advanced pT stage, pN stage and AJCC stage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430527/herc4-is-overexpressed-in-hepatocellular-carcinoma-and-contributes-to-the-proliferation-and-migration-of-hepatocellular-carcinoma-cells
#18
Yi Zheng, Jie Li, Chenwei Pan, Guangyao Zhou, Lu Zhuge, Lingxiang Jin, Peipei Fang
Recently, more and more evidences unveiled that ubiquitin-proteasome system (UPS) makes an important contribution to the occurrence and development of cancer. HERC4 is one identified Ubiqutin ligase E3, a member of UPS. Although some studies showed that HERC4 abnormally expresses in many cancer cells, till now, nothing has been reported about the function of HERC4 in the development of hepatoma carcinoma. To this end, in this study, we studied the function of HERC4 for the first time in hepatoma carcinoma cells...
April 21, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28429188/18f-fluorodeoxyglucose-uptake-on-positron-emission-tomography-computed-tomography-is-associated-with-metastasis-and-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma
#19
Misu Lee, Jeong Yong Jeon, Micheal L Neugent, Jung-Whan Kim, Mijin Yun
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. Several studies have investigated the relationship between (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography and the prognosis of patients with HCC, although the relationship between (18)F-FDG uptake and expression of EMT-related proteins in these patients remains unclear. We retrospectively enrolled 116 patients with HCC treated by curative surgical resection and who underwent (18)F-FDG positron emission tomography/computed tomography (PET/CT) for preoperative staging...
April 20, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28429008/anticancer-effects-of-novel-resveratrol-analogues-on-human-ovarian-cancer-cells
#20
Daniele Vergara, Stefania De Domenico, Andrea Tinelli, Eleonora Stanca, Loretta L Del Mercato, Anna M Giudetti, Pasquale Simeone, Nicola Guazzelli, Marco Lessi, Chiara Manzini, Angelo Santino, Fabio Bellina, Michele Maffia
Resveratrol, a naturally occurring phytoalexin, has long been known to play an important regulatory role in key functions in cell physiology. This multifunctional role of resveratrol is explained by its ability to interact with several targets of various cell pathways. In the recent past, synthetic chemical modifications have been made in an attempt to enhance the biological effects of resveratrol, including its anti-cancer properties. In this study, we investigated the molecular mechanisms of action of novel trans-restricted analogues of resveratrol in which the C-C double bond of the natural derivative has been replaced by diaryl-substituted imidazole analogues...
April 21, 2017: Molecular BioSystems
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