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Cancer Biology
Suppressor of cytokine signaling-1 gene therapy induces potent antitumor effect in patient-derived esophageal squamous cell carcinoma xenograft mice
Feb 24, 2017   International Journal Of Cancer
Sugase T, Takahashi T, Serada S, Nakatsuka R, Fujimoto M,   . . . . . .   , Takiguchi S, Kishimoto T, Mori M, Doki Y, Naka T
Suppressor of cytokine signaling-1 gene therapy induces potent antitumor effect in patient-derived esophageal squamous cell carcinoma xenograft mice
Feb 24, 2017
International Journal Of Cancer
Chronic inflammation is involved in cancer growth in esophageal squamous cell carcinoma (ESCC), which is a highly refractory cancer with poor prognosis. This study investigated the antitumor effect and mechanisms of SOCS1 gene therapy for ESCC. Patients with ESCC showed epigenetics silencing of SOCS1 gene by methylation in the CpG islands. We infected ten ESCC cells with an adenovirus-expressing SOCS1 (AdSOCS1) to examine the antitumor effect and mechanism of SOCS1 overexpression. SOCS1 overexpression markedly decreased the proliferation of all ESCC cell lines and induced apoptosis. Also, SOCS1 inhibited the proliferation of ESCC cells via multiple signaling pathways including Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and focal adhesion kinase (FAK)/ p44/42 mitogen-activated protein kinase (p44/42 MAPK). Additionally, we established two xenograft mouse models in which TE14 ESCC cells or ESCC patient-derived tissues (PDX) were subcutaneously implanted. Mice were intra-tumorally injected with AdSOCS1 or control adenovirus vector (AdLacZ). In mice, tumor volumes and tumor weights were significantly lower in mice treated with AdSOCS1 than that with AdLacZ as similar mechanism to the in vitro findings. The Ki-67 index of tumors treated with AdSOCS1 was significantly lower than that with AdLacZ, and SOCS1 gene therapy induced apoptosis. These findings demonstrated that overexpression of SOCS1 has a potent antitumor effect against ESCC both in vitro and in vivo including PDX mice. SOCS1 gene therapy may be a promising approach for the treatment of ESCC. This article is protected by copyright. All rights reserved.© 2017 UICC.
Paracrine effect of CXCR4-overexpressing mesenchymal stem cells on ischemic heart injury
Feb 24, 2017   Cell Biochemistry And Function
Wu SZ, Li YL, Huang W, Cai WF, Liang J, Paul C, Jiang L, Wu ZC, Xu M, Zhu P, Wang Y
Paracrine effect of CXCR4-overexpressing mesenchymal stem cells on ischemic heart injury
Feb 24, 2017
Cell Biochemistry And Function
It has been reported that CXCR4-overexpressing mesenchymal stem cells (MSCCopyright © 2017 John Wiley & Sons, Ltd.
Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment
Feb 24, 2017   BioMed Research International
Zhang GL, Chen YM, Zhang T, Cai QX, Zhang XH, Zhao ZX, Lin CS, Gao ZL
Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment
Feb 24, 2017
BioMed Research International
Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, -1.33 versus 0.86,
Up-front and Salvage Transoral Robotic Surgery for Head and Neck Cancer: A Belgian Multicenter Retrospective Case Series
Feb 24, 2017   Frontiers In Oncology
Meulemans J, Vanclooster C, Vauterin T, D'heygere E, Nuyts S, Clement PM, Hermans R, Delaere P, Vander Poorten V
Up-front and Salvage Transoral Robotic Surgery for Head and Neck Cancer: A Belgian Multicenter Retrospective Case Series
Feb 24, 2017
Frontiers In Oncology
INTRODUCTION/AIM: We analyzed the functional and oncologic outcomes of primary and salvage transoral robotic surgery (TORS) procedures, performed in three Belgian institutions with a similar philosophy. PATIENTS AND METHODS: A total of 86 patients who underwent TORS between 24-12-2009 and 25-09-2015 were retrospectively reviewed. Descriptive statistics, overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS; Kaplan-Meier), and the variation of these outcomes according to whether patients had primary or salvage TORS were evaluated (univariate log-rank analysis). RESULTS: Of 86 patients, 56 (65.1%) underwent TORS as a primary treatment and 30 (34.9%) as a salvage procedure for recurrent or second primary cancer. Tumor location was mainly oropharynx ( CONCLUSION: This retrospective study confirms favorable oncologic and functional outcomes of TORS for selected head and neck malignancies, both in the primary and in the salvage setting.
Intrinsic disorder in spondins and some of their interacting partners
Feb 24, 2017   Intrinsically Disordered Proteins
Alowolodu O, Johnson G, Alashwal L, Addou I, Zhdanova IV, Uversky VN
Intrinsic disorder in spondins and some of their interacting partners
Feb 24, 2017
Intrinsically Disordered Proteins
Spondins, which are proteins that inhibit and promote adherence of embryonic cells so as to aid axonal growth are part of the thrombospondin-1 family. Spondins function in several important biological processes, such as apoptosis, angiogenesis, etc. Spondins constitute a thrombospondin subfamily that includes F-spondin, a protein that interacts with Aβ precursor protein and inhibits its proteolytic processing; R-spondin, a 4-membered group of proteins that regulates Wnt pathway and have other functions, such as regulation of kidney proliferation, induction of epithelial proliferation, the tumor suppressant action; M-spondin that mediates mechanical linkage between the muscles and apodemes; and the SCO-spondin, a protein important for neuronal development. In this study, we investigated intrinsic disorder status of human spondins and their interacting partners, such as members of the LRP family, LGR family, Frizzled family, and several other binding partners in order to establish the existence and importance of disordered regions in spondins and their interacting partners by conducting a detailed analysis of their sequences, finding disordered regions, and establishing a correlation between their structure and biological functions.
Triptolide suppresses alkali burn-induced corneal angiogenesis along with a downregulation of VEGFA and VEGFC expression
Feb 24, 2017   Anatomical Record (Hoboken, N.J. : 2007)
Wang G, Li N, Lv X, Ahmed N, Li X, Liu H, Ma J, Zhang Y
Triptolide suppresses alkali burn-induced corneal angiogenesis along with a downregulation of VEGFA and VEGFC expression
Feb 24, 2017
Anatomical Record (Hoboken, N.J. : 2007)
Triptolide (TPL) is an active compound extracted from a Chinese herbal medicine tripterygium wilfordii Hook. f. (Celastraceae), which has been used as an anti-inflammatory drug for years. It also inhibits the growth and proliferation of different types of cancer cells. The inhibitory effect of TPL on angiogenesis after chemical induced corneal inflammation was studied in vivo. The effects of TPL on the proliferation, apoptosis, migration and tube formation of rat aortic endothelial cells (RAECs) were studied in vitro. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Migration was analyzed using the scratch wound healing assay and transwell assay. Tube formation assay was used to examine angiogenesis. Real-time PCR and Western blot were used to determine the expression of VEGFA and VEGFC. To study the in vivo effects of TPL, the mouse model of alkali burn-induced corneal angiogenesis was used. The angiogenesis was analyzed by determining the density of the newly generated blood vessels in corneas. We found that TPL induced apoptosis and inhibited the proliferation of RAECs in a dose-dependent manner. TPL inhibited migration and tube formation of RAECs and decreased the expression of VEGFA and VEGFC in vitro. Furthermore, TPL suppressed alkali burn-induced corneal angiogenesis and inhibited the expression of VEGFA and VEGFC in corneas in vivo. In conclusion, topical TPL as a pharmacological agent has the ability to reduce angiogenesis in cornea and may have clinical indications for the treatment of corneal angiogenesis diseases which have to be further explored. This article is protected by copyright. All rights reserved.© 2017 Wiley Periodicals, Inc.
Selectively Inducing Cancer Cell Death by Intracellular Enzyme-Instructed Self-Assembly (EISA) of Dipeptide Derivatives
Feb 24, 2017   Advanced Healthcare Materials
Li J, Shi J, Medina JE, Zhou J, Du X, Wang H, Yang C, Liu J, Yang Z, Dinulescu DM, Xu B
Selectively Inducing Cancer Cell Death by Intracellular Enzyme-Instructed Self-Assembly (EISA) of Dipeptide Derivatives
Feb 24, 2017
Advanced Healthcare Materials
Tight ligand-receptor binding, paradoxically, is a major root of drug resistance in cancer chemotherapy. To address this problem, instead of using conventional inhibitors or ligands, this paper focuses on the development of a novel process-enzyme-instructed self-assembly (EISA)-to kill cancer cells selectively. Here it is demonstrated that EISA as an intracellular process to generate nanofibrils of short peptides for selectively inhibiting cancer cell proliferation, including drug resistant ones. As the process that turns the non-self-assembling precursors into the self-assembling peptides upon the catalysis of carboxylesterases (CES), EISA occurs intracellularly to selectively inhibit a range of cancer cells that exhibit relatively high CES activities. More importantly, EISA inhibits drug resistant cancer cells (e.g., triple negative breast cancer cells (HCC1937) and platinum-resistant ovarian cells (SKOV3, A2780cis)). With the IC© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression
Feb 24, 2017   Cell Death And Differentiation
Sun X, Yang Q, Rogers CJ, Du M, Zhu MJ
AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression
Feb 24, 2017
Cell Death And Differentiation
Impairment in gut epithelial integrity and barrier function is associated with many diseases. The homeostasis of intestinal barrier is based on a delicate regulation of epithelial proliferation and differentiation. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism, and cellular metabolites are intrinsically involved in epigenetic modifications governing cell differentiation. We aimed to evaluate the regulatory role of AMPK on intestinal epithelial development and barrier function. In this study, AMPK activator (AICAR) improved the barrier function of Caco-2 cells as indicated by increased transepithelial electrical resistance and reduced paracellular FITC-dextran permeability; consistently, AICAR enhanced epithelial differentiation and tight junction formation. Transfection of Caco-2 cells with AMPK WT plasmid, which enhances AMPK activity, improved epithelial barrier function and epithelial differentiation, while K45R (AMPK dominant negative mutant) impaired; these changes were correlated with the expression of caudal type homeobox 2 (CDX2), the key transcription factor committing cells to intestinal epithelial lineage. CDX2 deficiency abolished intestinal differentiation promoted by AMPK activation. Mechanistically, AMPK inactivation was associated with polycomb repressive complex 2 regulated enrichment of H3K27me3, the inhibitory histone modification, and lysine-specific histone demethylase-1-mediated reduction of H3K4me3, a permissive histone modification. Those histone modifications provide a mechanistic link between AMPK and CDX2 expression. Consistently, epithelial AMPK knockout in vivo reduced CDX2 expression, impaired intestinal barrier function, integrity and ultrastructure of tight junction, and epithelial cell migration, promoted intestinal proliferation and exaggerated dextran sulfate sodium-induced colitis. In summary, AMPK enhances intestinal barrier function and epithelial differentiation via promoting CDX2 expression, which is partially mediated by altered histone modifications in the Cdx2 promoter.Cell Death and Differentiation advance online publication, 24 February 2017; doi:10.1038/cdd.2017.14.
Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
Feb 24, 2017   Blood Cancer Journal
Chavan SS, He J, Tytarenko R, Deshpande S, Patel P,   . . . . . .   , Barlogie B, Mughal TI, Davies FE, Morgan GJ, Walker BA
Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
Feb 24, 2017
Blood Cancer Journal
The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.
IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting
Feb 24, 2017   Nature Communications
Takeda K, Nakayama M, Hayakawa Y, Kojima Y, Ikeda H, Imai N, Ogasawara K, Okumura K, Thomas DM, Smyth MJ
IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting
Feb 24, 2017
Nature Communications
Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution.
Foamy Histiocyte-Like Hepatocellular Carcinoma (HCC): A New Variant of HCC?
Feb 24, 2017   Annals Of Hepatology
Dunn R, Zhang W, Lai J, Litton T, Zhou Y, Lai JP
Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence
Feb 24, 2017   Scientific Reports
Zheng HY, Zhang MX, Chen M, Jiang J, Song JH, Lian XD, Tian RR, Zhang XL, Zhang LT, Pang W, Zhang GH, Zheng YT
Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence
Feb 24, 2017
Scientific Reports
The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4
LINC00672 contributes p53-mediated gene suppression and promotes endometrial cancer chemosensitivity
Feb 24, 2017   The Journal Of Biological Chemistry
Li W, Li H, Zhang L, Hu M, Li F, Deng J, An M, Wu S, Ma R, Lu J, Zhou Y
LINC00672 contributes p53-mediated gene suppression and promotes endometrial cancer chemosensitivity
Feb 24, 2017
The Journal Of Biological Chemistry
Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals in genome-wide sequencing studies. Some of these RNAs have been consistently conserved during the evolution of species and, could presumably function in important biological processes. We, therefore, measured the levels of 26 highly conserved lincRNAs in a total of 176 pairs of endometrial carcinoma (EC) and surrounding non-tumor tissues of two distinct Chinese populations. Here, we report that a lincRNA, LINC00672, which possesses an ultra-conserved region, is aberrantly downregulated during the development of EC. Nevertheless, LINC00672 is a p53-targeting lincRNA acting along with hnRNPs as a suppressive cofactor, which locally reinforces p53-mediated suppression of LASP1, an evolutionarily conserved neighboring gene of LINC00672 and putatively associated with increased tumor aggressiveness, during anti-tumor processes. LINC00672 overexpression could lower the levels of LASP1 and slow the development of malignant phenotypes of EC both in vitro and in vivo. Moreover, LINC00672 significantly increased the 50% inhibitory concentration of paclitaxel in EC cells and increased the sensitivity of xenograft mice to paclitaxel. These findings indicate that LINC00672 can influence LASP1 expression as a locus-restricted cofactor for p53-mediated gene suppression, thus impacting EC malignancies and chemosensitivity to paclitaxel.Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
NOR1 promotes hepatocellular carcinoma cell proliferation and migration through modulating the Notch signaling pathway
Feb 24, 2017   Experimental Cell Research
You K, Sun P, Yue Z, Li J, Xiong W, Wang J
NOR1 promotes hepatocellular carcinoma cell proliferation and migration through modulating the Notch signaling pathway
Feb 24, 2017
Experimental Cell Research
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Previous studies have reported that the oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor in several tumors. Recent evidence suggests that NOR1 is strongly expressed in HCC cells. However, its role and mechanism in HCC are unclear. In the current study, Western blot and qPCR detected strong NOR1 mRNA and protein expression in HepG2 and Hep3B cells. After transfection with NOR1 siRNA or pcDNA3.1-myc-his-NOR1, the proliferation and migration of HepG2 and Hep3B cells were analyzed in vitro. HepG2 or Hep3B cells overexpressing NOR1 showed an increased proliferation and migration, whereas siRNA-mediated silencing of NOR1 showed the opposite effect. Furthermore, NOR1 activated the Notch signaling pathway, indicated by increased levels of Notch1, NICD, Hes1, and Hey1 in protein. Importantly, the Notch inhibitor DAPT downregulated Notch activation and further enhanced siNOR1-induced reduction of cell proliferation and migration in HepG2 and Hep3B cells, whereas DAPT reversed the effect of NOR1 overexpression on cell proliferation and migration. In conclusion, these results indicate that NOR1 may be involved in the progression of HCC and thus may be a potential target for the treatment of liver cancer.Copyright © 2017. Published by Elsevier Inc.
Neoadjuvant Therapy in Microsatellite Stable Colorectal Carcinoma Induces Concomitant Loss of MSH6 and Ki67 Expression
Feb 24, 2017   Human Pathology
Kuan SF, Ren B, Brand R, Dudley B, Pai RK
Neoadjuvant Therapy in Microsatellite Stable Colorectal Carcinoma Induces Concomitant Loss of MSH6 and Ki67 Expression
Feb 24, 2017
Human Pathology
Universal screening using immunohistochemistry for DNA mismatch-repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) is advocated by major professional medical organizations to identify Lynch syndrome-associated colorectal carcinoma. Loss of MSH6 expression independent of MSH2 expression has been reported in microsatellite stable (MSS) colorectal carcinoma following neoadjuvant therapy. The mechanism remains unclear. We studied the immunohistochemical expression of MSH2, MSH6, and Ki67 in MSS colorectal carcinoma with (n=50) or without (n=64) preoperative neoadjuvant therapy and Lynch syndrome-associated colorectal carcinoma with confirmed MSH6 germline mutation (n=3). Twelve of 50 MSS colorectal carcinoma post-neoadjuvant resections demonstrated reduced MSH6 expression with loss of expression ranging from 20 to 100% of tumor cells. Eight of 64 MSS colorectal carcinoma without neoadjuvant therapy also exhibited reduced MSH6 expression but to a lesser degree (10 to 50% of tumor cells with loss of expression). In both subgroups, concomitant loss of MSH6 and Ki67 expressions was demonstrated in the same tumor areas in consecutive tissue sections. However, 3 cases of Lynch syndrome-associated colorectal carcinoma due to germline MSH6 mutation revealed complete loss of MSH6 expression with discordant positive Ki67 staining in the tumor cells. The MSH2-independent, Ki67-related expression of MSH6 in colorectal carcinoma helps to explain the heterogeneous MSH6 staining in MSS colorectal carcinoma with or without neoadjuvant therapy.Copyright © 2017. Published by Elsevier Inc.
Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells
Feb 24, 2017   The American Journal Of Chinese Medicine
Fu S, Yang Y, Liu D, Luo Y, Ye X, Liu Y, Chen X, Wang S, Wu H, Wang Y, Hu Q, You P
Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells
Feb 24, 2017
The American Journal Of Chinese Medicine
In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells, were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.
Orai1 mediates tumor-promoting store-operated Ca
Feb 24, 2017   Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Wang L, Hao J, Zhang Y, Yang Z, Cao Y, Lu W, Shu Y, Jiang L, Hu Y, Lv W, Liu Y, Dong P
Orai1 mediates tumor-promoting store-operated Ca
Feb 24, 2017
Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Gastrointestinal stromal tumors originate from interstitial cells of Cajal, the pacemaker cells of the gut. Ca
Beta-1,4-galactosyltransferase II predicts poor prognosis of patients with non-metastatic clear-cell renal cell carcinoma
Feb 24, 2017   Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Zhang H, Liu Y, Xie H, Fu Q, Liu Z, Zhu Y, Xu L, Zhang W, Yang Y, Xu J
Beta-1,4-galactosyltransferase II predicts poor prognosis of patients with non-metastatic clear-cell renal cell carcinoma
Feb 24, 2017
Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Beta-1,4-galactosyltransferase II is found to be associated with the alterations of tumor-related glycosylation. However, the clinical significance of beta-1,4-galactosyltransferase II in non-metastatic clear-cell renal cell carcinoma has not been reported up to now. Herein, our researches suggested that the expression level of beta-1,4-galactosyltransferase II was first found to be positively associated with tumor size, Fuhrman grade, lymphovascular invasion, rhabdoid differentiation, tumor necrosis and poor overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma, both in training set and validation set. Moreover, beta-1,4-galactosyltransferase II expression was identified as an independent adverse prognosticator for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Ultimately, prognostic accuracy of the nomogram integrating beta-1,4-galactosyltransferase II with other independent prognostic parameters was dramatically improved for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Taken together, beta-1,4-galactosyltransferase II is a potential independent adverse prognostic factor for postoperative recurrence and survival, which could be developed as a useful biomarker for non-metastatic clear-cell renal cell carcinoma by a series of further independent and retrospective studies, so as to help the postsurgical management of clear-cell renal cell carcinoma patients.
Bone marrow mesenchymal stem cells attenuate silica-induced pulmonary fibrosis via paracrine mechanisms
Feb 24, 2017   Toxicology Letters
Li X, Wang Y, An G, Liang D, Zhu Z, Lian X, Niu P, Guo C, Tian L
Bone marrow mesenchymal stem cells attenuate silica-induced pulmonary fibrosis via paracrine mechanisms
Feb 24, 2017
Toxicology Letters
The purpose of this study was to investigate the anti-fibrotic effect and possible mechanism of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung injury and fibrosis in vivo and in vitro. In vivo, rats were exposed to 50mg/ml silica intratracheally. The rats were sacrificed on day 15 or day 30 after intravenous injection of BMSCs. Histopathological examination demonstrated that BMSCs decreased the blue areas of collagen fibers and the number of nodules. Alveolar epithelium was damaged by silica, but it was restored by BMSCs. In vitro, BMSCs co-cultured with RLE-6TN cells in 6-Transwell plates were evaluated to determine the possible mechanism. The results demonstrated that BMSCs downregulated the expression of collagen I and III. BMSCs reversed morphological abnormalities and reduced the proliferation of RLE-6TN cells. These data showed that BMSCs did not give rise to alveolar epithelial cells directly, while the levels of hepatocyte growth factor, keratinocyte growth factor and bone morphogenetic protein -7 increased and expression of tumor necrosis factor-α and transforming growth factor-β1 decreased in the 6TN+Silica+BMSCs group compared with the 6TN+Silica group. Our results revealed that BMSCs exerted anti-fibrotic effects on silica-induced pulmonary fibrosis, which might be associated with paracrine mechanisms rather than differentiation.Copyright © 2017 Elsevier B.V. All rights reserved.
The Calreticulin control of human stress erythropoiesis is impaired by JAK2V617F in polycythemia vera
Feb 24, 2017   Experimental Hematology
Falchi M, Varricchio L, Martelli F, Marra M, Picconi O, Tafuri A, Girelli G, Uversky VN, Migliaccio AR
The Calreticulin control of human stress erythropoiesis is impaired by JAK2V617F in polycythemia vera
Feb 24, 2017
Experimental Hematology
Calreticulin is a CaCopyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Feb 24, 2017   The Journal Of Experimental Medicine
Öhlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS,   . . . . . .   , Fearon DT, Crawford JM, Clevers H, Park Y, Tuveson DA
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Feb 24, 2017
The Journal Of Experimental Medicine
Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated αSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.© 2017 Öhlund et al.
C-Myc dysregulation is a co-transforming event for NF-κB activated B-cells
Feb 24, 2017   Haematologica
David A, Arnaud N, Fradet M, Lascaux H, Ouk-Martin C, Gachard N, Zimber-Strobl U, Feuillard J, Faumont N
C-Myc dysregulation is a co-transforming event for NF-κB activated B-cells
Feb 24, 2017
Haematologica
While c-Myc dysregulation is constantly associated with highly proliferating B-cell tumors, NF-κB addiction is found in indolent lymphomas as well as diffuse large B-cell lymphomas either with an activated B-cell like phenotype or associated with Epstein-Barr virus. We raised the question of the effect of c-Myc in B-cells with NF-κB activated by three different inducers: Epstein-Barr Virus-latency III program, TLR-9 and CD40. Induction of c-Myc overexpression increased proliferation of Epstein-Barr Virus-latency III immortalized B-cells, an effect that was dependent on NF-κB. Results from transcriptomic signatures and functional studies showed that c-Myc over-expression increased Epstein-Barr Virus-latency III driven proliferation depending on NF-κB. In vitro, induction of c-Myc increased proliferation of B-cell with TLR9 dependant activation of Myd88, with decreased apoptosis. In the transgenic λc-Myc mouse model with c-Myc over expression in B-cells, in vivo activation of Myd88 by TLR9 induced splenomegaly related to increased S-phase entry of B-cells. Transgenic mice with both continuous CD40 signaling in B-cells and the λc-Myc transgene developed very aggressive lymphomas with characteristics of activated diffuse large B-cell lymphomas. The main characteristic gene expression profile signatures of these tumors were those of proliferation and energetic metabolism. These results suggest that c-Myc is an NF-κB co-transforming event in aggressive lymphomas with an activated phenotype, activated B-cell like diffuse large B-cell lymphomas. This would explain why NF-κB is associated with both indolent and aggressive lymphomas and opens new perspectives on the possibility of combinatory therapies targeting both c-Myc proliferating program and NF-κB activation pathways in diffuse large B-cell lymphomas.Copyright © 2017, Ferrata Storti Foundation.
Core cross-linked poly(ethylene glycol)-graft-Dextran nanoparticles for reduction and pH dual responsive intracellular drug delivery
Feb 24, 2017   Journal Of Colloid And Interface Science
Lian H, Du Y, Chen X, Duan L, Gao G, Xiao C, Zhuang X
Core cross-linked poly(ethylene glycol)-graft-Dextran nanoparticles for reduction and pH dual responsive intracellular drug delivery
Feb 24, 2017
Journal Of Colloid And Interface Science
A kind of core cross-linked poly(ethylene glycol)-graft-Dextran nanoparticles (CPD NPs) was prepared by a simple chemical cross-linking method for reduction and pH dual response drug delivery. The resultant CPD NPs are of homogeneous spherical structure with sizes from 69±11 to 107±18nm. Doxorubicin (DOX) was then loaded into the CPD NPs in high efficiency, and showing typical reduction and pH dual responsive release profiles. The flow cytometric analysis and confocal laser scanning microscopy (CLSM) confirmed that the DOX-loaded CPD NPs could be internalized into cancer cell efficiently and release DOX in intracellular environment. Furthermore, cell cytotoxicity assays indicated that the CPD NPs had good biocompatibility toward both cancerous and normal cells, while the Dox-loaded CPD NPs exhibited significant inhibition of cell proliferation in various cancer cells. Therefore, this biocompatible CPD NP may have great potential for intracellular drug delivery in clinical cancer therapy.Copyright © 2017 Elsevier Inc. All rights reserved.
Cytotoxicity of Polycations: Relationship of Molecular Weight and the Hydrolytic Theory of the Mechanism of Toxicity
Feb 24, 2017   International Journal Of Pharmaceutics
Monnery BD, Wright M, Cavill R, Hoogenboom R, Shaunak S, Steinke JH, Thanou M
Cytotoxicity of Polycations: Relationship of Molecular Weight and the Hydrolytic Theory of the Mechanism of Toxicity
Feb 24, 2017
International Journal Of Pharmaceutics
The mechanism of polycation cytotoxicity and the relationship to polymer molecular weight is poorly understood. To gain an insight into this important phenomenon a range of newly synthesized uniform (near monodisperse) linear polyethylenimines, commercially available poly(L-lysine)s and two commonly used PEI-based transfectants (broad 22kDa linear and 25kDa branched) were tested for their cytotoxicity against the A549 human lung carcinoma cell line. Cell membrane damage assays (LDH release) and cell viability assays (MTT) showed a strong relationship to dose and polymer molecular weight, and increasing incubation times revealed that even supposedly "non-toxic" low molecular weight polymers still damage cell membranes. The newly proposed mechanism of cell membrane damage is acid catalysed hydrolysis of lipidic phosphoester bonds, which was supported by observations of the hydrolysis of DOPC liposomes.Copyright © 2017. Published by Elsevier B.V.
Long non-coding RNA XIST promotes cell growth by regulating miR-139-5p/PDK1/AKT axis in hepatocellular carcinoma
Feb 24, 2017   Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Mo Y, Lu Y, Wang P, Huang S, He L, Li D, Li F, Huang J, Lin X, Li X, Che S, Chen Q
Long non-coding RNA XIST promotes cell growth by regulating miR-139-5p/PDK1/AKT axis in hepatocellular carcinoma
Feb 24, 2017
Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Abnormal expression of long non-coding RNA often contributes to unrestricted growth of cancer cells. Long non-coding RNA XIST expression is upregulated in several cancers; however, its modulatory mechanisms have not been reported in hepatocellular carcinoma. In this study, we found that XIST expression was significantly increased in hepatocellular carcinoma tissues and cell lines. XIST promoted cell cycle progression from the G1 phase to the S phase and protected cells from apoptosis, which contributed to hepatocellular carcinoma cell growth. In addition, we revealed that there was reciprocal repression between XIST and miR-139-5p. PDK1 was identified as a direct target of miR-139-5p. We proposed that XIST was responsible for hepatocellular carcinoma cell proliferation, and XIST exerted its function through the miR-139-5p/PDK1 axis.

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