scholarly journals In Vivo Expression of HGF/NK1 and GLP-1 From dsAAV Vectors Enhances Pancreatic  -Cell Proliferation and Improves Pathology in the db/db Mouse Model of Diabetes

Diabetes ◽  
2010 ◽  
Vol 59 (12) ◽  
pp. 3108-3116 ◽  
Author(s):  
D. F. Gaddy ◽  
M. J. Riedel ◽  
S. Pejawar-Gaddy ◽  
T. J. Kieffer ◽  
P. D. Robbins
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Pancreatic Cell ◽  
In Vivo Expression

scholarly journals TMOD-08A MOUSE MODEL OF YOUNG ADULT GLIOBLASTOMA: IN VIVO EXPRESSION OF MUTATED IDH1 (R132H) GENE USING THE SLEEPING BEAUTY TRANSPOSASE SYSTEM

2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v227.4-v227
Author(s):  
Felipe J. Nunez ◽  
Flor Mendez ◽  
Carl Koshmann ◽  
Alexandra Calinescu ◽  
Marta Dzaman ◽  
...  
Keyword(s):  
Young Adult ◽  
Mouse Model ◽  
Sleeping Beauty ◽  
Idh1 R132h ◽  
In Vivo Expression

In Vivo Fluorescence Microendoscopic Monitoring of Stent-Induced Fibroblast Cell Proliferation in an Esophageal Mouse Model

2018 ◽  
Vol 29 (12) ◽  
pp. 1756-1763
Author(s):  
Eun Jung Jun ◽  
Ho-Young Song ◽  
Jung-Hoon Park ◽  
Yoon Sung Bae ◽  
Bjorn Paulson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Fibroblast Cell ◽  
In Vivo Fluorescence

Su1671 Antibiotic-Based In Vivo Expression Technology Screen for Helicobacter pylori Genes Expressed in Mouse Model

2012 ◽  
Vol 142 (5) ◽  
pp. S-478
Author(s):  
Aparna Singh ◽  
Nathaniel Hodgson ◽  
Ming Yan ◽  
Sharon Jackson ◽  
William G. Coleman
Keyword(s):  
Helicobacter Pylori ◽  
Mouse Model ◽  
In Vivo Expression

scholarly journals Robo2 Predicts a Better Prognosis and Inhibits Malignant Behavior in Vivo in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Author(s):  
Cheng Ding ◽  
Yatong Li ◽  
Shunda Wang ◽  
Cheng Xing ◽  
Lixin Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Rna Sequencing ◽  
Cell Lines ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Pdac Cell ◽  
Pancreatic Cell

Abstract BackgroundPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with an extremely poor prognosis and a high mortality rate. Genome-wide studies have shown that the SLIT/ROBO signaling pathway plays an important role in pancreatic tumor development and progression. However, the effect and mechanism of ROBO2 in the progression of pancreatic cancer remains largely unknown.MethodsIn this study, real-time polymerase chain reaction (RT-PCR) and western blot analyses were adopted to evaluate the expression level of ROBO2 and proteins in pancreatic cell lines. Cell migration and invasion and cell proliferation were conducted in AsPC-1 and MIA PaCa-2 cell lines. RNA sequencing and western blot were undertaken to explore the mechanisms and potential targeted molecules. ROBO2 expression in tumor tissues was evaluated by immunohistochemistry in 95 patients.ResultsROBO2 expression was downregulated in PDAC cell lines and tissue samples. A high level of ROBO2 was associated with good overall survival. Upregulation of ROBO2 inhibited PDAC cell proliferation, migration, and invasion, whereas the opposite results were found in the ROBO2 downregulation group. In addition, xenograft animal models further confirmed the effect of ROBO2 on proliferation. Finally, the RNA sequencing results indicated that ROBO2 facilitates anti-tumorigenicity partly via inhibiting ECM1 in PDAC. ConclusionsOur work suggests that ROBO2 inhibits tumor progression in PDAC and may serve as a predictive biomarker and therapeutic target in PDAC.

Effect of AdipoR agonist in cholangiocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 323-323
Author(s):  
Khac Cuong Bui ◽  
Mai Ly Thi Nguyen ◽  
Samarpita Barat ◽  
Xi Chen ◽  
Vikas Bhuria ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Cell Lines ◽  
Colony Formation ◽  
Tumor Burden ◽  
Potential Candidate ◽  
Anti Cancer ◽  
Apoptosis Assay

323 Background: Adiponectin is the key adipokine, which plays an important role in health and disease such as obesity, diabetes, and cancer. Adiponectin is reduced in different tumor types, especially in obesity-related cancer, and recent studies showed that Adiponectin had a potential anti-cancer effect. Obesity is a risk factor for various tumor diseases including cholangiocarcinoma (CC), the second most common primary hepatic cancer. The aim of this study is to investigate for the first time the anti-cancer effect of AdipoR agonist in CC cell lines and a CC engineered mouse model. Methods: Human CC cell lines (TFK-1 and SZ-1) and CC engineered mice (Alb-Cre/KRASG12D/p53L/L) were used to investigate the anti-cancer effects of an AdipoR agonist (2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide). Cell proliferation, migration, invasion, colony formation, apoptosis assay were applied to evaluate the effect of AdipoR agonist in vitro. In addition, important cancer signalling pathways and targets were analysed by Western Blot. Mice (n = 12) were treated with AdipoR or verhicle and tumor burden and survival were monitored. Results: AdipoR agonist suppressed proliferation, migration, invasion, colony formation and apoptosis in CC cells. AdipoR agonist regulated the expression of different proteins such as EMT markers, pAMPK, pSTAT3, and PARP, which have pivotal functions in cholangiocarcinogenesis. AdipoR agonist also prolonged survival time in a CC engineered mouse model. Conclusions: Our data revealed that AdipoR agonist inhibited successfully cell proliferation, migration, invasion, colony formation and apoptosis in vitro, and prolonged mice survival in vivo through regulation of crucial signaling pathways in cholangiocarcinogenesis. These results suggested that AdipoR agonist might become a new potential candidate for CC treatment in the future.

Abstract 3033: Generation of a mouse model of young adult glioblatoma: In vivo expression of mutated IDH1-R132H gene using the sleeping beauty transposase system

2015 ◽  
Author(s):  
Felipe J. Nunez ◽  
Flor M. Mendez ◽  
Carl Koschmann ◽  
Alexandra Calinescu ◽  
Pedro R. Lowenstein ◽  
...  
Keyword(s):  
Young Adult ◽  
Mouse Model ◽  
Sleeping Beauty ◽  
Idh1 R132h ◽  
In Vivo Expression

The ATP-Competitive mTOR Inhibitor AZD8055 Reduces Cell Proliferation and Tumour Load in Chronic Lymphocytic Leukaemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5287-5287
Author(s):  
Emilio Cosimo ◽  
Anuradha Tarafdar ◽  
Ailsa Holroyd ◽  
Karen Dunn ◽  
Mark Catherwood ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Chronic Lymphocytic Leukaemia ◽  
Mtor Inhibitor ◽  
Lymphocytic Leukaemia ◽  
Lymphoid Organs ◽  
Tumour Burden ◽  
Drug Concentrations

Abstract Chronic lymphocytic leukaemia (CLL), often diagnosed in the elderly, is incurable with current therapeutic regimes. Recent studies demonstrate that the microenvironment within CLL patient lymphoid organs protects leukaemic cells from chemotherapy induced apoptosis. This highlights the need for novel therapies that can overcome such cytoprotective signals. Serine/threonine protein kinase mammalian target for rapamycin (mTOR) is a key regulator of cell survival and proliferation and is commonly deregulated in cancer. mTOR is active in two complexes mTORC1 and mTORC2. We demonstrate that mTORC1 and mTORC2 substrates, including S6 (pS6S235/236) and Akt (pAktS473) respectively, are active although differentially regulated, in CLL cells from distinct prognostic subsets ex vivo, which suggests that mTOR may represent a valid therapeutic target for CLL. Initial studies with everolimus, an analogue of rapamycin, showed only limited antitumor activity in recurrent/refractory CLL patients, possibly because mTORC1 inhibition releases the "brake" that normally active mTORC1 has on mTORC2, thus enabling mTORC2 mediated signalling. To test the impact of inhibiting both mTORC1 and mTORC2 on cell proliferation and survival, we treated primary CLL cells and an aggressive CLL mouse model with the novel ATP-competitive mTOR inhibitor AZD8055 in vitro and in vivo. CLL proliferation and mTORC1/2 activity were significantly reduced upon addition of AZD8055 to NTL-CD154/IL4 co-cultures, which mimic pro-proliferative conditions present in the microenvironment of lymphoid organs. However, in the same conditions use of AZD8055 did not induce apoptosis at clinically-achievable drug concentrations (<150 nM), likely due to ineffective inhibition of Mcl-1 upregulation mediated by the NTL-CD154/IL4 co-cultures. In contrast, B cell receptor (BCR)-mediated survival was inhibited by AZD8055 treatment, inducing significant levels of apoptosis, concomitant with a decreased Mcl-1 expression. These findings suggest that the BCR and CD154/IL4 mediated pathways regulate Mcl-1 expression by distinct mechanisms. In vivo studies using the PKCa-KR-induced CLL mouse model revealed that AZD8055 treatment efficiently reduced tumour burden in the organs (spleen and bone marrow) and blood of mice with established CLL. This was reflected by in vitro studies showing that use of AZD8055 increased apoptosis and reduced proliferation in mouse CLL cells. Overall these data indicate that AZD8055 inhibits CLL proliferation, in vitro and in vivo, and disrupts BCR mediated survival, by downregulating Mcl-1 protein levels. Therefore dual mTOR inhibitors through reduction of tumour burden, show promise as a future therapy for CLL. Disclosures No relevant conflicts of interest to declare.

A Novel BRD4 Inhibitor CA2 Suppresses MM Cell Proliferation in an Orthotopic Myeloma Mouse Model

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4722-4722
Author(s):  
Natsuki Imayoshi ◽  
Makoto Yoshioka ◽  
Susumu Nakata ◽  
Jay Chauhan ◽  
Yoko Kado ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Medical Center ◽  
Subcutaneous Administration ◽  
Vehicle Control ◽  
Care Organization ◽  
Dependent Manner ◽  
Proliferation In Vitro

Abstract We previously demonstrated that a novel BRD4 inhibitor, CA2, suppressed MM cell proliferation in vitro in the 57th ASH Annual Meeting. In the present study, we investigated the inhibitory mechanisms of CA2 on myeloma cell proliferation in vitro and in vivo. CA2 has a unique quinolinone core and inhibited the proliferation of MM cell lines, MM.1s, AMO-1, NCI-H929, OPM-2, and IM-9. As expected, CA2 suppressed the expression of c-MYC mRNA and protein in a dose- and time-dependent manner. In addition, CA2 decreased BRD4 binding to c-MYC promoters and c-MYC enhancers in a ChIP assay using IM-9 cells and an anti-BRD4 antibody (Figure 1). Flow cytometric Annexin-V/propodium iodide staining analyses demonstrated that CA2 induced apoptosis in MM cells. Taken together, CA2 may induce apoptosis in MM cells by inhibiting the binding of BRD4 to promoters and enhancers of c-MYC gene thereby suppressing c-MYC expression. We next performed a pharmacokinetic study of CA2 in mice. Half-lives (t1/2) of CA2 following oral administration (50 mg/kg) and subcutaneous administration (10 mg/kg) were approximately 61 min and 139.8 min, respectively. The values of area under the curve for oral and subcutaneous administrations were 179,000 hr·ng/mL and 31,000 hr·ng/mL, respectively. Lastly, we assessed the in vivo effects of CA2 using orthotopic MM mouse model, where IM-9Luc cells were inoculated intravenously through the tail veins of SCID mice that had received 2 Gy of irradiation. The mice in the vehicle-control arm died of MM by approximately 30 days after transplantation; IM-9Luc cells engrafted in many organs including bone marrow of spine and femurs, kidneys, ovaries, and stomach. CA2 treatment consisting of 20 cycles of 100 mg/kg/day b.i.d. oral dosing resulted in reduced luminescence intensity of IM-9Luc cells and prolonged the survival of mice (mean 33.7 days) compared to the vehicle-control arm (mean 27.1 days; p=0.029, Figure 2). In conclusion, CA2 is a BRD4 inhibitor with a novel structure and could be a promising molecular targeting-agent against MM. Disclosures Yoshioka: ConverGene LLC: Employment. Kado:Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center: Employment. Strovel:ConverGene LLC: Employment.

scholarly journals Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 49 ◽  
Author(s):  
Young Yun Jung ◽  
Muthu K. Shanmugam ◽  
Acharan S. Narula ◽  
Chulwon Kim ◽  
Jong Hyun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Mouse Model ◽  
A549 Cells ◽  
Xenograft Model ◽  
Signaling Cascade ◽  
Anticancer Effects ◽  
Anti Cancer

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

scholarly journals ICG-001, an Inhibitor of the β-Catenin and cAMP Response Element-Binding Protein Dependent Gene Transcription, Decreases Proliferation but Enhances Migration of Osteosarcoma Cells

2021 ◽  
Vol 14 (5) ◽  
pp. 421
Author(s):  
Geoffroy Danieau ◽  
Sarah Morice ◽  
Sarah Renault ◽  
Régis Brion ◽  
Kevin Biteau ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Cell Lines ◽  
Gene Transcription ◽  
Pediatric Population ◽  
Wnt Signaling Pathway ◽  
Osteosarcoma Cell ◽  
Metastatic Dissemination

High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/β-catenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.

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