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Find video protocols related to scientific articles indexed in Pubmed.
Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice.
Cancer Biol. Ther.
PUBLISHED: 01-04-2013
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Esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive cancers with poor prognosis regardless of a several reports that indicate a better therapeutic efficacy using some new chemotherapeutic agents. Recent drug development has contributed to an improved specificity to suppress mTOR activity by which many types of malignancies can be explosively progressed. Temsirolimus (CCI-779, TricelTM) is one of recently synthesized analogs of rapamycin and has provided better outcomes for patients with renal cell carcinoma. In this study, we experimentally evaluated an efficacy of targeting mTOR by temsirolimus for ESCC treatment, with an assessment of its survival advantage using an advanced ESCC animal model. First, we confirmed that the expression of phosphorylated mTOR was increased in 46 of 58 clinical ESCC tumor tissues (79.3%) and appeared to get strengthened with tumor progression. All of ESCC cell lines used in this study revealed an increase of mTOR phosphorylation, accompanied with the upregulation of hypoxia inducible factor-I ? (HIF-1?), one of the critical effectors regulated by mTOR. Temsirolimus treatment apparently suppressed the activation of mTOR and its downstream effectors, resulting in the reduced ability of ESCC cell proliferation. Finally, the weekly administration of temsirolimus significantly diminished the size of subcutaneous tumors (vehicle, 3261.6 ± 722.0; temsirolimus, 599.2 ± 122.9; p = 0.007) in nude mice and effectively prolonged orthotopic esophageal cancer-bearing mice (median survival periods: control, 31 d; temsirolimus, 43 d; p = 0.0024). These data suggests that targeting mTOR by temsirolimus may become a therapeutic alternative for esophageal cancer, with a contribution to a better outcome.
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Inhibition of the growth factor MDK/midkine by a novel small molecule compound to treat non-small cell lung cancer.
PLoS ONE
PUBLISHED: 01-01-2013
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Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. MDK activates the PI3K pathway and induces anti-apoptotic activity, in turn enhancing the survival of tumors. Therefore, the inhibition of MDK is considered a potential strategy for cancer therapy. In the present study, we demonstrate a novel small molecule compound (iMDK) that targets MDK. iMDK inhibited the cell growth of MDK-positive H441 lung adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous cell lung cancer cells, both of which are types of untreatable lung cancer. However, iMDK did not reduce the cell viability of MDK-negative A549 lung adenocarcinoma cells or normal human lung fibroblast (NHLF) cells indicating its specificity. iMDK suppressed the endogenous expression of MDK but not that of other growth factors such as PTN or VEGF. iMDK suppressed the growth of H441 cells by inhibiting the PI3K pathway and inducing apoptosis. Systemic administration of iMDK significantly inhibited tumor growth in a xenograft mouse model in vivo. Inhibition of MDK with iMDK provides a potential therapeutic approach for the treatment of lung cancers that are driven by MDK.
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Porcine Fc?RIIb mediates enhancement of porcine reproductive and respiratory syndrome virus (PRRSV) infection.
PLoS ONE
PUBLISHED: 08-11-2011
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Antibody-dependent enhancement (ADE) of virus infection caused by the uptake of virus-antibody complexes by Fc?Rs is a significant obstacle to the development of effective vaccines to control certain human and animal viral diseases. The activation Fc?Rs, including Fc?RI and Fc?RIIa have been shown to mediate ADE infection of virus. In the present paper, we showed that pocine Fc?RIIb, an inhibitory Fc?R, mediates ADE of PRRSV infection. Stable Marc-145 cell lines expressing poFc?RIIb (Marc-poFc?RII) were established. The relative yield of progeny virus was significantly increased in the presence of sub-neutralization anti-PRRSV antibody. The Fab fragment and normal porcine sera had no effect. Anti-poFc?RII antibody inhibited the enhancement of infection when cells were infected in the presence of anti-PRRSV antibody, but not when cells were infected in the absence of antibody. These results indicate that enhancement of infection in these cells by anti-PRRSV virus antibody is Fc?RII-mediated. Identification of the inhibitory Fc?R mediating ADE infection should expand our understanding of the mechanisms of pathogenesis for a broad range of infectious diseases and may open many approaches for improvements to the treatment and prevention of such diseases.
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HSP90 and its inhibitors.
Oncol. Rep.
PUBLISHED: 04-30-2010
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The HSP90 molecular chaperone family is highly conserved and expressed in various organisms ranging from prokaryotes to eukaryotes. HSP90 proteins play essential housekeeping functions, such as controlling the activity, turnover and trafficking of various proteins, promoting cell survival through maintaining the structural and functional integrity of some client proteins which control cell survival, proliferation and apoptosis, and play an important role in the progression of malignant disease. HSP90 proteins are ATP-dependent chaperones and the binding and hydrolysis of ATP are coupled to conformation changes of HSP90, which facilitate client protein folding and maturation. Many natural and synthetic molecular compounds have been proposed as promising cancer therapy via disrupting the formation of complex ATP-HSP90-client proteins.
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Focal adhesion kinase as potential target for cancer therapy (Review).
Oncol. Rep.
PUBLISHED: 09-30-2009
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Focal adhesion kinase (FAK) is a 125-kDa non-receptor and non-membrane protein tyrosine. FAK can function with integrins and growth factor receptors to promote cell survival dependent kinase activity and nuclear FAK promotes cell proliferation and survival through FERM (FAK, ezrin, radixin, moesin) domain-enhanced p53 degradation independent kinase activity. Many previous studies have indicated that FAK plays a critical role in the biological processes of normal and cancer cells and FAK has been proposed as a potential target in cancer therapy. Small molecule inhibitors (PF-573,228; PF-562,271 and NVP-226) for use as potential cancer therapies have been developed. However, the detailed mechanism of the role for FAK in tumor cell generation and progression remain unclear, so future work is needed to explore these issues. New inhibitors that can be effectively inhibit the function of FAK still need to be explored due to the low specificity, and resistance.
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Characterization and ligand specificity of sheep IgG2 receptor.
Immunogenetics
PUBLISHED: 03-06-2009
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Neutrophils and macrophages in cattle express a novel class of immunoglobulin Fc receptor, specific for bovine IgG2, termed boFcgamma2R. In cows, the ability of neutrophils to kill immunoglobulin-opsonized microorganisms appears to depend largely on this subclass. Although related to other mammalian FcgammaRs, boFcgamma2R belongs to a novel gene family that includes the human killer Ig-like receptor and FcalphaRI (CD89) proteins. In this study, we describe the presence and characterization of this novel class of FcgammaR in sheep. The comparative analysis of this novel FcgammaR has allowed us to begin an exploration of some immunological characteristic of ruminants.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.