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Find video protocols related to scientific articles indexed in Pubmed.
Low incidence of IL6ST (gp130) mutations in exon 6 in lung cancer of a Chinese cohort.
Cancer Genet
PUBLISHED: 02-12-2014
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Lung cancer is an inflammation-associated epithelial carcinoma. A highly active interleukin 6 (IL-6)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway has been identified in a subset of primary lung cancer and closely correlated with tumor progression and poor prognosis. In a previous study, the frequent occurrence of somatic gain-of-function mutations was observed in the gp130-encoding IL6ST gene in exon 6 in 60% of inflammatory hepatocellular adenomas. Prompted by this finding, we assessed 110 Chinese lung carcinomas using PCR and direct DNA sequencing but found no somatic mutation of IL6ST in exon 6. However, one new potential germline missense mutation c.599C>G was identified in one adenocarcinoma that harbors wild-type epidermal growth factor receptor and KRAS. Protein modeling analysis showed that this mutation might not affect the gp130 protein conformation. Moreover, activated STAT3 was observed in most of the lung tumor tissues at a higher level than that in matched normal lung tissues. In conclusion, the c.599C>G mutation may be a new single nucleotide polymorphism of IL6ST, but mutations in exon 6 of this gene are not apparently common genetic variations occurring and leading to constitutive activation of STAT3 in lung cancer.
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CaMK IV phosphorylates prohibitin 2 and regulates prohibitin 2-mediated repression of MEF2 transcription.
Cell. Signal.
PUBLISHED: 04-29-2011
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Prohibitin 2 (PHB2) is an evolutionarily conserved and ubiquitously expressed multifunctional protein which is present in various cellular compartments including the nucleus. However, mechanisms underlying various functions of PHB2 are not fully explored yet. Previously we showed that PHB2 interacts with Akt and inhibits muscle differentiation by repressing the transcriptional activity of both MyoD and MEF2. Here we show that Calcium/Calmodulin-dependent kinase IV (CaMK IV) specifically binds to the C terminus of PHB2 and phosphorylates PHB2 at serine 91. Ectopic expression of CaMK IV and PHB2 in C2C12 cells results effectively in decreased PHB2-mediated repression of MEF2-dependent gene expression. Conversely, PHB2 mutant (S91A) resistant to CaMK IV phosphorylation has less effective in relieving the inhibition of MEF2 transcription by PHB2. Our findings suggest that CaMK IV interacts with and regulates PHB2 through phosphorylation, which could be one of the mechanisms underlying the CaMK-mediated activation of MEF2.
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Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration.
Cell Res.
PUBLISHED: 10-19-2010
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Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.
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Inhibition of a C-rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice.
Immunology
PUBLISHED: 07-22-2010
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To explore the possibility that human mitochondrial genomic DNA-mimicking oligodeoxynucleotides could regulate the immune response, a series of mitochondrial DNA-based oligodeoxynucleotides (MTODNs) were designed and studied to determine their immunoregulatory effects on immune cells activated by toll-like receptor (TLR) stimulation. The results showed that a C-rich MTODN, designated MT01, was able to inhibit the proliferation of human peripheral blood mononuclear cells (PBMCs) induced by cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) and the production of type I interferon (IFN) from human PBMCs stimulated by TLR agonists, including inactivated influenza virus, imiquimod, inactivated herpes simplex virus-1 (HSV-1) and CpG ODNs. In addition, MT01 inhibited the CpG ODN-enhanced antibody response and this inhibition could be related to the antagonism of TLR9-activation pathways in B cells. Notably, unlike the G-rich suppressive ODNs reported, MT01 is composed of ACCCCCTCT repeats. These data imply that MT01 represents a novel class of immunosuppressive ODNs that could be candidate biologicals with therapeutic use in TLR activation-associated diseases.
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Vaccination with B16 tumor cell lysate plus recombinant Mycobacterium tuberculosis Hsp70 induces antimelanoma effect in mice.
Cancer Biother. Radiopharm.
PUBLISHED: 04-29-2010
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Tumor cell lysate (TCL) has an advantage of containing an extensive repertoire of tumor antigens but requires proper adjuvants to enhance its immunogenicity when used as an efficient tumor vaccine. Mycobacterium tuberculosis-derived heat shock protein 70 (TBHsp70) has been shown to assist crosspresentation of exogenously applied tumor antigens and activate innate immunity against tumor cells. In this study, TBHsp70-B16TCL, a preparation generated by mixing recombinant TBHsp70 and TCL of B16 melanoma cells directly, was tested for its immunogenicity as a tumor vaccine. The TBHsp70-B16TCL induced a significant inhibition of the growth and metastasis of B16 melanoma in mice and prolonged the survival of B16 melanoma-bearing mice. The inhibition was correlated with the specific immune responses induced by TBHsp70-B16TCL. The data suggest that recombinant TBHsp70-adjuvanted TCL might be developed into effective tumor vaccines for melanomas and possibly for other tumors.
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Vaccination with TCL plus MHSP65 induces anti-lung cancer immunity in mice.
Cancer Immunol. Immunother.
PUBLISHED: 01-20-2010
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To develop effective anti-lung cancer vaccines, we directly mixed mycobacterial heat shock protein 65 (MHSP65) and tumor cell lysate (TCL) from Lewis lung cancer cells in vitro and tested its efficacy on stimulating anti-tumor immunity. Our results showed that MHSP65-TCL immunization significantly inhibited the growth of lung cancer in mice and prolonged the survival of lung cancer bearing mice. In vivo and in vitro data suggest that MHSP65-TCL could induce specific CTL responses and non-specific immunity, both of which could contribute to the tumor inhibition. Thus, this report provides an easy approach to prepare an efficient TCL based tumor vaccine.
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A novel canine favored CpG oligodeoxynucleotide capable of enhancing the efficacy of an inactivated aluminum-adjuvanted rabies vaccine of dog use.
Vaccine
PUBLISHED: 01-10-2010
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In order to develop novel canine CpG ODNs as adjuvant for rabies vaccine of dog use, a panel of CpG ODNs containing different CpG motifs was designed and screened for their ability to induce the proliferation of canine splenocytes. Three AACGTT motif-containing CpG ODNs, designated as YW07, YW08 and YW09, respectively, were outshined with stronger ability to activate canine immune cells. The CpG ODNs were tested for their adjuvant activity for rabies vaccine in mice and dogs. It was found that YW07 could facilitate the rabies vaccine to induce more vigorous and long-lasting specific antibody response in mice and dogs, respectively. These findings suggest that YW07, a canine favored CpG ODN, could be used as a novel adjuvant for developing more efficient rabies vaccine of dog use.
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STAT3 induces muscle stem cell differentiation by interaction with myoD.
Cytokine
PUBLISHED: 02-14-2009
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Signal transducers and activators of transcription (STAT) family proteins transduce pivotal biological effects of various cytokines and hormones. STAT3 proteins are known to play a central role in the regulation of growth, differentiation, and survival of many types of cells. However, the function of STAT3 in myogenesis still remains largely unknown. We now provided direct evidence that STAT3 could induce myogenic differentiation and this effect might be mediated by interaction with MyoD--the essential transcription factor during myogenic differentiation. Furthermore, leukemia inhibitory factor (LIF) might be the upstream factor which activated JAK2/STAT3 pathway to stimulate muscle cell differentiation. Taken together, these results provide a molecular basis for further understanding of the muscle regeneration mechanism.
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Human microsatellite DNA mimicking oligodeoxynucleotides down-regulate TLR9-dependent and -independent activation of human immune cells.
Mol. Immunol.
PUBLISHED: 02-07-2009
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To develop novel immunoregulatory oligodeoxynucleotides (ODNs), we have designed a series of ODNs based on the sequences in human microsatellite (MS) DNA. The ODNs, designated as human MS DNA mimicking ODNs (MS ODNs), have been studied for their inhibitory effects on human immune cells activated by TLR9-dependent and -independent stimulations. We find for the first time that MS08, a MS ODN composed entirely of TC dinucleotide (TC) repeats, inhibits CpG ODN (TLR9 ligand)-induced human PBMCs proliferation, CD80 and CD86 expression and production of interferon. In addition, MS08 also inhibits the proliferation of human PBMCs stimulated by PHA, PMA and alloantigens in a TLR9-independent manner. The inhibition correlates with competition of binding and uptake between MS08 and CpG ODN in human PBMCs. Structurally, TC, CT or CCT are revealed as essential suppressive motifs required for the inhibition. These findings suggest that TC repeat containing MS ODN could be of therapeutic use in pathologic situations due to excessive activation of immune cells.
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Therapeutic injection of C-class CpG ODN in draining lymph node area induces potent activation of immune cells and rejection of established breast cancer in mice.
Clin. Immunol.
PUBLISHED: 01-14-2009
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In order to develop novel CpG ODNs for the treatment of breast cancer, we have designed a series of CpG ODNs and evaluated their anti-tumor activity in a breast cancer mouse model. Interestingly, a C-class CpG ODN, designated as YW002, showed a vigorous activity on the inhibition of tumor growth in mice and completely cured some of the tumor-bearing mice through injection at tumor draining lymph node (TDLN) area. The expansion of immune cells in the TDLN and tumor and the generation of tumor specific immune memory were found associated with YW002-induced anti-tumor activity in mice. These results indicate that C-class CpG ODN could be developed into a medicament in a monotherapeutic regimen for the treatment of breast cancer through injection at TDLN area in clinic.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.