JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Related JoVE Video
Significant Association of oncogene YAP1 with Poor Prognosis and Cetuximab Resistance in Colorectal Cancer Patients.
Clin. Cancer Res.
PUBLISHED: 11-13-2014
Show Abstract
Hide Abstract
Purpose: Activation of YAP1, novel oncogene in Hippo pathway, has been observed in many cancers including colorectal cancer (CRC). We investigated if activation of YAP1 is significantly associated with prognosis or treatment outcomes in CRC Experimental Design: A gene expression signature reflecting YAP1 activation was identified in CRC cells, and CRC patients were stratified into two groups according to this signature: activated YAP1 CRC (AYCC) or inactivated YAP1 CRC (IYCC). Stratified patients in five test cohorts were evaluated to determine the effect of the signature on CRC prognosis and response to cetuximab treatment. Results: The activated YAP1 signature was associated with poor prognosis for CRC in four independent patient cohorts with stage I-III disease (total n = 1,028). In a multivariate analysis, the impact of the YAP1 signature on the disease-free survival was independent of other clinical variables [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.25-2.13; P < 0.001]. In patients with stage IV CRC and wild-type KRAS, IYCC patients had a better disease control rate and progression-free survival (PFS) after cetuximab monotherapy than did AYCC patients; however, in patients with KRAS mutations, PFS duration after cetuximab monotherapy was not different between IYCC and AYCC patients. In multivariate analysis, the effect of YAP1 activation on PFS was independent of KRAS mutation status and other clinical variables (HR, 1.82; 95% CI, 1.05-3.16; P = 0.03). Conclusions: Activation of YAP1 is highly associated with poor prognosis for CRC and may be useful in identifying patients with metastatic CRC resistant to cetuximab.
Related JoVE Video
Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas.
Gut
PUBLISHED: 11-12-2014
Show Abstract
Hide Abstract
Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome.
Related JoVE Video
Nodular fasciitis on temple area resulting in surgical trauma.
J Craniofac Surg
PUBLISHED: 11-04-2014
Show Abstract
Hide Abstract
Nodular fasciitis (NF) is a pseudosarcomatous reactive proliferative lesion that commonly occurs as a solitary, well-circumscribed, painful, rapidly growing soft tissue mass. It appears at any age, but incidence peaks in the third decade, with a slight predilection for women. It is most commonly located on the extremities, followed by the chest and trunk. Although a common site in the pediatric population, NF is found on the head and neck only in 7% to 20% in the adult population and includes the cheek, parotid region, zygoma, periorbital area, eyelid, forehead, and intraoral sites. The cause of NF is unknown, but an association with trauma may be present. A case of NF over the temple area in a 28-year-old man who has no trauma history but has surgical incisional biopsy history and tenderness on palpation is reported.
Related JoVE Video
Conformational coupling between the active site and residues within the KC-channel of the Vibrio cholerae cbb3-type (C-family) oxygen reductase.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-06-2014
Show Abstract
Hide Abstract
The respiratory chains of nearly all aerobic organisms are terminated by proton-pumping heme-copper oxygen reductases (HCOs). Previous studies have established that C-family HCOs contain a single channel for uptake from the bacterial cytoplasm of all chemical and pumped protons, and that the entrance of the K(C)-channel is a conserved glutamate in subunit III. However, the majority of the K(C)-channel is within subunit I, and the pathway from this conserved glutamate to subunit I is not evident. In the present study, molecular dynamics simulations were used to characterize a chain of water molecules leading from the cytoplasmic solution, passing the conserved glutamate in subunit III and extending into subunit I. Formation of the water chain, which controls the delivery of protons to the K(C)-channel, was found to depend on the conformation of Y241(Vc), located in subunit I at the interface with subunit III. Mutations of Y241(Vc) (to A/F/H/S) in the Vibrio cholerae cbb3 eliminate catalytic activity, but also cause perturbations that propagate over a 28-Å distance to the active site heme b3. The data suggest a linkage between residues lining the K(C)-channel and the active site of the enzyme, possibly mediated by transmembrane helix ?7, which contains both Y241(Vc) and the active site cross-linked Y255(Vc), as well as two CuB histidine ligands. Other mutations of residues within or near helix ?7 also perturb the active site, indicating that this helix is involved in modulation of the active site of the enzyme.
Related JoVE Video
Growth Suppression of Colorectal Cancer by Plant-Derived Multiple mAb CO17-1A × BR55 via Inhibition of ERK1/2 Phosphorylation.
Int J Mol Sci
PUBLISHED: 09-16-2014
Show Abstract
Hide Abstract
We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAbP) CO17-1A and mAbP CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAbP CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAbP CO17-1A × BR55-treated. The mAbP CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAbP CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAbP CO17-1A × BR55. In addition, the mAbP CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAbP CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAbP CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.
Related JoVE Video
In silico analysis of genomic data for construction of nuclear receptor network.
Methods Mol. Biol.
PUBLISHED: 09-04-2014
Show Abstract
Hide Abstract
Availability of genome-wide information in public database provides unprecedented opportunity for developing new strategy to uncover potential interactions of members in large functional family. Here we describe a systematic strategy for constructing and analyzing potential interaction map to uncover novel interaction between nuclear receptors that may play important roles in human disease. This in silico approach can prioritize candidate interactions for further functional validation and assess its clinical relevance.
Related JoVE Video
Mesenchymal Stem/Stromal Cells Protect the Ocular Surface by Suppressing Inflammation in an Experimental Dry Eye.
Mol. Ther.
PUBLISHED: 08-25-2014
Show Abstract
Hide Abstract
Dry eye syndrome (DES) is one of the most common ocular diseases affecting nearly 10% of the US population. Most of the currently available treatments are palliative, and few therapeutic agents target biological pathway of DES. Although DES is a multifactorial disease, it is well-known that inflammation in the ocular surface plays an important role in the pathogenesis of DES. Mesenchymal stem/stromal cells (MSCs) have been shown to repair tissues by modulating excessive immune responses in various diseases. Therefore, we here investigated the therapeutic potential of MSCs in a murine model of an inflammation-mediated dry eye that was induced by an intraorbital injection of concanavalin A. We found that a periorbital administration of MSCs reduced the infiltration of CD4(+) T cells and the levels of inflammatory cytokines in the intraorbital gland and ocular surface. Also, MSCs significantly increased aqueous tear production and the number of conjunctival goblet cells. Subsequently, corneal epithelial integrity was well-preserved by MSCs. Together, the results demonstrate that MSCs protect the ocular surface by suppressing inflammation in DES, and suggest that MSCs may offer a therapy for a number of ocular surface diseases where inflammation plays a key role.Molecular Therapy (2014); doi:10.1038/mt.2014.159.
Related JoVE Video
TSG-6 protects corneal endothelium from transcorneal cryoinjury in rabbits.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-19-2014
Show Abstract
Hide Abstract
To investigate the effect of an anti-inflammatory protein, TNF-? stimulated gene/protein (TSG)-6 and an antiapoptotic protein, stanniocalcin (STC)-1 on corneal endothelium in rabbits with transcorneal cryoinjury.
Related JoVE Video
Intraperitoneal infusion of mesenchymal stem/stromal cells prevents experimental autoimmune uveitis in mice.
Mediators Inflamm.
PUBLISHED: 07-17-2014
Show Abstract
Hide Abstract
Autoimmune uveitis is one of the leading causes of blindness. We here investigated whether intraperitoneal administration of human mesenchymal stem/stromal cells (hMSCs) might prevent development of experimental autoimmune uveitis (EAU) in mice. Time course study showed that the number of IFN-?- or IL-17-expressing CD4(+) T cells was increased in draining lymph nodes (DLNs) on the postimmunization day 7 and decreased thereafter. The retinal structure was severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time of immunization protected the retina from damage and suppressed the levels of proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels of IL-1?, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation. Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells. However, hMSCs increased the level of an immunoregulatory cytokine IL-10 and the population of IL-10-expressing B220(+)CD19(+) cells. Together, data demonstrate that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10-expressing B220(+)CD19(+) cells. Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.
Related JoVE Video
Characterization of biomaterial-free cell sheets cultured from human oral mucosal epithelial cells.
J Tissue Eng Regen Med
PUBLISHED: 07-15-2014
Show Abstract
Hide Abstract
The purpose of this study was to report the characteristics of biomaterial-free sheets cultured from human oral mucosal epithelial cells without fibrin support, in vitro and after transplantation to limbal-deficient models. Human oral mucosal epithelial cells and limbal epithelial cells were cultured for 2 weeks, and the colony-forming efficiency (CFE) rates were compared. Markers of stem cells (p63), cell proliferation (Ki-67) and epithelial differentiation (cytokeratin; K1, K3, K4, K13) were observed in colonies and in biomaterial-free sheets. Biomaterial-free sheets which had been detached with 1% dispase or biomaterial-free sheets generated by fibrin support were transplanted to 12 limbal-deficient rabbit models. In vitro cell viability, in vivo stability and cytokeratin characteristics of biomaterial-free sheets were compared with those of sheets formed by fibrin-coated culture 1 week after transplantation. Mean CFE rate was significantly higher in human oral mucosal epithelial cells (44.8%) than in human limbal epithelial cells(17.7%). K3 and K4 were well expressed in both colonies and sheets. Biomaterial-free sheets had two to six layers of stratified cells and showed an average of 79.8% viable cells in the sheets after detachment. Cytokeratin expressions of biomaterial-free sheets were comparable to those of sheets cultured by fibrin support, in limbal-deficient models. Both p63 and Ki-67 were well expressed in colonies, isolated sheets and sheets transplanted to limbal-deficient models. Our results suggest that biomaterial-free sheets cultured from human oral mucosal epithelial cells without fibrin support can be an alternative option for cell therapy in use for the treatment of limbal-deficient diseases. Copyright © 2014 John Wiley & Sons, Ltd.
Related JoVE Video
Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis.
Oncotarget
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
nc886 (= vtRNA2-1 or pre-miR-886) is a recently discovered noncoding RNA that is a cellular PKR (Protein Kinase RNA-activated) ligand and repressor. nc886 has been suggested to be a tumor suppressor, solely based on its expression pattern and genomic locus. In this report, we have provided sufficient evidence that nc886 is a putative tumor suppressor in esophageal squamous cell carcinoma (ESCC). In 84 paired specimens from ESCC patients, nc886 expression is significantly lower in tumors than their normal adjacent tissues. More importantly, decreased expression of nc886 is significantly associated with shorter recurrence-free survival of the patients. Suppression of nc886 is mediated by CpG hypermethylation of its promoter, as evidenced by its significant negative correlation to nc886 expression in ESCC tumors and by induced expression of nc886 upon demethylation of its promoter. Knockdown of nc886 and consequent PKR activation induce FOS and MYC oncogenes as well as some inflammatory genes including oncogenic NF-?B. When ectopically expressed, nc886 inhibits proliferation of ESCC cells, further demonstrating that nc886 could be a tumor suppressor. All these findings implicate nc886 as a novel, putative tumor suppressor that is epigenetically silenced and regulates the expression of oncogenes in ESCC.
Related JoVE Video
nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer.
Oncotarget
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
nc886 is a 101 nucleotide long non-coding RNA that has been designated as a precursor microRNA or a vault RNA based upon it sequence. nc886 has also been suggested to be a tumor suppressor, mainly inferred by its expression pattern as well as its genomic location at human chromosome 5q31, a locus for a tumor suppressor gene(s). However, legitimate data based on nc886's correct identity for its functional cellular roles as a tumor suppressor have not been provided yet. Here we have investigated nc886 in gastric cancer where its expression is suppressed due to CpG DNA hypermethylation at its promoter region in a cohort of paired tumor/normal tissues from 88 gastric cancer patients. CpG hypermethylation of nc886 and thus its diminished expression is significantly associated with poor survival in these cancer patients. nc886 inhibits cell proliferation when ectopically expressed in gastric cancer cells. nc886's tumor suppressive role is corroborated by the induction of well-known oncogenes such as FOS, NF-?B, and MYC upon its knockdown. All these activities of nc886 are undoubtedly independent of mature microRNA or vault RNA. Our data indicate that nc886 is a putative tumor suppressor and could potentially be used as a diagnostic marker in gastric cancer.
Related JoVE Video
A rapid and non-invasive 2-step algorithm for diagnosing tuberculous peritonitis using a T cell-based assay on peripheral blood and peritoneal fluid mononuclear cells together with peritoneal fluid adenosine deaminase.
J. Infect.
PUBLISHED: 07-04-2014
Show Abstract
Hide Abstract
A recently developed RD-1 gene-based assay for diagnosing tuberculous peritonitis (TBP) has given promising results. We therefore created a clinical algorithm for differentiating TBP from other diagnoses using peripheral blood and peritoneal fluid mononuclear cells (PBMC/PF-MC) along with conventional tests.
Related JoVE Video
Potentially functional variants in the core nucleotide excision repair genes predict survival in Japanese gastric cancer patients.
Carcinogenesis
PUBLISHED: 07-02-2014
Show Abstract
Hide Abstract
Functional genetic variants of DNA repair genes may alter the host DNA repair capacity, and thus influence efficiency of therapies. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in genes (i.e. ERCC1, XPA, XPC, XPD and XPG) involved in the nucleotide excision repair (NER) pathway in 496 Japanese gastric cancer patients, and assessed overall survival and recurrence-free survival. The combined effects of risk genotypes of these eight SNPs in Japanese patients were further replicated in 356 North-American gastric cancer patients. In Japanese patients, we found that the XPC rs2228000 TT genotype was associated with shorter overall survival [hazards ratio (HR) = 1.75, 95% confidence interval (95% CI) = 1.07-2.86] and recurrence-free survival (HR = 2.17, 95% CI = 1.19-3.95), compared with CC/CT genotypes, and the XPG rs17655 CC genotype was associated with shorter overall survival (HR = 1.60, 95% CI = 1.08-2.36), compared with GG/CG genotypes. The number of observed risk genotypes in the combined analysis was associated with shorter overall survival and recurrence-free survival in a dose-response manner (P(trend) = 0.006 and P(trend) < 0.000) in Japanese patients; specifically, compared with those with ?1 risk genotypes, those with ?2 risk genotypes showed markedly shorter overall survival (HR = 1.79, 95% CI = 1.18-2.70) and recurrence-free survival (HR = 2.80, 95% CI = 1.66-4.73). The association between ?2 risk genotypes and shorter overall survival was not significant (HR = 1.26, 95% CI = 0.82-1.94) in North-American patients, but the trends were similar in these two groups of patients. These data show that functional SNPs in NER core genes may impact survival in Japanese gastric cancer patients.
Related JoVE Video
Rosiglitazone, a peroxisome proliferator-activated receptor-? agonist, restores alveolar and pulmonary vascular development in a rat model of bronchopulmonary dysplasia.
Yonsei Med. J.
PUBLISHED: 06-28-2014
Show Abstract
Hide Abstract
We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-? agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD).
Related JoVE Video
Engineering cellular redox balance in Saccharomyces cerevisiae for improved production of L-lactic acid.
Biotechnol. Bioeng.
PUBLISHED: 06-05-2014
Show Abstract
Hide Abstract
Owing to the growing market for the biodegradable and renewable polymer, polylactic acid, world demand for lactic acid is rapidly increasing. However, the very high concentrations desired for industrial production of the free lactic acid create toxicity and low pH concerns for manufacturers. Saccharomyces cerevisiae is the most well characterized eukaryote, a preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust, commercially compatible workhorse to be exploited for the production of diverse chemicals. S. cerevisiae has also been explored as a host for lactic acid production because of its high acid tolerance. Here, we constructed an L-lactic acid-overproducing S. cerevisiae by redirecting cellular metabolic fluxes to the production of L-lactic acid. To this end, we deleted the S. cerevisiae genes encoding pyruvate decarboxylase 1 (PDC1), L-lactate cytochrome-c oxidoreductase (CYB2), and glycerol-3-phosphate dehydrogenase (GPD1), replacing them with a heterologous L-lactate dehydrogenase (LDH) gene. Two new target genes encoding isoenzymes of the external NADH dehydrogenase (NDE1 and NDE2), were also deleted from the genome to re-engineer the intracellular redox balance. The resulting strain was found to produce L-lactic acid more efficiently (32.6% increase in final L-lactic acid titer). When tested in a bioreactor in fed-batch mode, this engineered strain produced 117?g/L of L-lactic acid under low pH conditions. This result demonstrates that the redox balance engineering should be coupled with the metabolic engineering in the construction of L-lactic acid-overproducing S. cerevisiae. Biotechnol. Bioeng. © 2014 Wiley Periodicals, Inc.
Related JoVE Video
Alveolar soft part sarcoma of the uterine cervix: a case report and review of the literature.
Korean J Pathol
PUBLISHED: 05-16-2014
Show Abstract
Hide Abstract
Alveolar soft part sarcoma (ASPS) of the uterine cervix is a rare malignancy, and 21 cases have been reported the literature from every language (including our case). Herein, we describe a 17-yearold female patient who presented with active vaginal bleeding. Pelvic examination revealed a 1.6 ×1.0×0.5-cm-sized soft mass protruding from the uterine cervix. The final pathological diagnosis was ASPS of the uterine cervix. Immunohistochemically, tumor cells were strongly nuclear positive for transcription factor E3. The patient remained disease free for 24 months without adjuvant therapy. The prognosis of ASPS in the cervix is considerably better than that of ASPS in soft tissues due to early clinical detection, small size, and resectability. ASPS should be considered in the differential diagnosis of an unusual epithelioid neoplasm showing organoid appearance with mild cytologic atypia and no/rare mitotic figures, particularly in young women. Pathologists should be aware of those unusual locations where ASPS may originate.
Related JoVE Video
p63-Mediated activation of the ?-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis.
Cancer Lett.
PUBLISHED: 05-02-2014
Show Abstract
Hide Abstract
The development of esophageal squamous carcinomas (ESC) results from numerous genetic alterations. Our previous study demonstrated that p63 is highly expressed in human ESC cells and stimulates their growth; however, the mechanism by which p63 regulates ESC cell adhesion and invasion remains unclear. In the present study, we further elucidated the underlying molecular mechanisms by which p63 regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63 significantly increased the migration rates of BE3 and OE33 cells. The mRNA and protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in p63-knockdown ESC cells, while overexpression of p63 induced an increase in vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells significantly reduced levels of ?-catenin and c-Myc, while overexpression of p63 increased ?-catenin, but reduced p-?-catenin level. Therefore, p63 regulates the migration and invasion of ESC cells through activation of the ?-catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a potential therapeutic strategy for ESC.
Related JoVE Video
Hematogenous metastasis of ovarian cancer: rethinking mode of spread.
Cancer Cell
PUBLISHED: 05-01-2014
Show Abstract
Hide Abstract
Ovarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin 1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis.
Related JoVE Video
Dose-dependent embryotrophic effect of recombinant granulocyte-macrophage colony-stimulating factor and brain-derived neurotrophic factor in culture medium for mouse preimplantation embryo.
Obstet Gynecol Sci
PUBLISHED: 04-23-2014
Show Abstract
Hide Abstract
To evaluate the dose effect of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) or brain-derived neurotrophic factor (BDNF) in culture medium on the development of in vitro fertilized mouse embryos.
Related JoVE Video
Bone and joint infection as a predictor of community-acquired methicillin-resistant Staphylococcus aureus bacteraemia: a comparative cohort study.
J. Antimicrob. Chemother.
PUBLISHED: 04-02-2014
Show Abstract
Hide Abstract
A new clone of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), sequence type (ST) 72-staphylococcal chromosomal cassette mec (SCCmec) type IV/IVA without the Panton-Valentine leucocidin (PVL) genes, has been the major clonal type in Korea since 2007. However, there have been no evaluations of the clinical features, risk factors and outcomes associated with CA-MRSA bacteraemia in Korea.
Related JoVE Video
Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients.
J Breast Cancer
PUBLISHED: 03-28-2014
Show Abstract
Hide Abstract
The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor.
Related JoVE Video
Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity.
J Neuroinflammation
PUBLISHED: 03-07-2014
Show Abstract
Hide Abstract
Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats.
Related JoVE Video
Factors affecting the spontaneous expulsion of the levonorgestrel-releasing intrauterine system.
Int J Gynaecol Obstet
PUBLISHED: 02-06-2014
Show Abstract
Hide Abstract
To estimate the incidence of, and identify risk factors for, spontaneous expulsion of the levonorgestrel-releasing intrauterine system (LNG-IUS).
Related JoVE Video
Intravenous infusion of mesenchymal stem/stromal cells decreased CCR7(+) antigen presenting cells in mice with corneal allotransplantation.
Curr. Eye Res.
PUBLISHED: 02-06-2014
Show Abstract
Hide Abstract
To investigate the effects of intravenous (IV) infusion of human mesenchymal stem/stromal cells (hMSCs) on activation and migration of CCR7(+) antigen presenting cells (APCs) in allogeneic corneal transplantation.
Related JoVE Video
Surgical Ligation on Significant Patent Ductus Arteriosus in Very Low Birth Weight Infants: Comparison between Early and Late Ligations.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 02-04-2014
Show Abstract
Hide Abstract
We aimed to evaluate the efficacy and safety of early surgical ligation (within 15 days of age) over late surgical ligation (after 15 days of age) by a comparative analysis of very low birth weight (VLBW) infants undergoing surgical correction for symptomatic patent ductus arteriosus (PDA) over the course of 6 years in our hospital.
Related JoVE Video
Psychosocial risk factors associated with internet addiction in Korea.
Psychiatry Investig
PUBLISHED: 01-06-2014
Show Abstract
Hide Abstract
The aim of this study was to examine the prevalence of Internet addiction in middle school students and to identify associated psychosocial risk factors and depression.
Related JoVE Video
Effect on thermoregulatory responses in patients undergoing a tympanoplasty in accordance to the anesthetic techniques during PEEP: a comparison between inhalation anesthesia with desflurane and TIVA.
Korean J Anesthesiol
PUBLISHED: 01-06-2014
Show Abstract
Hide Abstract
It has been known that positive end-expiratory pressure (PEEP) increases the vasoconstriction threshold by baroreceptor unloading. We compared the effect on the thermoregulatory responses according to anesthetic techniques between an inhalation anesthesia with desflurane and a total intravenous anesthesia (TIVA) with propofol and reminfentanil when PEEP was applied in patients undergoing tympanoplasty.
Related JoVE Video
Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.
Int J Mol Epidemiol Genet
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Males have excess advanced liver disease and cirrhosis risk including from chronic hepatitis C virus (HCV) infection though the reasons are unclear.
Related JoVE Video
Analysis of macrophage phenotype in rejected corneal allografts.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-26-2013
Show Abstract
Hide Abstract
We investigated the phenotype of macrophages infiltrating rejected corneal allografts.
Related JoVE Video
LIN28B promotes growth and tumorigenesis of the intestinal epithelium via Let-7.
Genes Dev.
PUBLISHED: 10-22-2013
Show Abstract
Hide Abstract
The RNA-binding proteins LIN28A and LIN28B have diverse functions in embryonic stem cells, cellular reprogramming, growth, and oncogenesis. Many of these effects occur via direct inhibition of Let-7 microRNAs (miRNAs), although Let-7-independent effects have been surmised. We report that intestine targeted expression of LIN28B causes intestinal hypertrophy, crypt expansion, and Paneth cell loss. Furthermore, LIN28B fosters intestinal polyp and adenocarcinoma formation. To examine potential Let-7-independent functions of LIN28B, we pursued ribonucleoprotein cross-linking, immunoprecipitation, and high-throughput sequencing (CLIP-seq) to identify direct RNA targets. This revealed that LIN28B bound a substantial number of mRNAs and modestly augmented protein levels of these target mRNAs in vivo. Conversely, Let-7 had a profound effect; modulation of Let-7 levels via deletion of the mirLet7c2/mirLet7b genes recapitulated effects of Lin28b overexpression. Furthermore, intestine-specific Let-7 expression could reverse hypertrophy and Paneth cell depletion caused by Lin28b. This was independent of effects on insulin-PI3K-mTOR signaling. Our study reveals that Let-7 miRNAs are critical for repressing intestinal tissue growth and promoting Paneth cell differentiation. Let-7-dependent effects of LIN28B may supersede Let-7-independent effects on intestinal tissue growth. In summary, LIN28B can definitively act as an oncogene in the absence of canonical genetic alterations.
Related JoVE Video
Discussion on the alteration of 18F-FDG uptake by the breast according to the menstrual cycle in PET imaging.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
Show Abstract
Hide Abstract
18F-FDG PET/CT is a useful modality for identifying high-glucose-consuming cells, such as cancer cells by the glucose metabolism of FDG. FDG is taken up by cancer and inflammatory cells but occasionally, there is some FDG uptake on normal tissues as a result of their individual physiological characteristics. In particular, in fertile females, unusual FDG uptake in the breast changes according to the stages in the menstrual cycle, which can adversely affect a diagnosis. Therefore, this study examined the change in breast FDG uptake in the menstrual cycle on 18F-FDG PET/CT. One hundred and sixty females (34 ± 3.5 years old), who had not undergone a gynecologic anamnesis and had a regular menstrual cycle over the previous 6 months, were examined from March 2011 to February 2012. The subjects were divided into the following 4 groups (each with 40 patients): flow phase, proliferative phase, ovulatory phase and secretory phase using Pregnancy Calculator 0.14 and history taking. Discovery STE (GE Healthcare, USA) was used as the PET/CT. The SUVs on the accumulated region on the breast were analyzed, and 3 nuclear medicine specialists performed a blind test. The SUVs on the breast were the flow phase (1.64 ± 0.25), proliferative phase (0.93 ± 0.28), ovulatory phase (1.66 ± 0.26) and secretory phase (1.77 ± 0.28). Higher uptake values were observed in the secretory, flow phase and ovulatory phase (p< 0.05). The accumulation of the breast was divided into the following 3 grades compared to the lung and liver by gross analysis: the breast uptake was equal to the lung (Grade I); between the lung and liver (Grade II); and equal to or greater than the liver (Grade III). These results showed a high uptake value in the secretory, flow phase and ovulatory phase (p <0.05). In fertile females, the FDG uptake of the breast showed changes according to the menstrual cycle, which can be used to improve the diagnosis of breast disease. Therefore, the false-negative findings of breast disease can be reduced by performing an examination at the appropriate period through history taking and considering the individual menstrual cycle.
Related JoVE Video
Large conserved domains of low DNA methylation maintained by Dnmt3a.
Nat. Genet.
PUBLISHED: 07-26-2013
Show Abstract
Hide Abstract
Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into the mechanisms that promote shifts in DNA methylation and contribute to changes in cell fate, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified mouse hematopoietic stem cells. We discovered extended regions of low methylation (canyons) that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. About half of the genes in these methylation canyons are coated with repressive histone marks, whereas the remainder are covered by activating histone marks and are highly expressed in hematopoietic stem cells (HSCs). Canyon borders are demarked by 5-hydroxymethylcytosine and become eroded in the absence of DNA methyltransferase 3a (Dnmt3a). Genes dysregulated in human leukemias are enriched for canyon-associated genes. The new epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development.
Related JoVE Video
Risk Factors Associated with Nephrocalcinosis in Preterm Infants.
Am J Perinatol
PUBLISHED: 06-03-2013
Show Abstract
Hide Abstract
Purpose The objective was to identify the risk factors associated with nephrocalcinosis (NC) in preterm infants.Methods NC was diagnosed by renal sonography at 4 or 8 weeks of life, and 10 infants who had findings of type 3 or 4 NC were classified as the NC group. Various clinical and laboratory factors were compared between NC and control groups.Results Serum sodium (Na) on day 1, serum creatinine and fractional excretion of calcium (FeCa) at 1 and 2 weeks, and serum calcium (Ca), fractional excretion of sodium (FeNa), and urine Na on 2 weeks of life were significantly different between the two groups: the NC group showed significantly higher serum creatinine, FeNa, and FeCa than the control group, suggesting a greater decrease in renal function in the NC group. Differences of the laboratory findings disappeared after 4 weeks of life. The strongest risk factor was birth weight.Conclusion A transient decrease in renal function during the first 2 weeks of life was associated with development of NC in preterm very low-birth-weight infants, and the risk of NC increased as birth weight decreased.
Related JoVE Video
The Aristotle score predicts mortality after surgery of patent ductus arteriosus in preterm infants.
Ann. Thorac. Surg.
PUBLISHED: 04-05-2013
Show Abstract
Hide Abstract
Outcomes after surgical ligation of patent ductus arteriosus (PDA) in preterm infants are often complicated by prematurity associated comorbidities. The Aristotle comprehensive complexity score (ACCS) has been proposed as a useful tool for complexity adjustment in the analysis of outcome after congenital heart surgery. The aims of this study were to define preoperative risk factors for mortality and to demonstrate the usefulness of ACCS to predict mortality after surgical ligation of PDA in the preterm.
Related JoVE Video
Expression of autoantibodies in patients with sudden sensorineural hearing loss.
Ann. Otol. Rhinol. Laryngol.
PUBLISHED: 03-29-2013
Show Abstract
Hide Abstract
The aim of this study was to establish the expression rate of autoimmunity in patients with sudden sensorineural hearing loss and to determine whether a positive marker is associated with a higher rate of hearing recovery after steroid treatment.
Related JoVE Video
Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype.
World J. Gastroenterol.
PUBLISHED: 03-26-2013
Show Abstract
Hide Abstract
To identify molecular biologic differences between two gastric adenocarcinoma subgroups presenting different prognoses through the analysis of microRNA and protein expression.
Related JoVE Video
Double exposure to intra-amniotic lipopolysaccharide and maternal betamethasone induces sustained increase of neutrophils in the lungs and disrupts alveolarization in newborn rats.
J Perinat Med
PUBLISHED: 03-24-2013
Show Abstract
Hide Abstract
We investigated the combined effects of intra-amniotic lipopolysaccharide (LPS) and maternal betamethasone (BMZ) on alveolarization using a newborn rat model.
Related JoVE Video
Antibody response to pneumococcal vaccination in children with chronic or recurrent rhinosinusitis.
Korean J Pediatr
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
Although chronic and recurrent rhinosinusitis is prevalent in children, little is known about its causes. Here, we investigated the humoral immunity in children with chronic or recurrent rhinosinusitis.
Related JoVE Video
The heme-copper oxidase superfamily shares a Zn2+-binding motif at the entrance to a proton pathway.
FEBS Lett.
PUBLISHED: 01-30-2013
Show Abstract
Hide Abstract
Heme-copper oxidases (HCuOs) catalyse the reduction of oxygen, using the liberated free energy to maintain a proton-motive force across the membrane. In the mitochondrial-like A-type HCuOs, binding of heavy metal ions at the surface of the protein inhibits proton transfer. In bacterial C-type oxidases, the entry point to the proton pathway is on an accessory subunit unrelated to any subunit in A-type HCuOs. Despite this, we show here that heavy metal ions such as Zn(2+) inhibit O2-reduction very similarly in C-type as in A-type HCuOs, and furthermore that the binding site shares the same Glu-His motif.
Related JoVE Video
Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2.
Mol Oncol
PUBLISHED: 01-22-2013
Show Abstract
Hide Abstract
In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-?TM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.
Related JoVE Video
Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosine Kinase Inhibito
Korean J Pathol
PUBLISHED: 01-21-2013
Show Abstract
Hide Abstract
The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs).
Related JoVE Video
Assessing soil and groundwater contamination in a metropolitan redevelopment project.
Environ Monit Assess
PUBLISHED: 01-02-2013
Show Abstract
Hide Abstract
The purpose of this study was to assess contaminated soil and groundwater for the urban redevelopment of a rapid transit railway and a new mega-shopping area. Contaminated soil and groundwater may interfere with the progress of this project, and residents and shoppers may be exposed to human health risks. The study area has been remediated after application of first remediation technologies. Of the entire area, several sites were still contaminated by waste materials and petroleum. For zinc (Zn) contamination, high Zn concentrations were detected because waste materials were disposed in the entire area. For petroleum contamination, high total petroleum hydrocarbon (TPH) and hydrocarbon degrading microbe concentrations were observed at the depth of 7 m because the underground petroleum storage tank had previously been located at this site. Correlation results suggest that TPH (soil) concentration is still related with TPH (groundwater) concentration. The relationship is taken into account in the Spearman coefficient (?).
Related JoVE Video
Stanniocalcin-1 protects retinal ganglion cells by inhibiting apoptosis and oxidative damage.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Optic neuropathy including glaucoma is one of the leading causes of irreversible vision loss, and there are currently no effective therapies. The hallmark of pathophysiology of optic neuropathy is oxidative stress and apoptotic death of retinal ganglion cells (RGCs), a population of neurons in the central nervous system with their soma in the inner retina and axons in the optic nerve. We here tested that an anti-apoptotic protein stanniocalcin-1 (STC-1) can prevent loss of RGCs in the rat retina with optic nerve transection (ONT) and in cultures of RGC-5 cells with CoCl2 injury. We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage. In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2. The expression of HIF-1? that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment. The results suggested that intravitreal injection of STC-1 might be a useful therapy for optic nerve diseases in which RGCs undergo apoptosis through oxidative stress.
Related JoVE Video
Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer lines.
Korean J Hepatol
PUBLISHED: 11-22-2011
Show Abstract
Hide Abstract
JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines.
Related JoVE Video
Systems biology approaches to decoding the genome of liver cancer.
Cancer Res Treat
PUBLISHED: 11-03-2011
Show Abstract
Hide Abstract
Molecular classification of cancers has been significantly improved patient outcomes through the implementation of treatment protocols tailored to the abnormalities present in each patients cancer cells. Breast cancer represents the poster child with marked improvements in outcome occurring due to the implementation of targeted therapies for estrogen receptor or human epidermal growth factor receptor-2 positive breast cancers. Important subtypes with characteristic molecular features as potential therapeutic targets are likely to exist for all tumor lineages including hepatocellular carcinoma (HCC) but have yet to be discovered and validated as targets. Because each tumor accumulates hundreds or thousands of genomic and epigenetic alterations of critical genes, it is challenging to identify and validate candidate tumor aberrations as therapeutic targets or biomarkers that predict prognosis or response to therapy. Therefore, there is an urgent need to devise new experimental and analytical strategies to overcome this problem. Systems biology approaches integrating multiple data sets and technologies analyzing patient tissues holds great promise for the identification of novel therapeutic targets and linked predictive biomarkers allowing implementation of personalized medicine for HCC patients.
Related JoVE Video
GLIPR1 suppresses prostate cancer development through targeted oncoprotein destruction.
Cancer Res.
PUBLISHED: 10-24-2011
Show Abstract
Hide Abstract
Downregulation of the proapoptotic p53 target gene glioma pathogenesis-related protein 1 (GLIPR1) occurs frequently in prostate cancer, but the functional meaning of this event is obscure. Here, we report the discovery of functional relationship between GLIPR1 and c-Myc in prostate cancer where c-Myc is often upregulated. We found that the expression of GLIPR1 and c-Myc were inversely correlated in human prostate cancer. Restoration of GLIPR1 expression in prostate cancer cells downregulated c-myc levels, inhibiting cell-cycle progression. Downregulation was linked to a reduction in ?-catenin/TCF4-mediated transcription of the c-myc gene, which was caused by GLIPR1-mediated redistribution of casein kinase 1? (CK1?) from the Golgi apparatus to the cytoplasm where CK1? could phosphorylate ?-catenin and mediate its destruction. In parallel, GLIPR1 also promoted c-Myc protein ubiquitination and degradation by glycogen synthase kinase-3?- and/or CK1?-mediated c-Myc phosphorylation. Notably, genetic ablation of the mouse homolog of Glipr1 cooperated with c-myc overexpression to induce prostatic intraepithelial neoplasia and prostate cancer. Together, our findings provide evidence for CK1?-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1? phosphorylation site for c-Myc degradation. Furthermore, they reveal parallel mechanisms of c-myc downregulation by GLIPR1 that when ablated in the prostate are sufficient to drive c-Myc expression and malignant development.
Related JoVE Video
Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer.
Gut
PUBLISHED: 10-13-2011
Show Abstract
Hide Abstract
Despite continual efforts to develop prognostic and predictive models of colorectal cancer by using clinicopathological and genetic parameters, a clinical test that can discriminate between patients with good or poor outcome after treatment has not been established. Thus, the authors aim to uncover subtypes of colorectal cancer that have distinct biological characteristics associated with prognosis and identify potential biomarkers that best reflect the biological and clinical characteristics of subtypes.
Related JoVE Video
Entrance of the proton pathway in cbb3-type heme-copper oxidases.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-12-2011
Show Abstract
Hide Abstract
Heme-copper oxidases (HCuOs) are the last components of the respiratory chain in mitochondria and many bacteria. They catalyze O(2) reduction and couple it to the maintenance of a proton-motive force across the membrane in which they are embedded. In the mitochondrial-like, A family of HCuOs, there are two well established proton transfer pathways leading from the cytosol to the active site, the D and the K pathways. In the C family (cbb(3)) HCuOs, recent work indicated the use of only one pathway, analogous to the K pathway. In this work, we have studied the functional importance of the suggested entry point of this pathway, the Glu-25 (Rhodobacter sphaeroides cbb(3) numbering) in the accessory subunit CcoP (E25(P)). We show that catalytic turnover is severely slowed in variants lacking the protonatable Glu-25. Furthermore, proton uptake from solution during oxidation of the fully reduced cbb(3) by O(2) is specifically and severely impaired when Glu-25 was exchanged for Ala or Gln, with rate constants 100-500 times slower than in wild type. Thus, our results support the role of E25(P) as the entry point to the proton pathway in cbb(3) and that this pathway is the main proton pathway. This is in contrast to the A-type HCuOs, where the D (and not the K) pathway is used during O(2) reduction. The cbb(3) is in addition to O(2) reduction capable of NO reduction, an activity that was largely retained in the E25(P) variants, consistent with a scenario where NO reduction in cbb(3) uses protons from the periplasmic side of the membrane.
Related JoVE Video
Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer models.
Mol. Cancer Ther.
PUBLISHED: 10-12-2011
Show Abstract
Hide Abstract
Tumor cell proliferation requires both growth signals and sufficient cellular bioenergetics. The AMP-activated protein kinase (AMPK) pathway seems dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and metformin. We evaluated the in vitro antitumor activity of 2DG, metformin or AICAR alone, and 2DG in combination either with metformin or AICAR. We examined in vivo efficacy using xenograft mouse models. 2DG alone was not sufficient to promote tumor cell death, reflecting the limited efficacy showed in clinical trials. A combined use of 2DG and AICAR also failed to induce cell death. However, 2DG and metformin led to significant cell death associated with decrease in cellular ATP, prolonged activation of AMPK, and sustained autophagy. Gene expression analysis and functional assays revealed that the selective AMPK agonist AICAR augments mitochondrial energy transduction (OXPHOS) whereas metformin compromises OXPHOS. Importantly, forced energy restoration with methyl pyruvate reversed the cell death induced by 2DG and metformin, suggesting a critical role of energetic deprivation in the underlying mechanism of cell death. The combination of 2DG and metformin inhibited tumor growth in mouse xenograft models. Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors.
Related JoVE Video
Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-10-2011
Show Abstract
Hide Abstract
Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior.
Related JoVE Video
Antiulcer activity of anthocyanins from Rubus coreanus via association with regulation of the activity of matrix metalloproteinase-2.
J. Agric. Food Chem.
PUBLISHED: 10-07-2011
Show Abstract
Hide Abstract
Anthocyanins were extracted from the fruits of Rubus coreanus. Whether their antioxidant properties and antiulcer activity in gastric ulceration have been accompanied by the activation of matrix metalloproteainse-2 (MMP-2) was investigated. To assess the effect of anthocyanins on gastric ulcer, the rats were administered with anthocyanins (20, 50, and 80 mg/kg of body weight) before treatment with naproxen (80 mg/kg of body weight) to induce gastric ulceration. Lipid peroxidation and the activities of radical scavenging enzymes such as catalase, superoxide dismutase, and glutathione peroxidase were determined. The MMP-2 level was tested by zymography and Western blot. Anthocyanins of R. coreanus exhibit possible antiulcer activity in acute ulcer in a rat model by preventing lipid peroxidation and a significant increase in the activities of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase. Also, anthocyanins induce activation of MMP-2 and attenuate the activity of the proinflammatory molecules, such as tumor necrosis factor-? and interleukin-1?.
Related JoVE Video
ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression.
Cancer Res.
PUBLISHED: 09-21-2011
Show Abstract
Hide Abstract
Prostaglandin E(2) (PGE(2)), the most abundant COX-2-derived prostaglandin found in colorectal cancer, promotes tumor cell proliferation and survival via multiple signaling pathways. However, the role of PGE(2) in tumor hypoxia is not well understood. Here, we show a synergistic effect of PGE(2) and hypoxia on enhancing angiopoietin-like protein 4 (ANGPTL4) expression and that elevation of ANGPTL4 promotes colorectal cancer growth. PGE(2) induces ANGPTL4 expression at both the mRNA and protein levels under hypoxic conditions. Moreover, hypoxia induces one of the PGE(2) receptors, namely EP1. Activation of EP1 enhances ANGPTL4 expression, whereas blockage of EP1 by an antagonist inhibits PGE(2) induction of ANGPTL4 under hypoxic conditions. Importantly, overexpression of ANGPTL4 promotes cell proliferation and tumor growth in vitro and in vivo. In addition, treatment with ANGPTL4 recombinant protein increases colorectal carcinoma cell proliferation through effects on STAT1 signaling. The MAP kinase and Src pathways mediate ANGPTL4-induced STAT1 expression and activation. These results are relevant to human disease because we found that the expression of ANGPTL4 and STAT1 are elevated in 50% of human colorectal cancers tested and there is a positive correlation between COX-2 and ANGPTL4 as well STAT1 expression in colorectal carcinomas. Collectively, these findings suggest that PGE(2) plays an important role in promoting cancer cell proliferation via ANGPTL4 under hypoxic conditions.
Related JoVE Video
Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.
Pediatr Transplant
PUBLISHED: 09-16-2011
Show Abstract
Hide Abstract
EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT.
Related JoVE Video
Quality of roof-harvested rainwater--comparison of different roofing materials.
Environ. Pollut.
PUBLISHED: 09-09-2011
Show Abstract
Hide Abstract
The objective of the study reported in this paper was to assess the quality of harvested rainwater on the basis of the roofing materials used and the presence of lichens/mosses on the roofing surface. Four pilot structures with different roofing materials (i.e., wooden shingle tiles, concrete tiles, clay tiles [Gi-Wa] and galvanized steel) were installed in a field. The galvanized steel was found to be the most suitable for rainwater harvesting applications, with their resulting physical and chemical water quality parameters meeting the Korean guidelines for drinking water quality (e.g., pH (5.8-8.5), TSS <500 mg/L, NO(3)(-) < 10 mg/L, SO(4)(2-) < 200 mg/L, Al < 0.2 mg/L, Cu < 1 mg/L, Fe < 0.3 mg/L, Pb < 0.05 mg/L, Zn < 1 mg/L, and E. coli (No detection)). In the galvanized steel case, the relatively high water quality was probably due to ultraviolet light and the high temperature effectively disinfecting the harvested rainwater. It was also found that the presence of lichens and mosses may adversely affect the physical, chemical and microbiological quality of rainwater.
Related JoVE Video
Functional proton transfer pathways in the heme-copper oxidase superfamily.
Biochim. Biophys. Acta
PUBLISHED: 09-05-2011
Show Abstract
Hide Abstract
Heme-copper oxidases (HCuOs) terminate the respiratory chain in mitochondria and most bacteria. They are transmembrane proteins that catalyse the reduction of oxygen and use the liberated free energy to maintain a proton-motive force across the membrane. The HCuO superfamily has been divided into the oxygen-reducing A-, B- and C-type oxidases as well as the bacterial NO reductases (NOR), catalysing the reduction of NO in the denitrification process. Proton transfer to the catalytic site in the mitochondrial-like A family occurs through two well-defined pathways termed the D- and K-pathways. The B, C, and NOR families differ in the pathways as well as the mechanisms for proton transfer to the active site and across the membrane. Recent structural and functional investigations, focussing on proton transfer in the B, C and NOR families will be discussed in this review.
Related JoVE Video
Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy.
Cell. Mol. Immunol.
PUBLISHED: 08-08-2011
Show Abstract
Hide Abstract
Dendritic cell (DC)-based vaccines continue to be considered an attractive tool for cancer immunotherapy. DCs require an additional signal from the environment or other immune cells to polarize the development of immune responses toward T helper 1 (Th1) or Th2 responses. DCs play a role in natural killer (NK) cell activation, and NK cells are also able to activate and induce the maturation of DCs. We investigated the types of NK cells that can induce the maturation and enhanced function of DCs and the conditions under which these interactions occur. DCs that were activated by resting NK cells in the presence of inflammatory cytokines exhibited increased expression of several costimulatory molecules and an enhanced ability to produce IL-12p70. NK cell-stimulated DCs potently induced Th1 polarization and exhibited the ability to generate tumor antigen-specific cytotoxic T lymphocyte responses. Our data demonstrate that functional DCs can be generated by coculturing immature DCs with freshly isolated resting NK cells in the presence of Toll-like receptor agonists and proinflammatory cytokines and that the resulting DCs effectively present antigens to induce tumor-specific T-cell responses, which suggests that these cells may be useful for cancer immunotherapy.
Related JoVE Video
The significance of the j-curve in hypertension and coronary artery diseases.
Korean Circ J
PUBLISHED: 07-30-2011
Show Abstract
Hide Abstract
The J-curve effect describes an inverse relation between low blood pressure (BP) and cardiovascular complications. This effect is more pronounced in patients with preexisting coronary artery disease (CAD), hypertension or left ventricular hypertrophy (LVH). The recent large clinical outcomes trials have observed a J-curve effect between a diastolic BP of 70-80 mmHg as well as a systolic BP <130 mmHg. The J-curve phenomenon does not appear in stroke or renal disease. This is because the coronary arteries are perfused during diastole, but the cerebral and renal perfusion mainly occurs in systole. Therefore, caution should be taken to maintain the diastolic blood pressure (DBP) at minimum of 70 mmHg and possibly to maintain the DBP between 80-85 mmHg in patients with severe LVH, CAD or vascular diseases. BP control in high-risk elderly patients should be carefully done as undergoing aggressive therapy to lower the systolic blood pressure below 140 mmHg can cause cardiovascular complications due to the severely reduced DBP and increased pulse pressure.
Related JoVE Video
The validity of the Canadian Triage and Acuity Scale in predicting resource utilization and the need for immediate life-saving interventions in elderly emergency department patients.
Scand J Trauma Resusc Emerg Med
PUBLISHED: 07-12-2011
Show Abstract
Hide Abstract
We evaluated the validity of the Canadian Triage and Acuity Scale (CTAS) in elderly emergency department (ED) patients. In particular, we examined the sensitivity and specificity of the CTAS for identifying elderly patients who received an immediate life-saving intervention in the ED.
Related JoVE Video
Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer.
EMBO Mol Med
PUBLISHED: 07-01-2011
Show Abstract
Hide Abstract
ESR1 is one of the most important transcription factors and therapeutic targets in breast cancer. By applying systems-level re-analysis of publicly available gene expression data, we uncovered a potential regulator of ESR1. We demonstrated that orphan nuclear receptor NR2E3 regulates ESR1 via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3 to the promoter in breast cancer cells, and is essential for physiological cellular activity of ESR1 in estrogen receptor (ER)-positive breast cancer cells. Moreover, expression of NR2E3 was significantly associated with recurrence-free survival and a favourable response to tamoxifen treatment in women with ER-positive breast cancer. Our results provide mechanistic insights on the regulation of ESR1 by NR2E3 and the clinical relevance of NR2E3 in breast cancer.
Related JoVE Video
Effect of ?Gal on corneal xenotransplantation in a mouse model.
Xenotransplantation
PUBLISHED: 06-24-2011
Show Abstract
Hide Abstract
It has been reported that hyperacute rejection (HAR) does not occur after pig-to-nonhuman corneal xenotransplantation. However, considering that immune privilege is already disrupted in most human corneal recipients, and the expression of ?Gal can be gradually reduced after pig-to-rat corneal transplantation, the long-term survival of corneal grafts from wild-type pigs cannot be guaranteed. Accordingly, we aimed to investigate the effect of ?Gal on the change in anti-Gal antibodies, using sensitized ?1,3-galactosyltransferase gene-knockout (GTKO) mice recipients.
Related JoVE Video
Regeneration of completely transected spinal cord using scaffold of poly(D,L-lactide-co-glycolide)/small intestinal submucosa seeded with rat bone marrow stem cells.
Tissue Eng Part A
PUBLISHED: 06-14-2011
Show Abstract
Hide Abstract
Using a complete spinal cord transection model, the present study employed a combinatorial strategy comprising rat bone marrow stem cells (rBMSCs) and polymer scaffolds to regenerate neurological function after spinal cord injury (SCI) of different lengths. SCI models with completely transected lesions were prepared by surgical removal of 1?mm (SC1) or 3?mm (SC3) lengths of spinal cord in the eighth-to-ninth spinal vertebrae, a procedure that resulted in bilateral hindlimb paralysis. A cylindrical poly(D,L-lactide-co-glycolide)/small intestinal submucosa scaffold 1 or 3?mm in length with or without rBMSCs was fitted into the completely transected lesion. Rats in SC1 and SC3 groups implanted with rBMSC-containing scaffolds received Basso-Beattie-Bresnahan scores for hindlimb locomotion of 15 and 8, respectively, compared with ?3 for control rats in SC1-C and SC3-C groups implanted with scaffolds lacking rBMSCs. The amplitude of motor-evoked potentials recorded in the hindlimb area of the sensorimotor cortex after stimulation of the injured spinal cord averaged ?100??V in SC1-C and 10-50??V in SC3-C groups at 4 weeks, and then declined to nearly zero at 8 weeks. In contrast, the amplitude of motor-evoked potentials increased from ?300 to 350??V between 4 and 8 weeks in SC1 rats and from ?200 to ?250??V in SC3 rats. These results demonstrate functional recovery in rBMSC-transplanted rats, especially those with smaller defects. Immunohistochemically stained sections of the injury site showed clear evidence for axonal regeneration only in rBMSC-transplanted SC1 and SC3 models. In addition, rBMSCs were detected at the implanted site 4 and 8 weeks after transplantation, indicating cell survival in SCI. Collectively, our results indicate that therapeutic rBMSCs in a poly(D,L-lactide-co-glycolide)/small intestinal submucosa scaffold induced nerve regeneration in a complete spinal cord transection model and showed that functional recovery further depended on defect length.
Related JoVE Video
Pulmonary aspergillosis in immunocompetent patients without air-meniscus sign and underlying lung disease: CT findings and histopathologic features.
Acta Radiol
PUBLISHED: 05-19-2011
Show Abstract
Hide Abstract
Pulmonary aspergillosis in immunocompetent patients has been described as a saprophytic infection with pre-existing lung lesions showing an air-meniscus sign on chest radiograph or CT scans. There have been rare articles dealing with pulmonary aspergillosis in immunocompetent patients without pre-existing lung lesions.
Related JoVE Video
A case of balanced type double aortic arch diagnosed incidentally by transthoracic echocardiography in an asymptomatic adult patient.
J Cardiovasc Ultrasound
PUBLISHED: 05-06-2011
Show Abstract
Hide Abstract
A 36-year-old male patient with no remarkable medical history was admitted to our hospital for a health check up. On chest radiography, bilateral aortic notches at the level of aortic arch were shown suggesting aortic arch anomaly without any clinical symptoms. Two aortic arches were almost same-in-size on suprasternal view of transthoracic echocardiography. In addition, multidetector computed tomography showed balanced type double aortic arch forming a complete vascular ring which encircled the trachea and esophagus. The trachea was slightly compressed by the vascular ring whereas the esophagus was intact. Nevertheless, the pulmonary function test was normal. The patient was discharged from hospital with instructions for periodic follow-up.
Related JoVE Video
Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling.
J. Korean Med. Sci.
PUBLISHED: 04-23-2011
Show Abstract
Hide Abstract
Gene expression is suppressed by DNA methylation. The goal of this study was to identify genes whose CpG site methylation and mRNA expression are associated with recurrence after surgical resection for hepatocellular carcinoma (HCC). Sixty-two HCCs were examined by both whole genome DNA methylation and transcriptome analysis. The Cox model was used to select genes associated with recurrence. A validation was performed in an independent cohort of 66 HCC patients. Among fifty-nine common genes, increased CpG site methylation and decreased mRNA expression were associated with recurrence for 12 genes (Group A), whereas decreased CpG site methylation and increased mRNA expression were associated with recurrence for 25 genes (Group B). The remaining 22 genes were defined as Group C. Complement factor H (CFH) and myosin VIIA and Rab interacting protein (MYRIP) in Group A; proline/serine-rich coiled-coil 1 (PSRC1), meiotic recombination 11 homolog A (MRE11A), and myosin IE (MYO1E) in Group B; and autophagy-related protein LC3 A (MAP1LC3A), and NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) in Group C were validated. In conclusion, potential tumor suppressor (CFH, MYRIP) and oncogenes (PSRC1, MRE11A, MYO1E) in HCC are reported. The regulation of individual genes by methylation in hepatocarcinogenesis needs to be validated.
Related JoVE Video
Cloning and characterization of a modular GH5 ?-1,4-mannanase with high specific activity from the fibrolytic bacterium Cellulosimicrobium sp. strain HY-13.
Bioresour. Technol.
PUBLISHED: 04-22-2011
Show Abstract
Hide Abstract
The gene (1272-bp) encoding a ?-1,4-mannanase from a gut bacterium of Eisenia fetida, Cellulosimicrobium sp. strain HY-13 was cloned and expressed in Escherichia coli. The recombinant ?-1,4-mannanase (rManH) was approximately 44.0 kDa and has a catalytic GH5 domain that is 65% identical to that of the Micromonospora sp. ?-1,4-mannosidase. The enzyme exhibited the highest catalytic activity toward mannans at 50 °C and pH 6.0. rManH displayed a high specific activity of 14,711 and 8498 IU mg?¹ towards ivory nut mannan and locust bean gum, respectively; however it could not degrade the structurally unrelated polysaccharides, mannobiose, or p-nitrophenyl sugar derivatives. rManH was strongly bound to ivory nut mannan, Avicel, chitosan, and chitin but did not attach to curdlan, insoluble oat spelt xylan, lignin, or poly(3-hydroxybutyrate). The superior biocatalytic properties of rManH suggest that the enzyme can be exploited as an effective additive in the animal feed industry.
Related JoVE Video
Assessment of Young Dong tributary and Imgok Creek impacted by Young Dong coal mine, South Korea.
Environ Geochem Health
PUBLISHED: 04-05-2011
Show Abstract
Hide Abstract
An initial reclamation of the Young Dong coal mine site, located in northeastern South Korea, was completed in 1995. Despite the filling of the adit with limestone, acid rock drainage (ARD) enters Young Dong tributary and is then discharged to Imgok Creek. This ARD carries an average of 500 mg CaCO(3)/l of mineral acidity, primarily as Fe(II) and Al. Before spring runoff, the flow of Imgok Creek is 3.3-4 times greater than that of the tributary and has an alkalinity of 100 mg CaCO(3)/l, which is sufficient to eliminate the mineral acidity and raise the pH to about 6.5. From April through September 2008, there were at least two periods of high surface flow that affects the flow of ARD from the adit. Flow of ARD reaches 2.8 m(3)/min during spring runoff. This raised the concentrations of Fe and Al in the confluence with Imgok Creek. However, by 2 km downstream the pH of the Imgok Creek is 6.5 and only dissolved Fe is above the Korean drinking water criteria (0.30 mg/l). This suggests only a minor impact of Young Dong Creek water on Imgok Creek. Acid digestion of the sediments in Imgok Creek and Young Dong Tributary reveals considerable abundances of heavy metals, which could have a long-term impact on water quality. However, several water-based leaching tests, which better simulate the bioavailable metals pool, released only Al, Fe, Mn, and Zn at concentrations exceeding the criteria for drinking water or aquatic life.
Related JoVE Video

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.