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Find video protocols related to scientific articles indexed in Pubmed.
KGFR promotes Na+ channel expression in a rat acute lung injury model.
Afr Health Sci
PUBLISHED: 10-30-2014
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Binding of keratinocyte growth factor (KGF) to the KGF receptor (KGFR) plays an important role in the recovery of alveolar epithelial cells from acute lung injury (ALI).
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Coxsackievirus B3 Engineered to Contain microRNA Targets for Muscle-specific microRNAs Display Attenuated Cardiotropic Virulence in Mice.
J. Virol.
PUBLISHED: 10-24-2014
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Coxsackievirus B3 (CVB3) is trophic for cardiac tissue and is a major causative agent for viral myocarditis, where local viral replication in the heart may lead to heart failure or even death. Recent studies show that inserting microRNA target sequences into the genomes of certain viruses can eradicate these viruses within local host tissues that specifically express the cognate microRNA. Here, we demonstrated both in vitro and in vivo that incorporating target sequences for miRNA-133 and -206 into the 5' untranslated region of the CVB3 genome ameliorated CVB3 virulence in skeletal muscle and myocardial cells that specifically expressed the cognate cellular microRNAs. Compared to wild-type CVB3, viral replication of the engineered CVB3 was attenuated in human TE671 (rhabdomyosarcoma) and L6 (skeletal muscle) cell lines in vitro that expressed high levels of miRNA-206. In the in vivo murine CVB3-infection model, viral replication of the engineered CVB3 was attenuated specifically in the heart that expressed high levels of both miRNAs, but not in certain tissues, which allowed the host to retain the ability to induce a strong and protective humoral immune response against CVB3. The results of this study suggest that a microRNA-targeting strategy to control CVB3 tissue tropism and pathogenesis may be useful for viral attenuation and vaccine development.
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[Comparative study on the efficacy of Hyper CVAD/MA regimen and CHOP or CHOP like regimen in the treatment of primary peripheral T cell lymphoma].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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To evaluate the curative efficacy and safety of two regimens, Hyper CVAD/MA and CHOP/CHOP, in the treatment of primary peripheral T cell lymphoma (PTCL).
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Mucosal immunization with a live attenuated vaccine SPY1 induces humoral and Th2-Th17-Treg cellular immunity and protects against pneumococcal infection.
Infect. Immun.
PUBLISHED: 10-15-2014
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Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the function was unknown. Our study found that mucosal delivery with the live attenuated vaccine SPY1 strain can confer T cells and B cells dependent protection against pneumococcal colonization and invasive infection, yet it's still unclear which cell subsets contribute to the protection and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naïve ?MT mice and immune T cells were indispensable to protection examined in nude mice. A critical role of IL-17A in colonization was demonstrated in mice lacking IL-17A and vaccine-specific Th2 immune subset was necessary for systemic protection. Of note, we found that SPY1 could stimulate immunoregulatory response and SPY1-elicited regulatory T cells participated in protection against colonization and lethal infection. The data presented here aid our understanding of how live attenuated strains are able to function as effective vaccines, and may be contribute to a more comprehensive evaluation of live vaccines and other mucosal vaccines.
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Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT.
Clin Transplant
PUBLISHED: 09-19-2014
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Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse five-yr survival (78.6% vs. 100%, p = 0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT.
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A simple model clarifies the complicated relationships of complex networks.
Sci Rep
PUBLISHED: 08-27-2014
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Real-world networks such as the Internet and WWW have many common traits. Until now, hundreds of models were proposed to characterize these traits for understanding the networks. Because different models used very different mechanisms, it is widely believed that these traits origin from different causes. However, we find that a simple model based on optimisation can produce many traits, including scale-free, small-world, ultra small-world, Delta-distribution, compact, fractal, regular and random networks. Moreover, by revising the proposed model, the community-structure networks are generated. By this model and the revised versions, the complicated relationships of complex networks are illustrated. The model brings a new universal perspective to the understanding of complex networks and provide a universal method to model complex networks from the viewpoint of optimisation.
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[Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation: two cases report and literature review].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-26-2014
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To investigate the clinical characteristics, treatment and prognosis of Guillain-Barre syndrome (GBS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
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[Long-term follow-ups of comprehensive therapies for stage 4 neuroblastoma].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-23-2014
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To evaluate the long-term outcomes of childhood stage 4 neuroblastoma (NB) and its correlative prognostic factors.
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[The impact and mechanism of glutamate transporter 1-mediated visceral nociception and hyperalgesia following exposure to post-traumatic stress disorder-like stress in spinal cord of rats].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 08-23-2014
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To investigate the expression of glutamate transporter 1 (GLT-1) and determine the effect of GLT-1 overexpression on the visceromotor response ( VMR ) to colorectal distention (CRD) following exposure to post-traumatic stress disorder (PTSD)-like stress.
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Dysfunction of bone marrow vascular niche in acute graft-versus-host disease after MHC-haploidentical bone marrow transplantation.
PLoS ONE
PUBLISHED: 08-13-2014
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Acute graft-versus-host disease (aGvHD) is the most common complication of allogeneic hematopoietic stem cell transplantation (HSCT), which is often accompanied by impaired hematopoietic reconstitution. Sinusoidal endothelial cells (SECs) constitute bone marrow (BM) vascular niche that plays an important role in supporting self-renewal capacity and maintaining the stability of HSC pool. Here we provide evidences that vascular niche is a target of aGvHD in a major histocompatibility complex (MHC)-haploidentical matched murine HSCT model. The results demonstrated that hematopoietic cells derived from GvHD mice had the capacity to reconstitute hematopoiesis in healthy recipient mice. However, hematopoietic cells from healthy donor mice failed to reconstitute hematopoiesis in GvHD recipient mice, indicating that the BM niche was impaired by aGvHD in this model. We further demonstrated that SECs were markedly reduced in the BM of aGvHD mice. High level of Fas and caspase-3 expression and high rate of apoptosis were identified in SECs, indicating that SECs were destroyed by aGvHD in this murine HSCT model. Furthermore, high Fas ligand expression on engrafted donor CD4(+), but not CD8(+) T cells, and high level MHC-II but not MHC-I expression on SECs, suggested that SECs apoptosis was mediated by CD4(+) donor T cells through the Fas/FasL pathway.
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Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China.
Tumour Biol.
PUBLISHED: 07-24-2014
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This stud y examined the epidemiology, risk factors, management, and outcome of invasive fungal infection (IFI) in patients receiving chemotherapy for hematological malignancy in China. IFI risk factors were analyzed using univariate analysis and multivariate logistic regression. In total, 4,192 patients receiving 4,889 chemotherapy courses were enrolled [mean age 40.7 years, 58.4 % male, 16.9 % children (<18 years)]. The most common hematological diseases were acute myeloid leukemia (AML, 28.5 %), non-Hodgkin lymphoma (NHL, 26.3 %), and acute lymphoblastic leukemia (ALL, 20.2 %). Severe neutropenia (absolute neutrophil count [ANC] <500/mm(3)) occurred after one third (1,633/4,889, 33.4 %) of chemotherapy courses. Incidence of proven/probable IFI was 2.1 % per chemotherapy course and higher in patients with myelodysplastic syndrome (MDS, 4.94 %), acute hyperleukocytic leukemia (AHL, 4.76 %), AML (3.83 %), or induction chemotherapy. Risk factors included ANC <500/mm(3) [odds ratio (OR) 3.60], AML or MDS (OR 1.97), induction chemotherapy (OR 2.58), previous IFI (OR 3.08), and being male (OR 1.74). Antifungal agents, prescribed in one quarter (1,211/4,889, 24.8 %) of chemotherapy courses, included primary/secondary prophylaxis (n?=?827, 16.9 %) and/or treatment (n?=?655, 13.4 %; 86.9 % triazoles), which was empirical (84.3 %), pre-emptive (8.6 %), or targeted (7.1 %). Overall mortality following each chemotherapy course (1.5 %) increased in proven/probable (11.7 %) and possible IFI (8.2 %). In summary, IFI was more common in MDS, AHL, AML, or induction chemotherapy, and substantially increased mortality. Neutropenic patients receiving induction chemotherapy for AML or MDS and those with previous IFI were at particular risk. Antifungal prophylaxis showed an independent protective effect but was not commonly used, even in high-risk patients. By contrast, empiric antifungals were widely used.
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Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma.
Hematology
PUBLISHED: 07-18-2014
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Objectives The randomized phase 3 PRIMA trial established that 2 years of rituximab maintenance therapy after attaining disease response to immunochemotherapy as first-line treatment of follicular lymphoma, reduced the risk of disease progression, compared with observation, without adversely affecting patient-reported quality of life (QoL). We now report additional analyses of symptom burden and toxicity. Methods Symptom burden was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items. The proportion of patients with worsening, no change, or improvement in symptoms from maintenance baseline was compared between rituximab maintenance and observation groups with Pearson ?(2) tests. Improvement in symptoms after 1 and 2 years of maintenance was further analyzed using generalized mixed models. The adverse event (AE) rate was calculated from the toxicity checklist at each visit to explore the frequency and timing of the toxicity AE in each treatment arm. The study protocol was approved by local ethics committees and is registered at ClinicalTrials.gov under NCT00140582. Results Being tired, needing to rest, feeling weak, and trouble sleeping were the most frequently reported symptoms at the end of immunochemotherapy. By the end of maintenance, notable improvement was seen for fatigue symptoms, trouble sleeping, shortness of breath, lack of appetite, and nausea, with no significant difference in QoL symptoms between the rituximab maintenance and observation groups. The rate of AEs was low, and hematologic toxicity induced during chemotherapy treatment improved in both rituximab maintenance and observation groups. Discussion These results indicated that rituximab maintenance did not negatively impact disease- or treatment-related symptoms.
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[Survey on overweight and obesity of preschool children in rural areas from ten provinces of China].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 07-11-2014
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To analyze the status of overweight and obesity among preschool children in rural areas of ten provinces in China.
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Effects of transplantation of olfactory ensheathing cells in chronic spinal cord injury: a systematic review and meta-analysis.
Eur Spine J
PUBLISHED: 06-08-2014
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The debate on the effects and outcome of olfactory ensheathing cell (OEC) transplantation for the treatment of spinal cord injury (SCI) has remained unresolved for nearly 20 years. This study aimed to evaluate the safety and efficacy of OEC transplantation in chronic SCI patients.
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Evaluation of surgical and non-surgical interventions for clavicle fractures.
Acta Orthop Traumatol Turc
PUBLISHED: 06-06-2014
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The aim of this study was to review all systematic reviews and meta-analyses and provide an overview of the evidence of efficacy of interventions for clavicle fractures.
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Effect of weak magnetic field on arsenate and arsenite removal from water by zerovalent iron: an XAFS investigation.
Environ. Sci. Technol.
PUBLISHED: 05-28-2014
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In this study, a weak magnetic field (WMF), superimposed with a permanent magnet, was utilized to improve ZVI corrosion and thereby enhance As(V)/As(III) removal by ZVI at pHini 3.0-9.0. The experiment with real arsenic-bearing groundwater revealed that WMF could greatly improve arsenic removal by ZVI even in the presence of various cations and anions. The WMF-induced improvement in As(V)/As(III) removal by ZVI should be primarily associated with accelerated ZVI corrosion, as evidenced by the pH variation, Fe(2+) release, and the formation of corrosion products as characterized with X-ray absorption fine structure spectroscopy. The arsenic species analysis in solution/solid phases at pHini 3.0 revealed that As(III) oxidation to As(V) in aqueous phase preceded its subsequent sequestration by the newly formed iron (hydr)oxides. However, both As(V) adsorption following As(III) oxidation to As(V) in solution and As(III) adsorption preceding its conversion to As(V) in solid phase were observed at pHini 5.0-9.0. The application of WMF accelerated the transformation of As(III) to As(V) in both aqueous and solid phases at pHini 5.0-9.0 and enhanced the oxidation of As(III) to As(V) in solution at pHini 3.0.
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[Impact of graft versus host disease on outcome of allogeneic peripherial blood stem cell transplantation for leukemia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-27-2014
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To analyze the impact of the occurrence and severity of acute and chronic graft versus host disease (GVHD) on the long-term outcome of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for leukemia.
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Blast-induced traumatic brain injury of goats in confined space.
Neurol. Res.
PUBLISHED: 04-15-2014
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To study blast-induced traumatic brain injury (bTBI) characteristics in confined space.
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High prognostic value of minimal residual disease detected by flow-cytometry-enhanced fluorescence in situ hybridization in core-binding factor acute myeloid leukemia (CBF-AML).
Ann. Hematol.
PUBLISHED: 04-04-2014
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Acute myeloid leukemia (AML) is generally regarded as a disorder of stem cells, known as leukemic initiating cells (LICs), which initiate the disease and contribute to relapses. Although the phenotype of these cells remains unclear in most patients, they are enriched within the CD34(+)CD38(-) population. In core-binding factor (CBF) AML, the cytogenetic abnormalities also exist in LIC. The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy. Thirty-six patients under 65 years of age with de novo CBF-AML treated with intensive chemotherapy were retrospectively included in this study. Correlations with relapse-free survival (RFS) and overall survival were evaluated with univariate and multivariate analyses. FISH efficiently identified LICs in the CD34(+)CD38(-) population. The presence of FISH(+)CD34(+)CD38(-) cells before consolidation was negatively associated with cumulative incidence of relapse (64 vs 18 %, P = .012), which showed prognostic value for RFS (12 vs 68 %, P = .008) and OS (11 vs 75 %, P = .0005), and retained prognostic significance for RFS in multivariate analysis. The detection of FISH(+)CD34(+)CD38(-) cells before consolidation therapy significantly correlated with long-term survival. Fluorescence-activated cell sorting (FACS)-FISH could be potentially adopted as a MRD monitor approach in clinical practice to identify CBF-AML patients at risk of treatment failure during therapy.
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Clinical Efficacy and Safety in Relapsed/Refractory Mantle Cell Lymphoma: A Systematic Literature Review.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 03-11-2014
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A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.
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Pathological features and clinical outcomes of breast cancer according to levels of oestrogen receptor expression.
Histopathology
PUBLISHED: 03-08-2014
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Historically, nuclear staining of ?10% of invasive tumour cells has been used for oestrogen receptor (ER) positivity. In 2010, ASCO/CAP guidelines recommended the cut-off value be changed to nuclear staining of ?1%. This study will analyse the relationships between levels of ER expression and clinicopathological features and clinical outcomes, with an emphasis on the ER 1-10% subgroup.
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Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma.
Cell Rep
PUBLISHED: 03-03-2014
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Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs) exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%-53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods.
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Incorporation of arsenic trioxide in induction therapy improves survival of patients with newly diagnosed acute promyelocytic leukaemia.
Eur. J. Haematol.
PUBLISHED: 02-26-2014
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For patients with acute promyelocytic leukaemia (APL), negative reading of a promyelocytic leukaemia/retinoic acid receptor-alpha (PML-RAR?) transcript after induction therapy correlates with a good prognosis. However, in the majority of patients given all-trans retinoic acid (ATRA)/anthracycline-based induction therapy, PML-RAR? transcript remains even when haematologic complete remission is achieved. To facilitate maximal therapeutic efficacy for patients with APL, this study tested whether the addition of arsenic trioxide (ATO) would increase the rate of molecular complete remission after ATRA/anthracycline-based induction therapy.
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Clinical efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 02-20-2014
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This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a meta-analysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.
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Graft-versus-host disease causes broad suppression of hematopoietic primitive cells and blocks megakaryocyte differentiation in a murine model.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-06-2014
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Cytopenia and delayed immune reconstitution with acute graft-versus-host disease (aGVHD) indicate a poor prognosis. However, how donor-derived cell hematopoiesis is impaired in aGVHD is not well understood. We addressed this issue by studying the kinetics of hematopoiesis and the functions of hematopoietic stem and progenitor cells in an aGVHD model with haplo-MHC-matched murine bone marrow transplantation. Although hematopoiesis was progressively suppressed during aGVHD, the hematopoietic regenerative potential of donor-derived hematopoietic stem cells remains intact. There was a dramatic reduction in primitive hematopoietic cells and a defect in the ability of these cells to generate common myeloid progenitors (CMPs) and megakaryocyte/erythrocyte progenitors (MEPs). These effects were observed along with a concomitant increase in granulocyte/macrophage progenitors, suggesting that differentiation into MEPs is blocked during aGVHD. Interestingly, cyclosporine A was able to partially reverse the hematopoietic suppression as well as the differentiation blockage of CMPs. These data provide new insights into the pathogenesis of aGVHD and may improve the clinical management of aGVHD.
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Relationship between diclofenac dose and risk of gastrointestinal and cardiovascular events: meta-regression based on two systematic literature reviews.
Clin Ther
PUBLISHED: 02-04-2014
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NSAIDs are associated with risks of gastrointestinal (GI) and cardiovascular (CV) toxicities. It has been reported that the risks of GI and CV events are dose related, resulting in guidance explicitly emphasizing the use of NSAIDs at the lowest effective dose for the shortest duration. To understand the potential benefits of using lower doses of diclofenac, a more detailed understanding of the relationship of diclofenac dose and the risks of GI and CV events is required.
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Nrf2 amplifies oxidative stress via induction of Klf9.
Mol. Cell
PUBLISHED: 01-28-2014
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Reactive oxygen species (ROS) activate NF-E2-related transcription factor 2 (Nrf2), a key transcriptional regulator driving antioxidant gene expression and protection from oxidant injury. Here, we report that in response to elevation of intracellular ROS above a critical threshold, Nrf2 stimulates expression of transcription Kruppel-like factor 9 (Klf9), resulting in further Klf9-dependent increases in ROS and subsequent cell death. We demonstrated that Klf9 independently causes increased ROS levels in various types of cultured cells and in mouse tissues and is required for pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Mechanistically, Klf9 binds to the promoters and alters the expression of several genes involved in the metabolism of ROS, including suppression of thioredoxin reductase 2, an enzyme participating in ROS clearance. Our data reveal an Nrf2-dependent feedforward regulation of ROS and identify Klf9 as a ubiquitous regulator of oxidative stress and lung injury.
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Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-27-2014
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Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as "stitchers," to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication-licensing complex. A second group (two bladder tumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in bladder cancer.
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LIFR?-CT3 induces differentiation of a human acute myelogenous leukemia cell line HL-60 by suppressing miR-155 expression through the JAK/STAT pathway.
Leuk. Res.
PUBLISHED: 01-22-2014
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The distal cytoplasmic motifs of the leukemia inhibitory factor receptor ?-chain (LIFR?-CT3) and its TAT fusion protein (TAT-CT3) can independently suppress cell viability and induce myeloid differentiation in human leukemia HL-60 cells in our previous studies. But its underlying mechanism remains undefined. Herein, we show that a prokaryotic expressed TAT-CT3 induced a rapid elevation of STAT3 phosphorylation (pSTAT3), and then suppress the transcription of miR-155 and induce the elevation of SOCS-1, which further inhibited STAT3 phosphorylation for a long-term period. Our result indicated a novel mechanism of TAT-CT3 to promote HL60 cells differentiation, which provides some potential therapeutic targets for future acute myelogenous leukemia therapy.
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Identification of functional cooperative mutations of SETD2 in human acute leukemia.
Nat. Genet.
PUBLISHED: 01-15-2014
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Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase). Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development.
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HBsAg is an independent prognostic factor in diffuse large B cell lymphoma patients in rituximab era: result from a multicenter retrospective analysis in China.
Med. Oncol.
PUBLISHED: 01-15-2014
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This study mainly focused on the impact of Hepatitis B virus (HBV) infection on the prognosis of diffuse large B cell lymphoma (DLBCL) patients in rituximab era, using a Cox regression model to ascertain the prediction value of the serum HBV marker in survivals. Three hundred and eighty four DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin/epirubicin, vincristine and prednisone (R-CHOP-like regimens) or CHOP-like regimens were included. Progression-free survival (PFS) and overall survival (OS) of the patients have or have not received rituximab were analyzed separately. In the CHOP group, HBV infection has not been found a profound impact on the survivals. In the R-CHOP group, PFS and OS were inferior in HBsAg-positive patients (p=0.031 and p=0.006, respectively); after adjusting for International Prognostic Index parameters, HBsAg is an independent unfavorable factor for both PFS (RR=2.492) and OS (RR=2.589).
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Specific chemical interactions between metal ions and biological solids exemplified by sludge particulates.
Bioresour. Technol.
PUBLISHED: 01-08-2014
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The adsorption of metals onto biological surfaces was studied exemplified by municipal sludge particulates of the primary, the secondary, and the tertiary sludge types from four regional wastewater treatment plants. Major factors affecting the extent of metal adsorption including pH, DOM, total biomass, and total metal loading were studied. The acidity-basicity characteristics of the DOM, the metal ions (Lewis acids), and the surface of the sludge particulates make pH the most important parameter in metal adsorption. Change in pH can modify the speciation of the metal ions, the DOM, and the surface acidity of the sludge particulates and subsequently determines the degree of metal distribution between the aqueous phase and the sludge solids. Information on the acidity-basicity characteristics of the DOM and the sludge particulates are used to calculate the stability constant of metal ion-sludge complexes.
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Homoharringtonine and omacetaxine for myeloid hematological malignancies.
J Hematol Oncol
PUBLISHED: 01-03-2014
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Homoharringtonine (HHT), a plant alkaloid with antitumor properties originally identified nearly 40 years ago, has a unique mechanism of action by preventing the initial elongation step of protein synthesis. HHT has been used widely in China for the treatment of chronic myeloid leukemia (CML), acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Omacetaxine, a semisynthetic form of HHT, with excellent bioavailability by the subcutaneous route, has recently been approved by FDA of the United States for the treatment of CML refractory to tyrosine kinase inhibitors. This review summarized preclinical and clinical development of HHT and omacetaxine for myeloid hematological malignancies.
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Mediastinal Lymph Node Dissection versus Mediastinal Lymph Node Sampling for Early Stage Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients.
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A genome-wide RNAi screen identifies FOXO4 as a metastasis-suppressor through counteracting PI3K/AKT signal pathway in prostate cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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Activation of the PI3K/AKT signal pathway is a known driving force for the progression to castration-recurrent prostate cancer (CR-CaP), which constitutes the major lethal phenotype of CaP. Here, we identify using a genomic shRNA screen the PI3K/AKT-inactivating downstream target, FOXO4, as a potential CaP metastasis suppressor. FOXO4 protein levels inversely correlate with the invasive potential of a panel of human CaP cell lines, with decreased mRNA levels correlating with increased incidence of clinical metastasis. Knockdown (KD) of FOXO4 in human LNCaP cells causes increased invasion in vitro and lymph node (LN) metastasis in vivo without affecting indices of proliferation or apoptosis. Increased Matrigel invasiveness was found by KD of FOXO1 but not FOXO3. Comparison of differentially expressed genes affected by FOXO4-KD in LNCaP cells in culture, in primary tumors and in LN metastases identified a panel of upregulated genes, including PIP, CAMK2N1, PLA2G16 and PGC, which, if knocked down by siRNA, could decrease the increased invasiveness associated with FOXO4 deficiency. Although only some of these genes encode FOXO promoter binding sites, they are all RUNX2-inducible, and RUNX2 binding to the PIP promoter is increased in FOXO4-KD cells. Indeed, the forced expression of FOXO4 reversed the increased invasiveness of LNCaP/shFOXO4 cells; the forced expression of FOXO4 did not alter RUNX2 protein levels, yet it decreased RUNX2 binding to the PIP promoter, resulting in PIP downregulation. Finally, there was a correlation between FOXO4, but not FOXO1 or FOXO3, downregulation and decreased metastasis-free survival in human CaP patients. Our data strongly suggest that increased PI3K/AKT-mediated metastatic invasiveness in CaP is associated with FOXO4 loss, and that mechanisms to induce FOXO4 re-expression might suppress CaP metastatic aggressiveness.
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Class I ADP-ribosylation factors are involved in enterovirus 71 replication.
PLoS ONE
PUBLISHED: 01-01-2014
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Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.
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Inhibition of Enterovirus 71 replication by 7-hydroxyflavone and diisopropyl-flavon7-yl Phosphate.
PLoS ONE
PUBLISHED: 01-01-2014
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Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease, which has been continuously prevalent in Asia in recent years. In children, severe cases can lead to death, and no prophylactic or therapeutic measures against EV71 infection are available. The 3C proteases of EV71 play an important role in viral replication and are an ideal drug target. In previous work, we resolved the crystal structure for EV71 3Cpro. In this report, we took advantage of the automated docking program AutoDock 4.0 to simulate EV71 3Cpro-ligand conformation. 7-hydroxyflavone (HF) and its phosphate ester(FIP) were predicted to bind with EV71 3Cpro.In an in vitro protease inhibition assay, FIP inhibited EV71 3Cpro protease activity. Both flavones were highly active against EV71, protecting cells from EV71 infection. Replication of viral RNA and formation of EV71 plaque were all strongly inhibited in cells. These results indicated that HF and FIP may serve as potential protective agents in the treatment of patients with chronic EV71 infection.
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Anti-enterovirus 71 effects of chrysin and its phosphate ester.
PLoS ONE
PUBLISHED: 01-01-2014
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Enterovirus 71 (EV71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. The anti-EV71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. By using the predicting program Autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3Cpro activity. Replication of viral RNA and production of viral capsid protein and the infectious virion were strongly inhibited by chrysin, without noticeable cytotoxicity. Cytopathic effects on cells were also prevented. Diisopropyl chrysin-7-yl phosphate (CPI), the phosphate ester for chrysin, was generated through a simplified Atheron-Todd reaction to achieve stronger anti-viral activity. CPI was also able to bind with and inhibit viral 3Cpro activity in vitro. As expected, CPI demonstrated more potent antiviral activity against EV71.
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Analysis of differential gene expression and novel transcript units of ovine muscle transcriptomes.
PLoS ONE
PUBLISHED: 01-01-2014
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In this study, we characterized differentially expressed genes (DEGs) between the muscle transcriptomes of Small-tailed Han sheep and Dorper sheep and predicted novel transcript units using high-throughput RNA sequencing technology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that 1,300 DEGs were involved in cellular processes, metabolic pathways, and the actin cytoskeleton pathway. Importantly, we identified 34 DEGs related to muscle cell development and differentiation. Additionally, we were able to optimize the gene structure and predict the untranslated regions (UTRs) for some of the DEGs. Among the 123,678 novel predicted transcript units (TUs), 15,015 units were predicted protein sequences. The reliability of the sequencing data was verified through qRT-PCR analysis of 12 genes. These results will provide useful information for functional genetic research in the future.
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Large-Scale, Ion-Current-Based Proteomics Investigation of Bronchoalveolar Lavage Fluid in Chronic Obstructive Pulmonary Disease Patients.
J. Proteome Res.
PUBLISHED: 12-02-2013
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Proteomic analysis of bronchoalveolar lavage fluid (BALF) in chronic obstructive pulmonary disease (COPD) patients may provide new biomarkers and deeper understanding of the disease mechanisms but remains challenging. Here we describe an ion-current-based strategy for comparative analysis of BALF proteomes from patients with moderate and stable COPD versus healthy controls. The strategy includes an efficient preparation procedure providing quantitative recovery and a nano-LC/MS analysis with a long, heated column. Under optimized conditions, high efficiency and reproducibility were achieved for each step, enabling a "20-plex" comparison of clinical subjects (n = 10/group). Without depletion/fractionation, a total of 423 unique protein groups were quantified under stringent criteria with at least two quantifiable peptides. Seventy-six proteins were determined as significantly altered in COPD, which represent a diversity of biological processes such as alcohol metabolic process, gluconeogenesis/glycolysis, inflammatory response, proteolysis, and oxidation reduction. Interestingly, altered alcohol metabolism responding to oxidant stress is a novel observation in COPD. The prominently elevated key enzymes involved in alcohol metabolism (e.g., ADH1B, ALDH2, and ALDH3A1) may provide a reasonable explanation for a bewildering observation in COPD patients known for decades: the underestimation of the blood alcohol concentrations through breath tests. These discoveries could provide new insights for identifying novel biomarkers and pathological mediators in clinical studies.
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Meta-analysis of all-trans retinoic acid-linked arsenic trioxide treatment for acute promyelocytic leukemia.
Hematology
PUBLISHED: 11-25-2013
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To explore the combination therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) on acute promyelocytic leukemia (APL).
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Computational methods for detecting copy number variations in cancer genome using next generation sequencing: principles and challenges.
Oncotarget
PUBLISHED: 11-19-2013
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Accurate detection of somatic copy number variations (CNVs) is an essential part of cancer genome analysis, and plays an important role in oncotarget identifications. Next generation sequencing (NGS) holds the promise to revolutionize somatic CNV detection. In this review, we provide an overview of current analytic tools used for CNV detection in NGS-based cancer studies. We summarize the NGS data types used for CNV detection, decipher the principles for data preprocessing, segmentation, and interpretation, and discuss the challenges in somatic CNV detection. This review aims to provide a guide to the analytic tools used in NGS-based cancer CNV studies, and to discuss the important factors that researchers need to consider when analyzing NGS data for somatic CNV detections.
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6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer.
Oncotarget
PUBLISHED: 11-16-2013
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Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). In a comparative fashion much less is known about copy number alterations in TCC-UB, but it appears that amplification of chromosome 6p22 is one of the most frequent changes. Using fluorescence in situ hybridization (FISH) analyses, we evaluated chromosomal 6p22 amplification in a large cohort of bladder cancer patients with complete surgical staging and outcome data. We have also used shRNA knockdown candidate oncogenes in the cell based study. We found that amplification of chromosome 6p22.3 is significantly associated with the muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) (22%) in contrast to superficial TCC-UB (9%) (p=7.2-04). The rate of 6p22.3 amplification in pN>1 patients (32%) is more than twice that in pN0 (16%) patients (p=0.05). Interestingly, we found that 6p22.3 amplification is as twice as high (p=0.0201) in African American (AA) than European American (EA) TCC-UB patients. Moreover, we showed that the expression of some candidate genes (E2F3, CDKAL1 and Sox4) in the 6p22.3 region is highly correlated with the chromosomal amplification. In particular, knockdown of E2F3 inhibits cell proliferation in a 6p22.3-dependent manner, whereas knockdown of CDKAL1 and Sox4 has no effect on cell proliferation. Using gene expression profiling, we further identified some common as well as distinctive subset targets of the E2F3 family members. In summary, our data indicate that E2F3 is a key regulator of cell proliferation in a subset of bladder cancer and the 6p22.3 amplicon is a biomarker of aggressive phenotype in this tumor type.
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Alpha-lipoic acid-loaded nanostructured lipid carrier: sustained release and biocompatibility to HaCaT cells in vitro.
Drug Deliv
PUBLISHED: 10-21-2013
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Abstract ALA-loaded nanostructured lipid carrier (ALA-NLC) was designed to improve physicochemical stability and water solubility, and promote sustained release of ALA as well as determine the biocompatibility of ALA-NLC. The ALA-NLC manufactured using hot high-pressure homogenization technique was investigated in terms of size, zeta potential, FTIR analysis and release behavior. In vitro cytotoxicity and biocompatibility were determined by incubating with HaCaT cells using the MTT assay, HE staining and Hoechst 33342 staining. Cell behavior and cellular division of HaCaT cells untreated and treated by ALA-NLC were investigated in real-time images gathered using time-lapse imaging system. The release investigation illustrated that only 6.9% of ALA released in 30?min from ALA-NLC formation, whereas it was 30.3% in free ALA system. ALA-NLC possessed a satisfactory release behavior of sustained release up to 72?h. It showed that ALA-NLC did not exert hazardous effect on HaCaT cells up to 81.9?mg/L without morphological alterations, revealing a satisfactory biocompatibility. Evidence was provided from time-lapse imaging system that cell behavior and cellular division of ALA-NLC treated HaCaT cells were in accordance with the control. These results of this investigation demonstrated that NLC encapsulated ALA formation (ALA-NLC) can improve stability, solubility and release of ALA; ALA-NLC was biocompatible to HaCaT cells.
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Folate Receptor ? Associated With Triple-Negative Breast Cancer and Poor Prognosis.
Arch. Pathol. Lab. Med.
PUBLISHED: 09-13-2013
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Context.-Folate receptor ? (FRA) has been shown to be selectively expressed in several types of human cancer, including breast cancer. Currently, several FRA target therapies are under intensive study. Objective.-To investigate the expression pattern of FRA in a large cohort of patients with breast cancer and analyze its relationship with different clinicopathologic features, with expression of several key biomarkers, and with clinical outcome. Design.-Four hundred forty-seven cases of infiltrating ductal carcinoma diagnosed between 1997 and 2008 in our institution were identified and reviewed, and 25 blocks of tissue microassays were constructed. The association between expression of FRA and clinicopathologic features; expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67; and clinical outcome of these tumors were evaluated. Results.-The expression of FRA was significantly associated with tumors with high histologic grade, higher nodal stages, ER/PR negativity, and high proliferative activity (Ki-67 ? 15%), and was independent of HER2/neu overexpression. In all, 74% of ER/PR-negative and 80% of triple-negative breast cancers expressed FRA. The expression of FRA was significantly associated with a worse disease-free survival. Conclusions.-Our data demonstrate that a significant subgroup of ER/PR-negative and triple-negative breast cancers expresses FRA, and its expression is associated with worse clinical outcome.
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Fiber-based free-space optical coherent receiver with vibration compensation mechanism.
Opt Express
PUBLISHED: 08-14-2013
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We propose a novel fiber-based free-space optical (FSO) coherent receiver for inter-satellite communication. The receiver takes advantage of established fiber-optic components and utilizes the fine-pointing subsystem installed in FSO terminals to minimize the influence of satellite platform vibrations. The received beam is coupled to a single-mode fiber, and the coupling efficiency of the system is investigated both analytically and experimentally. A receiving sensitivity of -38 dBm is obtained at the forward error correction limit with a transmission rate of 22.4 Gbit/s. The proposed receiver is shown to be a promising component for inter-satellite optical communication.
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Thymic damage, impaired negative selection, and development of chronic graft-versus-host disease caused by donor CD4+ and CD8+ T cells.
J. Immunol.
PUBLISHED: 05-24-2013
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Prevention of chronic graft-versus-host disease (cGVHD) remains a major challenge in allogeneic hematopoietic cell transplantation (HCT) owing to limited understanding of cGVHD pathogenesis and lack of appropriate animal models. In this study, we report that, in classical acute GVHD models with C57BL/6 donors and MHC-mismatched BALB/c recipients and with C3H.SW donors and MHC-matched C57BL/6 recipients, GVHD recipients surviving for >60 d after HCT developed cGVHD characterized by cutaneous fibrosis, tissue damage in the salivary gland, and the presence of serum autoantibodies. Donor CD8(+) T cells were more potent than CD4(+) T cells for inducing cGVHD. The recipient thymus and de novo-generated, donor-derived CD4(+) T cells were required for induction of cGVHD by donor CD8(+) T cells but not by donor CD4(+) T cells. Donor CD8(+) T cells preferentially damaged recipient medullary thymic epithelial cells and impaired negative selection, resulting in production of autoreactive CD4(+) T cells that perpetuated damage to the thymus and augmented the development of cGVHD. Short-term anti-CD4 mAb treatment early after HCT enabled recovery from thymic damage and prevented cGVHD. These results demonstrate that donor CD8(+) T cells cause cGVHD solely through thymic-dependent mechanisms, whereas CD4(+) T cells can cause cGVHD through either thymic-dependent or independent mechanisms.
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Long-term low do enriches and shifts nitrifier community in activated sludge.
Environ. Sci. Technol.
PUBLISHED: 05-13-2013
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In the activated sludge process, reducing the operational dissolved oxygen (DO) concentration can improve oxygen transfer efficiency, thereby reducing energy use. The low DO, however, may result in incomplete nitrification. This research investigated the long-term effect of low DO on the nitrification performance of activated sludge. Results indicated that, for reactors with 10 and 40 day solids retention times (SRTs), complete nitrification was accomplished after a long-term operation with a DO of 0.37 and 0.16 mg/L, respectively. Under long-term low DO conditions, nitrite oxidizing bacteria (NOB) became a better oxygen competitor than ammonia oxidizing bacteria (AOB) and, as a result, no nitrite accumulated. Real-time PCR assays indicated that the long-term low DO enriched both AOB and NOB in activated sludge, increasing the sludge nitrification capacity and diminishing the adverse effect of low DO on the overall nitrification performance. The increase in the population size of nitrifiers was likely resulted from the reduced nitrifier endogenous decay rate by a low DO. Under long-term low DO conditions, Nitrosomonas europaea/eutropha remained as the dominant AOB, whereas the number of Nitrospira-like NOB became much greater than Nitrobacter-like NOB, especially for the 40 day SRT sludge. The enrichment and shift of the nitrifier community reduced the adverse effect of low DO on nitrification; therefore, low DO operation of a complete nitrification process is feasible.
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Targeting oxidative stress in embryonal rhabdomyosarcoma.
Cancer Cell
PUBLISHED: 05-03-2013
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Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS.
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A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial.
J Hematol Oncol
PUBLISHED: 04-23-2013
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BACKGROUND: There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. METHODS: MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with >=1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for >=1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie-Salmon stage III) and were heavily pretreated (56.7% had received >=4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. RESULTS: The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4--18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5--9.8). The most common grade 3--4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. CONCLUSIONS: Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options.Trial registration: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410.
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Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases.
Mod. Pathol.
PUBLISHED: 03-27-2013
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Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study was to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs without invasive ductal carcinoma, the former had 11q22.1-23.3 loss (P=0.031) and chr5 gain (P=0.085), and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041) and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor. We offer herein a proposal of intracystic papillary carcinoma pathogenesis through its relation to invasive ductal carcinoma and ductal carcinoma in situ.Modern Pathology advance online publication, 2 August 2013; doi:10.1038/modpathol.2013.136.
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Facilitates chromatin transcription complex is an "accelerator" of tumor transformation and potential marker and target of aggressive cancers.
Cell Rep
PUBLISHED: 03-25-2013
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The facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compounds and is not expressed in normal cells of adult mammalian tissues, except for undifferentiated and stem-like cells. Here, we show that FACT expression is strongly associated with poorly differentiated aggressive cancers with low overall survival. In addition, FACT was found to be upregulated during in vitro transformation and to be necessary, but not sufficient, for driving transformation. FACT also promoted survival and growth of established tumor cells. Genome-wide mapping of chromatin-bound FACT indicated that FACTs role in cancer most likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses.
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Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.
Nat. Genet.
PUBLISHED: 03-21-2013
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The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs.
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Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced mesenchymal-to-epithelial transition and induced pluripotent stem cell generation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-05-2013
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Fibroblasts can be reprogrammed to induced pluripotent stem cells (iPSCs) by application of transcription factors octamer-binding protein 4 (Oct4), SRY-box containing gene 2 (Sox2), Kruppel-like factor 4 (Klf4), and c-Myelocytomatosis oncogene (c-Myc) (OSKM), but the underlying mechanisms remain unclear. Here, we report that exogenous Oct4 and Sox2 can bind at the promoter regions of mir-141/200c and mir-200a/b/429 cluster, respectively, and induce the transcription activation of miR-200 family during the OSKM-induced reprogramming. Functional suppression of miR-200s with specific inhibitors significantly represses the OSKM-caused mesenchymal-to-epithelial transition (MET, an early event in reprogramming of fibroblasts to iPSCs) and iPSC generation, whereas overexpression of miR-200s promotes the MET and iPSC generation. Mechanistic studies showed that miR-200s significantly repress the expression of zinc finger E-box binding homeobox 2 (ZEB2) through directly targeting its 3 UTR and direct inhibition of ZEB2 can mimic the effects of miR-200s on iPSC generation and MET process. Moreover, the effects of miR-200s during iPSC generation can be blocked by ZEB2 overexpression. Collectively, our findings not only reveal that members of the miR-200 family are unique mediators of the reprogramming factors Oct4/Sox2, but also demonstrate that the miR-200/ZEB2 pathway as one critical mechanism of Oct4/Sox2 to induce somatic cell reprogramming at the early stage.
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The resistance mechanisms of proteasome inhibitor bortezomib.
Biomark Res
PUBLISHED: 02-02-2013
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The proteasome inhibitor, bortezomib, a boronic dipeptide which reversibly inhibit the chymotrypsin-like activity at the ?5-subunit of proteasome (PSMB5), has marked efficacy against multiple myeloma and several non-Hodgkins lymphoma subtypes, and has a potential therapeutic role against other malignancy diseases. However, intrinsic and acquired resistance to bortezomib may limit its efficacy. In this article, we discuss recent advances in the molecular understanding of bortezomib resistance. Resistance mechanisms discussed include mutations of PSMB5 and the up-regulation of proteasome subunits, alterations of gene and protein expression in stress response, cell survival and antiapoptotic pathways, and multidrug resistance.
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Physicochemical characterization, identification and improved photo-stability of alpha-lipoic acid-loaded nanostructured lipid carrier.
Drug Dev Ind Pharm
PUBLISHED: 01-22-2013
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Abstract Objective: The ultimate goal of this research is to corroborate the physicochemical characterization of nanostructured lipid carrier (NLC) loading unstable lipophilic active ingredients with an antioxidant function, such as alpha-lipoic acid (ALA), and monitoring its photochemical stability of ALA-NLC against natural daylight. NLC is an innovative active compound delivery system in pharmaceutical and cosmetic fields. It has been recommended as active substance carriers to enhance the effectiveness of lipophilic compounds. Methods: ALA-NLC was manufactured using hot high pressure homogenization technique to increase the water solubility and photo-stability. The physicochemical characterization properties of ALA-NLC have been determined in terms of nanoparticle size, zeta potential, polydispersity index value and size distribution. Size analysis was implemented through photon correlation spectroscopy and laser diffractometry. Morphological profile of nanoparticles was observed via atomic force microscopy. The loading of NLC containing ALA was evaluated by high performance liquid chromatography. ALA-NLC was subjected to UV-Vis spectrophotometer to validate the existence of ALA. Water contact angle measurement was manipulated to determine the hydrophilicity of the sample. The photo-stability of ALA-NLC within 120 days was assessed by the retention of ALA. Results: The ALA-NLC provided maximum ALA retention of 93.9% in 30 days exposure to natural daylight, the retention of free ALA only 42.5%. About 88.5% of the initial ALA in NLC system remained after 120 days under the same conditions, while the retention of free ALA only 0.7% under natural daylight irradiation. The photo-stability of ALA was considerably enhanced by NLC formulation compared with free ALA itself. Therefore, the NLC formulation provided a reliable protection of ALA against natural daylight, enhancing its photochemical stability. Conclusion: The present investigation elucidated that the NLC drastically improved the water solubility, particularly the facilitation of photo-stability of ALA exposure to natural daylight.
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Relationship between changes in the cochlear blood flow and disorder of hearing function induced by blast injury in guinea pigs.
Int J Clin Exp Pathol
PUBLISHED: 01-11-2013
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The auditory system is the most susceptible to damages from blast waves. Blast injuries always lead to varying degrees of hearing impairment. Although a disorder of the cochlear blood flow (CoBF) has been considered to be related to many pathological processes of the auditory system and to contribute to various types of hearing loss, changes in the CoBF induced by blast waves and the relationship between such changes and hearing impairment are undefined. To observe the changes in the cochlear microcirculation after exposure to an explosion blast, investigate the relationship between changes in the CoBF and hearing impairment and subsequently explore the mechanism responsible for the changes in the CoBF, we detected the perfusion of the cochlear microcirculation and hearing threshold shift after exposure to an explosion blast. Then, an N-nitro-L-arginine-methyl ester (L-NAME, NO synthase inhibitor) solution and artificial perilymph were applied to the round window (RW) of the cochlea before the blast exposure, followed by an evaluation of the CoBF and hearing function. The results indicated that the changes in the CoBF were correlated to the strength of the blast wave. The cochlear blood flow significantly increased when the peak value of the blast overpressure was greater than approximately 45 kPa, and there was no significant change in the cochlear blood flow when the peak value of the blast overpressure was less than approximately 35 kPa. Following local administration of the NO synthase inhibitor L-NAME, the increase in the CoBF induced by the blast was inhibited, and this reduction was significantly associated with the hearing threshold.
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FUSIM: a software tool for simulating fusion transcripts.
BMC Bioinformatics
PUBLISHED: 01-11-2013
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Gene fusions are the result of chromosomal aberrations and encode chimeric RNA (fusion transcripts) that play an important role in cancer genesis. Recent advances in high throughput transcriptome sequencing have given rise to computational methods for new fusion discovery. The ability to simulate fusion transcripts is essential for testing and improving those tools.
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Quinacrine impairs enterovirus 71 RNA replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.
PLoS ONE
PUBLISHED: 01-03-2013
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Since the 1980s, epidemics of enterovirus 71 (EV71) and other enteroviruses have occurred in Asian countries and regions, causing a wide range of human diseases. No effective therapy is available for the treatment of these infections. Internal ribosome entry sites (IRESs) are indispensable for the initiation of translation in enteroviruses. Several cellular factors, as well as the ribosome, are recruited to the conserved IRES during this process. Quinacrine intercalates into the RNA architecture and inhibits RNA transcription and protein synthesis, and a recent study showed that quinacrine inhibited encephalomyocarditis virus and poliovirus IRES-mediated translation in vitro without disrupting internal cellular IRES. Here, we report that quinacrine was highly active against EV71, protecting cells from EV71 infection. Replication of viral RNA, expression of viral capsid protein, and production of virus were all strongly inhibited by quinacrine. Interaction of the polypyrimidine tract-binding protein (PTB) with the conserved IRES was prevented by quinacrine. Coxsackieviruses and echovirus were also inhibited by quinacrine in cultured cells. These results indicate that quinacrine may serve as a potential protective agent for use in the treatment of patients with chronic enterovirus infection.
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Characteristics and mechanisms of cardiopulmonary injury caused by mine blasts in shoals: a randomized controlled study in a rabbit model.
PLoS ONE
PUBLISHED: 01-01-2013
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Because the characteristics of blast waves in water are different from those in air and because kinetic energy is liberated by a pressure wave at the water-air interface, thoracic injuries from mine blasts in shoals may be serious. The aim of the present study was to investigate the characteristics and mechanisms of cardiopulmonary injury caused by mine blasts in shoals.
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Hypoxia-inducible C-to-U coding RNA editing downregulates SDHB in monocytes.
PeerJ
PUBLISHED: 01-01-2013
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Background. RNA editing is a post-transcriptional regulatory mechanism that can alter the coding sequences of certain genes in response to physiological demands. We previously identified C-to-U RNA editing (C136U, R46X) which inactivates a small fraction of succinate dehydrogenase (SDH; mitochondrial complex II) subunit B gene (SDHB) mRNAs in normal steady-state peripheral blood mononuclear cells (PBMCs). SDH is a heterotetrameric tumor suppressor complex which when mutated causes paraganglioma tumors that are characterized by constitutive activation of hypoxia inducible pathways. Here, we studied regulation, extent and cell type origin of SDHB RNA editing. Methods. We used short-term cultured PBMCs obtained from random healthy platelet donors, performed monocyte enrichment by cold aggregation, employed a novel allele-specific quantitative PCR method, flow cytometry, immunologic cell separation, gene expression microarray, database analysis and high-throughput RNA sequencing. Results. While the editing rate is low in uncultured monocyte-enriched PBMCs (average rate 2.0%, range 0.4%-6.3%, n = 42), it is markedly upregulated upon exposure to 1% oxygen tension (average rate 18.2%, range 2.8%-49.4%, n = 14) and during normoxic macrophage differentiation in the presence of serum (average rate 10.1%, range 2.7%-18.8%, n = 17). The normoxic induction of SDHB RNA editing was associated with the development of dense adherent aggregates of monocytes in culture. CD14-positive monocyte isolation increased the percentages of C136U transcripts by 1.25-fold in normoxic cultures (n = 5) and 1.68-fold in hypoxic cultures (n = 4). CD14-negative lymphocytes showed no evidence of SDHB editing. The SDHB genomic DNA remained wild-type during increased RNA editing. Microarray analysis showed expression changes in wound healing and immune response pathway genes as the editing rate increased in normoxic cultures. High-throughput sequencing of SDHB and SDHD transcripts confirmed the induction of C136U RNA editing in normoxic cultures but showed no additional verifiable coding edits. Analysis of SDHB RNA sequence data from 16 normal human tissues from the Illumina Body Map and from 45 samples representing 23 different cell types from the ENCODE projects confirmed the occurrence of site-specific C136U editing in whole blood (1.7%) and two primary CD14+ monocyte samples (1.9% and 2.6%). In contrast, the other cell types showed an average of 0.2% and 0.1% C136U editing rates in the two databases, respectively. Conclusions. These findings demonstrate that C-to-U coding RNA editing of certain genes is dynamically induced by physiologically relevant environmental factors and suggest that epigenetic downregulation of SDHB by site-specific RNA editing plays a role in hypoxia adaptation in monocytes.
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Characterization and comparative analyses of muscle transcriptomes in Dorper and small-tailed Han sheep using RNA-Seq technique.
PLoS ONE
PUBLISHED: 01-01-2013
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The sheep is an important domestic animal and model for many types of medically relevant research. An investigation of gene expression in ovine muscle would significantly advance our understanding of muscle growth. RNA-seq is a recently developed analytical approach for transcriptome profiling via high-throughput sequencing. Although RNA-seq has been recently applied to a wide variety of organisms, few RNA-seq studies have been conducted in livestock, particularly in sheep. In this study, two cDNA libraries were constructed from the biceps brachii of one Small-tailed Han sheep (SH) and one Dorper sheep (DP). The Illumina high-throughput sequencing technique and bioinformatics were used to determine transcript abundances and characteristics. For the SH and DP libraries, we obtained a total of 50,264,608 and 52,794,216 high quality reads, respectively. Approximately two-thirds of the reads could be mapped to the sheep genome. In addition, 40,481 and 38,851 potential coding single nucleotide polymorphisms (cSNPs) were observed, respectively, of which a total of 59,139 cSNP coordinates were different between the two samples. Up to 5,116 and 5,265 respective reference genes had undergone 13,827 and 15,684 alternative splicing events. A total of 6,989 reference genes were extended at the 5, 3 or both ends, and 123,678 novel transcript units were found. A total of 1,300 significantly differentially expressed genes were identified between the two libraries. These results suggest that there are many differences in the muscle transcriptomes between these two animals. This study addresses a preliminary analysis and offers a foundation for future genomic research in the sheep.
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MicroRNA-200a regulates Grb2 and suppresses differentiation of mouse embryonic stem cells into endoderm and mesoderm.
PLoS ONE
PUBLISHED: 01-01-2013
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The mechanisms by which microRNAs (miRNAs) affect cell fate decisions remain poorly understood. Herein, we report that miR-200a can suppress the differentiation of mouse embryonic stem (ES) cells into endoderm and mesoderm. Interestingly, miR-200a directly targets growth factor receptor-bound protein 2 (Grb2), which is a key adaptor in the Erk signaling pathway. Furthermore, high levels of miR-200a dramatically decrease Grb2 levels and suppress the appearance of mesoderm and endoderm lineages in embryoid body formation, as well as suppressing the activation of Erk. Finally, Grb2 supplementation significantly rescues the miR-200a-induced layer-formation bias and the Erk suppression. Collectively, our results demonstrate that miR-200a plays critical roles in ES cell lineage commitment by directly regulating Grb2 expression and Erk signaling.
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Concurrent infection of hepatitis B virus negatively affects the clinical outcome and prognosis of patients with non-Hodgkins lymphoma after chemotherapy.
PLoS ONE
PUBLISHED: 01-01-2013
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Hepatitis B virus (HBV) is hepatotropic and lymphotropic. HBV-infected individuals have an increased risk of developing malignant lymphoma, and the HBV infection rate in lymphoma patients is significantly higher than that in the general population. However, the exact mechanism and correlation between HBV infection and lymphoma onset and progression currently remain unclear. We retrospectively analyzed clinical data from non-Hodgkins lymphoma (NHL) patients with different HBV infection statuses. The results showed that the HBV infection rate was significantly higher in patients with B-cell type and late stage of NHL. The chemotherapy efficacy for NHL patients with chronic active HBV infection was significantly lower than that for the patients with chronic inactive HBV infection, the patients with HBV carriers and the patients without HBV infection. In addition, the NHL chemotherapy activated HBV replication and caused significant liver dysfunction, which could further reduce the chemotherapy efficacy. Through Kaplan-Meier survival curve and log-rank analysis, we found that the HBV infection status in NHL patients was significantly correlated with the patients progression-free survival (PFS) and overall survival (OS). Compared with the patients without HBV infection (PFS: 95% CI 47.915 to 55.640; OS: 95% CI 81.324 to 86.858), the PFS and OS of the patients with chronic active HBV infection were significantly shorter (PFS: 95% CI 9.424 to 42.589, P < 0.001; OS: 95% CI 42.840 to 82.259, P = 0.006). The study demonstrated that the sustained HBV replication in patients with chronic active HBV infection could be a key factor that influences the prognosis of NHL patients after chemotherapy, and thus may provide information for designing rational clinical treatments for NHL patients with different HBV infection statuses and improve the treatment efficacy and prognosis.
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Neurological, functional, and biomechanical characteristics after high-velocity behind armor blunt trauma of the spine.
J Trauma
PUBLISHED: 12-21-2011
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Behind armor blunt trauma (BABT) describes a nonpenetrating injury to the organs of an individual wearing body armor. The aim of this study was to investigate the neurologic and functional changes that occur in the central nervous system after high-velocity BABT of the spine as well as its biomechanical characteristics.
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Expression of the androgen receptor and its correlation with molecular subtypes in 980 chinese breast cancer patients.
Breast Cancer (Auckl)
PUBLISHED: 12-06-2011
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Recent studies have shown that androgen displays an inhibitory effect on breast cancer cell lines that express androgen receptor (AR) but not estrogen receptor (ER) and progesterone receptor (PR). We have previously reported that approximately 1/3 of ER negative high grade invasive ductal carcinomas express AR. Thus, AR can serve as a potential therapeutic target for this group of patients.
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Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in China: a 10-year retrospective follow-up analysis of 437 cases from Shanghai Lymphoma Research Group.
Ann. Hematol.
PUBLISHED: 11-14-2011
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The purpose of the study is to evaluate the 10 years follow-up of the efficacy in Chinese patients receiving cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) regimen as the initial treatment for diffuse large B cell lymphoma (DLBCL). We have retrospectively analyzed 437 patients with DLBCL who were newly diagnosed and received CHOP or R-CHOP regimen in six university hospitals and closely followed up after the completion of treatment. For all patients, there were significant differences between R-CHOP and CHOP for overall survival (OS) (median follow-up 86 months, 84.1% vs 70.2%, p = 0.018) and progression-free survival (PFS) (81.5% vs 66.7%, p = 0.015), while elder patients (>60 years old) received higher OS (median follow-up 66 months, 80.7% vs 53.0%, p = 0.011). But for younger patients (?60 years old), the treatments with rituximab did not demonstrate a significant effect on OS (85.5% vs 79.4%, p = 0.428). In the R-CHOP group, International Prognostic Index (IPI) distinguished three risk groups instead of four risk groups. But in the CHOP group, IPI still distinguished four risk groups. Furthermore, for 212 of 437 patients diagnosed with extranodal involvement DLBCL, R-CHOP regimen provided a longer OS than CHOP regimen did (OS, 89.9% vs 71.7%, p = 0.014). Moreover, patients with extranodal lymphoma had a significant longer survival in rituximab era (OS, 89.9% vs 79.2% for extranodal and nodal, respectively; p = 0.048). The results of this large-scale study suggested that R-CHOP provided a greater survival benefit in the initial treatment of DLBCL. As for the patients with extranodal lymphoma, R-CHOP was also a good choice as first-line treatment. Extranodal disease seems to be an independent good prognostic factor in rituximab era.
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Risk factors for invasive mold infections following allogeneic hematopoietic stem cell transplantation: a single center study of 190 recipients.
Scand. J. Infect. Dis.
PUBLISHED: 11-08-2011
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Invasive mold infection (IMI) is a major cause of infection-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
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Macular sensitivity and fixation patterns in normal eyes and eyes with uveitis with and without macular edema.
J Ophthalmic Inflamm Infect
PUBLISHED: 09-19-2011
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This study aims to investigate the relationship between macular sensitivity and thickness in eyes with uveitic macular edema (UME).
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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.