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.
A plausible mechanism, based upon SHORT-ROOT movement, for regulating the number of cortex cell layers in roots.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-28-2014
Show Abstract
Hide Abstract
Formation of specialized cells and tissues at defined times and in specific positions is essential for the development of multicellular organisms. Often this developmental precision is achieved through intercellular signaling networks, which establish patterns of differential gene expression and ultimately the specification of distinct cell fates. Here we address the question of how the SHORT-ROOT (SHR) proteins from Arabidopsis thaliana (AtSHR), Brachypodium distachyon (BdSHR), and Oryza sativa (OsSHR1 and OsSHR2) function in patterning the root ground tissue. We find that all of the SHR proteins function as mobile signals in A. thaliana and all of the SHR homologs physically interact with the AtSHR binding protein, SCARECOW (SCR). Unlike AtSHR, movement of the SHR homologs was not limited to the endodermis. Instead, the SHR proteins moved multiple cell layers and determined the number of cortex, not endodermal, cell layers formed in the root. Our results in A. thaliana are consistent with a mechanism by which the regulated movement of the SHR transcription factor determines the number of cortex cell layers produced in the roots of B. distachyon and O. sativa. These data also provide a new model for ground tissue patterning in A. thaliana in which the ability to form a functional endodermis is spatially limited independently of SHR.
Related JoVE Video
Feasibility of Low-Throughput Next Generation Sequencing for Germline DNA Screening.
Clin. Chem.
PUBLISHED: 10-24-2014
Show Abstract
Hide Abstract
Next generation sequencing (NGS) promises many benefits for clinical diagnostics. However, current barriers to its adoption include suboptimal amenability for low clinical throughputs and uncertainty over data accuracy and analytical procedures. We assessed the feasibility and performance of low-throughput NGS for detecting germline mutations for Lynch syndrome (LS).
Related JoVE Video
The induction of the p53 tumor suppressor protein bridges the apoptotic and autophagic signaling pathways to regulate cell death in prostate cancer cells.
Oncotarget
PUBLISHED: 10-10-2014
Show Abstract
Hide Abstract
The p53 tumor suppressor protein plays a crucial role in influencing cell fate decisions in response to cellular stress. As p53 elicits cell cycle arrest, senescence or apoptosis, the integrity of the p53 pathway is considered a key determinant of anti-tumor responses. p53 can also promote autophagy, however the role of p53-dependent autophagy in chemosensitivity is poorly understood. VMY-1-103 (VMY), a dansylated analog of purvalanol B, displays rapid and potent anti-tumor activities, however the pathways by which VMY works are not fully defined. Using established prostate cancer cell lines and novel conditionally reprogrammed cells (CRCs) derived from prostate cancer patients; we have defined the mechanisms of VMY-induced prostate cancer cell death. Herein, we show that the cytotoxic effects of VMY required a p53-dependent induction of autophagy, and that inhibition of autophagy abrogated VMY-induced cell death. Cancer cell lines harboring p53 missense mutations evaded VMY toxicity and treatment with a small molecule compound that restores p53 activity re-established VMY-induced cell death. The elucidation of the molecular mechanisms governing VMY-dependent cell death in cell lines, and importantly in CRCs, provides the rationale for clinical studies of VMY, alone or in combination with p53 reactivating compounds, in human prostate cancer.
Related JoVE Video
Intercellular protein movement: deciphering the language of development.
Annu. Rev. Cell Dev. Biol.
PUBLISHED: 10-08-2014
Show Abstract
Hide Abstract
Development in multicellular organisms requires the coordinated production of a large number of specialized cell types through sophisticated signaling mechanisms. Non-cell-autonomous signals are one of the key mechanisms by which organisms coordinate development. In plants, intercellular movement of transcription factors and other mobile signals, such as hormones and peptides, is essential for normal development. Through a combination of different approaches, a large number of non-cell-autonomous signals that control plant development have been identified. We review some of the transcriptional regulators that traffic between cells, as well as how changes in symplasmic continuity affect and are affected by development. We also review current models for how mobile signals move via plasmodesmata and how movement is inhibited. Finally, we consider challenges in and new tools for studying protein movement.
Related JoVE Video
Targeting GPR30 with G-1: a new therapeutic target for castration-resistant prostate cancer.
Endocr. Relat. Cancer
PUBLISHED: 10-06-2014
Show Abstract
Hide Abstract
Castration-resistant prostate cancer (CRPC) is an advanced-stage prostate cancer (PC) associated with high mortality. We reported that G-1, a selective agonist of G protein-coupled receptor 30 (GPR30), inhibited PC cell growth by inducing G2 cell cycle arrest and arrested PC-3 xenograft growth. However, the therapeutic actions of G-1 and their relationships with androgen in vivo are unclear. Using the LNCaP xenograft to model PC growth during the androgen-sensitive (AS) versus the castration-resistant (CR) phase, we found that G-1 inhibited growth of CR but not AS tumors with no observable toxicity to the host. Substantial necrosis (approximately 65%) accompanied by marked intratumoral infiltration of neutrophils was observed only in CR tumors. Global transcriptome profiling of human genes identified 99 differentially expressed genes with 'interplay between innate and adaptive immune responses' as the top pathway. Quantitative PCR confirmed upregulation of neutrophil-related chemokines and inflammation-mediated cytokines only in the G-1-treated CR tumors. Expression of murine neutrophil-related cytokines also was elevated in these tumors. GPR30 (GPER1) expression was significantly higher in CR tumors than in AS tumors. In cell-based experiments, androgen repressed GPR30 expression, a response reversible by anti-androgen or siRNA-induced androgen receptor silencing. Finally, in clinical specimens, 80% of CRPC metastases (n=123) expressed a high level of GPR30, whereas only 54% of the primary PCs (n=232) showed high GPR30 expression. Together, these results provide the first evidence, to our knowledge, that GPR30 is an androgen-repressed target and G-1 mediates the anti-tumor effect via neutrophil-infiltration-associated necrosis in CRPC. Additional studies are warranted to firmly establish GPR30 as a therapeutic target in CRPC.
Related JoVE Video
Interaction of platelet-derived autotaxin with tumor integrin ?V?3 controls metastasis of breast cancer cells to bone.
Blood
PUBLISHED: 10-02-2014
Show Abstract
Hide Abstract
Autotaxin (ATX), through its lysophospholipase D activity controls physiological levels of lysophosphatidic acid (LPA) in blood. ATX is overexpressed in multiple types of cancers, and together with LPA generated during platelet activation promotes skeletal metastasis of breast cancer. However, the pathophysiological sequelae of regulated interactions between circulating LPA, ATX, and platelets remain undefined in cancer. In this study, we show that ATX is stored in ?-granules of resting human platelets and released upon tumor cell-induced platelet aggregation, leading to the production of LPA. Our in vitro and in vivo experiments using human breast cancer cells that do not express ATX (MDA-MB-231 and MDA-B02) demonstrate that nontumoral ATX controls the early stage of bone colonization by tumor cells. Moreover, expression of a dominant negative integrin ?v?3-?744 or treatment with the anti-human ?v?3 monoclonal antibody LM609, completely abolished binding of ATX to tumor cells, demonstrating the requirement of a fully active integrin ?v?3 in this process. The present results establish a new mechanism for platelet contribution to LPA-dependent metastasis of breast cancer cells, and demonstrate the therapeutic potential of disrupting the binding of nontumor-derived ATX with the tumor cells for the prevention of metastasis.
Related JoVE Video
Significant genotype difference in the CYP2E1 PstI polymorphism of Indigenous groups in Sabah, Malaysia with Asian and non-Asian populations.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
Show Abstract
Hide Abstract
CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations.
Related JoVE Video
Autotaxin, LPA Receptors (1 and 5) Exert Disparate Functions in Tumor Cells Versus the Host Tissue Microenvironment in Melanoma Invasion and Metastasis.
Mol. Cancer Res.
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
Autotaxin (ENPP2/ATX) and lysophosphatidic acid (LPA) receptors represent two key players in regulating cancer progression. The present study sought to understand the mechanistic role of LPA G protein-coupled receptors (GPCR), not only in the tumor cells but also in stromal cells of the tumor microenvironment. B16F10 melanoma cells predominantly express LPA5 and LPA2 receptors but lack LPA1. LPA dose-dependently inhibited invasion of cells across a Matrigel layer. RNAi-mediated knockdown of LPA5 relieved the inhibitory effect of LPA on invasion without affecting basal invasion. This suggests that LPA5 exerts an anti-invasive action in melanoma cells in response to LPA. In addition, both siRNA-mediated knockdown and pharmacological inhibition of LPA2 reduced the basal rate invasion. Unexpectedly, when probing the role of this GPCR in host tissues, it was found that the incidence of melanoma-derived lung metastasis was greatly reduced in LPA5 knockout (KO) mice compared to wild-type (WT) mice. LPA1- but not LPA2-KO mice also showed diminished melanoma-derived lung metastasis, suggesting that host LPA1 and LPA5 receptors play critical roles in the seeding of metastasis. The decrease in tumor cell residence in the lungs of LPA1- and LPA5-KO animals was apparent 24 h after injection. However, KO of LPA1, LPA2 or LPA5 did not affect the subcutaneous growth of melanoma tumors. Implications: These findings suggest that tumor- and stromal-LPA receptors, in particular LPA1 and LPA5, play different roles in invasion and the seeding of metastasis.
Related JoVE Video
Prescription of psychotropic drugs in patients with chronic renal failure on hemodialysis.
Ren Fail
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
Abstract Objective: Patients on hemodialysis commonly have comorbid depression and require treatment with psychotropic drugs. This study aimed to investigate the prevalence of the use of psychotropic drugs among patients on hemodialysis and to elucidate the factors associated with use of each class of psychotropic medication.
Related JoVE Video
Determinants of maternal satisfaction with diagnosis disclosure of autism.
J. Formos. Med. Assoc.
PUBLISHED: 07-20-2014
Show Abstract
Hide Abstract
Diagnosis disclosure is an important clinical issue in developmental disabilities, which may influence parents' ability to cope with their child's conditions. This paper presents the content and patterns of diagnosis-informed counseling for mothers of children with autism and investigates the determinants for maternal satisfaction with this counseling, in order to improve clinical practice.
Related JoVE Video
Protein-Bound Uremic Toxins Induce Tissue Remodeling by Targeting the EGF Receptor.
J. Am. Soc. Nephrol.
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
Indoxyl sulfate and p-cresol sulfate have been suggested to induce kidney tissue remodeling. This study aimed to clarify the molecular mechanisms underlying this tissue remodeling using cultured human proximal renal tubular cells and half-nephrectomized mice treated with indoxyl sulfate or p-cresol sulfate as study models. Molecular docking results suggested that indoxyl sulfate and p-cresol sulfate dock on a putative interdomain pocket of the extracellular EGF receptor. In vitro spectrophotometric analysis revealed that the presence of a synthetic EGF receptor peptide significantly decreased the spectrophotometric absorption of indoxyl sulfate and p-cresol sulfate. In cultured cells, indoxyl sulfate and p-cresol sulfate activated the EGF receptor and downstream signaling by enhancing receptor dimerization, and increased expression of matrix metalloproteinases 2 and 9 in an EGF receptor-dependent manner. Treatment of mice with indoxyl sulfate or p-cresol sulfate significantly activated the renal EGF receptor and increased the tubulointerstitial expression of matrix metalloproteinases 2 and 9. In conclusion, indoxyl sulfate and p-cresol sulfate may induce kidney tissue remodeling through direct binding and activation of the renal EGF receptor.
Related JoVE Video
Erlotinib Salvage Therapy in Pulmonary Adenocarcinoma Patients With Disease Progression After Previous EGFR-TKI Treatment.
Am. J. Clin. Oncol.
PUBLISHED: 06-18-2014
Show Abstract
Hide Abstract
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with promising efficacy in treating pulmonary adenocarcinoma. Treatment choices are few when patients with pulmonary adenocarcinoma have failed both EGFR-TKI and chemotherapy. The purpose of this study was to demonstrate the efficacy of erlotinib as salvage treatment for these nonresponsive patients.
Related JoVE Video
Role of stereotactic body radiotherapy for symptom control in head and neck cancer patients.
Support Care Cancer
PUBLISHED: 06-03-2014
Show Abstract
Hide Abstract
Our aim was to determine the efficacy and quality of life outcomes of head and neck (HN) stereotactic body radiotherapy (SBRT) in a palliative population with significant proportions of de novo HN tumors not amenable to surgery or protracted course of curative radiotherapy (RT).
Related JoVE Video
Budesonide/formoterol maintenance and reliever therapy in asthma control: Acute, dose-related effects and real-life effectiveness.
Respirology
PUBLISHED: 05-23-2014
Show Abstract
Hide Abstract
The efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real-life effectiveness are seldom reported.
Related JoVE Video
An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells.
Analyst
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
The detection and characterization of rare circulating tumor cells (CTCs) from the blood of cancer patients can potentially provide critical insights into tumor biology and hold great promise for cancer management. The ability to collect a large number of viable CTCs for various downstream assays such as quantitative measurements of specific biomarkers or targeted somatic mutation analysis is increasingly important in medical oncology. Here, we present a simple yet reliable microfluidic device for the ultra-high-throughput, label-free, size-based isolation of CTCs from clinically relevant blood volumes. The fast processing time of the technique (7.5 mL blood in less than 10 min) and the ability to collect more CTCs from larger blood volumes lends itself to a broad range of potential genomic and transcriptomic applications. A critical advantage of this protocol is the ability to return all fractions of blood (i.e., plasma (centrifugation), CTCs and white blood cells (WBCs) (size-based sorting)) that can be utilized for diverse biomarker studies or time-sensitive molecular assays such as RT-PCR. The clinical use of this biochip was demonstrated by detecting CTCs from 100% (10/10) of blood samples collected from patients with advanced-stage metastatic breast and lung cancers. The CTC recovery rate ranged from 20 to 135 CTCs mL(-1) and obtained under high purity (of 1 CTC out of every 30-100 WBCs which gives ?4 log depletion of WBCs). They were identified with immunofluorescence assays (pan-cytokeratin+/CD45-) and molecular probes such as HER2/neu.
Related JoVE Video
Renal cell carcinoma in tuberous sclerosis complex.
Am. J. Surg. Pathol.
PUBLISHED: 05-17-2014
Show Abstract
Hide Abstract
Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term "TSC-associated papillary RCC (PRCC)." The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC.
Related JoVE Video
Soft Tissue Infection Caused by Rapid Growing Mycobacterium following Medical Procedures: Two Case Reports and Literature Review.
Ann Dermatol
PUBLISHED: 04-30-2014
Show Abstract
Hide Abstract
Non-tubecrulosis mycobacterium infections were increasingly reported either pulmonary or extrapulmonary in the past decades. In Taiwan, we noticed several reports about the soft tissue infections caused by rapid growing mycobacterium such as Mycobacterium abscessus, Mycobacterium chelonae, on newspaper, magazines, or the multimedia. Most of them occurred after a plastic surgery, and medical or non-medical procedures. Here, we reported two cases of these infections following medical procedures. We also discussed common features and the clinical course of the disease, the characteristics of the infected site, and the treatment strategy. The literatures were also reviewed, and the necessity of the treatment guidelines was discussed.
Related JoVE Video
Hyperbaric oxygen therapy as an effective adjunctive treatment for chronic Lyme disease.
J Chin Med Assoc
PUBLISHED: 04-13-2014
Show Abstract
Hide Abstract
Lyme disease is the most commonly reported vector-borne illness in the United States, but it is relatively rare in Taiwan. Lyme disease can be treated with antibiotic agents, but approximately 20% of these patients experience persistent or intermittent subjective symptoms, so-called chronic Lyme disease (CLD). The mechanisms of CLD remain unclear and the symptoms related to CLD are difficult to manage. Hyperbaric oxygen therapy (HBOT) was applied in CLD therapy in the 1990s. However, reported information regarding the effectiveness of HBOT for CLD is still limited. Here, we present a patient with CLD who was successfully treated with HBOT.
Related JoVE Video
Number of liver metastatic nodules affects treatment options for pulmonary adenocarcinoma patients with liver metastases.
Lung Cancer
PUBLISHED: 04-11-2014
Show Abstract
Hide Abstract
In patients with non-small cell lung cancer (NSCLC), the development of liver metastasis (LM) is a poor prognostic factor. Whether systemic treatment combined with local treatment for LM has benefit for NSCLC patients with LM is unknown.
Related JoVE Video
Latent TB infection in newly diagnosed lung cancer patients - A multicenter prospective observational study.
Lung Cancer
PUBLISHED: 04-11-2014
Show Abstract
Hide Abstract
Lung cancer and tuberculosis (TB) share common risk factors and are associated with high morbidity and mortality. Coexistence of lung cancer and TB were reported in previous studies, with uncertain pathogenesis. The association between lung cancer and latent TB infection (LTBI) remains to be explored.
Related JoVE Video
Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a randomized crossover study.
Nephrol. Dial. Transplant.
PUBLISHED: 04-08-2014
Show Abstract
Hide Abstract
Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients.
Related JoVE Video
Circulating free mitochondrial DNA concentration and its association with erlotinib treatment in patients with adenocarcinoma of the lung.
Oncol Lett
PUBLISHED: 03-14-2014
Show Abstract
Hide Abstract
Changes in circulating free DNA concentrations have been correlated with chemotherapeutic effects in solid tumors. The present study was designed to determine and compare the changes in circulating free mitochondrial DNA (mtDNA) concentrations prior to and following erlotinib treatment, as well as the potential prognostic value of plasma mtDNA. Patients with adenocarcinoma of the lung who were to receive erlotinib treatment were enrolled in the present study once informed consent had been obtained. Patient plasma samples were collected immediately prior to starting erlotinib treatment, on days 15 and 29 following the initiation of erlotinib treatment and also when the patient's disease had progressed. The most common erlotinib treatment response was a partial response (PR), achieved in 26 (49.1%) of the 53 enrolled patients, followed by stable disease (SD) in 13 patients (24.5%) and progressive disease (PD) in 14 patients (26.4%). Plasma mtDNA concentrations were significantly decreased on day 15 compared with day 0 in the patients with PD (P=0.028) or in those patients without a response to erlotinib treatment (SD and PD; P=0.007). Plasma mtDNA concentrations were similar or elevated on day 15 compared with day 0 in the patients with a PR (P=0.808). The concentration of plasma mtDNA did not correlate with progression-free survival (PFS). Tumor epidermal growth factor receptor (EGFR) mutation status (activating mutations in 16 patients and wild-type in 14 patients) did not correlate with the concentration of plasma mtDNA (P=0.951). Plasma mtDNA levels did not correlate with the PFS of the patients when they received erlotinib treatment. The plasma mtDNA levels were decreased on day 15 in those patients who had disease progression following erlotinib treatment. These results demonstrate that plasma mtDNA is of weak clinical utility as a screening, diagnostic or prognostic tool in lung cancer patients.
Related JoVE Video
Suppression of prolactin signaling by pyrrolidine dithiocarbamate is alleviated by N-acetylcysteine in mammary epithelial cells.
Eur. J. Pharmacol.
PUBLISHED: 02-28-2014
Show Abstract
Hide Abstract
Prolactin is the key hormone to stimulate milk synthesis in mammary epithelial cells. It signals through the Jak2-Stat5 pathway to induce the expression of ?-casein, a milk protein which is often used as a marker for mammary differentiation. Here we examined the effect of pyrrolidine dithiocarbamate (PDTC) on prolactin signaling. Our results show that PDTC downregulates prolactin receptor levels, and inhibits prolactin-induced Stat5 tyrosine phosphorylation and ?-casein expression. This is not due to its inhibitory action on NF-?B since application of another NF-?B inhibitor, BAY 11-7082, and overexpression of I-?B? super-repressor do not lead to the same results. Instead, the pro-oxidant activity of PDTC is involved as inclusion of the antioxidant N-acetylcysteine restores prolactin signaling. PDTC triggers great extents of activation of ERK and JNK in mammary epithelial cells. These do not cause suppression of prolactin signaling but confer serine phosphorylation of insulin receptor substrate-1, thereby perturbing insulin signal propagation. As insulin facilitates optimal ?-casein expression, blocking insulin signaling by PDTC might pose additional impediment to ?-casein expression. Our results thus imply that lactation will be compromised when the cellular redox balance is dysregulated, such as during mastitis.
Related JoVE Video
Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC).
Fam. Cancer
PUBLISHED: 02-15-2014
Show Abstract
Hide Abstract
Hereditary leiomyomatosis-renal cell cancer (HLRCC) is an autosomal dominant disorder characterised by cutaneous leiomyomas, symptomatic uterine leiomyomas and aggressive type II papillary renal cell carcinoma. It is caused by heterozygous mutations in the fumarate hydratase (FH) gene on chromosome 1q43. We present evidence of genetic anticipation in HLRCC syndrome. A comprehensive literature review was performed to determine the potential for genetic anticipation in HLRCC syndrome. The normal random effects model was used to evaluate for genetic anticipation to ensure reduction in bias. A total of 11 FH kindreds with available multi-generational data were identified for analysis. The mean difference in age at diagnosis of RCC between the first and second generation was -18.6 years (95 % CI -26.6 to -10.6, p < 0.001). The mean difference in age at diagnosis of RCC between the first and third generation was -36.2 years (95 % CI -47.0 to -25.4, p < 0.001). No evidence of anticipation for uterine leiomyomas was observed (p = 0.349). We report preliminary evidence of genetic anticipation of RCC in HLRCC syndrome. Additional clinical validation is important to confirm this observation, which may have practical implications on counseling and timing of surveillance initiation. Exploration of the underlying mechanisms of anticipation in HLRCC would be of considerable biological interest.
Related JoVE Video
Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.
Urology
PUBLISHED: 02-03-2014
Show Abstract
Hide Abstract
This study aimed evaluate the safety and feasibility of endoscopic potassium titanyl phosphate (KTP) laser application in the management of patients with radiation-induced hemorrhagic cystitis (RHC).
Related JoVE Video
The genomic landscape of nasopharyngeal carcinoma.
Nat. Genet.
PUBLISHED: 01-27-2014
Show Abstract
Hide Abstract
Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.
Related JoVE Video
Nocturnal Stem Cell Mobilization in Patients with Obstructive Sleep Apnea: A Pilot Study.
Eur. J. Clin. Invest.
PUBLISHED: 01-26-2014
Show Abstract
Hide Abstract
Patients with obstructive sleep apnea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA.
Related JoVE Video
Comparing Effectiveness of High-Fidelity Human Patient Simulation vs Case-Based Learning in Pharmacy Education.
Am J Pharm Educ
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
Objective. To determine whether human patient simulation (HPS) is superior to case-based learning (CBL) in teaching diabetic ketoacidosis (DKA) and thyroid storm (TS) to pharmacy students. Design. In this cross-over, open-label, single center, randomized control trial, final-year undergraduate pharmacy students enrolled in an applied therapeutics course were randomized to HPS or CBL groups. Pretest, posttest, knowledge retention tests, and satisfaction survey were administered to students. Assessment. One hundred seventy-four students participated in this study. The effect sizes attributable to HPS were larger than CBL in both cases. HPS groups performed significantly better in posttest and knowledge retention test compared to CBL groups pertaining to TS case (p<0.05). Students expressed high levels of satisfaction with HPS sessions. Conclusion. HPS was superior to CBL in teaching DKA and TS to final-year undergraduate pharmacy students.
Related JoVE Video
MicroRNA-30c serves as an independent biochemical recurrence predictor and potential tumor suppressor for prostate cancer.
Mol. Biol. Rep.
PUBLISHED: 01-11-2014
Show Abstract
Hide Abstract
MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P<0.05). In addition, the downregulation of miR-30c in PCa tissues was significantly associated with higher Gleason score (P=0.009), advanced pathological stage (P=0.016) and biochemical recurrence (P=0.034). Moreover, Kaplan-Meier survival analysis showed that the reduced expression of miR-30c was correlated with shorter biochemical recurrence-free survival (P=0.023). The multivariate analysis also identified miR-30c as an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation, migration and invasion of PCa cells in vitro. Our data indicated the involvement of miR-30c in PCa progression and suggested its potential role as an independent predictor of biochemical recurrence in PCa. On cellular level, miR-30c may function as a tumor suppressor for PCa cells by inhibiting tumor cell proliferation, migration and invasion.
Related JoVE Video
MicroRNA-224 inhibits progression of human prostate cancer by downregulating TRIB1.
Int. J. Cancer
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
Our previous microarray data showed that microRNA-224 (miR-224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR-224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR-224. Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR-224 in PCa tissues was negatively correlated with that of TRIB1. miR-224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR-224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence-free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR-224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis.
Related JoVE Video
Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease.
BMC Nephrol
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
Chronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited.
Related JoVE Video
RsaI but not DraI polymorphism in CYP2E1 gene increases the risk of gastrointestinal cancer in Malaysians: a case-control study.
BMJ Open
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
Our study aimed to investigate the association of CYP2E1 C-1019T RsaI and T7678A DraI polymorphisms and factors such as age, gender and ethnicity to the risk of gastrointestinal cancer (GIC) in Malaysians.
Related JoVE Video
Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells.
J. Exp. Med.
PUBLISHED: 01-06-2014
Show Abstract
Hide Abstract
Lymphangioleiomyomatosis (LAM) is a progressive neoplastic disorder that leads to lung destruction and respiratory failure primarily in women. LAM is typically caused by tuberous sclerosis complex 2 (TSC2) mutations resulting in mTORC1 activation in proliferative smooth muscle-like cells in the lung. The female predominance of LAM suggests that estradiol contributes to disease development. Metabolomic profiling identified an estradiol-enhanced prostaglandin biosynthesis signature in Tsc2-deficient (TSC(-)) cells, both in vitro and in vivo. Estradiol increased the expression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin biosynthesis, which was also increased at baseline in TSC-deficient cells and was not affected by rapamycin treatment. However, both Torin 1 treatment and Rictor knockdown led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin production was also increased in TSC-deficient cells. In preclinical models, both Celecoxib and aspirin reduced tumor development. LAM patients had significantly higher serum prostaglandin levels than healthy women. 15-epi-lipoxin-A4 was identified in exhaled breath condensate from LAM subjects and was increased by aspirin treatment, indicative of functional COX-2 expression in the LAM airway. In vitro, 15-epi-lipoxin-A4 reduced the proliferation of LAM patient-derived cells in a dose-dependent manner. Targeting COX-2 and prostaglandin pathways may have therapeutic value in LAM and TSC-related diseases, and possibly in other conditions associated with mTOR hyperactivation.
Related JoVE Video
Multidisciplinary predialysis education reduced the inpatient and total medical costs of the first 6 months of dialysis in incident hemodialysis patients.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The multidisciplinary pre-dialysis education (MPE) retards renal progression, reduce incidence of dialysis and mortality of CKD patients. However, the financial benefit of this intervention on patients starting hemodialysis has not yet been evaluated in prospective and randomized trial.
Related JoVE Video
Patient experience and use of probiotics in community-based health care settings.
Patient Prefer Adherence
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
To investigate patient experience with probiotics and factors that influence probiotic use among adult patients.
Related JoVE Video
Gender disparities in latent tuberculosis infection in high-risk individuals: a cross-sectional study.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Male predominance in active tuberculosis (TB) is widely-reported globally. Gender inequalities in socio-cultural status are frequently regarded as contributing factors for disparities in sex in active TB. The disparities of sex in the prevalence of latent TB infection (LTBI) are less frequently investigated and deserve clarification. In this cross-sectional study conducted in a TB endemic area, we enrolled patients at high-risk for LTBI and progression from LTBI to active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In-Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical predictors for LTBI were investigated. Associations among age, smoking status, and sex disparities in LTBI were also analyzed. A total of 1018 high-risk individuals with definite QFT-GIT results were included for analysis, including 534 males and 484 females. The proportion of LTBI was significantly higher in males than in females (32.6% vs. 25.2%, p?=?0.010). Differences in the proportion of LTBI between sexes were most prominent in older patients (age ?55 years). In multivariate analysis, independent clinical factors associated with LTBI were age (p?=?0.014), smoking (p?=?0.048), and fibro-calcified lesions on chest radiogram (p?=?0.009). Male sex was not an independent factor for LTBI (p?=?0.88). When stratifying patients according to the smoking status, the proportion of LTBI remained comparable between sexes among smokers and non-smokers. In conclusion, although the proportion of LTBI is higher in men, there is no significant disparity in terms of sex in LTBI among high-risk individuals after adjusting for age, smoking status, and other clinical factors.
Related JoVE Video
Validity and clinical utilization of the Chinese version of the Gotland Male Depression Scale at a men's health polyclinic.
Neuropsychiatr Dis Treat
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Symptoms of depression in males, such as aggression and irritability, are different from those in females. However, there are no adequate scales for detecting possible diagnoses in the Chinese population. The aim of this study was to assess whether the Chinese version of the Gotland Male Depression Scale (CV-GMDS) could identify male depression as effectively as the English version.
Related JoVE Video
The association of uremic toxins and inflammation in hemodialysis patients.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear.
Related JoVE Video
Depression, 5HTTLPR and BDNF Val66Met polymorphisms, and plasma BDNF levels in hemodialysis patients with chronic renal failure.
Neuropsychiatr Dis Treat
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Depression is the most prevalent comorbid psychiatric disease among hemodialysis patients with end-stage renal disease. This cross-sectional study investigated whether depression in hemodialysis patients is associated with the polymorphism of the 5' flanking transcriptional region (5-HTTLPR) of the serotonin transporter gene, the valine (Val)-to-methionine (Met) substitution at codon 66 (Val66Met) polymorphism of the brain-derived neurotrophic factor (BDNF) gene, or plasma BDNF levels.
Related JoVE Video
Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation.
Related JoVE Video
Serum estradiol levels predict survival and acute kidney injury in patients with septic shock--a prospective study.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Sex hormones have diverse immunomodulatory effects that may be involved in the pathogenesis of sepsis. However, the roles of serum sex hormones in predicting outcomes and the severity of organ dysfunction, especially acute kidney injury (AKI), in septic shock patients remains controversial. We prospectively enrolled 107 clinically diagnosed pneumonia-related septic shock patients and serum sex hormone levels were measured on the day of shock onset. The aim of the present study was to investigate the predictive values of serum sex hormones levels for 28-day mortality and organs dysfunction, especially AKI. Compared with survivors, serum levels of progesterone (p<0.001) and estradiol (p<0.001) were significantly elevated in non-survivors. In multivariate Cox regression analysis, serum level of estradiol >40 pg/mL (p?=?0.047) and APACHE II score ?25 (p?=?<0.001) were found to be independent predictors of day 28 mortality. Inclusion of estradiol levels further enhanced the ability of APACHE II scores to predict survival in patients with high mortality risk. A serum level of estradiol >40 pg/mL was also an independent predictor of concomitant AKI (p?=?0.002) and correlated well with severity of renal dysfunction using RIFLE classification. Elevated serum estradiol levels also predicted the development of new AKI within 28 days of shock onset (p?=?0.013). In conclusion, serum estradiol levels appear to have value in predicting 28-day mortality in septic shock patients. Increased serum estradiol levels are associated with higher severity of concomitant AKI and predict development of new AKI.
Related JoVE Video
Chronic kidney disease stage is a modulator on the association between high-sensitivity C-reactive protein and coronary vasospastic angina.
ScientificWorldJournal
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1-3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.
Related JoVE Video
Models of care and NCCN guideline adherence in very-low-risk prostate cancer.
J Natl Compr Canc Netw
PUBLISHED: 11-15-2013
Show Abstract
Hide Abstract
NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.
Related JoVE Video
Architectural heterogeneity and cribriform pattern predict adverse clinical outcome for Gleason grade 4 prostatic adenocarcinoma.
Am. J. Surg. Pathol.
PUBLISHED: 10-23-2013
Show Abstract
Hide Abstract
Gleason grade 4 defines a group of prostatic adenocarcinomas with a variety of architectural patterns, including poorly formed glands, fused glands, and cribriform pattern. To address the relative contribution to clinical prognosis by these distinct patterns, the histology of 241 consecutive radical prostatectomy specimens with the highest Gleason grade of 4 was reviewed. The presence of poorly formed glands, fused glands, and cribriform pattern was recorded for each case, and the types of architectural patterns present were associated with patient outcome. In this population, prostatic adenocarcinomas demonstrated architectural heterogeneity, with 17% of cases exhibiting a single Gleason grade 4 pattern, and 41% of cases exhibiting all 3 morphologic patterns. Patients exhibiting all 3 architectural patterns had lower rates of biochemical disease-free survival (66% vs. 76% at 5 y; log rank P=0.006). Twenty-two of 165 patients (13.3%) with cribriform pattern adenocarcinoma developed metastasis, whereas 2 of 76 patients (2.6%) without cribriform pattern developed metastasis at a median postoperative follow-up of 10.0 years. The presence of a cribriform pattern was an independent predictor for biochemical recurrence (hazard ratio 2.41; 95% confidence interval, 1.34-4.32; P=0.003) as well as metastasis after radical prostatectomy (hazard ratio 5.62; 95% confidence interval, 1.29-24.5; P=0.02). These results suggest that the morphologic subclassification of distinct Gleason grade 4 architectural patterns provides prognostic information beyond the current Gleason classification system.
Related JoVE Video
NCOA5 Haploinsufficiency Results in Glucose Intolerance and Subsequent Hepatocellular Carcinoma.
Cancer Cell
PUBLISHED: 08-26-2013
Show Abstract
Hide Abstract
Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers. Blockading IL-6 overexpression averts glucose intolerance and partially deters HCC development. Moreover, reduced NCOA5 expression is associated with a fraction of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a haploinsufficient tumor suppressor and that NCOA5 deficiency increases susceptibility to both glucose intolerance and HCC, partially by increasing IL-6 expression. Thus, our findings open additional avenues for developing therapeutic approaches to combat these diseases.
Related JoVE Video
The "Aging Males Symptoms" (AMS) Scale assesses depression and anxiety.
Aging Male
PUBLISHED: 07-04-2013
Show Abstract
Hide Abstract
Emotional distress may be associated with severe aging symptoms. This study aimed to investigate aging symptoms in male psychiatric outpatients and their relationship with anxiety and depression.
Related JoVE Video
Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase
Lancet Oncol.
PUBLISHED: 07-01-2013
Show Abstract
Hide Abstract
We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer.
Related JoVE Video
Epidemiological Features of Kawasaki Disease in Taiwan, 1976-2007: Results of Five Nationwide Questionnaire Hospital Surveys.
Pediatr Neonatol
PUBLISHED: 06-21-2013
Show Abstract
Hide Abstract
Kawasaki disease (KD) affects mainly children younger than 5 years of age, leading to coronary artery lesions, and even to life-threatening myocardial infarction. In Taiwan, KD was encountered for the first time in 1976; then, it continued to occur in increasing numbers.
Related JoVE Video
Mitigation of radiation injury by selective stimulation of the LPA(2) receptor.
Biochim. Biophys. Acta
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
Due to its antiapoptotic action, derivatives of the lipid mediator lysophosphatidic acid (LPA) provide potential therapeutic utility in diseases associated with programmed cell death. Apoptosis is one of the major pathophysiological processes elicited by radiation injury to the organism. Consequently, therapeutic explorations applying compounds that mimic the antiapoptotic action of LPA have begun. Here we present a brief account of our decade-long drug discovery effort aimed at developing LPA mimics with a special focus on specific agonists of the LPA(2) receptor subtype, which was found to be highly effective in protecting cells from apoptosis. We describe new evidence that 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), a prototypic nonlipid agonist specific to the LPA(2) receptor subtype, rescues apoptotically condemned cells in vitro and in vivo from injury caused by high-dose ?-irradiation. GRI977143 shows the features of a radiomitigator because it is effective in rescuing the lives of mice from deadly levels of radiation when administered 24h after radiation exposure. Our findings suggest that by specifically activating LPA(2) receptors GRI977143 activates the ERK1/2 prosurvival pathway, effectively reduces Bax translocation to the mitochondrion, attenuates the activation of initiator and effector caspases, reduces DNA fragmentation, and inhibits PARP-1 cleavage associated with ?-irradiation-induced apoptosis. GRI977143 also inhibits bystander apoptosis elicited by soluble proapoptotic mediators produced by irradiated cells. Thus, GRI977143 can serve as a prototype scaffold for lead optimization paving the way to more potent analogs amenable for therapeutic exploration. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
Related JoVE Video
Bladder preservation therapy for muscle-invading bladder cancers on Radiation Therapy Oncology Group trials 8802, 8903, 9506, and 9706: vascular endothelial growth factor B overexpression predicts for increased distant metastasis and shorter survival.
Oncologist
PUBLISHED: 05-31-2013
Show Abstract
Hide Abstract
From 1988 to 1999, the Radiation Therapy Oncology Group (RTOG) conducted four prospective studies (8802, 8903, 9506, 9706) of patients with clinical stage T2-4a muscle-invasive bladder cancer. Treatment was selective bladder preservation using transurethral surgery (TURBT) plus cisplatin-based induction and consolidation chemoradiation regimens, reserving radical cystectomy for invasive tumor recurrence. We investigated vascular endothelial growth factor (VEGF) pathway biomarkers in this unique clinical dataset (median follow-up of 3.1 years).
Related JoVE Video
Comparison of real-time polymerase chain reaction and serological tests for the confirmation of Mycoplasma pneumoniae infection in children with clinical diagnosis of atypical pneumonia.
J Microbiol Immunol Infect
PUBLISHED: 05-29-2013
Show Abstract
Hide Abstract
BACKGROUND: Mycoplasma pneumoniae is a common pathogen of respiratory tract infection in children, and its correct and rapid diagnosis is a clinical challenge. Real-time polymerase chain reaction (RT-PCR) has been used frequently for the detection of this pathogen. MATERIALS AND METHODS: Medical records from all children with a clinical diagnosis of mycoplasma pneumonia and whose respiratory samples were tested for M. pneumoniae (using RT-PCR) during 2011 were reviewed retrospectively. We compared the sensitivity and specificity of serological assays versus those of RT-PCR for diagnosis of M. pneumoniae infections. We also reviewed retrospectively clinical characteristics, and laboratory and imaging findings of children with laboratory evidence of M. pneumoniae infection. RESULTS: In 2011, 290 children were diagnosed to have mycoplasma pneumonia clinically and had their respiratory samples tested for M. pneumoniae by RT-PCR. Fifty-four children (19%) had a positive result. Meanwhile, 63% (182/290) of these children also underwent serological tests, out of whom 44 (24%) were found to be positive for immunoglobulin M (IgM). Using PCR as a gold standard, M. pneumoniae IgM assay was found to show a sensitivity of 62.2% and a specificity of 85.5%. Positive and negative predictive values of IgM were 52.3% and 89.9%, respectively. In M. pneumoniae IgM-positive children, a negative PCR result was associated with more coinfection by other pathogens and longer duration of prehospitalization fever. Bacterial loads of M. pneumoniae were not correlated with clinical outcomes. CONCLUSION: The majority of clinically diagnosed mycoplasma pneumonia was unconfirmed. Mycoplasma pneumoniae IgM has poor sensitivity and a positive predictive value. Interpretation of Mycoplasma pneumoniae IgM should be done with caution.
Related JoVE Video
Correlation and presentation of thyroid functional status with thyroid autoantibodies in long-term follow-up of autoimmune thyroiditis: A study of 116 cases.
J. Formos. Med. Assoc.
PUBLISHED: 05-07-2013
Show Abstract
Hide Abstract
The most common diagnostic finding of autoimmune thyroid disease (AITD) is the presence of antithyroid antibodies. While autoimmune thyroiditis (AT) is a common AITD, aspiration cytology is one of the important diagnostic tools of AT.
Related JoVE Video
Weight Gain While Switching from Polypharmacy to Ziprasidone.
Clin Schizophr Relat Psychoses
PUBLISHED: 05-07-2013
Show Abstract
Hide Abstract
Second-generation antipsychotics (SGAs), valproate, and sulpiride are related to significant weight gain and risk of metabolic syndrome (MetS). Among SGA, olanzapine and clozapine are associated with the highest metabolic risk while ziprasidone is among one of SGAs with the lowest risk. Several reports suggest that weight loss is observed in switching other antipsychotics to ziprasidone. Here we described a female patient with chronic paranoid schizophrenia who had an unexpected weight gain and developed MetS during a cross-switch from polypharmacy of olanzapine, valproate and sulpiride to ziprasidone monotherapy.
Related JoVE Video
The Association Between Tumor Epidermal Growth Factor Receptor (EGFR) Mutation and Multiple Primary Malignancies in Patients With Adenocarcinoma of the Lungs.
Am. J. Clin. Oncol.
PUBLISHED: 04-24-2013
Show Abstract
Hide Abstract
OBJECTIVES:: An increased incidence of multiple primary malignancies has been found in recent decades. However, the nature of the association between the epidermal growth factor receptor (EGFR) mutation status and multiple primary malignancies in patients with adenocarcinoma of the lungs is not clearly understood at this time. METHODS:: We retrospectively reviewed the data of our patients with adenocarcinoma of the lungs, and evaluated the association between the tumor EGFR mutation status and multiple primary malignancies. RESULTS:: From December 2008 to November 2011, 655 pulmonary adenocarcinoma patients with tumor EGFR mutation data were available for analysis. Of them, 359 had EGFR mutations (including 336 classic EGFR mutations), 63 had double primary malignancies, and 7 had triple primary malignancies. Patients with classic EGFR mutations had a higher incidence of multiple primary malignancies than those without (P=0.042). Multiple primary malignancies occurred more frequently in patients with exon 19 mutations (including insertions, point mutations, or deletions) or exon 19 deletions than in patients without (P=0.037 and 0.032, respectively). Patients with any EGFR mutations or classic EGFR mutations survived longer than those who did not (P<0.001 and <0.001, respectively). Patients with multiple primary malignancies survived for a longer period than those without (P=0.006). CONCLUSIONS:: Multiple primary malignancies occurred more frequently in patients with classic EGFR mutations, especially those with exon 19 deletions.
Related JoVE Video
Midterm oncological outcomes of laparoscopic vs open radical prostatectomy (RP).
BJU Int.
PUBLISHED: 04-19-2013
Show Abstract
Hide Abstract
To compare the midterm risks of biochemical recurrence (BCR) and salvage radiation therapy (SRT) after laparoscopic (LRP) and open retropubic radical prostatectomy (RRP). Strong evidence that these techniques are comparable to the gold standard of open RRP is lacking, as most comparative studies are limited by short follow-up or rely on historical controls.
Related JoVE Video
Peutz-Jeghers syndrome: a critical look at colonic Peutz-Jeghers polyps.
Mod. Pathol.
PUBLISHED: 04-19-2013
Show Abstract
Hide Abstract
Peutz-Jeghers syndrome is an autosomal dominant condition characterized by gastrointestinal hamartomatous polyps. The pathologic identification of a Peutz-Jeghers polyp is integral to the diagnosis of this syndrome that often remains undiagnosed until after these polyps are identified. Histologically, Peutz-Jeghers polyps are characterized by a distinctive arborization of smooth muscle within the lamina propria. Colonic Peutz-Jeghers polyps, however, may mimic mucosal prolapse polyps or virtually any colonic polyp that undergoes prolapse. In this paper, we explore the morphological features of colonic Peutz-Jeghers polyps and the diagnostic challenges associated with these polyps. Colonic polyps from patients with Peutz-Jeghers syndrome were identified (n=34). The control cohort, included mucosal prolapse polyps (n=5), hyperplastic polyps (n=10) and tubular adenomas with prolapse (n=9), ganglioneuromatous polyps (n=2) and juvenile polyps (n=14). Intramucosal smooth muscle fibers were identified in all classes of polyps. Twenty-three of the 34 colonic Peutz-Jeghers polyps were characterized by lobulated clusters of colonic crypts. On immunohistochemistry, desmin-positive smooth muscle fibers were seen surrounding these lobules. This lobular organization of the crypts was not identified in mucosal prolapse polyps and hyperplastic polyps or tubular adenomas with prolapse; only one of the 14 juvenile polyps showed this pattern of reactivity on a desmin stain. Our data suggests that the histologic hallmark of colonic Peutz-Jeghers polyps is the lobular organization of the crypts, and that an arborizing pattern of smooth muscle proliferation is neither sensitive nor a specific marker of colonic Peutz-Jeghers polyps. The presence of desmin-positive smooth muscle fibers surrounding the lobules is a helpful diagnostic feature of colonic Peutz-Jeghers polyps, and facilitates the distinction of these polyps from non-Peutz-Jeghers polyps with prolapse-like changes.
Related JoVE Video
Runx1-deficient afferents impair visceral nociception, exacerbating dextran sodium sulfate-induced colitis.
Brain Behav. Immun.
PUBLISHED: 04-17-2013
Show Abstract
Hide Abstract
Colitis is a group of inflammatory and auto-immune disorders that affect the tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced animal models of colitis have indicated that nociceptive afferents or neuropeptides have differing effects on GI inflammation. However, the molecular mechanisms involved in visceral pain and the role of visceral sensory afferents involved in the modulation of colitis remains unclear. A previous study demonstrated that Runx1, a Runt domain transcription factor, is restricted to nociceptors. In these neurons, Runx1 regulates the expression of numerous ion channels and receptors, controlling the lamina-specific innervation patterns of nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit specific defects in thermal and neuropathic pain. To examine the function of Runx1 in visceral nociception, we employed double-transgenic mice (WntCre: Runx1(F)(/)(F)), in which the expression of Runx1 was specifically disrupted in the sensory neurons. To determine the role of Runx1 in visceral pain sensation, the WntCre: Runx1(F)(/)(F) mice and their control littermates (Runx1(F)(/)(F)) were treated using dextran sodium sulfate (DSS) to induce colitis. The results indicated that disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the phenotypes in murine DSS-induced colitis; (3) a differential effect on the production of pro- and anti-inflammatory cytokines in the colon tissues isolated from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and (4) alteration of the distribution of lymphocytes and mast cells in mucosa. These results show that the function of Runx1 in sensory afferents is vital for modulating visceral pain and the neuro-immune axis.
Related JoVE Video
Estimation of the Incidence of Kawasaki Disease in Taiwan. A Comparison of Two Data Sources: Nationwide Hospital Survey and National Health Insurance Claims.
Pediatr Neonatol
PUBLISHED: 04-15-2013
Show Abstract
Hide Abstract
Kawasaki disease (KD), first described by Dr. Tomisaku Kawasaki in 1967, was found for the first time in Taiwan in 1976. It continued to occur in increased numbers. For the study of incidence rates and epidemiological features of KD, we conducted five nationwide hospital surveys (NHS) in 1987, 1992, 1994, 2001 and 2008, respectively. We estimated also the annual incidence rates of KD during 1996-2007, based on the National Health Insurance (NHI) database, which had been implemented since 1995, covering 98% of the population in Taiwan.
Related JoVE Video
Differentiating progressive from nonprogressive T1 bladder cancer by gene expression profiling: Applying RNA-sequencing analysis on archived specimens.
Urol. Oncol.
PUBLISHED: 04-09-2013
Show Abstract
Hide Abstract
To identify gene signatures in transitional cell carcinoma that can differentiate high-grade T1 nonprogressive (T1NP) bladder cancer (BCa) from those T1 progressive (T1P) tumors that progress to muscularis propria-invasive T2 tumors.
Related JoVE Video
Amiodarone and the risk of cancer: a nationwide population-based study.
Cancer
PUBLISHED: 04-08-2013
Show Abstract
Hide Abstract
In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy.
Related JoVE Video
Abnormal renal resistive index in patients with mild-to-moderate chronic obstructive pulmonary disease.
COPD
PUBLISHED: 04-04-2013
Show Abstract
Hide Abstract
Arterial rigidity and endothelial dysfunction are systemic manifestations of chronic obstructive pulmonary disease (COPD). The decrease in renal vascular resistance in order to adapt the increase in glomerular filtration rate after oral protein loading is known as normal renal functional reserve. We tested the hypothesis that COPD patients, even in those with mild-to-moderate airflow obstruction, are affected by systemic inflammation associated with abnormal renal functional reserve.
Related JoVE Video
Sleep apnoea patients have higher mortality when confronting sepsis.
Eur. J. Clin. Invest.
PUBLISHED: 04-02-2013
Show Abstract
Hide Abstract
Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea.
Related JoVE Video
Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls.
Hum. Mol. Genet.
PUBLISHED: 03-27-2013
Show Abstract
Hide Abstract
In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ~10% of excess familial risk of breast cancer in Asian populations.
Related JoVE Video
Development and validation of a 32-gene prognostic index for prostate cancer progression.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-26-2013
Show Abstract
Hide Abstract
The accurate determination of the risk of cancer recurrence is an important unmet need in the management of prostate cancer. Patients and physicians must weigh the benefits of currently available therapies against the potential morbidity of these treatments. Herein we describe the development of a gene expression-based continuous risk index and a validation of this test in an independent, blinded cohort of post-radical prostatectomy (RP) patients. A gene expression signature, prognostic for prostate-specific antigen (PSA) recurrence, was identified through a bioinformatic analysis of the expression of 1,536 genes in malignant prostate tissue from a training cohort of consecutive patients treated with RP. The assay was transferred to a real-time RT-PCR platform, and a continuous risk index model was constructed based on the expression of 32 genes. This 32-gene risk index model was validated in an independent, blinded cohort of 270 RP patients. In multivariate analyses, the risk index was prognostic for risk of PSA recurrence and had added value over standard prognostic markers such as Gleason score, pathologic tumor stage, surgical margin status, and presurgery PSA (hazard ratio, 4.05; 95% confidence interval, 1.50-10.94; P = 0.0057). Furthermore, RP patients could be stratified based on the risk of PSA recurrence and the development of metastatic disease. The 32-gene signature identified here is a robust prognostic marker for disease recurrence. This assay may aid in postoperative treatment selection and has the potential to impact decision making at the biopsy stage.
Related JoVE Video
Re-evaluating the predictive roles of metabolic complications and clinical outcome according to eGFR levels--a four-years prospective cohort study in Taiwan.
BMC Nephrol
PUBLISHED: 03-20-2013
Show Abstract
Hide Abstract
Metabolic complications are associated with clinical outcomes in patients with chronic kidney disease (CKD). These outcomes differ among patients according to the different stages of disease. The prevalence and association of type and number of metabolic complications with renal progression and death in patients having different eGFR levels has high clinical value, but this fact has been rarely evaluated in prospective studies.
Related JoVE Video
Characteristics of IFN-? responses in IGRA among pulmonary TB suspects in a TB-endemic area.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
Although the diagnostic value of interferon-? (IFN-?) release assays for active tuberculosis (TB) is limited, the characteristic of non-TB-specific IFN-? responses among TB suspects deserves further evaluation. We enrolled clinically suspected pulmonary TB (PTB) patients, and QuantiFERON-TB Gold In-Tube (QFT-GIT) was performed. The characteristics of IFN-? responses were analyzed. Among 392 patients, active PTB patients had stronger IFN-? responses to TB antigen (TBAg-Nil, P < 0.001) and lower responses to mitogen (Mitogen-Nil, P < 0.001). Lower body mass index (P = 0.001), without bacille Calmette-Guerin vaccination (P = 0.026), and active PTB (P = 0.011) were independent factors associated with lower non-TB-specific IFN-? responses. Among TB suspects with higher TBAg-Nil (>1.02 U/mL) and lower Mitogen-Nil (<5.5 U/mL), 84.3% were active PTB cases. Among TB suspects with lower TBAg-Nil and higher Mitogen-Nil, only 4.7% were active PTB. The present study suggested that the possibilities of active PTB should be carefully excluded in TB suspects with stronger TB-specific and lower non-TB-specific IFN-? responses in QFT-GIT.
Related JoVE Video
Sleep apnea and risk of peptic ulcer bleeding: a nationwide population-based study.
Am. J. Med.
PUBLISHED: 02-16-2013
Show Abstract
Hide Abstract
Patients with sleep apnea sustain cessation of breath during sleep, leading to intermittent hypoxia, systemic inflammation, and sympathetic activation. These insults may contribute to initiation or progression of peptic ulcers. This retrospective matched-control cohort study explored the relationship of sleep apnea and subsequent development of peptic ulcer bleeding.
Related JoVE Video
Recommendations for rotavirus vaccine.
Pediatr Neonatol
PUBLISHED: 02-08-2013
Show Abstract
Hide Abstract
Rotavirus infection has been the leading cause of gastroenteritis among children in Taiwan. Studies have shown that 40% of hospitalization for acute gastroenteritis can be prevented through the use of vaccines, including a live, attenuated monovalent rotavirus vaccine and a pentavalent, human-bovine reassortant rotavirus vaccine. In 2009, the World Health Organization suggested that rotavirus vaccine should be included in all national immunization programs. This review summarizes issues and recommendations discussed during an expert meeting in Taiwan. The recommendations included: (1) rotavirus vaccine should be offered to all healthy infants (including those without contraindications, such as immunodeficiency) at an appropriate age; (2) either monovalent or pentavalent vaccine can be administered concurrently with routine injected vaccines; (3) the administration of rotavirus vaccine must be administered at least 2 weeks prior to oral polio vaccination; (4) the first vaccine dose for infants should be administered between age 6 weeks and age 14 weeks 6 days and the course should be completed by age 8 months 0 day; (5) pentavalent vaccines can be administered at 2 months, 4 months, and 6 months while monovalent vaccines can be taken at 2 months and 4 months; (6) a combined use of monovalent and pentavalent vaccine is justified only when the previous dose is unavailable or unknown; and (7) rotavirus vaccines may be given to premature infants, human immunodeficiency virus infected infants and infants who have received or are going to receive blood products.
Related JoVE Video
TSC1 involvement in bladder cancer: diverse effects and therapeutic implications.
J. Pathol.
PUBLISHED: 01-23-2013
Show Abstract
Hide Abstract
TSC1 is often mutated in bladder cancer. However the importance of this event in disease pathogenesis and its implications for therapy are uncertain. We used genomic sequencing to examine the involvement of TSC1 in bladder cancer, and signalling pathway analysis and small-molecule screening to identify targeted therapeutic strategies in TSC1 mutant bladder cancer cell lines. TSC1 loss of heterozygosity was seen in 54% of bladder cancers. Two (4.9%) of these 41 bladder cancers had TSC1 mutations by exon-based sequencing. Analysis of 27 bladder cancer cell lines demonstrated inactivating TSC1 mutations in three: RT-4, HCV29, 97-1. Interestingly, only RT-4 showed classic feedback inhibition of AKT, and was highly sensitive to treatment with mTOR inhibitors rapamycin and Torin1. 97-1 cells showed constitutive EGFR activation, and were highly sensitive to combined treatment with the mTOR inhibitor Torin1 and EGFR inhibitors Lapatinib or Afatinib. A BRAF missense mutation G469V was found in HCV29 cells, and AKT activation was dependent on BRAF, but independent of ERK. A kinase inhibitor screen of HCV29 cells showed strong growth inhibition by the Hsp90 inhibitor NVP-AUY922, and we then found synergistic inhibitory effects of NVP-AUY922 combined with either Torin1 or rapamycin on cell survival for both HCV29 and 97-1 cells. In aggregate, these findings indicate that there are highly variable mutation profiles and signalling pathway activation in TSC1-mutant bladder cancer. Furthermore, combined Hsp90/mTOR inhibition is a promising therapeutic approach for TSC1 mutant bladder cancer.
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.