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Find video protocols related to scientific articles indexed in Pubmed.
Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease.
Taiwan J Obstet Gynecol
PUBLISHED: 10-08-2014
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A twin pregnancy consisting of a complete hydatidiform mole with a coexisting normal fetus is extremely rare with an incidence of 1/22,000 to 1/100,000. The incidence of preterm delivery is high and few pregnancies reach near term with a viable fetus.
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Cdc6 cooperates with c-Myc to promote genome instability and epithelial to mesenchymal transition EMT in zebrafish.
Oncotarget
PUBLISHED: 07-23-2014
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Aberration in DNA replication is a major cause to genome instability that is a hallmark of cancer cells. Cell division cycle 6 (Cdc6) and c-Myc have a critical role in the initiation of DNA replication. However, whether their interaction induces epithelial-mesenchymal transition (EMT) and promotes tumorigenesis in in vivo animal model remains unclear. Since using zebrafish as a cancer model has been restricted by the late onset of tumorigenesis and extreme difficulty in transformation on skin, we tried to establish a novel non-melanoma skin model in zebrafish to study their role in tumorigenesis. A stable transgenic zebrafish was created by using tol2 transposon, in which cdc6 and c-myc were co-overexpressed in epidermis driven by a skin-specific krt4 promoter. Intriguingly, co-overexpression of cdc6 and c-myc in transgenic zebrafish skin triggered tumor-like transformation, apoptosis attenuation, genomic instability, and EMT, hallmarks of malignant tumorigenesis. Our findings and other characteristics of zebrafish, including optical clarity and small molecule treatment, provide the future utility of this model for easy and non-invasive detection and for identification of new anti-cancer drug.
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MTOR inhibition enhances NVP-AUY922-induced autophagy-mediated KIT degradation and cytotoxicity in imatinib-resistant gastrointestinal stromal tumors.
Oncotarget
PUBLISHED: 06-19-2014
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Our previous study demonstrated NVP-AUY922, a HSP90AA1 inhibitor, could enhance mutant KIT degradation in gastrointestinal stroma tumor (GIST) cells through both proteasome- and autophagy-mediated pathways. Herein, we showed rapamycin, a MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT expression levels and enhance apoptosis in imatinib-resistant GIST cells. The involvement of autophagy in rapamycin-induced KIT downregulation was further confirmed by co-localization of KIT and autophagosome, and partial recovery of KIT expression level by either siRNA-mediated BECN1 and ATG5 silencing or autophagy inhibitors after rapamycin. Rapamycin and NVP-AUY922 synergistically inhibited GIST cells growth in vitro. The combination of low-dose NVP-AUY922 with rapamycin had comparable effects on reducing KIT expression, increasing MAP1LC3B puncta and tumor necrosis, and inhibiting tumor growth as high-dose NVP-AUY922 did in GIST430 xenograft model. Our results suggest the addition of a MTOR inhibitor may reduce NVP-AUY922 dose requirement and potentially improve its therapeutic index in mutant KIT-expressing GISTs.
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Identification of aurora kinase A as an unfavorable prognostic factor and potential treatment target for metastatic gastrointestinal stromal tumors.
Oncotarget
PUBLISHED: 06-06-2014
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Although imatinib mesylate (IM) has revolutionized the management of gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge. Previous studies have shown that the expression of aurora kinase A (AURKA) predicts recurrence in patients with primary, surgically resected GISTs. The current study aimed to evaluate the significance of AURKA expression as an unfavorable prognostic marker for advanced GISTs, and provide evidence that AURKA could be a potential therapeutic target in GISTs. The prognostic significance of the expression of AURKA, along with other clinicopathological factors, was analyzed in a cohort of 99 IM-treated patients with advanced GISTs. The potential use of an inhibitor of AURKA as a therapeutic agent against GISTs was also tested in GIST cell lines. Among 99 enrolled patients, poor performance status, large tumor size, drug response, and AURKA overexpression were independent prognostic factors for poor progression-free survival (PFS). For overall survival (OS), only large tumor size and AURKA overexpression were identified as independent unfavorable factors. In an in vitro study, MLN8237, an AURKA inhibitor, inhibited growth of both IM-sensitive and IM-resistant GIST cells in a concentration-dependent manner, and exhibited synergistic cytotoxicity with IM in GIST cells. The inhibitory effect of MLN8237 in GIST cells could be attributed to the induction of G2/M arrest, apoptosis, and senescence. Our study shows that AURKA expression independently predicted poor PFS and OS in patients with advanced GISTs who were treated with IM. An AURKA inhibitor may have potential as a therapeutic agent for both IM-sensitive and IM-resistant GISTs.
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Experience of Pediatric Osteosarcoma of the Extremity at a Single Institution in Taiwan: Prognostic Factors and Impact on Survival.
Ann. Surg. Oncol.
PUBLISHED: 04-21-2014
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To identify the prognostic factors and evaluate the impact of chemotherapy regimens on the outcomes of pediatric osteosarcoma of the extremities.
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Comparison of cetuximab to bevacizumab as the first-line bio-chemotherapy for patients with metastatic colorectal cancer: Superior progression-free survival is restricted to patients with measurable tumors and objective tumor response-a retrospective study.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-18-2014
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We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer.
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Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition.
Oncotarget
PUBLISHED: 02-26-2014
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Polo-like kinase 1 (PLK1), a critical cell cycle regulator, has been identified as a potential target in osteosarcoma (OS). 15-deoxy-?12, 14-prostaglandin J2 (15d-PGJ2), a prostaglandin derivative, has shown its anti-tumor activity by inducing apoptosis through reactive oxygen species (ROS)-mediated inactivation of v-akt, a murine thymoma viral oncogene homolog, (AKT) in cancer cells. In the study analyzing its effects on arthritis, 15d-PGJ2 mediated shear-induced chondrocyte apoptosis via protein kinase A (PKA)-dependent regulation of PLK1. In this study, the cytotoxic effect and mechanism underlying 15d-PGJ2 effects against OS were explored using OS cell lines. 15d-PGJ2 induced significant G2/M arrest, and exerted time- and dose-dependent cytotoxic effects against all OS cell lines. Western blot analysis showed that both AKT and PKA-PLK1 were down-regulated in OS cell lines after treatment with 15d-PGJ2. In addition, transfection of constitutively active AKT or PLK1 partially rescued cells from 15d-PGJ2-induced apoptosis, suggesting crucial roles for both pathways in the anti-cancer effects of 15d-PGJ2. Moreover, ROS generation was found treatment with 15d-PGJ2, and its cytotoxic effect could be reversed with N-acetyl-l-cysteine. Furthermore, inhibition of JNK partially rescued 15d-PGJ2 cytotoxicity. Thus, ROS-mediated JNK activation may contribute to apoptosis through down-regulation of the p-Akt and PKA-PLK1 pathways. 15d-PGJ2 is a potential therapeutic agent for OS, exerting cytotoxicity mediated through both AKT and PKA-PLK1 inhibition, and these results form the basis for further analysis of its role in animal studies and clinical applications.
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3D bioelectronic interface: capturing circulating tumor cells onto conducting polymer-based micro/nanorod arrays with chemical and topographical control.
Small
PUBLISHED: 02-15-2014
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The three-dimensional (3D) poly(3,4-ethylenedioxythiophene) (PEDOT)-based bioelectronic interfaces (BEIs) with diverse dimensional micro/nanorod array structures, varied surface chemical pro-perties, high electrical conductivity, reversible chemical redox switching, and high optical transparency are used for capturing circulating tumor cells (CTCs). Such 3D PEDOT-based BEIs can function as an efficient clinical diagonstic and therapeutic platform.
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Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-20-2014
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A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer.
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Incidence patterns of primary bone cancer in taiwan (2003-2010): a population-based study.
Ann. Surg. Oncol.
PUBLISHED: 01-15-2014
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Primary bone cancer (BC) incidence by age has not been surveyed in Asia.
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Adaptive human CDKAL1 variants underlie hormonal response variations at the enteroinsular axis.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent analyses have identified positively selected loci that explain differences in immune responses, body forms, and adaptations to extreme climates, but variants that describe adaptations in energy-balance regulation remain underexplored. To identify variants that confer adaptations in energy-balance regulation, we explored the evolutionary history and functional associations of candidate variants in 207 genes. We screened single nucleotide polymorphisms in genes that had been associated with energy-balance regulation for unusual genetic patterns in human populations, followed by studying associations among selected variants and serum levels of GIP, insulin, and C-peptide in pregnant women after an oral glucose tolerance test. Our analysis indicated that 5' variants in CDKAL1, CYB5R4, GAD2, and PPARG are marked with statistically significant signals of gene-environment interactions. Importantly, studies of serum hormone levels showed that variants in CDKAL1 are associated with glucose-induced GIP and insulin responses (p<0.05). On the other hand, a GAD2 variant exhibited a significant association with glucose-induced C-peptide response. In addition, simulation analysis indicated that a type 2 diabetes risk variant in CDKAL1 (rs7754840) was selected in East Asians ?6,900 years ago. Taken together, these data indicated that variants in CDKAL1 and GAD2 were targets of prior environmental selection. Because the selection of the CDKAL1 variant overlapped with the selection of a cluster of GIP variants in the same population ?11,800 to 2,000 years ago, we speculate that these regulatory genes at the human enteroinsular axis could be highly responsive to environmental selection in recent human history.
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Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 06-19-2013
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CRNN gene expression is downregulated in esophageal squamous cell carcinoma (ESCC), although its clinical implications in esophageal cancer remain unclear.
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TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma.
J. Gastroenterol.
PUBLISHED: 04-17-2013
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The molecular and genetic changes underlying esophageal squamous cell carcinoma (ESCC) tumor formation and rapid progression are poorly understood. Using high-throughput data analysis, we examined molecular changes involved in ESCC pathogenesis and investigated their clinical relevance.
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Selecting tyrosine kinase inhibitors for gastrointestinal stromal tumor with secondary KIT activation-loop domain mutations.
PLoS ONE
PUBLISHED: 01-01-2013
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Advanced gastrointestinal stromal tumors (GIST), a KIT oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary KIT mutations to confer IM-resistant phenotype. Second-line sunitinib malate (SU) therapy is largely ineffective for IM-resistant GISTs with secondary exon 17 (activation-loop domain) mutations. We established an in vitro cell-based platform consisting of a series of COS-1 cells expressing KIT cDNA constructs encoding common primary±secondary mutations observed in GISTs, to compare the activity of several commercially available tyrosine kinase inhibitors on inhibiting the phosphorylation of mutant KIT proteins at their clinically achievable plasma steady-state concentration (Css). The inhibitory efficacies on KIT exon 11/17 mutants were further validated by growth inhibition assay on GIST48 cells, and underlying molecular-structure mechanisms were investigated by molecular modeling. Our results showed that SU more effectively inhibited mutant KIT with secondary exon 13 or 14 mutations than those with secondary exon 17 mutations, as clinically indicated. On contrary, at individual Css, nilotinib and sorafenib more profoundly inhibited the phosphorylation of KIT with secondary exon 17 mutations and the growth of GIST48 cells than IM, SU, and dasatinib. Molecular modeling analysis showed fragment deletion of exon 11 and point mutation on exon 17 would lead to a shift of KIT conformational equilibrium toward active form, for which nilotinib and sorafenib bound more stably than IM and SU. In current preclinical study, nilotinib and sorafenib are more active in IM-resistant GISTs with secondary exon 17 mutation than SU that deserve further clinical investigation.
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The prognosis of patients with primary osteosarcoma who have undergone unplanned therapy.
Jpn. J. Clin. Oncol.
PUBLISHED: 10-11-2011
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For diagnosing osteosarcoma correctly, a combination of clinical, radiological and histological examinations is required. Erroneous treatment may cause local contamination and systemic seeding in patients. The purpose of this study was to compare outcomes of planned and unplanned treatment for osteosarcoma.
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The efficacy of chemotherapy in patients with high-grade metastatic colon cancer.
Hepatogastroenterology
PUBLISHED: 07-15-2011
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This study was undertaken to assess the prognostic role of histological grade in colon cancer and the efficacy of either oxaliplatin or irinotecan after incorporation into an infusional regimen of 5-fluorouracil and leucovorin in patients with high-grade metastatic colon cancer.
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A new classification scheme for recurrent or metastatic colon cancer after liver metastasectomy.
J Chin Med Assoc
PUBLISHED: 07-05-2011
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Metastasectomy is the standard treatment for patients with resectable liver metastasis from colon cancer. This study aimed to determine the impact of initial stage on overall survival (OS) after metastasectomy.
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Effective salvage therapy of imatinib-resistant gastrointestinal stromal tumor with combination of imatinib and pegylated liposomal doxorubicin.
J Chin Med Assoc
PUBLISHED: 05-13-2011
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Here we presented a 60-year-old Taiwanese man with advanced gastrointestinal stromal tumor. Disease progression was noted during imatinib treatment. Surgical resection was done and mutation analysis of KIT gene in all the resected tumors revealed deletion mutations of codons 558-565 in exon 11, whereas a missense mutation was also identified at codon 822 in exon 17 in one resected tumor. Patients disease was refractory to escalating dose of imatinib and dasatinb. Surprisingly, combination of imatinib with pegylated liposomal doxorubicin produced a substantial response and resulted in a 5-month progression free period for this imatinib-resistant gastrointestinal stromal tumor.
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Targeted nuclear delivery using peptide-coated quantum dots.
Bioconjug. Chem.
PUBLISHED: 05-10-2011
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Core/shell quantum dots (CdSe/Zns) conjugated with various nuclear localization signaling (NLS) peptides, which could facilitate the transportation of quantum dots across the plasma membrane into the nucleus, have been utilized to investigate the uptake mechanism of targeted delivery. Because of their brightness and photostability, it was possible to trace the trajectories of individual quantum dots in living cells using both confocal and total internal reflection microscopes. We found that, when the quantum dots were added to a cell culture, the peptide-coated quantum dots entered the cell nucleus while the uncoated quantum dots remained in the cytoplasm. At 8 nM, most of the peptide coated quantum dots were found in the cytoplasm due to aggregation. However, at a lower concentration (0.08 nM), approximately 25% of the NLS peptide-coated quantum dots entered the cell nucleus. We also found that some quantum dots without NLS coating could also enter the nucleus, suggesting that the size of the quantum dots may play an important role in such a process.
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Exploring the formation of focal adhesions on patterned surfaces using super-resolution imaging.
Small
PUBLISHED: 04-18-2011
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The formation of focal adhesions on various sizes of fibronectin patterns, ranging from 200 ?m to 250 nm, was systematically investigated by total internal reflection fluorescence microscopy and super-resolution imaging. It was found that cells adhered to and spread on these micro/nanopatterns, forming focal adhesions. On a micrometer scale the shape of the focal adhesions was elongated. However, on the nanometer scale, the shape of focal adhesions became dotlike. To further explore the distribution of focal adhesion proteins formed on surfaces, a localization-based super-resolution imaging technique was employed in order to determine the position and density of vinculin proteins. A characteristic distance of 50 nm was found between vinculin molecules in the focal adhesions, which did not depend on the size of the fibronectin nanopatterns. This distance was found to be crucial for the formation of focal adhesions. In addition, the density of vinculin at the focal adhesions formed on the nanopatterns increased as the pattern size decreased. The density of the protein was found to be 425 ± 247, 584 ± 302, and 703 ± 305 proteins ?m(-2) on the 600, 400, and 250 nm fibronectin patterns respectively. Whereas 226 ± 77 proteins ?m(-2) was measured for the matured focal adhesions on homogeneous fibronectin coated substrates. The increase in vinculin density implies that an increase in mechanical load was applied to the focal adhesions formed on the smaller nanopatterns.
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Brain, the last fortress of sarcoma: similar dismal outcome but discrepancy of timing of brain metastasis in bone and soft tissue sarcoma.
J Surg Oncol
PUBLISHED: 03-16-2011
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Brain metastasis is a rare but dismal event in sarcomas. However, the pattern of occurrence and the prognostic factors associated with post-brain metastasis survival (PBMS) are not yet well-characterized.
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Liver abscess after liver metastasectomy is a poor prognostic factor in patients with colorectal cancer.
J. Gastrointest. Surg.
PUBLISHED: 03-06-2011
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More and more complications of extensive hepatic resection are being encountered in patients treated for liver metastases from colorectal cancer. This study aimed to determine the impact of liver abscess after hepatic resection on overall survival (OS) and the role of adjuvant chemotherapy.
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Identification of metabolic modifiers that underlie phenotypic variations in energy-balance regulation.
Diabetes
PUBLISHED: 02-07-2011
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Although recent studies have shown that human genomes contain hundreds of loci that exhibit signatures of positive selection, variants that are associated with adaptation in energy-balance regulation remain elusive. We reasoned that the difficulty in identifying such variants could be due to heterogeneity in selection pressure and that an integrative approach that incorporated experiment-based evidence and population genetics-based statistical judgments would be needed to reveal important metabolic modifiers in humans.
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Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study.
Support Care Cancer
PUBLISHED: 02-04-2011
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This open-label pilot study is aimed to evaluate the efficacy and tolerability of the antidepressant duloxetine, which is effective for diabetic neuropathic pain, in the treatment of chronic oxaliplatin-induced peripheral neuropathy (OIPN).
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Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma.
J Surg Oncol
PUBLISHED: 01-15-2011
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We aimed to study the prevalence and prognostic influence of epidermal growth factor receptor (EGFR) and its downstream effectors in synovial sarcoma (SS).
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PML protein as a prognostic molecular marker for patients with esophageal squamous cell carcinomas receiving primary surgery.
J Surg Oncol
PUBLISHED: 01-15-2011
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We evaluated the clinicopathological associations and prognostic implications of promyelocytic leukemia gene (PML) expressions in patients with esophageal squamous cell carcinomas (ESCC) receiving primary surgery.
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Elevated amniotic fluid F?-isoprostane: a potential predictive marker for preeclampsia.
Free Radic. Biol. Med.
PUBLISHED: 01-02-2011
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In the complex mechanism of preeclampsia, oxidative stress is an important pathogenic factor, and F?-isoprostane is a marker of oxidative stress and lipid peroxidation. The objective of this study was to identify if the amniotic fluid (AF) levels of F?-isoprostanes were elevated in women who later developed preeclampsia. In this study, we analyzed AF F?-isoprostane concentrations with enzyme immunoassay (EIA), and the EIA results could be validated by quantitative mass spectrometry. The mean AF concentration of F?-isoprostanes was significantly higher in pregnancies with subsequent development of preeclampsia (123.1 ± 57.6 pg/ml, n = 85) than in controls (73.8 ± 36.6 pg/ml, n = 85). The AF elevation of F?-isoprostanes was even higher in the preeclampsia with intrauterine growth restriction group (138.3 ± 65.2 pg/ml, n = 39). The area under the curve of the receiver operating characteristics analysis for AF F?-isoprostanes assay was 0.81, supporting its potential as a biomarker for preeclampsia. These results indicate that oxidative stress existed before the onset of clinical preeclampsia, further suggesting that the elevation of AF F?-isoprostanes may be used as a guide for antioxidant supplementation to reduce the risk and/or severity of preeclampsia.
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Pneumothorax after bevacizumab-containing chemotherapy: a case report.
Jpn. J. Clin. Oncol.
PUBLISHED: 10-28-2010
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Bevacizumab added to 5-fluorouracil-based chemotherapy can improve outcomes in patients with metastatic colorectal cancer. Bevacizumab had several notable adverse effects including bowel perforation but pneumothorax had never been reported in the available English literature. We reported a 45-year-old male with lung metastases from colorectal cancer who had spontaneous pneumothorax after the second cycle of bevacizumab-containing chemotherapy. His pneumothorax resolved after tube thoracostomy with a small caliber catheter. The mechanism of pneumothorax developed after bevacizumab therapy was not clear as bowel perforation but tumor necrosis with ruptured parietal pleura might be the cause. In patients who had chest discomfort after bevacizumab-containing therapy, pneumothorax should never be overlooked as one of the differential diagnoses.
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Maternal homocysteine level and markers used in first-trimester screening for fetal Down syndrome.
Reprod Sci
PUBLISHED: 09-27-2010
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This study examined possible relationships between homocysteine and markers used in first-trimester screening for Down syndrome. Pregnancies were categorized into 4 groups according to quartile ranking of maternal plasma homocysteine concentration. Of the 595 pregnancies, 147 were assigned to group 1 (homocysteine level 0.6-3.5 ?mol/L), 156 to group 2 (homocysteine level 3.6-4.5 ?mol/L), 142 to group 3 (homocysteine level 4.6-5.6 ?mol/L), and 150 pregnancies to group 4 (homocysteine level 5.7-12.6 ?mol/L). No significant difference in mean nuchal translucency and mean free ?-human chorionic gonadotropin (free-?hCG) multiples of the median (MoM) levels were observed. However, the mean pregnancy-associated plasma protein A (PAPP-A) MoM levels were significantly decreased in inverse relationship with homocysteine level among all 4 groups (F = 31.127, P < .001). If homocysteine is assayed as part of the first-trimester maternal serum testing, it is important to adjust for homocysteine concentration when using PAPP-A serum level for calculating the risk of fetal aneuploidy.
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High early mortality rate in elderly patients with multiple myeloma receiving a vincristine-doxorubicin-dexamethasone regimen.
Am. J. Hematol.
PUBLISHED: 08-25-2010
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Treatment-related mortality (TRM) is not uncommon in patients after the first course of vincristine-doxorubicin-dexamethasone (VAD) chemotherapy,but quite rare after melphalan-prednisolone (MP). This motivated us to compare the rates of TRM after the first course of VAD with those after the first course of MP. We retrospectively assessed survival and TRM in 179 patients treated for multiple myeloma with either MP or VAD. Survival was similar in two groups (P 50.463 in log-rank test). However, TRM was significantly higher inpatients after the first course of VAD (11 in 100 patients, 11.0%) than that after the first course of MP (1 in 79, 1.3%; P 5 0.010). Poor performance status (P 5 0.004) and advanced age (P 5 0.009) before treatment were independent significant factors associated with TRM after the first course of induction therapy. Pyogenic infection was the major cause of TRM after VAD (9 in 11, 81.8%). We concluded that VAD should be cautiously used as induction therapy in multiple myeloma patients, especially in elderly and/or those with poor performance status.
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Effect of maternal hepatitis B carrier status on first-trimester markers of Down syndrome.
Reprod Sci
PUBLISHED: 03-23-2010
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Up to 10% of women of reproductive age in our country are carriers of hepatitis B virus. This study examined whether maternal hepatitis B carrier status has any effect on markers used in first-trimester screening for Down syndrome. Records for 2 major Taiwanese hospitals were retrospectively examined to identify women with singleton pregnancies resulting in normal live births from June 2002 through 2008. Maternal hepatitis B data were used to define 3 groups: seronegative women, inactive carrier women, and active carrier women. Women with active or inactive carrier status were significantly older than seronegative women. The results of the study show that maternal hepatitis B carrier status does not influence first-trimester levels of maternal serum free beta-human chorionic gonadotropin (free beta-hCG) multiples of the median (MoM), pregnancy-associated plasma protein A (PAPP-A) MoM, and median fetal nuchal translucency and screening false-positive rate; therefore, correction in the risk calculation algorithm for maternal hepatitis B carrier status is not necessary.
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Soft tissue sarcoma of extremities: the prognostic significance of adequate surgical margins in primary operation and reoperation after recurrence.
Ann. Surg. Oncol.
PUBLISHED: 03-09-2010
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Adult soft tissue sarcomas (STS) of extremities are prone to recurrence despite apparently complete resection. This study aimed to explore the impact of clinicopathological factors on outcome and to define an "oncological safe margin" in these patients.
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Factors influencing womens decisions regarding pertussis vaccine: A decision-making study in the Postpartum Pertussis Immunization Program of a teaching hospital in Taiwan.
Vaccine
PUBLISHED: 02-25-2010
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We conducted surveys to determine factors influencing womens decisions to accept or decline postpartum pertussis (Tdap) vaccination. Survey response rate among eligible individuals was 97%. Of respondents, 53% accepted and 47% declined postpartum Tdap. Women, who declined vaccination were more likely to rate maternal or infant risk of exposure to pertussis as low, report that they did not trust information about postpartum pertussis vaccination, and report being very concerned about the safety of the vaccine. Awareness about pertussis, its risk to infants, and prevention via vaccination need to be further increased among women of child-bearing age, particularly pregnant women.
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Low rate of cerebral injury in monochorionic twins with selective intrauterine growth restriction.
Twin Res Hum Genet
PUBLISHED: 02-18-2010
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This study was conducted to determine the incidence of cerebral injury as detected by postnatal brain scan in monochorionic twins with selective intrauterine growth restriction. Having excluded cases complicated with twin-to-twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a total of 73 monochorionic twin pregnancies divided into absence (group I, n = 46) or presence (group II, n = 27) of selective intrauterine growth restriction. Mild cerebral injury was defined as presenting one of the following abnormal cranial scan findings: intraventricular hemorrhage grade I, grade II, lenticulostiate vasculopathy and/or subependymal pseudocysts, while severe cerebral injury was defined as presenting intraventricular hemorrhage grade III, grade IV, cystic periventricular leukomalacia (PVL) grade II or higher, porencephalic cysts, and/or ventricular dilatation. The incidence of mild cerebral injury was not significantly different between these two groups (eight cases in group I and six cases in group II). Except for one case that later developed a seizure, the majority (13 out of 14) of cases with minor brain scan anomalies were only transient, without significant clinical impact. There was only one case diagnosed with a major brain scan anomaly (periventricular leukomalacia) in group II. One severe brain injury and three neonatal deaths all belonged to group II with abnormal umbilical artery Doppler in the growth restricted twin. In conclusion, the incidence of severe cerebral injury in monochorionic twin pregnancies with selective intrauterine growth restriction was low, at 3.7%.
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A novel E1B-55kD-deleted oncolytic adenovirus carrying mutant KRAS-regulated hdm2 transgene exerts specific antitumor efficacy on colorectal cancer cells.
Mol. Cancer Ther.
PUBLISHED: 02-02-2010
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E1B-55kD-deleted adenoviruses have been used as conditionally replicative adenoviruses (CRAds) for therapeutic purposes in tumors with loss-of-function p53 mutation. To target cancer cells that harbor activating mutant KRAS (KRAS(aMut)) but spare p53(wild) normal cells, we constructed and examined by reporter assays a KRAS(aMut) but not p53-responsive promoter, the Deltap53REP2 promoter. The Deltap53REP2 promoter, derived from human double minute 2 (hdm2) P2 promoter with its p53 response elements being deleted, was used to regulate the expression of the hdm2 transgene in a novel E1B-55kD-deleted CRAd, the Ad-KRhdm2. The Ad-KRhdm2 selectively replicated in and exerted cytopathic effects on KRAS(aMut) colorectal cancer cell lines (HCT116, LoVo, LS174T, LS123, and SW620), regardless of their p53 gene statuses, by forming plaques and exhibiting cytopathic effect in cultured cells. Ad-KRhdm2, like other E1B-55kD-deleted adenoviruses, also exerted selective cytopathic effects on tumor cells with loss-of-function p53 mutant. The multiplicities of infection of Ad-KRhdm2 required to decrease 50% viability of KRAS(aMut) tumor cells cultured for 7 days were 440 to 3,400 times less than those of MRC5 normal fibroblasts and KRAS(wild)/p53(wild) RKO tumor cells. Intratumoral injection of Ad-KRhdm2 vectors exhibited specific lytic activities in nude mouse xenografts of KRAS(aMut) cell lines (LoVo, SW620, and LS174T) but not in xenografts of RKO cells. Transduction of KRAS(aMut)/p53(wild) HCT116, LoVo, and LS174T cells by Ad-KRhdm2 significantly increased Hdm2 expression, decreased p53 level, and abolished the p53-transactivating p21(Cip1) promoter activity. Ad-KRhdm2 has shown its therapeutic potential in KRAS(aMut) cancer cells and warrants further clinical trials.
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Evaluation of fetal spine biometry between 11 and 14 weeks of gestation.
Ultrasound Med Biol
PUBLISHED: 01-31-2010
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This study was designed to establish a fetal spine nomogram for age 11 through 14 weeks of gestation and to document relations among fetal spine length, distance and angle. These parameters were prospectively measured during the first trimester of singleton pregnancies, along with nuchal translucency, over a 3-year period. A total of 430 fetuses were included in the study. The regression equations among fetal spine parameters and gestational age were as follows: Spine length (mm) = 1.116 x gestational age (days) - 59.169; spine distance (mm) = 1.079 x gestational age (days) - 59.038; head-spine angle = 0.740 x gestational age (days) + 4.735; spine length:spine distance ratio = -0.002 x gestational age (days) + 1.234. Prenatal age-specific reference intervals for fetal spine biometry between 11 and 14 weeks of gestation may assist in evaluation of fetuses investigated for genetic abnormalities that can be expressed by deviation in spine length, distance, or angle.
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Difference in nuchal translucency between monozygotic and dizygotic spontaneously conceived twins.
Prenat. Diagn.
PUBLISHED: 01-12-2010
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To assess nuchal translucency (NT) thickness and differences in inter-twin NT thickness among naturally conceived monozygotic and dizygotic twins.
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Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma.
Int. J. Oncol.
PUBLISHED: 09-03-2009
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Five osteosarcoma (OS) cell lines, 37 OS tumors and 9 corresponding non-neoplastic samples were genotyped by Affymetrix 10 K 2.0 SNP array. Regions of high level amplification and homozygous deletion were identified and validated by quantitative PCR and FISH. Certain recurrent cytogenetic alterations were more frequent in recurrent/metastatic than in primary OS. These included deletion of 6q14.1, 6q16.2-q22.31, and 8p23.2-p12, amplification of 8q21.12, 8q22.3-q24.3 and 17p12, and loss of heterozygosity (LOH) at 2q24.3-q31.2, 5q11.2, 6p21.31-p21.1, 6q14.1-q16.2, 8p22-p12, 9q22.1, 10q21.1-q22.1, 10q23.31-q24.1, 12q15-q21.1 and 21q21.2-q21.3. Most of the LOH calls were associated with deletion, but a subset of them was associated with normal or increased copy number (CN). A consensus 3q13.31 deletion localized to a region within the limbic system-associated membrane protein (LSAMP) gene was also identified. The FISH evaluations demonstrated highly-localized homozygous or heterozygous LSAMP deletions in 6 of 11 primary OS. qRT-PCR evaluations of the two major alternative LSAMP transcripts demonstrated reduced expression of 1b isoform transcript in each of three OS with LSAMP exon 1b deletion. Further, the 1a isoform transcripts in these same OS had either reduced expression or a premature termination codon in LSAMP exon 2. This SNP genotyping study identified chromosomal aberrations associated with disease progression in OS and disclosed LSAMP as a novel tumor suppressor gene in OS. The study also demonstrated that CN and LOH analyses were able to detect distinct subsets of genetic abnormalities in OS.
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Malignant lymphoma in an atomic-bomb survivor.
J Chin Med Assoc
PUBLISHED: 07-08-2009
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Atomic bomb survivors outside of Japan are few and often hard to follow-up. Spinal malignant lymphoma among these survivors is rare in established studies from Japan or the United States. Here, we report an 81-year-old woman, who experienced the atomic bomb explosion in Nagasaki when she was 19 years old, who presented with papillary thyroid carcinoma when she was 70 years old. Both follicular lymphoma over the right elbow region and vertebral malignant lymphoma were found when she turned 81 years old. Bone scan did not show any increased uptake of isotope. However, thoracolumbar spine magnetic resonance imaging showed multiple infiltrative soft tissue masses involving vertebral bodies at the T10-11 level. Computed tomography-guided biopsy further showed lymphocyte infiltration. Fortunately, the neurological deficit was improved after chemotherapy. The diagnosis of malignant lymphoma in atomic bomb survivors should be more careful and aggressive, even when their bone scan results show negative findings. In addition, the authors suggest that atomic bomb survivors should be followed-up carefully throughout their entire life.
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Pml and TAp73 interacting at nuclear body mediate imatinib-induced p53-independent apoptosis of chronic myeloid leukemia cells.
Int. J. Cancer
PUBLISHED: 03-18-2009
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Bcr-abl signals for leukemogenesis of chronic myeloid leukemia (CML) and activates ras. Since the function of promyelocytic leukemia protein (pml) is provoked by ras to promote apoptosis and senescence in untransformed cells, the function is probably masked in CML. Imatinib specifically inhibits bcr-abl and induces apoptosis of CML cells. As reported previously, p53(wild) CML was more resistant to imatinib than that lacking p53. Here, we searched for an imatinib-induced p53 independent proapoptotic mechanism. We found imatinib up-regulated phosphorylation of p38 mitogen-activated protein kinase (MAPK), checkpoint kinase 2 (chk2) and transactivation-competent (TA) p73; expression of pml and bax; formation of PML-nuclear body (NB); and co-localization of TAp73/PML-NB in p53-nonfunctioning K562 and p53(mutant) Meg-01 CML cells, but not in BCR-ABL(-) HL60 cells. In K562 cells, with short interfering RNAs (siRNAs), knockdown of pml led to dephosphorylation of TAp73. Knockdown of either pml or TAp73 abolished the imatinib-induced apoptosis. Inhibition of p38 MAPK with SB203580 led to dephosphorylation of TAp73, abolishment of TAp73/PML-NB co-localization, and the subsequent apoptosis. Conversely, interferon alpha-2a (IFNalpha), which increased phosphrylated TAp73 and TAp73/PML-NB co-localization, increased additively apoptosis with imatinib. The imatinib-induced TAp73/PML-NB co-localization was accompanied by co-immpunoprecipitation of TAp73 with pml. The imatinib-induced co-localization was also found in primary CML cells from 3 of 6 patients, including 2 with p53(mutant) and one with p53(wild). A novel p53-independent proapoptotic mechanism using p38 MAPK /pml/TAp73 axis with a step processing at PML-NB and probably with chk2 and bax being involved is hereby evident in some imatinib-treated CML cells.
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Combination of microarray profiling and protein-protein interaction databases delineates the minimal discriminators as a metastasis network for esophageal squamous cell carcinoma.
Int. J. Oncol.
PUBLISHED: 02-25-2009
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Microarray profiling of 15 adjacent normal/tumor-matched esophageal squamous cell carcinoma (ESCC) specimens identified 40 up-regulated and 95 down-regulated genes. Verification of the microarray measurement by quantitative real-time reverse transcription PCR in the same set of samples as well as an additional 15 normal/tumor-matched samples revealed >95% consistency. These signatures can also be used to classify a recently reported ESCC microarray dataset. Moreover, these molecular signatures were used as templates to elucidate their corresponding protein-protein interaction (PPI) networks using the PPI databases, POINT and POINeT. As a result, 18 genes, of which six were not disclosed in the initial expression profile analysis, were found to be able to serve as the minimal discriminators for distinguishing ESCC tumors from normal specimens. Of these discriminators, ten (BGN, COL1A1, COL1A2, MMP9, CD44, FN1, TGFBI, PXN, SPARC and VWF) were associated with tumor metastasis and formed a highly interactive network with the first four molecules as hubs. Our study not only reveals how novel insights can be obtained from gene expression profiling, but also highlights a group of highly interacting genes associated with metastasis in ESCC.
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Prognostic factors of Chinese patients with primary pulmonary non-Hodgkins lymphoma: the single-institute experience in Taiwan.
Ann. Hematol.
PUBLISHED: 01-13-2009
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Primary pulmonary lymphoma (PPL) accounts for less than 1% of patients with non-Hodgkins lymphoma, with no report in Chinese patients. This study aims to analyze the clinical features and prognosis of this population. Patients with biopsy-proven pulmonary lymphoma were reviewed and re-classified by a hema-pathologist. Between 1992 and 2005, a total of 22 patients were identified (16 men and six women), with a mean age of 70 years. The histological subtypes included marginal zone B-cell lymphoma of mucosa-associated lymphoid tissues (MALT) in 12 patients (54%), diffuse large B-cell lymphoma in nine (41%), and one case of lymphomatoid granulomatosis. Diseases mainly manifested as pulmonary nodules or masses in 73% of patients, with a higher rate of hilar/mediastinal lymphadenopathy in non-MALT patients (8% vs. 80%, P = 0.002). In eight patients (36% of 22), diagnoses were only conclusive until the biopsy via thoracotomy. Eighteen patients (82%) received chemotherapy. The 5-year rates of overall survival (OS) were 91% and 21% for MALT and non-MALT types of PPL, respectively. Patients who had received surgical resection tended to have a better 5-year OS rate (P = 0.077). The Cox-regression analysis showed that two factors -- elevated serum lactate dehydrogenase level and hilar/mediastinal lymphadenopathy at diagnosis -- were independently associated with a poor OS, with a hazard ratio of 10.370 and 5.171 (P = 0.01 and 0.033), respectively. In conclusion, the histological subtypes of Chinese PPL patients were similar to those in previous reports, with no increasing incidence of T-cell immunophenotype. The two prognostic factors provided additional information in managing these patients.
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Prognostic Factors and Treatment Efficacy in Patients with Primary Diffuse Large B-cell Lymphoma of the Bone: Single Institute Experience Over 11 Years.
Intern. Med.
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Objective Primary bone lymphoma is a rare disorder, accounting for less than 1% of all cases of malignant lymphoma. Primary bony diffuse large B-cell lymphoma (PBDLBCL) is the most common histological type. In our study, a favorable response and lower risk of emergent surgery were observed following the administration of systemic chemotherapy with or without rituximab. Methods Patients diagnosed with malignant lymphoma at our hospital between 2000 and 2011 were evaluated for PBDLBCL. Pertinent data, including the clinical presentation, histological type, treatment modalities, long-term outcome, survival curve and prognostic factors, were analyzed. Results Twenty-four patients with a median age of 63 years were diagnosed with PBDLBCL. A complete response (CR) was achieved in 58.4% (n=14) of the patients. With treatment of the disease, nine of 10 patients with initially impending pathological bone fractures ultimately did not undergo surgery. The median follow-up duration was 48 months. Two patients experienced disease relapse. In a Kaplan-Meier analysis, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 66.7% and 77.8%, respectively. In the univariate analyses, the significantly favorable prognostic factors for OS were an International Prognostic Index (IPI) score of <3, an age of ?60 years, a performance status with an Eastern Cooperative Oncology (ECOG) score of <2, a CR and chemotherapy ?6 cycles. For DFS, a CR was the only favorable factor. In the multivariate analysis, a CR was the only independent factor for both OS and DFS. Conclusion Our study confirms the good prognosis of this rare disorder. Once a CR is achieved, even elderly patients may exhibit long-term survival, possibly obviating the need for surgery for less severe bone lesions.
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Hybrid contact and interfacial adhesion on well-defined periodic hierarchical pillars.
Nanoscale
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Herein, we describe a simple fabrication procedure for creating artificial hierarchical micro/nanopillars on silicon substrates that allows an effective, precise control of the interfacial adhesion and surface hydrophobicity. These well-defined hierarchical micro/nanostructures have four possible wetting states: Cassie-Cassie (C-C), Cassie-Wenzel (C-W), Wenzel-Cassie (W-C) and Wenzel-Wenzel (W-W). By controlling the critical height of the micro/nanopillars, it is possible to fabricate hierarchical micro/nanostructures in these four states. Thus, the hierarchical superhydrophobic surfaces proposed and fabricated in this study are promising for mimicking either lotus leaves with low adhesion or rose petals with high adhesion.
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Autophagy is involved in endogenous and NVP-AUY922-induced KIT degradation in gastrointestinal stromal tumors.
Autophagy
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Gastrointestinal stromal tumor (GIST) is a prototype of mutant KIT oncogene-driven tumor. Prolonged tyrosine kinase inhibitor (TKI) treatment may result in a resistant phenotype through acquired secondary KIT mutation. Heat shock protein 90 (HSP90AA1) is a chaperone protein responsible for protein maturation and stability, and KIT is a known client protein of HSP90AA1. Inhibition of HSP90AA1 has been shown to destabilize KIT protein by enhancing its degradation via the proteasome-dependent pathway. In this study, we demonstrated that NVP-AUY922 (AUY922), a new class of HSP90AA1 inhibitor, is effective in inhibiting the growth of GIST cells expressing mutant KIT protein, the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells. The growth inhibition was accompanied with a sustained reduction of both total and phosphorylated KIT proteins and the induction of apoptosis in both cell lines. Surprisingly, AUY922-induced KIT reduction could be partially reversed by pharmacological inhibition of either autophagy or proteasome degradation pathway. The blockade of autophagy alone led to the accumulation of the KIT protein, highlighting the role of autophagy in endogenous KIT turnover. The involvement of autophagy in endogenous and AUY922-induced KIT protein turnover was further confirmed by the colocalization of KIT with MAP1LC3B-, acridine orange- or SQSTM1-labeled autophagosome, and by the accumulation of KIT in GIST cells by silencing either BECN1 or ATG5 to disrupt autophagosome activity. Therefore, the results not only highlight the potential application of AUY922 for the treatment of KIT-expressing GISTs, but also provide the first evidence for the involvement of autophagy in endogenous and HSP90AA1 inhibitor-induced KIT degradation.
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Phosphorylated mammalian target of rapamycin expression is associated with the response to chemoradiotherapy in patients with esophageal squamous cell carcinoma.
J. Thorac. Cardiovasc. Surg.
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The mammalian target of rapamycin signaling pathway has been implicated in therapeutic resistance in several types of cancer. However, the significance of mammalian target of rapamycin activation in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma treated with chemoradiotherapy remain unknown. However, this pathway is of particular interest because an effective inhibitor is available.
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Factors associated with the intention to recommend pertussis vaccination for postpartum women: a survey in Taiwan of obstetrician-gynecologists knowledge, beliefs, and attitudes.
Taiwan J Obstet Gynecol
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To examine obstetrician-gynecologists knowledge, beliefs, and attitudes associated with the intention to recommend adult tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccination to postpartum women.
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Evaluation of prognosis for carcinoma of unknown origin in elderly patients.
Oncology
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Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site (CUP) for treatment considerations.
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Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.
PLoS ONE
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Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene.
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Integrating bioinformatics and clinicopathological research of gastrointestinal stromal tumors: identification of aurora kinase A as a poor risk marker.
Ann. Surg. Oncol.
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For completely resected primary gastrointestinal stromal tumors (GISTs), mitotic rate, tumor size, and tumor location are important risk factors for recurrence. However, molecular markers for recurrence are still lacking.
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Magnetic resonance imaging guided biopsy of musculoskeletal lesions.
J Chin Med Assoc
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Minimally invasive interventional biopsy procedures have the advantages of accurate localization, small incisions, and rapid recovery. The purpose of this study was to clinically test and evaluate the efficacy of the magnetic resonance imaging (MRI)-guidance techniques for obtaining musculoskeletal biopsies using the appropriate imaging modalities and instruments.
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Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound.
Int J Nanomedicine
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High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors.
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BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy.
J Surg Oncol
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In metastatic colorectal cancer, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti-epidermal growth factor receptor (EGFR) treatment and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver metastases specimens on overall survival (OS) in patients following colorectal liver metastasectomy.
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CIP2A is a predictor of poor prognosis in colon cancer.
J. Gastrointest. Surg.
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The cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer.
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Evaluation of prognostic factors and the role of chemotherapy in unfavorable carcinoma of unknown primary site: a 10-year cohort study.
BMC Res Notes
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Carcinoma of unknown primary site (CUP) has a poor prognosis and the prognostic factors in these patients are not well established. Furthermore, there are no selection criteria for patients who should benefit from chemotherapy.
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Color Doppler ultrasonography evaluation for chemotherapy treatment response of osteogenic sarcoma.
Ultrasound Med Biol
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The aim of this study was to evaluate the vascular parameters of the proximal peripheral arteries of limbs by color Doppler ultrasonography (CDUS) in individuals with osteogenic sarcoma (OGS) after neoadjuvant chemotherapy and their relation to the tumor necrosis rate. We recruited 50 individuals with osteogenic sarcoma who were scheduled for neoadjuvant chemotherapy before elective surgery from 2003 to 2010. Once enrolled, we evaluated these 50 subjects using color Doppler sonography to identify vascular parameters of tumor vessels before and after neoadjuvant therapy. The vascular parameters of the proximal peripheral arteries of limbs (peak systolic velocity [PSV], end-diastolic velocity [EDV], resistive index [RI]) and tumor neovascularity were compared before and after neoadjuvant chemotherapy using CDUS. Before chemotherapy, the PSV, EDV and RI differed significantly between the diseased and contralateral normal limbs (p < 0.001). Among the factors relating to the tumor necrosis rate before chemotherapy, the EDV of the diseased limb (p = 0.047) and tumor neovascularity (p = 0.027) showed significant differences. After chemotherapy, the PSV of the diseased limb (p = 0.022) and the difference in PSV between the diseased and contralateral limbs (p = 0.003) showed significant differences. The vascular parameters of the proximal peripheral arteries of limbs owing to tumor burden differ significantly between the diseased and contralateral normal limbs. For individuals with osteogenic sarcoma who still have a higher difference in PSV between the diseased and contralateral limbs after chemotherapy, another course of chemotherapy after surgery and close follow-up should be considered.
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What is Visualize?

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

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

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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.