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Find video protocols related to scientific articles indexed in Pubmed.
Risk Factors for Malignancy in Branched-Type Intraductal Papillary Mucinous Neoplasms of the Pancreas During the Follow-Up Period.
World J Surg
PUBLISHED: 10-08-2014
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The international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas were revised in 2012 Tanaka (Pancreatology 12(3):183-197, 2012), making the indications for operation less aggressive. Therefore, the number of branch duct-type IPMN (BD-IPMN) patients requiring follow-up care is expected to increase in the future.
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Recurrence patterns of esophagogastric junction adenocarcinoma according to Siewert's classification after radical resection.
Anticancer Res.
PUBLISHED: 07-31-2014
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The treatment strategy for adenocarcinoma of the esophagogastric junction (AEG) remains controversial. In the present study, the recurrence pattern of AEGs according to Siewert's classification after radical resection was reviewed, and predictive factors of recurrence were examined.
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Usefulness of resection for hepatocellular carcinoma with macroscopic bile duct tumor thrombus.
Anticancer Res.
PUBLISHED: 07-31-2014
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The prognostic significance of bile duct tumor thrombus (BDTT) in hepatocellular carcinoma (HCC) is unclear and the usefulness of resection for HCC with BDTT is still controversial. The aim of the present study was to evaluate the impact of BDTT on prognosis in HCC and to determine whether resection of HCC with BDTT was useful.
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Allo-antigen stimulated CD8+ T-cells suppress NF-?B and Ets-1 DNA binding activity, and inhibit phosphorylated NF-?B p65 nuclear localization in CD4+ T-cells.
Viral Immunol.
PUBLISHED: 05-20-2014
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CD8+ T-cells of asymptomatic HIV-1 carriers (AC) suppress human immunodeficiency virus type 1 (HIV-1) replication in a class I major histocompatibility complex (MHC-I)-restricted and -unrestricted manner. In order to investigate the mechanism of MHC-I-unrestricted CD8+ T-cell-mediated HIV-1 suppression, we previously established allo-antigen stimulated CD8+T-cells from HIV-1-uninfected donors. These allo-antigen stimulated CD8+ T-cells suppressed HIV-1 replication in acutely infected autologous CD4+ T-cells when directly co-cultured. To elucidate the mechanism of HIV-1 replication suppression, we analyzed DNA-binding activity and phosphorylation of transcriptional factors associated with HIV-1 replication by electrophoresis mobility shift assay and Western blotting. When CD4+ T-cells were cultured with allo-antigen stimulated CD8+ T-cells, the reduction of NF-?B and Ets-1 DNA-binding activity was observed. Nuclear localization of NF-?B p65 and Ets-1 was suppressed in CD4+ T-cells. Although NF-?B p65 and Ets-1 are known to be regulated by protein kinase A (PKA), no difference was observed in the expression and phosphorylation of the PKA catalytic subunit in CD4+ T-cells cultured with PHA-treated CD8+ T-cells or allo-antigen stimulated CD8+ T-cells. Cyclic AMP is also known to enter through gap junctions, but the suppression of HIV-1 replication mediated by allo-antigen stimulated CD8+ T-cells was not affected by the gap junction inhibitor. The nuclear transport of phosphorylated NF-?B p65 (Ser276) was inhibited only in CD4+ T-cells cultured with allo-antigen stimulated CD8+ T-cells. Our results indicate that allo-antigen stimulated CD8+ T-cells suppress the transcriptional activity of NF-?B p65 or Ets-1 in an antigen-nonspecific manner, and inhibit the nuclear transport of phosphorylated NF-?B p65 (Ser276).
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The differentiation effect of low-dose cytosine arabinoside is disturbed in PU.1-knockdown K562 cells.
Biomed Rep
PUBLISHED: 03-13-2014
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We recently demonstrated by using PU.1-knockdown K562 (K562 PU.1KD) cells stably expressing PU.1 short inhibitory RNAs and PU.1-overexpressing K562 (K562 PU.1OE) cells, that therapeutic concentrations of 5-aza-2'-deoxycytidine (5-azadC) induce erythroid differentiation of these cells and that the PU.1 expression level is closely associated with the differentiating and apoptotic effects of 5-azadC on K562 cells. In this study, we investigated whether the effects of low-dose cytosine arabinoside (Ara-C), which is another erythroid differentiation inducer in K562 cells, is associated with the expression level of PU.1 in these cells. As a result, we demonstrated that the effect of Ara-C on cell viability and differentiation, as determined by the WST-8 assay and ?-globin mRNA expression analysis, respectively, was suppressed in K562 PU.1KD cells compared to their controls. Collectively, these findings suggest that sufficient expression of PU.1 is indispensable for the erythroid differentiation of K562 cells.
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Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas.
Eur. J. Cancer
PUBLISHED: 03-11-2014
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Neural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC.
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Surgical procedure depending on the depth of tumor invasion in duodenal cancer.
Jpn. J. Clin. Oncol.
PUBLISHED: 01-26-2014
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Duodenal cancer excluding Vater's papilla cancer is a relatively rare disease entity; therefore, the most appropriate operative methods depending on the tumor condition, such as the tumor site and/or depth of invasion, still remain unclear. The aim of this study is to determine an appropriate operative method and an appropriate extent of lymph node dissection depending on tumor site or tumor invasion depth.
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A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation.
PLoS ONE
PUBLISHED: 01-01-2014
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We recently revealed that myeloid master regulator SPI1/PU.1 directly represses metallothionein (MT) 1G through its epigenetic activity of PU.1, but the functions of MT1G in myeloid differentiation remain unknown. To clarify this, we established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE) cells, and investigated whether MT1G functionally contributes to all-trans retinoic acid (ATRA)-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by ATRA were significantly attenuated in NB4MTOE cells. Morphological examination revealed that the percentages of differentiated cells induced by ATRA were reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we observed a decrease in G1 accumulation, as well as decreases in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue tetrazolium (NBT) reduction assays revealed that the proportions of NBT-positive cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray analyses showed that the changes in expression of several myeloid differentiation-related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic factor 2 and oncostatin M) induced by ATRA were disturbed in NB4MTOE cells. Collectively, overexpression of MT1G inhibits the proper differentiation of myeloid cells.
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Infection control for prevention of pancreatic fistula after pancreaticoduodenectomy.
Hepatogastroenterology
PUBLISHED: 06-05-2013
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Effectiveness of infection control for prevention of pancreatic fistula (PF) after pancreaticoduodenectomy (PD) is not clear. We analyzed the impact of infection on the development of PF and examined the effect of enhanced infection control to prevent PF.
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Role of adjuvant surgery for patients with initially unresectable pancreatic cancer with a long-term favorable response to non-surgical anti-cancer treatments: results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pan
J Hepatobiliary Pancreat Sci
PUBLISHED: 05-11-2013
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PURPOSE: A multicenter survey was conducted to explore the role of adjuvant surgery for initially unresectable pancreatic cancer with a long-term favorable response to non-surgical cancer treatments. METHODS: Clinical data including overall survival were retrospectively compared between 58 initially unresectable pancreatic cancer patients who underwent adjuvant surgery with a favorable response to non-surgical cancer treatments over 6 months after the initial treatment and 101 patients who did not undergo adjuvant surgery because of either unchanged unresectability, a poor performance status, and/or the patients or surgeons wishes. RESULTS: Overall mortality and morbidity were 1.7 and 47 % in the adjuvant surgery group. The survival curve in the adjuvant surgery group was significantly better than in the control group (p < 0.0001). The propensity score analysis revealed that adjuvant surgery was a significant independent prognostic variable with an adjusted hazard ratio (95 % confidence interval) of 0.569 (0.36-0.89). Subgroup analysis according to the time from initial treatment to surgical resection showed a significant favorable difference in the overall survival in patients who underwent adjuvant surgery over 240 days after the initial treatment. CONCLUSION: Adjuvant surgery for initially unresectable pancreatic cancer patients can be a safe and effective treatment. The overall survival rate from the initial treatment is extremely high, especially in patients who received non-surgical anti-cancer treatment for more than 240 days.
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Schematic pancreatic configuration: a risk assessment for postoperative pancreatic fistula after pancreaticoduodenectomy.
J. Gastrointest. Surg.
PUBLISHED: 04-30-2013
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Postoperative pancreatic fistula (POPF) remains a serious complication after pancreaticoduodenectomy (PD). Preoperative risk assessment of POPF is desirable in careful preparation for operation. The aim of this study was to assess simple and accurate risk factors for clinically relevant POPF based on a schematic understanding of the pancreatic configuration using preoperative multidetector computed tomography.
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Epigenetic regulation of the metallothionein-1A promoter by PU.1 during differentiation of THP-1 cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-04-2013
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We recently demonstrated that metallothionein (MT)-1 A is a direct target gene negatively regulated by PU.1. In this study, we revealed that the expression of PU.1 was increased and accompanied by downregulation of MT-1A expression during TPA-induced THP-1 monocyte differentiation. Chromatin immunoprecipitation (ChIP) analysis demonstrated that PU.1 and the methyl CpG binding protein (MeCP) 2 bound to the same -887 to -602 region in the MT-1A promoter, and the binding of these proteins to this promoter was enhanced during differentiation. Consistently, bisulfite sequencing analyses around this region revealed that the proportion of methylated CpG sites was obivously increased during differentiation. In addition, ChIP analysis demonstrated that acetylated histone H4 around this region tended to be reduced and this may also play a role in the reduction of MT-1A expression during differentiation. Taken together, these findings suggest that MT-1A is epigenetically regulated by PU.1 during monocytic differentiation.
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Risk factor analysis and prevention of postoperative pancreatic fistula after distal pancreatectomy with stapler use.
J Hepatobiliary Pancreat Sci
PUBLISHED: 02-23-2013
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Postoperative pancreatic fistula (POPF) is a major, intractable complication after distal pancreatectomy (DP). Risk factor evaluation and prevention of this complication are important tasks for pancreatic surgeons.
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Epigenetic aberrations in myeloid malignancies (Review).
Int. J. Mol. Med.
PUBLISHED: 02-15-2013
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The development of novel technologies, such as massively parallel DNA sequencing, has led to the identification of several novel recurrent gene mutations, such as DNA methyltransferase (Dnmt)3a, ten-eleven-translocation oncogene family member 2 (TET2), isocitrate dehydrogenase (IDH)1/2, additional sex comb-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX) mutations in acute myeloid leukemia (AML) and other myeloid malignancies. These findings strongly suggest a link between recurrent genetic alterations and aberrant epigenetic regulations, resulting from an abnormal DNA methylation and histone modification status. This review focuses on the current findings of aberrant epigenetic signatures by these newly described genetic alterations. Moreover, epigenetic aberrations resulting from transcription factor aberrations, such as mixed lineage leukemia (MLL) rearrangement, ecotropic viral integration site 1 (Evi1) overexpression, chromosomal translocations and the downregulation of PU.1 are also described.
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Limited subtotal gastrectomy for early remnant gastric cancer.
Gastric Cancer
PUBLISHED: 02-09-2013
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Detection of early remnant gastric cancer (ERGC) is increasing as a result of the development of endoscopic technology and a surveillance program. The aim of this study was to evaluate the results of limited subtotal gastrectomy (SG) surgery for ERGC compared to total gastrectomy (TG).
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Pancreatic resection for metastatic melanoma originating from the nasal cavity: a case report and literature review.
Anticancer Res.
PUBLISHED: 02-09-2013
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Metastatic pancreatic malignant melanoma is considered to be a highly aggressive neoplasm, and only few metastasectomies for lesions originating from the skin or the ocular region have been reported. We report a case of resection of pancreatic metastasis of malignant melanoma originating from the nasal cavity. An isolated pancreatic tumor was detected in a 46-year-old man who had undergone proton-beam therapy for nasal melanoma 12 months earlier. He underwent distal pancreatectomy with splenectomy and the pathological diagnosis was metastatic malignant melanoma. We review cases of malignant melanoma metastatic to the pancreas and further discuss their incidence, therapeutic strategy, and outcome of mucosal melanoma of the head and neck.
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Short-term outcome of total laparoscopic distal gastrectomy for overweight and obese patients with gastric cancer.
Surg Endosc
PUBLISHED: 02-07-2013
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Laparoscopic distal gastrectomy for gastric cancer has been firmly established in recent decades but still is a difficult procedure, especially for obese patients, as with open surgery. This study aimed to evaluate the perioperative outcome of total laparoscopic distal gastrectomy (TLDG) for early gastric cancer patients with a body mass index (BMI) exceeding 25 kg/m(2) and to consider countermeasures to this.
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Efficacy of the predicted operation time (POT) strategy for synchronous colorectal liver metastasis (SCLM): feasibility study for staged resection in patients with a long POT.
J. Gastrointest. Surg.
PUBLISHED: 01-30-2013
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The optimal surgical strategy for resectable synchronous colorectal liver metastases (SCLM), whether simultaneous or staged resections, still remains obscure. The aim of this study was to assess the efficacy of the predicted operation time (POT) strategy, which recommends staged resections in case of POT ?6 h, otherwise selecting simultaneous resection.
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Predictors for early recurrence after hepatectomy for initially unresectable colorectal liver metastasis.
J. Gastrointest. Surg.
PUBLISHED: 01-30-2013
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Early recurrence correlates with poor survival following various cancer surgeries and puts considerable stress on patients both physically and mentally. This retrospective study investigated the predictive factors for early recurrence after surgical resection for initially unresectable colorectal liver metastasis to elucidate indications for conversion strategies.
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Surgical management for the reduction of postoperative hospital stay following distal pancreatectomy.
Hepatogastroenterology
PUBLISHED: 09-23-2011
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Pancreatic fistula remains a major cause of postoperative morbidity in patients undergoing pancreatectomy and is generally difficult to cure. None of the several surgical techniques and devices available for managing pancreatic remnant have been clinically evaluated.
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Reactive lymphoid hyperplasia of the liver: literature review and 3 case reports.
Hepatogastroenterology
PUBLISHED: 09-23-2011
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Reactive lymphoid hyperplasia (RLH) is a benign non-specific lesion having an unknown etiology and pathogenesis. The lesion is found in various organs but is rare in the liver. We report 3 cases of hepatic RLH associated with an extrahepatic malignant tumor. We also provide a literature review based on a search of the PubMed database from 1983 to 2009. The 3 cases showed radiological findings similar to those for malignant tumors and all cases were misdiagnosed as malignant tumors on the basis of these findings. It is difficult to distinguish RLH from malignant or metastatic tumors on the basis of imaging findings. Hepatic RLH is a rare entity and may cause a false diagnosis of malignancy. Because RLH occurs most commonly in middle-aged females, diagnosis of a hypervascular tumor of the liver requires particular care in these patients, especially if an extrahepatic malignancy is present.
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Predictive factors for anastomotic leakage after simultaneous resection of synchronous colorectal liver metastasis.
J. Gastrointest. Surg.
PUBLISHED: 09-15-2011
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The optimal surgical strategy for resectable, synchronous, colorectal liver metastases remains unclear. The objective of this study was to determine which patients could benefit from staged resections instead of simultaneous resection by identifying predictive factors for postoperative morbidity and anastomotic leakage after simultaneous resection of synchronous, colorectal liver metastases and the primary colorectal tumor.
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Predictive value of baseline neutrophil/lymphocyte ratio for T4 disease in wall-penetrating gastric cancer.
World J Surg
PUBLISHED: 09-14-2011
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Multimodality therapy has been used in the management of gastric cancer associated with locoregional spread. However, the accurate clinical staging still remains to be established. The neutrophil/lymphocyte ratio (NLR) in the peripheral blood is reported to be an easily assessable prognostic factor in cancer patients. We evaluated the predictive significance of the NLR and other serological parameters in patients with wall-penetrating gastric cancer.
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Correlation of PU.1 and signal regulatory protein ?1 expression in PU.1 transgenic K562 cells.
Int. J. Mol. Med.
PUBLISHED: 09-07-2011
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PU.1 is a key transcription factor for hematopoiesis and the reduction of this protein expression plays important roles in various hematological malignancies. To identify PU.1 downstream target genes, we recently reported dual microarray analyses, using PU.1 knockdown K562 (K562PU.1KD) cells stably expressing short inhibitory RNAs versus control cells and PU.1-overexpressing K562 (K562PU.1OE) cells versus control cells. Several PU.1 candidate target genes, including cell surface receptor, signal regulatory protein (SIRP) ?1, were identified. In this study, we revealed that the expression of SIRP?1 is positively correlated with the expression of PU.1 in various K562PU.1KD and K562PU.1OE cells, shown by real-time PCR and flow cytometry analyses. SIRP?1 is a negative regulator of signaling and its reduced expression is considered to play a role in the pathogenesis of hematological malignancies through the activation of downstream signaling pathways. By comparing 3 different clones of K562PU.1KD cells to their controls, we found constitutive phosphorylation of the extracellular signal-regulated kinase (ERK), but not of Akt, in these cells. Taken together, the down-regulation of PU.1 expression suppresses the expression of SIRP?1, which may play a role in the aberrant activation of ERK in these cells.
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Surgical outcomes of multicentric adenocarcinomas of the biliary tract.
Jpn. J. Clin. Oncol.
PUBLISHED: 08-31-2011
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In comparison to single biliary cancers, distinct features of biliary multicentric adenocarcinomas are not yet clear.
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Current findings for recurring mutations in acute myeloid leukemia.
J Hematol Oncol
PUBLISHED: 07-25-2011
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The development of acute myeloid leukemia (AML) is a multistep process that requires at least two genetic abnormalities for the development of the disease. The identification of genetic mutations in AML has greatly advanced our understanding of leukemogenesis. Recently, the use of novel technologies, such as massively parallel DNA sequencing or high-resolution single-nucleotide polymorphism arrays, has allowed the identification of several novel recurrent gene mutations in AML. The aim of this review is to summarize the current findings for the identification of these gene mutations (Dnmt, TET2, IDH1/2, NPM1, ASXL1, etc.), most of which are frequently found in cytogenetically normal AML. The cooperative interactions of these molecular aberrations and their interactions with class I/II mutations are presented. The prognostic and predictive significances of these aberrations are also reviewed.
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Influence of excess body weight on the surgical outcomes of total gastrectomy.
Surg. Today
PUBLISHED: 07-12-2011
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We conducted this retrospective study to identify the influence of excess body weight on the surgical outcome of total gastrectomy (TG) and to evaluate recent advances in this operation.
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Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes.
Int. J. Oncol.
PUBLISHED: 07-09-2011
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Glypican-3 (GPC3), a carcinoembryonic antigen, is an ideal target for anticancer immunotherapy against hepatocellular carcinoma (HCC). In this study, we attempted to compare the induction of the GPC3-specific T-cell-mediated immune response after locoregional therapies in HCC patients and tumor-bearing mice. Twenty-seven HCC patients treated with locoregional therapies, including radiofrequency ablation (RFA), surgical resection and transcatheter arterial chemo-embolization (TACE), were prospectively enrolled in this study. Additionally, we performed RFA experiments using a mouse model. GPC3-specific T-cell response was investigated pre-treatment and post-treatment by an interferon-? enzyme-linked immunospot assay using peripheral blood mononuclear cells from HCC patients and lymph node cells from tumor-bearing mice. Circulating GPC3-specific cytotoxic T lymphocytes (CTLs) were increased in 5 of 9 patients after RFA and in 4 of 9 patients after TACE, but in only 1 of 9 patients after surgical resection. All 7 patients with GPC3-expressing HCCs exhibited an increase in GPC3-specific CTLs after RFA or TACE, whereas none of the 7 patients did after surgical resection. The number of increased GPC3-specific CTLs after RFA was significantly larger than that after surgical resection (P=0.023). Similarly, the frequency of GPC3-specific CTLs after RFA was significantly greater than that after surgical resection in the mouse model (P=0.049). We validated for the first time the stronger effect on the immune system brought by RFA compared with surgical resection for HCC patients and tumor-bearing mice. Combined treatment of RFA and immunotherapy is a reasonable strategy against HCC.
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Regulatory mechanism of silkworm hemocyte adhesion to organs.
Zool. Sci.
PUBLISHED: 06-02-2011
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Circulating hemocytes in the body fluid of the silkworm are increased during the larval-larval molting period. We investigated hemocyte adhesion to organs mediating the selectin-selectin ligands during the feeding period and the larval-larval molting period using the lectin staining method, sugar chain digestion test with glycoside hydrolases, and the hemocyte adhesion inhibition test using monosaccharides. The results of these tests suggested that the selectin ligand involved in hemocyte adhesion was the Sialyl Lewis x-type, and the structure was changed from the feeding period to the larval-larval molting period. Beta-galactosidase appears to be an enzyme that eliminates N-acetylgalactosamine and sialylated N-acetylgalactosamine from the terminal of Sialyl Lewis x. Beta-galactosidase activation in skin basement membranes, muscle, fat bodies, midguts, and hemocytes increased markedly during the larval-larval molting period, and at that time, hemocytes were detached from organs. Adding 20-hydroxyecdysone or its analog, tebufenozide to cultured fat bodies increased ?-galactosidase activity in these tissues. Therefore, 20-hydroxyecdysone may induce a structural change in Sialyl Lewis x type sugar chains on the cell surface of silkworms organs by increasing the ?-galactosidase activity to detach hemocytes from organs and increase the number of circulating hemocytes during the larval-larval molting period.
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Clinicopathological features of stomach cancer with invasive micropapillary component.
Gastric Cancer
PUBLISHED: 05-11-2011
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Invasive micropapillary carcinoma has been recognized as a rare disease entity with aggressive tumor behavior. However, few reports have described invasive micropapillary carcinoma in the gastrointestinal tract, particularly its involvement in gastric cancer.
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Borderline resectable pancreatic cancer: rationale for multidisciplinary treatment.
J Hepatobiliary Pancreat Sci
PUBLISHED: 02-19-2011
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Borderline resectable pancreatic cancer (BRPC) appears to be most frequently related to a positive surgical margin and has a poor prognosis after resection. However, few reports are available on differences in tumor characteristics and prognoses among resectable pancreatic cancer (PC), BRPC, and unresectable PC.
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Surgical treatment of lymph node metastases from hepatocellular carcinoma.
J Hepatobiliary Pancreat Sci
PUBLISHED: 02-19-2011
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No consensus has been reached on the feasibility and efficacy of surgery for lymph node metastases (LNM) from hepatocellular carcinoma (HCC).
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Induction of ?-catenin by the suppression of signal regulatory protein ?1 in K562 cells.
Int. J. Mol. Med.
PUBLISHED: 02-04-2011
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The signal regulatory protein (SIRP) ?1 is a cell surface receptor expressed predominantly in monocytes, granulocytes, dendritic cells, as well as hematopoietic stem cells. In contrast, SIRP?1 expression is significantly reduced in the majority of myeloid malignancies. SIRP?1 is a negative regulator of signaling and its reduced expression is considered to play a role in the pathogenesis of these diseases through aberrant signaling. To identify SIRP?1 downstream target genes, we established SIRP ?1-knockdown chronic myeloid leukemia K562 (K562SIRP?1KD) cells expressing reduced levels of SIRP?1 by stably transfecting SIRP?1 siRNAs. Microarray analysis demonstrated that several genes, including ?-catenin, were significantly induced in K562SIRP?1KD cells. Real-time PCR and Western blot analyses, confirmed the induction of this gene. Phosphorylation of Ser9 of glycogen synthesis kinase (GSK) -3?, results in the inactivation of GSK-3?, leading to the induction of ?-catenin. We found significant phosphorylation of extracellular signal-regulated kinase (ERK), Akt, as well as of GSK-3?-Ser9, which may play a role in the up-regulation of ?-catenin in K562SIRP?1KD cells. To our knowledge, this is a first report demonstrating the relationships between SIRP?1 and ?-catenin in leukemia cells.
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Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications.
J Hematol Oncol
PUBLISHED: 01-31-2011
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FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells.
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Clinicopathological features and prognostic factors of adenocarcinoma of the esophagogastric junction according to Siewert classification: experiences at a single institution in Japan.
Ann. Surg. Oncol.
PUBLISHED: 01-14-2011
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Treatment strategy for adenocarcinoma of the esophagogastric junction (AEG) remains controversial. The aims of this study are to evaluate results of surgery for AEG, to clarify clinicopathological differences according to the Siewert classification, and to define prognostic factors.
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Intraductal tubular carcinoma of the pancreas: case report with review of literature.
Anticancer Res.
PUBLISHED: 12-01-2010
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A 67-year-old man presented with leg edema. Laboratory data showed elevated blood glucose and carbohydrate antigen (CA) 19-9 levels, and anemia. Further imaging studies revealed a relatively clear-margined tumor totally occupying the main pancreatic duct (MPD) from the head to the tail of the pancreas (maximum diameter 10 cm) without mucin hypersecretion. Total pancreatectomy with splenectomy and regional lymphadenectomy were performed. Intraductal tubular carcinoma (ITC) was diagnosed by immunohistochemical staining and electron microscopic examination. Previous reports showed that this tumor is characterized by slow growth, with a favorable prognosis and intraductal nodular growth occupying the MPD and no macroscopic mucus. Whether ITC should be distinguished from other types of pancreatic neoplasm is controversial, and the accumulation of more ITC cases and multi-institutional analysis are necessary to establish the diagnostic criteria and characteristics of this histological entity.
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Clinical and histopathological study of "follicular cholangitis": Sclerosing cholangitis with prominent lymphocytic infiltration masquerading as hilar cholangiocarcinoma.
Hepatol. Res.
PUBLISHED: 09-28-2010
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Aim:? Sclerosing cholangitis which mimic hilar biliary carcinoma have not been fully categorized. In this study, we investigated the clinicopathological features of sclerosing cholangitis of unknown origin, so-called "follicular cholangitis". Methods:? Patients who had undergone surgery of the proximal bile duct from 1993-2008 on suspicion of proximal bile carcinoma were evaluated. Of these, we investigated the cases compatible with follicular cholangitis. Then, we reviewed the previous reports of follicular cholangitis showing similar clinicopathological findings. Results:? Among 176 patients, two who were diagnosed with benign sclerosing cholangitis of unknown origin shared the common histopathological findings compatible with follicular cholangitis. Histopathological findings showed dense fibrosis with prominent lymph follicles and germinal centers, being appropriate for neither primary sclerosing cholangitis nor immunoglobulin G4-related sclerosing cholangitis. Review of previous published work revealed two other cases diagnosed with follicular cholangitis and showing histopathological findings similar to ours. All these cases were middle-aged patients with no history of autoimmune disease with focal strictures mainly involved in the hilar bile duct, mimicking hilar cholangiocarcinoma. Conclusion:? Benign sclerosing cholangitis has not been fully categorized, yet. Follicular cholangitis shows unique histopathological features and can be categorized as an independent entity.
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Combination therapy with arsenic trioxide for hematological malignancies.
Anticancer Agents Med Chem
PUBLISHED: 08-02-2010
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Arsenic trioxide (ATO) has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL). However, the risk/benefit ratios of ATO in hematologic malignancies other than APL are still unclear. In this review, the author attempts to provide current experimental and clinical challenges to gain more knowledge of the effects of ATO by examining combination therapies with other agents, especially for non-APL hematologic malignancies, such as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and multiple myeloma (MM). The drugs combined with ATO can be roughly classified into (1) signaling inhibitors (imatinib, PD184352, LY294002, 17-Allylamino-17-demethoxygeldanamycin: 17-AAG), (2) oxidative stress pathway modulators (ascorbic acid, 2-methoxyestradiol: 2-ME, dl-buthionine-[S,R]-sulfoximine: BSO), (3) a chemotherapeutic drug (melphalan) and (4) others (bortezomib, ATRA). Some of these combination therapies have shown promising results in MM not only at the experimental level but also at the clinical level. However, studies are still ongoing for other non-APL hematologic malignancies. Since ATO is well tolerated and its toxicities are manageable and reversible, cell type-specific and efficient combination therapies with ATO are advantageous for non-APL hematological malignancies and should be developed in the near future.
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Postoperative serum alpha-fetoprotein level is a useful predictor of recurrence after hepatectomy for hepatocellular carcinoma.
Oncol. Rep.
PUBLISHED: 07-03-2010
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We evaluated the clinical value of perioperative alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels in predicting recurrence of hepatocellular carcinoma (HCC) after curative resection, with a focus on the time course as surveillance tools. A total of 165 consecutive HCC patients who had undergone curative hepatectomy at our institution from 2005 to 2007 and whose serum AFP and DCP had been measured before and after hepatectomy were included in this study. The minimum postoperative levels within a 4-month period were used for analysis. Among the patients with a positive level of AFP before operation, the number of patients whose AFP level did not change from positive to negative after operation in the group with recurrence exceeded that in the group without recurrence (48/60, 80.0% vs. 4/23, 17.4%), and the difference was significant (P<0.001). Minimum postoperative AFP level was found to be a significant independent risk factor for recurrence by multivariate analysis (P<0.001). There was no statistically significant correlation between AFP level and grade of hepatitis activity (P=0.599). Postoperative AFP level is a useful tool for predicting recurrence after curative hepatectomy. A positive level of AFP after operation might suggest a site of residual viable cancer. The need for effective adjuvant therapy and close follow-up is suggested in patients with a positive postoperative AFP level.
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Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 06-03-2010
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To evaluate the safety and efficacy of radiotherapy using proton beam (PRT) for unresectable hepatocellular carcinoma.
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Aryl hydrocarbon receptor is a transcriptional activator of the human breast cancer resistance protein (BCRP/ABCG2).
Mol. Pharmacol.
PUBLISHED: 05-11-2010
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Breast cancer resistance protein (BCRP/ABCG2) is a membrane-bound efflux transporter important in cellular detoxification and multidrug resistance. Some aryl hydrocarbon receptor (AHR) agonists were reported to induce BCRP expression in human colon carcinoma cells. However, a direct involvement of AHR transcriptional regulation remains unexplored. In this study, we show that BCRP induction by AHR ligands occurs in human intestinal, liver, and mammary carcinoma cells and in primary colonocytes and hepatocytes. Increased BCRP transporter activity consistent with gene induction was also evident in the Caco2 subclone C2bbe1 cells. Using RNA interference and ectopic expression techniques to manipulate cellular AHR status, we confirmed AHR dependence of ABCG2 gene regulation. By gene promoter analysis, chromatin immunoprecipitation, and electrophoretic mobility shift assays, an active, proximal dioxin-response element at -194/-190 base pairs upstream of the transcription start site of the human ABCG2 gene was identified. Despite a common observation in human-derived cells, our in vitro and in vivo studies supported by phylogenetic footprinting analysis did not find that mouse Abcg2 is subject to AHR regulation. We conclude that AHR is a direct transcriptional regulator of human BCRP and provide an unprecedented role of AHR in cellular adaptive response and cytoprotection by up-regulating an important ATP-binding cassette efflux transporter.
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Metallothionein-1 isoforms and vimentin are direct PU.1 downstream target genes in leukemia cells.
J. Biol. Chem.
PUBLISHED: 02-05-2010
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PU.1 is a key transcription factor for hematopoiesis and plays important roles in various hematological malignancies. To clarify the molecular function of PU.1, we initially tried to identify bona fide target genes regulated by PU.1. Dual microarrays were employed for this study to compare PU.1-knockdown K562 cells (K562PU.1KD) stably expressing PU.1 short inhibitory RNAs versus control cells and PU.1-overexpressing K562 cells (K562PU.1OE) versus control cells. In these analyses, we found that several genes, including metallothionein (MT)-1 isoforms (MT-1G and MT-1A) and vimentin (VIM), were markedly induced while Jun dimerization protein (JDP) 2 was suppressed in K562PU.1KD cells. Furthermore, the mRNA expressions of the MT-1 and VIM genes were inversely correlated and the mRNA expression of JDP2 was positively correlated with PU.1 mRNA expression in 43 primary acute myeloid leukemia specimens (MT-1G: R = -0.50, p < 0.001; MT-1A: R = -0.58, p < 0.0005; VIM: R = -0.39, p < 0.01; and JDP2: R = 0.30, p < 0.05). Next, we analyzed the regulation of the MT-1 and VIM genes. We observed increased associations of acetylated histones H3 and H4 with the promoters of these genes in K562PU.1KD cells. Sequence analyses of the regions approximately 1 kb upstream from the transcription start sites of these genes revealed numerous CpG sites, which are potential targets for DNA methylation. Chromatin immunoprecipitation assays revealed that methyl CpG-binding protein 2 (MeCP2) and PU.1 bound to the CpG-rich regions in the MT-1 and VIM promoters. Bisulfite sequencing analyses of the PU.1-bound regions of these promoters revealed that the proportions of methylated CpG sites were tightly related to the PU.1 expression levels.
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Predictive factors improving survival after gastrectomy in gastric cancer patients with peritoneal carcinomatosis.
World J Surg
PUBLISHED: 01-19-2010
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The aim of this study was to review prognosis following gastrectomy for gastric cancer patients with synchronous peritoneal carcinomatosis and to identify predictive factors for improving survival after gastrectomy in this setting.
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Invasive micropapillary carcinoma of the ampulla of Vater with extensive lymph node metastasis: Report of a case.
Surg. Today
PUBLISHED: 01-06-2010
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Invasive micropapillary carcinoma is characterized by extensive lymph node metastasis and a poor prognosis. This histological variant was first described in breast cancer, with a few subsequent reports of it in the ampullo-pancreato-biliary region. We report a case of invasive micropapillary carcinoma of the papilla of Vater. A 53-year-old man was admitted to our hospital with signs of obstructive jaundice. Detailed investigations revealed a tumor in the periampullary region, and pancreatoduodenectomy was performed for cancer of the ampulla of Vater. Microscopic examination of the resected specimen revealed a tumor composed mainly of carcinoma cells arranged in micropapillary structures, with extensive regional lymph node metastasis. The patient had an uneventful postoperative course and was followed up in the outpatient clinic. Tumor recurrence with progressive ascites and hydronephrosis was found 8 months after surgery, and the patient died of the disease 20 months after surgery.
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FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-16-2009
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Fms-related tyrosine kinase 3-internal tandem duplications (FLT3-ITD) are strongly associated with the refractory nature of acute myeloid leukemia (AML) by the standard combined chemotherapy. FLT3-ITD-expressing murine and human myeloid cell lines, HF6/FLT3-ITD and K562/FLT3-ITD cells, respectively, were developed in order to clarify whether FLT3-ITD is involved in the resistance to cytotoxic agents in AML. Both of these cell lines were specifically resistant to the pyrimidine analogue cytosine arabinoside (ara-C), an essential agent for AML, accompanied by the downregulation of equilibrative nucleoside transporter 1 (ENT1), a transporter responsible for the cellular uptake of ara-C. The ENT1 promoter activity and the cellular uptake of ara-C were reduced in K562/FLT3-ITD cells, and rescued by pretreating the cells with PKC412, a FLT3 inhibitor. In addition, the expression of hypoxia inducible factor 1 alpha subunit (HIF1A) transcripts was upregulated in K562/FLT3-ITD cells, and the induction of HIF-1alpha reduced the promoter activity of ENT1 gene in K562 cells. Taken together, these findings suggest that FLT3-ITD specifically induces ara-C resistance in leukemic cells by the repression of ENT1 expression, possibly through the upregulation of HIF-1alpha, while also partially accounting for the poor prognosis of AML with FLT3-ITD due to resistance to the standard chemotherapy protocols which include ara-C.
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Clinical and histopathological features of remnant gastric cancers, after gastrectomy for synchronous multiple gastric cancers.
J Surg Oncol
PUBLISHED: 08-05-2009
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Remnant gastric cancers have been extensively investigated; however, little has been unveiled the features of remnant gastric cancers with regard to the existence of synchronous multiple lesions. We evaluated the clinicopathological features of remnant gastric cancers, after initial gastrectomy for both single and multiple gastric cancers.
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Inferior head resection of the pancreas for intraductal papillary mucinous neoplasms.
J Hepatobiliary Pancreat Sci
PUBLISHED: 07-01-2009
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Previous reports have suggested that patients with intraductal papillary mucinous neoplasm (IPMN) have a favorable prognosis after surgical resection. Thus, a variety of types of partial pancreatic resections have been advocated for treating these low-grade malignant tumors. However, the surgical outcome of IPMN after such limited pancreatectomy has not been fully clarified.
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Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma.
Cancer Sci.
PUBLISHED: 05-04-2009
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The relationship between overexpression of glypican (GPC)-3 that is specific for hepatocellular carcinoma (HCC) and the prognosis has not yet been clarified. We attempted to determine the expression profile of GPC3 in association with the clinicopathological factors by immunohistochemical analysis in HCC patients and investigated the potential prognostic value of GPC3 by comparing the survival rate between the GPC3-positive and GPC3-negative HCC patients. Primary HCC tissue samples (n = 107) obtained from patients who had undergone hepatectomy between 2000 and 2001 were analyzed. GPC3 expression was less frequently observed in well-differentiated HCC than in moderately and poorly differentiated HCC, the difference in the frequency being statistically significant. GPC3-positive HCC patients had a significantly lower 5-year survival rate than the GPC3-negative HCC patients (54.5 vs 87.7%, P = 0.031). Among 80 of the 107 (74.6%) patients with initial treatment who underwent hepatectomy, none of GPC3-negative HCC patients (n = 16, 20.0%) died during the follow-up period. No deaths were noted in the GPC3-negative HCC patients among the 71 (88.7%) patients with moderately and poorly differentiated HCC. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for the overall survival. We showed that GPC3 expression is correlated with a poor prognosis in HCC patients.
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Risk factors of surgical site infection after hepatectomy for liver cancers.
World J Surg
PUBLISHED: 04-17-2009
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Risk factors of surgical site infection (SSI) after hepatectomy under the guideline of Centers for Disease Control and Prevention (CDC) are not well examined.
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The p38 pathway inhibitor SB202190 activates MEK/MAPK to stimulate the growth of leukemia cells.
Leuk. Res.
PUBLISHED: 04-07-2009
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In this study, the biological effects of signal transduction inhibitors on leukemia cells were examined. We found that the p38 inhibitor SB202190 enhanced the growth of THP-1 and MV4-11 cells. To determine the pathway affected by SB202190, we examined the 50% effective dose (ED(50)) values for THP-1 cell growth in combination with several inhibitors. In the presence of SB202190, the ED(50) values for the farnesyltransferase inhibitor FPT inhibitor II and MEK inhibitor U0126 were significantly decreased. Western blot analysis revealed that SB202190 increased the phosphorylation of C-Raf and extracellular regulated kinase (ERK), suggesting that Ras-Raf-MEK-mitogen-activated protein kinase (MAPK) pathway activation is involved in the leukemia cell growth induced by SB202190.
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Anesthetic management for ascending aorta replacement in a patient who refused autologous transfusion for religious reasons.
J Anesth
PUBLISHED: 03-13-2009
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We report on the anesthetic management of a 69-year-old female Jehovahs Witness undergoing cardiopulmonary bypass to replace the ascending aorta; the patient refused transfusion of stored autologous or allogeneic blood products for religious reasons. The strategy involved preoperative hematopoiesis with recombinant human erythropoietin and iron, intraoperative acute normovolemic hemodilution, the use of a cell-saver system, administration of high-dose tranexamic acid, controlled hypotension, avoidance of low body temperature, simplification of the surgery, and lower blood dilution during cardiopulmonary bypass.
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Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer.
Int. J. Oncol.
PUBLISHED: 02-13-2009
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Primary liver cancers are classified into three types based on their morphology and cytogenetic characteristics hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (CHC). It is often difficult to distinguish these liver tumors. Glypican-3 (GPC3) is serological and histochemical marker of hepatocellular carcinoma. In order to separate these three types of liver cancers, we analyzed the GPC3 expression in 85 liver resection specimens, including 46 HCCs, 28 ICCs and 11 CHCs. GPC3 immunohistochemical staining was used to distinguish HCC from ICC by comparing with the conventional biomarker, alpha-fetoprotein (AFP). The immunostaining of GPC3 was identified in 78.3% (36/46) of HCCs, 60% (9/15) of well differentiated, 88.9% (16/18) of moderately differentiated and 84.6% (11/13) of poorly differentiated HCCs. It was negative in the ICCs. We confirmed that GPC3 expression is specific to HCC component (8/11, 72.7%) but few samples also showed weakly in ICC component (2/11, 18.2%) of CHC sections among 11 cases compared with HCC biomarkers including AFP and hepatocyto paraffin 1 (HepPar1), and ICC biomarkers cytokeratin (CK) 7 and CK19. Three cases in which the macroscopic features resembled ICC did not express GPC3 even in the pathological HCC component. Most (10/11, 91%) of the pathological cholangiocarcinoma components in CHC showed positive staining for CK7 and CK19. The results of this study suggest that GPC3 is a biomarker that is sensitive and specific to HCC component of CHC, and CK7 and CK19 are markers for pathological cholangiocarcinoma component of CHC.
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Incidence, clinical presentation and pathological features of benign sclerosing cholangitis of unknown origin masquerading as biliary carcinoma.
J Hepatobiliary Pancreat Sci
PUBLISHED: 01-25-2009
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Benign obstructions of the liver hilum are occasionally encountered in surgically resected cases. Some of these cases are pathologically classified as benign sclerosing cholangitis and are not clearly categorized. This study aims to elucidate the clinicopathological features of benign sclerosing cholangitis of unknown origin.
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Identification of annexin 1 as a PU.1 target gene in leukemia cells.
Leuk. Res.
PUBLISHED: 01-19-2009
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To identify PU.1 downstream target genes, we first established PU.1-knockdown K562 (K562PU.1KD) cells expressing reduced levels of PU.1 by stably transfected PU.1 siRNAs. From microarray analysis, we found that several genes including annexin 1 were markedly induced in K562PU.1KD cells. Annexin 1 is a calcium- and phospholipid-binding protein and increased expression leads to the constitutive activation of extracellular signal-regulated kinase (ERK). Consistent with this, we observed constitutive activation of ERK in K562PU.1KD cells. Furthermore, we revealed the mRNA expression of annexin 1 was negatively correlated with PU.1 mRNA expression in 43 primary AML specimens (R=-0.31, p<0.042).
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Salinity affects the photoacclimation of Chlamydomonas raudensis Ettl UWO241.
Photosyn. Res.
PUBLISHED: 01-10-2009
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Chlamydomonas raudensis Ettl UWO241, a natural variant of C. raudensis, is deficient in state transitions. Its habitat, the deepest layer of Lake Bonney in Antarctica, features low irradiance, low temperature, and high salinity. Although psychrophily and low-light acclimation of this green alga has been described, very little information is available on the effect of salinity. Here, we demonstrate that this psychrophile is halotolerant, not halophilic, and it shows energy redistribution between photosystem I and II based on energy spillover under low-salt conditions. Furthermore, we revealed that C. raudensis exhibits higher non-photochemical quenching in comparison with the mesophile Chlamydomonas reinhardtii, when grown with low-salt, which is due to the lower proton conductivity across the thylakoid membrane. Significance of the C. raudensis UWO241 traits found in the low salinity culture are implicated with their natural habitats, including the high salinity and extremely stable light environments.
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Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
PLoS ONE
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Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10) and idiopathic thrombocytopenic purpura (n = 13), and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01). Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.
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Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head.
Cancer Sci.
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Tumor-associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumor-associated macrophages can be affected by cancer-related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM-related factors and the clinical impact of TAMs. CD68 (a pan-macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease-free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC.
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Laparoscopic transhiatal resection for Siewert type II adenocarcinoma of the esophagogastric junction: operative technique and initial results.
Surg Laparosc Endosc Percutan Tech
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Laparoscopic distal gastrectomy has gained wide acceptance, and laparoscopic total gastrectomy (LTG) and laparoscopic proximal gastrectomy (LPG) are now also performed for gastric cancer. We extended these techniques to treat Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Ten patients with clinical T1 AEG type II underwent laparoscopic transhiatal (LTH) resection combined with LTG reconstructed by Roux-en-Y (LTH+LTG: n=2) or LPG reconstructed by jejunal interposition (LTH+LPG: n=8). Intracorporeal esophagojejunostomy was performed using a circular stapler, of which the anvil head was introduced transabdominally or transorally. The median operation time was 243 minutes, and blood loss was 25.5 g. There were no intraoperative complications or conversion to open surgery. No anastomotic leak was observed, but 1 diaphragmatic herniation to the left thoracic cavity occurred postoperatively. The median length of the proximal margin was 14.5 mm. This operation is technically feasible and can be safely performed after adequate experience of LTG or LPG, though esophagojejunostomy in the mediastinum is technically demanding.
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Molecular functions of metallothionein and its role in hematological malignancies.
J Hematol Oncol
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Metallothionein (MT) was reported to be a potential negative regulator of apoptosis, and various reports have suggested that it may play roles in carcinogenesis and drug resistance, in at least a portion of cancer cells. The author summarizes the current understanding of the molecular functions of MT for tumor cell growth and drug resistance. These activities are regulated through intracellular metal ion modulation and free radical scavenging. Compared with analyses of solid tumors, few studies have analyzed the roles of MT in hematological malignancies. This review mainly describes the functions of MT in hematopoietic cells. Furthermore, through expression analyses of leukemias and lymphomas, the roles of MT in the biology of these diseases are particularly focused upon.
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Intraductal oncocytic papillary neoplasm of the extrahepatic bile duct: report of a case.
Surg. Today
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We report a rare case of an intraductal oncocytic papillary neoplasm (IOPN) of the extrahepatic bile duct. A 66-year-old man was admitted to our hospital for investigation of right-sided back pain. Ultrasonography, computed tomography and magnetic resonance imaging showed a papillary lesion, 3 cm in diameter, in the middle bile duct, invaginating into the cystic duct. We made a provisional diagnosis of middle bile duct cancer and performed substomach-preserving pancreatoduodenectomy. Macroscopically, the middle bile duct contained a two-humped papillary tumor, one tip of which invaginated into the cystic duct. Microscopically, the tumor consisted of cuboidal cells with abundant eosinophilic cytoplasm resembling that of oncocytes and a fine fibrovascular core. The tumor cells were stained strongly with antimitochondria antibody. Based on these findings, the tumor was diagnosed histologically as IOPN of the extrahepatic bile duct. The patient died of prostate cancer 51 months after surgery, but without evidence of recurrence of the IOPN.
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Laparoscopic proximal gastrectomy with jejunal interposition for gastric cancer in the proximal third of the stomach: a retrospective comparison with open surgery.
Surg Endosc
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The incidence of cancer in the proximal third of the stomach is increasing. Laparoscopic proximal gastrectomy (LPG) seems an attractive option for the treatment of early-stage proximal gastric cancer but has not gained wide acceptance because of technical difficulties, including the prevention of severe reflux. In this study, we describe our technique for LPG with jejunal interposition (LPG-IP) and evaluate its safety and feasibility.
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Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival.
Clin. Cancer Res.
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The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC.
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Surgical outcome of liver transection by the crush-clamping technique combined with Harmonic FOCUS™.
World J Surg
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New energy devices are constantly being introduced for all types of surgery, including liver surgery. These devices help surgeons perform operations. Meanwhile, intraoperative blood loss is a concern of liver surgeons. Various methods to reduce intraoperative bleeding during liver resection have been reported. There are some reports that the use of energy devices was effective for liver transection. Recently, the Harmonic FOCUS™ (HF), an ultrasonically activated device, was developed. The shape of the HF is similar to that of Kelly forceps. Hepatectomy can be performed by the clamp-crushing method using the HF instead of Kelly forceps. We obtained good results of liver resection with the HF, and report these outcomes in this study.
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Role of misfolded N-CoR mediated transcriptional deregulation of Flt3 in acute monocytic leukemia (AML)-M5 subtype.
PLoS ONE
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The nuclear receptor co-repressor (N-CoR) is a key component of the generic multi-protein complex involved in transcriptional control. Flt3, a key regulator of hematopoietic cell growth, is frequently deregulated in AML (acute myeloid leukemia). Here, we report that loss of N-CoR-mediated transcriptional control of Flt3 due to misfolding, contributes to malignant growth in AML of the M5 subtype (AML-M5). An analysis of hematopoietic genes in AML cells led to the identification of Flt3 as a transcriptional target of N-CoR. Flt3 level was inversely related to N-CoR status in various leukemia cells. N-CoR was associated with the Flt3 promoter in-vivo, and a reporter driven by the Flt3 promoter was effectively repressed by N-CoR. Blocking N-CoR loss with Genistein; an inhibitor of N-CoR misfolding, significantly down-regulated Flt3 levels regardless of the Flt3 receptor mutational status and promoted the differentiation of AML-M5 cells. While stimulation of the Flt3 receptor with the Flt3 ligand triggered N-CoR loss, Flt3 antibody mediated blockade of Flt3 ligand-receptor binding led to N-CoR stabilization. Genetic ablation of N-CoR potentiated Flt3 ligand induced proliferation of BA/F3 cells. These findings suggest that N-CoR-induced repression of Flt3 might be crucial for limiting the contribution of the Flt3 signaling pathway on the growth potential of leukemic cells and its deregulation due to N-CoR loss in AML-M5, could contribute to malignant growth by conferring a proliferative advantage to the leukemic blasts. Therapeutic restoration of N-CoR function could thus be a useful approach in restricting the contribution of the Flt3 signaling pathway in AML-M5 pathogenesis.
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The differentiating and apoptotic effects of 2-aza-5-deoxycytidine are dependent on the PU.1 expression level in PU.1-transgenic K562 cells.
Biochem. Biophys. Res. Commun.
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The use of 5-aza-2-deoxycytidine (5-azadc) for myelodysplastic syndrome, acute myeloid leukemia and chronic myeloid leukemia is becoming an effective and attractive option for these hematological malignancies. The PU.1 transcription factor is important for cellular differentiation through the control of its target genes not only in myeloid and B-lymphoid cells, but also in erythroid cells. Downregulation of PU.1 was reported to play a role in the pathogenesis of various hematological malignancies. In this study, we sought to identify the relationship between the effects of 5-azadc and PU.1. For this purpose, we employed PU.1-knockdown K562 (K562 PU.1KD) cells stably expressing PU.1 short inhibitory RNAs and PU.1-overexpressing K562 (K562 PU.1OE) cells. Therapeutic concentrations (0.1 and 0.5 ?M) of 5-azadc resulted in growth arrest in the G2/M phase. Strikingly, however, K562 PU.1OE cells had significantly increased rates of G2/M and apoptotic sub-G1 phase cells. We observed the induction of cyclin B1, a regulator of the G2/M transition, after the addition of 5-azadc. This induction was abolished in K562 PU.1KD cells, but significantly induced in K562 PU.1OE cells. Further analyses revealed potent induction of hemoglobin A1 expression in K562 PU.1OE cells. Taken together, these findings suggest that the PU.1 expression level is tightly related to the differentiating and apoptotic effects of 5-azadc in K562 cells.
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