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Find video protocols related to scientific articles indexed in Pubmed.
Expression of glucagon-like Peptide 1 receptor and its effects on biologic behavior in pancreatic neuroendocrine tumors.
Pancreas
PUBLISHED: 08-16-2014
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Glucagon-like peptide 1 (GLP-1) interacts with its specific high-affinity receptor, glucagon-like peptide 1 receptor (GLP-1R), and induces cellular growth and inhibition of apoptosis in pancreatic ? cells. The aim of this study was to investigate the significance of GLP-1R expression in pancreatic neuroendocrine tumors (PNETs).
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Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion.
Ann. Surg. Oncol.
PUBLISHED: 04-19-2014
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Micro RNAs (miRNAs) are small noncoding RNAs that have gained attention as key molecules in the malignant characteristics of cancers, and several recent investigations also have identified some miRNAs as potential key regulators to inhibit the malignant characteristics of tumors. MiRNA-373 (miR-373) has recently been reported to induce E-cadherin, which is a key regulator of epithelial-mesenchymal transition (EMT). However, the role of miR-373 in the characteristics of cancer cells is not still well known.
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Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer.
Int. J. Oncol.
PUBLISHED: 04-16-2014
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Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.
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Technical feasibility of laparoscopic total gastrectomy with splenectomy for gastric cancer: clinical short-term and long-term outcomes.
Surg Endosc
PUBLISHED: 04-04-2014
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Since its widespread acceptance for the treatment of early gastric cancer, laparoscopic gastrectomy has been gaining popularity as a treatment option for advanced gastric cancer. However, laparoscopic total gastrectomy (LTG) with splenectomy is seldom performed, because of its difficulty of removal of station 10 lymph nodes; splenectomy is technically essential for complete removal of these lymph nodes. The purpose of this study was to describe the details of the LTG procedure and to evaluate the short- and long-term outcomes of LTG with splenectomy.
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Mass spectrometry-based metabolic profiling of gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells.
Pancreas
PUBLISHED: 02-13-2014
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Gemcitabine resistance (GR) is one of the critical issues for therapy for pancreatic cancer, but the mechanism still remains unclear. Our aim was to increase the understanding of GR by metabolic profiling approach.
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Podoplanin expression in the cyst wall correlates with the progression of intraductal papillary mucinous neoplasm.
Virchows Arch.
PUBLISHED: 02-05-2014
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A thickened, enhanced cyst wall on imaging examinations is one of the "worrisome features" described in the consensus guidelines for management of intraductal papillary mucinous neoplasm of the pancreas (IPMN). Podoplanin (PDPN) expression by cancer-associated fibroblasts is known to be an indicator of poor prognosis in some types of cancer. We performed immunohistochemical staining for alpha-smooth muscle actin (?-SMA) in IPMN lesions and determined the pathological wall thickness by measuring the thinnest and thickest ?-SMA-positive parts of the wall of the largest cyst in each case, and the mean of these two values was recorded as the wall thickness. The thickness of the pathological wall increased with progression from IPMN with low-grade dysplasia to IPMN with an invasive carcinoma. The pathological wall was thicker in IPMN with main duct involvement, nongastric-type IPMN, and IPMN with mural nodules. We also stained for PDPN and assessed the thickness of cyst wall staining as for ?-SMA. The thickness of the PDPN-positive cyst wall varied in a pattern similar to the thickness of the ?-SMA-positive pathological cyst wall. PDPN-positive stromal fibroblasts in the invasive component of IPMN-IC were evaluated as a ratio to ?-SMA-positive fibroblasts. A high ratio (>50 %) of PDPN-positive stromal fibroblasts was a predictor of poor outcome. PDPN expression in the cyst wall correlates with the progression of IPMN. PDPN may be a significant prognostic marker of IPMN-IC.
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Tissue tablet method: an efficient tissue banking procedure applicable to both molecular analysis and frozen tissue microarray.
Hum. Pathol.
PUBLISHED: 02-05-2014
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Frozen human tissues are necessary for research purposes, but tissue banking methods have not changed for more than a decade. Many institutions use cryovial tubes or plastic molds with an optimal cutting temperature compound. However, these methods are associated with several problems, such as samples sticking to one another and the need for a larger storing space. We established an efficient tissue freezing and storing procedure ("tissue tablet method") applicable to both molecular analysis and frozen tissue microarray. Tissue samples were chopped into tiny fragments and embedded into tablet-shaped frozen optimal cutting temperature compound using our original tissue-freezing plate. These tablets can be sectioned and stored in cryovial tubes. We compared the tissue quality of tablet-shaped samples with that of conventional optimal cutting temperature blocks and found no significant difference between them. Tissue microarray is a key method to utilize tissue-banking specimens. However, most tissue microarrays require the coring out of cylindrically shaped tissues from formalin-fixed, paraffin-embedded tissue blocks. Antigenic changes and mRNA degradation are frequently observed with formalin-fixed, paraffin-embedded samples. Therefore, we have applied tablet-shaped samples to construct frozen tissue microarrays with our original mounting base. Constructed tissue microarray sections showed good morphology without obvious artifact and good immunohistochemistry and in situ hybridization results. These results suggest that the quality of arrayed samples was sufficiently appropriate for research purposes. In conclusion, the tissue tablet method and frozen tissue microarray procedure can save time, provides easy tissue handling and processing, and satisfies the demands of research methodologies and tissue banking.
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Objective assessment of the suture ligature method for the laparoscopic intestinal anastomosis model using a new computerized system.
Surg Endosc
PUBLISHED: 01-22-2014
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The purpose of this study was to develop a new objective assessment system for the suture ligature method employed in the laparoscopic intestinal anastomosis model. Suturing skills were evaluated objectively using this system.
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Analysis of hand motion differentiates expert and novice surgeons.
J. Surg. Res.
PUBLISHED: 01-15-2014
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The number of operations performed by a surgeon may be an indicator of surgical skill. The hand motions made by a surgeon also reflect skill and level of expertise. We hypothesized that the hand motions of expert and novice surgeons differ significantly, regardless of whether they are familiar with specific tasks during an operation.
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CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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CD166, also known as activated leukocyte cell adhesion molecule (ALCAM), is expressed by various cells in several tissues including cancer. However, the role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer.
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Significance of metacognitive skills in laparoscopic surgery assessed by essential task simulation.
Minim Invasive Ther Allied Technol
PUBLISHED: 12-16-2013
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Abstract Background: Metacognition is the knowledge about ones own methods of perceiving, remembering, thinking, and acting. This study determined the significance of metacognitive skills in laparoscopic surgery with the aim of applying the findings in a laparoscopic surgery training program. Material and methods: Eighteen medical students with no experience in laparoscopic surgery (novice group) and eight expert surgeons who had each performed >100 laparoscopic surgeries (expert group) were enrolled. The examinees in each group performed an evaluation task using a virtual reality simulator and answered questions about the task. Results: The longest performance times, longest path lengths, and most frequent tissue damage occurred at 135° in the novice group and at 180° in the expert group. The greatest recognition of task difficulties, impatience, and irritation occurred at 135° in the novice group and at 180° in the expert group. There were statistically significant correlation coefficients between the instrument path length and task difficulty (metacognition) at 135° (R = 0.74, p = 0.03) and 180° (R = 0.79, p = 0.02) in the expert group, but there were no significant correlations in the novice group. Conclusion: We elucidated the significance of metacognitive skills in laparoscopic surgery. A training program should include recognition feedback systems.
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Migratory activity of CD105+ pancreatic cancer cells is strongly enhanced by pancreatic stellate cells.
Pancreas
PUBLISHED: 12-06-2013
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CD105 expression correlates with prognosis for several cancers. However, its significance in pancreatic cancer is unclear.
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An augmented reality navigation system for pediatric oncologic surgery based on preoperative CT and MRI images.
J. Pediatr. Surg.
PUBLISHED: 08-25-2013
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In pediatric endoscopic surgery, a limited view and lack of tactile sensation restrict the surgeons abilities. Moreover, in pediatric oncology, it is sometimes difficult to detect and resect tumors due to the adhesion and degeneration of tumors treated with multimodality therapies. We developed an augmented reality (AR) navigation system based on preoperative CT and MRI imaging for use in endoscopic surgery for pediatric tumors.
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Three-dimensional high-definition neuroendoscopic surgery: a controlled comparative laboratory study with two-dimensional endoscopy and clinical application.
J Neurol Surg A Cent Eur Neurosurg
PUBLISHED: 07-25-2013
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The purpose of this research was to investigate the usefulness of three-dimensional (3D) endoscopy compared with two-dimensional (2D) endoscopy in neuroendoscopic surgeries in a comparative study and to test the clinical applications.
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Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.
Mol. Cancer
PUBLISHED: 07-16-2013
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Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.
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MAL2 expression predicts distant metastasis and short survival in pancreatic cancer.
Surgery
PUBLISHED: 03-28-2013
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Pancreatic cancer is associated with a devastating prognosis, partially because of its aggressive metastatic ability. Identification of prognostic markers of metastasis would be useful in the clinical management of postoperative patients with pancreatic cancer. Mal, T-cell differentiation protein 2 (MAL2) has been identified as a molecule predictive of metastases; the clinical relevance of MAL2 in pancreatic cancer is unknown.
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Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype.
Ann. Surg.
PUBLISHED: 03-28-2013
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To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes.
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Robotic surgery for cancer.
Cancer J
PUBLISHED: 03-27-2013
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Currently, robot-assisted surgery is the most common type of robotic surgery used. In robot-assisted surgery, the operator is a surgeon, not a robotic system. Robotic systems assist the surgeons, but do not operate automatically. In this section, we focus on the master-slave type, which is the predominant type of robotic surgery used in cancer treatment, and discuss the role, present status, and the future of surgical robotic system in cancer treatment. In addition, the advantages and disadvantages of a robotic system are discussed, but further development of technologies and equipment is necessary to allow the safe, widespread introduction of a robotic system in more advanced surgery for malignant tumors. Such advances in the surgical robotic system will hopefully overcome the remaining problems and provide the ultimate minimally invasive surgery for cancer treatment.
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Kindlin-2 expression in peritumoral stroma is associated with poor prognosis in pancreatic ductal adenocarcinoma.
Pancreas
PUBLISHED: 03-20-2013
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Kindlin-2 is a novel focal adhesion protein reported to be expressed in breast, lung, and gastric cancers. This study aimed to investigate the significance of kindlin-2 expression in pancreatic ductal adenocarcinomas (PDACs).
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S100A4 mRNA expression level is a predictor of radioresistance of pancreatic cancer cells.
Oncol. Rep.
PUBLISHED: 02-26-2013
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Improving poor outcomes in patients with pancreatic cancer requires a greater understanding of the biological mechanisms contributing to radioresistance. We, therefore, sought to identify genes involved in the radioresistance of pancreatic cancer cells. Two pancreatic cancer cell lines, CFPAC-1 and Capan-1, were repeatedly exposed to radiation, establishing two radioresistant cell lines. Gene expression profiling using cDNA microarrays was performed to identify genes responsible for radioresistance. The levels of expression of mRNAs encoded by selected genes and their correlation with radiation dose resulting in 50% survival rate were analyzed in pancreatic cancer cell lines. The radiation dose resulting in a 50% survival rate was significantly higher in irradiated (IR) compared to parental CFPAC-1 cells (8.31 ± 0.85 Gy vs. 2.14 ± 0.04 Gy, P<0.0001), but was lower in IR compared with parental Capan-1 cells (2.66 ± 0.24 Gy vs. 2.25 ± 0.03 Gy, P=0.04). cDNA microarray analysis identified 4 genes, including S100 calcium binding protein A4 (S100A4), overexpressed and 23 genes underexpressed in the IR compared with the parental cell lines. The levels of S100A4 mRNA expression were correlated with radiation dose resulting in a 50% survival rate (Pearsons test, R2=0.81, P=0.0025). S100A4 mRNA expression may predict radioresistance of pancreatic cancer cells and may play an important role in the poor response of pancreatic cancer cells to radiation therapy.
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Kindlin-1 expression is involved in migration and invasion of pancreatic cancer.
Int. J. Oncol.
PUBLISHED: 02-22-2013
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Kindlin-1 is a novel focal adhesion protein that belongs to the kindlin family. Expression of kindlin-1 has recently been reported in lung and colon cancers, but there have been no studies on its expression in pancreatic cancer. This study aimed to investigate the expression and function of kindlin-1 in pancreatic cancer. Quantitative RT-PCR of Kindlin-1 mRNA was performed in various pancreatic cancer cell lines as well as normal pancreatic epithelial cells and fibroblasts. Immunohistochemical analysis of kindlin-1 was performed for pancreatic cancer tissues. The effects of kindlin-1 on the proliferation, migration and invasion of pancreatic cancer cells were investigated using an RNA interference technique. Kindlin-1 mRNA was highly expressed in the pancreatic cancer cell lines, but only slightly expressed in normal pancreatic epithelial cells and fibroblasts. The Kindlin-1 protein was heterogeneously expressed in the cytoplasm and membrane of pancreatic cancer cells, while normal ductal epithelial cells and stromal cells showed no expression. In vitro experiments involving knockdown of kindlin-1 in AsPC-1 and KP-2 cells revealed that the migratory and invasive abilities of the cells were significantly decreased (P<0.001), while the proliferation abilities were not affected. The present findings suggest that kindlin-1 expression is involved in the progression of pancreatic cancer via enhancement of cell migration and invasion.
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A minimally invasive and simple screening test for detection of pancreatic ductal adenocarcinoma using biomarkers in duodenal juice.
Pancreas
PUBLISHED: 02-15-2013
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The aim of this study was to establish a minimally invasive and simple screening test for detection of pancreatic ductal adenocarcinoma (PDAC) using duodenal juice (DJ).
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Laparoscopic total gastrectomy for remnant gastric cancer: feasibility study.
Surg Endosc
PUBLISHED: 02-14-2013
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The benefits and feasibility of laparoscopic surgery for remnant gastric cancer are still unclear. The purpose of this study was to describe the detailed procedure and to evaluate the clinical short-term outcomes of laparoscopic total gastrectomy (LTG) compared with open total gastrectomy (OTG) for remnant gastric cancer (RGC).
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Pirfenidone inhibits pancreatic cancer desmoplasia by regulating stellate cells.
Cancer Res.
PUBLISHED: 01-24-2013
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Pancreatic stellate cells (PSC), which are implicated in desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress desmoplasia and exert antitumor effects against pancreatic cancer. Primary PSCs were established from pancreatic cancer tissue obtained during surgery. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of PSCs in a dose-dependent manner. Although supernatants of untreated PSCs increased the proliferation, invasiveness, and migration of pancreatic cancer cells (PCC), supernatants of pirfenidone-treated PSCs decreased these effects. Exposure to PCC supernatant increased the production of platelet-derived growth factor-A, hepatic growth factor, collagen type I, fibronectin, and periostin in PSCs, which was significantly reduced by pirfenidone. Mice were subcutaneously implanted with PCCs (SUIT-2 cells) and PSCs into the right flank and PCCs alone into the left flank. Oral administration of pirfenidone to these mice significantly reduced tumor growth of co-implanted PCCs and PSCs, but not of PCCs alone. Pirfenidone also decreased the proliferation of PSCs and the deposition of collagen type I and periostin in tumors. In mice with orthotopic tumors consisting of PCCs co-implanted with PSCs, pirfenidone suppressed tumor growth, reduced the number of peritoneal disseminated nodules, and reduced the incidence of liver metastasis. Pirfenidone in combination with gemcitabine more effectively suppressed orthotopic tumor growth compared with pirfenidone or gemcitabine alone. In conclusion, our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of desmoplasia through regulating PSCs.
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Feasibility and safety of intracorporeal esophagojejunostomy after laparoscopic total gastrectomy: inverted T-shaped anastomosis using linear staplers.
Surgery
PUBLISHED: 01-07-2013
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Although laparoscopic distal gastrectomy has been widely accepted in clinical practice, laparoscopic total gastrectomy (LTG) is not yet familiar because of the difficulty in esophagojejunostomy. The purpose of this study was to evaluate perioperative and short-term outcomes of our procedure of intracorporeal gastrojejunostomy using linear staplers after LTG.
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Biological evaluation of protein nanocapsules containing doxorubicin.
Int J Nanomedicine
PUBLISHED: 01-01-2013
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This study describes the applications of a naturally occurring small heat shock protein (Hsp) that forms a cage-like structure to act as a drug carrier. Mutant Hsp cages (HspG41C) were expressed in Escherichia coli by substituting glycine 41 located inside the cage with a cysteine residue to allow conjugation with a fluorophore or a drug. The HspG41C cages were taken up by various cancer cell lines, mainly through clathrin-mediated endocytosis. The cages were detected in acidic organelles (endosomes/lysosomes) for at least 48 hours, but none were detected in the mitochondria or nuclei. To generate HspG41C cages carrying doxorubicin (DOX), an anticancer agent, the HspG41C cages and DOX were conjugated using acid-labile hydrazone linkers. The release of DOX from HspG41C cages was accelerated at pH 5.0, but was negligible at pH 7.2. The cytotoxic effects of HspG41C-DOX against Suit-2 and HepG2 cells were slightly weaker than those of free DOX, but the effects were almost identical in Huh-7 cells. Considering the relatively low release of DOX from HspG41C-DOX, HspG41C-DOX exhibited comparable activity towards HepG2 and Suit-2 cells and slightly stronger cytotoxicity towards Huh-7 cells than free DOX. Hsp cages offer good biocompatibility, are easy to prepare, and are easy to modify; these properties facilitate their use as nanoplatforms in drug delivery systems and in other biomedical applications.
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Augmented reality navigation system for laparoscopic splenectomy in children based on preoperative CT image using optical tracking device.
Pediatr. Surg. Int.
PUBLISHED: 11-16-2011
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In endoscopic surgery, limited views and lack of tactile sensation restrict the surgeons abilities and cause stress to the surgeon. Therefore, an intra-operative navigation system is strongly recommended. We developed an augmented reality (AR) navigation system based on preoperative CT imaging. The purpose of this study is to evaluate the usefulness, feasibility, and accuracy of this system using laparoscopic splenectomy in children.
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Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer.
Cancer Sci.
PUBLISHED: 11-07-2011
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In the present study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histological and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P < 0.001) and invasion (P < 0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P < 0.05) and the development of liver metastasis (P < 0.05). These data revealed that ZOL and GEM, when used in combination, have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer.
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Expression of activation-induced cytidine deaminase in ulcerative colitis-associated carcinogenesis.
Histopathology
PUBLISHED: 11-01-2011
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Activation-induced cytidine deaminase (AID) is a DNA/RNA-editing enzyme that is essential for hypermutation and class-switch recombination in immunoglobulin genes. The aim of this study was to investigate the expression of AID and its association with p53 mutation in ulcerative colitis (UC)-associated carcinogenesis.
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Single-incision laparoscopy-assisted surgery for bowel obstruction: report of three cases.
Surg. Today
PUBLISHED: 10-04-2011
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We applied single-incision laparoscopy-assisted surgery for several different types of bowel obstruction in selected patients. Before the operation, a long nasal tube was inserted for intestinal decompression and assessment of a stenotic lesion. A specially-designed instrument for single-incision laparoscopic surgery, the SILS Port, was introduced at the umbilicus or proposed ileostomy site. After intracorporeal procedures, extracorporeal resection and reconstruction of the intestine was performed as needed. Three patients with bowel obstruction due to jejunal carcinoma, colonic stenosis, and adhesion underwent single-incision laparoscopy-assisted surgery. The port site was used for subsequent extracorporeal resection and anastomosis of the jejunum in two patients, and for ileostomy in the remaining patient. All of the procedures were completed safely, and there were no postoperative complications. Single-incision laparoscopy can therefore be applied for selected patients with bowel obstruction. In such cases, the preoperative insertion of a long nasal tube for decompression of intestinal contents and assessment of the stenotic lesion is necessary.
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Bone marrow-derived monocyte lineage cells recruited by MIP-1? promote physiological revascularization in mouse model of oxygen-induced retinopathy.
Lab. Invest.
PUBLISHED: 09-12-2011
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Recent clinical observations have indicated that vascular endothelial growth factor (VEGF) is a key factor that stimulates the development of preretinal pathological neovascularization (NV). However, it has not been established how intraretinal physiological revascularization of hypoxic avascular areas is regulated. Our earlier study on the gene expression profile of hypoxic retinas in a mouse model of oxygen-induced retinopathy (OIR) showed that macrophage inflammatory protein-1? (MIP-1?) was the most upregulated protein. The purpose of this study was to investigate the role played by MIP-1? in recruiting bone marrow-derived monocyte lineage cells (BM-MLCs) in a mouse model of OIR. Our results showed that MIP-1? was upregulated, and its receptor, CCR5, was expressed in BM-MLCs in the hypoxic inner retina. Neutralizing Ab against MIP-1? reduced the infiltration of BM-MLCs into the OIR retinas and increased the avascular area and preretinal neovascular tufts. A very strong significant correlation was found between the area of the preretinal neovascular tufts and the avascular area, regardless of the extent of BM-MLC infiltration into the OIR retinas. Additional treatment with VEGF-A-neutralizing Ab showed that the MIP-1?-regulated pathological NV strongly depended on VEGF-A, which was probably secreted by the hypoxic avascular retinas. These results indicate that MIP-1? is involved in the recruitment of BM-MLCs, which have a significant role in the physiological revascularization of hypoxic avascular retinas. Overall, these findings indicate that the MIP-1? induction of BM-MLCs might possibly be used to promote intraretinal revascularization and thus prevent the abnormal NV in ischemic vision-threatening retinal diseases.
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Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 08-12-2011
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Identification of prognostic markers would be useful in the clinical management of patients with pancreatic ductal adenocarcinoma (PDAC). The clinical relevance of claudin-4 (CLDN4), recently identified as overexpressed in PDAC, is unknown.
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MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis.
Surgery
PUBLISHED: 06-15-2011
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MicroRNAs (miRNAs) have been gaining attention as new, key molecules that contribute to carcinogenesis. In pancreatic cancer, previous profiling analyses of miRNA expression have shown that several miRNAs are differently expressed in normal and cancerous tissues. Several pancreatic cancer-specific miRNAs differed, however, in each analysis.
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Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia.
Cancer Sci.
PUBLISHED: 04-27-2011
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A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2 ). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P?
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Adenoviral therapy is more effective in gemcitabine-resistant pancreatic cancer than in gemcitabine-sensitive cells.
Anticancer Res.
PUBLISHED: 04-22-2011
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Although gemcitabine is the standard treatment for pancreatic cancer, this particular type of cancer develops rapidly and has intrinsic chemoresistance. Chemoresistance plays a critical role in tumor progression, invasion and migration. Nevertheless, the effect of adenoviral therapy on chemoresistant cancer cells has not been studied. In this study, we compared the efficacy of adenoviral therapy in parental and chemoresistant pancreatic cancer cells.
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Invasive carcinoma derived from intestinal-type intraductal papillary mucinous neoplasm is associated with minimal invasion, colloid carcinoma, and less invasive behavior, leading to a better prognosis.
Pancreas
PUBLISHED: 04-19-2011
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Although intestinal-type intraductal papillary mucinous carcinoma (IPMC) is reported to have a better prognosis, few studies have addressed its invasive pattern. The meaning of "minimal invasion" (MI) in IPMC also remains unclear. We investigated the prognosis of intraductal papillary mucinous neoplasm (IPMN) focusing on MI and subtypes.
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Predicting the chemosensitivity of pancreatic cancer cells by quantifying the expression levels of genes associated with the metabolism of gemcitabine and 5-fluorouracil.
Int. J. Oncol.
PUBLISHED: 03-01-2011
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Gemcitabine (GEM) is the standard treatment for advanced/metastatic pancreatic cancer. However, there is a substantial subset of patients in whom the efficacy of GEM, when used as a single agent, is inadequate. Recently, the 5-fluorouracil (5-FU) prodrugs capecitabine and S-1 have been used as an alternative, either alone or in combination with GEM. The aim of the present study was to investigate the expression pattern of genes that render pancreatic cancer cells sensitive to GEM and 5-FU, and to identify markers for individualized chemotherapy, even in patients who have developed resistance. We investigated the correlation between the expression of genes associated with the metabolism of GEM and 5-FU, and sensitivity to these drugs in 15 human pancreatic cancer cell lines. We also established GEM- and 5-FU-resistant pancreatic cancer cell lines to investigate changes in the expression levels of these genes and the effects of one drug on cells resistant to the other. We found no correlation between pancreatic cancer cell sensitivity to either GEM- or 5-FU. GEM-resistant cells did not become resistant to 5-FU and vice versa. High expression of RRM1 (P=0.048) and TS x DPD (P=0.035) correlated significantly with sensitivity to GEM and 5-FU, respectively. 5-FU-resistant cells expressed significantly higher levels of TP than parental cells (P<0.05). In conclusion, pancreatic cancer cells showed no cross-resistance to GEM and 5-FU. Quantitative analyses of RRM1, TP, DPD and TS mRNA levels in pancreatic cancer cells may be useful for predicting their sensitivity to GEM and 5-FU.
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Senescence in intraductal papillary mucinous neoplasm of the pancreas.
Hum. Pathol.
PUBLISHED: 02-26-2011
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Intraductal papillary mucinous neoplasm of the pancreas is attracting attention as a precursor lesion of the invasive ductal adenocarcinoma, whereas it has been reported that some intraductal papillary mucinous neoplasms do not display progression to malignancy and remain almost unchanged in size and morphology. Recent studies have reported that oncogene-induced senescence has been observed in neoplasms, especially in premalignant lesions, and that it can play an important role in preventing malignant progression. To clarify the presence of senescence in intraductal papillary mucinous neoplasms, we analyzed the expression of several markers of senescence. The intraductal papillary mucinous neoplasms evaluated in this study were classified into 4 groups according to the degree of dysplasia. Senescence-associated ?-galactosidase activity and senescence-associated heterochromatin foci formation were investigated in 33 cases of intraductal papillary mucinous neoplasms and 6 normal controls. Immunohistochemical analysis of p16(INK4a) and p15(INK4b) was performed in 158 cases of intraductal papillary mucinous neoplasms and 10 normal controls. In the normal controls, neither senescence-associated ?-galactosidase activity nor senescence-associated heterochromatin foci formation was observed. Most of the normal epithelia were negative for either p16(INK4a) or p15(INK4b). For all 4 markers, the percentages of positive cases reached a peak in intraductal papillary mucinous neoplasm with low-grade dysplasia and showed significant decreasing trends in the transition from intraductal papillary mucinous neoplasm with low-grade dysplasia to intraductal papillary mucinous neoplasm with an associated invasive carcinoma. Our results indicate that senescence is induced in the early stage of intraductal papillary mucinous neoplasm and gradually attenuated according to the progression. It is suggested that senescence plays a role in preventing malignant progression of intraductal papillary mucinous neoplasm.
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Inhibition of p600 expression suppresses both invasiveness and anoikis resistance of gastric cancer.
Ann. Surg. Oncol.
PUBLISHED: 02-24-2011
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Advanced gastric cancers often metastasize to distant organs and the peritoneum, leading to a poor prognosis. Both invasiveness and resistance to anchorage-independent cell death (anoikis) are important factors in the process of metastasis. p600 (600-kDa protein), recently identified from a cervical cancer cell line, plays a role in both anoikis resistance and cell migration. In this study, we examined whether p600 is involved in the progression of gastric cancer.
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MicroRNA expression as a predictive marker for gemcitabine response after surgical resection of pancreatic cancer.
Ann. Surg. Oncol.
PUBLISHED: 02-23-2011
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To improve the prognosis of patients after resection of pancreatic cancer, the most appropriate and efficient treatment should be provided to specific subsets of patients. Our aim was to identify promising microRNAs as markers to predict responses to gemcitabine in patients with resected pancreatic cancer.
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High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy.
Int. J. Oncol.
PUBLISHED: 01-17-2011
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Pancreatic ductal adenocarcinoma (PDAC) still presents a major therapeutic challenge and a phase III clinical trial has revealed that the combination of gemcitabine and a human epidermal growth factor receptor type I (HER1/EGFR) targeting agent presented a significant benefit compared to treatment with gemcitabine alone. The aim of this study was to investigate EGFR mRNA expression in resected PDAC tissues and its correlation with patient prognosis. We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 88 patients with PDAC who underwent pancreatectomy, and measured EGFR mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction. The high-level EGFR group had significantly shorter disease-free-survival (p=0.029) and overall-survival (p=0.014) as shown by univariate analyses, although these did not reach statistical significance, as shown by multivariate analyses. However, we found that high EGFR expression was an independent prognostic factor in patients receiving gemcitabine-based adjuvant chemotherapy (p=0.023). Furthermore, we measured EGFR mRNA levels in 20 endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytological specimens. Altered EGFR levels were distinguishable in microdissected neoplastic cells from EUS-FNA cytological specimens compared to those in whole cell pellets. In conclusion, quantitative analysis of EGFR mRNA expression using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytological specimens could be useful in predicting prognosis and sensitivity to gemcitabine in PDAC patients.
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Tumor-stroma interactions reduce the efficacy of adenoviral therapy through the HGF-MET pathway.
Cancer Sci.
PUBLISHED: 11-24-2010
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Many preclinical studies have shown the potential of adenovirus-based cancer gene therapy. However, successful translation of these promising results into the clinic has not yet been achieved. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant desmoplastic stroma, and tumor-stromal cell interactions play a critical role in tumor progression. Therefore, we hypothesized that tumor-stroma interactions reduce the efficacy of adenoviral therapy. We investigated the effect of fibroblasts on adenovirus-based gene therapy using SUIT-2 and PANC-1 pancreatic cancer cells cultured with or without fibroblast-conditioned culture supernatant then infected with Ad-LacZ. After 48 h, the cells were stained for ?-galactosidase. The results showed that the number of ?-galactosidase-positive cells was significantly reduced after culture with fibroblast-conditioned supernatant (P < 0.05). Because the hepatocyte growth factor (HGF)/MET pathway plays an important role in tumor-stroma interactions we next investigated the involvement of this pathway in tumor-stroma interactions leading to the decreased efficacy of adenoviral therapy. SUIT-2 cells were cultured with or without SU11274 (a MET inhibitor) and/or fibroblast-conditioned culture supernatant, then infected with Ad-GFP. After 48 h, GFP-positive cells were counted. The number of GFP-positive cells in cultures containing fibroblast-conditioned supernatant plus SU11274 was significantly greater than in cultures without SU11274. In conclusion, our results suggest that stromal cells in PDAC reduce the efficacy of adenoviral therapy through a mechanism involving the HGF/MET pathway. Control of such tumor-stroma interactions may lead to improvements in adenoviral gene therapy for PDAC.
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Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas.
Mod. Pathol.
PUBLISHED: 11-19-2010
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Claudin-4, encoding a protein for tight junction formation and function, is highly overexpressed in pancreatic ductal adenocarcinoma and is also associated with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms of the pancreas. However, the expression pattern of claudin-4 during neoplastic progression of intraductal papillary mucinous neoplasms remains unknown. Using quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffin-embedded tissues from 80 patients with intraductal papillary mucinous neoplasms of different histological grades and papillary subtypes. Increased expression of claudin-4 was confirmed in all the pancreatic cancer cell lines tested as compared with normal ductal epithelial cells and fibroblast cultures. The claudin-4 expression was significantly higher in high-grade intraductal papillary mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade intraductal papillary mucinous neoplasms (adenoma) (P<0.0001). In addition, claudin-4 mRNA levels were significantly higher in intestinal-type intraductal papillary mucinous neoplasms than in non-intestinal-type intraductal papillary mucinous neoplasms based on papillary subclassification (P<0.0001). Our findings suggest that claudin-4 expression is associated with neoplastic progression of intraductal papillary mucinous neoplasms and, especially, with a distinct pathway to intestinal differentiation.
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MicroRNA expression analyses in preoperative pancreatic juice samples of pancreatic ductal adenocarcinoma.
JOP
PUBLISHED: 11-12-2010
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Cytological assessment of pancreatic juice is commonly used to diagnose pancreatic ductal adenocarcinoma; however, the sensitivity of cytological assessment has been reported to be low. MicroRNAs are small RNAs regulating various cellular processes and have recently been identified as possible markers of malignant diseases including pancreatic ductal adenocarcinoma.
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MicroRNA miR-17-5p is overexpressed in pancreatic cancer, associated with a poor prognosis, and involved in cancer cell proliferation and invasion.
Cancer Biol. Ther.
PUBLISHED: 10-15-2010
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The microRNA-17-92 cluster is an oncogene in human B cell lymphomas and lung cancers. Previous microRNA microarray data revealed that miR-17-5p, a member of the miR-17-92 cluster, is upregulated in pancreatic cancer. However, the involvement of miR-17-5p expression in pancreatic carcinogenesis has not well been studied. In the present study, we measured the miR-17-5p expression levels in pancreatic cancer cell lines, primary cultures of normal human pancreatic ductal cells, formalin-fixed paraffin-embedded (FFPE) tissue samples derived from 80 patients who underwent pancreatectomy for pancreatic cancer and microdissected cells (including normal ductal epithelial, pancreatic intraepithelial neoplasia-1B and invasive ductal carcinoma cells) by qRT-PCR. Furthermore, we investigated the effects of upregulation of miR-17-5p expression on the proliferation and invasion of pancreatic cancer cells. We found that pancreatic cancer cells expressed higher levels of miR-17-5p than primary cultured normal ductal cells. miR-17-5p was also overexpressed in pancreatic cancer in FFPE and microdissected samples. Furthermore, analysis of macrodissected FFPE samples revealed that high miR-17-5p expression was associated with a poor prognosis (p = 0.03). In addition, in vitro experiments revealed that SUIT-2 and KP-2 pancreatic cancer cells transfected with the miR-17-5p precursor showed significantly higher cell growth ratios than the corresponding control cells (p < 0.001 and p = 0.012, respectively), as well as significantly higher numbers of invading cells (p < 0.0001 for both). The present findings suggest that miR-17-5p plays important roles in pancreatic carcinogenesis and cancer progression, and is associated with a poor prognosis in pancreatic cancer.
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Effectiveness of basic endoscopic surgical skill training for pediatric surgeons.
Pediatr. Surg. Int.
PUBLISHED: 07-16-2010
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Pediatric surgeons require highly advanced skills when performing endoscopic surgery, but their experience with such cases tend to be limited in comparison to general surgeons. The aim of this study was to evaluate the effectiveness of basic endoscopic surgery training for less-experienced young pediatric surgeons and then compare their skills with those of general surgeons.
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Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells.
Cancer
PUBLISHED: 06-22-2010
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Recently, cancer stem cells have been reported as a new therapeutic target in pancreatic cancer as well as other cancers, but the specific role of these cells is unknown.
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alpha-Smooth Muscle Actin Expressing Stroma Promotes an Aggressive Tumor Biology in Pancreatic Ductal Adenocarcinoma.
Pancreas
PUBLISHED: 05-15-2010
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OBJECTIVES:: Pancreatic ductal adenocarcinoma (PDAC) is often characterized by a prominent desmoplastic stroma that is induced partially by alpha-smooth muscle actin (SMA)-expressing activated pancreatic stellate cells (PSCs). This study aimed to investigate the significance of alpha-SMA expression in PDAC and the correlation between alpha-SMA mRNA levels and the patient prognosis. METHODS:: We obtained formalin-fixed, paraffin-embedded tissue samples from 109 patients with PDAC, who underwent pancreatectomy at our institution from 1992 to 2007. We measured alpha-SMA mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction and investigated the association of alpha-SMA mRNA expression with clinicopathologic parameters and survival time. We also assessed the influence of activated PSCs on malignant behaviors of pancreatic cancer cells using in vitro experiments. RESULTS:: alpha-SMA immunoreactivity was detected exclusively in the stroma of PDAC. The group with high alpha-SMA expression showed a significantly shorter survival, as shown by univariate analysis (P = 0.005) and multivariate analysis (P < 0.0001). alpha-SMA-expressing activated PSCs enhanced the invasiveness, proliferation, and colony formation of pancreatic cancer cells. CONCLUSIONS:: Quantitative analysis of alpha-SMA mRNA expression using formalin-fixed, paraffin-embedded tissue samples was useful to predict the prognosis of patients with PDAC. Activated PSCs may regulate the malignant behavior of pancreatic cancer cells.
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CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer.
Gastroenterology
PUBLISHED: 05-05-2010
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Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer by producing extracellular matrix and soluble factors. However, the functional heterogeneity of PSCs has not been identified until now. Detailed characterization of the PSCs in human pancreatic cancer would provide a set of potential targets for stroma-directed therapy.
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SPARC mRNA expression as a prognostic marker for pancreatic adenocarcinoma patients.
Anticancer Res.
PUBLISHED: 04-16-2010
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Secreted protein acidic and rich in cysteine (SPARC) is a protein which governs diverse cellular functions and matrix remodeling systems. It was reported that SPARC expression of peritumoral fibroblasts was correlated with poor prognosis in resectable pancreatic cancer patients in immunohistochemical analysis. However, the significance of SPARC mRNA expression in pancreatic adenocarcinoma remains unclear.
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Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy.
Neoplasia
PUBLISHED: 03-24-2010
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The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome.
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MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation.
Mol. Cancer
PUBLISHED: 03-16-2010
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Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of miR-200c has been shown to be associated with upregulating the expression of E-cadherin, a gene known to be involved in pancreatic cancer behavior. However, the significance of miR-200c in pancreatic cancer is unknown.
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Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells.
PLoS ONE
PUBLISHED: 03-08-2010
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Although CD133 has been reported to be a promising colon cancer stem cell marker, the biological functions of CD133+ colon cancer cells remain controversial. In the present study, we investigated the biological differences between CD133+ and CD133- colon cancer cells, with a particular focus on their interactions with cancer-associated fibroblasts, especially CD10+ fibroblasts. We used 19 primary colon cancer tissues, 30 primary cultures of fibroblasts derived from colon cancer tissues and 6 colon cancer cell lines. We isolated CD133+ and CD133- subpopulations from the colon cancer tissues and cultured cells. In vitro analyses revealed that the two populations showed similar biological behaviors in their proliferation and chemosensitivity. In vivo analyses revealed that CD133+ cells showed significantly greater tumor growth than CD133- cells (P=0.007). Moreover, in cocultures with primary fibroblasts derived from colon cancer tissues, CD133+ cells exhibited significantly more invasive behaviors than CD133- cells (P<0.001), especially in cocultures with CD10+ fibroblasts (P<0.0001). Further in vivo analyses revealed that CD10+ fibroblasts enhanced the tumor growth of CD133+ cells significantly more than CD10- fibroblasts (P<0.05). These data demonstrate that the in vitro invasive properties and in vivo tumor growth of CD133+ colon cancer cells are enhanced in the presence of specific cancer-associated fibroblasts, CD10+ fibroblasts, suggesting that the interactions between these specific cell populations have important roles in cancer progression. Therefore, these specific interactions may be promising targets for new colon cancer therapies.
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MicroRNA-203 expression as a new prognostic marker of pancreatic adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 02-26-2010
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Detection of aberrant microRNA (miR) expression may contribute to diagnosis and prognosis of various cancers. The aim of this study is to evaluate the correlation between miR-203 expression and prognosis of patients with pancreatic adenocarcinoma after curative resection.
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S100P is a novel marker to identify intraductal papillary mucinous neoplasms.
Hum. Pathol.
PUBLISHED: 02-12-2010
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Intraductal papillary mucinous neoplasms of the pancreas are subclassified based on morphological features, and different immunohistochemical profiles have been identified in association with the subtypes. We previously reported that S100P was an early developmental marker of pancreatic carcinogenesis and that there was higher S100P expression in intraductal papillary mucinous neoplasms than in normal pancreatic ductal epithelium. However, there have been no reports on novel diagnostic markers to distinguish intraductal papillary mucinous neoplasm from nonneoplastic lesions. Surgical specimens of intraductal papillary mucinous neoplasm obtained from 105 patients were investigated using immunohistochemistry. S100P expression was not detected in normal pancreatic ductal epithelium but was detected in all intraductal papillary mucinous neoplasm cells (100%) with diffuse nuclear or nuclear/cytoplasmic staining. MUC5AC was also expressed in most of the intraductal papillary mucinous neoplasms (102/105; 97%). Furthermore, S100P was clearly expressed in the invasive component of intraductal papillary mucinous neoplasms (32/32; 100%), including perineural and lymphatic and minimal invasion. On the other hand, MUC5AC was expressed in only 23 cases of 32 invasive components (P < .01). These data suggest that the S100P antibody may be a useful marker for detecting all types of intraductal papillary mucinous neoplasms.
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Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer.
Cancer Lett.
PUBLISHED: 01-26-2010
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To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.
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Skills assessment using a virtual reality simulator, LapSim, after training to develop fundamental skills for endoscopic surgery.
Minim Invasive Ther Allied Technol
PUBLISHED: 01-26-2010
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Education and training to maintain medical safety are very important within clinical settings. We have established a training center for endoscopic surgery and we regularly hold a unique training course, which focuses on the development of fundamental skills. One hundred and ninety-four surgeons who participated in our training course were divided into four groups according to their experience in performing laparoscopic procedures. Group 1: 0-19 laparoscopic procedures (n=44). Group 2: 20-49 laparoscopic procedures (n=53). Group 3: 50-99 laparoscopic procedures (n=46). Group 4: more than 100 laparoscopic procedures (n=55). All subjects underwent evaluation for "Lifting & Grasping" using a virtual reality (VR) simulator, LapSim, before and after the training course. The mean efficiency score, time to completion and tissue damage after training were significantly improved after the training as compared with before training. Before training, subjects with greater experience had better scores. However, the only significant difference in the score was between the low experience group and greatest experience group. After training, the score increased in all groups compared with that before training, and there was no significant difference between groups. This study demonstrates the feasibility of using a VR simulator to assess fundamental skills for endoscopic surgery after training. We found that the scores for the task were associated with the level of experience of the surgeons.
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Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type.
Surgery
PUBLISHED: 01-08-2010
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Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is divided into 4 subtypes: an intestinal type, a gastric type, a pancreatobiliary type, and an oncocytic type. The purposes of this study were to clarify the outcomes and the characteristics of invasive carcinoma derived from IPMN (invasive IPMC) by focusing on these subtypes with a comparison to conventional invasive ductal carcinoma (IDC) of the pancreas.
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Characterization of CD24 expression in intraductal papillary mucinous neoplasms and ductal carcinoma of the pancreas.
Hum. Pathol.
PUBLISHED: 01-05-2010
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CD24 is a molecule involved in cell adhesion and tumor metastasis. The aims of this study were (1) to evaluate the association between CD24 expression and the progression of intraductal papillary mucinous neoplasms of the pancreas and (2) to investigate the association between CD24 expression in pancreatic cancer and the prognosis of patients who underwent curative pancreatectomy. Immunohistochemical analysis of CD24 was performed for 95 intraductal papillary mucinous neoplasms of the pancreas and 83 pancreatic cancers. We investigated the association between CD24 expression and the histologic grade of intraductal papillary mucinous neoplasms of the pancreas, the clinicopathologic parameters of pancreatic cancers, and the survival time of pancreatic cancer patients who underwent pancreatectomy. The positive rates of CD24 expression in intraductal papillary mucinous adenoma, borderline intraductal papillary mucinous neoplasm, noninvasive intraductal papillary mucinous carcinoma, and invasive intraductal papillary mucinous carcinoma were 5 (20%) of 24, 12 (48%) of 25, 10 (43%) of 23, and 15 (65%) of 23, respectively. The CD24-positive rates were significantly higher in borderline intraductal papillary mucinous neoplasm and intraductal papillary mucinous carcinoma compared with intraductal papillary mucinous adenoma (P = .046 and P = .007, respectively). The staining scores, which were determined from the percentage of stained cells and the staining intensity, were significantly higher in invasive intraductal papillary mucinous carcinoma than in noninvasive intraductal papillary mucinous carcinoma (P = .043). In the pancreatic cancers, higher tumor stage (P = .007), nodal metastasis (P = .021), and higher-grade tumors (P < .001) were more frequent in the CD24-positive group compared with the CD24-negative group. CD24 expression was associated with shorter survival in univariate analysis (P = .028) However, based on the multivariate analysis, the CD24 expression was not associated with survival. In conclusion, CD24 is involved in the progression of intraductal papillary mucinous neoplasms of the pancreas and in the malignant behavior of pancreatic cancers.
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hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells.
Cancer Sci.
PUBLISHED: 11-18-2009
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Adenovirus-mediated gene therapy shows promise for cancer therapy, but transgene expression of replication-defective adenovirus may be low and transient in clinical settings. Recent reports have shown that the use of a conditionally replication-competent adenovirus (CRAd) enhanced the gene transduction of a replication-defective adenovirus vector. The control of tumor-stromal interactions has also been determined to be important in cancer therapy. In this study, we investigated the effect of the human telomerase reverse transcriptase (hTERT)-CRAd, Ad5/3hTERTE1, which possesses the tumor-specific hTERT promoter with the chimeric fiber 5/3, on the transgene expression and therapeutic efficacy of a replication-defective adenovirus vector expressing NK4 under the control of the CMV promoter, Ad-NK4. In addition, we established a new strategy to target both cancer cells and cancer-stromal interactions. Human pancreatic cancer cells were infected with Ad-NK4 and either Ad5/3hTERTE1 (CRAd-combination group) or Ad5/3hTERTLuc (control-combination group). In the CRAd-combination group, Ad-NK4-delivered transgene expression was increased, leading to an enhanced inhibitory effect on the invasion of cancer cells. In in vivo experiments, NK4 expression within tumors and its inhibitory effect on tumor growth, angiogenesis, and metastasis were enhanced in the CRAd-combination group. These results suggest that hTERT-CRAd enhances the transgene expression and therapeutic efficacies of Ad-NK4, possibly through the in-trans replication of Ad-NK4 induced by adenovirus E1 derived from co-infected hTERT-CRAd. This approach may be a promising combination therapy against advanced pancreatic cancer.
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Tumor-stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cells.
Cancer Sci.
PUBLISHED: 08-19-2009
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Pancreatic ductal adenocarcinoma is often characterized by an abundant desmoplastic stroma that is partially induced by activated pancreatic stellate cells (PSCs). Indirect co-culture has often been used to investigate the effects of cancer-stromal interactions on the proliferation of cancer cells, but the effects of cell-cell adhesion and juxtacrine signaling between cancer and stromal cells cannot be evaluated using this method. This study aimed to establish a simplified direct co-culture system that could be used to quantify populations of cancer cells in co-culture with PSCs, and to evaluate the effects of direct cell contact on the proliferation of cancer cells. We established three green fluorescent protein (GFP)-expressing pancreatic cancer cell lines and were able to quantify them with high reliability and reproducibility, even when co-cultured directly with PSCs, using a color plate reader. We assessed the differential effects of direct and indirect co-culture with PSCs on the proliferation of cancer cells, and found that the proliferation of GFP-expressing pancreatic cancer cell lines was dramatically enhanced by direct co-culture with PSCs, compared with the indirect co-culture system. We also found that direct co-culture of cancer cells and PSCs activated the Notch signaling pathway in both cell types. Direct cell contact between cancer cells and PSCs plays an important role in the control of cancer cell proliferation, and is essential to the understanding of tumor-stromal interactions.
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Intraabdominal Roux-en-Y reconstruction with a novel stapling technique after laparoscopic distal gastrectomy.
Gastric Cancer
PUBLISHED: 08-03-2009
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Laparoscopic gastrectomy is widely used as minimally invasive surgery for gastric carcinoma. Billroth I or Roux-en-Y reconstruction is commonly performed after laparoscopic distal gastrectomy (LDG). Roux-en-Y reconstruction after LDG is one of the best methods for reconstruction of the alimentary tract when Billroth I reconstruction is difficult. There are few reports of intracorporeal Roux-en-Y reconstruction after LDG because of the technical difficulties of such a procedure. In particular, in the case of a very small gastric remnant, gastrojejunostomy using endoscopic linear staplers becomes more complicated. We developed a new technique for intracorporeal Roux-en-Y reconstruction: a modified stapling technique to allow the gastrojejunostomy to be made on the stomach transecting line that is applicable even when the residual stomach is very small. Roux-en-Y reconstruction with our modified technique was performed in six patients. There was no intraoperative complication or conversion to minilaparotomy or conventional celiotomy in any patient. Oral intake was easy and adequate after surgery. The present Roux-en-Y reconstruction procedure is feasible. Herein we describe an intraabdominal Roux-en-Y reconstruction with a modified stapling technique after LDG.
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Up-regulation of integrin beta3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy.
Cancer Sci.
PUBLISHED: 06-17-2009
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Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P < 0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin beta3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin beta3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin beta3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy.
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S100A4 mRNA is a diagnostic and prognostic marker in pancreatic carcinoma.
J. Gastrointest. Surg.
PUBLISHED: 06-02-2009
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The aim of this study is to evaluate the clinical significance of S100A4 mRNA expression in pancreatic cancer.
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MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance.
Mol. Cancer Ther.
PUBLISHED: 05-12-2009
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Due to the poor prognosis of pancreatic cancer, novel diagnostic modalities for early diagnosis and new therapeutic strategy are urgently needed. Recently, microRNA-21 (miR-21) was reported to be strongly overexpressed in pancreatic cancer as well as in other solid cancers. We investigated the functional roles of miR-21, which have not been fully elucidated in pancreatic cancer. miR-21 expression was assessed in pancreatic cancer cell lines (14 cancer cell lines, primary cultures of normal pancreatic epithelial cells and fibroblasts, and a human normal pancreatic ductal epithelial cell line) and pancreatic tissue samples (25 cancer tissues and 25 normal tissues) by quantitative real-time reverse transcription-PCR amplification. Moreover, we investigated the proliferation, invasion, and chemoresistance of pancreatic cancer cells transfected with miR-21 precursor or inhibitor. miR-21 was markedly overexpressed in pancreatic cancer cells compared with nonmalignant cells, and miR-21 in cancer tissues was much higher than in nonmalignant tissues. The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor. These data suggest that miR-21 expression is increased in pancreatic cancer cells and that miR-21 contributes to the cell proliferation, invasion, and chemoresistance of pancreatic cancer.
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Midkine mRNA is overexpressed in pancreatic cancer.
Dig. Dis. Sci.
PUBLISHED: 04-01-2009
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Midkine (MK) has been reported to be a possible molecular marker for the diagnosis of pancreatic cancer. We investigated the feasibility of quantitative analysis of MK mRNA by quantitative real-time RT-PCR (qRT-PCR) as a promising tool for the diagnosis of pancreatic cancer.
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Chemotherapeutic agents potentiate adenoviral gene therapy for pancreatic cancer.
Cancer Sci.
PUBLISHED: 03-11-2009
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Adenovirus-mediated gene therapy combined with chemotherapeutic agents is expected to represent a new approach for treating pancreatic cancer. However, there have been no reports of definitive effects of chemotherapeutic agents on adenovirus-mediated gene therapies. In the present study, we investigated the effects of chemotherapeutic agents on the transduction efficiency of an adenovirus-based gene therapy. Adenovirus (Ad-NK4) expressing NK4, which acts as a hepatocyte growth factor antagonist, was used as a representative gene therapy. Pancreatic cancer cells infected with Ad-NK4 were treated with chemotherapeutic agents (5-fluorouracil [5FU], cisplatin or etoposide), and the NK4 levels in their culture media were measured. To examine the effects of chemotherapeutic agents in vivo, Ad-NK4 was administered to subcutaneous tumors in mice after treatment with the agents, and the tumor NK4 levels were measured. The NK4 levels in culture media from cells treated with 5FU, cisplatin and etoposide were 5.2-fold (P = 0.026), 6-fold (P < 0.001) and 4.3-fold (P < 0.001) higher than those of untreated cells, respectively. The chemotherapeutic agents also increased Ad-NK4 uptake. The NK4 levels in tumors treated with 5FU, cisplatin and etoposide were 5.4-fold (P = 0.006), 11.8-fold (P < 0.001) and 4.9-fold (P = 0.017) higher than those in untreated tumors, respectively. The present findings suggest that chemotherapeutic agents significantly improve the efficiency of adenovirus-mediated gene transfer in pancreatic cancer. Furthermore, they will contribute to decreases in the adenovirus doses required for gene transfer, thereby controlling the side-effects of adenovirus infection in normal tissues.
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LMO2 is a novel predictive marker for a better prognosis in pancreatic cancer.
Neoplasia
PUBLISHED: 03-03-2009
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LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer.
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The effect of CyberDome, a novel 3-dimensional dome-shaped display system, on laparoscopic procedures.
Int J Comput Assist Radiol Surg
PUBLISHED: 02-04-2009
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Laparoscopic surgeons require extended experience of cases to overcome the lack of depth perception on a two-dimensional (2D) display. Although a three-dimensional (3D) display was reported to be useful over two decades ago, 3D systems have not been widely used. Recently, we developed a novel 3D dome-shaped display (3DD) system, CyberDome.
Related JoVE Video

What is Visualize?

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

How does it work?

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

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.