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Find video protocols related to scientific articles indexed in Pubmed.
Upregulation of microRNA-31 associates with a poor prognosis of malignant pleural mesothelioma with sarcomatoid component.
Med. Oncol.
PUBLISHED: 10-07-2014
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Malignant pleural mesothelioma (MPM) is a neoplastic disease with a poor prognosis. The complete resection of tumor with extra-pleural pneumonectomy is effective only for early stage epithelioid-type MPM. An accurate pathological diagnosis including the histological subtype and also clinical staging are crucial to decide on the therapeutic approach. However, the pathological diagnosis is difficult when the amount of biopsy sample is small. We performed a comparative analysis of the miR-31 expression in MPM and reactive mesothelial proliferations (RMPs), by RT-qPCR of formaldehyde-fixed paraffin-embedded samples, and compared the expression levels of miR-31 with the results of a survival analysis for the diagnosis and prognosis of MPM. The expression of miR-31 was found to be significantly reduced in MPMs compared with RMPs (P < 0.01). The pathological subtype of four among five cases with upregulated miR-31 levels was MPM with a sarcomatoid component. (i.e., biphasic or sarcomatoid type). Furthermore, these four cases were significantly associated with a worse prognosis compared with the five cases of biphasic or sarcomatoid MPM without upregulated miR-31 expression (P = 0.0027). In conclusion, the analysis of miR-31 expression levels may be a good biomarker for diagnosis of MPM histological typing and predicting the prognosis.
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A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures.
EMBO J.
PUBLISHED: 02-20-2014
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Growth factor-dependent epithelial morphological changes and proliferation are essential for the formation of tubular structures, but the underlying molecular mechanisms are poorly understood. Co-stimulation with Wnt3a and epidermal growth factor (Wnt3a/EGF) induced development of tubes consisting of intestinal epithelial cells by inducing expression of Arl4c, an Arf-like small GTP-binding protein, in three-dimensional culture, while stimulation with Wnt3a or EGF alone did not. Arl4c expression resulted in rearrangement of the cytoskeleton through activation of Rac and inactivation of Rho properly, which promoted cell growth by inducing nuclear translocation of Yes-associated protein and transcriptional co-activator with PDZ-binding motif (YAP/TAZ) in leading cells. Arl4c was expressed in ureteric bud tips and pretubular structures in the embryonic kidney. In an organoid culture assay, Wnt and fibroblast growth factor signaling simultaneously induced elongation and budding of kidney ureteric buds through Arl4c expression. YAP/TAZ was observed in the nucleus of extending ureteric bud tips. Thus, Arl4c expression induced by a combination of growth factor signaling mechanisms is involved in tube formation.
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Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.
Mol. Biol. Cell
PUBLISHED: 10-02-2013
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Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling-dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.
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Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology.
Cancer Cytopathol
PUBLISHED: 02-28-2013
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In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH).
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Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis.
Am. J. Clin. Pathol.
PUBLISHED: 02-21-2013
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The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.
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Cell Cycle-Dependent Rho GTPase Activity Dynamically Regulates Cancer Cell Motility and Invasion In Vivo.
PLoS ONE
PUBLISHED: 01-01-2013
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The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.
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[A long-term survival case after two resections of the peritoneal metastasis from hepatocellular carcinoma].
Gan To Kagaku Ryoho
PUBLISHED: 12-29-2011
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A 70-year-old man with type B hepatitis had ruptured HCC in segment 5, and he underwent with TAE at other hospital in June 2007. Then, he was introduced to our hospital in July 2007. Partial hepatectomy( S5) was performed in August 2007 (pT2N0M0, Stage II). Afterward, he underwent TACE therapy twice because of multiple intrahepatic recurrences. Abdominal CT revealed a viable recurrence lesion (S5), and peritoneal dissemination (surface of S3) in June 2009. We carried out partial hepatectomy (S5), and removal of peritoneal dissemination because of good liver function and without any other extra hepatic recurrence in July 2009. Histologically, the intrahepatic lesion( S5) and the S3 surface lesion were diagnosed as moderately differentiated HCC. In July 2010, abdominal CT revealed three lesions of peritoneal dissemination (right subphrenic lesion, hepatic flexure of the colon, neighborhood of left ureter, then the second removal of peritoneal dissemination was performed. In January 2011, he had multiple lung metastatic lesions, and multiple bone metastatic lesions were occurred in March 2011, then his general condition was getting worse. In April 2011, he was dead 46 months after the first TAE therapy for ruptured HCC, or 21 months after the first resection of peritoneal dissemination. Surgical resection of peritoneal dissemination of HCC may improve a survival for patients whose intrahepatic lesion is contorollable.
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[A case of pancreatic mucinous carcinoma which includes calcification].
Gan To Kagaku Ryoho
PUBLISHED: 12-29-2011
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A 60-year-old woman was pointed out a tumor, 2.6 cm in diameter, at the pancreas body, by screening ultrasonography examination. Jaundice and anemia were absent and no abdominal mass was palpable on physical examination. Enhanced CT revealed the tumor directly invaded to splenic vein, but lymph node metastases were not detected. ERCP showed a pancreatic duct was obstructed by the tumor, accompanied with dilatation of the peripheral pancreas duct. Because we cannot rule out the malignancy tumor, pancreatoduodenectomy and lymphadenectomy was done. The tumor was very hard and serosal invasion was suspicious in the operative findings. Histopathological study showed that the tumor was occupied with colloid differentiation, in which free mucinous epithelial malignant cells were floating. Then we diagnosed the tumor to be pancreatic mucinous carcinoma. Extra pancreatic extension such as vascular involvement was not proved microscopically. However, ten months after the resection, CT scan showed a recurrent tumor sized 4 cm diameter, at the middle abdominal cavity, which suspected to be disseminated diseases. Mucinous carcinoma occurs relatively rare in pancreas, of which the incidence is 1 .4% in pancreatic adenocarcinomas. We report herein the pancreatic mucinous carcinoma case with a calcificated region, which resulted in early recurrence with abdominal seeding.
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[Gallbladder carcinomas with a single lymph node involvement behind biliary tract -two resected cases].
Gan To Kagaku Ryoho
PUBLISHED: 12-29-2011
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Case 1 was an 85-year-old man, who was pointed out a gallbladder tumor by screening CT scan after bladder cancer. The tumor was arisen in the gallbladder body, 1 .5 cm in diameter. He underwent a radical surgery; the gallbladder-bed was resected with more than 1 cm margin, and lymphadenectomy was done preserving biliary tract. Pathologically his tumor was papillary adenocarcinoma suspected to invade to the liver-bed minimally. A lymph node involvement was solitary located at right side of hepatoduodenal ligament (behind biliary tract). Case 2 was a 73-year-old man who was pathologically diagnosed to be advanced gallbladder carcinoma after laparoscopic cholecystectomy. CT scan and MRI revealed a mass sized 2 cm in diameter, at the gallbladder-bed, and PET exam showed a hot spot at this site only. Therefore, he underwent a radical surgery like case 1. Pathologically the tumor was moderately differentiated adenocarcinoma, and a lymph node involvement was solitary and located behind a biliary tract. Both patients have been recurrent free for more than 22 months and 15 months, respectively. Two lymphatic drainage routes have been suggested, one is the route which runs right side of hepatoduodenal ligament, another runs via left side of the ligament, along hepatic artery. Our two cases are considered to be solitary metastatic cases along the right side route. A clinical case of solitary node positive seems to be known for its relatively good prognosis. In order to justify our cases, we need a longer follow-up period, or we should have more cases to be experienced.
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[A case of anstomotic stricture after esophagectomy sufficiently treated by endoscopic triamcinolone injection therapy].
Gan To Kagaku Ryoho
PUBLISHED: 11-18-2011
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We report a case of 50-year-old man with refractory anastomotic stricture after esophagectomy, which was successfully treated with endoscopic triamcinolone injection therapy. He received a curative operation for advanced thoratic esophageal carcinoma (Mt, Type 3, cT3, cN1, MO, Stage III). Anastomotic leakage was occurred as post-operative adverse event, which recovered conservatively, and subsequently resulted in refractory anastomotic stricture. He had a recurrence of dysphagia despite of repeated bougienage and endoscopic balloon dilatation. Four years later, he received an intralesional triamcinolone injection in anastomotic stricture every four weeks. According to the 5 courses of treatment, anastomotic stricture was cured and there was no recurrence confirmed. Intralesional triamcinolone injection may be one of the promising options for the treatment of refractory anastomotic stricture after esophagectomy.
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An anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis.
Mol. Cancer Ther.
PUBLISHED: 11-18-2011
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Wnt5a is a representative ligand that activates the ?-catenin-independent pathway in Wnt signaling. It was reported that the expression of Wnt5a in human gastric cancer is associated with aggressiveness and poor prognosis and that knockdown of Wnt5a reduces the ability of gastric cancer cells to metastasize in nude mice. Therefore, Wnt5a and its signaling pathway might be important targets for the therapy of gastric cancer. The aim of this study was to examine whether an anti-Wnt5a antibody affects metastasis of gastric cancer cells. One anti-Wnt5a polyclonal antibody (pAb5a-5) inhibited migration and invasion activities in vitro of gastric cancer cells with a high expression level of Wnt5a. Previously, it was shown that Wnt5a induces the internalization of receptors, which is required for Wnt5a-dependent activation of Rac1. pAb5a-5 inhibited Wnt5a-dependent internalization of receptors, thereby suppressed Wnt5a-dependent activation of Rac1. Laminin ?2 is one of target genes of Wnt5a signaling and Rac1 was involved in its expression. pAb5a-5 also inhibited Wnt5a-dependent expression of laminin ?2. In an experimental liver metastasis assay, gastric cancer cells were introduced into the spleens of nude mice. Laminin ?2 was required for liver metastatic ability of gastric cancer cells in vivo. Furthermore, intraperitoneal injection of pAb5a-5 inhibited the metastatic ability of gastric cancer cells. These results suggest that an anti-Wnt5a antibody was capable of suppressing Wnt5a-dependent internalization of receptors, resulting in the prevention of metastasis of gastric cancer cells by inhibiting the activation of Rac1 and the expression of laminin ?2.
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New insights into the mechanism of Wnt signaling pathway activation.
Int Rev Cell Mol Biol
PUBLISHED: 10-25-2011
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Wnts compromise a large family of secreted, hydrophobic glycoproteins that control a variety of developmental and adult processes in all metazoan organisms. Recent advances in the Wnt-signal studies have revealed that distinct Wnts activate multiple intracellular cascades that regulate cellular proliferation, differentiation, migration, and polarity. Although the mechanism by which Wnts regulate different pathways selectively remains to be clarified, evidence has accumulated that in addition to the formation of ligand-receptor pairs, phosphorylation of receptors, receptor-mediated endocytosis, acidification, and the presence of cofactors, such as heparan sulfate proteoglycans, are also involved in the activation of specific Wnt pathways. Here, we review the mechanism of activation in Wnt signaling initiated on the cell-surface membrane. In addition, the mechanisms for fine-tuning by cross talk between Wnt and other signaling are also discussed.
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A multivariate statistical study to obtain effective criteria to detect well-differentiated adenocarcinoma in endometrial cytology.
Diagn. Cytopathol.
PUBLISHED: 01-06-2011
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Consistency in endometrial cytology is relatively poor. This can be partly attributed to generally accepted criteria based on cellular features. The cytological distinction between grade-1 adenocarcinoma and endometrial hyperplasia is more reliant on architectural features than cellular features. We examined statistical criteria based on cytoarchitecture for detecting grade-1 adenocarcinoma in endometrial cytology. Histologically, the study population consisted of 11 cases of grade-1 adenocarcinoma, 6 of atypical endometrial hyperplasia, 16 of endometrial hyperplasia without atypia, and 74 of a normal proliferative endometrium. In each case, all cellclumps were divided into five patterns (tubular; sheet; dilated and/or branched tubular; regular overlapping; atypical). The frequencies of each pattern were submitted to five-variate cluster analysis. The validity and reproducibility of cluster analysis were tested by canonical discriminant analysis and multigroup linear discriminant analysis, respectively. All 107 cases were classified into three groups, A (11), B (36), and C (60), by five-variate cluster analysis. In comparison with this classification and histopathologic diagnosis, group A corresponded to adenocarcinoma, and groups B and C correlated with non-carcinoma. Most cases of atypical endometrial hyperplasia were included in group B. These data suggest that statistical groupings based on cytoarchitecture are useful in the discrimination of grade-1 adenocarcinoma from endometrial hyperplasia and normal tissue.
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[Three-time resection of the rib metastasis from hepatocellular carcinoma after two hepatic resections--a case report].
Gan To Kagaku Ryoho
PUBLISHED: 10-15-2010
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A 40s woman, who had undergone hepatic resection twice for hepatocellular carcinoma (HCC), was admitted to our hospital because of a tumor with pain on the right 9th rib. From the findings of chest computed tomography (CT), abdominal CT and bone scintigraphy, we diagnosed the rib metastasis of HCC without any other recurrences. Local resection of the right 9th rib was performed in July 2008. Histologically, the tumor of the rib was diagnosed as the metastasis of HCC. The patients pain on the right rib was disappeared after the operation. After the rib resection, the recurrence of the remnant of the right 9th rib occurred in June 2009. Local resection of the rib was performed in July 2009. Afterward, the recurrence of the remnant of the right 9th rib occurred again in April 2010. Local resection of the tumor of the same rib was performed in May 2010. The patient is still alive five years after the first hepatectomy. For HCC patients whose intrahepatic lesion or other metastatic lesions are controllable and the metastatic bone lesion is solitary and easily resectable, a resection for bone metastasis from HCC is thus locally effective in patients pain control.
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Fluidic supramolecular nano- and microfibres as molecular rails for regulated movement of nanosubstances.
Nat Commun
PUBLISHED: 03-11-2010
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Nano- and micro-sized fibrous architectures are ubiquitous in nature; in particular, microtubules have an essential role within live cells, as tracks for transporting objects to a desired place, driven by molecular motors such as dynein and kinesin. Such functions of bionanofibres motivated us to construct an artificial supramolecular rail using the fluidic property of self-assembled glycolipid nanofibres. Artificial supramolecular nanofibres constructed through molecular self-assembly of small molecules have recently attracted considerable attention for their unique properties, such as reversible formation/destruction under mild conditions and various stimuli responsiveness. In this paper, we show that a supramolecular nanofibre has sufficient fluidity, on the basis of its non-crystalline nature, to function as a molecular track for the directional movement of attached molecules, proteins and nanobeads along the fibre.
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Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cells.
EMBO J.
PUBLISHED: 02-09-2010
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Wnt5a is a representative ligand that activates the Wnt/beta-catenin-independent pathway, resulting in the regulation of cell adhesion, migration, and polarity, but its molecular mechanism is poorly understood. This report shows that Dishevelled (Dvl) binds to adenomatous polyposis coli (APC) gene product, and this binding is enhanced by Wnt5a. Dvl was involved in the stabilization of the plus end dynamics of microtubules as well as APC. Frizzled2 (Fz2) was present with Wnt5a at the leading edge of migrating cells and formed a complex with APC through Dvl. Fz2 also interacted with integrins at the leading edge, and Dvl and APC associated with and activated focal adhesion kinase and paxillin. The binding of APC to Dvl enhanced the localization of paxillin to the leading edge and was involved in Wnt5a-dependent focal adhesion turnover. Furthermore, this new Wnt5a signalling pathway was important for the epithelial morphogenesis in the three-dimensional culture. These results suggest that the functional and physical interaction of Dvl and APC is involved in Wnt5a/Fz2-dependent focal adhesion dynamics during cell migration and epithelial morphogenesis.
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[A case of advanced gastric cancer treated with S-1 and S-1/paclitaxel showing complete response twice].
Gan To Kagaku Ryoho
PUBLISHED: 12-29-2009
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The patient was a 76-year-old man with advanced gastric cancer located in cardia, and was diagnosed to have an invasion to diaphragma and multiple lymph node metastases. We treated successfully with 12-course of S-1 chemotherapy. But second primary gastric cancer was detected in antrum 26 months after primary therapy. We treated with S-1/paclitaxel ( PTX) combined chemotherapy. S-1 (80 mg/m2) was orally administered for 2 weeks followed by a week interval and PTX (50 mg/m2) was also administered days 1 and 8. One course of chemotherapy was 21 days. GIF and abdominal CT revealed complete response (CR) after 3 courses of chemotherapy. We are now going on 6 courses of chemotherapy and the patient did not experience any grade 3 adverse effects.
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[Hepatectomy with microwave coagulation therapy for multiple liver metastases of rectal carcinoid--a case report].
Gan To Kagaku Ryoho
PUBLISHED: 12-29-2009
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A woman in her 50s was admitted to our hospital for the evaluation of liver masses. Low density areas at S5, S6 and S8 of the liver were revealed by enhanced abdominal CT scan. While exploring for the primary site, we observed a flat tumor, 10 mm in diameter, in the rectum at 10 cm from the anal ring, and local resection of the tumor was performed transanally. It was histologically diagnosed as a rectal carcinoid. During surgery, ultrasonography revealed eight hypoechoic masses at S4, S5, S6 and S8 of the liver. We conducted a partial hepatectomy (S8, S5/6) and microwave coagulation therapy. Histologically, the masses were diagnosed as liver metastases of rectal carcinoid. As of 27 months since surgery, liver metastases control is favorable, and no local recurrence has been observed. Hepatectomy with microwave coagulation therapy is believed to be locally effective in multiple liver metastases of rectal carcinoid tumor.
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Primary yolk sac tumor within the lateral ventricle.
Neurol. Med. Chir. (Tokyo)
PUBLISHED: 11-27-2009
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A 13-year-old girl presented with an exceedingly rare case of primary yolk sac tumor located within the lateral ventricle, manifesting as headache, nausea, and diplopia. Magnetic resonance imaging revealed a 4-cm-diameter solid enhanced mass within the left inferior horn of the lateral ventricle. The tumor was removed subtotally via left middle temporal corticotomy. The histological and immunohistochemical diagnosis was pure yolk sac tumor. The serum alpha-fetoprotein (AFP) level was elevated at 1957.2 ng/ml and the serum beta-human chorionic gonadotropin level was 4 mIU/ml after surgery. The patient underwent radiotherapy (whole brain, 30 Gy; tumor bed, 21 Gy; whole spinal axis, 30 Gy) and chemotherapy (ifosfamide, cisplatin, etoposide). After three treatment cycles, the serum AFP level had decreased to 4.5 ng/ml. However, the tumor recurred with cerebrospinal fluid dissemination after nine cycles of chemotherapy. She died 18 months after surgery. The possibility of germ cell tumor should be considered in pediatric patients with brain tumors occurring outside the pineal or suprasellar region.
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Management of pilomyxoid astrocytomas: our experience.
Anticancer Res.
PUBLISHED: 05-06-2009
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Pilomyxoid astrocytoma (PMA) shows a higher rate of recurrence and cerebrospinal fluid (CSF) dissemination than does pilocytic astrocytoma (PA). In this article, we discuss the treatment of PMA.
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A case of a heavily pigmented orbital melanocytoma.
Brain Tumor Pathol
PUBLISHED: 04-30-2009
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We present an extremely rare case of an orbital melanocytoma that occurred in a 51-year-old man. The patient suffered from diplopia and mild exophthalmos of the right eye for 2 months. Brain magnetic resonance imaging showed a well-demarcated round mass 3.5 cm in diameter in the right orbit. We performed total resection of this tumor. Histological findings revealed a proliferation of large polygonal cells with fine pigment granules in the cytoplasm and prominent nucleoli. Although these tumor cells revealed immunohistochemical reactivity in HMB-1, there was no S-100 or Melan A antibody reactivity. Also, there were no malignant findings of nuclear polymorphism, mitoses, or necrosis. The brown pigments were confirmed to be melanin by bleaching and the Fontana-Masson silver stain method. The MIB-1 labeling index was less than 1%. This tumor also consisted of 50% melanophages, which revealed immunohistochemical reactivity in CD68, CD163, and in (1-AT antibodies. These histological findings led us to diagnose an orbital melanocytoma with partial tumor regression.
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Supramolecular hydrogel exhibiting four basic logic gate functions to fine-tune substance release.
J. Am. Chem. Soc.
PUBLISHED: 04-01-2009
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Logic-gate operations displaying macroscopic outputs are promising systems for the development of intelligent soft materials that can perform effective functions in response to various input patterns. A supramolecular hydrogel comprising the phosphate-type hydrogelator 1 exhibits macroscopic gel-sol behavior in response to four distinct input stimuli: temperature, pH, Ca(2+), and light. We characterized this performance through microscopic, spectroscopic, and rheological measurements. On the basis of its multiple-stimulus responsiveness, we constructed gel-based supramolecular logic gates from hydrogelator 1 that demonstrated AND, OR, NAND, and NOR types of stimulus-responsive gel-sol behavior in the presence of various combinations of the four stimuli. Implementation of such logic-gate functions into semiwet soft materials (e.g., supramolecular hydrogels) is an important step toward the design of controlled drug delivery and release systems. Indeed, we demonstrate herein that one of our gel-based supramolecular logic gates is capable of holding and releasing bioactive substances in response to logic triggers. Furthermore, combining our supramolecular gel-based AND logic gate with a photoresponsive supramolecular gel could temporarily modulate the release rate of the bioactive substance.
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[A case of invasive ductal carcinoma of the pancreas originating from an intraductal papillary mucinous tumor that was initially misdiagnosed as a mucinous cystic tumor].
Gan To Kagaku Ryoho
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A 57-year-old woman was discovered to have a cystic tumor, 8 cm in diameter, at the pancreas tail, during routine screening with ultrasonography. The patient did not complain of tenderness, and no abdominal mass was palpable at physical examination. Enhanced computed tomography(CT) revealed that the tumor had mural nodules in the cyst wall, and we suspected it to be a malignant tumor that had occurred in the mucinous cystic neoplasm(MCN). Therefore, surgical resection was attempted, upon which the tumor was found to be hard and the surrounding tissue adhered widely to the stomach. We separated it carefully from the stomach and then performed a distal pancreatectomy. The cut surface revealed that the posterior wall of the cystic tumor was partly thickened, and microscopic examination revealed it to be invasive ductal carcinoma. No ovarian-like stroma was involved and some degree of dysplasia(PanIN 1-3) was found in the neighboring tissues. Therefore, we re-diagnosed it to be invasive ductal carcinoma of the pancreas derived from intraductal papillary mucinous tumor(IPMT), not from MCN. The patient received adjuvant chemotherapy, although 5 months later multiple lung metastases had appeared. The international consensus guidelines for management of IPMN and MCN of the pancreas suggest that they can usually be distinguished preoperatively, if there is a complete understanding of their clinical and imaging features. However, we sometimes find it difficult to distinguish the 2, because some IPMN or MCN cases have shared preoperative features. Herein, we report the case of invasive ductal carcinoma of the pancreas derived from IPMT that was originally misdiagnosed as a MCN.
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[Total pancreatectomy for pancreatic head cancer accompanied with multiple lesions].
Gan To Kagaku Ryoho
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Our patient was a 67-year-old man, with a chief complaint of brown urine. He subsequently underwent medical examination in June. Because the results of his blood examination revealed liver dysfunction, he was admitted to our hospital for further careful examination. An abdominal computed tomography(CT) scan showed the presence of a pancreas tumor, with a diameter of 2 cm, at the pancreas head, as well as common biliary duct dilatation and main pancreatic duct dilation from the head to the tail of the pancreas. The patient was diagnosed with pancreatic cancer[cT3( CH+, DU+), cN0, cM0, cStage III], with obstructive jaundice. After biliary drainage, we performed laparotomy in August. During the operation, other than the tumor on the pancreas head, identified at the preoperative diagnosis, we found 2 white nodules on the pancreas surface. One nodule was located at the body of the pancreas and the other, at its tail. On intraoperative pathological examination of the nodules, they were found to be invasive ductal carcinomas. On the basis of these findings, we suspected multiple cancers or overall pancreatic cancer; therefore, we performed total pancreatectomy, not pancreaticoduodenectomy (PD). We choose pancreatectomy over PD because it was impossible to confirm the cancerous area. Pathological examination of the resected specimen did not reveal any malignant lesion. Thus, if we had not performed pancreatectomy, assuming that the pancreas body or tail had no cancer lesion, based on the pathological examination result, the cancer would have persisted. Further, careful examination involving inspection and palpation is considered to be essential before resection of the pancreas tumor.
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[Laparoscopic reconstruction of jejunostomy catheter deviations in gastric and esophageal cancer patients who underwent jejunostomy].
Gan To Kagaku Ryoho
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Jejunostomy feeding is useful for maintaining nutrition in patients with gastric cancer and esophageal cancer. Special provisions must be made in cases of occlusion or dislocation of the jejunostomy catheter, and when the catheter is narrow and difficult to approach by endoscopy. Between 2007 and 2011, we encountered 69 cases of jejunostomy: 40 performed for gastric cancer and 29 for esophageal cancer. Catheter occlusion was seen in 7 cases and catheter dislocation in 9. Of these 16 cases, 14 could be recovered using interventional radiology (IVR), and the remaining 2 could not be because of fistel closure.
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[A surgical case of solitary lymph node metastasis of hepatocellular carcinoma after nonsurgical treatment].
Gan To Kagaku Ryoho
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A 66-year-old man with multiple hepatocellular carcinomas(HCCs) underwent transcatheter arterial chemoembolization(TACE) twice and radiofrequency ablation(RFA) twice at another hospital in June 2009. In November 2010, abdominal computed tomography(CT) revealed a solitary lymph node metastasis( 23 mm in diameter) in the hepatoduodenal ligament, after which he was admitted to our hospital in December 2010. In February 2011, ethoxybenzyl diethylenetriamine pentaceric acid-enhanced magnetic resonance imaging (EOB-MRI) showed revealed a growing solitary lymph node metastasis(33 mm in diameter) and good control of the intrahepatic lesion. Positron emission tomography(PET)-CT confirmed the solitary lymph node metastasis without any other extrahepatic recurrence. We performed lymph node resection in March 2011 because of good control of the intrahepatic lesion and the lack of extrahepatic recurrence. He was discharged from our hospital 11 days after surgery with a good postoperative course. Histologically, the tumor was diagnosed as a lymph node metastasis of poorly differentiated HCC. Subsequent abdominal CT in January 2012 revealed multiple recurrent lesions, and he underwent TACE therapy in February 2012. Currently, the patient is alive 1 year 3 months after lymph node resection without any other extrahepatic recurrence.
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[Focal nodular hyperplasia that was difficult to differentiate from hepatocellular carcinoma].
Gan To Kagaku Ryoho
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A 59-year-old man had received medical treatment for alcoholic hepatopathy. He stopped drinking 3 years before visiting the hospital. On medical examination, the abdominal echo showed a hepatic mass lesion that was HBs-Ag (-) and HCV-Ab (-). Computed tomography (CT) revealed a tumor of more than 25 mm in diameter at S7 of the liver. Dynamic CT showed that it was stained in the early phase but washed out in the delay phase. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor in both T1-and T2-weighted images, and it was also stained in the EOB Primovist MRI hepatobiliary phase. The findings from the images were not typical for hepatocellular carcinoma(HCC) or other benign tumors. We therefore performed an S7 partial hepatectomy. We diagnosed the tumor as focal nodular hyperplasia (FNH) by histology.
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The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility.
Nat Commun
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Dishevelled is the common mediator of canonical and non-canonical Wnt signalling pathways, which are important for embryonic development, tissue maintenance and cancer progression. In the non-canonical Wnt signalling pathway, the Rho family of small GTPases acting downstream of Dishevelled has essential roles in cell migration. The mechanisms by which the non-canonical Wnt signalling pathway regulates Rac activation remain unknown. Here we show that Daple (Dishevelled-associating protein with a high frequency of leucine residues) regulates Wnt5a-mediated activation of Rac and formation of lamellipodia through interaction with Dishevelled. Daple increases the association of Dishevelled with an isoform of atypical protein kinase C, consequently promoting Rac activation. Accordingly, Daple deficiency impairs migration of fibroblasts and epithelial cells during wound healing in vivo. These findings indicate that Daple interacts with Dishevelled to direct the Dishevelled/protein kinase ? protein complex to activate Rac, which in turn mediates the non-canonical Wnt signalling pathway required for cell migration.
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Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling.
J. Cell. Sci.
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Glypicans are members of the heparan sulfate proteoglycans (HSPGs) and are involved in various growth factor signaling mechanisms. Although HSPGs affect the ?-catenin-dependent and -independent pathways of Wnt signaling, how they regulate distinct Wnt pathways is not clear. It has been suggested that the ?-catenin-dependent pathway is initiated through receptor endocytosis in lipid raft microdomains and the independent pathway is activated through receptor endocytosis in non-lipid raft microdomains. Here, evidence is presented that glypican-4 (GPC4) is localized to both membrane microdomains and that the localization affects its ability to regulate distinct Wnt pathways. GPC4 bound to Wnt3a and Wnt5a, which activate the ?-catenin-dependent and -independent pathways, respectively, and colocalized with Wnts on the cell surface. LRP6, one of Wnt3a coreceptors, was present in lipid raft microdomains, whereas Ror2, one of Wnt5a coreceptors, was localized to non-lipid raft microdomains. Expression of GPC4 enhanced the Wnt3a-dependent ?-catenin pathway and the Wnt5a-dependent ?-catenin-independent pathway, and knockdown of GPC4 suppressed both pathways. A GPC4 mutant that was localized to only non-lipid raft microdomains inhibited the ?-catenin-dependent pathway but enhanced the ?-catenin-independent pathway. These results suggest that GPC4 concentrates Wnt3a and Wnt5a to the vicinity of their specific receptors in different membrane microdomains, thereby regulating distinct Wnt signaling.
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Regulation of focal adhesion dynamics by Wnt5a signaling.
Methods Mol. Biol.
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Wnt5a is a representative ligand that activates the ?-catenin-independent pathway of Wnt signaling in mammals. This pathway might be related to planar cell polarity signaling in Drosophila. Because reliable biochemical assays to measure Wnt5a pathway activity have not yet been established, we examined whether Wnt5a signaling stimulates focal adhesion turnover in migrating cells using live immunofluorescence imaging and immunocytochemical analysis. These assays demonstrated that the Wnt5a pathway cooperates with integrin signaling to regulate cell migration and adhesion through focal adhesion dynamics.
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What is Visualize?

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

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

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