The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component.
In order to determine if metastatic malignant mesothelioma cells are more aggressive than primary malignant mesothelioma cells, an analysis of the expression of the adhesion molecules E-cadherin and ?-catenin, concomitant with an assessment of the proliferative activity at primary and metastatic sites, was conducted in post-mortem samples.
Survivin is expressed in the nucleus and/or cytoplasm of various types of malignant tumor cells. Nuclear survivin is indispensable for complete mitosis, while cytoplasmic survivin functions as an apoptosis inhibitor. We examined the difference in the survivin expression among stromal cells of fibroadenoma, and benign and malignant phyllodes tumors.
Regulatory dendritic cells (DCregs) represent a potential therapeutic tool for assessing a variety of immune overreaction conditions; however, current approaches for generating DCregs for therapeutic purposes are limited. We attempted to generate and characterize DCregs from murine induced pluripotent stem (iPS) cells. The iPS cells co-cultured with OP9 cells displayed mesodermally differentiated flat colonies. GM-CSF drove most of the colonies exhibiting a differentiated morphology. Thereafter, cells became morphologically heterologous under the effects of TGF-? and IL-10. Most of the floating cells developed an irregular shape with areas of protrusion. The generated iPS-DCregs demonstrated high CD11b/c and low CD40, CD80, CD86 and MHC-II expressions with a high antigen uptake ability and poor T-cell stimulatory function. Importantly, iPS-DCregs showed immune responsiveness regulation effects both in vitro and in vivo and the ability to generate regulatory T-cells in vitro. Our result illustrates a feasible approach for generating functional DCregs from murine iPS cells.
Survivin is expressed in the cytoplasm and/or nucleus of various types of malignant tumor cells. Cytoplasmic survivin functions as an apoptosis inhibitor, while nuclear survivin is indispensable for complete mitosis completion. To investigate the effect of cigarette smoking on the survivin expression in lung adenocarcinomas at the early developmental stage, we examined the expression of nuclear and cytoplasmic survivin in pathological Stage IA lung adenocarcinomas resected from 38 non-smokers and 44 smokers (current smokers and ex-smokers) using an immunohistochemical method. Labeling indices of nuclear survivin in tumors of smokers were significantly greater than those of non-smokers. The labeling index of nuclear survivin was above 3 % in only 1 (2.6 %) of the 38 tumors of the non-smokers, while the labeling indices in 19 (43.2 %) of 44 tumors of the smokers were above 3 % with a significantly greater frequency. There was no significant difference in the labeling index of nuclear survivin between current smokers and ex-smokers. There was no significant difference in the labeling index of cytoplasmic survivin between tumors of the non-smokers and the smokers. The present results show that cigarette smoking is associated with the higher nuclear surviving expression in lung adenocarcinomas at the early stage, suggesting that cigarette smoking affects the nuclear survivin expression in lung adenocarcinomas at the early developmental stage.
The oral administration of thioacetamide to rats induces cholangiofibrosis characterized by hyperplasia of ductules surrounded by fibrous tissue. In the present study, we examined the expression of markers of cholangiocyte and hepatocyte phenotypes in these hyperplastic ductule cells and their proliferative activity immunohistochemically. The oral administration of thioacetamide to 21-day-old male Fisher 344 rats for 12 weeks induced multiple areas of various sizes with hyperplastic ductules. The ductules consisted of two types of ductules; ductules composed of cholangiocyte-like cuboidal cells with transparent nuclei and cytoplasm, and of intestinal epithelium-like (IE-like) cells of basophilic nuclei and cytoplasm, and the transition of these two types of cells in the same ductule was sometimes observed. The cholangiocyte-like cells expressed cytokeratin (CK)-7, CK-19 and OV-6 (cholangiocyte phenotype markers) but not Hep Par-1 antigen or HNF4? (hepatocyte phenotype markers). In contrast, the IE-like cells expressed Hep Par-1 antigen and HNF4? but not CK-7, CK-19 or OV-6. The examination of Ki-67 expression showed a much higher proliferative activity for the IE-like cells compared to the cholangiocyte-like cells. The present results show that the hyperplastic ductules induced by thioacetamide are composed of IE-like cells with a high proliferative activity expressing the hepatocyte phenotype markers and of cholangiocyte-like cells with a low proliferative activity expressing the cholangiocyte phenotype markers.
In this study, the expression of hepatocyte markers, including ?-fetoprotein (AFP), HepPar-1 antigen and arginase-1, was examined immunohistochemically in 14 mass-forming peripheral intrahepatic cholangiocarcinomas (ICCs) that arose from the peripheral portion of the biliary tree, and in 14 periductal-infiltrating hilar ICCs that arose from intrahepatic large bile ducts. Only 2 (14.3%) of the 14 hilar ICCs and 2 (14.3%) of the 14 peripheral ICCs expressed AFP or HepPar-1 antigen. Conversely, arginase-1 was expressed in 8 (57.1%) and 11 (78.6%) of the hilar and peripheral ICCs, respectively, and 4 (28.6%) hilar ICCs and 7 (50%) peripheral ICCs expressed arginase-1 in more than 10% of the cancer cells. The expression of arginase-1 did not differ between peripheral ICCs showing major histology of poorly differentiated adenocarcinoma and those showing other major histologies, including well-or moderately differentiated tubular adenocarcinoma or papillary adenocarcinoma. Results of the present study showed that common hepatocyte markers, including AFP and HepPar-1 antigen, are rarely but definitely expressed in hilar and peripheral ICCs, and that a third hepatocyte marker, arginase-1, is expressed at a high rate in both hilar and peripheral ICCs, irrespective of their histology. These results indicate that care should be taken when using arginase-1 as a hepatocyte marker for distinguishing between a poorly differentiated hepatocellular carcinoma and a mass-forming peripheral ICC showing the histology of poorly differentiated adenocarcinoma.
A 66-year-old male patient underwent a stomach-preserving pancreatoduodenectomy procedure because of a tumor located around the lower bile duct under the diagnosis of carcinoma of the lower bile duct. The tumor (3.5 × 2.5 cm) was found at the head of the pancreas and had invaded the papillae of Vater at the duodenum. Histology findings indicated both ductal adenocarcinoma and endocrine tumor. The ductal adenocarcinoma component expressed carcinoembryonic antigen, cytokeratin (CK)-19, CK-20, carbohydrate 19-9, and amylase, whereas the endocrine component, which occupied about one-third of the tumor, expressed glucagon, neuron-specific enolase, and chromogranin A. The Ki-67 labeling indices of the two components were 49.7% and 5.3%, respectively. Herein, we present this case of mixed ductal-endocrine carcinoma of the pancreas. Our findings indicate that its aggressive mass may be ascribable to the adenocarcinoma component with a high proliferative potential.
How the maintenance checks of the medical treatment system, including start of work check and the ending check, was effective for preventive maintenance and the safety improvement was verified. In this research, date on the failure of devices in multiple facilities was collected, and the data of the trouble repair record was analyzed by the technique of reliability engineering. An analysis of data on the system (8 general systems, 6 Angio systems, 11 CT systems, 8 MRI systems, 8 RI systems, and the radiation therapy system 9) used in eight hospitals was performed. The data collection period assumed nine months from April to December 2008. Seven items were analyzed. (1) Mean time between failures (MTBF) (2) Mean time to repair (MTTR) (3) Mean down time (MDT) (4) Number found by check in morning (5) Failure generation time according to modality. The classification of the breakdowns per device, the incidence, and the tendency could be understood by introducing reliability engineering. Analysis, evaluation, and feedback on the failure generation history are useful to keep downtime to a minimum and to ensure safety.
Pleomorphic carcinoma (PC) of the lung consists of an epithelial component showing the histology of poorly differentiated non-small cell carcinoma of the lung and a sarcomatous component, that is more aggressive compared to non-small cell carcinoma of the lung. To determine the differences between an epithelial component of PC and poorly differentiated non-small cell carcinoma, the expression of adhesion molecules (E-cadherin, ?-catenin and N-cadherin) and transforming growth factor-? (TGF-?) was compared immunohistochemically among 14 poorly differentiated adenocarcinomas of the lung (PDAs) and 14 PCs of the lung, with an epithelial component, showing the histology of PDA. Expression levels of E-cadherin and ?-catenin were significantly lower in epithelial or sarcomatous components of PCs than in PDAs while that of TGF-? was significantly higher in epithelial components of PCs than in PDAs. No significant difference was found in incidences of the expression of these molecules between epithelial and sarcomatous components of PCs. No significant difference was noted in the expression level of N-cadherin among PDAs and epithelial and sarcomatous components of PCs. The present results showed that E-cadherin and ?-catenin expression is reduced and TGF-? expression is increased in epithelial components of PCs with the same histology as PDA when compared to PDAs, suggesting that an epithelial component of PC is distinct from non-small cell carcinoma with the same histology.
A malignant mesothelioma (MM) is an aggressive neoplasm, although some patients have shown long-term survival, and factors related to survival remain uncertain. We present three cases of MM of the peritoneum including autopsy results, in which factors related to long-term survival were investigated. Case 1 was a 69-year-old man who died 6 years after the initial diagnosis. In case 2, a 67-year-old woman came to us with abdominal distention and, despite chemotherapy, died 9 months after the initial diagnosis. The patient in case 3 was a 68-year-old man who also had abdominal distention and died 9 months after the initial diagnosis. We studied the clinicopathological appearance and performed immunohistochemical staining including Ki-67 labeling index (Ki-67 LI) in primary and metastatic sites of these cases. The histological findings of case 1 indicated epithelioid type; case 2 and 3 were of biphasic type. Immunohistochemical results were consistent with MM. The Ki-67 LI value for both primary and metastatic sites of case 1 was significantly lower than those in cases 2 and 3. We consider Ki-67 LI to be a useful prognostic indicator for MM of the peritoneum.
Ulcerative colitis (UC) complicated by colonic lymphoma is rare, although UC is often accompanied by adenocarcinoma of the colon. A concurrent existence of adenocarcinoma and lymphoma in a patient with UC is extremely rare, and has not yet been analyzed at the molecular level. We report a 64-year-old female patient with concomitant adenocarcinoma and diffuse large B-cell lymphoma (DLBCL) in the colon of UC. The genetic changes in these two neoplasms were analyzed. The colon adenocarcinomas had a mutation in MSH6 gene, DNA methylation in CDKN2A gene, and increased microsatellite instability (MSI), although these genetic changes were not recognized in either DLBCL or non-neoplastic UC mucosa. The DLBCL was diagnosed as primary colonic lymphoma, and confirmed Epstein-Barr virus (EBV) infection. The adenocarcinomas and the non-neoplastic UC mucosa were EBV-negative. Our case presented here clearly shows that the development of adenocarcinoma and lymphoma in the colon with UC was caused by individual mechanisms.
Guidelines for treatment of hypertension are not available for chronic hemodialysis (HD) population, despite the high mortality rate due to cardiovascular disease (CVD). Survival is much better among hypertensive patients than normal to hypotensive patients. Target levels of blood pressure and the class of antihypertensive drugs have not been examined in prospective studies.
To achieve good care for stroke patients in the Hokumou Secondary Medical District, we reaffirmed the current status of the services, discovered the keypoints and issues, and searched for solutions to the current problems. The population, its age composition and the number of beds occupied by stroke patients--stratified in acute, convalescent and maintenance stages-were surveyed. The number of patients suffering from stroke under the jurisdiction of this district was compiled, by using the "regional alliance path for stroke," and the severity and outcome of each case were evaluated by using the mRS (modified Rankin Scale). We held seminars for citizens on the prevention and management of stroke and the attendees were asked to fill out questionnaires, and were organized: networks for medical care and nursing in the Okhotsk Sea area and peoples voices were heard at the network meetings; and at the town meetings held at Kitami, Abashiri and Bihoro, the challenges and problems in each area were discussed. The findings obtained from these activities were compiled for the current study. The rate of release of the patients to their home environment was high in the acute stage but low in the convalescent stage. To substantiate the regional management of stroke patients, it is essential that one be familiar with the availability of the limited medical recourses for and dynamics of patients. And yet, there is a limit to the efforts that the medical profession alone can make for the acute and convalescent stages. It is necessary that the health services assist in solving the problems, with the cooperation of the citizens and the nursing network that is involved in homes and nursing facilities for the care of patients in the maintenance stage.
We examined the expressions of adhesion molecules (E-cadherin, beta-catenin, CD44s, and CD44v6) and Ki-67 labeling index (Ki-67 LI) in low- and moderate-grade dysplasia and invasive carcinoma components in ten noninvasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and eight invasive carcinomas associated with IPMNs of the pancreas using immunohistochemical methods. There was no significant difference in regard to the proportion of components expressing either E-cadherin or beta-catenin in more than 70% of the tumor cells between the low- and moderate-grade dysplasia components. In contrast, the proportion of those in invasive carcinoma components was significantly lower than in low- or moderate-grade dysplasia components. Also, there was no significant difference in the proportion of components expressing CD44s or CD44v6 in more than 5% of tumor cells among low-grade dysplasia, moderate-grade dysplasia, and invasive carcinoma components. In contrast, the Ki-67 LI values increased in the order of low-grade dysplasia, moderate-grade dysplasia, and invasive carcinoma components, with significant differences among them. The present results indicate that carcinoma components are associated with a decrease in tumor cells expressing E-cadherin and beta-catenin and have the highest proliferative activity.
Mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the branch duct type (IPMN-BD) differ in biological and clinical behaviors, but MCN is often misdiagnosed as IPMN-BD. The purpose of this study was to find useful markers for the differential diagnosis of MCN and IPMN-BD.
Nephrin is an essential structural component of the glomerular slit diaphragm (SD), a highly organized intercellular junction that constitutes the ultrafiltration barrier of the kidney. Recent studies have identified two additional nephrin-interacting SD proteins (NEPH1 and NEPH2), suggesting that the zipper-like pattern of the SD is formed through complex intra- and intermolecular interactions of these proteins. However, the complexity of the SD structure suggests that additional SD components remain to be discovered. In this study, we identified galectin-1 (Gal-1) as a new component of the SD, binding to the ectodomain of nephrin. Using dual-immunofluorescence and confocal microscopy and dual-immunoelectron microscopy, we found Gal-1 co-localizing with the ectodomain of nephrin at the SD in normal human kidney. By immunoprecipitation and surface plasmon resonance, we confirmed a direct molecular interaction between Gal-1 and nephrin. Moreover, recombinant Gal-1 induced tyrosine phosphorylation of the cytoplasmic domain of nephrin and activation of the extracellular signal-regulated kinase 1/2 in podocytes. We also showed that podocytes are a major site of biosynthesis of Gal-1 in the glomerulus and that the normal expression patterns and levels of Gal-1 are altered in patients with minimal change nephrotic syndrome. Finally, in puromycin aminonucleoside-induced rat nephrosis, an apparent reduction in the levels of Gal-1 and nephrin around the onset of heavy proteinuria was also revealed. Our data present Gal-1 as a new extracellular ligand of nephrin localized at the glomerular SD, and provide further insight into the complex molecular organization, interaction, and structure of the SD, which is an active site of intracellular signaling necessary for podocyte function.
We evaluated the X-ray digital linear tomosynthesis reconstruction processing method for metal artifact reduction. A volumetric X-ray digital linear tomosynthesis instrument was used to image a hip prosthesis. Artifacts caused by high-attenuation features in hip prostheses were observed in digital linear tomosynthesis reconstruction due to the few projections and narrow angular range typically employed in tomosynthesis imaging. We developed artifact reduction methods based on a modified Shepp and Logan reconstruction filter kernel realized by taking into account additional weighing by direct current (DC) components in frequency domain space. Processing leads to an increase in the ratio of low-frequency components in an image. The effectiveness of the method in enhancing the visibility of a prosthetic case was quantified in terms of removal of ghosting artifacts. The potential of artifact reduction processing for digital linear tomosynthesis in the evaluation of hip prostheses was demonstrated. A modified Shepp and Logan reconstruction filter kernel causes artifact reduction and improved the quality of images affected by metal artifacts. Future investigations will study the ability of digital linear tomosynthesis to quantify the spatial relationship between the metallic components of these devices as well as the ability of the technique to identify bony changes of diagnostic significance.
A 77-year-old man developed pulmonary tumor thrombotic microangiopathy (PTTM) 2 days after undergoing transurethral resection for urothelial carcinoma (G3) of the urinary bladder and died of respiratory failure 6 days later. Histological findings demonstrated marked intimal fibrocellular proliferation, fibrin thrombi, and both cancer cells and fibrin thrombi in the arteries of the lungs, findings consistent with PTTM. Prominent stenosis in arteries smaller than 300 ?m was also seen. The Ki-67 labeling index of primary and metastasized cancer cells was 62.4 % and 70.2 %, respectively. The membranes of metastasized cancer cells expressed E-cadherin, similar to membranes in the urinary bladder. An aggressive PTTM course is affected by intimal fibrocellular proliferation and the high cell proliferation of cancer cells. Furthermore, prominent stenosis in small arteries and membranous staining of E-cadherin of metastasized cells suggest that cancer cells formed clusters by maintaining adhesion molecules and migrated into the arteries of the lungs, where they easily caused damage to the endothelium of small arteries, in contrast to dispersed cancer cells.
Extra-gastrointestinal stromal tumors (E-GISTs) not associated with the alimentary tract in the pelvic cavity are extremely rare. We treated a 49-year-old Japanese man with such an E-GIST in the pelvic cavity who underwent an intrapelvic tumorectomy with a total prostatectomy and partial rectum resection. Gross examination of the specimen revealed an 8.1 × 5 × 4 cm white-grayish mass. Histological findings showed uniform spindle cells with scant atypia that formed interlacing bundles or whorl patterns. These neoplastic cells did not invade adjacent organs, including the gut. Immunohistochemical findings revealed that the neoplastic cells were positive for c-kit, CD34, and vimentin. Molecular analysis showed a c-kit mutation at exon 9 with duplication of Ala and Tyr. Our diagnosis was E-GIST, which belongs to the intermediate group of GIST. Following the operation, we administered imatinib mesylate for 6 months. After stopping for 5 months, it was administered again for local recurrence. We are planning our future strategy for this case including surgical resection as necessary.
Expression of phenotype markers of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) in HCC and CC components of 20 combined hepatocellular and cholangiocarcinomas (CHCs) of the liver was investigated immunohistochemically. Both HCC and CC components of all CHCs expressed at least one of the CC phenotype markers [cytokeratin (CK)-7, CK-19, and carbohydrate (CA) 19-9]. HCC components in 90% of CHCs and CC components in 95% of CHCs expressed at least one of these CC phenotype markers in more than 40% of cancer cells. HCC components in all CHCs expressed at least one of the HCC phenotype markers [hepatocyte antigen (HA), ?-fetoprotein (AFP), and canalicular carcinoembryonic antigen]. HCC components in 90% of CHCs and CC components in 75% of CHCs expressed HA, AFP, or both. HCC components in 75% of CHCs and CC components in 60% of CHCs expressed HA, AFP, or both in more than 10% of cancer cells. The present results show that both HCC and CC components of most of the CHCs expressed both HCC and CC phenotypes, supporting the hypothesis that CHC originates from a hepatic progenitor cell capable of differentiating into hepatocytes and cholangiocytes.
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