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Biomedical subjects

Jun Amano

Publications and source records attributed to Jun Amano.

At least 37 records · Page 2Linked to original sources

Small cell carcinoma of the esophagus with reference to alternating multiagent chemotherapy: report of two cases.

We herein report the findings of two patients with small cell carcinoma of the esophagus (SCEC) who were treated with alternating chemotherapy using cisplatin and etoposide (PVP), and cyclophosphamide, adriamycin or epirubicin, and vincristine (CAV). Patient 1 was a 61-year-old woman with SCEC. Her serum level of pro-gastrin-releasing peptide (Pro-GRP) was elevated (79.8 pg/ml; normal range <46.0 pg/ml). The patient underwent an esophagectomy following PVP/CAV-therapy. Six months later her serum level of Pro-GRP became elevated, and multiple metastases to the liver and lung were detected. Two courses of PVP/CAV-therapy were performed, and these metastatic foci almost completely disappeared. The serum level of Pro-GRP was in the normal range. One year after surgery, multiple brain metastases and recurrence of liver metastases were detected, then the serum level of Pro-GRP became re-elevated. Two courses of PVP/CEV-therapy were performed, and the metastases to the brain and liver decreased in size. However, the brain metastases relapsed, and the patient died 21 months after the diagnosis. Patient 2 was treated with two courses of preoperative PVP/CAV-therapy; however, the patient died of multiple liver metastases 17 months after the diagnosis. In six previously documented patients and the two present patients who were treated with PVP/CAV-therapy, the primary or metastatic foci of SCEC decreased in size, and the mean survival of the patients was 19 months. In conclusion, PVP/CAV alternating chemotherapy is beneficial for prolonging the survival of SCEC patients; however, new chemotherapeutic modalities are still needed to further improve the prognosis of SCEC patients. Furthermore, the level of serum Pro-GRP in patients with SCEC may be both a diagnostic marker and a therapeutic monitor.

Aged↗

Basaloid-squamous carcinoma of the esophagus treated by preoperative chemotherapy: report of two cases.

Basaloid squamous carcinoma (BSC) of the esophagus has been associated with a poor outcome after surgery. We herein report two patients with esophageal BSC treated by preoperative chemotherapy. Patient 1 was a 55-year-old man who presented with a tumor of the middle esophagus diagnosed as BSC. He was treated by chemotherapy using a combination of 5-fluorouracil (5-FU: 750 mg/m(2), 1st-5th day, 24-h continuous infusion) and cisplatin (CDDP: 75 mg/m(2), 1st day, drip infusion per 2 h) before surgery, because of lymph node metastases of the mediastinum and around the left gastric artery. Even though the metastatic nodes were reduced and an esophagectomy was performed, the patient died of recurrence 12 months after chemotherapy. Patient 2 was a 57-year-old man who demonstrated BSC of the esophagus with direct invasion to the discending aorta, who was treated by preoperative chemotherapy using the same regimen as that of patient 1. The esophageal tumor was reduced, and a curative esophagectomy was performed. The patient is now alive without recurrence 38 months after chemotherapy. In conclusion, preoperative chemotherapy using a combination of 5-FU and CDDP may thus be an effective treatment for patients with advanced BSC of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗

Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen.

BACKGROUND: Early growth response factor-1 (Egr-1) plays an important role in regulating multiple factors involved in the progression of vascular lesions. This study examined our hypothesis that Egr-1 plays a critical role in the early stage of chronic cardiac allograft rejection and in the proliferation of the smooth muscle cell response to alloantigen. MATERIALS AND METHODS: Antisense Egr-1 oligodeoxynucleotide (ODN) was ex vivo gene transfected into the donor hearts from DBA/2 mice, followed by heterotopic allografting into B10.D2 recipients. The allografts were harvested on day 30. Egr-1 and its target molecules, such as platelet-derived growth factor (PDGF)-A, basic fibroblastic growth factor (bFGF), vascular cell adhesion molecule (VCAM)-1, transforming growth factor (TGF)-beta and nonmuscle myosin heavy chain B (SMemb), were identified immunohistochemically, and the percentage of the lumen occluded by the intima was calculated. For the cell proliferation assay, sensitized T cells were harvested from B10.D2 recipients as stimulator and then added to the SMCs, which were harvested from DBA/2 mouse aorta. Cellular proliferation was measured and Egr-1 and its target gene expression were examined by real-time RT-PCR. RESULTS: Egr-1 and its target genes were expressed in the thickened intima from untreated recipients. Egr-1 antisense ODN inhibited not only Egr-1 expression but also its target genes and significantly suppressed intimal thickening of coronary arteries. Egr-1 antisense ODN also significantly inhibited cell proliferation and expressions of Egr-1 and Egr-1 target genes in a mixed cell culture model. CONCLUSION: We conclude that Egr-1 plays an important role in the formation of the cardiac allograft vasculopathy responding to alloantigens.

Animals↗

Modification of depth and distance perception caused by long-term wearing of left-right reversing spectacles.

For 35 to 39 days, four observers wore continuously left-right reversing spectacles which pseudoscopically reverse the order of binocular disparity and direction of convergence. In three tests, we investigated how the visual system copes with the transformation of depth and distance information due to the reversing spectacles. In stereogram observation, after a few days of wearing the spectacles. the observers sometimes perceived a depth order which was opposite to the depth order that they had perceived in the pre-spectacle-wearing period. Monocular depth cues contributed more to depth perception in the spectacle-wearing period than they did in the pre-spectacle-wearing period. While the perceived distance significantly decreased during the spectacle-wearing period, we found no evidence of adaptive change in distance perception. The results indicate that the visual system adapts itself to the transformed situation by not only changing the processing of disparity but also by changing the relative efficiency of each cue in determining apparent depth.

Adaptation, Physiological↗

Significance of monocyte chemotactic protein-1 and thymidine phosphorylase in angiogenesis of human cardiac myxoma.

Angiogenesis is indispensable to tumor development and proliferation. The aim of this study was to investigate whether the expression of monocyte chemotactic protein-1 (MCP-1) and of thymidine phosphorylase (TP) correlates with the angiogenesis and clinicopathologic features in cardiac myxoma. Paraffin-embedded specimens of 17 resected cardiac myxomas were immunohistochemically stained for MCP-1, CC chemokine receptor-2 (CCR-2), TP, CD31, and CD68. Correlations among MCP-1 expression, TP expression, microvessel count (determined by CD31 staining), macrophage count (determined by CD68 staining), and the clinicopathologic features of the patients were analyzed statistically. Immunohistochemical analysis revealed that MCP-1 and TP were expressed in myxoma cells, as well as in stromal cells such as infiltrating cells, fibroblast-like cells and endothelial cells. CCR-2 was abundantly expressed in stromal infiltrating cells in all myxomas and occasionally in the endothelial cells. In the tumor stroma, the major source of MCP-1, TP and CCR-2 was macrophages, and the sites of positive staining for MCP-1, TP and CCR-2 matched in most of the myxomas. Statistical analysis revealed that the proportions of MCP-1-positive myxoma and stromal cells, and TP-positive myxoma and stromal cells significantly correlated with increased microvessel count. The proportions of MCP-1-positive myxoma and stromal cells significantly correlated with the proportion of TP-positive stromal cells. The mean microvessel count in myxomas with both high tumor and high stromal MCP-1 or TP expression was significantly higher than that in myxomas with low tumor and low stromal MCP-1 or TP expression. Small tumors (< or =55 mm in diameter) exhibited high MCP-1 or TP expression, and the microvessel count in small tumors was significantly higher than in large myxomas. Although the difference was not significant, myxomas with both high tumor and high stromal MCP-1 expression had a higher macrophage count than other myxomas. These results indicate that in cardiac myxoma, MCP-1 and TP may be regarded as important angiogenic signals accompanying growth.

Blood Vessels↗

Granular cell tumor of the mediastinum.

Mediastinal granular cell tumor is an exceptionally rare tumor; there are only a few previously reported cases. We report a 21-year-old man with a granular cell tumor in the right posterior mediastinum. Chest computed tomography scans and magnetic resonance imaging revealed a 15x20 mm well circumscribed, homogeneous mass, which was closely associated with the vertebral column. The T1-weighted magnetic resonance image showed low intensities, and moderate intensities were found on the T2-weighted magnetic resonance image. Gd-DTPA enhancement was remarkable on the tumor surface. The present case differed from ordinary neurogenic tumors in magnetic resonance imaging findings. Thoracoscopic resection of the tumor was performed. The tumor was associated with the sympathetic nerve. Histologic analysis revealed a benign granular cell tumor.

Adult↗

Cardiac myxoma: its origin and tumor characteristics.

Cardiac myxoma is most common among primary cardiac tumors, and its origin and tumor characteristics have been gradually elucidated by recent advances in molecular biology. Prichard's structure in the interatrial septum which was reported to be a candidate for the origin of cardiac myxoma, was revealed to be age-related changes. In hereditary cardiac myxoma "Carney complex", chromosomal abnormalities involving chromosomes 2p, 12 and 17q have been reported, however, no genetic abnormalities of these locus were found in the development of sporadic cases. Cardiac myxoma has multiple differentiating potentials, and recently various amounts of cardiomyocyte-specific transcription factor genes were identified. This indicates that cardiac myxoma might arise from mesenchymal cardiomyocyte progenitor cells. Various cytokines and growth factors such as vascular endothelial growth factor, basic fibroblast growth factor, monocyte chemotactic protein-1 and interleukin-6 were involved in tumor growth and angiogenesis. Although cardiac myxoma usually presents as a benign neoplasm, reports suggesting its malignancy, including recurrence of the tumor, locally invasive myxoma, extension from the heart, and distant metastasis are increasing. These genetic and molecular approaches to cardiac myxoma may prompt the development of therapeutic modalities for treatment of malignancies and cardiac cell regeneration.

Heart Neoplasms↗

Chest wall myxoma protruding into the thoracic cavity.

Myxoma protruding from the chest wall into the thoracic cavity is very rare. We report our experience in treating a 42-year-old man admitted for a painless mass on the anterior chest wall. Magnetic resonance imaging showed a sharply defined 5 x 4 x 4 cm mass protruding from the chest wall into the thoracic cavity, which we excised surgically. Histologically, the tumor proved to be a myxoma.

Adult↗

A 15-year retrospective study of hepatic resection for stage IV-A hepatocellular carcinoma shows value in hepatitis B negative patients.

BACKGROUND: The aim of this study is to identify the risk factors of survival and recurrence after curative hepatic resection for stage IV-A hepatocellular carcinoma (HCC). METHODS: Sixty-five patients with stage IV-A HCC who underwent curative hepatic resection and discharged from hospital were enrolled in this retrospective study. Prognostic factors were evaluated by univariate and multivariate analysis. Clinicopathologic features and survival with stage IV-A HCC were compared with those of 290 patients with stage I to III HCC who underwent curative hepatic resection during the same period. RESULTS: Disease-free and overall survival for patients with stage IV-A HCC was significantly lower than for those with stage I to III HCC. Positive hepatitis B virus (HBV) surface antigen was an independent prognostic factor of poor disease-free and overall survivals in patients with stage IV-A HCC. There were no significant differences in the disease-free and overall survivals between non-HBV-related stage IV-A HCC and stage I to III HCC. CONCLUSIONS: Even for patients with highly advanced HCC, curative hepatic resection may be a feasible therapeutic option for those with non-HBV-related HCC.

Aged↗

Expression of matrix metalloproteinases in cardiac allograft vasculopathy and its attenuation by anti MMP-2 ribozyme gene transfection.

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (SMCs) causes intimal thickening during cardiac allograft vasculopathy (CAV). This process requires the degradation or remodeling of extracellular matrix (ECM) surrounding the cells. Imbalance between degradation and accumulation of ECM also contributes to the development of CAV. In this study, we investigated the contribution of matrix metalloprotenases (MMPs), enzymes regulating ECM turnover, to the development of CAV. METHODS: Donor hearts from male DBA mice were heterotopically transplanted to male B10.D2 recipient mice, and harvested at days 15 and 30 post transplantation. We examined expression MMP-2, -3, -9 and -13 of graft vessels using immunohistochemistry. To clarify the role of MMP-2 in CAV, anti MMP-2 ribozyme was delivered into donor hearts just before transplantation, mediated by a hemagglutinating virus of Japan-liposome complex to specifically suppress MMP-2 activity. RESULTS: All MMPs were immunopositive in SMCs from the slightly thickened neointima at day 15. In the advanced stage of intimal thickening at day 30, in addition to increased number of SMCs, accumulation of collagenous fibers was observed; expression of MMP-3, -9 and -13 was decreased. In contrast, MMP-2 expression remained distinctly positive throughout the progression of the vascular remodeling. After the gene transfer of MMP-2 ribozyme, luminal occlusion was significantly decreased compared to non-treated allografts [25.0+/-6.5 vs. 55.1+/-7.0% (P<0.05)] at day 30 post transplantation. CONCLUSION: MMP-2 is a principle MMP throughout the progression of the vascular remodeling in CAV. Anti MMP-2 therapy could therefore be one of the candidates for a supplemental therapy for CAV.

Animals↗

Stromal sarcoma of the breast with leiomyosarcomatous pattern.

We report an unusual case of stromal sarcoma of the breast with leiomyosarcomatous pattern, which recurred locally and was finally treated by radical mastectomy. The tumor was composed of pleomorphic and hyperchromatic spindle-shaped cells arranged in an interdigitating fascicle. The nuclei were of moderate to severe atypia. An average of 10 mitoses per 10 high-power fields was seen. Immunohistochemically, the stromal cells were positive for vimentin and alpha-smooth muscle actin, but negative for S-100 protein, cytokeratin and desmin. The average Ki-67 (MIB1) labeling index in the stromal cells was 34%. Electron microscopic evaluation revealed further evidence of smooth muscle differentiation; stromal cells had frequently indented nuclei, well-developed rough endoplasmic reticulum, thin basal lamina and dense patch-like structures within the cytoplasm. Analysis of previous literature on 17 cases reveals mitotic activity of the tumor seemingly of little prognostic value. This case indicated difficulty in diagnosing leiomyosarcoma. The risk of local recurrence remains even if the surgical margin is free of tumor cells.

Breast Neoplasms↗

Quantification of cardiac stress during EGD without sedation.

BACKGROUND: Although the complication rate of endoscopy is low, EGD may induce cardiac stress. The aim of this study was to quantify cardiac stress during EGD. METHODS: Heart rate, blood pressure, cardiac output, and peripheral oxygen saturation were measured during endoscopy without sedation in 7 volunteers. Cardiac output was measured with an automated echocardiographic technique. Cardiac index, left ventricular work index, and rate-pressure product were calculated. Serum catecholamine concentrations were measured before and after the examination. RESULTS: Heart rate increased significantly when the endoscope was located in the esophagus compared with the rate before insertion (p < 0.05). No significant changes in cardiac index and left ventricular work index were observed during endoscopy. Rate-pressure product increased significantly at the point of esophageal observation compared with that before insertion (p < 0.05). The rate-pressure product was maximally increased during esophageal observation at 66% over baseline (95% CI [45%, 86%]). Serum concentration of norepinephrine rose significantly after the examination (p < 0.05). CONCLUSIONS: Cardiac output did not increase during EGD without sedation in healthy male volunteers. Cardiac stress increased during EGD as indicated by a 66% increase in rate-pressure product. The cardiac stress was approximately equal to that observed in 3.3 to 5 metabolic equivalents of treadmill exercises.

Adult↗

Cloned cytosine deaminase gene expression of Bifidobacterium longum and application to enzyme/pro-drug therapy of hypoxic solid tumors.

Bifidobacterium longum is a nonpathogenic anaerobic bacterium among normal bacterial flora. Recently, it was reported that B. longum accumulated in hypoxic solid tumors. The gene of interest was expressed in transfected B. longum by the shuttle vector pBLES100 in solid tumors. In this report, we constructed pBLES100-S-eCD, which included the cytosine deaminase gene. We confirmed by western blotting that transfected B. longum produced cytosine deaminase. In addition, transfected B. longum produced cytosine deaminase that converted 5-fluorocytosine into 5-fluorouracil. B. longum could be useful for enzyme/pro-drug therapy of hypoxic solid tumors.

Antimetabolites, Antineoplastic↗

The genus Bifidobacterium for cancer gene therapy.

A fundamental obstacle in cancer gene therapy is the specific targeting of therapy to solid tumor; as yet, no systemic delivery system exists. Bifidobacterium longum, a strain of domestic bacteria that is non-pathogenic and anaerobic, selectively localized to and proliferated in solid tumors after systemic application. We propose a novel approach to cancer gene therapy in which anaerobic bacteria of the genus B longum are used to achieve tumor-specific gene delivery and enzyme-prodrug therapy.

Animals↗

Simulation study of a selective cerebral perfusion system with a single centrifugal pump.

We previously successfully developed a simple nonroller extracorporeal circulation system (NRECC). In aortic arch surgery, more than two pumps are generally used for systemic perfusion and selective cerebral perfusion (SCP); we developed a new pressure-dependent perfusion system for SCP based on our NRECC and operated by a single centrifugal pump. The cerebral perfusion line was branched from the main perfusion line, and one 15 French and two 12 French cannulae were used for SCP. The perfusion pressure was regulated with a tube occluder. Afterload was changed from 30 to 80 mm Hg, the pressure of the SCP line was increased from 80 to 200 mm Hg, and flow volume was measured. When the afterload was set at 50 mm Hg, according to the increase of perfusion from 80 to 200 mm Hg, the flow volume of the 15 French cannula increased from 280 to 950 ml/min. Under the same conditions, flow volume of the 12 French cannula increased from 160 to 560 ml/min. Sufficient flow volume of the SCP lines was obtained when the SCP line pressure was over 80 mm Hg. As a result of the increased perfusion pressure, the flow volume showed a direct increase. These findings suggest that aortic arch surgery is possible using this SCP system.

Aorta, Thoracic↗

A pressure controller of selective cerebral perfusion with single centrifugal pump.

We are developing an original nonroller extracorporeal circulation system (NRECC). However, this NRECC could not perform selective cerebral perfusion (SCP). Therefore, we added cerebral perfusion lines and an automatic pressure controller to the system. The purpose of this study was to evaluate the stability and response of the pressure controller for the SCP in simulated clinical circulation. The NRECC consists of a centrifugal pump, four isolated vacuum suction lines and a conventional module. The SCP line branches from the main perfusion tubing and divides into three lines. Cerebral perfusion is regulated by a pressure controller, which is composed of an actuator, a pressure transducer, and a personal computer. The mock circuit was primed with normal saline, and the actual SCP pressure and flow were measured when the target pressure settled at 60, 80, and 100 mm Hg. The main perfusion flow was maintained at 4 L/min and the main perfusion pressure was altered from 120 to 300 mm Hg. The pressure and flow data were recorded. The SCP pressure was maintained within +/-1.47 mm Hg when the set pressure was 80 mm Hg. Fluctuation of flow in the SCP line was within the range of +/-2.8%. The time needed to reach the steady state pressure was 8+/-1 seconds when the initial setting of the roller occluder was full-open, and it took only 3+/-1 seconds to reach the next initial set pressure. We have developed the NRECC-SCP system. The SCP pressure is stable and quickly reaches steady state via the pressure controller. This system is useful for extracorporeal circulation during aortic arch operation.

Centrifugation↗