Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 19 recordsLinked to original sources

PubMed2006

Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment.

A recent study disclosed that breast cancer cases with low 'tau' expression can predict susceptibility to Paclitaxel administration. In the current study, the clinical significance of tau expression in gastric cancer cases was established by identifying candidates with Paclitaxel administration. Tissue specimens from 20 cases of in-operable or noncuratively resected gastric cancer were examined. Subsequent to the administration of 80 mg m(-2) of Paclitaxel in six 3-h intravenous infusions, the clinical effectiveness of Paclitaxel was evaluated by the size of metastatic lesions with computed tomography. The status of the tau expression was determined by immunohistochemistry. Based on a previously reported classification scheme, six were classified as tau-negative expression (0, 1+) cases and 14 were classified as tau-positive expression (2+, 3+) cases. All six (100%) cases of tau-negative expression showed a favourable response (partial response or minor response) to Paclitaxel administration. However, 12 (86%) of the 14 cases of tau-positive expression showed progressive disease (n = 11) or no change (n = 1) after Paclitaxel administration. The serum carcinoembryonic antigen values of the six cases of tau-negative expression were markedly decreased in comparison to the 14 tau-positive cases. These data indicate that tau-negative expression can be used to select gastric cancer patients, which will favourably respond to Paclitaxel treatment.

Adenocarcinoma↗

PubMed2003

Airway-directed gene transfer of interleukin-10 using recombinant Sendai virus effectively prevents post-transplant fibrous airway obliteration in mice.

Bronchiolitis obliterans (BO) after lung transplantation prevents a satisfactory prognosis, and recent studies suggested that interleukin-10 (IL-10) gene transfer to distant organs could inhibit BO in rodent models. Although delivery of the therapeutic gene to a local airway would be favored to minimize systemic effects, current limitations include lower gene transfer efficiency to airway epithelium. As recombinant Sendai virus (SeV) can produce dramatically efficient gene transfer to airway epithelium, we determined if SeV-mediated IL-10 gene transfer to the local airway would inhibit bronchial fibrous obliteration in murine tracheal allografts. Administration of cyclosporine A (CsA) significantly promoted not only recovery of the injured airway epithelium but also SeV-mediated IL-10 expression (CsA- versus CsA+ =228+/-78 versus 3627+/-1372 pg/graft with 5 x 10(7) pfu), thereby suggesting the requirement of epithelia for efficient gene transfer. Even at the highest expression, no significant leakage of IL-10 was evident in the systemic circulation, and the induction of interferon-gamma was completely diminished on day 7 by IL-10 gene transfer. As a result, luminal loss was significantly prevented in allografts treated with SeV-IL-10 (luminal opening, all control groups: 0% respectively, and SeV-IL-10 5 x 10(7) pfu: 25.7+/-10.5%), an effect that was enhanced by short-term CsA treatment (SeV-IL-10 5 x 10(7) pfu with CsA: 63.7+/-12.7%). We propose that SeV is a useful vector that can target airway epithelium to prevent BO avoiding putative systemic effect.

Animals↗

PubMed2003

Recombinant Sendai virus vectors for activated T lymphocytes.

T-lymphocyte-directed gene therapy has potential as a treatment of subjects with immunological disorders. One current limitation of this therapeutic strategy is low gene transfer efficiency, even when complex procedures are used. We report herein that a recombinant Sendai virus vector (SeV) was able to overcome this issue. Using jellyfish enhanced green fluorescent protein gene (EGFP), we found that SeV was able to transduce and express a foreign gene specifically and efficiently in activated murine and human T cells, but not in naive T cells, without centrifugation or reagents including polybrene and protamine sulfate; the present findings were in clear contrast to those demonstrated with the use of retroviruses. The transduction was selective in antigen-activated T cells, while antigen-irrelevant T cells were not transduced, even under bystander activation from specific T-cell responses by antigens ex vivo. Receptor saturation studies suggested a possible mechanism of activated T-cell-specific gene transfer, ie, SeV might attach to naive T cells but might be unable to enter their cytoplasm. We therefore propose that the SeV vector system may prove to be a potentially important alternative in the area of T-cell-directed gene therapy used in the clinical setting.

Animals↗

PubMed2003

Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma.

AIM: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the hypervascular type of human hepatocellular carcinoma (HCC). To gain a better understanding of the role of the Ang-Tie2 system in HCC the expression of these genes was investigated in a series of human HCCs. METHODS: The expression of the angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and 52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang-1, Ang-2, vascular endothelial growth factor (VEGF), and erythropoietin (EPO) expression was investigated in Hep3B cells. RESULTS: Ang-1, rather than Ang-2, was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly differentiated HCCs characterised by high vascularity (p = 0.02), and in tumours with a peliotic change (p = 0.02). Strong expression of Tie2 was seen in tumour vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli upregulated VEGF and EPO, but not Ang-1 or Ang-2. CONCLUSIONS: These data support the evidence that the reversal of Ang-1 and Ang-2 expression plays an important role in the angiogenic and dedifferentiation processes in HCC. The hypoxic stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in human HCC cells.

Aged↗

PubMed2003

Efficacy of a polyurethane foam/spheroid artificial liver by using human hepatoblastoma cell line (Hep G2).

We invesigated the availability of human hepatoblastoma cell line (Hep G2), compared with human primary hepatocytes (HH) and porcine primary hepatocytes (PH), as a cell source for the hybrid artificial liver support system (HALSS) by using polyurethane foam (PUF). All three kinds of hepatocytes spontaneously formed spherical multicellular aggregates (spheroids) of 100-200 microm diameter in the pores of PUF within 3 days of culture. In a PUF stationary culture, Hep G2 spheroids recovered the ammonia removal activity that was lost in monolayer culture, although the removal for each unit cell number was about one tenth that of HH spheroids and about one eighth of PH spheroids. The synthesis activities of albumin and fibrinogen of each unit cell number of Hep G2 were also upregulated by PUF spheroid culture, and were about twice as high as in monolayer culture. The albumin secretion activity of Hep G2 spheroids was almost the same as that of PH spheroids. HH scarcely secreted these proteins in this experiment, probably because they were cultured in a serum-free medium. In the PUF module in a circulation culture, HH had high ammonia removal and low synthesis activities similar to stationary culture. Hep G2 proliferated to a high cell density, such as about 4.8 x 10(7) cells/cm3-module at 10 days of culture. Although Hep G2 spheroids had low ammonia removal activity in each cell, the removal rate in the PUF module was almost the same as for PH at 7 days of culture because of the high cell density culture by cell proliferation. The albumin secretion rate by Hep G2 in the PUF module also increased with cell proliferation and was about 10 times higher than the initial for the rate for PH at 7 days of culture. These results suggest that Hep G2 is a potential cell source PUF-HALSS.

Albumins↗

PubMed2002

Laparoscopic hepatectomy and dissection of lymph nodes for intrahepatic cholangiocarcinoma. Case report.

Usually intrahepatic cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis. As a treatment for intrahepatic cholangiocarcinoma, dissection of lymph nodes alone does not seem to offer any significant advantages. The laparoscopic hepatectomy procedure, however, is a minimally invasive liver surgery. We recently had the case of a patient who underwent successful laparoscopic hepatectomy and dissection of lymph nodes for intrahepatic cholangiocarcinoma in the left lateral segment of the liver. The patient had intrahepatic cholangiocarcinoma with distant lymph node metastasis around the common hepatic artery determined to stage IVb according to TNM classification. The operation time was 335 min, and the total blood loss was only 225 ml. A left lateral hepatectomy and complete lymph node dissection around the hepatoduodenal ligament and celiac trunk was performed. In this case, a laparoscopic procedure enabled the patient to have an early discharge, and there was no recurrence for 14 months. Another advantage for this patient was that the hospital stay lasted only 10 days. As compared with conventional surgery, laparoscopic surgery reduces blood loss and shortens the hospital stay. In conclusion, laparoscopic surgery for intrahepatic cholangiocarcinoma is a good treatment for advanced intrahepatic cholangiocarcinoma because it allows a positive early postoperative outcome and possibly a better result over the long term.

Bile Duct Neoplasms↗

PubMed2002

Laparoscopy-assisted hepatectomy using the Endoclose: a case report.

Hemostasis of a resected stump of liver is extremely difficult in laparoscopic hepatectomy. Although Pringle's maneuver, which is a total clamping of the hepatoduodenal ligament, is a useful technique, it is often difficult in laparoscopic circumstances. Moreover, total inflow occlusion leads to postoperative liver damage. Therefore, the local bleeding method is ideal. The Endoclose, a device for port site closure, is formed from an outer sheath and an inner needle with a notch to load the suture. The Endoclose is loaded with a suture and passed through the liver. The suture is left under the liver, and the device is removed. Next, the suture carrier is passed through the liver at an appropriate distance, and the suture is regrasped by this suture carrier and brought out of the liver. Herein we report a case in which a new bleeding control method using Endoclose was introduced for laparoscopy-assisted hepatectomy.

Aged↗

PubMed2002

Early experiences of endoscopic procedures in general surgery assisted by a computer-enhanced surgical system.

We performed a variety of complete total endoscopic general surgical procedures, including colon resection, distal gastrectomy, and splenectomy, successfully with the assistance of the da Vinci computer-enhanced surgical system. The robotic system allowed us to manipulate the endoscopic instruments as effectively as during open surgery. It enhanced visualization of both the operative field and precision of the necessary techniques, as well as being less stressful for the endoscopic operating team. This technological innovation can therefore help surgeons overcome many of the difficulties associated with the endoscopic approach and thus has the potential to enable more precise, safer, and more minimally invasive surgery in the future.

Adult↗

PubMed2002

c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma.

AIMS: The c-erbB-2 and c-Met proto-oncogenes are important for tumour invasiveness and metastasis in many types of malignant tumours. Previous studies have indicated that these proteins are associated with carcinogenesis in intrahepatic cholangiocarcinoma. In this study, we examined c-erbB-2 and c-Met expression by immunohistochemistry in hepatolithiasis, intrahepatic cholangiocarcinoma and metastatic lymph node, in order to clarify whether these proteins play a role in carcinogenesis and tumour metastasis in intrahepatic cholangiocarcinoma. METHODS AND RESULTS: In hepatolithiasis, the staining for c-erbB-2 was positive in 14 of the 23 (61%) cases, while staining for c-Met was positive in eight of the 23 (35%) cases. In intrahepatic cholangiocarcinoma, staining for c-erbB-2 was positive in 45 of the 81 (55%) cases, while staining for c-Met was positive in 28 (35%) cases. The positivity of c-Met staining in intrahepatic cholangiocarcinoma was significantly higher in the differentiated type of cholangiocarcinoma than in the undifferentiated type. In addition, c-Met-positive staining had an inverted correlation with tumour size, the presence of perineural invasion and the presence of lymph node metastasis. c-Met staining had a significantly higher positivity in cases at an early stage of intrahepatic cholangiocarcinoma. In contrast, the positivity of c-erbB-2 staining in intrahepatic cholangiocarcinoma was significantly higher in cases with lymph node metastasis than in cases without. In metastatic lymph nodes, the staining for c-erbB-2 was positive in 20 of the 25 (80%) cases, while staining for c-Met was positive in six of the 25 (24%) cases. There was no difference in survival between c-erbB-2-positive and negative patients. However, the patients with c-Met-positive tumours had a significantly longer survival than those with c-Met-negative tumours in the medium survival term. The multivariate analysis showed the presence of lymph node metastasis, lymphatic permeation and histological differentiation to be independent prognostic factors. CONCLUSION: These results indicate that increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma, while increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis.

Adult↗

PubMed2002

Clinicopathological features of early esophageal squamous cell carcinoma with subsequent recurrence.

It has been well known that there is occasionally a postoperative recurrence in early esophageal carcinoma. However, the clinicopathologic characteristics of early squamous cell carcinoma of the esophagus with a postoperative recurrence have not been elucidated. The subjects were 103 patients with early carcinoma of the esophagus including 10 patients with subsequent recurrence, who had been surgically treated. Clinicopathologic features were compared between patients with the presence and absence of recurrence of carcinoma. No special clinicopathologic feature was observed in early esophageal carcinomas with subsequent recurrence, when compared with early carcinomas without recurrence. Physicians should realize that there is always a possibility of recurrence in early carcinomas of the esophagus, and that a leading clinical strategy for superficial carcinoma of the esophagus is the surgical treatment.

Adult↗

PubMed2002

Correlation of pre-operative nutritional condition with post-operative complications in surgical treatment for oesophageal carcinoma.

AIMS: The relationship between the pre-operative nutritional condition and the outcome of the surgical treatment in patients with oesophageal carcinoma has been discussed diversely. The aim of the current study was to demonstrate the relationship between pre-operative nutritional condition and post-operative complications and prognosis following surgical treatment for oesophageal carcinoma. METHODS: Two hundred and fifty-eight patients with oesophageal carcinoma treated with oesophageal resection and reconstruction were selected. The correlation of pre-operative values of prognostic nutritional index (PNI) with the incidence of post-operative complications and prognosis of the patients was investigated. RESULTS: The mean pre-operative value of PNI in patients with post-operative complications (41.8+/-5.4) was significantly lower than that in patients without post-operative complications (46.5+/-5.3; P<0.0001). The survival in patients with higher PNI value was significantly more favourable than that in patients with lower PNI value (P=0.0001). CONCLUSIONS: Pre-operative assessment of the nutritional condition could provide predictive information for post-operative complications in patients with oesophageal carcinoma.

Aged↗

PubMed2002

Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment.

We describe a preclinical study of our original hybrid artificial liver support system (HALSS) for a clinical trial. We designed a HALSS comprising a multi-capillary polyurethane foam packed-bed module (MC-PUF module) containing a total 200 g (2 x 10(10) cells) porcine hepatocytes, and an extracorporeal circulation device. Almost all porcine hepatocytes in the MC-PUF module formed many spherical multicellular aggregates (spheroids). This extracorporeal circulation device was improved to promote solute exchange between a living body and a MC-PUF module by including a plasma bypass line in the circulation loop. The efficacy of the HALSS was evaluated using a 25-kg pig with warm ischemic liver failure by portocaval shunt and ligation of hepatic artery (HALSS group, n=3). As a control experiment, the same system without hepatocytes in the module was used with the same kind of liver failure pig (Control group, n=3). The blood ammonia in the control group was 143 N-microg/dl at the start of circulation, and rapidly increased to 351 N-microg/dl at 2 hours and to 704 N-microg/dl at 6 hours. But the blood ammonia in the HALSS group was completely suppressed, and remained less than the hepatic coma level (over 200 N-microg/dl) during the circulation time. The blood glucose in the control group gradually decreased, and became less than 40 mg/dl within 6 hours of circulation. But the blood glucose in the HALSS group was maintained well, and remained the normal glucose level (50 - 105 mg/dl) for more than 20 hours of circulation. Improvement in blood creatinine and lactate, and the stabilization of vital signs and urinary excretion, were observed in the HALSS group. The survival time of the pigs in the HALSS group was 19.3 hours compared with 8.9 hours in the control group. In conclusion, our HALSS was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that our HALSS has a strong possibility to be used in treating liver failure patients. We have applied for approval of the clinical trial of our HALSS to our institutional ethics committee.

Animals↗

PubMed2002

Alternative approach to endoluminal treatment of an anastomotic aneurysm.

Conventional surgical treatment of patients with an anastomotic aneurysm can be a surgical challenge if severe adhesions are present. We report here effective treatment of an anastomotic aneurysm using an endoluminal stent graft. A 71-year-old man had undergone an aorto-bifemoral bypass for Leriche's syndrome in 1989 and partial gastrectomy for cancer in 1996. He was admitted to our department with a pseudoaneurysm of a proximal anastomosis located at the aorta below both renal arteries. Based on his medico-surgical history, we considered that an endovascular stent should be placed. This graft composed of an UBE(UBE-WOVEN GRAFT) graft and self-expandable Z stents were introduced through the right limb of the bifurcated graft previously implanted, then were placed using the delivery system while advancing under fluoroscopic control, using a pusher rod. Endoleakage was not evident and the postoperative course was uneventful. An endovascular graft is one alternative approach for treating patients with an anastomotic aneurysm as it is less invasive. This procedure proved satisfactory for this patient.

Aged↗

PubMed2002

Clinical significance of vascular endothelial growth factor expression in gastric cancer.

Vascular endothelial growth factor (VEGF) is an angiogenic factor in human cancer tissue. To clarify the clinical significance of this factor, we investigated the VEGF expression in early and advanced gastric cancer. This study included analysis of data on 243 patients with gastric cancer, including 118 in the early stage and 125 in the advanced stage. VEGF was immunohistochemically stained. Of 243 tumors, 102 (42%) were VEGF-positive. The VEGF-positive gastric cancers were larger, more invasive, and classified in the more advanced stage than VEGF negative ones. Patients with VEGF-positive cancers had significantly lower survival rates than did those with negative ones, both in early and advanced stages (P < 0.05, P < 0.01, respectively). The VEGF-positive isolates had more hematogenous metastases than VEGF-negative ones. Multivariate analysis revealed VEGF to be an independent prognostic factor and independent risk factor for liver metastasis. The VEGF expression in cancer cells can serve as a pertinent prognostic indicator both in early and advanced gastric cancer.

Adenocarcinoma↗

PubMed2001

Beneficial effects of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation using right lobe graft.

BACKGROUND: Recently, virtual operation planning and navigation systems have been introduced in the field of neurosurgery and orthopedic surgery. We report here the beneficial effects of 3-dimensional (3D) visualization on hepatic venous reconstruction in living donor liver transplantation (LDLT) using right lobe graft. METHODS: 3D-image reconstruction of the liver was rendered with 3-mm slices of helical computed tomography (CT) data using zioM900 (Zio Software Inc., Tokyo, Japan). To understand the anatomy of the donor's vessels and design an operation plan, a picture of the vessels in and around the liver was reconstructed. RESULTS: The 3D image demonstrated two short hepatic veins next to the inferior right hepatic vein (IRHV) as well as a large IRHV. The 3D image showed a more precise diameter of the right hepatic vein (RHV) and the IRHV and a more accurate distance between the two hepatic veins than did images measured by 2-dimensional CT. This preoperative information allowed the donor surgeon to dissect the inferior vena cava (IVC) and hepatic veins with reduced blood loss because of reduced risk of injury to the blood vessels. The 3D image revealed that both the RHV and the IRHV branched off at the same angle from the cylindrical IVC. Preoperative planning based on this information secured smooth anastomosis. CONCLUSIONS: 3D visualization is useful for hepatic venous reconstruction of the recipient as well as for donor surgery in LDLT using right lobe graft.

Female↗

PubMed2001

Despite activation of EGF-receptor-ERK signaling pathway, epithelial proliferation is impaired in portal hypertensive gastric mucosa: relevance of MKP-1, c-fos, c-myc, and cyclin D1 expression.

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Our previous study demonstrated increased ERK activation and MAP kinase phosphatase-1 (MKP-1) overexpression in PHT gastric mucosa. However, it remains unknown which tyrosine kinase receptors are involved in ERK activation and whether ERK activation results in increased cell proliferation. We examined whether EGF receptor (EGF-R) is involved in ERK activation and whether ERK activation triggers epithelial proliferation in PHT gastric mucosa. In gastric mucosa of PHT and sham-operated (SO) rats we studied: (1) EGF-R mRNA and protein expression as well as phosphorylation and membrane protein tyrosine kinase (PTK) activity; (2) ERK2 phosphorylation and activity; (3) MKP-1 mRNA and protein; (4) c-fos, c-myc and cyclin D1 mRNAs, and gastric epithelial proliferation. In PHT gastric mucosa: (1) EGF-R mRNA, protein and phosphorylation and membrane PTK activity were all significantly increased by 38%, 49%, 43% and 49%, respectively; (2) ERK2 phosphorylation and activity were significantly increased by 40% and 50 %, respectively; (3) MKP-1 mRNA and protein expression were significantly increased by 27% and 34%, respectively. In contrast, (4) c-fos, c-myc, and cyclin D1 mRNAs expression were all significantly decreased in PHT gastric mucosa by 36%, 33%, and 49%, respectively, and cell proliferation was significantly lower that in SO rats (11% in PHT vs. 18% in SO). These results suggest that in PHT gastric mucosa, ERK activation is mediated through EGF-R upregulation, but the gastric epithelial proliferation is impaired, possibly by MKP-1 overexpression, leading to reduction of c-fos, c-myc and cyclin D1.

Animals↗

PubMed2001

Unique minithoracotomy assisted by videothoracoscopy facilitates a maximal view even with a minimal wound for resection of primary lung cancer.

Resection for primary lung cancer with an unique minithoracotomy and use of videothoracoscopy is described. Through an incision of approximately 10 cm at an ausculatory triangle, the 5th intercostal thoracotomy is done following dissection of muscles. At the anterior and posterior portion of the 6th rib, the 6th intercostal vessels and nerve were dissected and the rib was resected. This approach makes feasible opening of a thoracic window without injury to the nerve and removal of the rib. Thoracoscopy is introduced through a midaxillary wound of 2 cm. We report nine patients in whom we achieved resection for primary lung cancer by using this approach. This technique facilitates a standard operation for lung cancer and an almost painless postoperative state.

Adult↗

PubMed2001

Growth pattern and expressions of cell cycle regulator proteins p53 and p21WAF1/CIP1 in early gastric carcinoma.

BACKGROUND: The growth pattern of early gastric carcinoma, as based on a volumetric analysis, reflects the biologic characteristics of a tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with the case of a superficially spreading (Super) type. The wild-type of the p53 protein plays an important role in cell growth regulation and apoptosis. The p21 protein, which is encoded by the WAF1/CIP1 gene, is a downstream target effector of wild-type p53 protein, and these proteins act as tumor suppressors in a negative cell-cycle regulation. METHODS: In 133 Japanese patients with early gastric carcinoma with submucosal invasion, expressions of p53 and p21 proteins were studied immunohistochemically, and the relation between growth pattern and expressions was analyzed. RESULTS: Early gastric carcinomas were grouped into the superficially spreading (Super) type 40 (30.1%) cases, expansively penetrating growth (Pen-A) type 28 (21.1%), infiltratively penetrating growth (Pen-B) type 20 (15.0%), small mucosal type 35 (26.3%), and mixed type 10 (7.5%). The Pen-A type tumors were characterized by the highest incidence of p53 expression and loss of p21 expression, and the rate of p53-positive and/or p21-negative cases was 71.4%. There were significant differences in the incidence of the p53 expression (50.0% vs.25.0%), the loss of p21 expression (53.6% vs. 27.5%), and the 5-year survival rate (83.2 %vs. 97.2%) between the Pen-A type and the Super type. CONCLUSIONS: Thus, deregulation of the cell cycle by p53 and p21 in this study was shown to play an important role in progression of Pen-A type early gastric carcinoma.

Aged↗