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Biomedical subjects

G Nakagawara

Publications and source records attributed to G Nakagawara.

At least 19 recordsLinked to original sources
PubMed1995

Possible involvement of protein-tyrosine kinases such as p72syk in the disc-sphere change response of porcine platelets.

We previously reported that p72syk, a non-receptor tyrosine kinase, was activated maximally at 10 s after thrombin or thromboxane A2 stimulation, even in platelets that were not allowed to aggregate [Taniguchi et al. (1993) J. Biol. Chem. 268, 2277-2279; Maeda et al. (1993) Biochem. Biophys. Res. Commun. 197, 62-67]. Then, the change in the shape of porcine platelets induced by the thromboxane A2 analogue, STA2, and the role of protein-tyrosine kinases including p72syk in this response were evaluated, using the shape-change parameter. We show that p72syk activation is correlated with the disc-sphere change in a time- and dose-dependent manner following stimulation by STA2. Tyrphostin B44, a potent protein-tyrosine kinase inhibitor, reduced the thromboxane A2-evoked p72syk activation and the disc-sphere change in a dose-dependent manner. Furthermore, the translocation of p72syk to the cytoskeleton-rich fraction and an increase in the tyrosine phosphorylation of an about 120 kDa protein were observed during the disc-sphere change induced by STA2. These lines of evidence suggest that the activation of protein-tyrosine kinases such as p72syk may be involved in the disc-sphere change response in thromboxane A2-stimulated porcine platelets.

Animals↗
PubMed1995

Expression of CD44 variant exons 8-10 in colorectal cancer and its relationship to metastasis.

Splice variants of CD44 are overexpressed in human lung, breast, and colon carcinoma cell lines. This study was conducted to clarify the association between the expression of CD44 variant exons 8-10 and metastatic potential in human colorectal cancer. We found that the expression of a CD44 splice variant containing exons v8-10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colerectal mucosa, as determined by Northern blotting. Expression of CD44 variant exons 8-10 did not significantly correlate with histological type, depth of tumor invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the level of CD44 variant exon 8-10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variant exons 8-10 in the liver metastases was more intense than that in the primary colorectal cancers. These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8-10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.

Blotting, Northern↗
PubMed1995

[The role of CD44 adhesion molecules].

CD44 is a transmembrane glycoprotein involved in the interaction between cells and extracellular matrix. CD44 is ubiquitously expressed on cells, and has been thought to be a cell adhesion molecule with proposed functions in extracellular matrix binding, cell migration and lymphocyte homing. In 1991, Stamenkovic et al. showed the existence of two forms of CD44: a hematopoietic (standard) and an epithelial form which was highly expressed by carcinomas. The alternative splicing of 10 variant exons encoding the membrane proximal portion of the external domain of CD44, in particular, results in many variant isoforms. These may play a critical role in malignant behavior and in determining organ specificity in metastasis.

Humans↗
PubMed1995

[A case of duodenal duplication and a review of reported cases].

We report a case of duodenal duplication and review of literatures on 43 cases reported in Japan including ours. A 34-year-old female who was admitted with chief complaints of epigastric pain and hematoemesis. An endoscopic examination and a hypotonic duodenography revealed a protruding tumor with bleeding ulcer. Wedge resection of the duodenum, including the lesion, was performed. A diagnosis of duodenal duplication was made by histopathological examination.

Adult↗
PubMed1995

[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (surgery group evaluation)].

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the surgery departments of 53 institutions between July 1991 and March 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 138 subjects enrolled, 129 (93.5%) were eligible and 119 (86.2%) completed the scheduled treatment (AO/MF group: 57, C/MF group: 62). The overall clinical response rates in the completed cases were 26.3% (15/57) in the AO/MF group and 8.1% (5/62) in the C/MF group, and the difference between the groups was significant (p = 0.015). In particular, the response rate in the postoperative recurrent patients with measurable lesions was 42.9% (12/28) in the AO/MF group versus 12.0% (3/25) in the C/MF group (p = 0.016). Further, in the patients who were previously treated with fluoropyrimidine drugs, 29.0% (9/31) responded to the AO/MF therapy versus 8.6% (3/35) in the C/MF group (p = 0.053). The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count and hemoglobin level, nausea/vomiting and stomatitis. The differences in the incidence were not significant between the groups. Based on these results, AO-90 in the MF regimen appears to be effective in the treatment of patients with advanced gastric cancer by significantly potentiating the effects of 5-FU.

Adolescent↗
PubMed1995

[Quality of life in patients with advanced gastric cancer receiving AO-90, a methionine-free intravenous amino acid solution, with 5-fluorouracil and mitomycin C].

We conducted a randomized, multicenter, controlled trial of AO-90, a methionine-free 7.43% intravenous amino acid solution, in patients with advanced recurrent gastric cancer. The regimen used in the study was comprised of two-week treatment cycles, with a withdrawal period between cycles. During treatment, patients were given either AO-90 (500-750 ml/day; AO/MF group) or a commercial amino acid solution (600-800 ml/day; C/MF group) by total parenteral nutrition (TPN) for 14 days concomitantly with MF therapy (5-fluorouracil 350 mg/m2/day, iv continuously for 14 days and mitomycin C 7 mg/m2, iv push on days 7 and 14). We interviewed 118 eligible and evaluable patients (72 men and 46 women; 59 cases in the AO/MF group and 59 in the C/MF group) about their quality of life immediately before the start of treatment, one week and two weeks after the start of treatment, and one week and two weeks after treatment. A 11-item questionnaire was used to interview the subjects: nine questions using a five-point scale, one question using a 100-mm linear visual analog scale, and one question using a five-grade face scale. Changes in the grades compared with baseline data were scored as 1 point (improvement of one grade or more, or 20 mm or more), 0 points (no changes), and-1 point (decline of one grade or more, or 20 mm or more). Before analyzing the significance, quality of life score data were adjusted by the Mantel-Haenszel method due to uneven distribution of subjects concerning baseline performance status and complications. Among the items questioned, subjects receiving AO-90 showed significantly higher scores in appetite, nausea, and ambulation at some evaluation time points than those receiving a methionine-containing TPN. The results show that AO-90 improved the quality of life of patients with advanced recurrent gastric cancer.

Adolescent↗
PubMed1994

Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma.

BACKGROUND: The expression of nm23-H1 and nm23-H2 proteins in 25 hepatocellular carcinomas was studied immunohistochemically. METHODS: Tissue specimens were reacted with anti-human nm23-H1 and nm23-H2 monoclonal antibodies (MoAb) (H1-229 and H2-206, respectively) and then stained by the biotin-streptoavidin complex method. RESULTS: Adjacent nontumorous tissues were intensely stained with nm23-H1 and nm23-H2. Of the 25 hepatocellular carcinomas, 60% were positive for MoAb H1-229, and 68% were positive for MoAb H2-206. These immunoreactivities were most common in the cytoplasm of tumor cells. There was no significant correlation between the expression of nm23-H1 protein and tumor size, Edmondson's histopathologic classification, or invasion of the capsule. However, the authors observed an inverse relationship between nm23-H1 expression and intrahepatic metastases of hepatocellular carcinomas. There was no significant correlation between the expression of nm23-H2 protein and clinicopathologic findings. Only a short survival period was observed in patients with hepatocellular carcinoma with reduced nm23-H1 or nm23-H2 proteins. CONCLUSIONS: The results suggest that nm23-H1 protein plays a role in the suppression of intrahepatic metastasis of hepatocellular carcinoma and that the combined expression of nm23-H1 is associated with favorable prognosis.

Carcinoma, Hepatocellular↗
PubMed1994

[Expression of human epidermal growth factor and its receptor of the gastric carcinomas with special reference to DNA ploidy patterns and nucleolar organizer regions].

In 68 cases of surgically resected gastric carcinomas, expression of human epidermal growth factor (EGF) and its receptor (EGFR) were examined immunohistologically using the Avidin-Biotin Peroxidase Complex Method, and their relation with DNA contents and nuclear protein synthesis in the tumor progression were studied by measuring DNA ploidy patterns and nucleolar organizer regions (NORs), respectively with cytofluorometry and AgNO3 stain method. EGF and EGFR expression were respectively found only in 2 (7%) and 1 (4%) in 28 early cancers, and significantly increased in advanced cancers, 25 (63%) and 9 (23%) out of 40 cases. The ratio of aneuploid tumor and the NORs numbers per tumor cell also increased in advanced cancers, compared with in early cancers. EGF and EGFR respectively expressed in 19 (51%) and 9 (23%) in 37 aneuploid cancers, significantly more frequent than 8 (26%) and 1 (3%) in 31 diploid cancers. In the EGF-positive tumors, the NORs numbers showed 4.11 +/- 0.72, significantly higher than 2.68 +/- 0.61 in the EGF-negative tumors. These results suggested that expression of EGF and EGFR in the gastric carcinomas increases during the tumor progression from the early to advanced stage, stimulates synthesis of DNA and nuclear protein, and consequently enhances (strengthens, heightens, or intensifies) the proliferative activity of the tumors.

DNA, Neoplasm↗
PubMed1993

Protein-tyrosine kinase p72syk is activated by thromboxane A2 mimetic U44069 in platelets.

We show that p72syk is rapidly activated following the stimulation of thromboxane A2 mimetics, U44069 and STA2 in porcine platelets. The activity of p72syk reached a maximum at 10 s and decreased to a basal level within 60 s after 1 microM U44069 stimulation. This activation was enhanced in a dose-dependent manner and completely canceled by the pretreatment of platelet suspension with ONO3708, a specific antagonist of thromboxane A2. Pretreatment of platelets with aspirin as well as apyrase did not affect the activation of p72syk. When both extra- and intra-cellular Ca2+ were depleted, the activation of p72syk was still persistent; in contrast, the deactivation process was completely abrogated even at 120 s after U44069 stimulation. These results suggest that p72syk is a responsible enzyme to the protein-tyrosine phosphorylation events, and that p72syk functions mainly before Ca2+ recruitment in thromboxane A2-stimulated platelets.

Animals↗
PubMed1993

Dimethyl sulfoxide (DMSO) increases expression of sialyl Lewis x antigen and enhances adhesion of human gastric carcinoma (NUGC4) cells to activated endothelial cells.

Dimethyl sulfoxide (DMSO) exerts a number of biological effects including the promotion of cell differentiation in cultured cells. In this study, we examined the effect of DMSO on the adhesion of tumor cells to endothelial cells. In vitro treatment of human gastric adenocarcinoma (NUGC4) cells with DMSO resulted in increased adhesion to interleukin-I (IL-I)-activated human endothelial cells compared with DMSO-untreated NUGC4 cells. In flow cytometry, treating NUGC4 cells with DMSO enhanced the expression of sialyl Lewis x (sialyl Le(x)) and sialyl dimeric Le(x) antigens on their surface. Also, the binding of Limulus polyphemus agglutinin (LPA), which specifically binds to cell-surface sialic acids, was increased by DMSO. The adhesion of DMSO-treated NUGC4 cells to activated endothelial cells was blocked by neuraminidase pre-treatment of tumor cells or by antibody against either endothelial leukocyte adhesion molecule-I (ELAM-I) or sialyl Le(x). Thus, it is suggested that enhanced adhesion following DMSO treatment is mediated by the interaction of sialyl Le(x) expressed on NUGC4 cells with ELAM-I of endothelial cells. The modulation of sialyl Le(x) antigen by DMSO provides a useful system for studying the regulatory mechanism of Lewis-related carbohydrate antigens and also for understanding the metastatic properties of cancer cells.

Antibodies, Monoclonal↗
PubMed1993

p53 immunoreaction in endoscopic biopsy specimens of colorectal cancer, and its prognostic significance.

The expression of p53 protein was immunohistochemically studied in formalin-fixed paraffin-embedded biopsy specimens of 203 colorectal carcinomas by use of a monoclonal antibody specific for the p53 protein. PAb1801. p53 protein expression with its reactivity localised in nuclei was found in 121 (59.6%) of the cancers. There was no correlation of p53 immunoreactivity with histological classification, wall invasion, lymphatic invasion, venous invasion, lymph node metastases, or peritoneal metastases. p53-positive cancers were more frequently associated with liver metastasis than p53-negative ones. Patients with p53-positive tumours had significantly poorer prognoses than those with p53-negative tumours. The 5 year survival rate was 58.1% for patients with p53-positive tumours, and 76.3% for those with p53-negative tumours. In Dukes' stage C tumours, an especially good correlation was found between p53 immunoreactivity and prognosis. In addition, patients with p53-positive tumours had higher recurrence rates. The results indicate that p53 immunoreactivity may be a useful prognostic marker of colorectal cancers.

Antibodies, Monoclonal↗
PubMed1993

Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis.

The expression of nm23-H1 mRNA and protein was studied in colorectal cancers by Northern blotting and immunohistochemistry. All 21 colorectal cancers studied by Northern blotting had increased levels of nm23-H1 mRNA relative to the adjacent normal colonic mucosa. Increased nm23-H1 protein expression was also observed in all 36 colorectal cancer cases including those studied by Northern blotting. There was no significant correlation between nm23-H1 expression and tumour histology, serosal invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the expression of both mRNA and protein was significantly lower in tumours associated with liver metastasis than in those without such metastasis. These observations indicate that the nm23 gene may play a role in the suppression of liver metastasis of colorectal cancer.

Antibodies, Monoclonal↗
PubMed1993

[Modes of spread and surgical strategy for gallbladder carcinoma with subserosal invasion].

The mode of spread and the prognosis were investigated in 22 patients with resected gallbladder carcinoma invading the subserosal layer. By the Kaplan-Meier method, the 5-year survival rate was 68.8% in patients receiving curative or relatively noncurative resection. On the other hand, no patient survived for more than 3 years after noncurative resection. The mode of subserosal infiltration was classified according to the general rules for gastric cancer study. At least systemic lymph node dissection (R2) should be performed in patients with ss alpha cancer, because lymph node metastasis in these patients were confined to the 1st group. More extensive lymph node dissection (R2 with 9, 16) is essential for patients with ss beta and ss gamma, because lymph node metastasis to at least the 2nd group were seen in 75% of them. The surgical margin was positive for cancer in all patient with infiltration of the hepatoduodenal ligament. Therefore, it was considered that hepatoligamentectomy should be performed in these patients to obtain a cancer free surgical margin. Among patients undergoing curative or relatively noncurative resection, the recurrence rate was 43% in those with lymph node metastasis and 50% in those with DNA aneuploidy. Therefore, it appears that adjuvant chemotherapy should be given to such patients.

Aged↗
PubMed1993

Anterior segmentectomy with caudate lobectomy for hilar cholangiocarcinoma.

When hepatic resection for hilar chol-angiocarcinoma with impaired hepatic function is performed, minimal resection of the involved segment on the basis of the extent of cancer invasion must be selected so as to minimize the risk of postoperative hepatic failure. We describe our experience with anterior segmentectomy with caudate lobectomy for hilar cholangiocarcinoma in two patients with impaired hepatic function and poor general health. These procedures were curative resections histologically, and were not followed by severe postoperative complications. Anterior segmentectomy together with caudate lobectomy was considered appropriate treatment for hilar cholangiocarcinoma without infiltration of the posterior hepatic branch in patients with impaired hepatic function.

Adenoma, Bile Duct↗
PubMed1992

Protein-tyrosine kinase p72syk is activated by wheat germ agglutinin in platelets.

We previously reported a molecular cloning of porcine gene syk encoding a non-receptor type 72-kDa protein-tyrosine kinase (Taniguchi et al. (1991) J. Biol. Chem. 266, 15790-15796). In this study, we have demonstrated that p72syk is expressed in porcine platelets at 0.1-0.2% of total protein and that the lectin wheat germ agglutinin induces an activation of p72syk against both auto- and exogenous-substrate-phosphorylation in porcine platelets. The activation of p72syk was abrogated by the coexistence of N-acetyl-D-glucosamine with wheat germ agglutinin. These data suggest that p72syk is a candidate of responsible protein-tyrosine kinase for platelet activation and that cell surface glycoprotein is involved in the activation of p72syk in platelets.

Acetylglucosamine↗