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S Takao

Publications and source records attributed to S Takao.

At least 37 records · Page 2Linked to original sources
PubMed2001

Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery.

OBJECTIVE: To evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. SUMMARY BACKGROUND DATA: Several studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. METHODS: Blood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. RESULTS: CEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. CONCLUSIONS: A high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

Aged↗
PubMed2001

Number of lymph node metastases determined by presurgical ultrasound and endoscopic ultrasound is related to prognosis in patients with esophageal carcinoma.

OBJECTIVE: To analyze the impact on prognosis of the number of lymph node metastases detected by ultrasound and endoscopic ultrasound in patients with esophageal carcinoma. SUMMARY BACKGROUND DATA: Ultrasound and endoscopic ultrasound are useful for diagnosing tumor depth and lymph node metastasis in patients with esophageal carcinoma. However, the clinical significance of the number of lymph node metastases before surgery has not been elucidated. METHODS: The authors evaluated lymph node metastases using preoperative ultrasound and endoscopic ultrasound in 329 consecutive patients who underwent esophagectomy with lymphadenectomy. TNM classification and one-to-one comparison of lymph node metastasis was performed between the preoperative and histologic diagnosis. The number of lymph node metastases was subdivided into four groups: zero, one to three, four to seven, and eight or more. RESULTS: The accuracy of preoperative ultrasound and endoscopic ultrasound diagnosis exceeded 70% in each category of TNM classification. The incidence of lymph node metastasis determined by preoperative and histologic diagnosis was 69.0% (234/339) and 59.3% (201/339), respectively. The correlation between preoperative and histologic diagnosis was significant (P <.0001). According to the subdivision of number of lymph node metastases, the accuracy rates associated with nodal involvement of zero, one to three, four to seven, and eight or more were 83.8%, 59.7%, 43.3%, and 96.0%, respectively. The clinical outcome between ultrasound and endoscopic ultrasound diagnosis and histologic diagnosis in stage grouping was almost similar. The 5-year survival rates of patients with zero, one to three, four to seven, and eight or more lymph node metastases determined by ultrasound and endoscopic ultrasound were 53.3%, 33.8% 17.0%, and 0%, respectively. The differences among groups were statistically significant. The survival curves associated with preoperative and histologic diagnosis were similar. CONCLUSIONS: Not only the stage grouping of TNM classification but also the number of lymph node metastases determined by ultrasound and endoscopic ultrasound before surgery may be useful for predicting prognosis in patients with esophageal carcinoma.

Adult↗
PubMed2001

Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels in gastric cancer.

Although serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are commonly measured before surgery for gastric carcinoma, this clinical significance is not fully understood. We evaluated a total of 549 patients with gastric cancer who underwent gastrectomy. Levels of CEA and CA19-9 were measured preoperatively in all patients. We retrospectively analyzed correlations between CEA or CA19-9 and clinicopathologic features, and estimated the prognostic utility of the tumor markers by analyzing clinicopathologic characteristics of the carcinoma as a function of seropositivity or negativity of the antigens in combination or by raising the levels. The positivity rates of CEA (> or =5 ng/mL) and CA19-9 (> or =37 U/mL) were 19.5% and 18%, respectively. Serum CEA and CA19-9 positivity significantly correlated with depth of invasion, hepatic metastasis, and curativity. Forty-nine patients positive for both CEA and CA19-9 had significantly higher frequencies of lymph node metastasis, deeper invasion by the tumor, lower rates of curative resection (p < 0.01), and higher rates of hepatic metastasis (p < 0.05) than 377 patients with normal levels of CEA and CA19-9. Surgical outcomes of patients who were CEA- and CA19-9-positive were poorer than those of patients with normal CEA and CA19-9 levels (p < 0.01). Significant correlation was found between serum CEA and CA19-9 level (p < 0.001, r = 0.24). Doubling the threshold level of serum positivity to 10 ng/mL (CEA) and 74 U/mL (CA19-9) improved the prognostic value of these factors. However, multivariate analysis using Cox's hazards model revealed that only CEA positivity using the doubled threshold value (10 ng/mL) (p = 0.04, hazard ratio = 1.7), nodal involvement (p = 0.01, hazard ratio = 1.9), and depth of invasion (p = 0.02 hazard ratio = 1.5) significantly predicted prognosis. Carcinoembryonic antigen positivity using the doubled threshold level (10 ng/mL) was an important prognostic factor in patients with gastric cancer.

Aged↗
PubMed2001

Structure, expression and chromosome mapping of MLZE, a novel gene which is preferentially expressed in metastatic melanoma cells.

We isolated a novel gene, termed MLZE, from a B16-BL6 cDNA library after subtraction of B16-F10 mRNA. Expression levels of mouse MLZE (mMLZE) increased in accordance with metastatic ability of B16 melanoma sublines. Human homolog of mMlze (hMlze) contained one leucine zipper structure and two potential nuclear localizing signals. Northern blot analysis of multiple human tissues showed that hMLZE was expressed primarily in trachea and spleen. We mapped the hMLZE gene (by fluorescence in situ hybridization) to 8q24.1 - 2, which contains the c-myc gene and is often amplified in malignant melanoma. Immunohistochemistry revealed that the number of hMlze-positive cases was significantly larger in Clark levels III, IV and V melanomas (6 / 11 = 55%) than in Clark levels I and II melanomas (2 / 15 = 13%). In two cases of hMlze-positive melanomas, the strength of hMlze staining increased substantially in the deep component of the tumor. Considering that melanomas above Clark level II are more metastatic than those below Clark level III, these findings suggested that MLZE is one of the genes whose expression is upregulated during the course of acquisition of metastatic potential in melanoma cells.

Adult↗
PubMed2001

Two cases of severe bronchopneumonia due to influenza A (H3N2) virus: detection of influenza virus gene using reverse transcription polymerase chain reaction.

We report two cases of severe bronchopneumonia due to influenza A (H3N2) virus. The severity of the disease necessitated initiation of empiric therapy based on the present illness and clinical data on admission. Both patients were improved by artificial ventilation with positive end-expiratory pressures and administration of broad spectrum antibiotics and corticosteroids before confirming the diagnosis of viral bronchopneumonia using viral culture and serological tests. Within 24 hours, influenza A (H3N2) virus was identified by amplification of the pathogen genes by reverse transcription polymerase chain reaction (RT-PCR) using the stored bronchoalveolar lavage (BAL) fluids of both cases. This suggests that a combination of detection methods of pathogens using RT-PCR and BAL fluid will facilitate determination of rational treatment aimed at influenza A virus.

Aged↗
PubMed2001

Preserved Smad4 expression in the transforming growth factor beta signaling pathway is a favorable prognostic factor in patients with advanced gastric cancer.

The signals of the transforming growth factor beta (TGF-beta) superfamily are conveyed through cell surface serine/threonine kinase receptors to the intracellular mediators known as Smads. Activation of Smads causes their translocation from the cytoplasm to the nucleus, where they function to control gene expression. The present study analyzed the expression of Smad4 and TGF-beta1 to determine their prognostic significance in advanced gastric cancer. Of 249 cases of advanced gastric cancer, 41 had invaded the muscular layer, 114 had invaded the subserosal layer, and 94 had invaded the serosa. Anti-Smad4 and TGF-beta1 antibodies were used for immunohistochemical staining. Reduced expression of Smad4 was 75.1%, whereas positive expression of TGF-beta1 was 39.6% in gastric cancer. Smad4 expression was related to the depth of tumor invasion (P < 0.05), and TGF-beta1 expression correlated with tumor gross type (P < 0.05). Postoperative survival analysis indicated that patients who had a tumor with reduced Smad4 expression had a poorer clinical outcome than those with preserved expression (P < 0.05). Furthermore, in patients with TGF-beta1-positive tumors, survival rate was significantly better in patients with preserved Smad4 expression than in those with reduced Smad4 expression (P < 0.05). According to multivariate analysis, Smad4 expression acted as an independent prognostic factor. Smad4 expression, particularly in the TGF-beta pathway, is an effective predictor of outcome for patients with advanced gastric cancer.

Adult↗
PubMed2001

Hand-assisted laparoscopic distal pancreatectomy with minilaparotomy for distal pancreatic cystadenoma.

Two patients with cystic tumors of the pancreas treated by laparoscopic distal pancreatectomy are presented. The first patient was a 34-year-old woman with a 6-cm cystadenoma of the tail of the pancreas treated with a complete laparoscopic distal pancreatectomy. After mobilization of the distal pancreas and spleen, the pancreas was transected proximally together with the splenic artery and vein using an endoscopic linear stapler. The second patient was a 71-year-old woman with a 6-cm cystadenoma of the body of the pancreas, treated by hand-assisted laparoscopic distal pancreatectomy with minilaparotomy because the tumor was adjacent to the portal vein and celiac axis. Using an upper median minilaparotomy, dissection of the gastrocolic ligament, division of the splenic artery, and transection and closure of the pancreas were performed. Division of the splenic vein and mobilization of the distal pancreas and spleen were performed via a hand-assisted laparoscopic approach. There were no postoperative complications (such as pancreatic fistulas) in either patient, and the postoperative courses were uneventful. The patients returned to normal activity within 1 week after the operation. Complete laparoscopic and hand-assisted laparoscopic distal pancreatectomy are preferable to conventional open surgery for benign tumors of the pancreas because of their less-invasive nature. Additionally, in tumors of the body of the pancreas, hand-assisted laparoscopic distal pancreatectomy might have the advantages of laparotomy and laparoscopy in terms of handling the splenic artery and vein just below the minilaparotomy site, suggesting an easier and safer procedure than complete laparoscopic distal pancreatectomy. Therefore, hand-assisted laparoscopic distal pancreatectomy can be recommended as a useful alternative to complete laparoscopic distal pancreatectomy for selected patients with benign tumors of the body and tail of the pancreas.

Adult↗
PubMed2001

Role of thymidine phosphorylase in Fas-induced apoptosis.

Thymidine phosphorylase (TP) has chemotactic and angiogenic activity in vitro, and it promotes tumor growth and inhibits apoptosis in vivo. It plays a key role in the invasiveness and metastasis of TP-expressing solid tumors. KB/TP cells transfected with a TP cDNA have been shown to be resistant to hypoxia-induced apoptosis, suggesting that TP has effects on tumor growth and cell death independent of its effects on angiogenesis. However, the mechanisms of cell death inhibition by TP are unknown. In the present study, we demonstrate that caspase-8 is cleaved in control transfectant KB cells early on during Fas-induced apoptosis. Caspase-8 activation leads to the loss of mitochondrial membrane potential, followed by the release of cytochrome c, the activation of caspase-3, and apoptosis. In contrast, Fas-induced caspase-8 cleavage is inhibited in KB/TP cells, which lead to inhibition of the downstream apoptotic cascade and inhibition of apoptosis. These findings indicate that TP plays an important role in intracellular apoptotic signal transduction in the Fas-induced apoptotic pathway. Therefore, inhibition of TP may suppress the progression of TP-overexpressing solid tumors by inducing apoptosis.

Apoptosis↗
PubMed2000

Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in the patients with esophageal carcinoma.

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Aged↗
PubMed2000

Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by chemotherapy.

The p53 gene is associated with G1 arrest during the cell cycle and with apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI) and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty patients with esophageal carcinoma who had received chemotherapy prior to surgery were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression, respectively. The histological response rate of chemotherapy was 20.0%. A significant correlation between p53-negative expression and response to chemotherapy was found (P<0. 01). The AIs and Ki-67LIs in p53-negative tumors with ineffective responses to chemotherapy were significantly higher than those in p53-positive tumors with ineffective responses (P<0.05). The AIs and Ki-67LIs were significantly lower in p53-negative tumors with effective responses to chemotherapy than those in p53-negative tumors with ineffective responses (P<0.05 and P<0.01, respectively). Furthermore, significant correlations were found between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P<0.05). In esophageal carcinoma, p53-negative tumors with highly proliferative cells might be susceptible to apoptosis induced by chemotherapy.

Adult↗
PubMed2000

Suppression of metastasis by thymidine phosphorylase inhibitor.

We developed a novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI), that is about 1000-fold more active than 6-amino-5-chlorouracil, one of the most potent TP inhibitors. TPI inhibited the high chemotactic motility and basement membrane invasion of KB/TP cells, a TP-positive clone transfected with Rous sarcoma virus (RSV)/TP, to the levels seen in KB/CV cells, a control clone transfected with RSV. In nude mice, oral administration of TPI suppressed not only macroscopic liver metastases of highly metastatic KB/TP cells but also the level of human beta-globin as a molecular marker of micrometastases in the livers of the mice. These findings demonstrate that TP plays a key role in the invasiveness and metastasis of TP-expressing solid tumors and suggest that TPI might be a novel antimetastatic agent for blood-borne metastasis.

Animals↗
PubMed2000

The cooperative role of p27 with cyclin E in the prognosis of advanced gastric carcinoma.

BACKGROUND: Cyclin E and p27 play opposing roles in the cell cycle. This study investigated the protein expression of p27 with cyclin E in the progression and prognosis of gastric carcinoma. METHODS: Of 241 patients with advanced gastric carcinoma, 38 had muscular layer invasion, 113 had subserosal layer invasion, and 90 had serosal invasion. Anti-p27 and cyclin E antibodies were used for immunohistochemical staining. RESULTS: Positive expression of p27 and cyclin E was 32.4% and 38.2%, respectively. Both p27 and cyclin E expression were related to histology of tumors but not to depth of invasion, lymph node metastasis, or stage grouping. A positive correlation was observed between p27 and cyclin E expression (P < 0. 05). Tumors were divided into two groups according to the expression of cyclin E. Within the cyclin E positive tumors, the five-year survival rate was higher in patients with a p27 positive tumor than in those with a p27 negative tumor (P < 0.05). Patients with cyclin E positive tumors showing low expression of p27 had a poor prognosis. In cyclin E negative group tumors, no significant differences were observed irrespective of p27 expression. CONCLUSIONS: Reduced p27 expression is a negative prognostic factor for patients with cyclin E positive tumors.

Adult↗
PubMed2000

Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma.

The lymph nodes of 59 patients with pN0 esophageal squamous cell carcinomas were examined immunohistochemically using cytokeratin (CK) antibody. Primary tumors were immunostained with cyclin D1 (CD1) and E-cadherin (E-cad) antibody. Lymph node micrometastasis (MM) was found in 39 (55.5%) patients. Tumor recurrence was found in 17 patients and all but one of them had MM. The 5-year survival rate was significantly poorer in patients with MM than in those without MM. Almost all patients with positive CD1 and negative E-cad expression had MM. The examination of CD1 and E-cad expression in primary tumors may be useful for predicting MM.

Adult↗
PubMed2000

p21 expression is a prognostic factor in patients with p53-negative gastric cancer.

The expression of p21 and p53 proteins was analyzed by immunohistochemistry in 256 patients with advanced gastric cancer. The results showed that strong, weak and negative expression of p21 were detected in 22.2 (57/256), 68.0 (174/256) and 9.8% (25/256) of the patients, respectively. p53 expression was found in 28.9% (74/256). The expression of p21 was not associated with clinicopathological features. In p53 negative tumors, p21 expression was associated with the survival of patients who underwent curative operations (P = 0.007). The 5-year survival rates were 20.1, 36.6 and 59.8% in patients with p21-negative, -weakly positive and -strongly positive tumors, respectively. In contrast, in p53-positive tumors, prognosis did not differ in spite of p21 expression. Multivariate analysis showed that p21 expression was an independent factor in patients with p53-negative tumors. These results indicate that examination of p21 expression in p53 negative tumors will be useful for estimating the prognosis of patients with advanced gastric cancer.

Adult↗