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Biomedical subjects

Kazuhiro Yanagihara

Publications and source records attributed to Kazuhiro Yanagihara.

28 records · Page 2Linked to original sources
PubMed2002

Expression of angiopoietins and its clinical significance in non-small cell lung cancer.

Angiopoietin (Ang)-1 and -2 have been recently identified as potent angiogenic factors which function in concert with vascular endothelial growth factor (VEGF), but no detailed clinical study on Ang expression has been reported. To assess the clinical significance of Ang expression in non-small cell lung cancer (NSCLC), a total of 236 patients with pathological stage-I-IIIA disease were retrospectively reviewed. Expression of Ang-1, Ang-2, or VEGF was examined immunohistochemically; intratumoral microvessel density (IMVD) was examined with immunohistochemical staining against CD34, a marker of pan-endothelial cells (CD34-IMVD), and that against CD105, a marker of proliferative endothelial cells (CD105-IMVD). Positive expression of Ang-1 and that of Ang-2 were seen in 101 (42.8%) and 40 patients (16.9%), respectively. There was no significant correlation between Ang-1 expression and CD34-IMVD or CD105-IMVD. In contrast, the average CD105-IMVD for Ang-2-positive tumor was significantly higher than that for Ang-2-negative tumor (56.7 versus 38.5; P = 0.032). More interestingly, such an angiogenic effect of Ang-2 was seen only when VEGF expression was high; when VEGF expression was high, the average CD105-IMVD for Ang-2-positive tumor was significantly higher than that for Ang-2-negative tumor (89.1 versus 63.6; P = 0.045); when VEGF expression was low, the average CD105-IMVD for Ang-2-positive tumor and that for Ang-2-negative tumor were almost the same (27.4 and 27.1, respectively). Moreover, positive expression of Ang-2, not Ang-1, was a significant factor to predict a poor postoperative survival (5-year survival rates for Ang-2-positive patients and -negative patients were 53.5 and 70.3%, respectively; P = 0.027), which was confirmed by a multivariate analysis. The influence of Ang-2 status on postoperative survival was enhanced when VEGF expression was high. That said, the 5-year survival of Ang-2-positive and VEGF-high patients was extremely low (41.4%) as compared with that for Ang-2-negative and VEGF-low patients (66.6%), as compared with that for Ang-2-positive and VEGF-low patients (63.6%), and as compared with that for Ang-2-negative and VEGF-low patients (71.8%). In conclusion, positive Ang-2 expression was significantly correlated with a poor prognosis, as well as with aggressive angiogenesis in resected NSCLC that was enhanced in the presence of high VEGF expression.

Aged↗
PubMed2002

Clinical significance of p21 expression in non-small-cell lung cancer.

PURPOSE: The clinical significance of p21 expression remains unclear, whereas many experimental studies have demonstrated that p21, the product of the WAF1/CIP1/SDI1 gene, plays an important role in regulation of the cell cycle as an inhibitor of cyclin-dependent kinases. The purpose of this study was to clarify the clinical significance in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 233 consecutive patients with completely resected pathologic stage I to IIIA NSCLC were retrospectively reviewed. Expression of p21 and the status of p53 were examined immunohistochemically. Proliferative activity was also evaluated immunohistochemically. The incidence of apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining. RESULTS: Expression of p21 was positive in 120 patients (51.5%). The 5-year survival rate of p21-positive patients was 73.8%, significantly higher than that of p21-negative patients (60.7%; P =.006). Aberrant expression of p53 was positive in 98 patients (42.1%). When combined with p53 status, the prognostic value of p21 status was enhanced: the 5-year survival rate of p21-positive and p53-negative patients was 80.7%, markedly higher than that of p21-negative and p53-positive patients (50.0% for both; P =.001). Multivariate analysis confirmed that positive expression of p21 was a significant factor for predicting a favorable prognosis. There was no significant correlation between p21 expression and p53 status, proliferative activity, or incidence of apoptosis. CONCLUSION: p21 expression was shown to be an independent prognostic factor in NSCLC.

Adenocarcinoma↗
PubMed2002

Predictive value of dihydropyrimidine dehydrogenase expression in tumor tissue, regarding the efficacy of postoperatively administered UFT (Tegafur + Uracil) in patients with p-stage I nonsmall-cell lung cancer.

BACKGROUND AND OBJECTIVES: Dihydropyrimidine dehydrogenase (DPD) activity in tumor cells has been suggested to be one of the factors determining the effectiveness of 5-fluorouracil (5-FU). In the present study, we analyzed DPD expression in tumors and investigated retrospectively the relationship between the efficacy of UFT (Tegafur + Uracil) as adjuvant chemotherapy and DPD expression in nonsmall-cell lung cancer (NSCLC). METHODS: DPD expression of 166 resected p-stage I NSCLC was examined immunohistochemically. Patients who were administered UFT alone as adjuvant therapy comprised the UFT group (n = 54), and those who underwent only surgery comprised the control group (n = 112). DPD expression was categorized as either high or low, according to intensity of staining. RESULTS: DPD expression was high in 98 patients (59.0%) and low in 68 patients (41.0%). Patients with low-DPD tumors who were administered UFT had a significantly better prognosis than those who did not receive adjuvant treatment (P = 0.021). No significant difference was found between the two groups of patients with high-DPD tumors (P = 0.598). CONCLUSIONS: DPD expression may predict the efficacy of UFT after surgery for p-stage I NSCLC. A prospective study is needed to confirm the role of DPD expression as a predictor of UFT efficacy.

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PubMed2002

Clinical significance of nm23 expression in resected pathologic-stage I, non-small cell lung cancer.

BACKGROUND: Clinical significance of the status of nm23 gene, originally identified as an antimetastatic gene, in non-small cell lung cancer remains unestablished, whereas many clinical studies have demonstrated that reduced nm23 expression is correlated with tumor progression and poor prognosis in a variety of malignant tumors such as breast carcinoma. METHODS: nm23 expression was examined immunohistochemically in a total of 117 patients with completely resected pathologic stage I non-small cell lung cancer. RESULTS: nm23 expression was positive in 73 (62.4%) patients, and there was no correlation between nm23 expression and age, sex, performance status, pathologic T factor, histologic type, or degree of cancer cell differentiation. The 5-year survival rates of nm23-positive and nm23-negative patients were 79.7% and 57.8%, respectively, demonstrating a significantly poorer prognosis in nm23-negative patients (p = 0.013), which was confirmed by a multivariate analysis. nm23 was not correlated with the incidence of apoptosis, proliferative activity, or p53 status. CONCLUSIONS: nm23 expression was a significant factor for predicting a favorable prognosis, suggesting antimetastatic potential of the nm23 gene in non-small cell lung cancer.

Antigens, Neoplasm↗
PubMed2002

Prognostic value of thymidylate synthase expression in patients with p-stage I adenocarcinoma of the lung.

We investigated thymidylate synthase (TS) expression in tumor tissues and examined the relationship between TS expression and post-operative survival in patients with p-stage I adenocarcinoma of the lung. A total of 104 patients, who underwent complete resection for p-stage I adenocarcinoma of the lung, were retrospectively reviewed. TS expression in tumor tissues was evaluated by immunohistochemical staining using rhTS polyclonal antibody. The intensity of immunohistochemical staining was classified into four categories using a visual grading system from 0 to 3. The percentage of each grade of TS staining was 9.6% for Grade 0, 18.3% for Grade 1, 35.6% for Grade 2 and 36.5% for Grade 3. Five-year survival rates of patients with Grade 0 to Grade 3 were 90.0, 83.9, 70.3 and 73.7%, respectively with no significant difference among all groups (P=0.236). When divided into two groups, according to the intensity of the grade, 5-year survival rates of TS low expression group (Grade 0 and Grade 1) and TS high expression group (Grade 2 and Grade 3) were 86.1 and 72.0%, respectively, with a significant difference (P=0.048). In conclusion, high level of TS expression was associated with poor prognosis. Immunohistochemical evaluation of TS expression may be useful to predict survival after complete resection in p-stage I adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed2002

Apoptotic tumor-cell death in response to cell proliferation is influenced by p53 status in resected non-small cell lung cancer.

To evaluate the influence of p53 status on postoperative survival and incidence of apoptosis (apoptotic index, AI) in non-small cell lung cancer (NSCLC), a total of 185 pathologic stage I patients were retrospectively analyzed. It was demonstrated by univariate and multivariate analyses that aberrant expression of p53 was a significant factor to predict a poor prognosis, which was caused by a significantly higher proliferative index (PI) in tumor with aberrant expression of p53 (52.7%) than that in tumor without aberrant expression of p53 (37.9%, P < 0.001). In addition, for tumor without aberrant expression of p53, mean AIs of the lowest-, the lower-, the higher-, and the highest-PI groups were 12.6, 12.9, 31.3, and 35.1, respectively, showing that incidence of apoptosis was markedly increased in response to cell proliferation (P = 0.002). In contrast, for tumor with aberrant expression of p53, no increase in incidence of apoptosis in response to cell proliferation was documented. These results clearly demonstrated that active cell proliferation and reduced apoptotic cell death in response to cell proliferation resulted in the poor postoperative prognosis in tumor with aberrant expression of p53.

Adenocarcinoma↗
PubMed2002

Primary lung carcinoma arising from emphysematous bullae.

To clarify clinical characteristics and biological features of primary lung carcinoma arising from emphysematous bullae (EB), a total of 50 patients (49 males and one female) among all 1478 patients who underwent operation for primary lung carcinoma cases were reviewed; biological features were examined in 31 patients whose resected specimens were available for immunohistochemical staining (IHS). Thirty-one patients (62.0%) had pathologic stage I disease, and 30 cases (60.0%) had poorly differentiated tumor, demonstrating earlier pathologic stages and poorer cell differentiation of lung carcinoma with EB as compared with that without EB. The mean proliferative index (PI) for carcinoma with EB was 64.0%, which was significantly higher than that for carcinoma without EB (47.2%, P = 0.001); no significant difference in Apoptotic index (AI) was demonstrated. Aberrant p53 expression was less frequent in carcinoma with EB (29.0%) than in carcinoma without EB (47.9%, P = 0.043). Five-year survival rates for carcinoma with and that without EB were 50.3 and 46.9%, respectively, showing no significant difference. Multivariate analysis did not demonstrate that association of EB was a significant prognostic factor. In conclusion, although with the poorer cell differentiation and accelerated proliferative activity of lung carcinoma arising from EB, this does not have a significantly different prognosis than primary lung carcinoma not associated with bullae.

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PubMed2002

Phase II study of repeated intrapleural chemotherapy using implantable access system for management of malignant pleural effusion.

STUDY OBJECTIVE: To examine the effectiveness of repeated intrapleural chemotherapy using an implantable access system (INFUSE-A-PORT; Horizon Medical Products; Manchester, GA) for the management of a malignant pleural effusion (MPE). METHODS: Twenty-two patients with histologically proven MPEs (11 men and 11 women; mean age, 63.8 years; age range, 51 to 81 years; performance status, less-than-or-equal 3) were enrolled in this study. There were 17 patients with MPEs resulting from primary lung cancer; of whom 7 had metastatic disease (stage IV), 3 had stage IIIB disease, and 7 had postoperative recurrences. Three patients had MPEs that were caused by mesothelioma, and two had MPEs caused by breast cancer. Intrapleural catheters were placed by a video-assisted thoracoscopic procedure. The intrapleural administration of 5-fluorouracil (5-FU; 250 mg per body) and cisplatin (10 mg per body) using the implantable access system was performed biweekly at the outpatient clinic. Drainage of the MPEs through the port was performed only when the patients had some manifestations that occurred due to increasing effusion. RESULTS: The mean total administered doses of 5-FU and cisplatin were 3,290 and 124 mg, respectively. The mean follow-up period was 431 days (range, 209 to 792 days). The median survival period was 403 days, and the longest survival period was 792 days. No treatment-related mortality, renal dysfunction, bone marrow suppression, or infection occurred. One patient experienced a hemothorax after eight instances of intrapleural administration. The port and the catheter were involved with the tumor in one patient. CONCLUSIONS: Repeated intrapleural chemotherapy using the implantable access system is useful and safe for patients with MPEs. In the future, prospective randomized studies will be necessary to compare the efficacy of therapy for MPE using the implantable access system with that of pleurodesis.

Aged↗