Biomedical subjects

Kazuhiro Yanagihara

Publications and source records attributed to Kazuhiro Yanagihara.

At least 19 recordsLinked to original sources

PubMed2007

Influence of epidermal growth factor receptor (EGFR) gene mutations on the expression of EGFR, phosphoryl-Akt, and phosphoryl-MAPK, and on the prognosis of patients with non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: In this paper we examined the influence of epidermal growth factor receptor (EGFR) gene mutations on EGFR expression, downstream mediators, and survival in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the tumors of 53 patients with completely resected pathological stage I-IIIA NSCLC for the presence of EGFR gene mutations, the expression of EGFR mRNA and protein, phosphoryl-Akt, and phosphoryl-mitogen-activated protein kinase (MAPK) using immunostaining, and patients' prognosis. RESULTS: EGFR mutations were associated with elevations in EGFR mRNA (P = 0.004) and protein (P = 0.029) expression, but not with the expression of phosphoryl-Akt or phosphoryl-MAPK. The 5-year survival rate for all patients who exhibited an EGFR mutation was similar to those who were free of such mutations (71% vs. 56%, P = 0.252). However, the 5-year survival rate of patients with either a stage I adenocarcinoma or large cell carcinoma who had an EGFR mutation was significantly greater than for those who did not have such a mutation (92% vs. 57%, P = 0.037). CONCLUSIONS: EGFR gene mutations were significantly associated with higher EGFR expression, but not with p-Akt or p-MAPK status. In early stage NSCLC, the presence of an EGFR gene mutation bode well for the patient's prognosis.

Adult↗

PubMed2006

Single-agent gemcitabine for biliary tract cancers. Study outcomes and systematic review of the literature.

OBJECTIVE: The aim of this study was to investigate the outcomes of gemcitabine-treated patients with inoperable biliary tract cancers. METHODS: We conducted a retrospective study of consecutively treated 22 inoperable biliary tract cancer patients with gemcitabine (500-1,000 mg/m(2) on days 1, 8, 15 every 4 weeks) as first-line, and 17 patients as second- or third-line treatment. RESULTS: The response rate of patients treated with gemcitabine as first-line and second- or third-line treatment was 5.3 and 28.5%, respectively. The median overall survival time in the first-, and second- or third-line treatment groups was 8.3 and 17.0 months, and the 1-year survival rate was 44.0 and 50.9%, respectively. The present study also suggests the possibility that the prognosis of patients with high levels of C-reactive protein and total bilirubin, or a low level of albumin might be worse. CONCLUSIONS: Our results indicate that the treatment of inoperable biliary tract cancers with gemcitabine is feasible. There was no difference in the response rate and overall survival between biliary tract cancer patients in the first- and second- or third-line treatment groups. We also present the systematic review of literature of the recent treatment results of biliary tract cancers treated with gemcitabine.

Adult↗

PubMed2006

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Maspin expression and its clinical significance in non-small cell lung cancer.

BACKGROUND: Maspin is a member of the serpin (serine protease inhibitor) superfamily, and its exact function in the development and progression of malignant tumors remains controversial, though some experimental studies have revealed potential tumor-suppressor activities. In addition, there have been only a few clinical studies on maspin expression in malignant tumors including non-small cell lung cancer (NSCLC). The purpose of this study was to assess maspin expression and its clinical significance in NSCLC. METHODS: A total of 210 consecutive patients with completely resected pathological (p-) stage I-IIIA NSCLC were retrospectively reviewed. Maspin expression along with intratumoral microvessel density, proliferative activity, and p53 status were evaluated immunohistochemically. The incidence of apoptotic cell death was also evaluated. RESULTS: The incidence of strong maspin expression was significantly higher in lung squamous cell carcinoma (56/76, 73.7%; P < .001) than in other histological types. The incidence of aberrant expression of p53 was significantly higher in maspin-strong than in maspin-weak tumors (56.2% and 35.8%, respectively; P = .005). There was no difference in prognosis according to maspin status for all patients. However, for squamous cell carcinoma patients, univariate analysis showed that enhanced maspin expression was a significant factor in predicting a favorable prognosis (5-year survival rates, 70.1% for maspin-strong tumors and 41.5% for maspin-weak tumors; P = .014), which was confirmed in a multivariate analysis (hazard ratio = .475, 95% confidence interval .241-.936; P = .032). CONCLUSIONS: Enhanced maspin expression was a significant and independent factor in predicting a favorable prognosis in lung squamous cell carcinoma.

Adenocarcinoma↗

PubMed2005

Prognostic significance of reversion-inducing cysteine-rich protein with Kazal motifs expression in resected pathologic stage IIIA N2 non-small-cell lung cancer.

BACKGROUND: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase inhibitor, and experimental studies have shown that RECK can suppress tumor progression through angiogenesis inhibition. We have already revealed that enhanced RECK expression is significantly correlated with a favorable prognosis in non-small-cell lung cancer (NSCLC). In this study, further analyses focused on pN2 disease were conducted to assess the clinical significance of RECK expression. METHODS: A total of 118 patients with completely resected pathologic stage IIIA N2 NSCLC were retrospectively examined. RECK expression in the primary tumor, along with involved N2 nodes, was examined immunohistochemically. RESULTS: RECK expression in the primary tumor was strong in 53 patients (44.9%) and was weak in the other 65 patients. The 5-year survival rate of patients with RECK-strong tumor (42.9%) was significantly higher than that of patients with RECK-weak tumor (23.1%; P = .017). Reduced RECK expression significantly correlated with a poor prognosis for patients with a single N2 node involved (P = .019), but not for patients with multiple N2 nodes involved (P = .440). A multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis (P = .031). RECK expression in involved N2 nodes was significantly higher than in primary tumors (P < .001). CONCLUSIONS: RECK status was a novel prognostic factor in pathologic stage IIIA N2 NSCLC.

Aged↗

PubMed2005

Expression of MDA-7/IL-24 and its clinical significance in resected non-small cell lung cancer.

PURPOSE: The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin (IL)-24, is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells including lung cancer cells. However, only one clinical study has documented that MDA-7/IL-24 expression is down-regulated with progression of melanoma. Thus, the present study was conducted to assess the clinical significance of MDA-7/IL-24 expression in non-small cell lung cancer. EXPERIMENTAL DESIGN: A total of 183 consecutive patients with resected pathologic stage I-IIIA, non-small cell lung cancer were retrospectively reviewed, and immunohistochemical staining was used to detect MDA-7/IL-24 expression. RESULTS: MDA-7/IL-24 expression was high in 97 (53.0%) patients and low in the other patients. There was no significant correlation between MDA-7/IL-24 status and any patients' characteristic including pathologic stage. There was no significant difference in tumor angiogenesis or proliferative activity according to MDA-7/IL-24 status, but MDA-7/IL-24-high adenocarcinoma showed a significantly higher incidence of apoptotic tumor cell death than MDA-7/IL-24-low adenocarcinoma. MDA-7/IL-24-high patients seemed to show a favorable postoperative prognosis as compared with MDA-7/IL-24-low patients (5-year survival rates, 75.9% and 62.0%, respectively), although the difference did not reach a statistical significance (P = 0.061). Subset analyses showed that positive MDA-7/IL-24 expression was a significant factor to predict a favorable prognosis in adenocarcinoma (P = 0.033), which was confirmed by a multivariate analysis; there was no difference in the prognosis according to MDA-7/IL-24 status in squamous cell carcinoma. CONCLUSIONS: MDA-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma.

Adenocarcinoma↗

PubMed2005

[18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancers and inflammatory lesions of the lung.

PURPOSE: The aim of this study was to evaluate the relationships among [18F]fluorodeoxyglucose ([18F]-FDG) uptake, Glut-1 and HK-II expressions, and grade of inflammation in resected lung lesions. MATERIALS AND METHODS: Sixty patients had undergone preoperative 18F-FDG-PET imaging and thoracotomy. For semiquantitative analysis of 18F-FDG uptake, partial volume effect corrected maximum standardized uptake values (pSUVs) were calculated. Immunohistochemical staining was performed in resected specimens using anti-Glut-1, anti-HK-II, and anti-proliferative cellular nuclear antigen (PCNA) antibodies, and immunoreactivities were scored as G-, H-, and P-indexes on a five-point scale (0: 0%; 1: 20%, 2: 40%; 3: 60%; 4: 80%, and 5: 100% percentages of strongly immunoreactive cells).Grade of inflammation was also evaluated. RESULTS: The malignant lesions had higher pSUV and higher G- and H- than nonmalignant lesions. pSUVs correlated with the G- (p < .001), H- (p < .01), and P-indexes (p < .01) in malignant lesions. In adenocarcinomas, cancers with lower differentiation showed higher expression of Glut-1 and HK-II than those with higher differentiation. A positive linear regression was observed between pSUVs and the grading of inflammation in nonmalignant lesions (p < .05). CONCLUSIONS: Our study indicates that 18F-FDG uptake in lung cancer correlates well with the Glut-1, HK-II, and PCNA expression. For nonmalignant lesions, the presence of a higher inflammatory process correlated with 18F-FDG uptake.

Adenocarcinoma↗

PubMed2004

Flt-4-positive endothelial cell density and its clinical significance in non-small cell lung cancer.

PURPOSE: Experimental studies have revealed that fms-like tyrosine kinase (Flt)-4 plays important roles in lymphangiogenesis in malignant tumors, but the clinical significance remains unclear. We assessed Flt-4 expression in tumor cells and in endothelial cells in correlation with clinical outcomes in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: A total of 206 consecutive patients with resected pathological stage I-IIIA NSCLC were reviewed. Expression of Flt-4 was examined immunohistochemically, and Flt-4-positive microvessels were quantitatively evaluated (Flt-4-positive endothelial cell density). RESULTS: There was no significant correlation between Flt-4-positive endothelial cell density and any characteristic of patients including nodal metastases. A significant correlation between Flt-4-positive endothelial cell density and Flt-4 status in tumor cells was documented (P < 0.001), but there was no significant difference in the mean Flt-4-positive endothelial cell density according to vascular endothelial growth factor-C or -D status in tumor cells. The 5-year survival rate for higher Flt-4-positive endothelial cell density tumor (56.4%) was significantly lower than that of lower Flt-4-positive endothelial cell density tumor (69.0%, P = 0.046); the prognostic significance was enhanced in pIIIA-N2 patients (5-year survival rates, 18.8% for higher Flt-4-positive endothelial cell density tumor and 50.0% for lower Flt-4-positive endothelial cell density tumor, respectively; P = 0.012). A multivariate analysis confirmed that higher Flt-4-positive endothelial cell density was a significant and independent prognostic factor (P = 0.019). CD34-positive vessel density or Flt-4 status in tumor cells was not a significant prognostic factor. CONCLUSIONS: Flt-4-positive endothelial cell density, not Flt-4 status in tumor cells, was a significant prognostic factor in NSCLC.

Biomarkers, Tumor↗

PubMed2004

Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer.

PURPOSE: The purpose is to assess clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal cells in non-small-cell lung cancer (NSCLC) because experimental studies have revealed that stromal MMP-2 plays important roles in progression of malignant tumors, but most clinical studies focused on tumoral MMP-2 expression, not stromal MMP-2 expression. EXPERIMENTAL DESIGN: We conducted a retrospective study on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of 218 consecutive patients with completely resected pathological stage I-IIIA, NSCLC. RESULTS: Strong MMP-2 expression in tumor cells and stromal fibroblasts were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP-2 expression in stromal fibroblasts was more frequently seen in squamous cell carcinoma (72.7%) than in adenocarcinoma (54.9%; P = 0.016). Tumors showing strong MMP-2 expression in stromal fibroblasts showed a significantly higher intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean intratumoral microvessel density, 50.9 versus 32.4, P = 0.003). In addition, postoperative prognosis of strong stromal MMP-2 patients was significantly poorer than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus 60.2%, P = 0.032), and the prognostic significance was enhanced in squamous cell carcinoma patients but disappeared in adenocarcinoma patients. Multivariate analyses confirmed that strong stromal MMP-2 expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was not a significant prognostic factor. CONCLUSIONS: MMP-2 status in stromal fibroblasts, not in tumor cells, was a significant prognostic factor associated with angiogenesis in NSCLC.

Antigens, CD↗

PubMed2004

Prognostic factors in resected pathologic (p-) stage IIIA-N2, non-small-cell lung cancer.

BACKGROUND: Postoperative prognosis for patients with pathologic (p-) stage IIIA-N2 non-small-cell lung cancer (NSCLC) is poor, and significant factors that influence the prognosis remain unclear. METHODS: A total of 99 patients who underwent complete resection for p-stage IIIA-N2 NSCLC without any preoperative therapy were retrospectively reviewed. Biological features such as tumor angiogenesis (intratumoral microvessel density [IMVD]), proliferative activity (proliferative index [PI]), and p53 status were also evaluated immunohistochemically. RESULTS: Univariate analysis revealed that the number of involved N2 stations was a significant prognostic factor; 5-year survival rates for a tumor with metastases in single N2 stations, tumor with metastases in two N2 stations, and tumor with metastases in 3 or more N2 stations were 41.6%, 35.3%, and 0.0%, respectively (P =.041) In addition, the 5-year survival rate for cN0-1 disease was significantly higher than that for cN2 disease (41.9% and 25.5%, respectively; P =.048) Tumor angiogenesis and proliferative activity were the most significant prognostic factors; 5-year survival rates for lower-IMDV tumor and higher-IMVD tumor were 53.6% and 15.9%, respectively (P =.002), and those for lower-PI tumor and higher-PI tumor were 47.0% and 20.4%, respectively (P =.019) There was no difference in the postoperative survival between tumor showing aberrant p53 expression and tumor showing no aberrant p53 expression. These results were confirmed by a multivariate analysis. CONCLUSIONS: P-stage IIIA-N2 NSCLC cases represented a mixture of heterogeneous prognostic subgroups, and the number of involved N2 stations, cN status, PI, and IMVD were significant predictors of the survival.

Biomarkers, Tumor↗

PubMed2004

Expression of a novel matrix metalloproteinase regulator, RECK, and its clinical significance in resected non-small cell lung cancer.

The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) was initially isolated as a transformation-suppressor gene by expression cloning and found to encode a membrane-anchored regulator of the matrix metalloproteinases (MMPs). Experimental studies have shown that RECK can suppress tumour - invasion, metastasis and angiogenesis. However, the clinical impact of RECK remains unclear. To assess the clinical significance of RECK-expression in non-small cell lung cancer (NSCLC), a total of 171 patients with completely resected pathological stage (p-stage) I-IIIA NSCLC were retrospectively examined. Expression of RECK and vascular endothelial growth factor (VEGF) in tumour tissues was assessed by immunohistochemical staining (IHS). Intratumoural microvessel density (IMVD), a measurement of angiogenesis, was also determined by IHS using an anti-CD34 antibody. A significant inverse correlation between RECK-expression and tumour angiogenesis was documented; the mean IMVD in tumours with strong RECK-expression (157.1) was significantly lower than that observed in tumours with weak RECK-expression (194.5; P = 0.008). Interestingly, this inverse correlation was seen only when VEGF was strongly expressed, which suggests that RECK could suppress the angiogenesis induced by VEGF. The 5-year survival rate for patients with tumours with strong RECK-expression (75.8%) was significantly higher than that for patients with weakly expressing tumours (54.3%; P = 0.016). Subset analyses showed that the prognostic impact of RECK-status was evident in patients with either adenocarcinoma, poorly differentiated tumours, or p-stage IIIA disease. A multivariate analysis confirmed that reduced RECK-expression was an independent and significant factor in predicting a poor prognosis (P = 0.009; Hazard ratio (HR), 0.474 with a 95% Confidence interval (CI) of 0.271-0.830). In conclusion, RECK-status is a significant prognostic factor correlated with tumour angiogenesis in NSCLC patients.

Apoptosis↗

PubMed2004

Skip mediastinal nodal metastases in non-small cell lung cancer.

OBJECTIVE: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases ('skip-N2 metastases') in non-small cell lung cancer (NSCLC). METHODS: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. RESULTS: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. CONCLUSIONS: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.

Aged↗

PubMed2004

Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC).

Many experimental studies have revealed that enhanced thymidylate synthase (TS) expression is significantly correlated with higher proliferative activity of tumor cells, which may account for a poor prognosis of high-TS patients. However, only a few clinical studies have focused on the correlation between TS status and cell proliferation. Therefore, we assessed the correlation between TS expression and proliferative index (PI) as a marker of cell proliferation or p53 status in a total of 109 patients with completely resected pathologic stage I, non-small cell lung cancer (NSCLC). PI was defined as the percentage of tumor cells with positive staining against proliferative cell nuclear antigen (PCNA). The mean PIs of TS-high and TS-low tumors were 48.2% and 34.4% respectively, showing a significantly higher proliferative activity of TS-high tumor (P=0.020); when stratified according to histological type, the difference was significant in adenocarcinoma (P=0.038), but not in squamous cell carcinoma. There was no significant correlation between TS expression and p53 status. In conclusion, tumor cells with higher TS expression have higher proliferative activity in NSCLC, especially in adenocarcinoma.

Aged↗

PubMed2004

Angiogenesis and the efficacy of postoperative administration of UFT in pathologic stage I non-small cell lung cancer.

UFT is an oral 5-fluorouracil derivative drug that may improve postoperative survival in non-small cell lung cancer (NSCLC), and experimental studies have shown that UFT inhibits tumor angiogenesis. In the present study, therefore, the correlation between tumor angiogenesis (intratumoral microvessel density, IMVD) and the efficacy of UFT in 162 patients with pathologic stage I NSCLC was examined. For higher IMVD tumors (IMVD > or = 20, n = 80), the 5-year survival rate of UFT-treated patients (82.5%) was significantly higher than that of surgery-alone patients (61.8%, P = 0.032). For lower IMVD tumors (n = 82), however, there was no difference in the survival between these groups (5-year survival rates, 84.9% and 82.6%, respectively; P = 0.657). Multivariate analyses confirmed that postoperative UFT administration was effective for higher IMVD tumors (P = 0.046; relative risk [RR] and the 95% confidence interval [CI], 0.288 [0.084-0.979]), but not for lower IMVD tumors (P = 0.616; 0.726 [0.208-2.539]). Moreover, vascular endothelial growth factor (VEGF) status was also a predictive factor. For tumor showing strong VEGF expression (n = 63), UFT administration improved the survival (5-year survival rates of UFT-treated patients and surgery-alone patients, 84.6% and 60.0%, respectively; P = 0.048); for weakly VEGF-expressing tumors (n = 99), UFT administration did not influence the survival (5-year survival rates, 83.4% and 79.1%, respectively; P = 0.455). Multivariate analyses demonstrated that UFT administration seemed to be effective for strong VEGF tumors (P = 0.063; RR and the 95% CI, 0.234 [0.051-10.81]), but not for weak VEGF tumors (P = 0.456; 0.673 [0.293-1.900]). In conclusion, the efficacy of postoperative UFT administration in NSCLC was correlated with tumor angiogenesis.

Aged↗

PubMed2004

[Advanced lung cancer of performance status 3 successfully treated by gefitinib--a case report].

The prognosis in cases of advanced lung cancer with poor performance status is poor. We report here a patient with advanced non-small cell lung cancer of performance status 3 who had severe cancer-induced pain, which was not controlable with morphine and radiation therapy. The cancer was successfully treated by oral administration of gefitinib (250 mg/day) without serious adverse effects of worsening of quality of life. Not only was the tumor controlled but rapid relief of severe cancer-induced pain was achieved.

Administration, Oral↗

PubMed2003

Glomeruloid microvascular proliferation is superior to intratumoral microvessel density as a prognostic marker in non-small cell lung cancer.

Glomeruloid microvascular proliferation (GMP) is a focal proliferative budding of endothelial cells (ECs) resembling a renal glomerulus. Whereas some experimental and clinical studies have suggested recently that GMPs indicate an aggressive angiogenic phenotype, the incidence and clinical significance of GMPs remains unclear. Thus, we conducted a retrospective study on GMPs in a total of 236 patients with completely resected pathological (p-) stage I-IIIA NSCLC. ECs were highlighted with immunohistochemical staining using an anti-CD34 antibody, and GMPs were defined as focal glomerulus-like aggregates of closely associated and multilayer CD34-positive ECs. Expression of vascular endothelial growth factor, angiopoietin (Ang)-1, and Ang-2 was also examined immunohistochemically. GMPs were positive in 60 (25.4%) patients, and the incidence was not correlated with age, gender, histological type, or p-stage. The mean intratumoral microvessel densities for GMP-negative tumor and GMP-positive tumor were 178.2 and 184.1, respectively, showing that the incidence of GMPs was not correlated with intratumoral microvessel density (P = 0.676). There was no correlation between vascular endothelial growth factor expression and the incidence of GMPs, but GMPs were more frequently seen in Ang-1-positive tumor than in Ang-1-negative tumor. The 5-year survival rate of GMP-positive patients was 54.2%, which was significantly lower than that of GMP-negative patients (72.3%; P = 0.016). The 5-year survival rate of higher-MVD patients (71.5%) seemed to be lower than that of the lower-MVD patients (63.7%), but the difference did not reach a statistical significance (P = 0.137). A multivariate analysis confirmed that the presence of GMPs was a significant prognostic factor (P = 0.003), whereas MVD was not. In conclusion, GMPs indicate an aggressive angiogenic phenotype associated with a poor prognosis in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis.

Only a few clinical studies have documented a significant correlation between intratumoral microvessel density (IMVD), a measurement of angiogenesis, and apoptotic index (AI), an incidence of apoptosis, although many experimental studies have confirmed that insufficient angiogenesis induces accelerated apoptotic cell death. In the present study, therefore, to assess AI in correlation with IMVD in resected non-small cell lung cancer, a total of 236 patients with pathologic stage I to IIIa were reviewed. IMVDs were determined immunohistochemically with an antibody against a pan-endothelial marker, CD34 (CD34-IMVD), and an antibody against a proliferation-related endothelial marker, CD105 (CD105-IMVD). AI was defined as the number of tumor cells positive for the terminal deoxynucleotidyl tranferase-mediated dUTP-biotin nick end-labeling staining per 1000 tumor cells. When CD34 was used as a marker of angiogenesis, the mean AIs for the lower-IMVD and the higher-IMVD patients were 20.1 and 17.5, respectively, demonstrating no significant difference between the lower- and the higher-IMVD patients. In contrast, when CD105 was used, the mean AI for the lower-IMVD patients was significantly higher than that for the higher-IMVD patients (22.0 and 15.6, respectively; P=0.019). There was no significant correlation between proliferative activity and CD34-IMVD or CD105-IMVD. These results demonstrated that that decreased angiogenesis may induce enhanced apoptotic tumor-cell death without affecting cell proliferation.

Aged↗

PubMed2003

[A case of endobronchial squamous cell lung cancer successfully treated with weekly chemotherapy of carboplatin and paclitaxel].

A 69-year-old man had undergone low anterior resection and a right lobe resection of the liver for rectum cancer and metastatic liver tumor at the age of 66 years. He presented at our hospital because of an abnormal shadow on a CT chest scan, which indicated a tumor shadow 2.5 cm in size in the lingular lobe and enlarged hilar and mediastinal lymph nodes. A bronchoscopic tumor biopsy revealed pulmonary metastasis from the rectum cancer. Bronchoscopic examination also identified an endobronchial squamous cell lung cancer, which almost completely obstructed the orifice of B1 and B2. We concluded that the patient had squamous cell lung cancer with metastases in the mediastinal lymph nodes. He was initially treated with weekly chemotherapy with carboplatin (AUC 1.25) and paclitaxel (70 mg/m2). The endobronchial tumor was markedly reduced in size after 2 weeks of the chemotherapy. Furthermore, after 6 weeks of the chemotherapy, the tumor had disappeared completely, and 11 days later, lower division segmentectomy and hilar and mediastinal lymph node dissection were performed. Pathological examination revealed no metastases in the lymph nodes. The patient has continued to receive chemotherapy as an outpatient and has been well without recurrence of any metastases for over 16 months.

Aged↗