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Kanji Nagai

Publications and source records attributed to Kanji Nagai.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of extratumoral lymphatic permeation in non-small cell lung cancer as a means of predicting outcome.

BACKGROUND: Lymphatic permeation (ly) has been described as a potential prognostic factor for non-small cell lung cancer (NSCLC). METHODS: The purpose of this study was to analyze whether evaluation of the presence or absence of ly and its location (ly 0: absent, N=464; ly 1: intratumoral, N=42; ly 2: extratumoral, N=52) provides an appropriate means of predicting the outcome of NSCLC. We investigated the clinical implications of ly in 558 consecutive patients with surgically resected NSCLC. RESULTS: Evaluation according to ly status showed that the recurrence-free survival (RFS) time of the ly 2 patients was significantly shorter than that of the ly 0 patients (P<0.0001), the ly 1 patients (P=0.0028). A significant difference in RFS time was also observed between the ly 0 patients and the ly 1 patients (P=0.0025). RFS time of the ly 0 patients was significantly longer than that of the ly 1 plus ly 2 patients (P<0.0001). We also evaluated the patients with pathological stage I disease (N=378) separately. The RFS time of the ly 2 patients (N=9) was significantly shorter than that of the ly 0 plus ly 1 patients (P<0.0001). In the nine ly 2 patients, six developed a distant metastasis within 1 year. A multivariate analysis revealed that ly status (ly 0 plus ly 1 versus ly 2) was an independent prognostic factor (P=0.0116), demonstrating the significant prognostic value of extratumoral lymphatic permeation in NSCLC. CONCLUSIONS: These results indicate that ly status is a good prognostic marker of poorer outcome in patients with resected NSCLC.

Adenocarcinoma↗
PubMed2006

Prostate-specific antigen induces apoptosis of osteoclast precursors: potential role in osteoblastic bone metastases of prostate cancer.

BACKGROUND: Prostate cancer is frequently associated with bone metastases with marked osteoblastic changes and low osteoclastic activity but its mechanism is not well understood. We previously reported that prostate-specific antigen (PSA) stimulated the proliferation and the activation of osteoblasts. In this study, we investigated the effect of PSA on osteoclastogenesis. METHODS: Two human prostate cancer cell lines and PSA were directly injected into human adult bone (HAB) implanted into NOD/SCID mice, followed by morphological analysis. RAW 264.7 cells, murine osteoclast precursor, were treated with PSA. RESULTS: PSA-producing LNCaP and PSA caused a significant decrease of osteoclast precursors and osteoclasts in HAB accompanied by osteoblast proliferation and new bone formation, while PSA-nonproducing PC3 showed increasing osteoclasts with osteolysis. PSA induced apoptosis of RAW 264.7 cells in vitro. PSA-induced apoptosis was dependent of enzymatic activity of PSA and was specific to immature tartrate-resistant acid phosphatase-negative mononuclear RAW 264.7 cells. CONCLUSIONS: PSA plays a crucial role for osteoblastic bone metastasis by promoting both osteoblasts proliferation and apoptosis of osteoclast precursors.

Adenocarcinoma↗
PubMed2006

Psychometric properties of the Japanese version of the Quality Of Life-Cancer Survivors Instrument.

The purpose of this study was to describe the psychometric properties of the Japanese version of the Quality of Life-Cancer Survivors Instrument (QOL-CS-J) developed in the U.S. This study was conducted as a mail survey to survivors of more than 5 years post curative resection for non-small-cell lung cancer (NSCLC) and who had participated in an earlier survey. This survey included the medical and demographic factors, the QOL-CS scores, and the Medical Outcome Study 36-Item Short Form (SF-36). A total of 113 survivors completed the survey. To confirm the reliability, the Cronbach's alpha coefficient of each subscale was calculated as an internal consistency (alpha = 0.65-0.89). To confirm the validity of the trial as conducted, Pearson's correlation coefficients between the subscales of the QOL-CS and the subscales of the SF-36 were calculated. There were moderate correlations between associated subscales including QOL-CS physical to SF-36 bodily pain (r = 0.45) and vitality (r = 0.52), QOL-CS psychological to SF-36 mental health (r = 0.55), QOL-CS social to SF-36 general health perception (r = 0.31) and mental health (r = 0.47), and QOL-CS total to each subscale of SF-36 (r = 0.25-0.64). Findings demonstrated that the QOL-CS-J adequately measured the QOL in long-term NSCLC survivors.

Adult↗
PubMed2006

Carbonic anhydrase IX expression is associated with tumor progression and a poor prognosis of lung adenocarcinoma.

Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into carbonic acid and participates in a variety of physiological and biological processes. The aim of this study was to evaluate the prognostic significance of CA IX expression in patients with lung adenocarcinoma. Standard immunohistochemical techniques were used to study CA IX expression in 134 patients who underwent curative resection for adenocarcinoma of the lung at our hospital between January 1995 and December 1996. We evaluated the correlations between CA IX expression levels on cancer cells and clinicopathological factors. CA IX expression was not observed in normal lung tissue or specimens from non-invasive adenocarcinomas. CA IX immunostaining was detected in 33 (24.6%) invasive adenocarcinoma cases. Poor differentiated histological phenotype (p=0.0015), pathological stage (p=0.0400), vascular invasion (p=0.0009) and lymphatic permeation (p=0.0050) were significantly related to CA IX expression. On univariate analysis, CA IX positive cases showed significantly shorter overall survival (p=0.0083) and disease-free survival (p=0.0122). In particular, the overall and disease-free survivals in stages I+II were significantly shorter in the CA IX positive than in the CA IX negative cases (p=0.0269 and 0.0011, respectively). Our results suggest that CA IX expression is strongly associated with tumor progression and indicates a poor prognosis for patients with stages I+II lung adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy.

BACKGROUND: Eg5 is a microtubule motor protein that functions in bipolar spindle assembly. We investigated the relationship between Eg5 expression and the response to chemotherapy of patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eg5 expression was investigated immunohistochemically in 122 formalin-fixed tumor samples from untreated stage IIIB or IV NSCLC patients. We also investigated cyclin B1 expression, which is involved in the G2/M transition. All patients received antimitotic agents combined with platinum chemotherapy. The response to chemotherapy was compared in relation to Eg5 and cyclin B1 expression and in relation to clinicopathological factors. RESULTS: The response rate to chemotherapy of patients with Eg5-positive tumors was 37%, as opposed to 10% for patients with Eg5-negative tumors, and Eg5 expression was significantly associated with the response to chemotherapy (P=0.002). The response rate of patients with cyclin B1-positive tumors (53%) was higher than that of patients with cyclin B1-negative tumors (23%) (P=0.009), and Eg5 expression was significantly correlated with cyclin B1 expression (P=0.005). A multivariate analysis confirmed Eg5 status to be an independent variable related to response to chemotherapy (P=0.008). CONCLUSIONS: Eg5 expression can predict a response to antimitotic agents combined with platinum chemotherapy among patients with advanced NSCLC.

Adult↗
PubMed2006

The lung cancer database project at the National Cancer Center, Japan: study design, corresponding rate and profiles of cohort.

BACKGROUND: The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. METHODS: Between July 1999 and July 2004, consecutive lung cancer patients were recruited into this project. The baseline survey consisted of self-administered questionnaires concerning various demographic data, health habits and psychological factors. Medical information was obtained from the patients' medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes. RESULTS: Out of the 2506 patients who were asked to participate in the project, 2036 (81%) patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up. CONCLUSIONS: This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.

Adult↗
PubMed2006

Inhibition of bone-derived insulin-like growth factors by a ligand-specific antibody suppresses the growth of human multiple myeloma in the human adult bone explanted in NOD/SCID mouse.

Multiple myeloma (MM) is a fatal disease that affects plasma cells. Patients with MM have 1 or more osteolytic lesions in their bone tissues, where insulin-like growth factors (IGFs; IGF-I and IGF-II) are mainly stored. The role of bone-derived IGFs in the development of MM has not been extensively studied because reliable animal models are lacking. We established an animal model using a human MM cell line, RPMI8226, in nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice implanted with human adult bone (HAB) fragments. Treatment with an anti-human IGF-neutralizing monoclonal antibody, KM1468, inhibited the IGF-I-stimulated phosphorylation of type-I IGF receptors (IGF-IR) in RPMI8226 cells and the activation of the downstream PI3-K/Akt signaling pathway in vitro. KM1468 inhibited IGF-I-mediated RPMI8226 cell growth in a dose-dependent manner. In the NOD/SCID-HAB model, treatment with KM1468 significantly inhibited the growth of RPMI8226 cells (p<0.02). These results indicated that the growth of MM cells was predominantly stimulated not by serum-derived IGFs, but by bone-derived IGFs. Furthermore, the targeting of bone-derived IGFs, using a neutralizing antibody, may offer a new therapeutic strategy for MM.

Animals↗
PubMed2006

Differences in clinicopathological and biological features between central-type and peripheral-type squamous cell carcinoma of the lung.

The central type and peripheral type squamous cell carcinoma (SCC) of the lung have different clinicopathological characteristics, but, little is known about their biological characteristics. We investigated differences between the properties and phenotypes of peripheral-type (P-type) and central-type (C-type) SCC by performing an immunohistochemical analysis of each type by tissue microarray analysis with a large panel of antibodies. To examine strictly, we selected 20 P-type SCCs that were pathological stage T1 and limited to more peripherally than the fifth bronchial bifurcation, and 21 C-type SCCs that were pathological stage T1 and limited to a lobar bronchus. The results of the clinicopathological study showed that the patients with P-type SCC were significantly older than the patients with C-type SCC and that squamous metaplasia was predominant in C-type SCC than in P-type SCC. The 36 antibodies revealed different expression patterns of cytokeratin 7 (CK 7) and cytokeratin 19 (CK 19) between C-type and P-type SCC. CK 7 expression was more predominant in P-type SCC than in C-type SCC, and CK 19 expression was more predominant in C-type SCC than in P-type SCC. These results suggest that C-type and P-type SCC have different clinicopathological and biological features.

Adult↗
PubMed2006

Neuroendocrine neoplasms of the lung: a prognostic spectrum.

PURPOSE: Neuroendocrine (NE) tumors of the lung include typical carcinoid (TC), atypical carcinoid (AC), large-cell NE carcinoma (LCNEC), and small-cell lung carcinoma (SCLC). Their clinicopathologic profiles and relative grade of malignancy have not been defined. PATIENTS AND METHODS: From 10 Japanese institutes, 383 surgically resected pulmonary NE tumors were collected. The histologic diagnosis was determined by the consensus of a pathology panel consisting of six expert pathologists as TC, AC, LCNEC, or SCLC on the basis of the WHO classification, and its relationship to clinicopathologic profiles was analyzed. RESULTS: Of the 383 tumors, 18 were excluded because of an improper specimen. The pathology panel reviewed the remaining 366 tumors, and a diagnosis of NE tumor was made in 318 patients (87.4%); 55 patients had TC, nine had AC, 141 had LCNEC, and 113 had SCLC. The 5-year survival rates of patients with all stages were as follows: 96.2% for TC, 77.8% for AC, 40.3% for LCNEC, and 35.7% for SCLC. There was significant prognostic difference between TC and AC as well as between AC and LCNEC+SCLC. However, there was no difference between LCNEC and SCLC, and their survival curves were superimposed. The multivariate analysis indicated that histologic type, completeness of resection, symptoms, nodal involvement, and age were significantly prognostic. CONCLUSION: The grade of malignancy of NE tumors was upgraded in the following order: TC, AC, LCNEC, and SCLC. No prognostic difference was noted between LCNEC and SCLC. The high-grade NE histology uniformly indicated poor prognosis regardless of its histologic type.

Carcinoma, Small Cell↗
PubMed2006

Pleural lavage cytology before and after lung resection in non-small cell lung cancer patients.

BACKGROUND: The aim of this study was to analyze on a multivariate basis the prognostic significance of pre-resection and post-resection pleural lavage cytologies in surgically resected primary non-small cell lung cancer (NSCLC) patients, in relation to pathologic TNM factors in a large cohort of almost 1,200 patients. METHODS: From August 1992 through March 2001, pleural lavage cytology (PLC) was performed in 1,214 NSCLC patients without pleural effusion or dissemination undergoing pulmonary resection. The cytologic evaluation was classified into three categories: negative, suggestive, and positive. To investigate the impact on patient survival, PLC results were analyzed with conventional clinicopathologic factors. RESULTS: Definitive pre-resection PLC result was obtained in 1,194 patients and 38 had a positive result. The 5-year survival rates were 27% if pre-resection PLC was positive and 71% if negative. Of 1,198 patients 54 had a positive post-resection PLC result. The 5-year survival rates were 10% if post-resection PLC was positive and 73% if negative. On multivariate analysis, post-resection PLC was an independent prognostic factor as significant as established clinicopathologic factors. CONCLUSIONS: Pre-resection and post-resection PLC should be recognized as an essential prognostic factor and should be performed in NSCLC patients without pleural effusion and dissemination. Post-PLC, compared with pre-PLC, had a greater and independent impact on survival and needs to be incorporated in the pathologic staging of NSCLC in the future.

Adenocarcinoma↗
PubMed2006

Is surgical resection indicated for a solitary non-small cell lung cancer recurrence?

OBJECTIVES: Some investigators have reported long-term survival after surgical resection of a solitary non-small cell lung cancer recurrence in various sites. However, the role and indications of the second operation remain unclear. METHODS: We reviewed 28 patients with a solitary recurrence after successful initial resection of primary non-small cell lung cancer who underwent resection of the recurrent lesion. The clinicopathologic factors associated with outcome were analyzed. RESULTS: There were 17 men and 11 women. Recurrence resection was performed for the following sites: 16 in the lung, 5 in the brain, 2 in the adrenal gland, and 1 each in the chest wall, stomach, skin, pelvic lymph node, and malar bone. The median survival time was 25 months, and the 1-, 2-, and 5-year survival rates after recurrence were 89%, 59%, and 32%, respectively. Advanced p-stage (p-stage II and III, n = 14) of the primary tumor was the significant negative prognostic factor. Patients with p-stage II or III had survival equivalent to that of those who had multiple recurrences or were unfit for further surgical intervention. CONCLUSIONS: Resection of a solitary non-small cell lung cancer recurrence might provide long-term survival in highly selected patients. However, surgical resection might be contraindicated if the primary tumor is stage II or III.

Adrenal Gland Neoplasms↗
PubMed2006

Marital status, social support and survival after curative resection in non-small-cell lung cancer.

It has been suggested that marital status and social support are associated with survival in cases of lung cancer, and that such an association may be mediated by several factors. In this prospective cohort study, we investigated the effect of marital status and social support on survival after curative resection for non-small cell lung carcinoma (NSCLC) in Japan. From June 1996 to April 1999, a total of 238 patients with resectable NSCLC were enrolled. Marital status and social support were assessed. The presence and absence of confidants and the satisfaction level with the confidants were used as factors reflecting social support. During the follow-up period, 57 deaths from all causes were identified through January 2004. For the statistical analysis, Cox proportional hazards regression analyses were used. With regard to marital status, the multivariable adjusted hazard ratio (HR) of unmarried patients versus married patients was 0.8 (95% confidence interval, 0.3-1.8) (P-value=0.53) after controlling for potential confounding factors, including age, sex, occasion of cancer diagnosis, pathological stage, smoking status, smoking status after surgery and serum albumin level. Similarly, the multivariable adjusted HR of patients without confidants versus those with confidants was 1.0 (0.5-2.2) (P-value=0.90), whereas the multivariable adjusted HR of the dissatisfied-with-confidants group versus the satisfied-with-confidants group was 0.7 (0.4-1.3) (P-value=0.28). The present data do not support the hypothesis that marital status and social support are associated with survival in NSCLC.

Aged↗
PubMed2006

Depression and survival in patients with non-small cell lung cancer after curative resection: a preliminary study.

Psychological depression is thought to be a predictor of poor survival among cancer patients. The objective of the present study was to investigate the association between depression and survival in surgically treated Japanese patients with non-small cell lung cancer (NSCLC). From June 1996 through April 1999, a total of 229 patients with postoperative lung cancer were enrolled. Three months after the patients' surgery, the Structured Clinical Interview for DSM-III-R (SCID) and the Profile of Mood States (POMS) were used to assess the patient for depression, based on the interviewers' rating and a self-report, respectively. The follow-up period consisted of a total of 14 342 person-months (median=69 months). As of January 2004, 55 deaths had occurred within the follow-up period. A Cox regression was used to estimate the hazard ratio (HR) of mortality adjusting for age, sex, smoking status, occasion of diagnosis, pathological stage and preoperative percentage forced expiratory volume in 1 s. The depression-dejection subscale on the POMS was divided into three score levels. The multivariate HR of survival for individuals with depression, as diagnosed by the SCID, was 2.2 (95% confidence interval 0.8-6.0) (P-value=0.14), compared with individuals without depression. The multivariate HR of survival for subjects in the highest level of the POMS Depression-Dejection subscale was 1.4 (0.7-2.6), compared with in the lowest level (trend P-value=0.0502). This prospective cohort study in Japan does not support the hypothesis that depression is associated with survival among NSCLC patients after curative resection, but further analysis involving a long-term follow-up period is needed.

Adult↗
PubMed2006

Immunohistochemical differential diagnosis between large cell neuroendocrine carcinoma and small cell carcinoma by tissue microarray analysis with a large antibody panel.

To elucidate additional phenotypic differences between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), we performed tissue microarray (TMA) analysis of surgically resected LCNEC and SCLC specimens. Immunostaining with 48 antibodies was scored based on staining intensity and the percentage of cells that stained positively. Four proteins were identified as significantly expressed in LCNEC as compared with SCLC: cytokeratin (CK)7, 113 vs 49 (P < .0301); CK18, 171 vs 60 (P < .0008); E-cadherin, 77 vs 9 (P < .0073); and beta-catenin, 191 vs 120 (P < .0286). Immunostaining of cross-sections containing LCNEC and SCLC components revealed significant expression of CK7, CK18 and beta-catenin in the LCNEC component compared with the SCLC component in 2 of 3 cases. Our results indicate that significant expression of CK7, CK18, E-cadherin, and beta-catenin is more characteristic of LCNEC than of SCLC, and these findings provide further support that these tumor types are separate entities morphologically and immunophenotypically, if not biologically.

Biomarkers, Tumor↗
PubMed2006

Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study.

STUDY OBJECTIVES: To clarify the possibility of a hereditary predisposition to lung cancer, we investigated the association between a family history of lung cancer and subsequent risk of lung cancer in a large-scale, population-based cohort study. DESIGN: We investigated 102,255 middle-aged and older Japanese subjects (48,834 men and 53,421 women) with 13-year follow-up. A total of 791 cases of lung cancer were newly diagnosed during the follow-up period. RESULTS: A family history of lung cancer in a first-degree relative was associated with a significantly increased risk of lung cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.31 to 2.88). The association was stronger in women than in men (HR, 2.65; 95% CI, 1.40 to 5.01 and HR, 1.69; 95% CI, 1.03 to 2.78, respectively), and in never-smokers than in current smokers (HR, 2.48; 95% CI, 1.27 to 4.84 and HR, 1.73; 95% CI, 0.99 to 3.00, respectively). In addition, family history was more strongly associated with the risk of squamous cell carcinoma than with other histologic types (HR, 2.79; 95% CI, 1.37 to 5.68), while no clear increase in risk was observed in adenocarcinoma and small cell carcinoma. A family history of overall cancer was not associated with an increased risk of lung cancer. CONCLUSIONS: These results suggest that those with a family history of lung cancer are more likely to acquire lung cancer themselves.

Adenocarcinoma↗
PubMed2006

[A resected case of sclerosing thymoma].

An asymptomatic 47-year-old man was found to have an anterior mediastinal nodule on an annual chest X-ray. Chest CT showed a 2cm nodule in the left anterior mediastinum. Because thymoma was suspected, total thymectomy was performed. Histologically, the greater part of the nodule was composed of hyalinized fibrous tissues and there was a scattered, small aggregation of spindle to oval cells, showing positive for AE 1/3. Therefore this nodule was diagnosed as sclerosing thymoma, which is a subtype of thymoma first reported in 1994. Since few reports of this disease have been made so far, needless to say its clinical features or pathogenesis, even its very existence is not well known. Sclerosing thymoma should be taken into account, when only fibrous tissues are obtained by biopsy in patients with anterior mediastinal tumors.

Humans↗
PubMed2005

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the thymus: report of four cases.

Mucosa-associated lymphoid tissue (MALT) lymphoma in the thymus is extremely rare, and little is known about its clinicopathological features. In this study, we examined four cases of MALT lymphoma in the thymus at our institute in terms of clinicopathological features. Most patients had autoimmune disease or hyperglobulinemia, and they also had cysts in the tumors. Both elevated serum levels of autoantibodies and the polyclonal increase in serum Ig remained almost unchanged after total thymectomy in all patients. We recommend that MALT lymphoma in the thymus should be considered in the differential diagnosis when a cystic thymic mass is found and if the patient is Asian and/or has autoimmune disease or hyperglobulinemia.

Adult↗