PubMed Health⌕ Search

Biomedical subjects

Chiaki Endo

Publications and source records attributed to Chiaki Endo.

18 recordsLinked to original sources
PubMed2006

Microarray analysis of promoter methylation in lung cancers.

Aberrant DNA methylation is an important event in carcinogenesis. Of the various regions of a gene that can be methylated in cancers, the promoter is the most important for the regulation of gene expression. Here, we describe a microarray analysis of DNA methylation in the promoter regions of genes using a newly developed promoter-associated methylated DNA amplification DNA chip (PMAD). For each sample, methylated Hpa II-resistant DNA fragments and Msp I-cleaved (unmethylated+methylated) DNA fragments were amplified and labeled with Cy3 and Cy5 respectively, then hybridized to a microarray containing the promoters of 288 cancer-related genes. Signals from Hpa II-resistant (methylated) DNA (Cy3) were normalized to signals from Msp I-cleaved (unmethylated+methylated) DNA fragments (Cy5). Normalized signals from lung cancer cell lines were compared to signals from normal lung cells. About 10.9% of the cancer-related genes were hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3, RASSF1A, FABP3, PRKCDBP, and PAX3 genes were hypermethylated in most lung cancer cell lines examined. The expression profiles of these genes correlated to the methylation profiles of the genes, indicating that the microarray analysis of DNA methylation in the promoter region of the genes is convenient for epigenetic study. Further analysis of primary tumors indicated that the frequency of hypermethylation was high for ASC (82%) and PAX3 (86%) in all tumor types, and high for RIPK3 in small cell carcinoma (57%). This demonstrates that our PMAD method is effective at finding epigenetic changes during cancer.

Adenocarcinoma↗
PubMed2006

Predicting postrecurrence survival among completely resected nonsmall-cell lung cancer patients.

BACKGROUND: Survival after recurrence subsequent to complete resection of nonsmall-cell lung cancer (NSCLC) has been considered a multifactorial process dependent on demographic, clinical, biological, and treatment characteristics. This study sought to quantify the prognostic effects of these characteristics on postrecurrence survival. METHODS: Three hundred ninety NSCLC patients who underwent complete resection and subsequently had recurrent cancer were studied. The associations between characteristics of both the initial and recurrent disease with postrecurrence survival were evaluated by Cox proportional hazards models. A multivariable Cox model determined those factors most strongly associated with postrecurrence survival . A simple algorithm based on this model facilitates estimating risk of postrecurrence mortality, as quantified by risk score points. RESULTS: The factors most strongly associated with postrecurrence survival were performance status at recurrence (3 or 4, 4.2 points; 2, 2.8 points; and 1, 1.5 points), symptoms at recurrence (3.6 points), liver recurrence (2.3 points), initial lung cancer stage IIB or worse (1.8 points), and multiple recurrences (1.0 points). Based on these factors, patients were stratified as low risk (4.0 or fewer total points), moderate-low risk (4.1 to 6.1 points), moderate-high risk (6.1 to 8.0 points), and high risk (more than 8.0 points), with 12-month survival of 75%, 51%, 25%, and 9%, respectively. Postrecurrence survival was significantly different across groups (p < 0.01). CONCLUSIONS: The proposed prediction instrument offers clinicians a succinct tool for rapidly evaluating mortality risk after recurrence. The characteristics comprising this instrument can be easily ascertained and measured, making it of potential clinical value.

Adult↗
PubMed2005

Computed tomographic images reflect the biologic behavior of small lung adenocarcinoma: they correlate with cell proliferation, microvascularization, cell adhesion, degradation of extracellular matrix, and K-ras mutation.

BACKGROUND: We previously reported that the computed tomographic M/L ratio (area of the tumor in the mediastinal computed tomographic image/area of the tumor in the lung computed tomographic image) of small peripheral lung adenocarcinoma is correlated with patient prognosis. METHODS: Immunostaining for p53, bcl-2, Ki-67, vascular endothelial growth factor, CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 2, and mutation of K-ras was assessed in 131 surgically resected, primary peripheral lung adenocarcinomas of 30 mm or less in maximum diameter to clarify the relationship between computed tomographic findings and biologic activities. RESULTS: The numbers of patients with high labeling indexes of Ki-67 and high expression of vascular endothelial growth factor, CD34, matrix metalloproteinase 2, and matrix metalloproteinase 9 in the solid-type group (computed tomographic M/L ratio > or = 50%) were significantly higher than those in the faint density-type group (computed tomographic M/L ratio < 50%; P = .04 for Ki-67, P = .03 for vascular endothelial growth factor, P = .0009 for CD34, P = .001 for matrix metalloproteinase 2, and P = .00001 for matrix metalloproteinase 9). The number of patients with high levels of CD44v6 or tissue inhibitor of matrix metalloproteinase 2 staining in the faint density-type group was significantly higher than that in the solid-type group (P = .02 for CD44v6 and P = .01 for tissue inhibitor of matrix metalloproteinase 2). Independent variables capable of predicting computed tomographic M/L ratio included CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 2 (P = .0093, P = .0003, P = .0027, and P = .01, respectively; binary logistic regression analysis). CONCLUSIONS: Our results suggest that the computed tomographic image of small lung adenocarcinoma is correlated with biologic activities and thus provides possible prognostic information.

Adenocarcinoma↗
PubMed2004

Can gene expression profiling predict survival for patients with squamous cell carcinoma of the lung?

BACKGROUND: Lung cancer remains to be the leading cause of cancer death worldwide. Patients with similar lung cancer may experience quite different clinical outcomes. Reliable molecular prognostic markers are needed to characterize the disparity. In order to identify the genes responsible for the aggressiveness of squamous cell carcinoma of the lung, we applied DNA microarray technology to a case control study. Fifteen patients with surgically treated stage I squamous cell lung cancer were selected. Ten were one-to-one matched on tumour size and grade, age, gender, and smoking status; five died of lung cancer recurrence within 24 months (high-aggressive group), and five survived more than 54 months after surgery (low-aggressive group). Five additional tissues were included as test samples. Unsupervised and supervised approaches were used to explore the relationship among samples and identify differentially expressed genes. We also evaluated the gene markers' accuracy in segregating samples to their respective group. Functional gene networks for the significant genes were retrieved, and their association with survival was tested. RESULTS: Unsupervised clustering did not group tumours based on survival experience. At p < 0.05, 294 and 246 differentially expressed genes for matched and unmatched analysis respectively were identified between the low and high aggressive groups. Linear discriminant analysis was performed on all samples using the 27 top unique genes, and the results showed an overall accuracy rate of 80%. Tests on the association of 24 gene networks with study outcome showed that 7 were highly correlated with the survival time of the lung cancer patients. CONCLUSION: The overall gene expression pattern between the high and low aggressive squamous cell carcinomas of the lung did not differ significantly with the control of confounding factors. A small subset of genes or genes in specific pathways may be responsible for the aggressive nature of a tumour and could potentially serve as panels of prognostic markers for stage I squamous cell lung cancer.

Carcinoma, Squamous Cell↗
PubMed2004

The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias.

OBJECTIVE: An overdiagnosis bias occurs with the diagnosis of a disease that does not produce signs or symptoms before the patient dies from other causes. We sought to determine whether overdiagnosis bias is a factor when screening for squamous cell carcinoma of the lung. DESIGN: Retrospective study of the Miyagi Population-Based Lung Cancer Screening Registry for high-risk patients who were seen between January 1, 1982 (when sputum cytology tests were added for men with long smoking histories), and December 31, 1996. SETTING: Miyagi Prefecture, Japan. PATIENTS: A total of 251 patients (all men) who had sputum cytology test results that were positive for squamous cell carcinoma but had normal radiograph findings, 44 of whom declined cancer treatment (mean age, 70 years) and 207 of whom were treated with resection within 12 weeks of diagnosis (mean age, 65.5 year). END POINTS: Five-year and 10-year survival rates from primary lung cancer in both groups as of August 15, 2001. RESULTS: Among the 44 untreated patients, 15 (34%) remained asymptomatic. The survival rate due to primary lung cancer death in the untreated group was 53.2% at 5 years and 33.5% at 10 years. The survival rate among treated patients was 96.7% at 5 years and 94.9% at 10 years. Of the 125 treated patients who died, 14 (11.2%) died from primary lung cancer. CONCLUSION: Given that the two thirds of the untreated patients with squamous cell carcinoma of the bronchus died from lung cancer within 10 years, overdiagnosis bias does not appear to be a factor in screening for this disease. Thus, we recommend that patients with radiographically occult squamous cell carcinoma of the bronchus undergo tumor treatment after localization.

Aged↗
PubMed2004

A new technique for endobronchial ultrasonography and comparison of two ultrasonic probes: analysis with a plot profile of the image analysis software NIH Image.

STUDY OBJECTIVES: Endobronchial ultrasonography (EBUS) is currently the sole clinical method available for delineating the bronchial wall structure; however, the image resolution is inadequate. Thus, an improved image analysis system is needed for both a more accurate and more readily interpretable endobronchial ultrasonogram. MATERIALS AND METHODS: A total of 10 patients underwent pulmonary resection for lung cancer. EBUS was performed on the bronchi of the resected lungs, which had been immersed in physiologic saline solution. The same bronchial lesion in each specimen was imaged with two probes: 20 MHz and 30 MHz. The images were analyzed using the plot profile derived from freeware image analysis software: NIH Image (National Institutes of Health; Bethesda, MD). The measured echo intensity of the bronchial wall was statistically analyzed. RESULTS: A normal bronchial wall image consists of five layers, and the plot profile shows a W-shaped curve. The mean value of the echo intensity of each peak or trough of the W-shaped curve was calculated and compared for both probes. The differences in the mean echo intensity between both the third and fourth layer and the second and fourth layer were found to be significantly greater with the 30-MHz probe than with the 20-MHz probe. The echo intensity curve of a central-type lung cancer was not W shaped, indicating that the bronchial wall was not composed of the normal five layers. CONCLUSION: We employed image analysis software and drew a plot to obtain a W-shaped curve from the EBUS image data. This enabled us to make an objective assessment of the laminar structure of the bronchial wall. In order to clearly recognize the laminar structure of the bronchial wall, the 30-MHz probe was found to be more useful than the 20-MHz probe.

Bronchi↗
PubMed2004

[Management of central-type early lung cancer: an evidence-based clinical guideline].

With the support of the Japan Ministry of Health, Labour and Welfare, clinical guidelines for the management of lung cancer have been completed according to evidence-based methods. In this article, we focus on the guidelines for central-type early lung cancer. Reviewing a total of 3,196 reports that include key words related to central-type early lung cancer, 41 were selected and applied to determine recommendations for diagnostic or therapeutic methods. Among diagnostic methods, sputum cytology for the high-risk group and bronchoscopy for patients with positive sputum cytology were evaluated as recommendable. Among therapeutic methods, surgery and photodynamic therapy were evaluated as recommendable. For some methods, including fluorescence bronchoscopy and endobronchial ultrasonography brachitherapy, there was insufficient evidence to conclude that they are efficacious. At present, efforts to clarify the efficacy of these methods should be continued.

Bronchoscopy↗
PubMed2003

Endobronchial carcinoid tumor combined with pulmonary non-tuberculous mycobacterial infection: report of two cases.

We report here two cases of endobronchial carcinoid tumor complicated with pulmonary infection with non-tuberculous mycobacteria (NTM). Case 1 was an 81-year-old woman with the left lower lobe atelectasis. Bronchoscopy showed complete obstruction of the left basal bronchus by a tumor and a sleeve lower lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left basal bronchus and many caseous granulomas containing mycobacteria in the lung parenchyma distal to the bronchus. Bacterial examinations of sputum and gastric juice after the operation showed a growth of Mycobacterium kansasii. Case 2 was a 50-year-old woman with the atelectasis of the left upper division. Bronchoscopy showed complete obstruction of the left upper division bronchus by a tumor and a left upper lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left upper division bronchus and many caseous granulomas in the lung parenchyma distal to the bronchus. The Ziehl-Neelsen stain showed many mycobacteria in these granulomas and they were identified as Mycobacterium avium by PCR analysis. Although NTM are not well recognized as possible pathogens of pulmonary infection related to bronchial obstruction by endobronchial carcinoma, our experiences rouse a caution to consider NTM as potential pathogens. We also discuss the possible mechanisms responsible for the specific relationship between carcinoid tumor and TNM.

Aged↗
PubMed2003

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery.

OBJECTIVE: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS: The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS: The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung.

Heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is an RNA-binding protein that is required for the maturation of mRNA precursor. It was previously reported that hnRNP A2/B1 was overexpressed at the early clinical stage of lung cancer, and that hnRNP B1 protein, a splicing variant of hnRNP A2 mRNA, was elevated in lung cancer tissues. In this study, we applied the immunohistochemical method, using anti-hnRNP B1 antibody to analyze the usefulness of the hnRNP B1 antibody as a prognostic marker and also as a marker useful for early detection. A total of 206 specimens were examined. Histological examination revealed this protein to be positive in 79 (71.2%) of 111 squamous cell carcinomas and in 45 (64.3%) of 70 adenocarcinomas, respectively. This protein was also expressed in 24 (63.2%) of 38 roentgenographically occult carcinomas and in seven (63.6%) of 11 dysplastic lesions. These findings suggest the possible participation of this protein in early carcinogenesis. Furthermore, the survival curve of the squamous cell carcinoma patients with hnRNP B1 overexpresseion showed a better prognosis compared with that of the patients without hnRNP B1 expression (P=0.014), whereas in adenocarcinoma patients, there was no such a difference between them (P=0.889). These findings indicate that hnRNP B1 could be a useful marker for the early detection of bronchogenic squamous cell carcinoma and that it may be a prognostic factor in this cell type.

Biomarkers, Tumor↗
PubMed2003

A prospective evaluation of transbronchial ultrasonography for assessment of depth of invasion in early bronchogenic squamous cell carcinoma.

In order to determine the appropriate treatment modality for roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC), it is essential to evaluate the depth of invasion, because ROSCC invading beyond the cartilaginous layer cannot be effectively treated by photodynamic therapy (PDT) due to spread of disease. Transtracheal endoscopic ultrasonography (TUS) was useful for predicting the depth of invasion in some ROSCCs. In order to assess the actual significance of TUS as a diagnostic tool for predicting the depth of carcinoma invasion, we have conducted a prospective trial with 22 lesions of ROSCCs. We ultrasonographically classified the degree of the depth of invasion into two groups; A: "invasion does not reach cartilaginous layer" and B: "invasion involves cartilaginous layer". Then the patients were treated by irradiation, PDT, or surgical resection. Pathological findings were also classified into A or B. In order to calculate the sensitivity for evaluating the depth of invasion by TUS, the cases without any tumor and/or malignant cells after PDT were regarded as pathological A. In the evaluation of the depth of carcinoma invasion staying inside the cartilaginous layer, the sensitivity and the positive predictive value were 85.7%, the specificity was 66.7%, and the accuracy was 80.0%. With TUS, preoperative evaluation of the depth of invasion would be more accurate, and the decision of treatment modality would be more appropriate, compared with the conventional bronchoscopic observation alone.

Aged↗
PubMed2003

Surgical treatment of stage I non-small cell lung carcinoma.

In stage I non-small cell lung cancer (NSCLC), the cancer is localized to the lung. For this early stage NSCLC, therefore, surgery is considered to be the treatment of choice. In this report, we reviewed the surgical treatment approaches for stage I NSCLC, placing emphasis on limited resection and video-assisted thoracic surgery (VATS). In regard to limited resection, sublobar resection (wedge resection and segmentectomy) may yield a good long-term outcome in selected cases, as does lobectomy. No strong evidence to recommend this procedure has, however, been published. On the other hand, many descriptive studies have indicated that VATS may be useful for the treatment of NSCLC, although the results have not shown any statistically significant differences from those of resection by conventional open thoracotomy. In addition to the low invasiveness, the curability of NSCLC using the VATS approach has been recognized to be similar to that of the standard thoracotomic approaches in clinical practice. Well-controlled studies with strong statistical results are needed to provide strong supportive evidence for the use of VATS for NSCLC. (Ann Thorac Cardiovasc Surg 2003; 9: 283-9)

Adult↗
PubMed2002

A prospective trial of systematic nodal dissection for lung cancer by video-assisted thoracic surgery: can it be perfect?

BACKGROUND: There have been no reports evaluating the completeness of systematic nodal dissection with video-assisted thoracic surgery (VATS). In order to elucidate the completeness of the dissection, we have conducted a prospective trial with patients having primary lung cancer. METHODS: Patients with clinical stage I lung cancer were the candidates for this study. Thoracotomy was performed with a small skin incision of 7 cm to 8 cm in length. Through these small wounds and two trocars, pulmonary resection was performed and then hilar and mediastinal lymph nodes were dissected. After that, a standard thoracotomy was carried out by another surgeon to complete systematic nodal dissection. RESULTS: Video-assisted thoracic surgery lobectomy with lymph node dissection was accomplished in 17 right lung cancer patients and 12 left lung cancer patients. On the right side, the average numbers of resected lymph nodes by VATS and remnant lymph nodes were 40.3 and 1.2, respectively. The average weights of dissected tissues by VATS and remnant tissues were 10.0 g and 0.2 g, respectively. On the left side, there were 37.1 and 1.2 lymph nodes and 8.3 g and 0.2 g of weight of dissected tissues. No nodal involvement was observed in the remnant lymph nodes. CONCLUSIONS: The lymph node dissection with VATS was technically feasible and the remnant ("missed" by VATS) lymph nodes and tissues were 2% to 3%, which seems acceptable for clinical stage I lung cancer.

Adult↗
PubMed2002

Roentgenographically occult bronchogenic squamous cell carcinoma involving mediastinal lymph nodes after removal of initial lesion by the diagnostic examination.

A 69-year-old male was suspected of having lung cancer by sputum cytology and diagnosed as roentgenographically occult squamous cell carcinoma (ROSCC) at the spur of left B(1+2)/B(3). However, after the first bronchoscopy, no suspicious lesion was detected by any examinations. Therefore, we considered that cancer cells had been removed completely by the initial examination, and the patient was followed up by sputum cytology, chest roentgenogram, and bronchoscopy. Sixteen months later from the initial examination, bronchoscopy was performed for follow-up. The bronchoscopic findings showed the elevation of the surface of left B(1+2) a+b, but the cytologic specimen by brushing toward B(1+2) a+b showed negative findings. However, the lesion had developed to polypoid-shaped tumor and obstructed B(1+2) a+b after the next 6 months. The tumor was diagnosed as squamous cell carcinoma, and hilar and mediastinal nodal involvement was suspected on chest computed tomography. The standard thoracotomy was performed and the pathological results showed positive for nodal involvement on hilus and mediastinum. The tumor is considered to arise from the residual cancer cells of initially detected ROSCC. In conclusion, although some ROSCCs regress by the diagnostic examinations, it is important to detect the recurrence of residual cancer cells as early as possible by intensive follow-up.

Aged↗
PubMed2002

Computed tomographic image comparison between mediastinal and lung windows provides possible prognostic information in patients with small peripheral lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to determine whether the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor of small peripheral lung adenocarcinoma. METHODS: We studied the computed tomographic images of 143 patients with primary peripheral lung adenocarcinoma of 30 mm or less in maximum diameter. Two groups were categorized according to the tumor's ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image (tumor's area in the mediastinal computed tomographic image/tumor's area in lung computed tomographic image x 100%), both faint density-type (<50%) and solid-type images (>/=50%). Clinical factors and prognoses of the 2 groups were analyzed. RESULTS: There were 58 patients with the solid-type tumor image and 85 patients with the faint density-type tumor image. The number of patients with tumor size of less than 20 mm in the faint density-type tumor group (n = 30) was significantly higher than that in the solid-type tumor group (n = 8, P =.008). The 5-year survival of patients with faint density-type tumors was 74.1%, whereas that in patients with solid-type tumors was 54.2% (P =.013). Furthermore, the survival curve of patients with the solid-type computed tomographic image combined with ground-glass opacity was similar to that of patients with the faint density-type image. Multivariate analysis revealed the prognostic influence of the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image on survival (P =.029, relative risk = 0.48) and showed to be of second highest influence after the N factor. CONCLUSIONS: It is suggested that the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor in patients with small peripheral lung adenocarcinoma.

Adenocarcinoma↗
PubMed2002

[Lung cancer screening--its efficacy and limitations].

Although the purpose of cancer screening is to decrease the number of cancer deaths, the efficacy of some cancer screening programs has not been proved. This article describes the authorized method for the lung cancer screening system in Japan, and introduces papers reporting the efficacy of lung cancer screening. The problems in the present lung cancer screening system in Japan are also discussed.

Cytodiagnosis↗
PubMedDate not supplied

The efficacy of sputum cytology in mass screening program for early detection of lung cancer.

BACKGROUND: In order to evaluate the efficacy of sputum cytology in lung cancer screening, we re-analyzed the data obtained in our previous case-control study. MATERIALS AND METHODS: The source population was defined as the previous screenees for reducing self-selection bias. Matching conditions were: gender, year of birth, municipality and smoking history. RESULTS: Smoking adjusted odds ratio (SAOR) of dying from lung cancer for those screened by chest roentgenogram (CXp) only vs. not screened was 0.47, and that for those screened by sputum cytology (SpC) & CXp vs. not screened was 0.36, which was approximately three-fourths of the former. In another analysis, SAOR for those screened by SpC & CXp vs. those screened by CXp only was 0.63. CONCLUSION: Although statistical significance was not obtained, there might be some possibility that the risk of lung cancer death in smokers would decrease by additional SpC, compared with CXp only.

Aged↗