Biomedical subjects

Motoki Yano

Publications and source records attributed to Motoki Yano.

34 records · Page 2Linked to original sources

PubMed2005

EGFR Mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler.

PURPOSE: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in approximately 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. EXPERIMENTAL DESIGN: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. RESULTS: In exon 21, EGFR mutations (CTG --> CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 < or = versus 600, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. CONCLUSIONS: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.

Adenocarcinoma↗

PubMed2005

Endoscopic thoracic sympathectomy for palmar hyperhidrosis: efficacy of T2 and T3 ganglion resection.

BACKGROUND: Endoscopic thoracic sympathectomy has been considered an effective treatment for palmar hyperhidrosis. However, the extent of resection has not been determined in terms of efficacy and complications. We compared the efficacy and complications of 2-ganglion and single-ganglion resection in patients with palmar hyperhidrosis. METHODS: From 1995 to 2000, 75 patients underwent resection of thoracic ganglion T2 and T3. From 2000 to 2003, 67 patients underwent resection of only the T2 ganglion. Eighty of the 142 patients (56%) answered a detailed questionnaire, the results of which were analyzed. RESULTS: Gender, age, family history, and distribution of sweating were similar in both groups. Recurrence rates 1 and 2 years after endoscopic thoracic ganglionectomy were between 0% and 3% in T2 and T3 resection, and between 15% and 19% in T2 resection only. In the combined T2 and T3 resection group, 100% of patients noticed compensatory sweating; in T2 resection, 90% of patients noticed compensatory sweating. As for rates of satisfaction, T2 and T3 resection was superior to T2 resection. CONCLUSIONS: High recurrence rates of palmar hyperhidrosis after single-ganglion resection are reported in the present study. Two-ganglion resection is a superior surgical method to prevent recurrence of palmar hyperhidrosis.

Adolescent↗

PubMed2004

Elevated serum epidermal growth factor receptor level in stage IV thymoma.

Using the enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as a predictor of the development and extension of thymoma. Serum samples were collected from 31 patients with thymoma and 16 patients with nonmalignant thoracic disease before clinical treatment. There was no difference between the serum EGFR levels of the patients with thymoma and the nonmalignant controls, being 49.1 +/- 136.3 and 22.6 +/- 7.3 fm/ml, respectively ( P = 0.11). However, patients with stage IV thymoma had significantly higher EGFR levels than those with stage I or stage II thymoma, the respective values being 127.8 +/- 243.9, 10.9 +/- 9.2 ( P = 0.02), and 19.7 +/- 10.6 ( P = 0.0433) fm/ml. The serum EGFR levels were similar in the pathological subtypes. These findings suggest that serum EGFR levels may serve as a marker that could be used as a diagnostic indicator of the invasion of thymoma.

Biomarkers, Tumor↗

PubMed2004

Endostatin gene transfection using a cationic lipid: advantages of transfection before tumor cell inoculation and repeated transfection.

Intravenous endostatin gene transfection results in tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma cells. Mice were observed for 14 days following fibrosarcoma cell inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant tumor suppression.

Animals↗

PubMed2004

Expression of Smac/DIABLO is a novel prognostic marker in lung cancer.

Recently Smac/DIABLO (second mitochondria-derived activator of caspase) has been identified as a proapoptotic protein that inhibits IAPs (inhibitors of apoptosis proteins). Smac is expressed ubiquitously in many organs, including the lung. Here we evaluated the expression of Smac mRNA with real-time reverse-transcription PCR in 88 primary lung cancers and matched normal tissues. Smac mRNA expression in tumor tissues was significantly lower than that in normal tissues (p<0.0001). In squamous cell carcinomas, Smac mRNA expression was significantly lower than that in adenocarcinomas (p=0.0072). Smac mRNA expression in T2-T4 tumors was significantly lower than that in T1 tumors (p=0.0006). The expression of Smac in the tumors of smokers was lower than that in the tumors of non-smokers (p=0.0011). The prognosis of patients with a tumor exhibiting a low expression of Smac mRNA was worse than that in those with a tumor exhibiting high Smac mRNA expression (log-rank test, p=0.047). These results indicate that Smac expression may play a role in the carcinogenesis, progression, and prognosis of primary lung cancer.

Apoptosis Regulatory Proteins↗

PubMed2003

Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in thymoma.

PURPOSE: Thymoma is one of the most common solid tumors in the mediastinum. However, there is no definitive consensus regarding the optimal adjuvant chemotherapy for advanced thymoma. METHODS: To predict tumor sensitivity to 5-fluorouracil (5-FU) in thymoma, we investigated the mRNA levels of thymidylate synthase (TS), the key enzyme that catalyzes the methylation of deoxyuridine monophosphate, and correlates with the resistance of 5-FU and dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU in thymoma. We used real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using the LightCycler to monitor the TS and DPD gene expression levels in thymoma tissue specimens from patients, coamplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. RESULTS: In the resected tumor specimens, TS and DPD mRNA levels were 3.876 and 14.651, respectively. Both the TS and DPD mRNA levels were significantly higher in the tumor tissue specimens than in the normal adjacent thymus tissue specimens. No significant correlations were observed between the TS or DPD levels and other clinicopathological factors. CONCLUSIONS: The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma. In general, 5-FU itself is not considered to be a useful treatment for thymoma. The usufulness of DPD-inhibiting fluoropyrimidine (DIF) drugs for thymoma should therefore be further considered.

Adult↗

PubMed2003

Multicystic mesothelial cyst of the mediastinum: report of a case.

We report the rare case of a multicystic mesothelial cyst of the mediastinum. A 43-year-old man was referred to our department after a routine chest X-ray showed an anterior mediastinum mass. The lesion was resected by thoracoscopy, which revealed multicystic, thin-walled tense masses arising in the anterior mediastinum. The cysts were not adherent to the pericardium or to the thymus of the right lobe. Immunohistochemistry revealed that the cyst was lined with a layer of mesothelial cells and there were no malignant foci. The lining cells were positive for keratin and negative for the lymphocyte marker. These findings were consistent with a diagnosis of multicystic mesothelial cyst.

Adult↗

PubMed2003

Elevated serum epidermal growth factor receptor level is correlated with lymph node metastasis in lung cancer.

BACKGROUND: Using an enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as predictors of the development and extent of lung cancer. METHODS: The study included 106 lung cancer patients and 16 patients with nonmalignant thoracic disease. Serum samples were collected before clinical treatment. RESULTS: There was no difference between serum EGFR levels in patients with lung cancer (21.275 +/- 22.035 fm/ml) in comparison with those in nonmalignant-disease controls (22.630 +/- 7.330 fm/ml; P = 0.8083). However, lung cancer patients with lymph node metastasis (23.515 +/- 20.065 fm/ml) had significantly higher EGFR levels compared with those in patients without lymph node metastasis (16.390 +/- 10.970 fm/ml; P = 0.0228). The serum EGFR levels were similar in samples from lung cancer patients with various pathological subtypes. There was no difference in the prognosis between the lung cancer group with normal EGFR levels (<850 ng/ml) and the group with elevated EGFR levels (>850 ng/ml). CONCLUSION: Serum EGFR levels may serve as a marker that can be used as an indicator of lymph node metastasis in lung cancer. However, there was no difference between levels in patients with lung cancer and those in nonmalignant-disease controls, indicating that the measurement of serum EGFR levels was of limited value in the detection of lung cancer.

Aged↗

PubMed2003

Hrad17 expression in thymoma.

OBJECTIVES: We used palindromic polymerase chain reaction-driven complementary deoxyribonucleic acid differential display to identify and isolate a gene, the human homolog of the Schizosaccharomyces pombe checkpoint gene rad17 (Hrad17), from colon cancer tissue. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes--events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in thymoma, especially in invasive thymoma. We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with thymoma who had undergone surgery. METHODS: Expression of Hrad17 messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction using a LightCycler in 38 thymomas and 10 adjacent histologically normal thymus samples from patients for whom follow-up data was available. RESULTS: Hrad17 transcripts were detected in all 38 tumor samples (8.789 +/- 7.337) at levels significantly higher than those in normal thymus samples (1.908 +/- 2.267, p < 0.0001). No relationship was seen between Hrad17 gene expression and age, gender, or pathological thymoma subtypes. Hrad17 mRNA expression in invasive thymomas (stage II-IV, 10.067 +/- 5.293) was significantly higher than that in stage I thymomas (5.193 +/- 4.485, p = 0.0168). Immunohistochemistry showed that Hrad17 protein was highly expressed in invasive thymoma tumor tissue but not within the normal thymus tissue. CONCLUSIONS: Hrad17 was highly expressed in invasive thymoma.

Cell Cycle Proteins↗

PubMed2003

Saber-sheath malacic trachea remodeled and fixed into a normal shape by long-term placement and then removal of gianturco wire stent.

We report the case of a 59-year-old man who presented with major dyspnea due to saber-sheath malacic trachea associated with chronic pulmonary obstructive disease. The placement of a temporary tracheal stent alleviated his dyspnea very well; hence the stent was replaced with a Gianturco wire stent (Cook Cardiology, Bloomington, IN). However, this required removal due to wire-stent-related complications 2 years after the replacement. Surprisingly the trachea had been remodeled to a normal shape resulting in comfortable, functional respiratory status. A review of the literature reveals our case to be the first report of curing saber-sheath malacic trachea without leaving any prostheses or other foreign materials.

Bronchoscopy↗

PubMed2003

Cten mRNA expression was correlated with tumor progression in lung cancers.

Cten is a recently isolated gene, which has homology with tensin suggesting that it is a focal adhesion molecule. Tensin family proteins play an important role in cell motility. We attempted to determine the influence of cten expression on clinicopathological features in patients with lung cancer who had undergone surgery. Expression of cten messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 89 lung carcinomas and adjacent histological normal lung samples using LightCycler. Cten/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was not significantly different between lung cancer tissue (1.479+/-2.060) and normal lung tissue (1.528+/-1.592, P=0.8267). There was no relationship between cten/GAPDH expression and age, gender or N-status. However, tumor/normal ratio (T/N ratio) of cten/GAPDH expression was significantly higher in stage II-IV lung cancer (3.113+/-6.493) when compared with stage I lung cancer (1.237+/-1.820, P=0.0316). T/N ratio of cten/GAPDH expression was significantly higher in T4 lung cancer (4.612+/-9.726) when compared with T1 lung cancer (0.896+/-0.860, P=0.0252), and T2 lung cancer (1.636+/-2.066, P=0.0470), respectively. Thus cten/GAPDH mRNA expression has been correlated with evidence of tumor progression in terms of T and overall stage of lung cancer. Alternatively, cell motility or migration might play a role in progression of lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

Ets-1 gene expression in patients with thymoma.

OBJECTIVES: The Ets-1 protooncogene transcription factor is involved in several cellular functions, including the activation of several proteases, and reportedly plays an important role in carcinoma invasion and metastasis. We hypothesize that Ets-1 mRNA expression could be a predictor of thymoma development and invasion. METHODS: Subjects were 37 patients with thymoma whose mRNA expression was quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR) using LightCycler, a microvolume multisample fluorimeter. RESULTS: No significant difference was found in Ets-1 mRNA expression for gender, age, or pathological subtype. Ets-1 mRNA expression in tumor tissues from stage II-IV thymoma (25.311 +/- 42.336) was more elevated than in that from stage I thymoma (2.097 +/- 4.492) (p = 0.0374). Ets-1 mRNA expression may thus serve as a marker of higher thymoma stages. CONCLUSIONS: With use of the Light Cycler RT-PCR assay, Ets-1 expression may play an important role in the extension and progression of thymoma as in other cancers. Further study and longer follow-up are, however, needed to confirm the Ets-1 impact on biological tumor behavior.

Adult↗

PubMed2002

Sclerosing hemangioma with metastases to multiple nodal stations.

We present a case of a large pulmonary sclerosing hemangioma with metastases to multiple lymph nodal stations and suspected contralateral pulmonary metastasis. Four cases (including the present) have been reported to have lymph node metastasis, and all had large tumors exceeding 3.5 cm in diameter. Accordingly, resection of sclerosing hemangioma is advisable while the tumor is small. Even in cases with a large sclerosing hemangioma, lymph node metastasis may be uncommon. However lymph node dissection may be necessary to detect lymph node metastasis in selected cases.

Aged↗

PubMed2002

Endobronchial neodymium:yttrium-aluminum garnet laser for noninvasive closure of small proximal bronchopleural fistula after lung resection.

BACKGROUND: Bronchopleural fistula (BPF) is a serious complication of lung resection. The management of persistent BPF is one of the most complex challenges encountered by thoracic surgeons. METHODS: We used neodymium:yttrium-aluminum garnet (Nd:YAG) laser in 8 patients with BPF who were treated at our hospital, between January 1991 and December 1997. Through the flexible fiberoptic bronchoscope, Nd:YAG laser beam was directed to the bronchial mucosa surrounding the BPF. One-half-second energy pulses of 8 to 20 W were used. Close follow-up of successful patients showed complete closure of the BPF without further treatment. RESULTS: The procedure was successful in 4 of 5 patients who had no infection or tumor at the bronchial stump. However, the procedure failed in 3 other patients, who had residual tumor or infection by aspergillus at the stump. CONCLUSIONS: Closure of small BPF by laser seems to be due to edema and to an inflammatory reaction of the bronchial mucosa surrounding the BPF. If the diagnosis of small proximal BPF is made in the absence of tumor or infection, Nd:YAG laser offers an option for endobronchial treatment of small (<2 mm) BPF. If this technique is successful, it avoids the morbidity associated with more invasive surgical procedures.

Adult↗

PubMed2002

Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology.

BACKGROUND: Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer. METHODS: Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion. RESULTS: Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology. CONCLUSIONS: This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.

Adenocarcinoma↗

PubMed2002

Ratio of expression of p16INK4a to p14ARF correlates with the progression of non-small cell lung cancer.

The CDKN2 gene is located on the short arm of chromosome 9p and encodes two unrelated proteins, p16(INK4a) and p14(ARF), through the use of independent first exons and shared exons 2 and 3. p16(INK4a) is a cyclin-dependent kinase inhibitor, whereas p14(ARF) regulates the cell cycle through a p53 and MDM2-dependent pathway. We have examined the expression of p16(INK4a) and p14(ARF) using competitive RT-PCR in 60 non-small cell lung cancers (NSCLCs) and matching normal lung tissues. The intensities of bands for p16(INK4a) and p14(ARF) were nearly equal or the intensity of the p16(INK4a) band slightly exceeded that of p14(ARF) in the normal lung tissues (n = 60). In 38 tumors the intensity of the p16(INK4a) band was similar to or slightly weaker than that of p14(ARF). In 6 tumors the intensity of the p16(INK4a) band was weaker than that of p14(ARF). In 15 tumors the intensity of the p14(ARF) band was very strong and the p16(INK4a) band was barely visible. In only one tumor was the intensity of the p16(INK4a) band very strong, while the band of p14(ARF) was barely visible. The ratio of the intensity of p16(INK4a) to p14(ARF) had an interesting correlation with the tumor's clinicopathological characteristics. The p stage II - IV tumors had significantly lower p16(INK4a) to p14(ARF) ratios than the p stage I tumors (P = 0.036). The T2 - 4 tumors had significantly lower p16(INK4a) to p14(ARF) ratios than the T1 tumors (P = 0.005). The N1 - 3 tumors had significantly lower p16(INK4a) to p14(ARF) ratios than the N0 tumors (P = 0.014). Our results suggest that the ratio of expression of p16(INK4a) to p14(ARF) tends to decrease during the progression of NSCLC.

Adult↗