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Biomedical subjects

Morio Ohtsuka

Publications and source records attributed to Morio Ohtsuka.

35 records · Page 2Linked to original sources

Expression of hnRNP A2/B1 proteins in small airway epithelial cells.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1 has been reported informative to detect pre-clinical lung cancer for early detection. However, relatively little work has been performed on the expression of hnRNP A2/B1 in non-malignant airway cells; such information is clearly required to investigate whether overexpression of this protein could be a specific marker for early lung cancer detection. In order to evaluate whether the expression of hnRNP A2/B1 is specific for cancer cells, we investigated the expression of the protein in human small airway epithelial (HSAE) cells. Using immunostaining and Western blotting with monoclonal antibodies, 4G8 (specifically reacts A2) and 2B2 (specific to B1), expression of hnRNP A2/B1 in HSAE cells was evaluated. Northern blotting and quantitative RT-PCR were also performed. In HSAE cells, hnRNP A2 as well as B1 were expressed primarily in the nucleus excluding the nucleolus, although the expression of A2 protein was weaker than that of B1 protein. Staining pattern of hnRNP A2/B1 in HSAE cells was similar to that observed in control cancer cells. Western blotting with 4G8 and 2B2 apparently demonstrated expression of A2 and B1 in HSAE cells. In Northern blotting, both hnRNP A2 mRNA and B1 mRNA were observed in HSAE cells as shown in control cancer cells. hnRNP A2/B1 was apparently expressed in HSAE cells, although the expression in HSAE cells was weaker than that of cancer cells. More quantitative determination of A2/B1 is required to elucidate their significance in early lung cancer detection.

Blotting, Northern↗

Cytokeratin 19 fragment in patients with nonmalignant respiratory diseases.

STUDY OBJECTIVE: Cytokeratin 19 fragment (CYFRA) is a specific tumor marker in patients with lung cancer; however, it has been reported that serum CYFRA levels are elevated in some patients with nonmalignant respiratory diseases such as interstitial pulmonary fibrosis (IPF) and collagen disease-associated pulmonary fibrosis (CDPF). To investigate the serum CYFRA levels in nonmalignant respiratory diseases in detail, we studied 413 patients with respiratory diseases. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Four hundred thirteen patients with nonmalignant respiratory diseases and lung cancer. MEASUREMENTS AND RESULTS: Serum CYFRA levels were measured with a commercially available enzyme immunoassay kit. Immunohistochemical study was performed using monoclonal antibody Ks 19.1 (Rosch Diagnosica; Bern, Switzerland) on surgically resected or autopsied lung specimens. Gel electrophoresis and immunoblotting was performed with serum samples. In 149 patients with nonmalignant diseases except IPF and CDPF, the ratio of patients with > 3.5 ng/mL of serum CYFRA was 13.4%. In 13 of 30 patients (43.3%) with IPF and CDPF, the serum CYFRA levels were abnormally elevated. The 95th percentile serum CYFRA level of the patients with nonmalignant respiratory diseases was 6.2 ng/mL, and none of them had CYFRA levels > 20.3 ng/mL. Survival in patients with IPF and CDPF with elevated serum CYFRA levels were significantly lower than in those with normal range (p = 0.0335). Western blotting using serum from nonmalignant lung diseases and patients with lung cancer showed no apparent difference between them. An immunohistochemical study indicated CYFRA was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in nonmalignant respiratory disease. CONCLUSION: Serum CYFRA was elevated in some nonmalignant respiratory diseases, especially in IPF and CDPF. The value of serum CYFRA would reflect the severity of lung injury in nonmalignant respiratory diseases and might be related to the prognosis in patients with IPF and CDPF.

Adult↗

Liver metastasis at the time of initial diagnosis of lung cancer.

In order to evaluate clinicopathological features associated with liver metastases from lung cancer, we reviewed our experience of lung cancer patients seen in our division. Of the 1073 lung cancer patients diagnosed between October 1976 and May 2002, 62 (5.8%) patients had liver metastasis. The incidence of liver metastasis was 17.5% in small-cell lung cancer (SCLC) patients, whereas the incidence in non-small-cell lung cancer patients was 3.8%. Of the 62 patients, 17 had sole liver metastasis, and the remaining 45 had synchronous spread to the liver and one or more other organs. Six of 12 squamous cell carcinoma patients and 10 of 28 SCLC patients had sole liver metastasis. However, 19 of 20 adenocarcinoma patients showed liver metastasis with one or more other organs. In morphological liver metastasis, 26 of the 28 SCLC patients had multiple nodules, whereas 16 of the 34 non-small-cell lung cancer patients had a solitary liver nodule (p = 0.0006). Liver is a possible site of extrathoracic spread of disease for some patients with lung cancer, especially with SCLC. When the histological types are squamous cell carcinoma or SCLC, it would also be considered likely that an isolated liver mass represents a metastasis even though there is no metastatic disease elsewhere.

Adenocarcinoma↗

[Severe community-acquired Acinetobacter pneumonia].

A 62-year-old man with atrial fibrillation, hypertension, and fatty liver was admitted to a hospital in October 2002 complaining of productive cough and fever up to 38 degrees C for 2 days. He was a heavy smoker and drank alcohol regularly. He was dyspneic at rest, and chest radiography showed lobar pneumonia in the right upper lobe. Despite the administration of antibiotics, his condition deteriorated rapidly, and he was transferred to our hospital on the next day. On admission, he had multi-lobar pneumonia, septic shock, and disseminated intravascular coagulation. Despite the ventilatory support and the administration of carbapenem, macrolides, and catecholamine, he died 9 hours after admission. Later, all cultures from sputum and blood grew Acinetobacter species. Although community-acquired Acinetobacter pneumonias are rarely reported in Japan, physicians must be aware of this disease because of its fulminant clinical course and high mortality.

Acinetobacter↗

Spontaneous regression of pulmonary bullae.

The natural history of pulmonary bullae is often characterized by gradual, progressive enlargement. Spontaneous regression of bullae is, however, very rare. We report a case in which complete resolution of pulmonary bullae in the left upper lung occurred spontaneously.

Adenocarcinoma↗

Small cell carcinoma of the pleura.

We describe a patient with small cell carcinoma of the pleura who survived more than 4 years despite no response to chemotherapy. The natural history of pleural small cell carcinoma is unknown, and similar cases in the medical experience will shed light on possible treatment.

Carcinoma, Small Cell↗

[Thromboembolism in lung cancer patients].

We reviewed 649 primary lung cancer patients with special reference to the occurrence of thromboembolism. Thirteen episodes of thromboembolism were detected in 12 (1.8%) of the 649. Eight of the 12 were men, and their mean age was 63. Adenocarcinoma was the predominant cell type. Most patients had an advanced stage of the disease, but in some in the cancer was at an early stage. In 5 cases, the finding of thromboembolisms led to diagnosis of the lung cancer (38.5%). Anticoagulant therapy was performed in 9 cases, of which 8 responded without serious complication. We emphasize the importance of anticoagulant therapy as a therapy indicated for thromboembolism in patients with lung cancer.

Adenocarcinoma↗

In vivo advantage of combined administration with CPT-11 and 5-fluorouracil in rats.

In vivo effect of a bolus combination with 5-fluorouracil (5-FU) and CPT-11 was studied against experimental rat lung cancer, SLC cells. 5-FU and CPT-11, when administrated individually, showed dose-dependent inhibition against the tumor (ID50, 7.0 mg/kg/day and 16.0 mg/kg/day, respectively). 5-FU synergistically enhanced the sensitivity of the tumor cells to CPT-11 and permitted the administration of approximately a one-third lower dose of CPT-11 to obtain the same inhibition against the tumor cell growth. The ID50 of CPT-11 alone (16.0 mg/kg/day) was reduced to 4.8 mg/kg/day when combined with 5-FU at 2.5 mg/kg. There were no deaths caused by toxicity in the combination group, and for lower doses (less than 4 mg/kg/day) of CPT-11 combined with 2.5 mg/kg/day of 5-FU, all rats showed less than 10% body weight loss at the end of the experiments. When the tumor weights were evaluated by using isoeffect plot analysis, the data points resulting from the combination showed a synergistic interaction between these agents. There was no significant increase of toxicity as assessed by the body weight. The results might support for the use of the combination of 5-FU and CPT-11 in cancer chemotherapy.

Animals↗

Cut-off levels of NSE to differentiate SCLC from NSCLC.

Neuron-specific enolase (NSE) is a specific tumor marker in small cell lung cancer (SCLC) patients, however, it has been reported that serum NSE levels are elevated in some patients with non-small cell lung cancer (NSCLC). To determine the most suitable cut-off level to distinguish between these two types of cancers, NSE levels were measured on serum samples of 417 patients with lung cancer without clinical information. Receiver operating characteristic (ROC) curve showed 14.5 ng/ml as a cut-off level and the 95 percentile serum NSE level in NSCLC was 20.5 ng/ml. None of the NSCLC patients had serum NSE levels more than 70 ng/ml. The measurement of serum NSE provides a discrimination between NSCLC and SCLC. If an NSCLC patient presents with a NSE level >20.5 ng/ml, pathological features must be examined with regard to the neuroendocrine differentiation.

Adult↗

Radiotherapy for elderly non-small cell lung cancer patients.

Elderly patients with lung cancer tend to have significant coexisting diseases and less aggressive treatment is often required. To investigate the clinicopathological features of non-small cell lung cancer (NSCLC) in elderly patients who were treated with radiotherapy, we reviewed the medical records at our division. Among the 189 patients 70 years or older between 1992 and 2001, 28 (14.8%) patients were treated with radiotherapy (elderly group). In the elderly group, there was a medical history of chronic obstructive pulmonary disease (COPD) (57.1%), cardiovascular disease (32.1%), diabetes mellitus (18.5%), malignant disease (18.5%), or cerebrovascular disease (10.7%). Moreover, in the elderly group, 17 (60.7%) patients had two or three coexisting diseases. There was statistical difference between the elderly group and the younger group (less than 70 years patients) with regard to COPD (p<0.001). Also there was statistical difference between the elderly group and the younger group with regard to number of coexisting diseases (p=0.002). In the elderly group, forced expiratory volume in one second (FEV1), forced expiratory volume (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (DLCO) were statistically significant impaired to compare with those in the younger group (p<0.001, p=0.030, p<0.001 and p=0.024, respectively). In the elderly group, 10.7% of patients had concurrent chemoradiotherapy, however, 38.5% of patients of the younger group received concurrent chemoradiotherapy. There was a statistical difference between the two groups (p=0.026). Adequate palliative care to provide prolonged quality survival is an appropriate primary goal of therapy for lung cancer in the elderly and radiotherapy is thought be one of the less invasive treatments.

Adult↗

Time from finding abnormality on mass-screening to final diagnosis of lung cancer.

Mass-screening for lung cancer is rather a unique system in Japan. This study illustrates time from finding abnormality on mass-screening to final diagnosis of lung cancer. Among the 517 patients with lung cancer who were admitted to our hospital over a 10-year period up to December 2001, 83 (16.1%) were detected by mass-screening. We reviewed medical records of the 83 patients and determined the intervals from the mass-screening to the pathological diagnosis with clinical staging. Time from the mass-screening to the date of hospital visit was <2 months in 62 (74.7%) cases. Five (6.0%) patients visited hospital more than 6 months after the mass-screening. With respect to the interval, there was no statistical difference in gender (p=0.0680) and age (p=0.1532). Among 60 patients who were referred from outside, on average, patients visited our hospital 0.5 month after they first sought medical attention at nearby clinic, and at our hospital 0.5 month was required to make a pathological diagnosis of lung cancer with TNM staging. There was a statistical difference in survival between the patients who were diagnosed <4 months and the patients who were diagnosed >4 months from the screening (p=0.0487). The interval in most cases was acceptable. However, further improvements are still needed to minimize the delay and to maximize the benefits of early cancer detection.

Adenocarcinoma↗