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Biomedical subjects

O Doi

Publications and source records attributed to O Doi.

At least 37 records · Page 2Linked to original sources

bcl-2 oncoprotein in surgically resected non-small cell lung cancer: possibly favorable prognostic factor in association with low incidence of distant metastasis.

BACKGROUND: The bcl-2 oncoprotein serves a regulatory function in permitting several cell types to die in an apoptotic process. Its overexpression probably plays a role in tumorigenesis and tumor development. The aim of this study was to determine the clinicopathological and prognostic significance of the bcl-2 oncoprotein in patients with nonsmall cell lung cancer (NSCLC). METHODS: Immunostaining for bcl-2 oncoprotein was performed on 182 operable NSCLCs. RESULTS: Thirty-six patients (19.8%) showed a positive immunostaining for bcl-2 oncoprotein. Histologically, its incidence was higher in squamous cell carcinomas (29.6%). Its expression status was inversely correlated with tumor development-associated parameters such as tumor stage in NSCLCs, especially in squamous cell carcinomas, bcl-2 positive patients with NSCLCs, especially squamous cell carcinomas, showed better overall survival and disease-free survival (DFS). In a multivariate analysis, this oncoprotein status had prognostic value in DFS for NSCLCs and in overall survival for squamous cell carcinomas. The recurrence of bcl-2 positive NSCLCs was significantly uncommon in distant extrathoracic organs. CONCLUSIONS: The expression of bcl-2 oncoprotein in NSCLCs may be an early event of tumor development, especially in squamous cell carcinomas, and may be of importance in determining tumor progression and prognosis.

Adult↗

Influence of cathepsin D expression in lung adenocarcinoma on prognosis: possible importance of its expression in tumor cells and stromal cells, and its intracellular polarization in tumor cells.

BACKGROUND: Cathepsin D, an aspartic lysosomal proteinase, has been described to be closely associated with tumor progression and prognosis in some human malignancies. The purpose of this study was to determine clinicopathological and prognostic significance of cathepsin D expression in lung adenocarcinoma. METHODS: Expression of cathepsin D in 152 lung adenocarcinoma patients was immunohistochemically studied using the antihuman cathepsin D antibody. RESULTS: Eighty patients (53%) showed negative immunoreactivities in tumor cells. The cathepsin D-positive patients (72 patients, 47%) were divided into two subgroups; granular type expression (48 patients, 31%) with its polarized expression mainly in the luminal side of the cytoplasm of tumor cells and basal type expression (24 patients, 16%) with its polarized expression mainly in the basal or infranuclear side of the cytoplasm. Patients with basal type expression showed significantly more marked scar formation (P = 0.042), and especially among the patients with stage I disease, those with basal type tended to show poorer prognosis (P = 0.071) than the others. Cathepsin D was also expressed in stromal cells within the tumor tissues, and 86 patients (57%) with moderate to massively infiltrating cathepsin D-positive stromal cells showed a lower grade of differentiation (P = 0.005) and higher scar grade (P = 0.0003) than those with few cathepsin D-positive stromal cells. Cathepsin D status in stromal cells was significantly associated with prognosis (P = 0.014), and in a multivariate analysis, its expression status in stomal cells was marginally an independent prognostic factor only among the stage I patients. CONCLUSIONS: In determining significance of cathepsin D expression in this disease, it is important to consider separately its expression cell type and its polarization pattern in tumor cells within the tumor tissue. How ever, only cathepsin D status in stromal cells within the tumor tissue is a marginal marker influencing prognosis among stage I patients.

Adenocarcinoma↗

Surgery for multiple lung metastases from alveolar soft-part sarcoma.

Between 1985 and 1993, six patients were surgically treated for alveolar soft-part sarcoma (ASPS) arising from the thighs or buttocks, four of whom underwent aggressive excision of multiple metastases using a neodymium:yttrium-aluminum garnet (Nd:YAG) laser. In total, 333 tumors were removed from these four patients during eight pulmonary operations. In patients 1, 3, and 4, uncontrollable extrapulmonary involvement and/or local recurrence at the primary site were noted during their treatment course, and they died of tumor progression 40, 68, and 46 months after excision of the primary lesion, respectively. In patient 1, a 37-year-old woman, prolonged survival with adequate lung function was achieved after the excision of metastases, including one bulky metastatic tumor located adjacent to the mediastinum, which might have led to a lethal complication. Patient 3, a 25-year-old woman who underwent aggressive metastasectomies for both pulmonary and extrapulmonary metastases combined with intermittent chemotherapy, died of widespread metastases to multiple organs. On the other hand, patient 2, a 23-year-old woman who underwent excision of 130 pulmonary and three brain metastases during four thoracotomies and two craniotomies, is still alive without any symptoms 98 months after excision of the primary lesion. These data suggest that repeated excisions of lung metastases from ASPS may influence long-term survival or maintenance of good performance status in patients in whom extrapulmonary metastasis and recurrence are either absent or controlled.

Adult↗

Dramatic response of postthymomectomy myasthenia gravis with multiple lung nodules to corticosteroids.

A 36-year-old woman underwent thymomectomy and left pneumonectomy with total pleurectomy for stage IVa invasive thymoma without myasthenia gravis. Six years later, a crisis of myasthenia gravis developed associated with multiple lung nodules. Steroid therapy induced remarkable regression of the lung nodules that has persisted for more than 11 months. Concurrently, the clinical severity of her myasthenia gravis markedly decreased and recovered to the extent of permitting her to return to normal life.

Adult↗

Intentional limited resection for selected patients with T1 N0 M0 non-small-cell lung cancer: a single-institution study.

OBJECTIVES: To comparatively evaluate lobectomy and limited resection for T1 N0 M0 non-small-cell lung cancer, we reviewed case series with concurrent nonrandomized controls. METHODS: Limited resection with curative intent was performed for 63 patients with T1 N0 M0 non-small-cell lung cancer over a 10-year period. These 63 patients included 46 patients who underwent a segmentectomy as an intentional limited resection. These patients had good pulmonary function and could tolerate a lobectomy in the management of their disease. The other 17 patients underwent wedge resection or segmentectomy as a compromised limited resection because they had poor pulmonary reserve or other limiting factors and could withstand a thoracotomy but could not tolerate a lobectomy in the management of their disease. RESULTS: The 5-year survival was 93% in the intentional resection group. The survival curve for this group was not different from that for 77 patients who underwent the standard operation (lobectomy plus complete mediastinal lymph node dissection) for T1 N0 M0 non-small-cell lung cancer during the same period. The frequency of local/regional recurrence in the intentional resection group was 8.7% (4/46); the recurrence in three patients was situated in the mediastinum. According to multivariate analysis, limited resection was not associated with poor survival. CONCLUSION: Segmentectomy with regional lymph node dissection, including the mediastinum, should be considered as an acceptable alternative treatment for selected patients with T1 N0 M0 disease.

Aged↗

Pneumostatic effect of gelatin-resorcinol formaldehyde-glutaraldehyde glue on thermal injury of the lung: an experimental study on rats.

OBJECTIVE: Recently, the use of gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG) glue has been reported in vascular surgery, especially in surgery for acute aortic dissection. However, reports concerning its use in lung surgery are quite rare. Although the strong adhesion and tensile strength of GRFG glue to fresh incisional wounds of the lung has been demonstrated experimentally, the effectiveness of this adhesive on thermal injury with severe tissue degeneration has not yet been reported. METHODS: We experimentally evaluated the ability of GRFG glue to seal air leaks through severely degenerated tissues after thermal injury on rat lung, and compared its performance with two reference adhesives: fibrin glue and EDH-adhesive. RESULTS: The GRFG glue provided complete pneumostasis immediately after the sealing in the presence of positive pressure ventilation, unlike the other two reference adhesives. The fate and biocompatibility of the three glues were examined histologically at 1 h and 3, 8, and 20 days after treatment. The GRFG glue tightly adhered to the degenerated tissue surface and was gradually fragmented and absorbed. The healing process was favorable, indicating good biocompatibility. Local tissue irritability was negligible. CONCLUSIONS: Even in the presence of tissue degeneration and positive pressure ventilation, the GRFG glue has proved efficacious as a surgical adhesive in lung surgery because of its ability to bind tissue rapidly and tightly.

Animals↗

MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation.

MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P = 0.062). In particular, among immunohistochemically p53-negative patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis.

Adult↗

[PyNPase activity in primary and metastatic colorectal cancer].

5'-Deoxy-5-fluorouridine (5'-DFUR) is converted to 5-FU by the enzyme of Pyrimidine nucleoside phosphorylase (PyNPase). Its efficacy for lung metastases from colorectal cancer is known. So we investigated PyNPase activity in primary and metastatic lesions of colorectal cancer patients. The results revealed that PyNPase activity (microgram 5-FU/mg protein/hour) (mean +/- SD) was 122.1 +/- 61.1 (n = 48) in primary lesions, 91.6 +/- 48.3 (n = 4) in lymph node metastases, 135.2 +/- 56.4 (n = 10) in liver metastases and 168.2 +/- 79.8 (n = 11) in lung metastases. In non-cancerous tissues adjacent to the cancer lesions, PyNPase activity was 51.5 +/- 18.8 in normal colorectal mucosa, 61.8 +/- 24.7 in normal liver and 43.0 +/- 21.2 in normal lung. These results demonstrated that PyNPase activity in the cancer lesions reached significantly higher levels than in the non-cancerous tissues (p < 0.01); and the T/N ratio of PyNPase activity in lung was also significantly higher than in primary or other metastatic lesions (p < 0.05). It was surmised that the clinical response of colorectal cancer to 5'-DFUR had been influenced by PyNPase activity.

Adenocarcinoma↗

[Usefulness of directional coronary atherectomy as a bail-out device for acute closure after coronary angioplasty].

The usefulness of directional coronary atherectomy (DCA) as a bail-out device for acute closure (reclosure) after percutaneous transluminal coronary angioplasty (PTCA) was evaluated. PTCA was performed in 1,023 patients (182 with acute myocardial infarction) between January 1993 and January 1994 in our hospital. Thirty-one patients (11 with acute myocardial infarction) suffered acute closure (reclosure) after PTCA. In six patients (five with acute myocardial infarction), DCA was performed as a rescue treatment for acute closure (reclosure). In three of these patients, angioscopy was performed before DCA, which demonstrated intimal tear and some thrombi although coronary angiography showed no evidence of thrombus. Bail-out DCA was successful in all six patients without complications. DCA is useful as a bail-out device for acute closure (reclosure) after PTCA when the thrombus is not massive.

Angioplasty, Balloon, Coronary↗

[Prediction of outcome after acute exacerbation of idiopathic interstitial pneumonia].

Some patients with chronic idiopathic interstitial pneumonia (IIP) experience acute exacerbations (AE). Because the precise mechanisms of AE in patients with IIP remain unclear, the treatment for AE is not established and the efficacy of steroids is controversial. Consequently, it is difficult to predict outcomes in patients with AE of IIP. We therefore studied the relationship between clinical findings, efficacy of treatment, and clinical outcome in patients with AE of IIP. Thirty-two patients were enrolled, and were divided into two groups: 10 who were alive more than one year after the onset of the AE survivors, 8 men and 2 women, and 22 who died within one year of the AE (non-survivors, 17 men and 5 women). Survivors were significantly younger than non-survivors (59.7 +/- 9.9 vs 67.5 +/- 8.2 years, respectively, p < 0.05). The values of PaCO2 measured before the AE were higher in survivors than in non-survivors (43.0 +/- 3.7 vs 38.4 +/- 4.0 torr, respectively, p < 0.05). At the onset of the AE the levels of C-reactive protein in serum were higher in survivors than in non-survivors (13.9 +/- 7.9 vs 7.3 +/- 5.8 mg/dl, respectively, p < 0.05). Chest X-ray films showed progression of ground-glass shadows in both groups when the AE occurred; the radiographic findings did not differ markedly between groups. Of the 22 non-survivors, 7 had received medication before the AE; none of the survivors had received medication before the AE. At the time of the AE all patients were treated with steroid pulse therapy, and the dose of methylprednisolone used, did not differ significantly between groups. These data suggest that three factors are closely related to responsiveness to steroid therapy and to clinical outcomes after AE in patients with IIP: 1) age at the onset on IIP, 2) respiratory status before the AE, and 3) disease activity as reflected by inflammatory reactions.

Age Factors↗

Ectopic primary pleural thymoma: report of a case.

We herein report an 83-year-old man who presented with a pleural tumor in the right thorax. The tumor was surgically resected and histopathologically diagnosed as ectopic primary pleural thymoma lacking any evidence of a mediastinal tumor. The clinicopathological aspects of this unusual thymoma are also discussed.

Aged↗

Bcl-2 oncoprotein expression is increased especially in the portion of small cell carcinoma within the combined type of small cell lung cancer.

Immunohistochemical analysis of Bcl-2 oncoprotein, one of the oncogenes associated with the regulation of programmed cell death, was performed on 12 surgically resected tumors of the combined type of small-cell lung cancer. Ten cases (83%) expressed Bcl-2 oncoprotein within the tumor tissues. Two of them showed its expression in both the small cell carcinoma and non-small cell carcinoma types, and 7 cases exhibited Bcl-2 expression only in the portion of the small cell carcinoma. Considering previous reports indicating a high prevalence of Bcl-2 oncoprotein expression in small cell lung cancer, it is suggested that Bcl-2 oncoprotein even in the combined type of lung cancer may play an important role in tumorigenesis and tumor development and ensuing histological alterations between small cell carcinoma and non-small cell carcinoma types.

Aged↗

Augmented sympathoadrenal activity during treadmill exercise in patients with Wolff-Parkinson-White syndrome and atrial fibrillation.

It is believed that reciprocating tachycardia and accessory pathways play important roles in atrial fibrillation (AF) in patients with Wolff-Parkinson-White (WPW) syndrome. However, the mechanism by which AF occurs is not yet fully understood. This study was performed to evaluate the contribution of sympathoadrenal activity to the onset of AF in patients with WPW syndrome. Symptom-limited treadmill exercise testing was performed and plasma norepinephrine and epinephrine concentrations were measured simultaneously in 27 patients with WPW syndrome and 20 control subjects. In 13 patients with WPW syndrome and AF, plasma norepinephrine and epinephrine concentrations increased to 3.69 +/- 2.44 and 0.76 +/- 0.69 ng/ml at maximum exercise, respectively. These values were significantly higher (p < 0.001) than those in control subjects and in patients without AF. Pretreatment with 0.2 mg/kg of propranolol significantly reduced the incidence of exercise-induced atrial premature complexes (chi 2 = 7.33, p < 0.05). With oral beta-blockade for an average of 22.8 months, the incidence of AF decreased significantly from 1.77 +/- 0.53/patient per year to 0.33 +/- 0.57/patient per year (p < 0.001). Augmented sympathoadrenal activity in patients with WPW syndrome may contribute to AF.

Adrenal Glands↗

Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.

Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to demonstrate that the level of MRP-1/CD9 expression was inversely related to the clinical stage of a given carcinoma of the breast. In addition, we found that the primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than their respective metastatic lymph nodes. In consideration of these findings, we have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP-1/CD9-positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than did other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence.

Antigens, CD↗

Alpha-1-antichymotrypsin expression in lung adenocarcinoma and its possible association with tumor progression.

BACKGROUND: Alpha-1-antichymotrypsin (ACT) is a serine protease inhibitor, expression of which has been shown in various tumor types, but its biologic and clinical implications in tumor tissues are obscure. The authors examined ACT expression in lung adenocarcinoma to determine its clinicopathologic and prognostic significance. METHODS: First, reverse transcriptase-polymerase chain reaction (RT-PCR) using oligonucleotide primers specific for ACT and Western blotting and immunohistochemical methods using anti-ACT antibodies were performed in several lung adenocarcinoma cell lines. Secondly, ACT expression in clinical materials was examined immunohistochemically. RESULTS: By RT-PCR, Western blotting, and immunohistochemical methods, ACT synthesis was confirmed in several lung adenocarcinoma cell lines. Seventy-five (52%) of 170 surgically resected lung adenocarcinomas showed positive staining for ACT mainly in the cytoplasm, and the incidence of ACT expression was significantly higher in advanced T classification tumors (P = 0.009) or large sized tumors (P = 0.004). Tumors with a higher rate of mitosis were significantly positive for ACT expression (P = 0.023). Patients with ACT-positive adenocarcinoma had a shorter disease free survival (DFS) and a poor prognosis compared with those who were ACT-negative, most significantly among Stage I tumors (DFS, P = 0.003; overall survival, P = 0.006). In a multivariate analysis, the P value of ACT expression status in Stage I tumors was marginally significant (overall survival; P = 0.058). CONCLUSIONS: These results using cell lines suggest the potential productivity of ACT by lung adenocarcinoma cells. The data in clinical materials, combined with results of the previous report that ACT in breast cancer acts as a minor growth factor-like substance, suggest that ACT expression in lung adenocarcinoma also may be associated closely with tumor progression and especially with tumor growth. Alpha-1-antichymotrypsin expression status in Stage I tumors may be a potential independent prognostic factor.

Adenocarcinoma↗

A new approach for performing a one-stage operation through the mediastinum to resect bilateral lung metastases: report of a case.

We describe herein a new operative technique for reaching the opposite lung from the thoracotomy site through the mediastinum. This procedure was successfully performed on a 76-year-old woman with bilateral lung metastases whose case is presented. After resection of the right lower lobe which contained two metastases, the anterior mediastinum was opened, and contralateral metastasis located in the lingular segment was resected using a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. A chest drainage tube was inserted through the mediastinal window. This transmediastinal approach seems to be a feasible technique for preserving the respiratory function of the chest wall in patients with imbalanced bilateral metastases.

Aged↗