[A retrospective study of carboplatin and weekly paclitaxel combination chemotherapy for elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: To perform a retrospective analysis of carboplatin (CBDCA) and weekly paclitaxel (PTX) combination chemotherapy for elderly patients with unresectable non-small cell lung cancer (NSCLC) in order to evaluate both treatment efficacy and toxicity. SUBJECTS: 48 patients aged more than 70 years with non-resectable NSCLC who received CBDCA+weekly PTX from January 2001 to March 2008. RESULTS: The median age of the patients (32 male, 16 female) was 74 years. Patients received 1-6 courses of this chemotherapy (median 4 courses). The overall response rate, time to progression, median survival time and 1-year survival rate was 51%, 183 days, 411 days and 52%, respectively. With regard to toxicity, grade 3-4 neutropenia was observed in 38% of patients and anemia in 25% of the patients, and 29% of the patients had grade 2 and above periferal nerve disorder. CONCLUSION: This regimen showed a good response and was safe for elderly patients with advanced NSCLC, but a high incidence of neuropathy was observed.

[Retrospective analysis of amrubicin hydrochloride monotherapy in patients with previously treated small-cell lung cancer].

We retrospectively investigated amrubicin hydrochloride(AMR)monotherapy as second or thirdline chemotherapy for small-cell lung cancer(SCLC)and assessed its efficacy and safety. AMR was intravenously administered at 25-45mg/m2 for 3 consecutive days every 3-4 weeks. Fifty-three patients were enrolled. Response rates and median survival times were as follows: total cases, 32% and 7. 4 months; sensitive relapse cases, 64% and 16. 4 months; refractory relapse cases, 27% and 5. 9 months. Neutropenia was major toxicity(Grade 3 or 4 was observed in 72% of the subjects), whereas nonhematologic toxicities were mild. Treatment with AMR appeared effective in SCLC patients previously treated with chemotherapy. On the other hand, it must be used carefully because of its relatively severe hematologic toxicities.

[Clinical investigation of weekly Carboplatin and Paclitaxel with concurrent radiation therapy for locally advanced non-small cell lung cancer].

PURPOSE: The aim of this study was to evaluate retrospectively chemotherapy of weekly carboplatin and paclitaxel with concurrent radiation therapy for patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between January 2000 and March 2008, 38 patients were treated by chemotherapy with carboplatin and paclitaxel once a week, repeated for 6 weeks, with thoracic radiation therapy of 1 or 2 times a day on weekdays. After concurrent chemoradiotherapy, we planned consolidation chemotherapy of carboplatin(AUC 5-6)and weekly paclitaxel(70- 80 mg/m(2)) on day 1, 8 and 15, when possible. RESULTS: The enrolled patients were 31 men and 7 women, with the median age of 59 years (39-76 years), stage III A/III B: 10/28, Ad/Sq/AdSq/Un: 17/17/2/2. The response rate of this chemoradiotherapy was 78. 9%. The median survival time and time to progression were 24. 7 months and 8. 1 months, respectively. Grade 3 or 4 hematological toxicities during concomitant chemoradiotherapy were leukocytopenia(5. 2%)and neutropenia(5. 2%). Grade 3 or 4 non-hematological toxicities were esophagitis(2. 6%)and pneumonitis (5. 2%). There was a therapy-associated death by radiation pneumonitis. CONCLUSION: Carboplatin and paclitaxel with concurrent radiation therapy for a patient with stage III NSCLC showed a good response with relatively mild side effects. We reached the conclusion that concurrent chemoradiotherapy would be a useful choice for locally advanced non-small cell lung cancer on the practical clinic.

[Two cases of lung injury due to inhalation of waterproofing spray--with special reference to pulmonary function disorder].

CASE 1: A 57-year-old man experienced severe dyspnea 24 hours after inhalation of waterproofing spray. Computed tomography (CT) revealed diffuse ground glass opacities in bilateral lungs. Pulmonary function tests showed mixed ventilatory disturbance with a low expiratory flow rate near the end of forced expiration and a normal diffusing capacity with normal functional residual capasity. The pulmonary function disorder was quickly improved by steroid therapy. CASE 2: A 59-year-old man smoked after inhaling waterproofing spray and soon developed dyspnea. The findings of CT were similar to those of case 1. His pulmonary function test revealed restrictive ventilatory disturbance and normal pulmonary diffusing capacity with low functional residual capacity. These findings improved without steroid treatment. However, it took more time for the pulmonary function to recover. There was probably specific inflammation around bronchioles, and the inflammation might have spread to the alveolar region in such cases with severe pulmonary function disorder. Steroid treatment seems to be useful to improve both the pulmonary function disorder and the clinical feature due to inhalation of waterproofing spray.

Aberrant methylation and loss of expression of O-methylguanine-DNA methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that protects cells against the carcinogenic effects of alkylating agents. The methylation status of the MGMT gene was investigated by methylation-specific polymerase chain reaction (PCR) and expression status was investigated by immunohistochemistry in 70 cases of pulmonary squamous cell carcinoma (pulmonary SqCC), including 23 cases of the central type and 47 cases of the peripheral type, and in 53 cases of the peripheral type of pulmonary adenocarcinoma (AC). The frequency of MGMT methylation was 36% in SqCC and 42% in AC. Cases with MGMT methylation correlated significantly with T factor in SqCC (P = 0.047) and AC (P = 0.03). In SqCC, the frequency of MGMT methylation was 26% in the central type and 40% in the peripheral type; a significant correlation was not found (P = 0.29). In AC with mixed subtypes showing MGMT methylation, the level of MGMT expression in the bronchioloalveolar carcinoma (BAC) area (non-invasive status) was significantly higher than that in the papillary or acinar AC area (invasive status; P = 0.0002). This trend was not found in AC with mixed subtypes showing no MGMT methylation (P = 0.10). These findings suggest that MGMT inactivation is an event that occurs in the late carcinogenic process in SqCC and AC, and that AC progress from non-invasive status to invasive status with MGMT inactivation induced by the promoter DNA methylation.

Loss of expression of E-cadherin and beta-catenin is associated with progression of pulmonary adenocarcinoma.

The aim of the present study was to determine the association of loss of membranous expression of epithelial (E)-cadherin and beta-catenin with the progression of pulmonary adenocarcinoma. The expression of E-cadherin and beta-catenin was examined in 154 cases of pulmonary adenocarcinoma, including 49 cases of atypical adenomatous hyperplasia (AAH), 40 cases of bronchioloalveolar carcinoma (BAC), 42 cases of BAC-dominant type of adenocarcinoma with mixed subtypes (early MX) and 23 cases of BAC-recessive type of adenocarcinoma with mixed subtypes (overt MX), by immunohistochemistry. E-cadherin expression was positive in all cases of AAH, in 37 cases (92.5%) of BAC and in 34 cases (81.0%) of early MX, while it was positive in three cases (13.0%) of overt MX. beta-Catenin expression was positive in 47 cases (95.9%) of AAH, in 28 cases (70%) of BAC, in 32 cases (76.2%) of early MX and in 11 cases (47.8%) of overt MX. The rates of expression of E-cadherin and beta-catenin among cases of AAH, BAC, early MX and overt MX were significantly reduced. Loss of expression of E-cadherin and beta-catenin may play an important role in the progression of pulmonary adenocarcinoma, and these events occur before structural destruction of the alveolar wall by invasion of carcinoma cell.

Aberrant methylation of p14(ARF), p15(INK4b) and p16(INK4a) genes and location of the primary site in pulmonary squamous cell carcinoma.

Aberrant methylation of cytosines in CpG islands of the promoter regions of tumor suppressor genes is found in human tumors as a common mechanism of gene silencing. We investigated the methylation status of the chromosome 9p21 gene cluster (p14(ARF), p15(INK4b) and p16(INK4a) genes) by methylation-specific polymerase chain reaction in 20 central and 40 peripheral types of pulmonary squamous cell carcinoma (SqCC) in order to determine the differences between the pathogeneses of the central and peripheral types of SqCC. The frequencies of methylation were 30% for the p14(ARF) gene, 20% for the p15(INK4b) gene and 40% for the p16(INK4a) gene in the central type and 25% for the p14(ARF) gene, 10% for the p15(INK4b) gene and 38% for the p16(INK4a) gene in the peripheral type. Cases in which there was methylation of the p16(INK4a) gene had a higher smoking index in the peripheral type (P = 0.007). This trend was not detected in the central type. Methylation of two or three genes was observed in 55% of methylation in at least one gene of the central type but in only 17% of the peripheral type. This overlap methylation of the chromosome 9p21 gene cluster was found more frequently in the central type (P = 0.02). These findings suggest one of the epigenetic differences between the central and peripheral types of SqCC.

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung.

We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung.

Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung.

We examined the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemical staining in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma with mixed subtypes (MX) to study the association between the biologic features of adenocarcinoma of the lung and mucin expression. MUC1 expression was decreased significantly in the progression from AAH through BAC to MX, while the levels of expression of MUC2, MUC5AC, MUC6, and depolarized MUC1 were increased significantly. Alterations in the expression of depolarized MUC1, MUC5AC, and MUC6 were correlated significantly with p53 gene abnormalities. Depolarized MUC1 expression also was correlated significantly with Ki-67 expression, and down-regulation of MUC1 expression and up-regulation of MUC6 expression were correlated significantly with tumor size. Our results suggest that the expression of these mucins might be associated with the progression of adenocarcinoma of the lung.

Myxopapillary ependymoma with anaplastic features.

A case of myxopapillary ependymoma with anaplastic features in 15-year-old boy is reported. The tumor was located in the intradural space extending to the 12th thoracic to 2nd lumbar vertebral level. It was excised with the accompanying spinal arch of the T12 to L2 vertebra. At operation, the tumor was not attached to the surrounding soft and bony tissues. The tumor, measuring 49 x 19 x 15 mm, was brownish-yellow in color and involved the conus medullaris and filum terminale. Histologically, the tumor was composed of biphasic features of a hypercellular papillary growth area and a hypocellular myxoid area. In the papillary growth area, ependymal rosettes and perivascular pseudorosettes were observed. These findings were consistent with those of a myxopapillary ependymoma, although multiple foci of punctate necrosis within the tumor and proliferation of endothelial cells showing glomeruloid structures were observed. Many mitotic figures were also observed. In addition, the Ki-67 labeling index of tumor cells was 10.1%. These findings are unusual for myxopapillary ependymoma, and therefore, it appeared that the diagnosis of myxopapillary ependymoma with anaplastic features was appropriate.