The significance of high-mobility group alarmins expression in the prognosis of NSCLC patients / 天津医药

@#Objective To explore the relationship between expressions of high mobility group B1 and N1(HMGB1 and HMGN1) and clinical pathological parameters and prognosis in patients with non-small cell lung cancer (NSCLC). Methods Ninety-one postoperative tumor tissue specimens from the patients with NSCLC were collected in Tianjin Medical University Cancer Institute and Hospital from January 2004 to May 2011. Immune histochemical assay was used to detect the expressions of HMGB1 and HMGN1. According to the staining intensity, expressions of HMGB1 and HMGN1 were divided into positive and negative groups. Kaplan-Meier was used to analyze the correlation between the expressions of HMGB1/HMGN1 and clinical pathological parameters/prognosis. Results The cytoplasmic expressions of HMGB1 (40%, 36/91) was positively correlated with cytoplasmic expression of HMGN1 (31%, 28/91, rs=0.319，P<0.001). The expression level of HMGN1 was significantly higher in patients with late stage of NSCLC (Ⅲ~Ⅳ) than that in patients with early stage of NSCLC (Ⅰ~Ⅱ, P＜0.05). It was also found that the expression level of HMGN1 was significantly higher in patients with lymph node metastasis than that in patients without lymph node metastasis (P＜0.05). The poor prognosis of NSCLC was slightly lower in patients with high expression of HMGN1 than that in patients with low expression of HMGN1, but the difference was not statistically significant. Conclusion The HMGN1 can be used as a promising prognostic biomarker for predicting the prognosis of NSCLC patients.

The Safety and Efficacy of Second-line Single Docetaxel (75 mg/m2) Therapy in Advanced Non-Small Cell Lung Cancer Patients who were Previously Treated with Platinum-based Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: When used in the second-line setting, single- agent chemotherapy has produced response rates of more than 10% or median survival times greater than 4 months. We studied the safety and efficacy of using second-line single docetaxel (75 mg/m2) for advanced NSCLC patients who were previously treated with platinum-based chemotherapy in Korea. MATERIALS AND METHODS: Thirty-three patients with advanced NSCLC received chemotherapy from May 2002 to January 2005. We retrospectively reviewed the charts of these patients. The patients received 75 mg/m2 of doxetaxel on day 1 and this was repeated at 3-week intervals. RESULTS: The median age was 63 years (range: 42~77 years); 16 patients had adenocarcinoma and 8 patients had squamous cell carcinoma. The median number of cycles was 4 (range: 1~7 cycles). Of the 33 patients, 6 patients had partial responses, 13 patients had stable disease and 14 patients had progressive disease. The response rate was 18.2%. The median overall survival was 11 months (range: 7~15 months), and the median progression free survival was 5 months (range: 3~7 months). The median response duration was 5 months (range: 4~9 months). A total of 137 cycles were evaluated for toxicity. We observed grade 3 or 4 neutropenia in 79 cycles (57.6%), grade 3 or 4 leukopenia in 46 cycles (33.6%), and grade 3 febrile neutropenia in 2 cycles (1.5%). The median nadir day was day 9 (range: day 5~19), and the median number of G-CSF injections was 2 (range: 0~6). The most common non-hematologic toxicities were myalgia/arthralgia and neurotoxicity, but any grade 3 or 4 non-hematologic toxicity was not observed. The major toxicity of this therapy was neutropenia. The absolute neutrophil count decreased relatively rapidly, but neutropenic fever or related infection was rare. There were no treatment-related deaths. CONCLUSION: These results revealed a satisfactory response rate (18.2%) with using docetaxel as the second- line chemotherapy for NSCLC. The second-line docetaxel was an active and well-tolerated regimen in patients with advanced NSCLC pretreated with platinum-based chemotherapy.

Analysis correlating clinical features and prognosis in the resected N2 non-small cell lung cancer / 中华胸心血管外科杂志

Objective Non-small-cell lung cancer with ipsilateral mediastinal lymph node metastasis (N2) belongs to heterogeneous subgroup. We analyzed the prognosis of patients with resected N2 NSCLC to determine the clinical significance. Methods The present study comprised 146 consecutive patients whom underwent surgical resection of N2 NSCLC between January 1997 and January 2000. Histological type, location, T primary tumor status, operation mode, clinical N2 (cN2) factor, N2 level(single or multiple), number of positive nodes(N2-num), and the cycles of adjuvant chemotherapy were estimated from the date of operation using the Kaplan-Meier and Log Rank analysis. The Cox regression model evaluated the influence of factors on the survival. Results The 3-and 5-year survival rate of these N2 NSCLC patients were 19.86% and 14.56%, respectively. The patients with tumor in the right lower lobe showed a significantly longer survival than left lobes. The histological type, tumor location, cN2 factor, N2 level and N2-number were associated with survival. A multivariate analysis using Cox regression identified 4 factors of prognosis: tumor site, T status, N2 level and clinical N2 status. Conclusion This article has identified N2 NSCLC subgroups and found that patients with mN2, N2L1 and single N2 have better prognosis.

A Multi-Center, Phase II Clinical Trial of Genexol(R) (Paclitaxel) and Cisplatin for Patients with Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A combination of paclitaxel and cisplatin is an effective and safe regimen for advanced non-small cell lung cancer (NSCLC). We conducted a multi-center, phase II trial to evaluate the efficacy and safety of Genexol(R) (paclitaxel) and cisplatin in patients with NSCLC. MATERIALS AND METHODS: Chemotherapy-na ve patients having histologically confirmed NSCLC were enrolled. Genexol(R) was administered at 175 mg/m2 as a 3-hour intravenous infusion and cisplatin at 75 mg/m2 as an intravenous infusion on day 1 every 3 weeks. RESULTS: Twenty-five of 27 patients that were entered from 5 hospitals between Jan 2001 and Aug 2001 received chemotherapy. On an intent-to-treat basis, 9 patients (36%) achieved a partial response, 7 patients (28%) a stable disease, and 5 patients (20%) The overall response rate was 36% (95% CI, 17 to 55%). progressed. The median duration of the response was 7.8 months (95% CI, 6.6 to 9.0 months). The median time to progression was 7.4 months (95% CI, 5.3 to 9.5 months), and median overall survival was 13.3 months (95% CI, 10.8 to 15.9 months) for the intent-to-treat population. The major oxicity was hematological, with grade 3 and 4 neutropenia in 10% (10/106) of the total cycles. The non-hematologic oxicity was mild, and grade 3 emesis was observed in 2 patients (8%). One patient experienced a moderate degree hypersensitivity reaction. CONCLUSION: The results suggest that a combination of Genexol(R) and cisplatin is an effective and well-tolerated regimen for patients with NSCLC.

Expression of Cyclin-dependent Kinase Inhibitor p21(WAF1/CIP1) in Non-small Cell Lung Carcinomas: Relationship with p53 Status and Proliferative Activity / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The objectives of this study are to elucidate the level of p21(WAF1/CIP1) expression in non-small cell lung carcinomas (NSCLCs) and to investigate the relationship between the p21(WAF1/CIP1) expression and clinicopathologic features; p53 overexpression; and proliferative activity measured by Ki-67 expression. MATERIALS AND METHODS: The expressions of p21(WAF1/CIP1), p53, and Ki-67 proteins were analyzed by immunohistochemistry in 45 formalin-fixed and paraffin-embedded NSCLC specimens. 43 patients underwent curative resections and 2 patients had bronchoscopic biopsy specimens only. The correlations between p21(WAF1/CIP1) immunoexpression and p53 status; Ki-67 proliferative activity; and clinicopathologic parameters were analyzed statistically by chi-square or Fisher's exact test. RESULTS: p21(WAF1/CIP1) expression in the carcinoma cells was found in 28 (62%) of 45 cases. There was no significant correlation between p21(WAF1/CIP1) expression and abnormal accumulation of p53 protein. In 16 (36%) of 45 cases, p21(WAF1/CIP1) was expressed inde pendently of p53 overexpressions. p21WAF1/CIP1 expression was not associated with patient sex, smoking history, pathological stage, tumor size, histological grade or type. However, p21WAF1/CIP1 immunoreactivity was significantly higher in older individuals over 59 years and tended to occur more intensely in the more highly differentiated portion of the squamous carcinoma. Also, a positive correlation between p21WAF1/CIP1 and Ki-67 expression was observed. CONCLUSIONS: The present findings overall suggest that aberrations in the relationship between p21(WAF1/CIP1) and p53 expressions may be important in the development of NSCLCs; that a p53-independent pathway may be substantially involved in the induction of p21(WAF1/CIP1) expression in NSCLCs; and that the proliferative activity of lung cancers might be dependent on positive control of the cell cycle by p21(WAF1/CIP1).