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The aim of this study was to determine the expressions of Rb, p16, and cyclin D1 in soft tissue sarcomas, and we also wanted to identify the prognostic factors according to the clinicalpathologic features.
We reviewed the charts and radiographic films of 66 sarcoma patients. Tissue samples were collected from these patients. Immunochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p16, Rb, and cyclin D1 proteins.
The median duration of overall survival was 47.8 months (range, 20.0 to 70.7 months) and the 5 years survival rate was 39%. As for the correlation between the degree of immunohistochemical staining for Rb protein and the histological tumor grades, there was a significant difference with a p-value of 0.019. However, no significant correlation was shown for p16 and cyclin D1. The overall survival duration of the Rb negative group (staining cell <20%) and the heterogeneous group (cell staining 20 to 80%) was 53.5±6.6 months and the overall survival duration of the Rb homogeneous group was 18.3±6.4 months, and there was a significant difference with a p-value of 0.016. However, no significant difference was shown between the survival rate according to the p16 and cyclin D1 expressions. On the multivariate analysis that was done with Rb, p16, the tumor size, grade and site, and patient age, the Rb gene expression was the most significant independent prognostic factor with a risk ratio of 3.01 (p=0.04).
The expression of Rb protein was correlated with the histologic grade and overall survival of patients with soft tissue sarcomas.
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A patient with adenocarcinoma of the lung was treated sequentially using two kinds of EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. The patient was a 73-year-old female who received gefitinib as a second line treatment, which resulted in a partial response with response duration of 6 months. After progression of the disease, the patient received erlotinib, which resulted in partial response again with response duration of 11.5 months. This observation suggests that treatment with erlotinib may be effective in patients who develop progressive disease after a primary treatment with gefitinib following an initial response.
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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.
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.
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.
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.
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92 kDa matrix metalloproteinase-9 (MMP-9) is believed to play an important role in degrading the matrix and basement membrane, contributing to the invasion and metastasis of malignant solid tumors. However, little is known about its involvement in a malignant fibrous histiocytoma. The aim of this study was to investigate the expression of MMP-9 and to correlate its expression with clinicopathologic parameters in human malignant fibrous histiocytomas.
Archival tumor tissues from 20 patients with a malignant fibrous histiocytoma were analyzed by immunohistochemistry for the expression of MMP-9. Clinical information was obtained through the computerized retrospective database from the tumor registry.
Seventeen of 20 (85%) tumors showed a positive reaction for MMP-9. MMP-9 activity was inversely correlated with patients' survival time (p=.011). There was no significant correlation between the activated MMP-9 expression and all the other clinicopathologic variables.
Our data demonstrate that MMP-9 activation is likely to occur in human malignant fibrous histiocytomas. It is also noteworthy that the expression of MMP-9 may aid in predicting patients' poor prognosis.
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Increasing experimental evidence indicates that abnormal expression of c-kit may be implicated in the pathogenesis of a variety of solid tumors. It has been reported that over 70% of small cell lung cancer (SCLC) contain the c-kit receptor. In the present study, a c-kit analysis has been extended to non-small cell lung cancer (NSCLC). The expressions of p53, vascular endothelial growth factor (VEGF) and cd34, in addition to c-kit, were evaluated to investigate the correlations between these proteins and to determine their potential relationships with the clinicopathological data.
Paraffin-embedded tumor sections, obtained from 147 patients with NSCLC, were immunohistochemically investigated using anti-c-kit, anti-p53, anti-VEGF and anti-cd34 antibodies.
c-kit was expressed in 40 (27%) of the tumors examined: 27% of the adenocarcinomas, 27% of the squamous cell carcinomas and 29% of the undifferentiated carcinomas. p53 and VEG F immunoreactivities were present in 107 (73%) and 110 (75%) carcinomas, respectively. Anti-cd34 was negative in all samples. No associations were established among these proteins. The c-kit, however, showed a strong correlation with the T factor: T1 (n=11), 0%; T2 (n=49), 16% and T3 (n=87), 37% (p=.006).
It is suggested that in NSCLC c-kit is expressed relatively frequently and may become a therapeutic target for the patients with inoperable or recurrent c-kit positive tumors. The alterations in p53 probably constitute an early event, whereas the activated c-kit may contribute to tumor progression.
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c-myc, bcl-2 and p53 are known to regulate apoptosis. There has been growing interest in analyzing their contribution to the pathogenesis and prognosis in a variety of human cancers. This study was undertaken to investigate the expression of these proteins in pulmonary adenocarcinomas and to determine their relationship with clinicopathologic parameters and survival.
Archival tumor tissues from 61 patients with adenocarcinoma of lung were analyzed by immunohistochemistry for the expression of c-myc, bcl-2 and p53 proteins. Clinical information was obtained through the computerized retrospect database from the tumor registry.
Of 61 patients, 32 were men and 29 women with the median age 63 years. 4 had stage I disease, 2 had stage II disease and 55 had stage III disease. The expression of c-myc protein was identified in 13% (8/61) tumors, bcl-2 protein was detected in 1.6% tumors (1/61) and p53 was detected in 77% (47/71) tumors. The association of the expression of c-myc, bcl-2 and p53 was not detected. The survival time was longer in patients expressing c-myc protein than in patients without the c-myc protein expression (p=.045). Neither bcl-2 nor p53 showed the correlation to clinicopathologic variables.
Our data suggest the involvement of p53 alteration in the pathogenesis of lung adenocarcinoma. The c-myc expression in some tumors indicates that c-myc alone may not contribute critically to the development and/or the progression of these tumors. It, however, correlated to the survival time, suggesting the c-myc expression as a favorable prognostic factor possibly through the apoptosis pathway.
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