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ABSTRACT: CK2 interacts and phosphorylates >300 proteins, including Stat3, and is linked to a number of human cancers. Constitutively activated Stat3 has been reported in 50% of human lung cancers. Inhibition of CK2 activity can induce apoptosis and suppression of Stat3 activation in cancer cells. This study examined the effects of CK2 inhibitors on growth inhibition of lung cancer cells and the therapeutic potential on lung cancer. The CK2 inhibitor and radiation both suppressed cancer cell growth in a dose-dependent manner. Besides, the cytotoxic effect of irradiation could be augmented by CK2 inhibitors (p<0.05, two-way analysis of variance and Tukey's Honestly Significant Difference). Moreover, the growth inhibition of CK2 inhibitor and irradiation was both associated with suppression of Stat3 activation. Taken together, inhibition of CK2 activity appears to be a promising treatment strategy for non-small cell lung cancer and CK2 inhibition results in reduced Stat3 activation. Our data warrant further effort to develop CK2-targeted radiosensitizer for lung cancer treatment.
Cancer Biotherapy & Radiopharmaceuticals 06/2011; 26(3):381-8. · 1.44 Impact Factor
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ABSTRACT: The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is one of the most important components of cytokine signaling cascades. JAK-STAT signaling pathway modulates various fundamental biological processes and cancer pathogenesis. JAK-STAT is controlled by negative regulators that include suppressors of cytokine signaling (SOCS) proteins. Failure of feedback suppression by SOCS proteins may result in activated JAK-STAT signaling. Methylation-mediated silencing of SOCS3 has been reported in non-small lung cancer (NSCLC) and other human cancers. In this study, we restored SOCS3 expression using adenovirus-mediated gene transfer in NSCLC cells. Infection with a SOCS3-expressing vector inhibited the growth of lung cancer cells, with or without SOCS3 expression, at 2-3 days after infection. The growth inhibition of lung cancer cells was associated with suppressing entry into the S-phase. Restoration of SOCS3 expression induced apoptosis of NSCLC cells that did not express SOCS3. In addition, overexpression of SOCS3 by adenoviral transfer enhanced the radiosensitivity of treated NSCLC cells. In conclusion, our findings may provide insights into the development of applications of SOCS3 gene therapy for lung cancer and, possibly, other human cancers.
Oncology Reports 12/2010; 24(6):1605-12. · 1.84 Impact Factor
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ABSTRACT: The prevalence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients is about 40-50% in Taiwan, and there are significant correlations between EGFR mutations and clinical responses after gefitinib treatment. For most patients with advanced disease, surgical intervention for tissue sampling is not feasible. We therefore conducted this study to survey EGFR mutations in cells from NSCLC malignant pleural effusions and to evaluate the clinical significance.
In the present study, malignant pleural effusion cells from 29 NSCLC patients were studied for EGFR mutations. Exons 18, 19, 20, 21 of the EGFR gene were analyzed by polymerase chain reaction (PCR) and automated sequencing. For 11 patients who had received gefitinib therapy, correlations between gefitinib effect and EGFR mutations were also evaluated.
EGFR mutations were detected in 12 of 29 specimens (41%). In-frame deletion mutations in exon 19 (8 of 12 specimens, 67%) and missense mutations in exon 21 (3 of 12 specimens, 25%) were the most frequent mutations detected. The frequency of EGFR mutations was significantly higher in gefitinib responders (4/4) than non-responders (1/7) (p = 0.015).
Our results suggest that detecting EGFR mutations in cells from malignant pleural effusions is a feasible adjunct method to finding the subgroup with favorable response to gefitinib therapy among patients with advanced NSCLC.
Chang Gung medical journal 29(4):373-9.
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ABSTRACT: House dust mites (HDM) are one of the major risk factors for the development of bronchial asthma. The percentage of sensitization to HDM was reported to be 71.9% in Taipei City. In southwestern Taiwan, the percentage of sensitization to HDM has not been estimated. We retrospectively reviewed the medical records of asthmatic patients treated at the Chiayi branch of Chang Gung Memorial Hospital to investigate the percentage and associations with demographic characteristics.
We analyzed the data of 194 asthmatic patients diagnosed between January 2003 and July 2005. Sensitization to indoor allergens was identified by serum specific immunoglobulin E (IgE) of ImmunoCAP. Demographic characteristics of age, gender and residence were evaluated for associations with allergic sensitization.
The percentage of sensitization to HDM was only 45.9% in patients in southwestern Taiwan. The majority of the studied group were elderly patients. The age variable significantly influenced the percentage of sensitization to HDM and cockroaches (p < 0.001 in both comparisons). The gender variable contributed to sensitization to cockroaches only (p = 0.002). For residential variables, there was no significant difference in the percentage of allergic sensitization to all tested indoor allergens among distinct areas of southwestern Taiwan.
The percentage of sensitization to HDM in asthmatic patients residing in southwestern Taiwan was lower than that in metropolitan patients. This discrepancy might be attributed to the larger proportion of aged patients.
Chang Gung medical journal 29(6):568-75.
