Biomedical subjects

Wen-Cheng Chang

Publications and source records attributed to Wen-Cheng Chang.

8 recordsLinked to original sources

PubMed2006

Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.

Adenocarcinoma↗

PubMed2006

The role of Ca2+ on the DADS-induced apoptosis in mouse-rat hybrid retina ganglion cells (N18).

Diallyl disulfide (DADS), a component of garlic, has been shown to induce growth inhibition and apoptosis in human cancer cell types. The present studies were designed to investigate the effects of DADS on mouse-rat hybrid retina ganglion cells (N18) to better understand its effect on apoptosis and apoptosis-related genes in vitro. Cell viability, cell cycle analysis, reactive oxygen species (ROS), Ca2+ production, mitochondria membrane potential, apoptosis induction, associated gene expression and caspases-3 activity were examined by flow cytometric assay and/or Western blot. After 24-h treatment with DADS, a dose- and time-dependent decrease in the viability of N18 cells was observed and the approximate IC50 was 27.6 microM. The decreased percentage of viable cells are associated with the production of ROS then followed by the production of Ca2+ which is induced by DADS. DADS induced apoptosis in N18 cells via the activation of caspase-3. DADS increased the protein levels of p53, cytochrome c and phosphated JNK within 24 h of treatment and it decreased the levels of Bcl-2 and those factors may have led to the mitochondria depolarization of N18 cells. DADS induced apoptosis were accompanied by increased levels of Ca2+ and decreased mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-3. Deleted levels of Ca2+ by BAPTA-AM 10 microM (intracellular calcium chelator) then led to decrease DADS-induced apoptosis. Inhibition of caspase-3 activation by inhibitor (z-VAD-fmk) completely blocked DADS-induced apoptosis on N18 cells. The results indicated that oxidative stress modulates cell proliferation and Ca2+ modulates the cell death induced by DADS.

Allyl Compounds↗

PubMed2005

Case analysis of purple urine-bag syndrome at a long-term care service in a community hospital.

BACKGROUND: Purple urine-bag syndrome (PUBS) is a rare phenomenon in which the contents of urine bags turn purple or blue following patient catheterization. The condition often causes care givers tremendous distress. We investigated the prevalence and possible causes of PUBS for a group of elderly patients. METHODS: A total of 157 patients featuring urine catheterization, 13 of whom exhibiting PUBS were analyzed with regards to age, functional status, duration of catheterization, number of daily medications, living location, feeding route, bowel habits, and the pattern of use of a urinary catheter. Urine samples were cultured from all the PUBS patients participating. RESULTS: Two men who underwent cystostomy and 11 women who underwent urethral catheterization who exhibited PUBS were observed for this study. The age, duration of catheterization, number of daily medications feeding pattern and functional status between the group exhibiting PUBS and the group of patients without PUBS demonstrated no significant differences. A total of 69.2% of the PUBS-affected patients, as compared to 43.1% of the non-PUBS patients, lived in nursing homes, and 84.6% of the PUBS-affected patients were constipated, as were 66% of the non-PUBD subjects. In total, 72.7% of PUBS patients were reported to be using a laxative suppository, compared with 41% of the non-PUBS group, whereas 92.3% of PUBS patients were catheterized using a plastic (PVC) foley, as compared to 70.8% of the non-PUBS patients. The pH for 12 out of 13 PUBS patients' urine was > or = 7. Escherichia coli, Provendicia var. spp., Proteus mirabilis, Klebsiella pneumoniae were the common pathogens isolated from the urine samples provided by our PUBS patients. CONCLUSION: We found that PUBS was more likely associated with the female gender, alkaline urine, constipation, institutionalization, the use of a plastic (PVC) urinary catheter, and certain bacteria such as Provendicia var. spp., Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.

Adult↗

PubMed2004

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

Adenocarcinoma↗

PubMed2004

Chemotherapy using 5-fluorouracil, mitoxantrone, and cisplatin for patients with advanced hepatocellular carcinoma: an analysis of 63 cases.

BACKGROUND: We evaluated the anti-tumor efficacy and toxicity of 5-fluorouracil (5-FU), mitoxantrone, and cisplatin (FMP) in patients with advanced hepatocellular carcinoma (HCC), and conducted an analysis of the prognostic factors for response to such therapy and patient survival. METHODS: Sixty-three patients suffering from unresectable and non-embolizable HCC and who had objectively measurable tumors, adequate liver and renal function, and adequate bone-marrow reserve were enrolled in this study. The therapeutic regimen consisted of cisplatin 80 mg/m(2) and mitoxantrone 6 mg/m(2) intravenously on day 1, and 5-FU 450 mg/m(2) per day continuous infusion for a period of 5 days. Univariate and multivariate analyses of patient and disease characteristics were used to identify factors predicting patient response and survival. RESULTS: The objective response was 23.8% (95% confidence interval [CI], 13.0-34.6%). The median survival for all 63 patients was 4.9 months (95% CI, 3.2-6.6 months). The median time to progression was 2.5 months (95% CI, 1.7-3.3 months). Multivariate analysis identified only performance status ( P = 0.050) and liver tumor size ( P = 0.012) as being significantly related to patient objective response. Independent variables associated with a better patient survival included: the absence of ascites ( P = 0.003), a lower total bilirubin level ( P = 0.026), and the patient being a positive chemotherapy responder ( P = 0.009). CONCLUSIONS: The response rate to an FMP regimen was still unsatisfactory, although a specific subgroup of patients (good performance status, smaller liver tumor mass, good liver reserve, and distant metastasis) may benefit from this regimen.We evaluated the anti-tumor efficacy and toxicity of 5-fluorouracil (5-FU), mitoxantrone, and cisplatin (FMP) in patients with advanced hepatocellular carcinoma (HCC), and conducted an analysis of the prognostic factors for response to such therapy and patient survival.

Adult↗

PubMed2004

Limitations of forehead infrared body temperature detection for fever screening for severe acute respiratory syndrome.

We investigated alternative measurement methodology for infrared body thermometry to increase accuracy for outdoor fever screening during the 2003 SARS epidemic. Our results indicate that the auditory meatus temperature is a superior alternative compared with the forehead body surface temperature due to its close approximation to the tympanic temperature.

Body Temperature↗

PubMed2003

A novel splicing regulator shares a nuclear import pathway with SR proteins.

Alternative splicing of precursor mRNA is often regulated by serine/arginine-rich proteins (SR proteins) and hnRNPs, and varying their concentration in the nucleus can be a mechanism for controlling splice site selection. To understand the nucleocytoplasmic transport mechanism of splicing regulators is of key importance. SR proteins are delivered to the nucleus by transportin-SRs (TRN-SRs), importin beta-like nuclear transporters. Here we identify and characterize a non-SR protein, RNA-binding motif protein 4 (RBM4), as a novel substrate of TRN-SR2. TRN-SR2 interacts specifically with RBM4 in a Ran-sensitive manner. TRN-SR2 indeed mediates the nuclear import of a recombinant protein containing the RBM4 C-terminal domain. This domain serves as a signal for both nuclear import and export, and for nuclear speckle targeting. Finally, both in vivo and in vitro splicing analyses demonstrate that RBM4 not only modulates alternative pre-mRNA splicing but also acts antagonistically to authentic SR proteins in splice site and exon selection. Thus, a novel splicing regulator with opposite activities to SR proteins shares an identical import pathway with SR proteins to the nucleus.

Active Transport, Cell Nucleus↗

PubMed2002

Phase II study of paclitaxel (Genaxol) and cisplatin combination in treating Chinese patients with advanced non-small cell lung cancer (NSCLC).

PURPOSE: To assess the efficacy of 3-h paclitaxel infusion (Genaxol) combined with cisplatin as the first line chemotherapy for patients with advanced/metastatic non-small cell lung cancer (NSCLC). The aim of the present study is to evaluate the efficacy, safety, and quality of life of the combination of paclitaxel (Genaxol) and cisplatin on Chinese patients. METHODS: Forty-five patients with histology confirmed NSCLC, who met the selection criteria were enrolled in this study between June 1999 and May 2000. They were all at an advanced stage, i.e. stage IIIB with pleural effusion, or stage IV. Paclitaxel (Genaxol) at a dose of 175 mg/m(2) and cisplatin at a dose of 75 mg/m(2) were administered every 3 weeks. RESULTS: Of the 45 eligible patients, one had a CR and 19 achieved a PR. The overall response was 44.4% (95% CI: 29.3-59.5%). Eleven (24.4%) patients were in stable disease. The median time to disease progression for all patients was 5.5 months (95% CI: 4.0-7.0 months). The median survival was 11.1 months (95% CI: 6.6-15.6 months), the 1-year survival probability was 46.5%. Major non-hematology toxicities were asthenia, paresthesias, nausea, and vomiting. Hematological toxicity results showed 18 (40%) patients experienced grade 3/4 neutropenia but there was no febrile neutropenia, three (6.6%) patients experienced Grade 3 anemia, and one (2.2%) patient experienced Grade 3 thrombocytopenia. CONCLUSIONS: The combined paclitaxel and cisplatin regimen is safe and effective in the treatment of NSCLC but the quality of life is disappointed.

Adult↗