Biomedical subjects

Yu-Jen Chen

Publications and source records attributed to Yu-Jen Chen.

36 records · Page 2Linked to original sources

PubMed2005

Induction of apoptosis by three marine algae through generation of reactive oxygen species in human leukemic cell lines.

In this study, we examined the antitumor effect of marine algae extracts on human hepatoma and leukemia cells. Ethyl acetate extracts from Colpomenia sinuosa (Cs-EA), Halimeda discoidae (Hd-EA), and Galaxaura oblongata (Go-EA) directly inhibited the growth of human hepatoma HuH-7 cells and leukemia U937 and HL-60 cells in a time- and dose-dependent manner. Specifically, these algae extracts induced apoptosis of U937 and HL-60 cells as evaluated by detection of hypodiploid cells using flow cytometry and observation of condensed and fragmented nuclei in algae extract-treated cells. Intracellular reactive oxygen species (ROS), especially hydrogen peroxide and superoxide anion, were increased about 2-3-fold in U937 cells treated with Cs-EA for 3-5 h. Interestingly, antioxidant N-acetylcysteine effectively blocked Cs-EA-, Hd-EA-, and Go-EA-induced apoptosis, suggesting that ROS is a key mediator in the apoptotic signaling pathway. In conclusion, our results show that algae extracts induce apoptosis in human leukemia cells through generation of ROS.

Apoptosis↗

PubMed2005

A novel polysaccharide of black soybean promotes myelopoiesis and reconstitutes bone marrow after 5-flurouracil- and irradiation-induced myelosuppression.

The aim of this study was to investigate the promotion of myelopoiesis by an active polysaccharide of black soybean (PSBS). Murine spleen cells were collected from ICR mice and conditioned media (SCM) was prepared by incubating these cells without PSBS (normal-SCM) or with PSBS in concentrations ranging from 12.5 to 100 microg/ml (PSBS-SCM). Murine bone marrow cells were treated with PSBS alone or SCM to induce the formation of colonies, including CFU-GM, CFU-GEMM, BFU-E and HPP-CFC. The concentrations of six hematopoietic growth factors contained in SCM were measured using enzyme-linked immunoassay. In the live animal experiment, PSBS was administered orally to total body-irradiated (TBI) and 5-fluorouracil (5-FU)-treated mice to assess the reconstitution of bone marrow after myelosuppression. PSBS-SCM stimulated CFU-GM, CFU-GEMM, BFU-E and HPP-CFC colony formation with 45.0, 5.0, 6.2 and 6.6-fold increases, respectively. However, neither PSBS alone nor normal-SCM had such a colony-stimulating effect. In PSBS-SCM, the levels of IL-6, IL-17, G-CSF and GM-CSF were markedly increased, but not those of IL-3 and SCF. Oral administration of PSBS in mice not only restored the leukocyte counts reduced by TBI and 5-FU treatment but also enhanced CFU-GM colony formation of bone marrow cells without a significant change in body weight. We conclude that PSBS promotes myelopoiesis activity in the bone marrow, stimulates production of various hematopoietic growth factors from spleen cells, and reconstitutes bone marrow that has been myelosuppressed by irradiation and 5-FU.

Administration, Oral↗

PubMed2005

Phospholipase A(2) activity of beta-bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons.

The aim of this study was to investigate the mechanism of the cytotoxic effect of beta-bungarotoxin (beta-BuTX), a presynaptic neurotoxin, on rat cerebellar granule neurons (CGNs). The maturation of CGNs is characterized by the prominent dense neurite networks that became fragmented after treatment with beta-BuTX, and this cytotoxic effect of beta-BuTX on CGNs was in a dose- and time-dependant manner. The cytotoxic effect of beta-BuTX was found to be more potent than other toxins, such as alpha-BuTX, cardiotoxin, melittin, and Naja naja atra venom phospholipase A(2). Meanwhile, undifferentiated neuroblastoma neuronal cell lines, IMR-32 and SK-N-MC, and astrocytes were found to be resistant to beta-BuTX. These results indicated that only the mature CGNs were sensitive to beta-BuTX insults. None of the following chemicals: antioxidants, K(+)-channel activator, K(+)-channel antagonists, intracellular Ca(2+) chelator, Ca(2+)-channel blockers, NMDA receptor antagonists, and nitric oxide synthase inhibitor tested, were able to reduce beta-BuTX-induced cytotoxicity. However, secretory type phospholipase A(2) inhibitors (glycyrrhizin and aristolochic acid) and a free radical scavenger (5,5-dimethyl pyrroline N-oxide, DMPO) could attenuate not only beta-BuTX-induced cytotoxicity but also ROS production and caspase-3 activation. These data suggest that phospholipase A(2) activity of beta-BuTX may be responsible for free radical generation and caspase-3 activation that accounts for the observed cytotoxic effect. It is proposed that the CGNs can be a useful tool for studying interactions of the molecules on neuronal plasma membrane with beta-BuTX that mediates the specific cytotoxicity.

Analysis of Variance↗

PubMed2005

Ileocolic free flap reconstruction, concomitant chemotherapy and radiotherapy and assessment of speech and swallowing function during management of advanced cancer of the larynx and hypopharynx: preliminary report.

CONCLUSION: The new technique of ileocolic free flap reconstruction provides a better quality of life in terms of swallowing and speech for patients who have undergone laryngopharyngectomy with concomitant chemotherapy and radiotherapy (CCRT). OBJECTIVES: To compare and contrast the swallowing and speech outcomes of patients who underwent total laryngopharyngectomy with ileocolic free flap reconstruction and to analyze the survival rate after surgery and CCRT. MATERIAL AND METHODS: This was a follow-up study of 12 patients with advanced (stages III, IVA and IVB) laryngeal and hypopharyngeal cancer who underwent major surgery, CCRT (with one exception) and ileocolic free flap reconstruction. RESULTS: All patients were able to tolerate single-stage combined management comprising total laryngopharyngectomy with or without radical neck dissection plus ileocolic free flap reconstruction and postoperative CCRT (with one exception), without immediate morbidity or mortality. Eleven patients were diagnosed with hypopharyngeal cancer and one with laryngeal cancer. The mean interval between surgery and CCRT was 34.1 days. The mean follow-up period was 16.5 months. Four patients died during the follow-up period as a result of local recurrence (n=2), distant metastasis (n=1) and suicide (n=1). One patient was alive with disease despite neck recurrence.

Adult↗

PubMed2005

Compound 278E, structurally modified from tanshinone, induces monocytic differentiation and regulates proto-oncogene expression in human leukemic HL-60 cells.

Tanshinone derivative compounds, isolated from Salvia miltiorrhiza Bunge (Labiatae), have been reported as microtubule inhibitors with antimitotic activity. In this study, we examined the growth-inhibiting and differentiation-inducing effect of these compounds on human leukemic HL-60 cells. The expression of protein kinase C (PKC) and proto-oncogenes in 278E-treated cells was also assessed. All tanshinone derivative compounds exhibited growth-inhibitory effects on HL-60 cells, but only 278E induced cell differentiation. Morphological observation of 278E-treated HL-60 cells showed a greater percentage of monocytes and macrophages (Mo/Mphi). Treatment with 5 microg/ml 278E resulted in a marked increase in the percentages of superoxide-producing (up to 95.5+/-1.8%) and non-specific esterase-positive cells (up to 80.3+/-9.1%). The differentiated cells also expressed cell surface antigens characteristic of Mo/Mphi, including CD11b, CD14 and CD68. Neither cellular changes in isozymes of PKC nor translocation of these isozymes from cytosol to cell membrane were seen in 278E-treated HL-60 cells. 278E caused a downregulation of c-myc as well as an up-regulation of c-fms, c-jun and c-fos.

Abietanes↗

PubMed2005

Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinoma cells.

Norcantharidin (NCTD), a potential anti-cancer drug, is the demethylated analog of cantharidin isolated from blister beetles. The present study investigated the effect of NCTD on tumor invasion and metastasis. A cytotoxicity assay of NCTD in CT26 colorectal adenocarcinoma cells showed a dose- and time-dependent decrease in cell viability. NCTD (50 microM)-treated CT26 cells not only showed an inhibited cell invasion of 65.6%, but also decreased the activity of matrix metalloproteinase-2 and -9. NCTD decreased the adhesive ability of CT26 cells in a dose-dependent manner. At a concentration of 100 microM, NCTD showed a down-expression of several cadherin-catenin adhesion molecules, including Desmoglein, N-cadherin, and alpha- and beta-catenin, while there were no obvious changes in E-cadherin and gamma-catenin. Intraperitoneal injection of NCTD (2 mg/kg/day) in BALB/c mice reduced both the pulmonary metastatic capacity of CT26 cells and prolonged the survival day of the mice. These results demonstrated that it was effective in blocking both tumor invasion and metastasis.

Adenocarcinoma↗

PubMed2005

Stereoselective esterase from Pseudomonas putida IFO12996 reveals alpha/beta hydrolase folds for D-beta-acetylthioisobutyric acid synthesis.

Esterase (EST) from Pseudomonas putida IFO12996 catalyzes the stereoselective hydrolysis of methyl dl-beta-acetylthioisobutyrate (dl-MATI) to produce d-beta-acetylthioisobutyric acid (DAT), serving as a key intermediate for the synthesis of angiotensin-converting enzyme inhibitors. The EST gene was cloned and expressed in Escherichia coli; the recombinant protein is a non-disulfide-linked homotrimer with a monomer molecular weight of 33,000 in both solution and crystalline states, indicating that these ESTs function as trimers. EST hydrolyzed dl-MATI to produce DAT with a degree of conversion of 49.5% and an enantiomeric excess value of 97.2% at an optimum pH of about 8 to 10 and an optimum temperature of about 57 to 67 degrees C. The crystal structure of EST has been determined by X-ray diffraction to a resolution of 1.6 A, confirming that EST is a member of the alpha/beta hydrolase fold superfamily of enzymes and includes a catalytic triad of Ser97, Asp227, and His256. The active site is located approximately in the middle of the molecule at the end of a pocket approximately 12 A deep. EST can hydrolyze the methyl ester group without affecting the acetylthiol ester moiety in dl-MATI. The examination of substrate specificity of EST toward other linear esters revealed that the enzyme showed specific activity toward methyl esters and that it recognized the configuration at C-2.

Bacterial Proteins↗

PubMed2005

Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation.

Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardioprotection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-kappaB) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using propidium iodide staining and flow cytometry. An ELISA-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-kappaB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 microM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-kappaB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G0/G1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-kappaB inhibition and S-phase arrest.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Effect of bracing on patellofemoral joint stress while ascending and descending stairs.

OBJECTIVE: To test the hypothesis that individuals who respond favorably to bracing will exhibit decreased patellofemoral joint stress during stair ambulation. DESIGN: A repeated-measures, cross-sectional study. BACKGROUND: Ascending and descending stairs is one of the most painful activities of daily living for persons with patellofemoral pain (PFP). Although patellar bracing has been shown to reduce symptoms during such tasks, the underlying mechanism has not been identified. METHODS: Fifteen subjects with a diagnosis of PFP completed 2 phases of data collection: (1) magnetic resonance imaging to determine patellofemoral joint contact area, and (2) gait analysis during stair ascent and descent. Data were obtained under braced and non-braced conditions. Variables obtained from both data collection sessions were used as input variables into a biomechanical model to quantify patellofemoral joint stress. RESULTS: Although subjects reported an average decrease in pain of 56%, bracing did not reduce peak stress during stair ascent and descent. This finding can be explained by the fact that despite improvements in contact area, bracing resulted in greater knee extensor muscle moments and joint reaction forces. CONCLUSIONS: Our results do not support the hypothesis that individuals with PFP would demonstrate reduced patellofemoral stress during stair ambulation following the application of a patellar brace. CLINICAL RELEVANCE: Although bracing did not decrease patellofemoral joint stress during stair ascent and descent, the decrease in pain, increase in quadriceps utilization, and tolerance of joint reaction forces would appear to be beneficial consequences of bracing.

Adolescent↗

PubMed2004

Inhibitory effect of tetrandrine on pulmonary metastases in CT26 colorectal adenocarcinoma-bearing BALB/c mice.

Tumor metastasis is a major cause of mortality in cancer patients. The anti-metastatic effect of tetrandrine, an alkaloid isolated from Stephania tetrandrae S. Moore, was investigated in a pulmonary metastatic model of colorectal cancer-bearing mice. Tetrandrine decreased the viability of murine colorectal adenocarcinoma CT26 cells in a time- and dose-dependent manner. CT26 cells were injected into BALB/c mice via a tail vein to establish pulmonary metastases. After this, the mice were given intraperitoneal injections of tetrandrine (10 mg/kg/day), 5-fluorouracil (5-FU) at the same dose, or vehicle for 5 consecutive days. Mice treated with tetrandrine had 40.3% fewer metastases than vehicle-treated mice, and those treated with 5-FU had 36.9% fewer metastases than controls. Both tetrandrine- and 5-FU-treated mice survived longer than mice in the untreated control group. There was no acute toxicity or obvious changes in body weight in any of the mice. These results suggest that tetrandrine may be a useful anti-metastatic agent.

Adenocarcinoma↗

PubMed2004

The effect of bracing on patella alignment and patellofemoral joint contact area.

PURPOSE: To examine the influence of two patellofemoral braces on pain response, patellar alignment, and patellofemoral joint contact area in persons with patellofemoral pain. METHODS: Fifteen women between the ages of 18 and 45 yr with a diagnosis of patellofemoral pain participated. After the assessment of pain response using a visual analog scale, subjects underwent axial plane magnetic resonance imaging of patellofemoral joint at 0 degrees, 20 degrees, 40 degrees, and 60 degrees of knee flexion. Imaging was done with the knee extensors contracted (25% body weight) under three conditions: 1) no brace, 2) On-Track brace, and 3) Patellar Tracking Orthosis (PTO). Measures of mediolateral patellar displacement and tilt and medial and lateral facet contact area were obtained from the magnetic resonance images. RESULTS: On average, the On-Track brace reduced symptoms by 50%, whereas the PTO reduced pain by 44%. When averaged across all knee flexion angles, the PTO and the On-Track brace significantly increased total patellofemoral joint contact area by 52.0 mm (21%) and 59.3 mm (24%), respectively, when compared with the no-brace condition. Bracing had no influence on lateral patellar tilt; however, small but significant changes in lateral patellar displacement were observed. CONCLUSION: Large changes in pain and contact area occurred without sizable changes in patellar alignment. The results of this study suggest that changes in patellar alignment by itself may not be responsible for pain alleviation after patellar bracing.

Adolescent↗

PubMed2004

Cell killing and radiosensitization by caffeic acid phenethyl ester (CAPE) in lung cancer cells.

Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of honeybee propoplis. The cytotoxicity and radiation sensitization effects of CAPE were evaluated in human lung cancer A549 cells and normal lung fibroblast WI-38 cells. A549 cells treated with 6 microg/ml CAPE showed marked growth inhibition (60%) at 48 hr after treatments. During the same time, the number of viable cells decreased to 46% of the control value. In contrast, WI-38 cells showed 20% growth inhibition with no change in the number of viable cells under the same treatment conditions. At 72 hr after CAPE treatment (6 microg/ml), the percentage of apoptotic cells in A549 cultures increased significantly to 67% and an S/G2 arrest was also detected in the culture. Furthermore, there was a significant decrease in the level of intracellular glutathione and hydrogen peroxide contents within one hr after CAPE treatment, and the expression of cyclin B1 was reduced 6 hr after treatment. The radiation sensitization effect of CAPE on A549 cells was determined from the clonogenic survival curves, and the results showed a small but significant difference in radiation survival between cells treated with or without CAPE. Taken together, our results suggest that the effects of CAPE on differential cytotoxicity, apoptosis, and radiosensitization are associated with glutathione depletion that occurred shortly after treatments.

Adenocarcinoma↗

PubMed2003

Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and metastasis.

Caffeic acid phenethyl ester (CAPE) derived from honeybee propolis has been used as a folk medicine and has several proven biological activities. The present study investigated the effect of CAPE on angiogenesis, tumor invasion, and metastasis. A cytotoxicity assay of CAPE in CT26 colon adenocarcinoma cells showed a dose-dependent decrease in cell viability but no significant influence on the growth of human umbilical vein epithelial cells (HUVEC). A low concentration of CAPE (1.5 microg/mL) inhibited 52.7% of capillary-like tube formation in HUVEC culture on Matrigel. CAPE (6 microg/mL)-treated CT26 cells showed not only inhibited cell invasion by 47.8% but also decreased expression of matrix metalloproteinase (MMP)-2 and -9. Vascular endothelial growth factor (VEGF) production from CT26 cells was also inhibited by treatment with CAPE (6 microg/mL). Intraperitoneal injection of CAPE (10 mg/kg/day) in BALB/c mice reduced the pulmonary metastatic capacity of CT26 cells accompanied with a decreased plasma VEGF level. CAPE treatment also prolonged the survival of mice implanted with CT26 cells. These results indicate that CAPE has potential as an antimetastatic agent.

Adenocarcinoma↗

PubMed2003

Combined effect of topical arsenic trioxide and radiation therapy on skin-infiltrating lesions of breast cancer-a pilot study.

It has been reported that arsenic trioxide (As2O3) is an apoptosis inducer and radiation sensitizer for various cancer cell lines. In this study of breast cancer patients, we examined the combined effect of topical As2O3 and radiation therapy on fungating and/or skin-infiltrating lesions of breast cancer. The dermatological, gastrointestinal, hematological, renal and hepatic toxicities of the treatment were also monitored. As2O3 gel (0.05%) was applied to tumor lesions 1 h prior to delivery of each fraction, with the gel removed about 5 min before the irradiation. Superficial radiation was delivered using an electron beam from a linear accelerator. Every week, the tumor lesions were photographed to evaluate effectiveness, and blood was sampled to monitor changes in hemogram and biochemical profile. Seven breast cancer patients with cutaneous metastasis were enrolled in this study. In terms of tumor, the rates for complete, partial response and stable disease were 42.9 (three of seven), 42.9 (three of seven) and 14.3% (one of seven), respectively. The skin pain, assessed by a visual analog scale, and secretion from all of the seven superficial and fungating wounds decreased markedly after treatment. Significant bone marrow suppression or granulocytosis was not noted. Further, changes in renal and hepatic function were also not significant. It seems reasonable to conclude that As2O3 may be an effective and safe radiosensitizer for palliative radiotherapy for skin-infiltrating lesions of breast cancer.

Adult↗

PubMed2002

Primary thymic carcinoma.

BACKGROUND: Thymic carcinoma is a malignancy of the anterior mediastinum, always with poor prognosis. Up to the present, very few articles have discussed and evaluated either the clinical or pathologic features or treatments of this tumor. Therefore, we are in a position to analyze our research data to support our belief as follows. METHODS: From January 1977 until December 1997, we received 614 patients who were diagnosed with anterior mediastinal tumors. Of the 614 patients, 38 patients (6.2%) were diagnosed with thymic carcinoma, including 26 men and 12 women. Data were collected from clinical records and personal interviews with the patients. Classification of these patients' tumor stages was based on the Masaoka staging system. RESULTS: We proceeded with surgery for 15 of the 38 patients to remove their tumors. Complete resection was done in 8 of these 15 patients (21.0%), whereas debulking was done in the other 7 (18.4%) patients. The mean survival time of all the patients in this study (excluding 3 patients who were lost to follow-up) was 53.0 months, with a median of 24.1 months. The overall cumulative survival rate was 38.6% at 3 years and 27.5% at 5 years. The data in this research show that tumor grading (p = 0.01), resectability (p = 0.02), and stage (p = 0.04) have statistically significant influence on patients' survival. CONCLUSIONS: The grade, stage, and resectability of the tumor are decisive factors of the effectiveness of either surgery or chemo/radiotherapies in the treatment of thymic carcinoma.

Adult↗

PubMed2002

Potential role of tetrandrine in cancer therapy.

Tetrandrine, a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra S Moore, exhibits very broad pharmacological actions, including anti-tumor activity. The beneficial effects of tetrandrine on tumor cell cytotoxicity and radiosensitization, multidrug resistance, normal tissue radioprotection, and angiogenesis are most promising and deserve great attention. Tetrandrine has potential either as a tumoricidal agent or as an adjunct to chemotherapy and radiotherapy. To evaluate the potential clinical efficacy of tetrandrine for cancer therapy, more mechanism-based pharmacological, pharmacokinetic, and pharmacodynamic studies are required.

Alkaloids↗

PubMedDate not supplied

Concurrent cisplatin-based chemoradiation for cervical carcinoma: tumor response, toxicity, and serum cytokine profiles.

PURPOSE: To evaluate the relation between tumor response, treatment toxicity, and serum cytokine profiles in patients with cervical cancer receiving cisplatin-based chemoradiation. PATIENTS AND METHODS: Forty-two patients with cervical carcinoma receiving chemoradiation were recruited. Hemogram, biochemistry profile, cytokine levels, tumor size, and toxicity were assessed weekly. RESULTS: The absolute neutrophil count decreased accompanied by an increase in serum levels of G-CSF during chemoradiation. The sudden elevation of serum TGF-beta 1 and VEGF levels after the first fraction of brachytherapy accompanied with the development of greater radiation therapy (RT) morbidity. Lower pretreatment TGF-beta 1 and VEGF levels are associated with tumor response to chemoradiation. CONCLUSION: The serial changes in serum cytokines during chemoradiation may correlate with tumor regression and treatment morbidity.

Adult↗

PubMedDate not supplied

Post-operative concurrent chemoradiation therapy using oral uracil-tegafur versus weekly intravenous fluorouracil for locally advanced rectal cancer.

BACKGROUND: This prospective, nonrandomized study was conducted to compare the efficacy and toxicity of post-operative concurrent chemoradiation therapy (CCRT) using daily oral uracil-tegafur plus leucovorin (UFUR/LV) vs. weekly intravenous fluorouracil plus leucovorin (5-FU/LV) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: From November 1996 through December 2004, 30 patients with stage II or III rectal cancer were enrolled. Either 5-FU (400 to 450 mg/m2) plus LV (80 to 100 mg/m2) weekly or oral UFUR (250 to 300 mg/m2/d) plus oral LV (30 to 45 mg/m2/d) were given during radiotherapy. Radiation (50.4 to 60.4 Gy) was delivered to the tumor bed in 28-33 fractions. RESULTS: The mean survival, 2-year overall survival and disease-free survival were 36 months vs. 30 months, 68% vs. 66% and 55% vs. 50%, (p > 0.05), in the UFUR/LV and 5-FU/LV groups, respectively. There were no treatment-related deaths or grade 4 toxicity in either group. Grade 3 dermatitis, gastrointestinal and hematologic toxicity were noted in the 5-FU/LV group. CONCLUSION: Because of a similar survival rate and lower toxicity, oral UFUR/LV is suggested as an alternative regimen to intravenous 5-FU/LV in post-operative CCRT of locally advanced rectal cancer.

Adult↗