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C J Wang

Publications and source records attributed to C J Wang.

At least 73 records · Page 4Linked to original sources

Specific induction of glutathione S-transferase GSTM2 subunit expression by epigallocatechin gallate in rat liver.

The antitumor effect of green tea polyphenols has been well characterized in numerous papers. However, the mechanism of their action is still poorly defined. In this study, epigallocatechin gallate (EGCG), the main ingredient of green tea extract, was studied for its effect on the expression of glutathione S-transferases (GSTs) in rat liver to examine the mechanism of action. Liver samples were collected from Sprague-Dawley rats treated with EGCG in H(2)O by portal vein perfusion and examined for total GST activity and GST expression. The results showed that the induction of GST activity by EGCG was dose- and time-dependent. GST activity was increased about 28-fold at 12 hr after treatment. Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for changes in protein level affected by EGCG (1 mg/kg weight). Only GSTM2 revealed a significant time-dependent increase, with a maximal induction of approximately 2.0-fold. The differential effect of EGCG on GST subunit expression was also verified by immunocytochemical examination and showed strong induction of the GSTM2 (but not the GSTA1/2 and GSTM1) level in liver section. This induction occurred as early as 3 hr after treatment and extended gradually outward from the hepatic veins as treatment time increased. The change in the GSTM2 protein level was accompanied by a corresponding alteration in mRNA quantity ( approximately 2.0-fold of control). Our report is the first to demonstrate a specific induction of the GSTM2 subunit by a chemopreventor and suggests a primary influence of EGCG on GSTM2 gene expression.

Animals↗

Induction of apoptosis by hibiscus protocatechuic acid in human leukemia cells via reduction of retinoblastoma (RB) phosphorylation and Bcl-2 expression.

Hibiscus protocatechuic acid (PCA), a phenolic compound isolated from the dried flower of Hibiscus sabdariffa L. (Malvaceae), demonstrated antioxidant and antitumor promotion effects in our previous study. In the present study, Hibiscus PCA was found to inhibit the survival of human promyelocytic leukemia HL-60 cells in a concentration- and time-dependent manner. The study revealed that HL-60 cells underwent internucleosomal DNA fragmentation and morphological changes characteristic of apoptosis after a 9-hr treatment with Hibiscus PCA (2 mM). Flow cytometric analysis of the DNA content of cells treated with PCA for 12 hr showed that the cells were distributed mainly in the hypodiploid phase (apoptotic peak, 46.7%), less in the G(1) (34.2%) and S phase (14.0%), and few in the G(2)/M phase (5.1%). Moreover, PCA treatment caused an increase in the level of hypophosphorylated retinoblastoma (RB; 180% of control at the 6-hr time point) and, on the contrary, a decline in hyperphosphorylated RB. A rapid loss of RB was observed when the treatment period was extended. Further studies showed that Hibiscus PCA application reduced Bcl-2 protein expression to 47%, and increased Bax protein expression to 181% after 1.5 hr as compared with time 0. Overexpression of Bcl-2 in HL-60 cells delayed the occurrence of Hibiscus PCA-induced apoptosis. These data suggest that Hibiscus PCA is an apoptosis inducer in human leukemia cells, and that RB phosphorylation and Bcl-2 protein may play a crucial role in the early stage.

Antineoplastic Agents↗

Tumor promotion of N-nitroso-N-(3-keto-1, 2-butanediol)-3'-nitrotyramine derived from nitrosation of Maillard reaction product in CD-1 mice.

N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of a model browning system generated in the presence of sodium nitrite. Our previous study showed that NO-NTA had genotoxicity and proved to be an initiator and promoter on mouse C3H10T1/2 cells. In this study, a two-stage skin carcinogenesis protocol was used to promote CD-1 mouse skin carcinogenesis using NO-NTA. Twice weekly, for 38 weeks, topical application of NO-NTA at the concentration of 250 nmol to mice previously initiated with benzo(a)pyrene (BaP) caused 90% tumor incidence. However, no tumors were observed in mice treated with BaP or treated with NO-NTA alone. The NO-NTA-promoted tumors that were observed histologically in mice showed well-differentiated squamous cell carcinoma with invasion into the subcutaneous region. Application of the same amount of NO-NTA not only caused significant induction of hyperplasia but also epidermal ornithine decarboxylase (ODC) activity. Treatment of mouse skin (1 cm(2)) with various amounts of NO-NTA (10, 50, or 250 nmol) caused production of hydrogen peroxide by 1.63-, 1.91-, and 2. 38-fold, respectively, and marked induction of myeloperoxidase (MPO) by 21-, 39-, and 61-fold. These results indicate that NO-NTA is a new tumor promoter and may induce tumor promotion by oxidant stress in CD-1 mouse skin.

Animals↗

Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study.

PURPOSE: The radiation therapy results for patients with inoperable non-small-cell lung cancer (NSCLC) have been disappointing. Tumor dose escalation using concomitant boost technique (CBT) has been shown to improve local control in a few prospective studies. This trial was carried out to prospectively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique (CTT). METHODS AND MATERIALS: Ninety-seven consecutive eligible patients were entered in this prospective clinical trial between November 1994 and February 1998. Patients were randomized to receive either CBT (43 patients) or CTT (54 patients) radiation therapy. These patients either refused chemotherapy or were judged as unsuitable for chemotherapy. Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease. A concomitant boost of 18.2 Gy (0.7 Gy per fraction) was delivered to the gross disease using small fields with 1.5-cm margins. The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions. Patients in the CTT group received 70.8 Gy in 38 fractions. The acute toxicity between each group was compared. The response rate was analyzed and compared by treatment group, gender, age, stage, histology, initial Karnofsky performance score (KPS), severity of acute toxicity, and maximum body weight loss (MBWL) during treatment course. RESULTS: The demographic parameters such as sex, age, and stage were evenly distributed in each treatment group. The majority of these patients had Stage IIIA and IIIB disease. Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group. No treatment-related mortality was found. There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity, and no Grade 3 lung or esophageal toxicity was observed in CBT group. The response rates, assessed by radiographic images, were 69.8% and 48.1% for the CBT and CTT patients, respectively. Univariate and multivariate analysis revealed that patients in the CBT group, patients with better KPS, and patients with more severe acute toxicity had a higher response rate. CONCLUSION: This study demonstrates that concomitant boost radiation therapy is tolerable, and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC. The length of treatment was reduced from 38 to 26 treatment days, almost a 30% reduction.

Adult↗

Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial.

PURPOSE: To evaluate the influence of oral glutamine on radiation-induced oral mucositis in the radiotherapy of head and neck cancer. METHODS AND MATERIALS: From July 1997 through June 1998, 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) (n = 8) or placebo (normal saline) (n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. All patients received half-mouth irradiation at least. Patients were treated 1.8 Gy per fraction daily, 5 days a week. We evaluated the grading of oral mucositis daily fraction at each day of treatment until 45 Gy/25 fractions. World Health Organization (WHO) step analgesic medication and body weight change were compared between the two arms. RESULTS: The duration of objective oral mucositis > or = Grade 1 (p = 0.0097), Grade 2 (p = 0.0232), and Grade 3 (p = 0.0168) was shorter in the glutamine arm. Mean maximum grade of objective oral mucositis was less severe in the glutamine arm (1.6 vs. 2.6) (p = 0.0058). Glutamine did not reduce the duration and severity of subjective oral mucositis except for duration > or = Grade 3 (p = 0.0386). In the analysis of mean maximum WHO step of analgesic medication, there was no statistical difference (p = 0.5374) between the two arms. Mean body weight change was also not significantly different (p = 0.8070). CONCLUSIONS: Oral glutamine may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. It may shorten the duration of > or = Grade 3 subjective mucositis.

Administration, Oral↗

Development of brain injury in mice by Angiostrongylus cantonensis infection is associated with the induction of transcription factor NF-kappaB, nuclear protooncogenes, and protein tyrosine phosphorylation.

Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we showed that A. cantonensis-caused eosinoplia and inflammation might lead to the induction of NF-kappaB and protooncogene expression via activation of the tyrosine phosphorylation signal pathway. After mice were infected daily with 30 third-stage larvae of A. cantonensis by oral adminstration for 6 weeks, no significant differences PKC-alpha, MEK-1, ERK-2, JNK, and p38 protein expression were found between the control and infected mice. However, the protein tyrosine phosphorylation levels, NF-kappaB, and iNOS protein products were significantly increased by 3.5-, 3.3-, and 6.3-fold, respectively, after 3 weeks of A. cantonensis infection. The same pattern was found for c-Myc, c-Jun, and c-Fos proteins, which were elevated by 3.2-, 2.3-, and 3.4-fold, respectively, compared to control animals after 3 weeks. The expression potency of these proteins started increasing in week 1, reaching maximal induction in week 3, and then declining in week 5 after A. cantonensis infection. Another consistent result was noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in brain tissues of infected mice. These data suggest that the development of brain injury by eosinophlia of A. cantonensis infection is associated with NF-kappaB and/or nuclear protooncogenes expression, which is activated by the tyrosine phosphorylation pathway.

Angiostrongylus cantonensis↗

High external parametrial dose can increase the probability of radiation proctitis in patients with uterine cervix cancer.

OBJECTIVE: The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer. METHODS: From May 1993 through December 1996, 191 patients with stage IB-IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44-45 Gy/ 22-25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4-14.4 Gy/ 3-8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2-24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44-45, 50-54, and >54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups. RESULTS: Three-year overall and Grade 2-4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P < 0.0001), respectively. Grade 2-4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2-4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively). CONCLUSION: Regardless of central shielding after 44-45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.

Adult↗

Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver.

Increasing evidence regarding free radical-generating agents and inflammatory processes suggests that accumulation of reactive oxygen species can cause hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydroperoxide (t-BHP), can be metabolized to free radical intermediates by cytochrome P-450 in hepatocytes, which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. In this study, we used t-BHP to induce hepatotoxicity in vitro and in vivo and determined the antioxidative bioactivity of esculetin, a coumarin compound. Our investigations showed that pretreatment with esculetin (5-20 microg/ml) significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT), and also decreased the formation of malondialdehyde (MDA) in primary cultured rat hepatocytes induced by a 30-min treatment with t-BHP. An in vivo study in rats showed that pretreatment with esculetin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that esculetin reduced the incidence of liver lesions induced by t-BHP, including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that esculetin may play a chemopreventive role via reducing oxidative stress in living systems.

Animals↗

Posterior cruciate ligament and coupled posterolateral instability of the knee.

We wanted to investigate the role of the posterior cruciate ligament (PCL) in the knee's posterolateral stability and the magnitude of the coupled posterolateral instability with the knee examined at 90 degrees of flexion. The coupled posterolateral instability of the knee was studied by selective ligament cutting in cadaver knees set at 90 degrees. The coupled posterolateral displacement after cutting the PCL was 173% of the intact knee. With an intact PCL, the coupled posterolateral displacement after cutting the popliteus tendon and lateral collateral ligament with the knee at 90 degrees of flexion was 299% of the intact knee. When the PCL was cut together with the popliteus tendon and lateral collateral ligament, the coupled posterolateral displacement was 367%. The PCL plays an important role in the posterolateral stability of the knee, and its injury may cause mild (< 5 mm) to moderate (5-10 mm) posterolateral instability. Thus, in a knee with posterolateral instability, injury of the PCL must be considered. With an intact PCL, the posterolateral instability was very recognizable with the knee at 90 degrees of flexion, and injury to the PCL further increased the posterolateral instability and caused posterior translation of the knee. Therefore, examination for posterolateral instability of the knee should also be performed with the knee at 90 degrees of flexion, which is much easier to perform in a clinical setting. A positive posterior translation rather than posterolateral instability at different knee positions differentiates knees with combined PCL and posterolateral instability from knees with isolated posterolateral instability.

Cadaver↗

Healing of superior vena cava defect in mediastinal seminoma with invasion.

We present an unusual case of mediastinal seminoma with direct intraluminal invasion into the superior vena cava (SVC) and extension to the right atrium. Magnetic resonance imaging demonstration of the SVC defect due to tumor invasion was important for determining treatment strategy because rapid posttherapeutic tumor regression may increase the risk of SVC rupture. Gradual healing of the SVC defect at the tumor entrance site was attained using a tailored treatment plan with radiotherapy and chemotherapy.

Adolescent↗

Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors.

BACKGROUND AND PURPOSE: To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. MATERIALS AND METHODS: From July 1987 through July 1994, 109 women with stage II and III breast cancer receiving modified radical mastectomies were managed by postoperative electron beam irradiation. Doses of 46 to 50.4 Gy were delivered to the chest wall covered with bolus, internal mammary nodes, supraclavicular nodes and axillary lymph nodes via 12 or 15 MeV single portal electron beam. Seventeen patients received additional 10-16 Gy surgical scar boost via 9 MeV electron beam. Comparison of pre-treatment and post-treatment chest X-ray films were used to monitor the development of pulmonary fibrosis. RESULTS: Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. CONCLUSIONS: In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis.

Adult↗

Dermatofibrosarcoma protuberans: treatment results of 35 cases.

BACKGROUND AND PURPOSE: This study evaluates the treatment results of patients with dermatofibrosarcoma protuberans. PATIENTS AND METHODS: Between August 1987 and July 1998, 35 consecutive patients with pathologically proved dermatofibrosarcoma protuberans received surgery with or without radiation therapy. Their treatment results were analyzed retrospectively. RESULTS: The patient ages ranged from 5 to 67 years (median 37 years). There were 24 males and 11 females. The anatomic sites of tumor were: trunk in 21, extremity in eight, and head and neck region in six. The maximal dimension of tumor ranged from 1.5 to 25 cm. Surgery techniques included local excision and wide excision with or without graft or flap. Adjuvant radiation therapy was given to 11 patients, with a dose ranging from 46 to 68 Gy (one pre-operative, ten post-operative). At a median follow-up of 50 months (range 11-131 months), there were 11 patients (nine patients without radiation therapy) who developed local failure. Salvage therapy (excision with or without radiation therapy) was given to all of them, and ten achieved disease control. Some patients had treatment-related moderate cosmetic or functional problems. CONCLUSIONS: Dermatofibrosarcoma protuberans is a malignancy of a high cure rate, and adjuvant radiation therapy can reliably decrease the local recurrence rate and prevent mutilation and functional deficit caused by repeated surgery.

Adolescent↗

Protective effect of Hibiscus anthocyanins against tert-butyl hydroperoxide-induced hepatic toxicity in rats.

Hibiscus anthocyanins (HAs), a group of natural pigments occurring in the dried flowers of Hibiscus sabdariffa L., which is a local soft drink material and medical herb, were studied for antioxidant bioactivity. The preliminary study showed that HAs were able to quench the free radicals of 1,1-diphenyl-2-picrylhydrazyl. This antioxidant bioactivitiy was further evaluated using the model of tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats. The results demonstrated that HAs, at the concentrations of 0.10 and 0.20 mg/ml, significantly decreased the leakage of lactate dehydrogenase and the formation of malondialdehyde induced by a 30-min treatment of t-BHP (1.5 mM). The in vivo investigation showed that the oral pretreatment of HAs (100 and 200 mg/kg) for 5 days before a single dose of t-BHP (0.2 mmol/kg, ip) significantly lowered the serum levels of hepatic enzyme markers (alanine and aspartate aminotransferase) and reduced oxidative liver damage. The histopathological evaluation of the liver revealed that Hibiscus pigments reduced the incidence of liver lesions including inflammatory, leucocyte infiltration, and necrosis induced by t-BHP in rats. Based on the results described above, we speculate that Hibiscus pigments may play a role in the prevention of oxidative damage in living systems.

Alanine Transaminase↗

Early catastrophic failure of rotating hinge total knee prosthesis.

The mechanical failure of a prosthesis component is usually observed as a late complication of total knee arthroplasty (TKA). In knees with severe ligament instability and bone deficiency, either a true hinge prosthesis or a rotating hinge implant is commonly used. Failure of the polyethylene bearing bush in a hinge-type prosthesis is a complication that has not been reported to date. We report the cases of 2 rotating hinge TKA prostheses that dislocated as a result of mechanical failure of the prosthetic component within 5 months of initial implantation. Clinicians should be aware of this potential complication when selecting rotating hinge prostheses for certain patients.

Arthroplasty, Replacement, Knee↗

Radical laparoscopic surgery for carcinoma of the cervical stump.

Traditionally, most women with cervical stump cancer underwent radiation therapy, as radical surgery was considered difficult. Given our success performing laparoscopic-assisted radical vaginal hysterectomy, we modified that technique to treat two women with carcinoma of the cervical stump. At follow-up of 14 and 17 months, respectively, both patients were free of recurrence.

Adenocarcinoma↗

Laparoscopic-assisted vaginal myomectomy.

STUDY OBJECTIVE: To evaluate the safety and efficacy of combined laparoscopic and vaginal approach in dealing with uterine myomas. DESIGN: Retrospective case study (Canadian Task Force classification II-2). SETTING: Tertiary care major teaching hospital. PATIENTS: Thirty-one women with symptomatic fundal and/or posterior wall uterine myomas. INTERVENTION: Laparoscopic-assisted vaginal myomectomy performed by one of the authors from July 1996 to December 1998. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD operating time, blood loss, and length of hospital stay were 79.19+/-18.31 minutes, 150.00+/- 103.28 ml, and 3.10+/-0.75 days, respectively. No patients developed serious complications, and only two minor complications occurred. CONCLUSION: After laparoscopic inspection and location of uterine myomas, dealing with posterior and fundal uterine myomas by the vaginal route makes hemostasis and uterine repair easier than by purely laparoscopic approach.

Adult↗

Intramedullary femoral nails: one or two lag screws? A preliminary study.

Failures of proximal femoral nails that treat unstable femoral fractures have been reported. In this communication, a finite element model to include a proximal femoral nail within a fractured femur was used to carry out preliminary investigations into configurations of single or double lag screws. The effects of the different types of fracture were investigated. The results show that in order to share the load evenly between two lag screws, a good configuration seems to be to have a slightly larger screw above the lower screw. This also ameliorates stresses in the nail at the lag screw insertion holes. However, using two screws in this way can lead to large stresses in the cancellous bone in the femoral head, and these stresses may be significant in the initiation of cut-out.

Bone Screws↗