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Biomedical subjects

C J Chang

Publications and source records attributed to C J Chang.

At least 19 recordsLinked to original sources

Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells.

BACKGROUND: The molecular mechanisms underlying the mitogenic effect of ferulic acid (FA), an active compound derived from Angelica sinensis, have never been elucidated. It was the aim of this study to investigate the proliferative effect of FA on human breast cancer cell lines and to elucidate its modulation mechanism on HER2 expression in MCF7 line. MATERIALS AND METHODS: By using MCF7 (oestrogen receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER-, HER2-low) and SKBR3 (ER-, HER2-high) human breast cancer cell lines as in vitro models, the mitogenic effects of FA were assessed by trypan blue dye exclusion assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2 gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR analysis. RESULTS: Ferulic acid ER-dependently stimulated cell proliferation on MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha; ERalpha) transcription were markedly up-regulated by FA treatment. Besides, HER2 signalling and its downstream molecules such as AKT and ERK1/2 were involved in FA-modulated ERalpha and cyclin D1 synthesis. Addition of anti-HER2 antibody, trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated a positive feedback control for the action of HER2 in this setting. The fact that the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that trastuzumab down-regulated ERalpha gene expression, suggested a cross-talk between ERalpha and HER2 signalling on MCF7 cells. CONCLUSION: The authors' conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression.

Antibodies, Neoplasm↗

Contribution of somatic cell-associated activation of plasminogen to caseinolysis within the goat mammary gland.

Functional regression of the mammary gland is partly reflected by proteolysis of milk protein and tissue protein. The involvement of the plasminogen activation system in degradation of milk protein and mammary tissue damage has been demonstrated under inflammatory conditions. In this study, mammary secretion from 23 dairy goats primarily grouped as lactation (milking twice daily) or involution (milking once daily or less) was used to determine the ratio of gravity-precipitated casein to total milk protein (casein ratio) as an index of caseinolysis, and activities of components of plasminogen activation system as well as their expressions on somatic cells. Based on the casein ratio, lactation goats were subcategorized as very active (71.8 +/- 1.0%) or less active (29.9 +/- 1.0%) in mammary function; involution goats were subcategorized as gradual (21.7 +/- 1.0%) or acute (5.9 +/- 0.2%) involution. This result suggests that caseinolysis occurred during regular lactation as well as during involution. On the other hand, activities of components of the plasminogen activation system in mammary secretion were increased along with the decreasing casein ratio, in contrast to the similar activities of their counterparts in circulation throughout various mammary statuses. Correlation analysis between casein ratio and activities of plasminogen activation system of goat milk indicated a significant negative relationship for plasmin (r = -0.64), plasminogen (r = -0.69), and urokinase-type plasminogen activator (uPA; r = -0.78) during involution but not during lactation. As for the cellular components of plasminogen activation system, there was an increase in immunoreactivity on somatic cells toward both monoclonal antibodies of human uPA and human uPA receptor under involution conditions suggesting their upregulation relative to lactation condition. Collectively, these results suggest that plasminogen activation system within the mammary gland differentially contribute to milk caseinolysis along the various stages of goat lactation. Meanwhile, a somatic cell-mediated local elevation of plasmin activity may be committed to extensive caseinolysis during involution.

Animals↗

Relationship of serum immunoglobulin and IgG subclass levels to race, ethnicity and behavioral characteristics in HIV infection.

BACKGROUND: To determine whether demographic and behavioral factors affect immunoglobulin regulation in HIV infection, we studied injection drug users, women, and minority ethnic and racial groups with and without HIV infection. MATERIAL/METHODS: A prospective cross-sectional study of ambulatory persons with or at risk for HIV infection was conducted. We enrolled 48 injection drug users (IDUs) and 43 non-IDUs seropositive for HIV and 22 seronegative at-risk individuals in the Bronx, New York City. Sixteen HIV-seronegative, non-IDUs controls were also studied. Total serum immunoglobulin levels, IgG subclasses and lymphocyte phenotypes were measured. RESULTS: Serum IgG, IgA, IgG(1) and IgG(3) were increased in all stages of HIV infection controlling for injection drug use, gender, race and age (p0.05). Serum IgM levels were significantly decreased in HIV seropositives compared to HIV seronegatives (p<0.02). Two patterns of serum immunoglobulin level elevation were found in HIV infection: 1) IgG, IgG(1) and IgG(3) levels were elevated in early and advanced HIV infection; 2) IgA, IgG(2) and IgG(4) levels were elevated only in advanced HIV infection. IgG levels were increased in Blacks compared to Caucasians with HIV infection (p=0.01). CONCLUSIONS: Serum IgG, IgG(1) and IgG(3) levels are increased in early HIV infection, while serum IgA, IgG(2), and IgG(3) levels are increased only in advanced HIV infection. In contrast, serum IgM levels are decreased in HIV infection. HIV-seropositive Blacks have higher serum IgG levels than HIV-seropositive Caucasians. Further studies are necessary to determine the mechanism(s) underlying the different patterns of immunoglobulin elevation in HIV infection.

Adult↗

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer.

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

Adult↗

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m(-2), days 1, 8, 15) and cisplatin (90 mg m(-2), day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

Adult↗

Simplified media for spiroplasmas associated with tabanid flies.

Traditionally, isolation, maintenance, and testing of Spiroplasma species (Mollicutes: Entomoplasmatales) from horse flies (Tabanus spp.) and deer flies (Chrysops spp.) (Diptera: Tabanidae) have been accomplished in the complex M1D medium. A relatively inexpensive, simplified medium for tabanid spiroplasmas could expedite procedures that require large quantities of growth medium. Nine strains of spiroplasmas, eight from tabanids and one from mosquitoes, were cultured in three simplified broth media, R2, R8-1, and C-3G, and in M1D. There was no significant difference in the rate of spiroplasma growth in M1D and the three simplified media. R2 medium supported the growth of tabanid spiroplasmas more consistently and with better morphology through 10 subcultures than did the other simplified media. Primary isolations were made in R2 medium from tabanids collected (i) in Georgia, U.S.A., with 10 isolations from 10 flies and (ii) in coastal Costa Rica, with isolation rates of 70% (28/40) and 73% (27/37), respectively, for R2 and M1D. Of the seven group VIII field isolates from Costa Rica, four were capable of sustained growth in R2, and three were triply cloned in this simplified medium. These results suggest that the simplified medium R2 is suitable for many procedures with tabanid spiroplasmas.

Animals↗

Synthesis, topoisomerase I inhibition and antitumor cytotoxicity of 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives.

For the development of new anticancer agents, 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were designed and evaluated for their topoisomerase I inhibitory activity and antitumor cytotoxicity. Structure-activity relationship studies indicated that 2,2':6',2"-terpyridine derivatives were highly cytotoxic toward several human tumor cell lines, whereas 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were potent topoisomerase I inhibitors.

Antineoplastic Agents↗

Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring.

To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence (percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits. Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates were highly correlated (r>.8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r=.43-.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection of nonadherence and should be used in adherence intervention studies.

Adult↗

Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study.

OBJECTIVE: To determine the current status of hyperhomocysteinemia, which is a known risk for venous thrombosis (DVT), in Taiwan. SUBJECTS: 101 unselected patients with a minimum of one episode of deep leg DVT, either initial inpatients or current compliant outpatients in a teaching hospital. METHODS: Various thrombophilic risks, gene polymorphism and clinical predisposition were evaluated. RESULTS AND CONCLUSIONS: Patients presented higher fast total plasma homocysteine (hcy) levels than age- and sex-matched controls did (14.1 vs. 9.94 microM). Based on the 95th percentile of control values, hyperhomocysteinemia had a four- to nine-fold risk for DVT, irrespective of clinical predisposition, as well as other thrombophilic risks surveyed. Polymorphism of a metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), was not associated with DVT, although homozygous thermolabile mutation tended to have higher plasma hcy levels. Factor V Leiden was absent in analysis of 80 patients. In complete evaluation (hcy, antithrombin (AT), protein S (PS), protein C (PC), lupus anticoagulant (LA), anticardiolipin antibody) of a subset of 83 patients hyperhomocysteinemia was the most prevalent risk (33.7%), with PC or PS deficiencies following (22.9%). Thus, hyperhomocysteinemia is a prominent risk for DVT in Taiwan.

Adult↗

Correlation between serum lipid concentrations and psychological distress.

This study examines the correlations between serum lipid levels and psychological distress. There were 4444 consecutive attendees of general health clinics who participated in the study. Psychological symptoms were measured by the Taiwanese version of the Symptoms Check List 90, revised (T-SCL-90-R). Levels of fasting serum lipids, including total cholesterol, total triglycerides and high-density lipoprotein cholesterol (HDL-C), were determined. Multiple linear regression analyses, with adjustment for confounders, revealed that the concentration of HDL-C had significant inverse associations with scores of depression, somatization and phobic anxiety. Women with an HDL-C level lower than 35 mg/dl scored significantly higher on depression, interpersonal sensitivity, phobia, anxiety, somatization and aggressive hostility, while subjects with a total cholesterol concentration lower than 160 mg/dl scored significantly higher on anxiety, aggressive hostility, phobia, and psychoticism. This study provides, for the first time, comprehensive data derived from the Taiwanese population on the link between lipids and psychological symptoms, revealing a reverse correlation between depression and serum concentrations of HDL-C.

Aggression↗

Differential changes in regional bone mineral density in healthy Chinese: age-related and sex-dependent.

To investigate the pattern of age-related and sex-dependent bone mineral density (BMD) changes in the six skeletal regions in healthy Chinese, total-body and regional BMD were measured by dual-energy X-ray absorptiometry (DXA) in 310 women and 387 men aged 20-80 years. In women, a five-phase change was discernible in the axial bones: (1) gradual bone increase from 20-29 years old to maximal BMD at 35-39 years old; (2) maintenance of this level from 35-39 to 40-44; (3) a mild bone decrease from 40-44 to 45-49; (4) a rapid bone decrease from 45-49 to 55-59; and (5) a decelerated bone decrease after 55-59 years old. After validation of menopause status, the decrease of BMD in the late 40s became insignificant in premenopausal women. In appendicular bones, no obvious peak was observed, and significant bone decrease started at 50-54 years old. The overall bone decrease from 35-39 to 70-80 years old was 19.3% for the total body, 16.4% for the head, 29% for the spine, 23% for the pelvis, 18.2% for the ribs, 23.9% for the arms, and 20.4% for the legs. In men, the maximal bone mass was attained at 30-34 and 35-39 years old for axial and appendicular bones, respectively. The age-related bone decrease in the skeletal regions was small, except from 60-64 to 65-69 years old. The overall bone decrease in each region from maximal bone mass to 70-80 years old was 6.7% for the total body, 1.7% for the head, 7.6% for the spine, 11.3% for the pelvis, 9.5% for the ribs, 7.8% for the arms, and 10.4% for the legs. The overall magnitude of reduction in total-body BMD in women was about three times greater than that in men. The pattern of BMD changes differs in each region and is age-related as well as sex-dependent. There appeared to be no significant premenopausal bone decrease.

Absorptiometry, Photon↗

Intraductal laser photocoagulation of the bilateral parotid ducts for reduction of drooling in patients with cerebral palsy.

Patients with cerebral palsy who experience drooling are often isolated from social interaction. Surgical treatment is effective in reducing abnormal, profuse drooling in patients who have low cognitive function, but it has a risk of complications. In this study, a new, simple procedure using laser intervention that minimizes surgical complications is described. Forty-eight patients with cerebral palsy and persistent drooling after more than 6 months of conservative treatment were enrolled in this study. An Nd:YAG laser (1064 nm) was used for intraductal laser photocoagulation of the bilateral parotid ducts at 7 to 10 W for 10 seconds. The outcome was evaluated by questionnaire-based, semiquantitative assessments of drooling severity and frequency, collection and measurement of stimulated saliva, and salivary amylase measurement. The entire procedure was completed in 25 to 65 minutes, with a mean duration of 38.4 minutes. Early complications included transient facial swelling in all patients. Swelling persisted for 6 to 37 days (mean, 11 days). One hematoma (2.1 percent of patients), two infections (4.2 percent of patients), and two cystic formations (4.2 percent of patients) also occurred. No obvious xerostomia or visible scar was noted after the procedure. In the final assessment, a significant improvement in drooling severity (p < 0.05) and frequency (p < 0.05) was noted in the majority of cases. Forty patients (83.3 percent) demonstrated remarkable improvement in drooling severity, seven patients (14.6 percent) showed significant improvement, and one patient (2.1 percent), who was also autistic, continued to experience severe drooling after the laser procedure. The decrease in the amount of saliva produced ranged from 20 to 60 percent at 12 weeks after surgery. The decrease in the amount of salivary amylase measured ranged from 4 to 97 percent at 12 weeks after surgery (p < 0.05). In conclusion, the intraductal laser photocoagulation of bilateral parotid ducts is a simple, effective procedure for reducing drooling in patients who have cerebral palsy. This procedure minimizes risks and complications, compared with those associated with conventional surgery.

Adolescent↗

Meta-analysis of effectiveness and safety of abciximab versus eptifibatide or tirofiban in percutaneous coronary intervention.

Three platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been evaluated in patients undergoing percutaneous coronary intervention (PCI). One of these agents, abciximab, is structurally and pharmacologically quite different from the other 2, eptifibatide and tirofiban. We conducted a meta-analysis to determine whether different antagonist types achieved different clinical outcomes, possibly related to their structural differences. Odds ratios (OR) were calculated and a random effects model was used to combine the outcomes of 14,644 patients enrolled in 8 prospective, randomized, placebo-controlled clinical trials assessing treatment with a GP IIb/IIIa inhibitor to prevent ischemic complications of PCI. Neither abciximab (OR 0.69; 95% confidence interval [CI] 0.4 to 1.9) nor eptifibatide or tirofiban treatment (OR 0.74; 95% CI 0.4 to 1.28) resulted in reductions in mortality. Only the abciximab-treated patients had reductions in myocardial infarction (4.3% vs 8.5%, OR 0.49; 95% CI 0.40 to 0.59). There was no effect of eptifibatide or tirofiban on myocardial infarction (OR 0.85; 95% CI 0.69 to 1.04). Urgent revascularization was reduced in both abciximab-treated (2.7% vs 6.2%, OR 0.42; 95% CI 0.34 to 0.53) and eptifibatide- and tirofiban-treated (4.2% vs 5.5%, OR 0.76; 95% CI 0.60 to 0.96) groups. Only abciximab-treated patients had increased major bleeding (5.8% vs 3.8%; OR 1.53; 95% CI 1.24 to 1.90). There was no effect of eptifibatide or tirofiban on major bleeding (5.0% vs 4.3%; OR 1.19; 95% CI 0.94 to 1.52). Thus, significant differences exist between clinical outcomes achieved by abciximab and those achieved by eptifibatide or tirofiban following PCl procedures.

Abciximab↗

Prevalence and predictive value of overweight in an urban HIV care clinic.

OBJECTIVE: To determine the prevalence and predictive value of overweight in an urban HIV clinic. METHODS: Medical records of all new adult, nonpregnant registrants in 1996 in an urban HIV clinic with at least one height and weight measurement were reviewed. Body mass index (BMI) at clinic enrollment was calculated, and prevalence of overweight was thus determined. The subsequent clinical course of the overweight group was compared with that of a randomly selected group of gender-stratified non-overweight patients. RESULTS: At baseline, 12.6% of men and 32.5% of women were overweight. Female gender and lack of AIDS diagnosis were independently associated with overweight. More than one half of women and 19.6% of men were overweight at some point during the study. Providers were more likely to properly acknowledge underweight than overweight. Among patients without AIDS, there was a trend toward slower disease progression and lower viral load in overweight patients, despite similar baseline CD4+ lymphocyte counts and similar time to initiation of highly active antiretroviral therapy. In multivariate proportional hazards analyses, lower baseline BMI and falling BMI during follow-up were independently predictive of progression to AIDS. CONCLUSIONS: Overweight was a common and underrecognized finding, particularly among women. Overweight patients may progress more slowly to AIDS than non-overweight patients.

Adult↗

Using data mining to address heterogeneity in the Southampton data.

When analyzing complex traits such as asthma, heterogeneity needs to be assumed. With this in mind, to identify a more homogeneous group of asthmatic patients, we analyzed the Southampton data using the data mining technique known as the regression tree method and the two most inheritable quantitative phenotypes (LnIgE and RAST) as the target variables. Two-point and multipoint nonparametric linkage analyses were carried out using one of the subgroups as affected. In addition, we performed quantitative trait loci nonparametric linkage analysis using each phenotype as the outcome. The results from the affected-sibpairs method and quantitative linkage analysis were compared.

Adult↗

Detection of putative periodontal pathogens in non-insulin-dependent diabetes mellitus and non-diabetes mellitus by polymerase chain reaction.

It has been assumed that there is a relationship between periodontal diseases and diabetes mellitus, however the putative periodontal microorganisms in non-diabetes mellitus (non-DM) individuals and non-insulin-dependent diabetes mellitus (NIDDM) patients have not been well studied. In this study, the detection rates of 5 putative periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Treponema denticola, and Candida albicans by polymerase chain reaction (PCR) between NIDDM and non-DM adults were compared. A total of 246 adults were randomly recruited and periodontal parameters including: plaque index (P1I), gingival index (GI), probing depth (PD) and attachment level (AL) were recorded. Subgingival plaque samples were collected by sterile curettes from the most diseased and healthy sites based on PD and AL. The differences in periodontal parameters and microbiological data in healthy and diseased sites between non-DM and NIDDM patients were compared by chi-square analysis. The results showed no significant differences in age, gender, GI, P1I, PD, and prevalence of the 5 microorganisms between the NIDDM and the non-diabetic groups. However, except for A. actinomycetemcomitans, the prevalence of the periodontal microorganisms tested was significantly higher (p <0.001) in diseased sites than in the healthy sites in both groups. The P1I, GI, PD and AL were significantly higher in T. denticola positive sites than in negative sites. The results suggested that P. gingivalis, T. denticola, E. corrodens and C. albicans may play important roles in the periodontitis of both NIDDM and non-DM individuals, however the etiology of periodontitis in both groups may not be different from each other.

Adult↗