Biomedical subjects

K K Chan

Publications and source records attributed to K K Chan.

At least 19 recordsLinked to original sources

PubMed2006

Testing for ovarian cancer.

Ovarian cancer is responsible for more deaths per annum than cervical and endometrial cancer combined. Patients are often diagnosed at a late stage because of the non-specific symptoms of this disease. It can be difficult to differentiate between benign and malignant ovarian pathology, and a malignancy risk index has been developed to guide clinicians. The accuracy of CA125 and ultrasound scans as screening tests is being assessed in randomised controlled trials and proteomic technology shows promise for the early detection of cancers. At present, without accurate screening and early diagnostic techniques, high-risk patients often chose to have prophylactic surgery.

Carcinoma↗

PubMed2006

Suicide in Hong Kong: a case-control psychological autopsy study.

BACKGROUND: The relative contribution of psychosocial and clinical risk factors to suicide among Chinese populations is an important issue. In Hong Kong, this issue requires vigorous examination in light of a 50% increase in suicide rate between 1997 and 2003. METHOD: Using a case-control psychological autopsy method, 150 suicide deceased were compared with 150 living controls matched by age and gender. Semi-structured interviews were conducted with the next-of-kin of the subjects. Data were collected on a wide range of potential risk and protective factors, including demographic, life event, clinical and psychological variables. The relative contribution of these factors towards suicide was examined in a multiple logistic regression model. RESULTS: Six factors were found to significantly and independently contribute to suicide: unemployment, indebtedness, being single, social support, psychiatric illness, and history of past attempts. CONCLUSIONS: Both psychosocial and clinical factors are important in suicides in Hong Kong. They seem to have mediated suicide risk independently. In addition, socio-economic adversities seem to have played a relatively important role in the increasing suicide rate in Hong Kong.

Adolescent↗

PubMed2006

Stereoselectivity in metabolism of ifosfamide by CYP3A4 and CYP2B6.

The aim was to identify the hepatic cytochromes P450 (CYPs) responsible for the enantioselective metabolism of ifosfamide (IFA). The 4-hydroxylation, N2- and N3-dechloroethylation of IFA enantiomers were monitored simultaneously in the same metabolic systems using GC/MS and pseudoracemate techniques. In human and rat liver microsomes, (R)-IFA was preferentially metabolized via 4-hydroxylation, whereas its antipode was biotransformed in favour of N-dechloroethylation. CYP3A4 was the major enzyme responsible for metabolism of IFA enantiomers in human liver. The study also revealed that CYP3A (human CYP3A4/5 and rat CYP3A1/2) and CYP2B (human CYP2B6 and rat CYP2B1/2) enantioselectively mediated the 4-hydroxylation, N2- and N3-dechloroethylation of IFA. CYP3A preferentially supported the formation of (R)-4-hydroxyIFA (HOIF), (R)-N2-dechloroethylIFA (N2D) and (R)-N3-dechloroethylIFA (N3D), whereas CYP2B preferentially mediated the generation of (S)-HOIF, (S)-N2D and (S)-N3D. The enantioselective metabolism of IFA by CYP3A4 and CYP2B1 was confirmed in cDNA transfected V79 cells.

Animals↗

PubMed2006

Enantiomer-enantiomer interaction of ifosfamide in the rat.

The objective of this study was to study the enantiomer-enantiomer interaction of ifosfamide (IFA) in a rat model. Following intravenous administration of individual IFA enantiomers or pseudo-racemates to male Sprague-Dawley rats, two enantiomers and their metabolites, 4-hydroxyIF (HOIF), N2-dechloroethylIF (N2D), N3-dechloroethylIF (N3D), and isophosphoramide (IPM), were quantified using gas chromatography/mass spectrometry (GC/MS) and isotope dilution techniques. In addition, the mutual inhibition in the metabolism between two stereoisomers was also investigated in vitro using rat liver microsomes. Pharmacokinetic parameters were similar between (R)-IFA and (S)-IFA when individual enantiomers were intravenously administered to rats separately. However, in the rats administered with the IFA racemate, half-life, mean residence time (MRT), and area under the concentration-time curve (AUC) values of (S)-IFA were significantly increased with total body clearance (CLT) being decreased. No significant difference in volumes of distribution (Vss), and renal clearance (CLr) and blood cell partition was observed between two enantiomers regardless of (R)-IFA and (S)-IFA being administered separately or in combination as a racemate. The results from the in vitro metabolism and inhibition experiment suggested that each IFA enantiomer inhibited the metabolism of its antipode in a competitive manner. It is concluded that the enantiomeric interaction of IFA mainly occurred in the process of metabolism with (S)-IFA being affected to a larger extent.

Animals↗

PubMed2006

Feasibility of transradial coronary angiography and angioplasty in Chinese patients.

OBJECTIVE: To assess the clinical applicability, efficacy, and safety of coronary angiography and angioplasty via a transradial approach in local Chinese patients. DESIGN: Prospective case series. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients undergoing coronary angiography and coronary angioplasty between 1 January and 30 June 2004. INTERVENTIONS: Transradial coronary angiography and coronary angioplasty. MAIN OUTCOME MEASURES: Feasibility, success rate, and complications. RESULTS: A total of 268 coronary angiographies (62% of all coronary angiographies) and 118 coronary angioplasties (48% of all coronary angioplasties) were performed via a transradial approach. The procedural success rate for coronary angiography was 93.7% with a mean duration of 21.8 (standard deviation, 13.5) minutes compared with 17.9 (10.0) minutes for angiography via a femoral approach. Most (99%) patients were free from any complications. Of those patients who underwent elective transradial coronary angiography in the morning, 64% were discharged on the same day. Comparison of data in the first half of the study period with those in the second half revealed a significant increase in the percentage of coronary angiographies performed via a transradial approach (from 52% to 73%, P<0.0001), and an improved procedural success rate (from 91.5% to 95.3%, P=0.1). For transradial coronary angioplasty, the procedural success rate was 98%. A total of 246 lesions (2.08 lesions per patient) were treated with no procedure-related complications. CONCLUSIONS: Transradial coronary angiography and angioplasty are feasible in a significant proportion of local Chinese patients and achieve a high success rate and low complication rate. It tends to prolong procedural duration, but improves patients' comfort and permits earlier ambulation and discharge. The procedural success rate improves with accumulating experience.

Aged↗

PubMed2006

Malaysian mosquitocidal soil bacterium (Bacillus thuringiensis) strains with selective hemolytic and lectin activity against human and rat erythrocytes.

The objective of this study is to determine the role of carbohydrates on the toxic effect of parasporal inclusion proteins isolated from Malaysian mosquitocidal Bacillus thuringiensis (Bt) strains on erythrocytes (human and rat). Dose response analyses on the effect of these parasporal inclusions on human and rat erythrocytes suggest that toxin action is selective depending on bacterial strains and source of erythrocytes. Results from this study suggest Bt toxin is a lectin which recognizes specific plasma membrane glycoconjugate receptor(s) with a terminal residue of either D-mannose (Man), N-acetyl-D-galactosamine (GalNAc), N-acetyl-D-glucosamine (GlcNAc) or even a combination of these monosaccharides.

Animals↗

PubMed2005

Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic stellate cell.

Hepatic stellate cells (HSC) play a central role in hepatic fibrosis and compounds that promote apoptosis in HSC may have anti-fibrotic potentials. Herbal medicine has long been used in chronic liver disease but there is little scientific evidence for their actions. The present study investigated the effects of 14 commonly used herbs on cellular proliferation and apoptosis of a rat hepatic stellate cell line, HSC-T6 and the underlying mechanism of herb-induced apoptosis. HSC-T6 cell were incubated with herbal extracts and their proliferation was assessed by colorimetric assay. Apoptosis was measured and confirmed by flow cytometry, terminal transferase uridyl nick end labeling (TUNEL) assay and morphological features in hematoxylin and eosin staining. Apoptotic pathways involving Fas receptor and Bcl-2 family were investigated by Western blot. Five herbs, namely Angelica sinensis (AS), Carthamus tinctorius (CT), Ligusticum chuanxiong (LC), Salvia miltiorrhiza (SM) and Stephania tetrandra (ST) demonstrated both anti-proliferative and pro-apoptotic activities in HSC-T6. The highest potency was detected in SM and ST with 51.63 and 44.52% of HSC-T6 showing apoptotic changes, respectively. This was associated with upregulation of Fas and Bax and down-regulation of Bcl-xL in HSC. Fas ligand and Bcl2 expressions remained unchanged. The potential anti-fibrotic effect of herbal medicine warrants further evaluation.

Animals↗

PubMed2005

Pregnancy following recurrent angiosarcoma of the ovary--a case report and review of literature.

BACKGROUND: Ovarian angiosarcomas are rare tumors which may to be distinguished from other unusual primary ovarian tumors such as clear cell carcinoma, yolk sac tumor and leiomyosarcoma on the basis of histological appearance and immunohistochemistry. Angiosarcomas of the ovary occur in all age groups but are more frequent in women of child bearing age (less than 40 years). Surgery and radiotherapy have been the traditional treatment modalities. CASE: The case we present is the only reported long-term survivor of recurrent ovarian angiosarcoma. Her initial treatment was surgical, both at presentation and relapse but since she wished conservation of fertility, radical surgery and radiotherapy were avoided and she underwent further adjuvant chemotherapy with doxorubicin and ifosfamide. She remains in remission 6 years after treatment of recurrence of the primary tumor and has had a successful pregnancy following treatment. CONCLUSION: Adjuvant chemotherapy of ovarian angiosarcoma with a combination of doxorubicin and ifosfamide appears effective and should be considered in women at risk of relapse who wish to conserve fertility.

Adult↗

PubMed2005

A phase I clinical and pharmacokinetic study of fenretinide combined with paclitaxel and cisplatin for refractory solid tumors.

BACKGROUND: Fenretinide is a semi-synthetic retinoid that has pro-apoptotic effects as a single agent and synergistically with chemotherapy in vitro. We performed this study to determine the toxicity of cisplatin, paclitaxel and fenretinide in patients with advanced cancer, the recommended phase II dose of these agents together, and the pharmacokinetics (PK) of fenretinide when administered with chemotherapy. PATIENTS AND METHODS: Fourteen patients (mean age 57.3) were assessable for pharmacokinetics, toxicity and response. Fenretinide was given orally in 2 divided daily doses for 7 days, starting 24 hours prior to cisplatin and paclitaxel. Cisplatin and paclitaxel were given in standard fashion. Cycles were repeated every 3 weeks. Cycle one fenretinide PK was obtained on days 2 and 8. RESULTS: Dose limiting toxicity (Gr 3 diarrhea and Gr 4 neutropenia) was encountered in two patients during cycle one at 80/175/1,800 mg/m(2) of cisplatin/paclitaxel/fenretinide (dose level 2), respectively. Seven patients received 2-8 cycles at the recommended level of 60/135/1,800 (dose level 1). Severe cumulative toxicities included fatigue, nausea/vomiting, neuropathy, and dehydration. Two patients had a partial response and 4 patients had stable disease for up to 8 cycles. PK analysis demonstrated a reduction in fenretinide Cmax on day 8 compared to day 2, accompanying a decrease in AUC. CONCLUSIONS: Cisplatin/paclitaxel/fenretinide can be administered safely at 60/135/1,800 mg/m(2) respectively on an every three-week schedule. This combination may have activity in a variety of tumors, however, the number of pills required complicates oral dosing of fenretinide, and limits the applicability of this regimen.

Administration, Oral↗

PubMed2005

Phe-Gly-Leu-amide allatostatin in the termite Reticulitermes flavipes: content in brain and corpus allatum and effect on juvenile hormone synthesis.

In the subterranean termite Reticulitermes flavipes, allatostatins (ASTs) with the C-terminus Phe-Gly Leu-amide were localized by immunocytochemistry with antibody against a cockroach AST, Dippu AST-7. AST-immunoreactivity occurred in the corpus cardiacum and corpus allatum and in the lateral and medial neurosecretory cells of the brain that innervate these organs as well as in many other nerve cells of the brain. This was observed in workers, nymphs, soldiers and secondary reproductives. A radioimmunoassay, using anti-Dippu AST-11, demonstrated about 40 fmole equivalents of AST in brains of soldiers and secondary reproductives. The product of the corpora allata in this species was determined to be juvenile hormone III. Its synthesis by corpora allata of secondary reproductives, determined by in vitro radiochemical assay, was inhibited in a dose-dependent fashion by two cockroach allatostatins, Dippu AST-7 and Dippu AST-11. Thus, as in cockroaches and crickets, allatostatin-containing nerves innervate the corpora allata of this termite species and their production of juvenile hormone is inhibited by these neuropeptides.

Animals↗

PubMed2005

Correlating gene expression with chemical scaffolds of cytotoxic agents: ellipticines as substrates and inhibitors of MDR1.

To facilitate a systematic study of chemoresistance across diverse classes of anticancer drug candidates, we performed correlation analyses between cytotoxic drug potency and gene expression in 60 tumor cell lines (NCI-60; NCI-National Cancer Institute). Ellipticine analogs displayed a range of correlation coefficients (r) with MDR1 (ABCB1, encoding multidrug resistance (MDR) protein MDR1 or P-glycoprotein). To determine MDR1 interactions of five ellipticines with diverse MDR1-r values, we employed MDR1-transport and cytotoxicity assays, using MDR1 inhibitors and siRNA-mediated MDR1 downregulation, in MDR1-overexpressing cells. Ellipticines with negative correlations-indicative of MDR1-mediated resistance-were shown to be MDR1 substrates, whereas those with neutral or positive correlations served as MDR1 inhibitors, which escape MDR1-mediated chemoresistance. Correlation with additional genes in the NCI-60 confirmed topoisomerases as ellipticine targets, but suggested distinct mechanisms of action and chemoresistance among them, providing a guide for selecting optimal drug candidates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Inhibition of cell proliferation in human breast tumor cells by antisense oligonucleotides against facilitative glucose transporter 5.

In recent years, successful examples of antisense oligonucleotide (AS) therapy for genetic diseases have stimulated scientists to investigate its application on cancer diseases. AS can be used to down-regulate the mRNA and protein expression by annealing to specific region of the target mRNA which is responsible for the malignancy. Glucose transporter 5 (Glut5) is a tissue specific transporter that can be found on breast cancer tissues but not on normal breast tissues. Therefore, it is of clinical interest to investigate whether AS against Glut5 mRNA can tackle breast cancer. In this study, two cell lines, MCF-7 which is estrogen-receptor positive and MDA-MB-231 which is estrogen-receptor negative, were used to mimic breast cancer tissues at early and late stages, respectively. A 15-base sequence around the start codon of Glut5 was used. It was found that AS against Glut5 exerted anti-proliferative effect on both of these two breast tumor cell lines and seemed to exert its effect via the suppression of expression of Glut5 proteins in the cells. AS against Glut5 exhibited no effect on human hepatoma HepG2 cells which do not possess any Glut5. The results imply an alternative way in treating breast tumor as the AS against Glut5, unlike tamoxifen, takes effect on breast tumor cells via suppressing the expression of Glut5 that they specifically possess, and regardless whether the breast tumors are estrogen dependent or not.

Blotting, Western↗

PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗

PubMed2004

Clinical profile and genetic basis of Brugada syndrome in the Chinese population.

OBJECTIVE: To study the clinical profile and genetic basis of Brugada syndrome in Chinese patients. DESIGN: Prospective observational study. SETTING: Seven regional public hospitals, Hong Kong. MAIN OUTCOME MEASURES: The clinical and follow-up data of 50 patients (47 men, 3 women; mean age, 53 years) were collected, and genetic data of 36 probands and eight family members of three genotyped probands were analysed. RESULTS: Eight patients survived sudden cardiac death (group A), 12 had syncope of unknown origin but no sudden death (group B), and 30 were asymptomatic before recognition of Brugada syndrome (group C). Programmed electrical stimulation induced sustained ventricular arrhythmias in 88% (7/8), 82% (9/11), and 27% (3/11) of patients in group A, group B, and group C, respectively. New arrhythmic events occurred in 50% (4/8) of patients in group A and 17% (2/12) of patients in group B after a mean follow-up period of 30 (standard deviation, 13) months and 25 (7) months, respectively. All group C patients remained asymptomatic during a mean follow-up period of 25 (standard deviation, 11) months. Five of 36 probands and three of eight family members who underwent genetic testing were found to have a mutation in their SCN5A gene. CONCLUSIONS: Chinese patients with Brugada syndrome who are symptomatic have a high likelihood of arrhythmia recurrence, whereas asymptomatic patients enjoy a good short-term prognosis. The prevalence of SCN5A mutation among probands is 14%. Thus, Chinese patients with Brugada syndrome share with their western counterparts similar clinical and genetic heterogeneity.

Adult↗

PubMed2003

Allatostatin in ovaries, oviducts, and young embryos in the cockroach Diploptera punctata.

The quantity and localization of -Phe-Gly-Leu-amide allatostatins (-F-G-L-amide AST) was determined by ELISA and immunohistochemistry in ovaries and oviducts and in pre-dorsal closure embryos. AST in the cytoplasm of basal oocytes gradually increased from 4 to 35 fmol/ovary pair from the start (day 2) to the completion of vitellogenesis (day 6), then rapidly increased to 121 fmol/ovary pair during choriogenesis. In oviducts, AST-immunoreactivity was found in nerves to the muscle layer and in epithelial cells. AST-immunoreactivity in oviduct epithelial cells increased during vitellogenesis. A marked increase in quantity of AST in oviduct tissue between completion of chorion formation and immediately after ovulation appears to result from AST released from oocytes as they travel down the oviducts because AST content of newly ovulated eggs was 40% lower than late stage chorionated oocytes, and these oocytes released AST when incubated in saline. AST in embryos, localized in yolk cells, decreased as embryos approached dorsal closure. That this material in ovaries and embryos is AST was confirmed by its ability to inhibit JH synthesis in vitro and identification by MALDI-TOF mass spectrometry of a peptide with a mass corresponding to that of a Diploptera punctata AST. These findings indicate likely novel functions for ASTs: facilitation of ovulation and utilization of yolk.

Animals↗

PubMed2003

Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells.

In t(8;21) acute myeloid leukemia (AML), the AML1/ETO fusion protein promotes leukemogenesis by recruiting histone deacetylase (HDAC) and silencing AML1target genes important for hematopoietic differentiation. We hypothesized that depsipeptide (FR901228), a novel HDAC inhibitor evaluated in ongoing clinical trials, restores gene transcription and cell differentiation in AML1/ETO-positive cells. A dose-dependent increase in H3 and H4 histone acetylation was noted in depsipeptide-treated AML1/ETO-positive Kasumi-1 cells and blasts from a patient with t(8;21) AML. Consistent with this biological effect, we also showed a dose-dependent increase in cytotoxicity, expression of IL-3, here used as read-out for silenced AML1-target genes, upregulation of CD11b with other morphologic changes suggestive of partial cell differentiation in Kasumi-1 cells. Some of these biologic effects were also attained in other myeloid leukemia cell lines, suggesting that depsipeptide has differentiation and cytotoxic activity in AML cells, regardless of the underlying genomic abnormality. Notably, the activity of depsipeptide was enhanced by 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor (DNMT). These two agents in combination resulted in enhanced histone acetylation, IL-3 expression, and cytotoxicity, suggesting HDAC and DNMT activities as a potential dual target in future therapeutic strategies for AML1/ETO and other molecular subgroups of AML.

Acetylation↗

PubMed2003

Isolated ventricular non-compaction presenting with ventricular tachycardia.

Isolated ventricular non-compaction is a rare congenital cardiomyopathy, manifested morphologically as prominent myocardial trabeculations and deep inter-trabecular recesses that communicate with the ventricular cavity. Heart failure is the most common presenting condition. Other manifestations include arrhythmia and cardioembolic events. This report is illustrative of isolated ventricular non-compaction in a 78-year-old woman. The diagnosis was made when she presented with ventricular tachycardia many years after a stroke. She subsequently underwent implantation of a cardioverter-defibrillator. This report documents an uncommon presentation of this disease entity in the oldest patient at presentation as yet reported in the literature.

Aged↗

PubMed2002

Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients.

Paradoxical deterioration during antituberculosis therapy, defined as the clinical or radiological worsening of pre-existing tuberculous lesions or the development of new lesions in a patient who initially improves, remains a diagnostic dilemma. Although different clinical presentations of paradoxical response have been described, a systematic analysis of the entity in non-HIV-infected patients is lacking. Reported here are two cases of paradoxical deterioration in which sequential changes in lymphocyte counts and tuberculin skin test results are emphasized. In addition, 120 episodes of paradoxical response after antituberculosis treatment were reviewed. Of the total 122 episodes, 101 (82.8%) were associated with extrapulmonary tuberculosis. The median time from commencement of treatment to paradoxical deterioration was 60 days. The median time to onset of central nervous system manifestations (63 days) was longer than the time to onset of manifestations at other sites (56 days) ( P=0.02). Development of new lesions in anatomical sites other than those observed at initial presentation was observed in 31 (25.4%) episodes. A surge in the lymphocyte count, accompanied by an exaggerated tuberculin skin reaction, was observed in our patients during the paradoxical deterioration, analogous to the findings in HIV-positive patients. Treatment of the paradoxical response included surgical intervention (60.7%) and administration of steroids (39.3%). The use of steroids appeared to be safe in this series, as 95% of the Mycobacterium tuberculosis isolates were susceptible to first-line antituberculosis therapy.

Abscess↗