Showing papers by "Winnie Yeo published in 2004"
TL;DR: Multivariate analysis revealed pre-chemotherapy HBV DNA level, the use of steroids and a diagnosis of lymphoma or breast cancer to be significant factors for the development of HBV reactivation.
Abstract: For cancer patients with chronic hepatitis B virus (HBV) infection, who receive cytotoxic chemotherapy, HBV reactivation is a well-described complication, which may result in varying degrees of liver damage. Several clinical features and the pre-chemotherapy HBV viral load have been suggested to be associated with an increased risk of developing the condition: (1). to assess the clinical and virological factors in a comprehensive manner and thereby identify those that are associated with the development of HBV reactivation; (2). to develop a predictive model to quantify the risk of HBV reactivation. In all, 138 consecutive cancer patients who were HBV carriers and undergoing chemotherapy were studied, of which 128 patients had sera available for real-time PCR HBV DNA measurement. They were followed up throughout their course of chemotherapy and the HBV reactivation rate was determined. The clinical and virological features between those who did and did not develop viral reactivation were compared. These included age, sex, baseline liver function tests, HBeAg status and viral load (HBV DNA) prior to the chemotherapy, and the use of specific cytotoxic agents. In all, 36 (26%) developed HBV reactivation. Multivariate analysis revealed pre-chemotherapy HBV DNA level, the use of steroids and a diagnosis of lymphoma or breast cancer to be significant factors. Based on real-time HBV DNA PCR assay, detectable baseline HBV DNA prior to the administration of cytotoxic chemotherapy, the use of steroids and a diagnosis of lymphoma or breast cancer are predictive factors for the development of HBV reactivation. A predictive model was developed from the current data, based on a logistic regression method.
288 citations
TL;DR: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.
Abstract: Purpose For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. Patients and Methods Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. Results In the ...
245 citations
TL;DR: HBV reactivation is a common cause of liver damage during CT in HBsAg-positive HCC patients and the only identifiable associated risk factor was elevated pre-treatment ALT.
157 citations
TL;DR: Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC and resulted in excellent local tumor control.
Abstract: Purpose To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. Patients and Methods Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. ...
116 citations
TL;DR: For breast cancer patients receiving standard cytotoxic chemotherapy, a high HBV viral load prior to the administration of cytot toxic chemotherapy is a significant predictive factor for the development of HBV reactivation.
Abstract: Hepatitis B virus (HBV) reactivation during cytotoxic chemotherapy for cancer may complicate treatment and cause liver damage. The complication has been reported to occur in 10% to over 50% of HBV carriers, but the factors that determine which patients will develop reactivation remain unclear. The objective of the study is to test the hypothesis that the prechemotherapy HBV DNA level is a risk factor for the development of HBV reactivation. We studied 41 women undergoing cytotoxic chemotherapy for breast cancer, 17 of whom developed reactivation and 24 who did not. We developed a novel, ultra-sensitive, real-time polymerase chain reaction assay for the measurement of HBV DNA. The sera of 37 patients (16 who developed reactivation and 21 who did not) were available for measurement of HBV DNA using this technique. The results showed that patients in the reactivation group had a significantly higher median HBV DNA load (1.03 x 10(6) copies/mL; range <2.9 x 10(3) to 8.723 x 10(7)) than did the nonreactivation group (<2.9 x 10(3) copies/ml; range <2.9 x 10(3) to 6.331 x 10(7)) (P < 0.001). The optimal cut-off between the two groups was found to be at serum HBV DNA level of 3 x 10(5), which gave a sensitivity of 81.0% and a specificity of 85.0%. In conclusion, for breast cancer patients receiving standard cytotoxic chemotherapy, a high HBV viral load prior to the administration of cytotoxic chemotherapy is a significant predictive factor for the development of HBV reactivation. Such information may be useful in determining which patients would benefit most from prophylactic antiviral therapy during cytotoxic chemotherapy.
94 citations
TL;DR: It is concluded that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.
Abstract: In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients' prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received 'prophylactic lamivudine' prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.
92 citations
TL;DR: In this article, a cDNA microarray examination of the expression profiles of eight primary ovarian cancers was performed and the response of these patients to chemotherapy from their expression profiles was predicted using a voice-speech-pattern recognition algorithm.
60 citations
TL;DR: This pilot study assesses the psychosocial impact of different modalities of breast cancer surgery in Chinese patients and their husbands and finds no significant differences in the impact on psychological well-being between patients and husbands.
Abstract: Background and purpose: This pilot study assesses the psychosocial impact of different modalities of breast cancer surgery in Chinese patients and their husbands.
Methods: Thirty-six patients who underwent conservative breast therapy (BCT) for breast cancer were compared with 36 women who underwent total mastectomy (TM) on four aspects of psychosocial adjustment. They were matched in pairs in terms of stage of disease, age and time since surgery. Where available, their husbands were also consented for similar assessment.
Results: Women who underwent BCT showed a significantly better response to their body and sexual image than those who underwent TM. This difference did not translate into any significant difference in terms of emotional and symptomatic aspects, daily activities, or fear of recurrences. The husbands of patients in the TM group showed significantly more emotional and symptomatic distress and greater change in the perception of their wives' body and sexual images.
Conclusion: This is the first of such study conducted in a Chinese population. The lack of differences in certain psychosocial aspects may indicate a generally good adjustment in the TM patients after their surgery. It may also relate to the fact that volunteers for the study were themselves representative only of the patient population who adapted well to the surgery, and those patients who were emotionally distressed tended to decline to participate. Psychosocial disruption in the patients' families is reflected in our study where patients' husbands in the TM group were significantly more disturbed. However, due to the limited number of patients studied, the findings are not yet conclusive and require further studies for confirmation. Copyright © 2003 John Wiley & Sons, Ltd.
55 citations
TL;DR: A woman with stage IIIb non-small cell lung cancer developed disease progression with brain metastases during chemotherapy and received gefitinib alone, without the use of corticosteroid treatment or radiotherapy, with dramatic clinical improvement within 1 week.
Abstract: A woman with stage IIIb non-small cell lung cancer (NSCLC) developed disease progression with brain metastases during chemotherapy. Due to unusual circumstances, the patient received gefitinib alone, without the use of corticosteroid treatment or radiotherapy. There was a dramatic clinical improvement within 1 week. Follow-up magnetic resonance imaging of the brain 1 month later showed decreases in both the size and number of brain metastases. The patient remains well 9 months after initiation of gefitinib. It is proposed that gefitinib may have a role in treatment of brain metastases from NSCLC.
32 citations
13 citations
TL;DR: Negative results on a screening abdominal sonogram among hepatitis B virus carriers with elevated alpha-fetoprotein levels does not rule out the presence of small hepatocellular carcinoma.
Abstract: OBJECTIVE. Routine screening for hepatocellular carcinoma among chronic carriers of hepatitis B virus using a combination of abdominal sonography and serum α-fetoprotein levels is widely practiced. Negative results on an abdominal sonogram generally indicate the absence of hepatocellular carcinoma despite the elevation of α-fetoprotein levels, but the false-negative rate of abdominal sonography has not been established prospectively.SUBJECTS AND METHODS. In our screening program, we routinely investigated patients with Lipiodol (iodized oil) CT when they presented with α-fetoprotein levels above 20 ng/mL or a focal lesion as depicted on abdominal sonography. Lipiodol CT comprised a hepatic angiogram with injection of Lipiodol selectively in the hepatic arteries, followed by an unenhanced CT scan 10 days later. Positive findings on Lipiodol CT were confirmed histologically by biopsy or surgical resection. We defined false-negative as histologic diagnosis of hepatocellular carcinoma within 3 months of norma...
TL;DR: This randomized phase III study compared concurrent weekly cisplatin-RT with RT alone in patients with locoregionally advanced NPC, finding that 3 cycles of 3-weekly chemotherapy concurrent with RT followed by3 cycles of adjuvant chemotherapy has improved survival over RT alone.
Abstract: 5523 Background/Objective: NPC is highly radiosensitive and chemosensitive. 3 cycles of 3-weekly chemotherapy concurrent with RT followed by 3 cycles of adjuvant chemotherapy has improved survival over RT alone in a previous randomized study. The regimen was associated with significant toxicities. This randomized phase III study compared concurrent weekly cisplatin-RT with RT alone in patients with locoregionally advanced NPC. Methods: Patients with Ho's N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m2 weekly up to 8 weeks concurrently with RT (CRT) or RT alone. The primary endpoints are progression-free survival (PFS) and overall survival (OS). Results: 350 eligible patients were randomized. Baseline patient characteristics, treatment toxicities and PFS analysis at median follow up of 2.71 years have been published previously. At a median follow up of 5.5 years where 58 and 73 deaths were found out of 174 CRT and 176 RT patients respectively (95th and 5th pe...
TL;DR: Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic, and Toxicity was minimal at the highest dose level.
Abstract: OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the capacity selectively to bind to asialoglycoprotein receptors that are found exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of this study was to establish the safety and to examine the pharmacokinetics of this novel compound in patients with liver cancer. Fourteen patients received a total of 37 cycles of OGT 719 at four dose levels ([500 mg/m2 first cycle, 1 000 mg/m2 subsequent cycles], 1000 mg/m2, 3 300 mg/m2 and 7500 mg/m2). OGT 719 was administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for 5 days every 4 weeks. Pharmacokinetic parameters were studied during the first cycle of dose levels 1 and 2 (500 mg/m2. and 1 000 mg/m2, respectively). The maximum plasma concentration was attained within 5 min of completing the infusion and almost doubled, dose dependently, with a doubling of the infused dose. The plasma level declined rapidly in a monophasic manner with an elimination half-life of 2.1 and 2.5 h for dose level 1 and 2, respectively The mean area under the curve (AUC(o - infinity) area under the curve to 24 h; AUC(o - infinity), area under the curve to infinity) doubled at the higher dose level. None of the patients had a significant tumor response. Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic. Toxicity was minimal at the highest dose level.
TL;DR: Examples of laboratory results generated from high‐throughput microarray analyses that illuminated previously unrecognized networks of regulatory genes and pathways that point to the mechanisms of action for the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate, and the green tea polyphenol, epi‐gallocatechin gallate are discussed.
Abstract: Expressed sequence tags and genome sequencing have virtually uncovered all the genes and transcripts in the human genome. Functional genomic analysis of these genes will undoubtedly reveal their physiological roles in cells in the near future. Coupled with the advent of DNA microarray, cellular response to perturbation can now be examined at genome-wide levels in a single analysis, yielding clues to the network of pathways and interacting pathways that underlie a comprehensive systems response to exposure to small molecule perturbants. This post-genomic information will be the foundation for knowledge-based in silico systems biology. It is envisioned that querying such relational databases will generate testable hypotheses as well as revealing information on networks of regulatory genes and pathways that could further fuel and shape molecular and drug target discovery, and ushering in a new era in genomic medicine. In this review, we will first discuss examples of laboratory results generated from high-throughput microarray analyses that illuminated previously unrecognized networks of regulatory genes and pathways that point to the mechanisms of action for the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate, and the green tea polyphenol, epi-gallocatechin gallate. We will then focus on the application of gene expression profiles in genomic medicine for predicting treatment response in cancer, using clinical specimens obtained from patients. These studies and others point to an increasing trend in modern biology in which high-throughput genome scale comprehensive biological information is incorporated into databases for constructing and reconstructing pathways and networks of interacting pathways that constitute a physiological response to environmental perturbation at the organism or systems levels. Drug Dev. Res. 62:124–133, 2004. © 2004 Wiley-Liss, Inc.
TL;DR: The clinical follow-up of a cohort of 1124 NPC cases first seen in the institute from 1993 to 2000 was reviewed, and 3 cases with intracranial mets on follow- up were identified.
Abstract: 5608 Background: Brain metastasis (mets) from nasopharyngeal carcinoma (NPC) is a controversial entity. Only 2 cases had ever been reported and no cohort study performed. Methods: We reviewed the clinical follow-up of a cohort of 1124 NPC cases first seen in our institute from 1993 to 2000, and identified 3 cases with intracranial mets on follow-up. All 3 patients received whole brain radiation therapy (WBRT) for the brain mets. Results: Case #1: A 45-year-old man presented with Stage T1N2M0 disease in 1996. In 2001, disease recurred in the neck and was inoperable. Static disease was achieved with chemotherapy. 1 year later, he experienced vertigo. Contrast CT brain revealed enhancing cystic lesions in both cerebellums. Histology of the lesion revealed metastatic undifferentiated carcinoma, staining positive for Epstein-Barr virus-encoded RNA (EBER). He received WBRT and remained alive at the most recent follow-up, which was 1 year after the diagnosis of brain mets. Case #2: A 51-year-old man presented wi...
01 Jan 2004
TL;DR: A cDNA microarray examination of the expression profiles of eight primary ovarian cancers stratified into two groups based on their chemotherapeutic response was conducted and gene expression profiling by means of DNA microarray may be applied diagnostically for predicting treatment response in ovarian cancer.
Abstract: Ovarian carcinoma is a leading cause of gynecologic cancer death in women. Despite treatment, a large number of women with ovarian cancer eventually relapse and die of the disease. Hence, recurrent ovarian cancer continues to be a therapeutic dilemma, possibly a result of the emergence of drug resistance during relapse. Recent advances in expression genomics enable global transcript analysis that leads to molecular classification of cancers and prediction of outcome and treatment re- sponse. We did a cDNA microarray examination of the expression profiles of eight primary ovarian cancers stratified into two groups based on their chemotherapeutic response. We applied a voice- speech-pattern recognition algorithm for microarray data analysis and were able to model and predict the response of these patients to chemotherapy from their expression profiles. Hence, gene expression profiling by means of DNA microarray may be applied diagnostically for predicting