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Biomedical subjects

Eric Tse

Publications and source records attributed to Eric Tse.

13 recordsLinked to original sources
PubMed2007

Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab.

Ten patients with refractory lymphomas or autoimmune cytopenias were treated with alemtuzumab, and monitored prospectively for cytomegalovirus (CMV) reactivation by antigenemia and polymerase chain reaction. All patients showed virologic CMV reactivation. Two patients developed pneumonitis and hepatitis respectively, necessitating alemtuzumab withdrawal. Eight patients were asymptomatic, and with pre-emptive anti-CMV treatment, alemtuzumab therapy was uninterrupted. All patients ultimately achieved virologic remission. The frequent CMV reactivation was due to a high background seropositivity rate for CMV, severely immunocompromized patients, a sensitive detection method, and the diligence of surveillance. Frequent monitoring for and early treatment of CMV reactivation is necessary during alemtuzumab therapy.

Adult↗
PubMed2006

Alemtuzumab induced complete remission of autoimmune hemolytic anemia refractory to corticosteroids, splenectomy and rituximab.

A 58-year-old man with warm-antibody-mediated autoimmune hemolytic anemia (AIHA) refractory to prednisolone, azathioprine, splenectomy, rituximab and combination chemotherapy, and with unacceptably high transfusion requirement, was treated with alemtuzumab. After a cumulative dose of 883 mg of alemtuzumab, the AIHA remitted completely, with normalization of hemoglobin and transfusion-independence. The major side effect was reactivation of cytomegalovirus, which was controlled with intravenous and oral ganciclovir. This case showed that alemtuzumab might be of use in therapy-refractory AIHA.

Alemtuzumab↗
PubMed2005

Molecular pathways in hepatocellular carcinoma.

Research over the past decade has unraveled important molecular pathways involved in hepatocellular carcinoma (HCC), and several chromosomal and genetic aberrations have been identified to be responsible for initiation of the carcinogenic process. HBx protein and HCV core protein appear to play a pivotal role in hepatocarcinogenesis related to hepatitis B virus and hepatitis C virus, respectively. These viral oncoproteins allow cells to bypass some of the multi-steps in hepatocarcinogenesis, accounting for the etiological role of the two viruses in HCC. Understanding of the molecular pathways of HCC facilitates the development of novel molecular strategies for chemoprevention and therapy of HCC.

Carcinoma, Hepatocellular↗
PubMed2004

PIN1 overexpression and beta-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma.

The peptidyl-proplyl-isomerase, PIN1, upregulates beta-catenin by inhibiting its interaction with APC. beta-catenin accumulation occurs in about 70% of hepatocellular carcinoma (HCC), of which only 20% are due to beta-catenin mutations. The role of PIN1 in beta-catenin upregulation in HCC was investigated. PIN1 was shown to be overexpressed in more than 50% of HCC. All cases with PIN1 overexpression also showed beta-catenin accumulation, with 68% of cases showing concomitant beta-catenin and cyclin D1 accumulation. PIN1 was shown to contribute to beta-catenin and cyclin D1 overexpression directly by in vitro cell-line transfection experiments. Finally, we showed that PIN1 overexpression and beta-catenin gene mutations appeared to be mutually exclusive events, leading to beta-catenin accumulation in HCC. These results showed that PIN1 overexpression leading to beta-catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.

Carcinoma, Hepatocellular↗
PubMed2004

HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects.

Few studies have examined Chinese patients with chronic hepatitis B who exhibit hepatitis B surface antigen (HBsAg) seroclearance. We comprehensively studied the biochemical, virological, histological, and clinical aspects of 92 patients with HBsAg seroclearance (median follow-up, 126 months). Ninety-two HBsAg-positive controls matched for age, sex, and duration of follow-up were also recruited. Liver biochemistry, serum hepatitis B virus (HBV) DNA levels, and development of clinical complications were monitored. Intrahepatic total and covalently closed circular (ccc) HBV DNA were measured quantitatively in 16 patients. HBV genotype was determined in 30 patients. The mean age at HBsAg seroclearance was 48.8 (+ 13.81) years. There was a significant improvement in serum alanine aminotransferase levels after HBsAg seroclearance (p<0.0001). Patients with genotype B had a higher chance of HBsAg seroclearance than those with genotype C (P =.014). Ninety-eight percent of patients had undetectable serum HBV DNA. Thirty-seven percent of patients had low titer of intrahepatic HBV DNA, mainly in the form of cccDNA (71%-100%). All 14 patients with liver biopsies had near normal histology. There was no difference in the risk of development of hepatocellular carcinoma (HCC) between patients with and without HBsAg seroclearance. However, the mean age of HBsAg seroclearance was significantly older in patients with HCC than in patients without HCC (P =.016). In conclusion, patients with HBsAg seroclearance had favorable biochemical, virological, and histological parameters. Intrahepatic HBV DNA level was low and predominantly in the form of cccDNA. However, HCC could still develop, particularly in patients with cirrhosis who had HBsAg seroclearance at an older age.

Adult↗
PubMed2004

Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients.

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, x3; mitoxantrone 10 mg/m2/d, x1; dexamethasone 20 mg/d, x5; monthly cycles, x6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50.5%, 18% and 68.5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37.5%, P = 0.03; OR: 84% vs. 47.5%, P < 0.001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0.039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0.001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0.001) and OS (67 months vs. 13 months, P < 0.001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas.

Adult↗
PubMed2004

Detection of intrahepatic hepatitis B virus DNA and correlation with hepatic necroinflammation and fibrosis.

Assessment of intrahepatic hepatitis B virus (HBV) DNA levels in patients with chronic hepatitis B is important in understanding the natural history of the disease and designing antiviral therapy regimens. However, there is no standardized method for the measurement of intrahepatic HBV DNA levels. We describe a convenient novel method for the measurement of intrahepatic HBV DNA levels based on a modified COBAS Amplicor HBV Monitor test for HBV DNA measurement and real-time PCR beta-actin gene detection for human genomic DNA (hgDNA) quantitation. Fifteen hepatitis B e antigen (HBeAg)-positive patients, 26 patients positive for antibody to HBeAg (anti-HBe), and 8 control patients were recruited. The mean between-run coefficient of variation for the beta-actin real-time PCR assay was 15.4%. All eight control patients had undetectable intrahepatic and serum HBV DNA levels. All chronic hepatitis B patients had detectable intrahepatic HBV DNA levels, and all but one anti-HBe-positive patient had detectable serum HBV DNA levels. HBeAg-positive patients had higher median intrahepatic and serum HBV DNA levels than anti-HBe-positive patients (6,950 versus 676 HBV DNA copies/ng of hgDNA, respectively [P < 0.001] and 184 x 10(6) versus 6.65 x 10(6) copies/ml, respectively [P < 0.001]). The intrahepatic HBV DNA levels correlated strongly with the serum HBV DNA levels (r = 0.842; P < 0.001) and with the degree of fibrosis (P = 0.014). We conclude that the method that we describe is reliable and convenient for the measurement of intrahepatic HBV DNA levels and has potential clinical significance.

Actins↗
PubMed2004

Natural killer cell neoplasms.

Lymphoid neoplasms that are derived from natural killer (NK) cells are uncommon but distinct clinicopathologic disease entities. Three types have been recognized and categorized in the latest World Health Organization classification: extranodal NK cell lymphoma, nasal-type; aggressive NK cell leukemia; and blastic NK cell lymphoma. All NK tumor cells express the NK cell marker CD56, but they lack the expression of surface CD3 and the rearrangement of T-cell receptor genes, which distinguish them from T-lymphoid neoplasms. There is also a strong association with the Epstein-Barr virus, except in blastic NK cell lymphoma. Extranodal involvement by the NK cell tumor is common, especially in the nasal cavity, the skin, and the gastrointestinal tract. All 3 NK cell neoplasms are characterized by aggressive clinical course and poor response to treatment. Although the optimal treatment modality remains to be determined, good initial response to combined radiation therapy and chemotherapy has been observed in localized disease. Further studies in the basic biology of the NK cell and the pathology of NK cell neoplasms may shed light on the development of newer and more effective therapy.

Adult↗
PubMed2002

Intracellular antibody capture technology: application to selection of intracellular antibodies recognising the BCR-ABL oncogenic protein.

The expression of antibodies inside cells to ablate protein function has the potential for disease therapy and for target validation in functional genomics. However, due to inefficient expression or folding, only a few antibodies or antibody fragments, usually as single-chain Fv antibody fragments (scFv), bind their antigens in an intracellular environment. We have established a genetic-selection technology (intracellular antibody capture, IAC) to facilitate the isolation of functional intracellular scFv from a diverse repertoire. This approach comprises an in vitro library screen with scFv-expressing bacteriophage, employing bacterially expressed antigen, followed by a yeast in vivo antibody-antigen interaction screen of the sub-library of in vitro scFv antigen-binders. Accordingly, we have isolated panels of scFv that bind intracellularly to the BCR or the ABL parts of the BCR-ABL oncogenic protein. Sequence analysis of the intracellular antibody scFv panels revealed a sequence conservation indicating an intracellular antibody consensus for both VH and VL, which could form the basis for the de novo synthesis of intracellular antibody libraries to be used with intracellular antibody-capture technology.

Amino Acid Sequence↗
PubMed1997

Restoration of lung volume using the Flutter VRP1 or breathing exercise.

A method of chest wall restriction imposed for 30 minutes demonstrated a mean (SD) decrease of 42 (14) per cent in forced vital capacity (FVC) during restrictor application. Following the application of chest wall restriction, 30 healthy subjects then underwent a 15 minute treatment with either Flutter VRP1 (Flutter) or breathing exercise with end-inspiratory hold (BE) after chest wall restriction release. Both Flutter and BE applied for 15 minutes immediately restored FVC to pre-restriction values. Tidal breathing control subjects demonstrated a clinically small but statistically significant decrease in FVC of 3 per cent (p<0.001). Visual analogue assessment of each treatment technique showed BE to be the subject- preferred technique for lung volume restoration. This study shows that in normal subjects, Flutter and BE are equally effective in restoring FVC and superior to tidal breathing.

Journal Article↗