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Biomedical subjects

R Liang

Publications and source records attributed to R Liang.

At least 55 records · Page 3Linked to original sources
PubMed2003

Aberrant p15 gene promoter methylation in therapy-related myelodysplastic syndrome and acute myeloid leukaemia: clinicopathological and karyotypic associations.

Seventeen patients with therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS/AML) were examined for aberrant p15 gene methylation by methylation-specific polymerase chain reaction. Ten patients (58%) showed p15 methylation, which was significantly related to monosomy/deletion of chromosome 7q, but not to antecedent chemotherapy, blast count, leukaemic evolution or survival. In three of six patients with marrow samples obtained prior to the diagnosis of t-MDS/AML, p15 methylation predated disease development by up to 2 years. Bone marrow transplantation led to the disappearance of p15 methylation in one patient. These results showed that p15 methylation was an early event in the evolution of some t-MDS/AML patients.

Acute Disease↗
PubMed2003

Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia.

BACKGROUND: The best overall treatment strategy for patients with acute promyelocytic leukaemia (APL) in relapse with chemotherapy, bone marrow transplantation (BMT) or arsenic trioxide (As(2)O(3)) based therapy remains undefined. PATIENTS AND METHODS: We reviewed the clinical course and treatment outcome of 143 APL cases seen in four major hospitals in Hong Kong over a 10-year period. RESULTS: Complete remission (CR) was attained in 113 cases (79%) with all-trans retinoic acid (ATRA) and chemotherapy. Relapse occurred at a median of 16 months in 54 cases, with a 3-year disease free survival of 56%. Post-relapse treatment was successful in 41 cases (76%), giving an actuarial 3-year overall survival (OS) of 81% from CR1. Three different protocols were used: chemotherapy alone (n = 19), allogeneic BMT (n = 14) and an As(2)O(3)-based regimen (n = 21). Chemotherapy was associated with the highest treatment-related mortality (TRM) at 53%, giving a CR2 rate of 47%. TRM was 36% for BMT. The CR2 rate for the As(2)O(3)-based regimen was 100%, with no TRM. However, 38% of As(2)O(3) treated patients had subsequent relapses, which were further salvaged in 75% by combined As(2)O(3) plus ATRA. The actuarial OS for the three protocols leveled off by 2 years at 82% for As(2)O(3), 43% for BMT and 23% for chemotherapy (P = 0.0004). CONCLUSIONS: Our results suggest that As(2)O(3) may be superior to chemotherapy and BMT for the treatment of APL in relapse.

Adolescent↗
PubMed2003

Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value.

Nasal NK/T-cell lymphoma is an Epstein-Barr virus-related, highly aggressive but localized disease in Orientals. The median survival is <1 year. Here, we update our experience on 18 patients treated with autologous stem cell transplantation (ASCT). Two patients died of mucositis and septicemia during ASCT. Relapse occurred in nine cases, including six local relapses. Compared with patients treated in remission, all patients treated in active or disseminated disease died of early relapse. Within this cohort, there was no significant survival difference between patients treated in first (CR1, n = 7) or second (CR2, n = 5) complete remissions. However, among consecutive cases analyzed, the patients receiving ASCT at CR1 showed a trend towards better overall survival compared with historical matched controls (P = 0.064). Disease relapse beyond 6 months was not seen after ASCT. Our retrospective data suggest that ASCT in CR1 is a viable consolidation therapy for local-stage NK/T lymphoma, but a randomized trial is needed to prove any definite survival benefit. For patients with relapsed, refractory or extranasal disease, early consideration for allogeneic transplantation and alternative therapy may be warranted.

Adult↗
PubMed2003

Modeling human breast cancer metastasis in mice: maspin as a paradigm.

Breast cancer is the most common cancer detected in women, accounting for nearly one out of every three cancers diagnosed in the United States. Most cancer patients do not die from the primary tumor but die due to metastasis. Therefore, the study of metastasis is of most importance both to the clinician and patient. In the past, animal models have been used in breast cancer research and mammary gland biology. Our group has also established several animal models to address the function of a novel tumor suppressor gene maspin in breast tumor progression. Maspin was initially isolated from normal mammary epithelial cells. Its expression was down regulated in breast tumors. To test the protective role of maspin overexpression in mammary tumor progression, we crossed maspin overexpression transgenic mice (WAP-maspin) with a strain of oncogenic WAP-SV40 T antigen mice. The bitransgenic mice had reduced tumor growth rate and metastasis. Maspin overexpression increased the rate of apoptosis of both preneoplastic and carcinomatous mammary epithelial cells. Maspin reduced tumor growth through a combination of reduced angiogenesis and increased apoptosis. In a separate animal experiment, maspin overexpressing mammary tumor cells (TM40D) were implanted into the fat pad of syngeneic mice. TM40D tumor cells were very invasive and metastatic. However, both primary tumor growth and metastasis were significantly blocked in TM40D cells that overexpress maspin as a consequence of plasmid or retrovirus infection. These evidences demonstrate that maspin function to inhibit primary tumor growth as well as invasion and metastasis. Elucidating the molecular mechanism of maspin action will shed light on our understanding of breast cancer invasion and metastasis.

Animals↗
PubMed2002

Newcastle disease outbreaks in western China were caused by the genotypes VIIa and VIII.

Twelve Newcastle disease virus (NDV) strains were isolated from chickens involved in outbreaks of Newcastle disease (ND) in western China (Shaanxi, Gansu, Xinjiang, Qinghai and Guangxi provinces) between 1979 and 1999. All strains were determined to be velogenic by plaque formation, the mean death time (MDT) of embryonated eggs, and the intracerebral pathogenicity index (ICPI). For preparation of virus RNA, the acid guanidinium-thiocyanate method was used. A 908bp fragment of nucleotide was amplified by RT-PCR starting from the N terminal of the F gene and the PCR segments were cloned into the PGEM-T vector and sequenced. The similarities of the nucleotide sequences (1-519bp) and predicted amino acid sequences of the F gene (1-125) were analyzed by comparing the 12 NDV isolates with the NDV vaccine strains Lasota, B1, H1 and V4, with classical NDV strains and recent epizootic strains. Phylogenetic analysis demonstrated that all strains were of two novel genotypes; the NDV strains that caused the outbreak of ND in western China during 1998-1999 was of the genotype VIIa, whereas the strains from the Qinghai province (1979-1985) were of genotype VIII, which has been found predominately in southern Africa.

Amino Acid Sequence↗
PubMed2002

High field phase diagram of cuprates derived from the Nernst effect.

Measurements of the Nernst signal in the vortex-liquid state of the cuprates to high fields (33 T) reveal that vorticity extends to very high fields even close to the zero-field critical temperature T(c0). In overdoped La2-xSrxCuO4, we show that the upper critical field H(c2)(T) curve does not end at T(c0), but at a much higher temperature. These results imply that T(c0) corresponds to a loss in phase rigidity rather than a vanishing of the pairing amplitude. An intermediate field H*(T)<<H(c2)(T) is shown to be the field scale for the flux-flow resistivity.

Journal Article↗
PubMed2002

Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease.

OBJECTIVE: To determine whether the Nurr1 gene, which is critical for the development and maintenance of nigral dopaminergic neurons, is a risk factor associated with PD. BACKGROUND: The Nurrl gene is highly expressed in the dopaminergic neurons in the midbrain. Knockout of the gene results in agenesis of nigral dopaminergic neurons and heterozygous knockout mice increases 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. METHODS: This study included 105 patients with familial PD (fPD) and 120 patients with sporadic PD (sPD) and 221 age-matched healthy control subjects. The polymorphisms and mutations of the Nurr1 gene in patients with PD were initially examined by heteroduplex analysis and sequencing analysis from PCR-amplified Nurr1 gene fragments. A polymorphism in the BseRI restriction site was identified, and a relatively large-scale analysis then was conducted by three independent investigators who were blinded to the clinical status of the subjects. RESULTS: A homozygous 7048G7049 polymorphism was found in intron 6 of the Nurr1 gene, which was significantly higher in fPD (10/105; 9.5%) and in sPD (5/120; 4.2%) compared with healthy control subjects (2/221; 0.9%). The mean age and the SD at onset of these homozygote patients with PD was 52 +/- 15 years for fPD and 46 +/- 7 years for sPD. The clinical features of these homozygote patients with PD did not differ from those of typical PD. CONCLUSIONS: The homozygote polymorphism of 7048G7049 in intron 6 of the Nurr1 gene is associated with typical PD.

Adult↗
PubMed2002

Evidence for static magnetism in the vortex cores of ortho-II YBa2Cu3O6.50.

Evidence for static alternating magnetic fields in the vortex cores of underdoped YBa2Cu3O6+x is reported. Muon spin rotation measurements of the internal magnetic field distribution of the vortex state of YBa2Cu3O6.50 in applied fields of H = 1 T and H = 4 T reveal a feature in the high-field tail of the field distribution which is not present in optimally doped YBa2Cu3O6.95 and which fits well to a model with static magnetic fields in the vortex cores. The magnitude of the fields is estimated to be 18(2) G and decreases above T = 10 K. We discuss possible origins of the additional vortex core magnetism within the context of existing theories.

Journal Article↗
PubMed2002

Hypermethylation of gene promoters in hematological neoplasia.

Cancer cells are associated with global hypomethylation but with focal hypermethylation of specific gene promoters organized as CpG island. DNA methyltransferases, DNMT1 and 3 (3a and 3b), have been implicated in mediating maintenance and de novo methylation. Hypermethylation of gene promoters results in the inactivation of the corresponding genes, by preclusion of the formation of the transcription complex, due to the recruitment of MBP, MeCPs and histone deacetylase. This results in the deacetylation of histone and thus a compact chromatin complex unfavourable for the initiation of transcription. This methylation-associated gene silencing has been demonstrated in various genes including tumour suppressor genes (p15, p16, p73, VHL). Therefore, gene promoter hypermethylation collaborates with other mechanisms of gene inactivation such as deletion and intragenic mutations to fulfil Knudson's hypothesis. Hypermethylation may serve as a molecular disease marker for the detection of minimal residual disease. Emerging evidence suggests a possible prognostic value of gene promoter hypermethylation. Moreover, gene hypermethylation may also serve as a target for therapeutic invention by hypomethylating agents.

Animals↗
PubMed2002

Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4 quality of life instrument into traditional Chinese.

The need for a culturally sensitive instrument to assess quality of life (QOL) of patients in international oncology clinical trials has been well documented. This study was designed to evaluate the psychometric properties of the traditional Chinese translation (TCHI) of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4. The FACT-BMT consists of the FACT-General and treatment-specific concerns of bone marrow transplantation. The Chinese translation follows the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology. Bilingual teams from the United States and Hong Kong reviewed the translation to develop a provisional TCHI FACT-BMT, which was then pre-tested by interviewing 20 native Chinese-speaking BMT patients in Hong Kong. The pre-test results indicated good content coverage and overall comprehensibility. A refined translation, taking into account patient comments, was validated by 134 BMT patients in Hong Kong. The results indicated the high internal consistency of the TCHI FACT-BMT scales, with Cronbach's alpha coefficients ranging from 0.71 (emotional well-being) to 0.92 (FACT-BMT total). The FACT-BMT also demonstrated good construct validity when correlated with SF-36 Health Survey scales. The QOL of Chinese BMT patients can now be evaluated using a well-validated international QOL instrument in their own language.

Adolescent↗
PubMed2002

Aggressive hepatocellular carcinoma complicating pregnancy after autologous bone marrow transplantation for non-Hodgkin's lymphoma.

In the Asia-Pacific region, autologous and allogeneic bone marrow transplantation (BMT) in patients infected with the hepatitis B virus (HBV) may be complicated by fatal hepatic failure due to viral reactivation. Survivors may suffer from accelerated hepatitis and cirrhosis. We report the first case of hepatocellular carcinoma (HCC) after autologous BMT for mediastinal B cell lymphoma. The tumor developed rampantly during a planned pregnancy 5 years after BMT. Less than 40 cases of HCC complicating pregnancy have been reported, and outcome is invariably poor. Immunosuppression and HBV reactivation after autologous BMT, as well as immune tolerance and hormonal changes associated with pregnancy may contribute to the rapid tumor growth. Biochemical and radiological surveillance for HCC should be strengthened in HBV carriers after BMT, especially in patients with the histology of chronic liver disease, or biochemical/ virological evidence of increased HBV activity.

Adult↗
PubMed2002

Glucose-6-phosphate dehydrogenase deficiency and hematopoietic stem cell transplantation.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hemolytic enzymopathy affecting 3% of Southern Chinese males. Among 275 adult allogeneic hematopoietic stem cell transplantations (SCT), five cases (1.8%) each of donors and recipients were G6PD deficient. Among 107 autologous SCT, four patients (3.7%) were G6PD deficient. All subjects were male, except for two female patients with chronic myeloid leukemia (CML). The incidence of G6PD deficiency in female CML patients was significantly higher than the background female incidence (P = 0.004), but comparable with that in the males (P = 0.664). There was no significant hemolysis or delay in red cell engraftment, and all but one patient converted to donor G6PD screening status. One female patient achieved partial correction of her G6PD status and relapsed at 10 months. We suggest that G6PD deficiency should be tested for in all marrow donors and recipients in susceptible populations. From our data, there is a suggestion of increased clinical incidence of G6PD deficiency in female patients with multi-lineage clonal marrow disorders.

Adolescent↗
PubMed2002

Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation.

Haemorrhagic cystitis (HC) is an important complication after bone marrow transplantation (BMT). Overt HC (grade > or =2, gross haematuria, clot retention and impairment of renal function), clinically more important than mild and occult HC (grade 1, microscopic haematuria), leads to substantial morbidity and occasional mortality. We retrospectively analyzed 32 cases of clinically overt HC from a series of 236 BMT patients. Significant risk factors included the use of busulphan during conditioning, allogeneic BMT and acute GVHD. Logistic regression showed GVHD to be the most important risk factor. According to the time of engraftment, HC could be divided into pre- and post-engraftment subtypes. Pre-engraftment HC was brief, not more severe than grade 2, and subsided with supportive treatment. In contrast, post-engraftment HC was protracted, often of grade > or =3, associated with severe GVHD, and required surgical intervention in many cases. Polyoma BK viruria, but not adenoviruria, could be demonstrated in both types of HC. The increased severity and association with GVHD of post-engraftment HC suggested that attack of urothelium by immunocompetent cells, possibly directed against BK viral antigens, might play a pathogenetic role.

Adenoviridae↗
PubMed2002

Macrophage migratory inhibitory factor (MIF) expression in acute graft-versus-host disease (GVHD) in allogeneic hemopoietic stem cell transplant recipients.

Graft-versus-host disease (GVHD) is a major complication after hemopoietic stem cell transplantation (HSCT), but its pathogenesis remains uncertain. Macrophage migratory inhibitory factor (MIF) is an important mediator in the allo-immune reaction during renal transplantation, yet its role in hemopoietic stem cell transplantation (HSCT) remains unexplored. This study investigated the potential role of MIF in acute graft-versus-host disease (aGVHD) following allogeneic HSCT. Forty-six randomly selected patients undergoing autologous or allogeneic HSCT were studied. Immunohistochemistry and in situ hybridization were performed to examine tissue MIF mRNA and protein expression on skin and colonic biopsy specimens. The associated T cell and macrophage activation was also studied by immunohistochemical studies. A semi-quantitative method was used to assess MIF staining, as well as T cell and macrophage staining. Serial blood samples were analyzed by ELISA for serum MIF levels. Immunohistochemistry and in situ hybridization performed in 15 skin and 19 colonic biopsies from 17 patients who developed moderate to severe aGVHD showed a significant increase in MIF mRNA and protein expression compared with normal controls (seven skin and five colonic biopsies). MIF was localized within the epidermis and the vascular area of skin, but diffusely expressed in the entire thickness of colon. Macrophage and T lymphocyte infiltration was confined to areas of strong MIF expression. Serial analysis by ELISA showed that only patients who developed aGVHD (n = 19) exhibited an increase (two- to three-fold) in serum MIF during HSCT, but not in the allogeneic HSCT recipients without aGVHD (n = 7) or those who received autologous HSCT (n = 8). In 14 out of 19 patients, serum MIF peaked before the onset of aGVHD. Local and systemic up-regulation of MIF expression is associated with the occurrence of acute GVHD. Its pathogenetic role remains to be further determined.

Acute Disease↗