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Biomedical subjects

C S Chim

Publications and source records attributed to C S Chim.

At least 19 recordsLinked to original sources
PubMed2006

Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic lymphocytic leukemia.

Dysregulation of apoptosis, and thus the p14/DAP kinase/HDM2/p53/Apaf-1 pathway, is potentially important in carcinogenesis. Chronic lymphocytic leukemia (CLL), uncommon in the Chinese, is a disease characterized by impaired apoptosis, of the neoplastic lymphocytes. Hypermethylation of p14, DAP kinase and Apaf-1 was studied by methylation-specific polymerase chain reaction (MSP) with primers for methylated (M-MSP) and unmethylated (U-MSP) alleles in 50 diagnostic marrow samples from patients with CLL. Chinese CLL patients had an indolent course similar to Caucasians with median overall survival (OS) of 96 months, which was adversely affected by advanced Rai stage (projected 5-year OS = 72% and 39% for Rai < or = 2 and Rai > 2; P = 0.01). DAP kinase was methylated in 18 (36%) patients while p14 and Apaf-1 were completely unmethylated in all the primary CLL samples. There was no correlation between DAP kinase hypermethylation and age, sex, poor-risk karyotype, lymphocyte count and Rai stage at diagnosis. Projected OS for patients with and without DAP kinase hypermethylation were 59 and 57% (P = 0.91). DAP kinase, but not p14 and Apaf-1, of the DAP kinase/p14/HDM2/p53/Apaf-1 pathway is frequently hypermethylated in CLL, but not of prognostic significance. Moreover Chinese patients with CLL share a similarly indolent clinical course, and this is the first comprehensive study on p14, DAP kinase and Apaf-1 hypermethylation in CLL.

Adult↗
PubMed2006

Methylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patients.

BACKGROUND: INK4 (p15, p16, p18 and p19) and CIP/KIP (p21, p27 and p57) are two families of cyclin-dependent kinase inhibitors (CKI) targeting CDK4/6 and CDK2, respectively. AIM: To study the role of methylation in the inactivation of CKI in chronic lymphocytic leukaemia (CLL). MATERIALS AND METHODS: Methylation-specific polymerase chain reaction was carried out on DNA obtained from the bone marrow of 56 newly diagnosed patients with CLL. RESULTS: Similar demographic features and clinical outcome were observed in our patients when compared with Caucasian patients, including an indolent clinical course (10-year overall survival 51%) and advanced Rai stage (p = 0.006), and a high-risk karyotype such as trisomy 12 and complex aberrations (p = 0.03). In the INK4 family, methylation in p15 and p16 occurred in 20 (35.7%) and 8 (14.3%) patients, respectively. In all, 5 (8.9%) CLL samples harboured concurrent methylation of both p15 and p16. Apart from an association of p16 methylation with higher presenting leucocyte count (64.5 x 10(9)/l in methylated p16 and 16.0 x 10(9)/l in unmethylated p16 patients; p = 0.016), there was no association between p15 and p16 methylation and age, sex and Rai stage. No difference was observed in the overall survival for patients with and without p15 and p16 methylation. By contrast, p18 and Rb were unmethylated in all samples. In the CIP/KIP family, apart from infrequent methylation of p57 in 4 (7.1%) patients, methylation of p21 and p27 was uniformly absent. CONCLUSION: p15 and, less frequently, p16 of the INK4 family of CKI, instead of the CIP or KIP family, were targeted by methylation in CLL. p16 methylation was associated with a higher lymphocyte count at presentation. This is the first comprehensive study of the epigenetic dysregulation of the INK4 and CIP/KIP families of CKI in Chinese patients with CLL.

Adult↗
PubMed2006

Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia.

The Wnt pathway has been shown recently, to be activated in patients with chronic lymphocytic leukemia (CLL). This is the first study to examine the role of Wnt inhibitory factor-1 (Wif-1) methylation in the pathogenesis of haematolymphoid malignancies. Wif-1, a putative tumor suppressor, is a soluble negative regulator of the Wnt pathway activated in CLL. We studied the role of methylation of Wif-1 in 43 Chinese patients with CLL. At diagnosis, Wif-1 methylation was detected in 5/43 (11.6%) CLL marrow samples. Wif-1 methylation occurred more frequently in patients with advanced age (p = 0.059) but there was no correlation between Wif-1 methylation and sex, lymphocyte count and Rai stage at diagnosis. In conclusion, Wif-1 is infrequently methylated in CLL. Other factors leading to activation of the Wnt pathway warrant further study.

Adaptor Proteins, Signal Transducing↗
PubMed2006

EBV-associated synovial lymphoma in a chronically inflamed joint in rheumatoid arthritis receiving prolonged methotrexate treatment.

A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.

Aged↗
PubMed2005

Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias.

Dysregulation of the cell cycle is important in oncogenesis. We analyzed the potential inactivation of the CIP/KIP family of the cyclin E/CDK/RB pathway by gene promoter hypermethylation in leukemias. The methylation-specific polymerase chain reaction (MSP) with primers for methylated (M-MSP) and unmethylated (U-MSP) alleles of the p21, p27, and p57 genes was used to study five leukemic cell lines, 50 acute myeloid leukemia (AML) samples, and 25 acute lymphoblastic leukemia (ALL) samples. p21 was hemizygously methylated in Raji and Jurkat but remained unmethylated in U937, HL60, and NB4. p27 was hemizygously methylated in Raji but unmethylated in the other cell lines. p57 was completely methylated in Raji and NB4, hemizygously methylated in U937, and unmethylated in HL60 and Jurkat. At diagnosis, p21 methylation was not detected in any case of AML or ALL. p27 methylation occurred in 2 (4%) AML patients and in 1 (4%) ALL patient. p57 methylation occurred in 1 (2%) AML patient and in 1 (4%) ALL patient. Therefore, methylation inactivation of the INK4/CDK/RB pathway in leukemia is infrequent. A review of the literature showed a marked variation in the frequencies of methylation of these genes, which might be attributable to difference in methodologies used to detect gene methylation.

Alleles↗
PubMed2005

Der(8)t(1;8) in myeloblastic transformation of ET with hydroxyurea as the sole prior treatment.

We described a patient with ET that evolved into MF and then subsequently developed myeloblastic transformation. A novel derivative chromosome der(8)t(1;8) was identified in the AML phase. The only prior treatment had been hydroxyurea. We hypothesized that AML in this case resulted from a complex pre-disposition by the natural progression of ET, prolonged use of HU, and the prior evolution into MF. The leukemogenic risk of HU is critically appraised.

Cell Transformation, Neoplastic↗
PubMed2005

Eosinophilic leukemic transformation in polycythemia rubra vera (PRV).

We report a rare case of eosinophilic leukemia transformation in a patient with polycythemia rubra vera on hydroxycarbamide (hydroxyurea) therapy only. Cytogenetic study showed complex abnormalities including -5, -7, +8, suggestive of a secondary leukemia. The leukemogenic risk of hydroxycarbamide, a ribonucleoside reductase, and the risk of natural leukemic transformation of polycythemia rubra vera is discussed in the context of previous PVSG studies.

Aged↗
PubMed2005

Primary anaplastic large cell lymphoma of the pancreas.

Most solid pancreatic tumors are exocrine adenocarcinomas. We presented a patient with primary ALCL of the pancreas masquerading as a carcinoma of the head of pancreas. She was scheduled for a Whipple's operation and the intra-operative frozen section showed anaplastic carcinoma. The proper diagnosis was only derived later with CD30 immunohistochemical study. This carries important implications on the management, as radical surgery is indicated in resectable carcinoma but not for a chemosensitive lymphoma.

Adult↗
PubMed2005

An epidemiological study of motor neuron disease in Hong Kong.

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

Adult↗