Biomedical subjects

Zhu Chen

Publications and source records attributed to Zhu Chen.

84 records · Page 5Linked to original sources

PubMed2002

Expanding the use of arsenic trioxide: leukemias and beyond.

Arsenic has a long history of use in Chinese and Western medicine but fell out of use in the mid-20th century because of the unacceptable side effects that occurred at the doses that were thought to be necessary. The re-emergence of arsenic trioxide (ATO) in clinical use is due largely to purification of this compound from traditional mixtures, and the definition of effective, low-dose regimens for the treatment of acute promyelocytic leukemia (APL). ATO was first purified and used in controlled studies in patients with APL in China in the 1970s. Studies have subsequently also been performed in the United States. Complete response (CR) rates reported in patients with relapsed or refractory APL have varied from 52% to 92%, with similar rates reported in patients with newly diagnosed disease. The mechanism of action of ATO suggests it may be active against other malignancies, and ATO has shown some activity in patients with accelerated phase chronic myelogenous leukemia (CML) and multiple myeloma (MM). Clinical trials are ongoing and planned to define the optimal use of this compound in hematologic malignancies. Preliminary results from studies in patients with primary hepatocellular and gallbladder tumors indicate that ATO may also prove active against some solid tumors.

Antineoplastic Agents↗

PubMed2002

Single nucleotide polymorphisms in CAPN10 gene of Chinese people and its correlation with type 2 diabetes mellitus in Han people of northern China.

OBJECTIVE: To investigate the distribution of single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was sequenced to detect SNPs in different nationalities of China. Five SNPs were chosen to perform case-control study and haplotype analysis in 156 normal Han people of Northern China and 173 type 2 diabetes. One SNP was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 people). RESULTS: A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp. The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese were different from those reported in Mexican American. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control, and the haplotype frequencies in the two groups were not significantly different. No positive results was found in TDT and STDT analysis. CONCLUSIONS: The SNP distribution of CAPN10 gene differs in different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.

Calpain↗

PubMed2002

[Experimental study of low dose arsenic trioxide in treatment of patients with acute promyelocytic leukemia].

BACKGROUND & OBJECTIVE: Low dose arsenic trioxide(As2O3) is one of the effective treatments for patients with acute promyelocytic leukemia (APL). As2O3 could induce complete remission in de novo APL patients as well as in relapsed APL patients who have been resistant to all-trans retinoic acid (ATRA). However, the underlying mechanisms of As2O3-induced remission remain obscure. Therefore, we designed this study to explore the possible mechanism of low dose As2O3 in treatment of the patients with APL. METHODS: The APL cell line NB4 and primary malignant cells isolated from APL patients were used as in vitro models. Cell differentiation was determined by cell morphology, NBT reduction test and cytometry assay of cell differentiation antigens. The change of PML-RAR alpha fusion protein was analyzed by immunofluorescence and Western blot. RESULTS: The 0.25 mumol/L As2O3 combined with cyclic adenosine monophosphate(cAMP) analogue, 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP), had induced differentiation in NB4 cell line and primary cells. It was also found that this effect could be attenuated by H89, a specific PKA inhibitor. Moreover, 8-CPT-cAMP was able to facilitate the As2O3-mediated degradation of PML-RAR alpha. CONCLUSIONS: The 8-CPT-cAMP could enhance As2O3-induced differentiation in APL cells.

Antineoplastic Agents↗

PubMed2002

[The association of two single nucleotide polymorphisms in PRKCZ and UTS2 respectively with type 2 diabetes in Han people of northern China].

OBJECTIVE: To probe the candidate susceptibility gene (s) of type 2 diabetes in the formal mapping region, 1p36.33-p36.23, in Han people of Northern China using single nucleotide polymorphisms (SNPs). METHODS: 23 SNPs located in 10 candidate genes in the mapping region were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method were used to genotype the loci in 192 sporadic type 2 diabetes patients and 172 normal individuals to perform case-control study. RESULTS: Among the 23 SNPs, 8 were found to be common in Chinese population. There were statistically different in the allele frequency of 2 SNP, rs436045 in the protein kinase C/xi gene and rs228648 in Urotensin II gene between case and control groups. CONCLUSIONS: The two SNP may be associated with type 2 diabetes in Han people of China, which makes base for further study of the relation between the genes they located with type 2 diabetes.

Alleles↗

PubMed2002

[Single nucleotide polymorphisms in CAPN10 gene of Chinese population and its correlation with type 2 diabetes mellitus in Han people of northern China].

OBJECTIVE: To investigate the distribution of the single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was sequenced to detect SNPs in 27 samples of different nationalities in China. 5 SNPs were genotyped with single-base extension (SBE) method to perform case-control study in 156 normal Han people of Northern China and 173 type 2 diabetes and the 3 positive loci reported in the article were performed haplotype analysis. One positive locus was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 cases). RESULTS: A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp; The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese was different from that reported in American Mexicans. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control (P > 0.05), and the haplotype frequencies in the two groups were not much different (P > 0.05). There was no positive results in TDT and STDT analysis (P > 0.05). CONCLUSIONS: The SNP distribution of CAPN10 gene varies with different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.

Alleles↗

PubMed2002

[Fine mapping of susceptibility genes loci within chromosome 1 in Chinese Han families with type 2 diabetes].

OBJECTIVES: To confirm previous whole-genome scan results of mapping type 2 diabetes susceptibility genes in chromosome 1 in Northern Chinese Han population by conducting a new genome scan with both an enlarged number of type 2 diabetes families and a new set of microsatellite markers. METHODS: A genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, size informations for all loci were obtained, and a further study was done using both parametric and non-parametric linkage analysis to calculate the P-values and Z-values of these loci. RESULTS: A total of 34 microsatellite markers distributed within 5 regions along chromosome 1 were surveyed, and 12,000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci (all the P-values of the 8 loci distributed in 3 regions were lower than 0.05, and the highest Z-value was 2.17). Interestingly, all the 5 markers at the P terminal 1p36.3-1p36.23 region, spanning a long range of 16.9 cM, suggested to be linked with the disease. The results of the other two regions were not consistent with the previous ones. CONCLUSIONS: The study results have confirmed those gained in the previous genome-wide scan. The fact that all 5 loci at the P terminal region displayed linkage with diabetes suggests that more than 1 susceptibility gene may reside in this region.

Asian People↗

PubMed2002

[Functional analysis of the single nucleotide polymorphisms in the PRKCZ gene].

OBJECTIVE: To study the function of 5 single nucleotide polymorphisms (SNPs) of the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, in the pathogenesis of the disease. METHODS: Bioinformatic methods and reporter gene activity determination were used to analyze the function of the 5 SNPs. RESULTS: The reporter gene activities of different alleles of 2 SNPs, rs427811 and rs809912, were obviously different, which implies that these 2 SNPs might be susceptibility loci of the disease. CONCLUSION: The PRKCZ gene is further confirmed to be a susceptibility gene for type 2 diabetes in Han population of North China. Two SNPs in the gene play a role in the pathogenesis of the disease by affecting the expression level of PRKCZ gene.

Alleles↗

PubMed2002

[Linkage disequilibrium analysis of the single nucleotide polymorphisms in the PRKCZ gene].

OBJECTIVE: To search for the disease-associated haplotype in the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, by case-control study and linkage disequilibrium (LD) analysis using single nucleotide polymorphisms (SNPs). METHODS: SNPs located in the PRKCZ gene were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method was used to genotype the loci in 173 sporadic type 2 diabetes patients and 152 normal individuals to perform case-control study and LD analysis. Haplotype block were constructed in these populations. RESULTS: Several SNPs in the PRKCZ gene were found to be associated with the disease. The SNPs formed different haplotype block pattern in case and control groups. The frequencies of the haplotypes formed by 5 SNPs were statistically different between the two groups. CONCLUSION: The haplotype formed by 5 SNPs in the PRKCZ gene may be associated with type 2 diabetes in Han population of China, which is confirmed from statistics to be a susceptibility gene for the disease.

Alleles↗

PubMed2000

[Development of Acute Promyelocytic Leukemia in PML-RARalpha Transgenic Mice]

To investigate the leukemogenic potential of PML-RARalpha fusion protein in vivo, hCG-PML-RARalpha transgene was constructed using molecular cloning technique and hCG-PML-RARalpha transgenic mice were generated. The genotype and phenotype of hCG-PML-RARalpha transgenic mice were analyzed by PCR, RT-PCR, morphology of peripheral blood and bone marrow cells, and pathological examination of spleen, liver and bone marrow. As a result, acute promyelocytic leukemia was developed in 3 hCG-PML-RARalpha transgenic mice in 1 - 5 months. The results demonstrated that PML-RARalpha fusion protein plays a crucial role in leukemogenesis.

Journal Article↗

PubMedDate not supplied

Transcriptome study in China.

The Chinese genome project was initiated in 1993 with the goal of contributing 1% to the Human Genome Program. The study of gene expression profiles with cDNA microarrays, and large-scale sequencing and analysis of 130928 expressed sequence tags (ESTs), allowed isolation and characterization of over 1000 novel full-length human cDNAs derived from human hematopoietic stem/progenitor cells, neuroendocrine tissues, liver, and cardiovascular cells. In addition, EST sequencing for model organisms, including rat, zebrafish, Schistosoma japonicum and rice was performed, aiming at identifying genes associated with physiological and/or pathological characteristics.

Animals↗

PubMedDate not supplied

Foreword: from the TRANSCRIPTOME conferences to the SYSTEMOSCOPE international consortium.

This thematic issue issue of the Comptes rendus Biologies contains review articles, original papers and conference reports presented at the first two TRANSCRIPTOME conferences From Functional Genomics to Systems Biology and IMAGE Consortium Invitational workshops (Paris, November 2000 and Seattle, March 2002), and discussed during the inaugural meetings of the SYSTEMOSCOPE International Consortium (Paris, June 2003). We describe the founding principles, missions, working plan and policy for partnership and industrial development of SYSTEMOSCOPE to promote the study of the complexity of biological systems by integrating scientific, medical, ethical and economic issues in implementation of interdisciplinary projects for human health.

Biology↗

PubMedDate not supplied

Treatment of acute promyelocytic leukemia with ATRA and As2O3: a model of molecular target-based cancer therapy.

Most acute promyelocytic leukemia (APL) cases have t(15;17)(q22;q21) chromosomal translocation and PML-RARalpha chimeric gene which blocks granulocytic differentiation. The introduction of all-trans-retinoic acid (ATRA) and arsenic compounds, especially arsenic trioxide (As(2)O(3)), has provided good models to study not only differentiation and/or apoptosis therapy but also molecular target-based cancer treatment. In vivo and in vitro investigations have shown that both agents are able to induce differentiation of APL cells: ATRA tends to induce terminal differentiation, while low-dose As(2)O(3) can induce partial differentiation. Significant progress has been made in understanding the molecular mechanisms of APL pathogenesis and differentiation therapy. Pharmacological concentrations (0.1 approximately 1 microM) of ATRA derepresses transcription by releasing CoR from, and recruiting CoA to PML-RARalpha, whereas As(2)O(3) triggers a rapid degradation of PML-RARalpha. In fact, the two drugs act on the same oncoprotein through targeting different moieties and in distinct ways and thereby abrogate its dominant-negative effects on regulatory pathways necessary for granulocytic differentiation. As to apoptosis, it is clear that high-dose As(2)O(3) can induce mitochondria-mediated cell death pathway in a thiol-dependent manner, while the mechanism of ATRA-induced apoptosis needs further elucidation. Transcriptomic and proteomic analysis are also expected to find new molecular targets. It is the hope that what we have learnt from APL will benefit further developments of anti-leukemia therapy.

Animals↗