Biomedical subjects

Sai-juan Chen

Publications and source records attributed to Sai-juan Chen.

9 recordsLinked to original sources

PubMed2006

The molecular cytogenetic aberration analyzed by comparative genomic hybridization and its significance in diffuse large B-cell lymphoma.

OBJECTIVE: To identify genetic alterations in diffuse large B-cell lymphoma (DLBCL) and to analyse the relationship between the genetic aberrations and the clinical characteristics. METHODS: Using comparative genomic hybridization (CGH) to investigate the genomic changes in 24 cases of DLBCL and to analyse the relationship between these aberrations and clinical parameters including Ann arbor stage, systemic symptoms, chemotherapy efficacy and survival. RESULTS: Aberrations were detected in 62.5% patients of 24 cases; the most common chromosomal alterations included loss of 6q15-21 as well as gain of 18q11-ter, of which the incidences were 20.8% and 16.7%, respectively; with comparing clinical parameters between patients with normal CGH and abnormal CGH, we found that patients with abnormal CGH suffered more from stage III-IV and had higher incidence of systemic symptoms, poor chemotherapy efficacy and poor survival (P<0.05), but there was no difference observed in the incidence of extranodal involvement between two groups. CONCLUSION: The gains and/or losses of genomic DNA from DLBCL patients are the common molecular cytogenetic aberrations; loss of 6q15-21 and gain of 18q11-ter are nonrandom event to DLBCL patients; abnormal CGH is a clinical parameter reflecting malignant progressive course and poor survival to DLBCL patients.

Chromosome Aberrations↗

PubMed2004

[Development of human myeloid leukemia-like phenotype in NUP98-PMX1 transgenic mice].

OBJECTIVE: In order to investigate the leukemogenic potential of NUP98-PMX1 fusion gene in vivo. METHODS: NUP98-PMX1 transgenic mice were generated, in which the fusion gene was driven by hCG promoter and expressed in myeloid cells at early stage of differentiation. Molecular cloning technology was used to construct NUP98-PMX1 transgenic plasmid. The genotype and phenotype of the NUP98-PMX1 transgenic mice were analyzed by PCR, RT-PCR, peripheral blood count (PBC), bone marrow (BM) cells morphology and pathological examination. RESULTS: NIH3T3 cells transfected with NUP98-PMX1 fusion gene grew faster, formed colonies in soft agar, and developed tumors in 10 inoculated nude mice. Among 8 disordered NUP98-PMX1 transgenic mice, 4 developed myeloid leukemia-like phenotype, including 3 resembling human chronic myeloid leukemia. CONCLUSION: NUP98-PMX1 has oncogenic activity and plays a crucial role in leukemogenesis.

Animals↗

PubMed2004

[Gene expression profile of yolk sac and fetal liver in mouse].

OBJECTIVE: To better understand the mechanisms of the fetal hematopoiesis turn over from primitive to definitive hematopoiesis through the expression level of c-kit(+) and sca-1(+), and major characters of gene expression profile of these cells. METHODS: c-kit and sca-1 expression level were monitored with fluorescence activated cell sorting (FACS) of the mononuclear cells from mouse yolk sac and fetal liver, while gene expression profile was carried out with EST sequencing strategy. RESULTS: The Sca-1(+) cells were increased while the c-kit(+) cells decreased with the embryonic development. Through profiling the functionally identified known genes, most of the highly expressed were globin genes, especially of embryonic types. CONCLUSION: The erythropoiesis played a key role in early fetal hematopoiesis in mammalian.

Animals↗

PubMed2004

[Establishment of CPP-SOM integrated cDNA microarray technology].

OBJECTIVE: To get an insight into the molecular mechanisms of diseases development and targeted therapy at the transcriptome level and search for potential therapeutic targets. METHODS: The present researchers established a cDNA microarray platform and applied component plane presentation integrated self-organizing map (CPP-SOM) to the microarray data obtained from a differentiation model, all trans retinoic acid-induced differentiation in NB4 cells. RESULTS: The platform included 12630 unique clones, including 9436 known genes. By CPP-SOM, the researchers were able to not only well classify the regulated genes into functionally distinct categories but also depict transcriptional changes throughout the process of the development of diseases or drug treatment. CONCLUSION: The platform has proven to be steady and reliable, and the CPP-SOM could serve as an important and good tool for analysis of microarray data.

Cell Line, Tumor↗

PubMed2003

[In vitro study of the effects of arsenic trioxide combined with 8-CPT-cAMP on differentiation induction in retinoic acid resistant acute promyelocytic leukemia cells].

OBJECTIVE: To investigate the potential effects of arsenic trioxide (As(2)O(3)) combined with 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells. METHODS: The RA resistant APL cell lines NB4-R1 and NB4-R2 were used as in vitro models. The effect of As(2)O(3) and/or 8-CPT-cAMP was evaluated according to cellular morphology, cell surface antigen and nitroblue-tetrazolium (NBT) assay. Meanwhile, immunofluorescence analysis and Western blot assay were used to detect the degradation of PML-RAR alpha fusion protein and the change of several key cell cycle regulatory proteins in these cells before and after the treatment. RESULTS: Low dose of As(2)O(3) (0.25 micromol/L) synergized with 8-CPT-cAMP (200 micromol/L) in inducing differentiation of NB4-R1 and NB4-R2 cells, while neither of these two drugs alone could induce differentiation of these cells. In addition, 8-CPT-cAMP was able to inhibit the cell growth by modulating the expression of some important cell cycle regulators and to facilitate the As(2)O(3)-mediated degradation of PML-RAR alpha fusion protein. CONCLUSIONS: As(2)O(3) combined with 8-CPT-cAMP could induce differentiation of RA-resistant APL cells.

Antineoplastic Agents↗

PubMed2003

[Clinical observation of the short-term efficacy of the treatment with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) in newly diagnosed acute promyelocytic leukemia (APL)].

OBJECTIVE: To study whether all-trans retinoic acid (ATRA) combined with arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment could further improve the clinical and molecular remission rate. METHOD: Thirty one newly-diagnosed APL patients of whom 15 were males, 16 females and median age 35.4 years entered into the study. They were treated with ATRA 25 mg x m(-2) x d(-1) combined with As(2)O(3) 0.16 mg x kg(-1) x d(-1) until complete remission (CR). The doses were adjusted according to white blood cell (WBC) counts, occurrence of RA syndrome and the status of liver function. CR rate, time of reaching clinical and molecular remission and side effects were observed. RESULT: Two patients died 2 approximately 3 days after the treatment due to intracranial hemorrhage, and 29 (93.5%) achieved CR. The average time for achieving CR was 25.1 +/- 3.9 days. Hyperleukocytosis emerged in 66.5% and hepatic damages in 65.5% of the patients, they were ameliorated within one week after reduction of the As(2)O(3) dose or its suspension. The PML/RAR alpha fusion gene that was positive in all 29 patients before treatment turned negative only in 3 cases (10.3%) after obtaining CR (CR1) and in 10/13 cases (77%) after consolidation treatment. Up to now (1-8 months follow-up), all 29 patients remain in CR1. CONCLUSION: ATRA combined with As(2)O(3) in de novo APL treatment can yield a high CR rate without intolerable side effects. Long term effect needs further observation.

Adolescent↗

PubMed2003

[Influence of irradiation on the dynamic three-dimension distribution of abl and bcr genes in the interphase nuclei of IM-9 cell].

OBJECTIVE: To investigate the material foundation of the fusion of bcr and abl genes, and to explore the pathogenesis of chronic myeloid leukemia. METHODS: By FISH combined with laser confocal scanning microscopy, the three-dimension (3D) distribution of bcr and abl genes in the interphase nuclei of normal and irradiated IM-9 cells was studied in each cell cycle phases. RESULTS: abl and bcr genes distributed non-randomly in the interphase nuclei of IM-9 cells. abl gene preferably located at the outer layer and bcr near the core of the nucleus. The two genes were drawn near each other most in G(0) phase. The relative distance between the homologous genes was greater at proliferation phase than at quiescence phase. After irradiation, the relative distances from the two genes to the core and between the two genes were shortened, with the shortest distance between the two genes in S phase. CONCLUSION: Irradiation could change the 3D-distribution of abl and bcr genes in the interphase nuclei of IM-9 cell and accelerate them to draw near each other.

Cell Nucleus↗

PubMed2003

[Establishment of transgenic mice for HRX-EEN fusion gene].

OBJECTIVE: To study the biological function of fusion gene HRX-EEN and its role in leukemogenesis, and to provide an ideal animal model for anti-leukemia drug screening. METHODS: HRX-EEN fusion gene was constructed by use of three different DNA fragments, and it was inserted into hCG transgenic vector. G(0) transgenic mice were obtained by microinjection of the recombined DNA into the pronucleus of zygotes, followed by implantation of the injected zygotes into pseudopregnant mice. The integration of the transgene was tested by PCR and its expression by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The sequence of recombined HRX-EEN gene was confirmed by sequencing. PCR testing revealed a total of 7 G(0) transgenic mice, these mice were then mated with C57 wild type mice. Except mouse No. 35 that died, the others all had their F1 offsprings. From these 6 lines of transgenic mice, HRX-EEN gene was found to be stably expressed in 3 lines by RT-PCR. Up to now, all transgenic mice expressing the fusion gene have no obvious abnormal phenotypes. CONCLUSION: A transgenic mice model in which the HRX-EEN fusion gene can be stably expressed has been established.

Animals↗

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↗