Biomedical subjects

Chun Cheng

Publications and source records attributed to Chun Cheng.

6 recordsLinked to original sources

PubMed2006

Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer.

Genetic gains and losses resulting from DNA strand breakage by ionizing radiation have been demonstrated in vitro and suspected in radiation-associated thyroid cancer. We hypothesized that copy number deviations might be more prevalent, and/or occur in genomic patterns, in tumors associated with presumptive DNA strand breakage from radiation exposure than in their spontaneous counterparts. We used cDNA microarray-based comparative genome hybridization to obtain genome-wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post-Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in tumors from cases in exposed individuals was two- to fourfold higher than for cases in unexposed individuals and up to 10-fold higher for the subset of recurrent gains. DNA losses for all cases were low and more prevalent in spontaneous cases. We identified unique patterns of copy variation (mostly gains) that depended on a history of radiation exposure. Exposed cases, especially the young, harbored more recurrent gains that covered more of the genome. The largest regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1-.31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33, 16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy number changes, particularly gains, in post-Chernobyl thyroid cancer are influenced by radiation exposure and age at exposure, in addition to the neoplastic process.

Adolescent↗

PubMed2005

Effect of endogenous catecholamines in lymphocytes on lymphocyte function.

Our previous work has showed that lymphocytes can synthesize catecholamines (CAs). However, role and mechanism of the endogenous CAs in lymphocytes in modulation of immune function are less known. In the present study, we used alpha-methyl-p-tyrosine (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), and pargyline, an inhibitor of monoamine oxydase, to block the synthesis and degradation of CAs in lymphocytes and then observed changes of lymphocyte proliferation induced by concanavalin A (Con A). Phentolamine and propranolol, antagonists respectively to alpha- and beta-adrenoreceptors, were employed to investigate the receptor mechanism. We found that TH mRNA in the Con A-activated lymphocytes was 2.4 times higher in relative density than that in the resting lymphocytes. Similarly, the intracellular and supernatant CAs, including DA, NE and E, of the Con A-stimulated lymphocytes were significantly raised relative to those of the resting cells. alpha-MT (10(-11), 10(-10) and 10(-9) M) facilitated the Con A-induced lymphocyte proliferation, but pargyline (10(-11), 10(-10) and 10(-9) M) attenuated the cell proliferation. Meanwhile, alpha-MT and pargyline respectively led to decrease and increase in the intracellular and supernatant CAs (DA, NE and E) of the Con A-stimulated lymphocytes. Propranolol completely blocked, but phentolamine partly reversed, the suppressive effect of pargyline on the Con A-induced lymphocyte proliferation. Content of cAMP was remarkably increased in the lymphocytes treated with pargyline alone, but it dropped to control level after these cells were treated with propranolol plus pargyline. These results on the one hand further demonstrate the ability of lymphocytes to synthesize CAs and the enhancive ability of the activated lymphocytes to synthesize CAs, and on the other hand reveal an important role of the endogenous CAs in regulation of function of lymphocytes themselves. Besides, our present findings suggest that CAs synthesized by lymphocytes can secrete out of the lymphocytes via paracrine or autocrine pathway and affect lymphocyte function by beta-adrenoreceptor and cAMP mediating mechanism. Thus, it can be implied that CAs in lymphocytes are also involved in the cross-talk in the neuro-endocrine-immune networks.

Adrenergic alpha-Antagonists↗

PubMed2005

[Expression, localization and interrelationship of P27kip1 and cyclin D3 in non-Hodgkin's lymphoma].

OBJECTIVE: To investigate the expression, localization and interrelationship of P27(kip1) and cyclin D3 in non-Hodgkin's lymphoma (NHL). METHODS: The expressions of P27(kip1), cyclin D3 and index Ki-67 was detected in 100 NHL and 20 reactive lymph nodes by immunohistochemical technique. The expression and localization of P27(kip1) and cyclin D3 in 3 NHL cell lines were detected by Western blot, double immunolabelling and laser scanning confocal microscopy, respectively. RESULTS: In general the expression of P27(kip1) in NHL was lower than in control group, and was negatively related to the tumor aggressiveness and proliferating activity; the expression of cyclin D3 in NHL was higher than in control group, and was positively related to the tumor aggressiveness and proliferating activity. There was a negative correlation between P27(kip1) and cyclin D3. Nevertheless, anomalous high P27(kip1) expression was found in a few NHL tissues with high expression of cyclin D3 and Ki-67. Overexpression and colocalization of P27(kip1) and cyclin D3 was found in Raji cell line. CONCLUSIONS: Under expression of P27(kip1) and overexpression of cyclin D3 may play a role in the occurrence and development of NHL. Anomalous high P27(kip1) expression and its interaction with cyclin D3 may be another mechanism for tumor genesis of NHL.

Cell Line, Tumor↗

PubMed2004

An emerging peri-urban pattern of infection with Leishmania chagasi, the protozoan causing visceral leishmaniasis in northeast Brazil.

Peri-urban visceral leishmaniasis (VL) caused by Leishmania chagasi is emerging in a new epidemiologic pattern in Brazilian cities. We studied peri-urban VL in endemic neighborhoods surrounding Natal, Brazil, identified through hospitalized individuals with VL. Clinical and environmental information obtained for 1106 members of 216 families living in endemic neighborhoods enabled us to identify 4 groups: VL: individuals with current or prior symptomatic visceral leishmaniasis (n = 135); DTH+: individuals with positive delayed-type hypersensitivity response with no history of VL (n = 390); Ab +: individuals with negative DTH response and seropositive (n = 21); DTH -: individuals with negative DTH and seronegative (n = 560). The mean +/-SD age of VL was 9.3+/-12.3 y. The gender distribution was nearly equal below age 5, but skewed toward males at higher ages. Acutely infected VL subjects had significantly lower hematocrits, neutrophils, and eosinophils than other categories. AB+ subjects also had lower eosinophil counts than others, a possible immune marker of early infection. VL was not associated with ownership of dogs or other animals, raising the question whether the reservoir differs in peri-urban settings. This new pattern of L. chagasi infection enables us to identify epidemiological and host factors underlying this emerging infectious disease.

Adolescent↗

PubMed2003

Array rank order regression analysis for the detection of gene copy-number changes in human cancer.

cDNA microarray technology has been applied to the detection of DNA copy-number changes in malignant tumors. Test and control genomic DNA samples are differentially labeled and cohybridized to a spotted cDNA microarray. The ratio of test to control fluorescence intensities for each spot reflects relative gene copy number. The low signal-to-noise ratios of this assay and the variable levels of gene amplification and deletion among tumors hamper the detection of deviations from the diploid complement. We describe a regression-based statistical method to test for altered copy number on each gene and apply the technique to copy-number profiles in 10 thyroid tumors. We show that a novel transformation of fluorescence ratios into array rank order efficiently normalizes the heterogeneity among copy-number profiles and improves the reproducibility of the results. Array rank order regression analysis enhances the detection of consistent changes in gene copy number in solid tumors by cDNA microarray-based comparative genome hybridization.

Fluorescence↗

PubMed2002

Transcriptional expression profiles of oral squamous cell carcinomas.

BACKGROUND: Currently, the classification of oral squamous cell carcinoma (OSCC) depends heavily on the clinical and pathologic examination of tissue. This system can lead to the classification of potentially heterogeneous tumors into single groups when they may have different degrees of aggressiveness. No system to date has incorporated genetic changes as a factor by which to classify OSCC tumors. METHODS: To test the hypothesis that OSCC has a genome-wide genetic expression profile that differs from normal oral tissue and that transcriptional expression profiling can be used to characterize the heterogeneity among tumors, the authors examined the genetic expression profiles of 26 invasive squamous cell carcinomas of the oral cavity and oropharynx, 2 premalignant lesions, and 18 normal oral tissue samples using oligonucleotide arrays that contained probes representing approximately 7000 full-length human genes. RESULTS: Using hierarchical clustering analysis, the data show that oral carcinomas are distinguishable from normal oral tissue based on genome-wide transcriptional expression patterns. However, there is genetic expression profile heterogeneity among tumors of a particular histopathologic grade and stage. In addition, using a statistical approach that integrated normalization and regression analysis, the authors found 314 genes that were expressed differentially in the OSCC samples with statistical significance (P <or= 0.05). Of these, 239 genes were overexpressed in the OSCC samples, whereas 75 genes were down-regulated. CONCLUSIONS: No statistically significant differences in gene expression were found between early-stage disease and late-stage disease or between metastatic tumors and nonmetastatic tumors. The implications of these findings for the prediction of clinical outcome and for the discovery of new OSCC tumor markers are discussed.

Carcinoma, Squamous Cell↗