p-SAGE：基因集合的参数统计分析方法(英文)

肿瘤的发生与发展通常是由重要的细胞通路表达水平的反常导致的.尽管目前已经有很多工作利用基因表达谱数据以及一些其他的先验知识来寻找那些与肿瘤相关的基因集合,但还是没有一个恰当的基因集合的统计学方法.大多数研究都是直接将单基因的检验方法直接应用到基因集合上来.提出了基因集合的参数统计分析方法(p-SAGE),这个方法应用到大脑肿瘤的实验中,识别了许多显著的基因集合.一些新发现的基因集合是与信号转导和免疫相关的.这个简便有效的方法可以得出有生物学意义的结果.

Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research, The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PublVled literature search was conducted using the following keywords and combination of terms： radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways： （1） to generate gene signatures to identify sensitive and resistant populations （prognosis）; （2） to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack （diagnosis）; （3） to identify genes and pathways involved in tissue response to injury （mechanistic）. In this article we will review all （relevant） papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

The role of sexual related Y gene detection in the diagnosis of patients with gonadal dysgenesis

Objective To clarify the role of sexual related Y (SRY) gene detection in the diagnosis of gonadal dysgenesis.Methods Sixteen cases of gonadal dysgenesis were included in this study: 5 with androgen insensitivity syndrome, 1 with 17-α-hydroxylase deficiency, 4 with true hermaphrodite, 2 with 45,X/46,XY gonadal dysgenesis, 1 with 45,X gonadal dysgenesis, 1 with XY pure gonadal dysgenesis, 1 with testicular regression, and 1 XY female who gave birth to a normal baby. SRY gene was detected by using polymerase chain reaction (PCR) in blood and gonad samples and by direct sequencing of the SRY motif.Results Among the 16 cases, 15 were blood SRY positive, among which 13 (86.7%) showed the presence of testicular tissue, and 2 showed ovaries without testicular tissue. One SRY negative case showed the presence of testicular tissue. In 3 cases, SRY detection in gonadal tissue correlated with pathological findings but not with blood karyotype. The correlation between peripheral blood SRY and the pathology of the gonads was 81.25% and the correlation between the presence of peripheral blood Y chromosome and pathology of the gonads was 68.75%. Sequencing of the SRY motif in an XY female who gave birth to a normal baby showed no mutation.Conclusions SRY detection is more sensitive and specific than blood karyotype in the prediction of the presence of testicular tissue. Peripheral blood karyotype does not necessarily reflect gonadal type. There may be testicular related factors other than the SRY gene.

Expression and function of c-kit receptor in bone marrow mononuclear cells of patients with myelodysplastic syndromes

Objective To determine the expression and function of the c-kit receptor in bone marrow mononuclear cells (BMMNC) of patients with myelodysplastic syndromes (MDS). Methods Direct immunofluorescence assay and reverse transcriptase-polymerase chain reaction (RTPCR) were used to detect c-kit protein and c-kit mRNA expressions in the BMMNC of 29 MDS patients and 10 normal controls. Cell culture was used to detect the function of the c-kit receptor. Results c-kit protein expression in the MDS group was significantly higher than that in the control group (8.58％ +5.28％ vs 3.04％ + 1.49％, P＜0.05). c-kit protien expression in the refractory anemia (RA)group was significantly lower than that in the RA with an excess of blasts (RAEB)/RAEB in transformation (RAEB-t) group (5.12％ +2.13％ vs 10.01％ +5.07％, P＜0.05). The rate of c-kit protein expression was 32.43％ in aoute myeloblastic leukemia (AML) cases transformed from MDS (t-AML). c-kit mRNA expression in the MDS group was correlated with c-kit protein expression. Interieukin-3 (IL-3) and erythropoietin (Epo), with or without stem cell factor (SCF), upregulated c-kit protein and its mRNA expression. In the presence of IL-3 and Epo, SCF showed significant stimulating effects on the formation of CFU-GM and BFU-E in semi-solid cultures of normal BMMNC, but had no effects on those of the MDS patients.Conclusion The protein and mRNA expression of the c-kit receptor in the BMMNC of MDS patients were higher than those of normal controls, and the function of this receptor in MDS BMMNC was abnormal. Chin Med J 2001; 114(5) :481-485