1.Molecular markers derived from ovarian cancer and its correlation with the types of oviductal epithelial lesions.
Yishu YUAN ; Wei ZHU ; Guanghui GONG ; Jing JIANG ; Yixuan WANG ; Xiaoying WU
Journal of Central South University(Medical Sciences) 2019;44(5):528-534
To explore the role of P53, pairing box gene 8 antibody (PAX8), and calcium omentum protein (Calretinin) in the origin of epithelial ovarian cancer.
Methods: A total of 63 tissue samples of ovarian tumor and fallopian tubes were collected. Immunohistochemistry methods were used to analyze the expression of P53, PAX8, and Calretinin. The relationship between these protein levels and the classification of ovarian tumors was evaluated.
Results: In epithelial ovarian cancer, the P53 or PAX8 was correlated with the occurrence of high-grade carcinoma, while the calretinin was correlated with the occurrence of low-grade carcinoma (P<0.05). The combination of PAX8 with Calretinin was correlated with the grade of ovarian tumor (P<0.05). The combination of P53 with Calretinin was correlated with the grade of tumor (P<0.05). The combination of P53 with PAX8 was correlated with the grade of tumor (P<0.05). The expression of P53 in fallopian tubes was correlated with the malignant degree of epithelial ovarian cancer (P<0.05). The degree of fallopian tube lesions in patients with ovarian cancer was correlated with epithelial ovarian cancer. The malignant lesions of tubal epithelium was correlated with high-grade carcinoma, while the normal or atypical hyperplasia of tubal epithelium was correlated with low-grade carcinoma (P<0.05).
Conclusion: P53 and Calretinin combined with PAX8 show a synergistic effect on the differentiation of epithelial ovarian cancer grade. The morphology of HE and the expression of TP53 in the fallopian tube epithelium play an auxiliary role in the diagnosis of epithelial ovarian cancer.
Carcinoma, Ovarian Epithelial
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Epithelium
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Fallopian Tubes
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Female
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Humans
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Ovarian Neoplasms
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PAX8 Transcription Factor
2.Impact of Pax-8 gene interference on mitochondrial function and cardiomyocyte apoptosis.
Xiao-chun DAI ; Xi ZHOU ; Xiao-yan HUANG ; Liang-guo WANG ; Su LIN ; De-ye YANG
Chinese Journal of Cardiology 2013;41(1):54-59
OBJECTIVETo observe the effects of paired box gene 8 (Pax-8) silencing by RNA interference on mitochondrial function and cardiomyocytes apoptosis.
METHODSThe cultured H9C2 (2-1) myocytes were divided into 3 groups: short interference RNA targeting Pax-8 (Pax-8 siRNA) group, non-specific siRNA group as the negative control (NC siRNA), and blank control group (BC siRNA). Fluorescence spectrophotometry was used to detect the activity of caspase-3. RT-PCR was performed to detect mRNA expression of Bcl2 and Bax. The protein expression of Bcl2, Bax and cytoplasm of Cytochrome was examined by Western blot. Changes of ΔΨm were detected by flow cytometry.ΔΨm with JC-1 monomer/polymer ratio was calculated for measuring mitochondrial depolarization proportion.
RESULTSCompared to NC siRNA and BC siRNA group (0.075 ± 0.021, 0.072 ± 0.019), the activity of caspase-3 in Pax-8 siRNA group (0.167 ± 0.012) was significantly increased (P < 0.05); Bcl2 mRNA and protein expression in Pax-8 siRNA group (0.61 ± 0.06, 0.94 ± 0.11) were significantly downregulated compared with NC siRNA group (0.90 ± 0.070, 1.39 ± 0.15) and BC siRNA group (0.94 ± 0.087, 1.49 ± 0.20) (P < 0.05); Bax mRNA and protein expression in Pax-8 siRNA group (1.05 ± 0.10, 1.25 ± 0.12) were markedly upregulated compared with NC siRNA group (0.72 ± 0.03, 0.99 ± 0.12) and BC siRNA group (0.64 ± 0.03, 0.92 ± 0.06), P < 0.05; cytosolic cytochrome expression in Pax-8 siRNA group (0.75 ± 0.14) was significantly upregulated compared with NC siRNA group (0.51 ± 0.06) and BC siRNA group (0.48 ± 0.07) (P < 0.05); JC-1 monomer/polymer ratio in Pax-8 siRNA group (0.163 ± 0.011) was significantly increased compared with NC siRNA group (0.092 ± 0.015) and BC siRNA group (0.072 ± 0.025) (P < 0.05) indicating mitochondrial membrane potential was significantly reduced in Pax-8 siRNA group. Above parameters were similar between NC siRNA group and BC siRNA group (P > 0.05).
CONCLUSIONInhibiting Pax-8 results in enhanced cardiomyocytes apoptosis through the mitochondrial pathway.
Animals ; Apoptosis ; Cells, Cultured ; Mitochondria, Heart ; metabolism ; Myocytes, Cardiac ; cytology ; metabolism ; PAX8 Transcription Factor ; Paired Box Transcription Factors ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; Rats ; Transfection
3.Advances in genetic research of congenital hypothyroidism in China.
Chinese Journal of Contemporary Pediatrics 2018;20(3):243-250
Congenital hypothyroidism (CH), which results from insufficient thyroid hormone biosynthesis, is one of the most common neonatal endocrine disorders. Thyroid dysgenesis and thyroid dyshormonogenesis are the two causes of CH and either one will lead to deficiencies of enzymes during thyroid hormone biosynthesis and insufficient thyroid hormone biosynthesis. Recently, researchers have performed extensive studies on genetics of CH. This paper reviews genes reported to be associated with CH in China.
Congenital Hypothyroidism
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genetics
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Humans
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Iodide Peroxidase
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genetics
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Membrane Proteins
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genetics
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PAX8 Transcription Factor
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genetics
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Receptors, Thyrotropin
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genetics
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Thyroglobulin
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genetics
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Transcription Factors
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genetics
4.Expression of carbonic anhydrase IX, PAX2 and PAX8 and their association with clinicopathologic characteristics in renal epithelial tumors.
Wei ZHANG ; Wen-juan YU ; Yan XIA ; Yan LIU ; Xiao-ling LIU ; Jie ZHUANG ; Yu-jun LI
Chinese Journal of Pathology 2013;42(7):442-445
OBJECTIVETo study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics.
METHODSImmunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls.
RESULTSCAIX was commonly expressed in CCRCC (94.0%, 63/67), of which 77.8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor.
CONCLUSIONSCAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.
Adenoma, Oxyphilic ; metabolism ; pathology ; Antigens, Neoplasm ; metabolism ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; Male ; PAX2 Transcription Factor ; metabolism ; PAX8 Transcription Factor ; Paired Box Transcription Factors ; metabolism
5.Diagnosis, histopathologic grading and prognostic moleculer marker analysis in patients with pancreatic neuroendocrine neoplasm.
Fang BAO ; Guo-rong CHEN ; Pei HUI ; Guo-ping CAI
Chinese Journal of Pathology 2013;42(6):426-432
Humans
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Hypoxia-Inducible Factor-Proline Dioxygenases
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metabolism
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Ki-67 Antigen
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metabolism
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MicroRNAs
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metabolism
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Neoplasm Grading
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Neoplasm Staging
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Neprilysin
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metabolism
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Neuroendocrine Tumors
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classification
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diagnosis
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metabolism
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pathology
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surgery
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PAX8 Transcription Factor
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Paired Box Transcription Factors
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metabolism
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Pancreatic Neoplasms
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classification
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diagnosis
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metabolism
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pathology
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surgery
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Prognosis
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Tumor Suppressor Proteins
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metabolism
6.A study on myocardial Pax-8 gene.
De-ye YANG ; Hou-yan SONG ; Huai-qin ZHANG ; Xiao-yan HUANG ; Shang-gong LI ; Xiao-qun GUAN
Chinese Journal of Pediatrics 2003;41(10):770-772
OBJECTIVEConventional deletion of ALK3, also termed as bone morphogenetic protein (BMP) receptor IA, in mice might result in early embryonic lethality. To investigate the function of ALK3 in cardiac development, the cardiac-specific deletion of ALK3 in mice was made by Dr. Schneider, using Cre recombinase driven by the alpha-MHC promoter that Dr. Fukushipe worked out. Such specific deletion of ALK3 caused death in mid-gestation with defects in the trabeculae, interventricular septum, and endocardial cushion. Since ALK3 is not a cardiac-specific gene, it is extremely important to identify ALK3 downstream genes.
METHODSAlpha-MHC Cre+/-, ALK3 F/- and alpha-MHC Cre+/-, ALK3 F/+ embryos were obtained after 20 alpha-MHC Cre+/-, ALK3 +/- mice and 20 ALK3 F/F mice were mating. The ALK3 downstream genes were screened using microarray made in Germany that could identify 25000 genes in mouse. Two populations of mRNA, one derived from the embryonic heart (11.5 days) of alpha-MHC Cre+/-, ALK3 F/- mice, and the other derived from the alpha-MHC Cre+/-, ALK3 F/+ mice, were compared. Cardiac-specific ALK3 downstream genes were identified using real time quantitative RT-PCR and in situ hybridization.
RESULTSThe expression of 12 genes, such as Pax-8 and Hox-3.5 were down-regulated in alpha-MHC Cre+/-, ALK3 F/- mouse heart. The expression of 16 genes including Ras-related protein Rab-5b and EPS-8 protein was up-regulated in the group of alpha-MHC Cre+/-, ALK3 F/-. It was found that the Box protein Pax-8 gene was down-regulated by 7.1 fold (P < 0.001) in the alpha-MHC Cre+/-, ALK3 F/- mice by real time quantitative RT-PCR. It was also revealed that the Box protein Pax-8 gene was expressed stronger in alpha-MHC Cre+/-, ALK3 F/+ than alpha-MHC Cre+/-, ALK3 F/- E11.5 days mouse heart by means of in situ hybridization.
CONCLUSIONThe Box protein Pax-8 gene is an important and cardiac-specific ALK3 downstream gene in the BMP signaling pathway during inter-ventricular septum development.
Animals ; Bone Morphogenetic Protein Receptors ; DNA-Binding Proteins ; genetics ; Down-Regulation ; Female ; Heart ; embryology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium ; metabolism ; pathology ; Nuclear Proteins ; Oligonucleotide Array Sequence Analysis ; PAX8 Transcription Factor ; Paired Box Transcription Factors ; Receptors, Growth Factor ; genetics ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Activators ; genetics
7.Preliminary study of ALK3 downstream genes related to ventricular septum defect.
De-Ye YANG ; Hou-Yan SONG ; Huai-Qin ZHANG ; Xiao-Yan HUANG ; Xiao-Qun GUAN
Chinese Journal of Biotechnology 2003;19(3):267-271
To investigate the function of ALK3 gene, the gene regulation and the signaling pathway related to ventricular septum defect during heart development. The model mice with ALK3 gene knock-out via alpha-MHC-Cre/lox P system were bred. The mRNA expression level of control group was compared with that of experiment group and ALK3 downstream genes were screened using PCR-select cDNA subtraction microarray. The mRNA of control group was extracted from E11.5 normal mouse hearts, and that of experiment group, from E11.5 hearts of mice with alpha-MHC Cre(+/-) ALK3(F/+) genotype. It was found that the mice with ALK3 gene knock-out produced heart defects involving the interventricular septum. The platelet-activating factors acetylhydrolase and the transcription factor Pax-8 and so on, were down-regulated. However, the Protein Tyrosine Kinase (PTK) of Focal Adhesion Kinase (FAK) subfamily and beta subtype protein 14-3-3 were up-regulated in the alpha-MHC Cre(+/-) ALK3(F/-) mice. These data provide support that ALK3 gene played an important role during heart development. The platelet-activating factors acetylhydrolase and Pax-8 genes could be important ALK3 downstream genes in the BMP signaling pathway during interventricular septum development. PTK and beta subtype protein 14-3-3 might be regulatory factors in this pathway.
1-Alkyl-2-acetylglycerophosphocholine Esterase
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genetics
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metabolism
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14-3-3 Proteins
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genetics
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metabolism
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Animals
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Bone Morphogenetic Protein Receptors, Type I
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genetics
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metabolism
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Genotype
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Heart Septal Defects, Ventricular
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genetics
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Mice
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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PAX8 Transcription Factor
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Paired Box Transcription Factors
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genetics
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metabolism
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Protein-Tyrosine Kinases
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genetics
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metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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genetics
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physiology