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ABSTRACT: To investigate the prevlance of 1q21 amplification in patients with multiple myeloma (MM) and its correlation with the progression and prognosis of the disease.
1q21 amplification was detected in 48 patients with MM using cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization analysis (cIg-FISH) and interphase fluorescence in situ hybridization (I-FISH) analysis combined with CD138 immunomagnetic cell sorting (MACS).
1q21 amplification (≥ 3 red signals) was detected in 26/48(54.2%) cases by cIg-FISH and 31/48 (64.6%) cases by I-FISH combined with CD138 MACS. There was a good consistency between the two methods (P>0.05). The mortality of patients with 1q21 amplification was significantly higher than those without (P< 0.05). No significant difference was detected in terms of sex, age, Durie-Salmon stage, subgroup and international staging system (ISS) stage between patients with 1q21 amplification and those without (P>0.05).
The frequency of 1q21 amplification in MM is high. There was also an association between the amplification and poor prognosis. cIg-FISH is consistent with CD138 MACS combined with I-FISH.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 12/2011; 28(6):686-9.
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ABSTRACT: Conventional cytogenetic analysis is often hampered owing to the low mitotic index of multiple myeloma (MM) cells in bone marrow samples of MM. Interphase fluorescence in situ hybridization (I-FISH) analysis combined with magnetic-activated cell sorting (MACS) has substantially enhanced the sensitivity of cytogenetic analysis. Here, we used I-FISH to explore the incidence of chromosomal abnormalities in 60 Chinese patients with newly diagnosed MM. Five different specific probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV), 1q21, 1p12, and 17p13 were used to detect chromosomal aberrations, and LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were further applied to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement. Fifty of the patients (83.3%) had at least one type of abnormalities regarding the regions analyzed. Nine patients (15%) had one abnormality; 10 patients (16.7%) had two abnormalities; 31 patients (51.7%) had three or more abnormalities. The most frequent abnormality in the patients was illegitimate IgH rearrangement (70%), followed by 13q14 deletion (63.3%), 1q21 amplification (61.7%), 1p12 deletion (33.3%), and 17p13 deletion (13.3%). These aberrations are not randomly distributed, but strongly interconnected. Patients with 17p13 deletion or t(4;14)(p16;q32) had significant higher β2-microglobulin level (P < 0.05). However, all these abnormalities had no correlation with age, gender, disease stage, and Ig isotype; yet, it was showed that the frequencies of the individual chromosomal abnormalities were very high. Taken together, MACS in combination with I-FISH may be a promising tool to detect the molecular cytogenetic abnormalities of MM.
Medical Oncology 05/2011; 29(3):2200-6. · 2.14 Impact Factor
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Chunming Li,
Lijuan Chen,
Xiao Gao,
Xiaoyan Qu,
Wenyi Shen, Ruifang Yang,
Run Zhang,
Hairong Qiu,
Jiaren Xu,
Hua Lu,
Jianyong Li
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ABSTRACT: Multiple myeloma (MM) is characterized by complex genetic and chromosomal abnormalities involving both numerical and structural aberrations, which have clinical prognostic value. The plasma cell labeling index (PCLI) is one of the most important prognostic factors in newly diagnosed MM, and indicates plasma cell proliferative capacity. In this study, we determined the PCLI and the deletion of 13q14, retinoblastoma-1 gene (RB-1), 1p13, and 17p13, 1q21 amplification, and IgH rearrangements in 42 newly diagnosed patients with MM. A high PCLI was observed in 18 patients (42.9%), and the del(13q14) was present in 25 patients (59.5%), del(RB-1) in 23 patients (54.8%), del(17p13) in eight patients (19.1%), amp(1q21) in 23 patients (54.7%), del(1p13) in 17 patients (40.5%), and IgH rearrangements in 28 patients (66.7%). We further detected the IgH translocation partners: t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in 19, 15, and five patients, respectively. The PCLI had a significant correlation with del(13q14) (p = 0.006), but no correlation with other chromosome abnormalities or clinical and laboratory features (p > 0.05). The PCLI was higher among patients with del(13q14), and patients with a high PCLI had a short time to disease progression. In conclusion, PCLI is a powerful and independent prognostic parameter in newly diagnosed MM, and correlates with del(13q14).
Leukemia & lymphoma 02/2011; 52(2):260-4. · 2.40 Impact Factor
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ABSTRACT: To investigate the incidence and prognosis of 1q21 amplification, 13q14 deletion, TP53 gene deletion and IgH translocation in patients with multiple myeloma (MM).
Interphase fluorescence in situ hybridization (I-FISH) with four different specific probes for the regions containing 1q21, 13q14.3 (D13S319), 14q32 and TP53 gene were performed in 43 MM patients.
Among the 43 MM patients, 1q21 amplification was observed in 28 (65.1%) cases, 13q14 deletion in 30 (69.7%) cases, TP53 gene deletion in 8 (18.6%) cases, and IgH translocation in 29 (67.4%) cases. The mortality of MM patients with 1q21 amplification, 13q14 deletion or TP53 gene deletion was higher than those without them.
There is high frequency of 1q21 amplification, 13q14 deletion, TP53 gene deletion and IgH translocation in multiple myeloma, and 1q21 amplification, 13q14 deletion and TP53 gene deletion are poor prognosis factors for MM patients.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 10/2010; 27(5):567-70.
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ABSTRACT: To investigate the correlation between chromosome 13q14 deletion [del(13q14)] and chromosome 1q abnormality in multiple myeloma (MM).
The bone marrow plasma cells of 48 previously untreated MM patients were purified by CD138 and magnetic cell sorting system, and interphase fluorescence in situ hybridization (I-FISH) was applied to detect the del(13q14) with D13S319 probe and the abnormalities of chromosome 1q with CEP1 SpectrumOrange probe in sorted MM cells.
Among the 48 MM patients, del(13q14) was observed in 22(45.8%) cases, the abnormalities of chromosome 1q were observed in 23 (47.9%) cases, among which 2 were 1q deletion and 21 were 1q duplication. The chromosome 1q abnormality was detected in 16 of the 22 cases of MM with del(13q14) and in 7 of the 26 cases of MM without del(13q14), and there was significant difference between the two groups (chi-square was 10.02, P was less than 0.01).
There is high frequency of chromosome 13q14 deletion and 1q abnormality in multiple myeloma. The chromosome 1q abnormalities are highly associated with 13q14 deletion.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 03/2009; 26(1):102-5.
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ABSTRACT: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a well-known Chinese medicine for treating cardiovascular disorders. Cardiomyocyte apoptosis plays a major role in the development of cardiovascular diseases. The present study was designed to investigate the effects of STS on cardiomyocyte apoptosis induced by in vivo acute myocardial infarction (MI) in adult rats and by in vitro H2O2-treated neonatal rat ventricular myocytes. In MI rats, STS significantly reduced the infarct sizes, the blood lactate dehydrogenase (LDH) level, and the number of apoptotic cardiomyocytes in the infarcted hearts. In the in vitro study, STS reversed the decreased effect of cell viability induced by H2O2. In addition, STS also markedly inhibited H2O2-induced cardiomyocyte apoptosis. C-Jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs) and p38 MAPK are classic oxidative stress-activated protein kinases. Our further mechanistic study revealed that increased JNK phosphorylation stimulated by H2O2 was abolished by STS treatment. In conclusion, inhibition of JNK activation plays a significant role in cardioprotective effects of STS.
Journal of Cardiovascular Pharmacology 05/2008; 51(4):396-401. · 2.29 Impact Factor
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ABSTRACT: Placental-derived corticotropin-releasing hormone (CRH) seems to play a major role in the mechanisms controlling human pregnancy and parturition. It has been suggested that CRH directly modulates the endocrine function of placental trophoblasts, including the production of estrogen, ACTH, and prostaglandin. In this study, we sought to investigate the effect of CRH, locally produced by placenta, on progesterone production. Percoll-purified placental trophoblasts were obtained from uncomplicated term pregnancies and cultured for 72 h. Progesterone concentration in culture media was measured by RIA. The mRNA transcripts encoding CYP11A1 and HSD3B1, the enzymes for progesterone synthesis, were determined by quantitative real-time reverse transcription (RT)-PCR. Results showed that CRH (10(-8)-10(-6) mol/l) caused a significant decrease in progesterone levels in a dose-dependent manner. The CRH antagonist, alpha-helical CRH 9-41, at 10(-7)-10(-5) mol/l stimulated progesterone secretion. Consistent with this thesis, CRH decreased, whereas alpha-helical CRH increased, the mRNA levels of CYP11A1 and HSD3B1. Since CRH has been shown to activate the phospholipase C-protein kinase C (PKC) signal pathway in placenta, we examined whether the effect of CRH on progesterone synthesis was dependent on PKC signal pathway. Treatment of cells with PKC inhibitor, Gö6976, resulted in a significant increase in progesterone production, and exogenous CRH restored progesterone production. In conclusion, placental CRH exhibits a tonic inhibitory effect on progesterone production in a PKC-dependent fashion.
Journal of Molecular Endocrinology 01/2007; 37(3):533-40. · 3.48 Impact Factor
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ABSTRACT: Estrogens and corticotrophin-releasing hormone (CRH) produced by the placenta play pivotal roles in the control of parturition in human and other primates. There is a strong correlation between maternal CRH and estrogen concentrations throughout gestation. To investigate whether CRH produced locally in the placenta could modulate estrogen production, we obtained human placental trophoblasts from uncomplicated term pregnancies and cultured them for 72 h. Cells were then treated with CRH and with a CRH receptor antagonist, alpha-helical CRH9-41. The results showed that CRH stimulated, but alpha-helical CRH9-41 inhibited, the production of estradiol in a time- and dose-dependent manner. Consistent with this thesis, CRH increased whereas alpha-helical CRH decreased the mRNA levels of STS, CYP19A1, and HSD17B1, the key enzymes for estrogen synthesis. These results suggest that, in the placenta, endogenously produced CRH exhibits a tonic stimulatory effect on estrogen production.
Biology of Reproduction 07/2006; 74(6):1067-72. · 4.01 Impact Factor
