Pathological features and survival of triple positive breast cancer in 271 cases / 中国现代普通外科进展

Objective:To explore pathological features and survival of triple positive breast cancer (TPBC).Methods:The clinical data of 271 cases of triple positive breast cancer from January 2010 to January 2017 in Suqian area were collected,compared with 283 cases of Luminal B I (HER2 negative).The clinical pathological features and survival were analyzed.Results:Among 271 cases of triple positive breast cancer,there were 89 cases (32.84％) of distant recurrence and metastasis in 2 years,and 137 cases (50.55％) of distant recurrence in 5 years.Among 283 cases of Luminal B I,there were 32 cases (11.31 ％) of distant recurrence and metastasis in 2 years.and 52 cases (18.37％) of distant recurrence in 5 years.There were significantly differences(P＜0.05).1 year Disease-free survival (DFS)and Overall survival (OS) of all patients were 100％,Among 271 cases of triple positive breast cancer,2-year DFS and OS were 64.94 ％,85.24％ respectively.3-year DFS and OS were 54.98 ％,69.74％ respectively,5-year DFS and OS were 43.54％,47.23％ respectively.Among 283 cases of Luminal B I,2-year DFS and OS were 86.22 ％,95.76％ respectively.3-year DFS and OS were 81.98 ％,80.92％ respectively,5-year DFS and OS were 76.33％,67.49％ respectively.There were significantly differences(P＜0.05).Conclusion:TPBC has the characteristics of poor biological behavior,large mass,pathological grade of grade Ⅲ,vascular or nerve infiltration,axillary lymph node metastasis,high proliferation index and high tumor load,and early distant recurrence,low DFS and OS.We Should choose individualized,targeted treatment programs,based on patient's hormone receptor and Ki67 expression,so as to benefit patients of TPBC.

Osteogenic Differentiation Potential of Bone Marrow Mesenchymal Stem Cells in Patients with Myelodysplastic Syndromes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMMSC) in patients with myelodysplastic syndromes (MDS) and to explore the role of BMMSC osteogenic differentiation in the pathogenesis of MDS.</p><p><b>METHODS</b>BMMSC were isolated from bone marrow of patients with MDS and healthy donors, then expanded in vitro. The expression of transcription factor gene RUNX2, Osterix and osteogenic differentiation markers (ALP, BSP, OPN, OCN) were measured by real-time PCR, the alkaline phosphatase(ALP) activity was assessed at 3, 7, 10 days after osteogenic differentiation. Mineralization analysis was performed at day 21 of osteogenic induction.</p><p><b>RESULTS</b>The expression level of RUNX2 and Osterix were significantly decreased in BMMSC from lower-risk MDS patients compared with normal controls (P<0.05). After osteogenic induction, low-risk MDS showed lower alkaline phosphatase activity at day 3 (P<0.05), less intense alizarin red S staining at day 21 (P<0.05), and lower gene expression of osteogenic differentiation markers (P<0.05), however, these expressions in higher-risk MDS were normal.</p><p><b>CONCLUTION</b>BMMSC from low-risk MDS have abnormalities in osteogenic differentiation, it may contribute to the ineffective hamatopoiesis of MDS.</p>

mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients / 中国实验血液学杂志

This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P < 0.05). According to WHO criteria, the mRNA expression of Delta-like-1 in RA/RAS, RCMD and RAEB groups were significantly higher than that in normal controls (P < 0.05), the mRNA expression of Jagged-1 in RAEB group was also significantly higher than that in normal controls (P < 0.05). The mRNA expression of Delta-like-1 was significantly correlated with the proportion of blasts in the bone marrow of MDS patients (r = 0.502, P < 0.05). The expression levels of Delta-like-1 and Jagged-1 in MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P < 0.05). The mRNA expression of Delta-like-1 in higher risk group according to International Prognostic Scoring System was significantly higher than that in lower risk group (P < 0.05), there was no significant difference in Jagged-1 expression levels between higher risk group and lower risk group (P > 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients / 中国实验血液学杂志

This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPO<1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P < 0.05). Obviously, the level of EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate EPO resistance in patients wtih anemic MDS, decrease the pathological level of EPO, enhance Hb levels and reduce the dependency on blood transfusion.

Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate phenotype, cell differentiation and cytogenetic properties of bone marrow (BM) mesenchymal stem cells (MSC) separated from the myelodysplastic syndrome (MDS) patients. And to analyze cytogenetic aberration of MSC derived from MDS (MDS-MSC) and its mechanism in pathogenesis of MDS.</p><p><b>METHODS</b>Adherent MSC from both myelodysplastic (n = 22) and normal (n = 7) marrow were obtained by a stromal culture procedure. Morphological features were observed by optical microscope. The cell-surface antigens were performed by flow cytometer(FCM). Adipogenic and osteogenic differentiation potential of MSC were identified under specific induction conditions. Standard cytogenetic analysis of both hematopoietic cells and MSC were performed by trypsin-Giemsa (GTG) banding. The karyotype analysis DNA content was determined by FCM to verify the results.</p><p><b>RESULTS</b>The morphology of MDS-MSC was typical slender spindle-shaped cells, MSC obtained from MDS patients had a MSC immunophenotype, lacked the expression of hematopoietic antigens-CD34, CD45 and expressed MSC markers, such as CD73, CD90, and CD105. MDS-MSC layers showed the capability to differentiate towards adipocytes, chondrocytes and osteoblasts. Cytogenetic aberrations were observed in MSC from 14 (64%) MDS patients, usually involve the loss of chromosomal material (92%), and the clonal loss (7 cases, 50%). Two cases of structural aberrations were also detected. Abnormal karyotypes in MSC were still more frequently identified in abnormal hematopoietic cells group (12 out of 13, 92% vs 3 out of 9, 33%, P < 0.05). There were not exactly the same type of chromosomal aberrations between hematopoietic cells and MSC, but different type of the aberrations in the same chromosome were involved.</p><p><b>CONCLUSION</b>MDS-MSC retains the phenotyping characteristics and differentiated function of normal MSC, but has different type of chromosomal abnormalities. A high proportion of loss of chromosomal may be a marker of chromosomal instability of MDS-MSC. Detection of abnormalities in MDS-MSC suggests enhanced genetic susceptibility of these cells in MDS. This may indicate potential involvement of MSC in the pathophysiology of MDS.</p>

Expression of p57kip2 in patients with de novo myelodysplastic syndrome and its relationship with SDF-1/CXCR4 axis / 中国实验血液学杂志

This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome (MDS) and its role in MDS pathogenesis, as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal. The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR. The percentage of CD34(+) cells in the bone marrow from MDS patients was measured by flow cytometry. 18 healthy volunteers were recruited for control. The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell (BMMNC) from MDS or normal controls was investigated in vitro, and difference between them was compared. The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group (P < 0.001) and there was a negative correlation between p57kip2 expression and percentage of CD34(+) (r = -0.458, P < 0.001); the patients with abnormal karyotype showed lower expression of p57kip2 gene, compared to patients with normal karyotype (P = 0.045). Although the expression of CXCR4 had no difference between MDS patients and normal controls, a positive correlation between p57kip2 and CXCR4 in MDS patients was still found (r = 0.609, P < 0.001). Moreover, SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner, but BMMNC from MDS patients showed no response to SDF-1. SDF-1-induced p57 expression was blocked by AMD3100. It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS. Furthermore, SDF-1-induced p57kip2 expression in BMMNC, and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.

Study of aberrant p73 promoter methylation in patients with myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the methylation status of p73 gene promoter in patients with myelodysplastic syndrome (MDS) and explore its significance with clinical prognosis.</p><p><b>METHODS</b>Methylation of p73 promoter was detected in bone marrow cells from 135 MDS patients and 13 healthy controls by methylation-specific PCR (MSP). The results of MSP were confirmed by bisulfite sequencing. The expression of p73 mRNA was detected by real-time quantitative PCR. Primary bone marrow cells from MDS patients were treated with decitabine, the changes of p73 methylation status and p73 mRNA expression were measured. The role of p73 methylation in the prognosis of MDS and the correlated clinical data were explored.</p><p><b>RESULTS</b>p73 hypermethylation was present in 37.04% of MDS cases and patients with high risk MDS (RAEB-1 and RAEB-2) exhibited a significantly higher frequency of p73 methylation than that of low risk MDS (58.8% vs 29.7%, P = 0.002). The expression of p73 mRNA in the methylated group was decreased compared to that of the unmethylated group (P = 0.032). Decitabine treatment decreased the level of p73 methylation and increased the level of p73 transcripts. Patients with p73 methylation progressed rapidly to AML (P < 0.001) and had shorter survival (P = 0.002) than those who did not have p73 methylation. In the multivariate Cox regression model, BM blast and p73 methylation status emerged as independent prognostic factor for overall survival and leukemia free survival.</p><p><b>CONCLUSION</b>p73 gene methylation is common in patients with MDS and may indicate poor prognosis. p73 may be a therapeutic target in MDS.</p>

Research advances of hepcidin expression and its regulation mechanism / 中国实验血液学杂志

Hepcidin can regulate cell irons' efflux transport. The expression of hepcidin can be influenced by the body signals (such as serum ferritin and erythropoietin levels) as well as inflammation, hypoxia and other disease states. These stimulus activate the signaling pathway of BMP-the SMAD, the JAK-STAT and HIF1 through the liver parenchymal cell surface type I transmembrane glycoprotein of HFE, transferrin receptor 1, 2, hepcidin regulatory proteins, thereby changing the hepcidin gene transcription, regulating the expression levels of hepcidin. However, the molecular mechanism that regulate hepcidin expression is unclear. From the signal factors that affect hepcidin expression and signaling pathways involved in its expression, the latest research progress on regulatory mechanism of hepcidin are summarized.

Next-generation sequencing and its application in acute myeloid leukemia and myelodysplastic syndrome / 中国实验血液学杂志

The next-generation sequencing (NGS), as the most practical and reliable method, has replaced the classical Sanger sequencing to help scientists to discover the genetics secrets of human tumor diseases. With the technique development, the whole genome sequencing will be no longer out of reach. Recently, some scientists used the NGS in the research of hematological malignancies and pushed the progress of the whole genome sequencing in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) actively in order to find out the pathogenesis of some hematological malignancies. The NGS and the application of the whole genome sequencing, the exome sequencing, the transcriptome sequencing in AML and MDS are reviewed in this article.

Biological behavior of SDF-1/CXCR4 in patients with myelodysplastic syndrome / 中国实验血液学杂志

The purpose of this study was to evaluate the biological behavior of stromal cell-derived factor-1 (SDF-1) in migration, adhesion and apoptosis as well as the related signaling transduction pathways in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). 37 patients with MDS, 10 patients with de novo AML and 14 patients with non-clonal cytopenia diseases were chosen for this study. The expression level of CXCR4 on CD34(+) cells and apoptosis of CD34(+) cells in bone marrow were detected by flow cytometry; the chemotaxis of SDF-1 on bone marrow mononuclear cells in 4 patients with low risk MDS (IPSS score ≤ 1.0) and 5 patients with high risk MDS (IPSS score ≥ 1.5) was assayed by transwell migration test of cells. The effect of SDF-1 on cell adhesion capability was measured by using CCK-8 method. The results indicated that the apoptosis rate of CD34(+) cells was significantly higher in MDS patients with low risk (IPPS score < 1.0) than that in MDS patients with high risk (IPSS score ≥ 1.5) (21.55% vs 7.52%, p < 0.001); as well, the apoptosis rate of CD34(+) cells was significantly higher in MDS patients with low risk than that in de novo AML patients (21.55% vs 7.33%, p < 0.001), no relation of CD34(+) cell apoptosis with age and sex of patients was found. SDF-1 could promote the cells of patients with CXCR4 high expression to adhere to the stroma cells, and induce migration of these cells, as well as, SDF-1 could trigger the polarization of the cells which highly expressed CXCR4. After addition of pertussis toxin, wortmannin and AMD3100, the ability of adhersion and migration of the cells with highly expressed CXCR4 decreased, but there was no above-mentioned phenomenon in patients who lowly expressed CXCR4. It is concluded that the SDF-1/CXCR4 axis enhances the ability of cell adhesion and migration through PI3K signaling pathway, thereby plays antiapoptosis role, moreover the above-mentioned effects can be blocked by PI3K pathway inhibitor and G protein inhibitor.