Application of interim PET-CT in first-line treatment decision-making for lymphoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Recent advances in lymphoma treatment have significantly improved the survival of patients; however, the current approaches also have varying side effects. To overcome these, it is critical to implement individualized treatment according to the patient's condition. Therefore, the early identification of high-risk groups and targeted treatment are important strategies for prolonging the survival time and improving the quality of life of patients. Interim positron emission tomography-computed tomography (PET-CT) has a high prognostic value, which can reflect chemosensitivity and identify patients for whom treatment may fail under this regimen. To date, many prospective clinical studies on interim PET (iPET)‍-adapted therapy have been conducted. In this review, we focus on the treatment strategies entailed in these studies, as well as the means and timing of iPET assessment, with the aim of exploring the efficacy and existing issues regarding iPET-adapted treatment. It is expected that the improved use of PET-CT examination can facilitate treatment decision-making to identify precise treatment options.

How are MCPIP1 and cytokines mutually regulated in cancer-related immunity?

Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.

The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia / 中华血液学杂志

Objective@#To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) .@*Methods@#Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression.@*Results@#The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ2=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ2=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) .@*Conclusion@#High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.

A prospective study of the efficacy and safety of maintenance therapy with recombinant human thrombopoietin in patients with primary immune thrombocytopenia: a multicenter study / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO.@*Methods@#Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×109/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×109/L.@*Results@#A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×109/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×109/L) at 4th week, 8th week and 12th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×109/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild.@*Conclusion@#Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

Influence of Bushenqingtou Decoction on serum IL-2,IL-4,IL-10,TNF-α and IFN-γin chronic hepatitis B patients with positive HBeAg / 国际检验医学杂志

Objective To observe the changes of peripheral blood interleukin-2(IL-2) ,interleukin-4(IL-4) ,interleukin-10(IL-10) ,tumor necrosis factor-alpha(TNF-α) and interferon gamma (IFN-γ) in chronic hepatitis B(CHB) patients with positive e-anti-gen(HBeAg) treated by Bushenqingtou Decoction .Methods 60 cases of CHB with positive HBeAg were randomly divided into the treatment group and the control group ,30 cases in each group .The CHB treatment group received Bushenqingtou Decoction with the treatment course of 48 week ,while the CHB control group did not received the medication therapy .In the beginning and at 48 weeks of treatment ,the blood in the two CHB groups were collected for detecting HBV DNA ,IL-2 ,IL-4 ,IL-10 ,TNF-αand IFN-γ. Results Compared with before treatments ,the levels of IL-2 ,TNF-αand IFN-γafter treatments in the CHB treatment group were obviously increased ,while the levels of HBV DNA ,IL-4 and IL-10 were remarkably decreased (P0 .05) .Conclusion Bushenqingtou Decoction could inhibit the replication of HBV DNA in the CHB patients with positive HBeAg and improve the body immune func-tion .

siRNA-Mediated Suppression of Synuclein gamma Inhibits MDA-MB-231 Cell Migration and Proliferation by Downregulating the Phosphorylation of AKT and ERK / 한국유방암학회지

PURPOSE: Synuclein-gamma (SNCG), which was initially identified as breast cancer specific gene 1, is highly expressed in advanced breast cancers, but not in normal or benign breast tissue. This study aimed to evaluate the effects of SNCG siRNA-treatment on breast cancer cells and elucidate the associated mechanisms. METHODS: Vectors containing SNCG and negative control (NC) siRNAs were transfected into MDA-MB-231 cells; mRNA levels were determined by real-time polymerase chain reaction. Cell proliferation was evaluated using the MTT assay, cell migration was assessed by the Transwell assay, apoptosis and cell cycle analyses were conducted with the flow cytometer, and Western blot analysis was performed to determine the relative levels of AKT, ERK, p-AKT, and p-ERK expression. RESULTS: SNCG mRNA levels were significantly reduced in MDA-MB-231 cells transfected with SNCG siRNA. Our results indicate that in SNCG siRNA-treated cells, cell migration and proliferation decreased significantly, apoptosis was induced, and the cell cycle was arrested. Western blot analysis indicated that the protein levels of p-AKT and p-ERK were much lower in the SNCG siRNA-treated groups, than in the control and NC groups. CONCLUSION: SNCG siRNA could decrease the migration and proliferation of breast cancer cells by downregulating the phosphorylation of AKT and ERK.

The effects of "a" determinant variants in chronic hepatitis B virus patients on the expression of hepatitis B surface antigen and anti-HBs / 中国医师杂志

Objective To investigate the effects of "a determinant variants in chronic hepatitis B(CHB)patients on the expression of hepatitis B surface antigen(HBsAg) and anti-HBs antibodies (HBsAb). Methods Eight hundred sixty-six chronic hepatitis B patients were enrolled, which HBs Ag carriage was beyond a 6 month period.77 patients(8.9%)concomitantly carried both HBs Ag and anti-HBs antibodies,789 patients(91.1%)were only HBs Ag positive. Selection criteria for patients with both HBs Ag and anti-HBs were mainly focused on anti-HBs titers at least three times above the analytical threshold of the technique(10 U/L)on at least three consecutive visits.14 patients were selected from77 patients, who presented both markers(group Ⅰ),and 12 patients from another 789 patients who positive for HBs Ag only(group Ⅱ)were randomly selected as controls. The HBs Ag-encoding gene was amplified and cloned, and at least 15clones per patient were sequenced and analyzed. Results The number of residue changes within the S protein group Ⅰ was 2.7 times more frequently than that in group Ⅱ patients, and "a" determinant of the major hydrophilic region(MHR)occurred mostly. Ten patients (71%)from group Ⅰ and three patients(25%)from group Ⅱ presented at least two residue changes in the MHR. The most frequent changes in group Ⅰ patients were located at positions s145,s129,s126,s144, and s123 as described for immune escape variants. Conclusions In CHB patients, the coexistence of HBsAg and HBsAb is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process play an important role in vaccine efficacy, diagnosis and clinical therapy.

Selection and amplification of the liver stem cell subset from rat bone marrow cells with a medium containing cholestatic serum in vitro / 中国病理生理杂志

AIM: To explore the feasibility of direct separat and selective enlargement of the bone marrow-derived liver stem cells (BDLSC) from bone marrow cells with a culture system containing cholestatic serum in vitro . METHODS: Bone marrow cells of rats were cultured with selective media containing 2%, 5%, 7% and 10% cholestatic rat serum, respectively. The BDLSC were then induced to proliferate with the addition of hepatocyte growth factor (HGF) on the firth day. BDLSC were characterized using immunocytochemistry and RT-PCR for lineage markers, glycogen staining and urea synthetic assay for functions 2 weeks later. RESULTS: Bone marrow cells were unble to form colony in the presence of 2% cholestatic serum and apopotosis appeared gradually in 7% or 10% cholestatic serum. The BDLSC survived in the medium containing 5% cholestatic serum while the other types of cells did not. The survival cells proliferated with a high speed during the second week and then formed hepatocyte-like colony-forming units (H-CFU). Cells in the H-CFU expressed the characteristic proteins of fetal hepatocytes. Furthermore, they had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. CONCLUSION: The selective micro-environment effectively selected BDLSC from the bone marrow cell, and will be a new way to provide an abundant source of donor hepatocytes for clinical cell therapy.

Expression of uridine diphosphate glucuronosyl transferase 1 A1 mRNA in mice with chronic liver injury / 中国普通外科杂志

Objective To investigate the effect of chronic liver injury on the expression of uridine diphosphate glucuronosyltransferase(UGT) 1A1 mRNA in mice. Methods Chronic liver injury model was induced by feeding CCl 4 in mice.Thirty mice were randomly divided into three groups:control group,experimental group 1(CCl 4 was given for 1 month),and experimental group 2(CCl 4 was given for 2 months).The liver function was tested;and the expression of UGT1A1 mRNA in the 3groups was analysed by RT-PCR. Results There was significant difference in the expression of UGT1A1 mRNA between the 3 groups(P

Identification and differentiation of bone marrow-derived liver stem cells / 中国普通外科杂志

Objective To identify the surface marker of bone marrow-derived liver stem cells and to isolate the stem cells, to investigate the differentiation of the stem cells. Methods The quantitative variations of the cells with stem cell surface markers, including ? 2-microglobulin negative (? 2m -), Thy-1 +,CD34 +,Flt-3 +,IL-3R +,and c-kit + markers, were detected by using flow cytometry in the bone marrow of several rat models with liver injury. Each stem cell population was then isolated using a magnetic bead cell-sorting procedure. The isolated cells were cultured in a system containing cholestatic serum and hepatocyte growth factor (HGF). The morphology of the cells was observed, and the expressions of albumin, AFP, and CK8/18 were detected with immunohistochemistry technique. Results ? 2m - cells elevated significantly in each of the rat models.After being co-cultured with cholestatic serum and HGF, ? 2m - cells showed multilateral transformation and resembled hepatcytes morphologically. The differentiated cells expressed albumin, AFP, and CK8/18, all known to be the characteristic markers of hepatocyte. The other cell population showed little quantitative changes, and did not express the same proteins. Conclusions The quantitative variation of ? 2m - cells corresponds to the severity of liver injury. ? 2m - cells have the ability to trans-differentiated into hepatocytes in vitro. They might be the marker of liver stem cells.

Effect of lovastatin on proliferation of cultured rat mesangial cells / 中华肾脏病杂志

Objective To investigate the effect of lovaslatin on proliferation of cultured rat mesangial cells. Methods Cultured rat mesangial cells were stimulated by 10% fetal calf serum (FCS) or platelet-derived growth factor (PDGF) in the absence or the presence of lovastain and mevalonate metabolites. 5-Bromo-2-deoxyuridine incorporation was used to assess DNA synthesis. Results FCS or PDGF caused a marked stimulation of DNA synthesis in the mesangial cells. Lovastatin inhibited FCS or PDGF-stimulated BrdU incorporation and cell proliferation. Mevalonic acid, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented inhibitory effect of lovastatin on mesangial proliferation induced by FCS. Mevalonic acid and geranylgeranyl pyrophosphate also significantly reversed inhibitory effect of lovastatin on mesangial proliferation induced by PDGF. But farnesyl pyrophosphate only partly reversed inhibitory effect of lovastatin. Conclusions Lovastatin, by inhibiting the synthesis of isoprenoid metabolites of mevalonate, can suppress mesangial cell proliferation. It is possible to provide a new approach for treatment of proliferative glomerular diseases.

Isolation and purification of Thy-1~(low) Lin~- Sca-1~+ bone marrow stem subset cells by magnetic activated cell sorting / 中国普通外科杂志

Objective To isolate and purify Thy 1 low Lin Sca 1 + bone marrow stem subset cells by magnetic activated cell sorting(MACS). Methods Thy 1 low Lin Sca 1 + cells from mouse bone marrow were collected through three processes by MACS.After Lin + cells were removed,Thy 1 low Lin Sca 1 + bone marrow stem cell subsets were harvasted.The purity of the cells was analysed by FACS and the reclaimation rate was counted. Results The purity and reclaimation rate of Thy 1 low Lin Sca 1 + cells were 72.36% and 82.43% respectively, which equaled to the level of isolation and purification of CD34 + cells by MACS. Conclusions It is effective to isolate and purify Thy 1 low Lin Sca 1 + bone marrow stem cell subsets by MACS, and the purity and reclaimation rate of the cells are high.