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Objective: To investigate the effects of up-regulating or silencing DJ-1 gene expression on the apoptosis, migration and invasion of colorectal cancer (CRC), and to explore the possible molecular mechanism. Methods: The expression level of DJ-1 in CRC tissues and cells was detected by immunohistochemistry, Western blotting and real-time fluorescent quantitative PCR, respectively. The SW480 and HCT116 cells were transfected with the recombinant lentiviral vector carrying human DJ-1 gene to obtain DJ-1 overexpressed SW480/OE-DJ-1 and HCT116/OE-DJ-1 cells, while the cells transfected with the empty vector was as the negative control (OE-NC). The SW480 and HCT116 cells were transfected with the recombinant lentiviral vector carrying the specific shRNA targeting DJ-1 gene to generate the SW480/shDJ-1 and HCT116/sh-DJ-1 cells with stable knockdown of DJ-1, while the cells transfected with the empty vector was as the negative control (sh-NC). Subsequently, the expressions of DJ-1 and p53 protein and mRNA were detected by immunohistochemistry and real-time fluorescent quantitative PCR, respectively; and their relationship was analyzed. The expressions of p53 and its downstream apoptosis-related proteins Bax and Bcl-2 in SW480 and HCT116 cells with DJ-1 over-expression or knockdown were detected by Western blotting. The effects of overexpressing and silencing DJ-1 gene expression on the invasion and migration abilities of SW480 and HCT116 cells were detected by Transwell chamber assay. The epithelial-mesenchymal transition (EMT) of CRC cells was induced by transforming growth factor-β1 (TGF-β1), then the expression levels of DJ-1 and EMT-related markers (N-cadherin, β-catenin, vimentin, E-cadherin) were analyzed by Western blotting. Results: DJ-1 was highly expressed in 34 CRC tissues (24/34, 70.59%) (P < 0.001). The overall survival time of the patients with DJ-1 high expression was significantly shorter than that of the patients with DJ-1 low expression (P < 0.001). The high expression of DJ-1 was correlated with TNM stage, tumor location, lymph node metastasis, and degree of differentiation (all P < 0.05). There was a negative correlation between DJ-1 and p53 expressions (r =-0.428, P = 0.015). Silencing DJ-1 increased the expression level of p53 and its downstream apoptotic protein Bax, decreased the expression of anti-apoptotic protein Bcl-2 (all P < 0.05), and decreased the invasion and migration capacities of SW480 and HCT116 cells (both P < 0.01); Conversely, overexpressing DJ-1 decreased the expression level of p53 and Bax, increased the expression of Bcl-2 (all P < 0.05), and increased the invasion and migration capacities of SW480 and HCT116 cells (both P < 0.01). Overexpression of DJ-1 induced by TGF-β1 increased the expressions of N-cadherin, β-catenin and vimentin, and decreased the expression of E-cadherin in the process of EMT (P < 0.05). Conclusion: DJ-1 promotes the apoptosis and invasion of CRC cells by negatively regulating the p53 signaling pathway.
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Objective@#The clinical characteristics and outcomes of patients with chronic myeloid leukemia (CML) who had discontinued tyrosine kinase inhibitors (TKI) therapy were analyzed retrospectively.@*Methods@#Clinical data of 109 cases of chronic CML patients who had discontinued TKI therapy in seven centers were retrospectively analyzed from June 1, 2005 to March 1, 2018. 91 cases with complete clinical data were enrolled in this study. We aimed to observe the status of patients with treatment free remission (TFR) after TKI therapy discontinuation and its prognostic factors.@*Results@#38 of 91 patients lost MMR after a median follow-up of 9 months and the estimated TFR was 52.6%. 31 of 38 patients who met the definition of molecular relapse resumed TKI treatment immediately and regained the major molecular response (MMR) with a median time of 3 months (range, 1-12 months). No significant difference was found in median course of imatinib therapy between the TFR group and the relapse. Similarly, duration to MMR, age and gender also showed no difference between the two groups. The longer duration of MMR maintenance (more than 24 months), the lower relapse rate was observed (P=0.027).@*Conclusion@#TKI might be safely discontinued in part of CML patients.
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No abstract available.
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Humans , Leukemia, Myelogenous, Chronic, BCR-ABL PositiveABSTRACT
A total of 8 099 outpatient prescriptions for treatment of Helicobacter pylori (Hp) infection in 9 community health service centers of Shanghai Jing′an district were collected from the regional health information platform.The prescriptions were reviewed and analyzed according to the criteria of the Forth National Consensus Report on the Treatment of Helicobacter pylori Infection.The results showed that only 195 prescriptions met the criteria (2.4%).For those not meeting the criteria, 611 prescriptions (7.5%) gave the right therapeutic protocol but incorrect treatment course;6 893 prescriptions (85.1%) gave the incorrect protocol.It is uggested that incorrect treatment for Hp eradication is common in community health service centers consist in the Helicobacter pylori herapy prescriptions in the community health service cente in Shanghai, Jing′an District, which should be paid more attention to.
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Objective To analyze the motivation of Chinese patients with chronic myelogenous leukemia (CML) who have stopped the tyrosine kinase inhibitor (TKI). Methods Forty-seven CML patients who have stopped TKI provided informed consent prior to their participation in the study. These patients were divided into relapse and non-relapse group at the endpoint of the observation. None of the patients received any CML-associated therapies after TKI cessation. The reasons of withdrawal were analyzed statistically. Results The reasons for cessation included patient's request due to cost(59.57 %, 28/47), patient's plan to getting pregnant(8.52 %,4/47),side-effect of TKI(23.40 %,11/47)and other reasons(8.52 %,4/47).At the endpoint of observation, 23 patients suffered molecular relapse. Among them, 15 cases (65.22 %) were due to cost; 1 case (4.35 %) was due to getting pregnant, 5 cases (21.74 %) were due to side-effect and 2 cases (8.69 %) were due to other reasons. There was more frequency relapse in the group of insufficient cost. Conclusion The motivation of Chinese CML patients who have stopped TKI might show impact on the outcome,and the motivation is mainly related with history of drug reduction and withdrawal.
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Objective To analyze the motivation of Chinese patients with chronic myelogenous leukemia (CML) who have stopped the tyrosine kinase inhibitor (TKI). Methods Forty-seven CML patients who have stopped TKI provided informed consent prior to their participation in the study. These patients were divided into relapse and non-relapse group at the endpoint of the observation. None of the patients received any CML-associated therapies after TKI cessation. The reasons of withdrawal were analyzed statistically. Results The reasons for cessation included patient's request due to cost(59.57 %, 28/47), patient's plan to getting pregnant(8.52 %,4/47),side-effect of TKI(23.40 %,11/47)and other reasons(8.52 %,4/47).At the endpoint of observation, 23 patients suffered molecular relapse. Among them, 15 cases (65.22 %) were due to cost; 1 case (4.35 %) was due to getting pregnant, 5 cases (21.74 %) were due to side-effect and 2 cases (8.69 %) were due to other reasons. There was more frequency relapse in the group of insufficient cost. Conclusion The motivation of Chinese CML patients who have stopped TKI might show impact on the outcome,and the motivation is mainly related with history of drug reduction and withdrawal.
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In recent years, the research hot in the field of solid tumor and blood tumor focuses on the myeloid-derived suppressor cells (MDSCs).In tumors, MDSCs not only exert immunosuppression by inhibiting T cell proliferation, destroying the functions of natural killer cells and recruiting regulatory T cells, but also play non-immunosuppression roles in the promotion of angiogenesis and tumor metastasis.All of these hinder the anti-tumor therapy, and particularly affect the curative effect, which are related with a poor clinical prognosis.MDSCs can be used as prognostic markers, which provide new targets for immunotherapy.
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Objective To investigate the clinical efficacy of electroacupuncture at specific points in treating different degrees of urgency-frequency syndrome. Methods Sixty patients with urgency-frequency syndrome were randomly allocated, according to the symptom score, to groups A (the symptom score≤ 24) and B (the symptom score>24), 30 cases each. Both groups received electroacupuncture at specific points (four sacral points and four abdominal points). In the two groups, the symptoms were scored before and after treatment and the clinical therapeutic effects were evaluated.Results There was a statistically significant pre-/post-treatment difference in the symptom score in the two groups (P0.05).Conclusion Electroacupuncture at specific points is an effective way to treat urgency-frequency syndrome.
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<p><b>OBJECTIVE</b>To exam the role of leukemia cells-derived microparticles in the post-complete molecular response stratification.</p><p><b>METHODS</b>Blood samples from 29 patients diagnosed with chronic myeloid leukemia (CML) were collected. Microparticles (MP) were extracted from the peripheral blood. Real-time PCR was performed to measure the level of BCR-ABL mRNA.</p><p><b>RESULTS</b>BCR-ABL mRNA could be stably detected both in MP and peripheral blood cells; BCR-ABL in MP showed significant difference within complete molecular response, major molecular response and complete cytogenetic response (9.1±2.8, 25.2±6.9 and 62.8±6.3 respectively, P<0.05). BCR-ABL was detected in MP even when it was negative in peripheral blood cells (3.7-15.3). For patients with complete molecular response, BCR-ABL in MP but not cells were significantly different between imatinib and stem cell transplant recipients (3.3±2.1 vs 9.1±2.8, P<0.05).</p><p><b>CONCLUSION</b>This study indicated that MP may serves as a new target for monitoring of CML. Quantification of BCR-ABL in MP may offer a novel strategy for stratification of molecular response.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Cell-Derived Microparticles , Fusion Proteins, bcr-abl , Genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Therapeutics , RNA, Messenger , Genetics , Real-Time Polymerase Chain ReactionABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a highly successful treatment for hematological malignancies,severe congenital immunodeficiencies and some other diseases.Approximate 50 ％ of the disease-free survival patients suffered from long-lasting severe cognitive impairment after allo-HSCT.Pathological evidences showed parenchymal lymphocytic inflammation,microglia activation,and mild cerebral angiitis-like changes in allogeneic transplanted animals and patients' autopsy.Pay much importance attention to the pathological changes of central nervous system and its impact on cognitive function and take suitable measures would help the patients to achieve a state of complete physical mental and social well-being.
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The retinoblastoma-protein-interacting zinc finger proteinl (RIZ1),a methyltransferase,contains the characteristic PR zinc finger domain.RIZ1 can methylate H3K9 of the histone,acted as a transcription suppression factor of cancers.Increasing numbers of human cancers are reported to hold decreased or absent RIZ1 expression,which is closely related to the progression of cancer.RIZ1 is defined as a candidate anti-oncogene.The mechanisms of the suppression involved in both oncocytogenetics and epigenetic changes.
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ObjectiveTo evaluate the primary effect of granulocyte-monocyte colony stimulating factor (GM-CSF) as an immunotherapy option for treatment of residual disease after alloHSCT.Methods Immunotherapy was performed on two patients with blood malignancy to treat residual disease after allo-HSCT. The patient one,who was diagnosed as having MDS-RAEB Ⅱ,showed bone marrow displasis and incomplete chimerism 6 months after unrelated donor HSCT.Immunosuppressive drug was withdrawn without induction of graft-versus-host disease (GVHD).The patient two B-ALL demonstrated a residual disease at molecular level 30 days post-transplantation.Both of them were given GMCSF (300 μg) subcutaneously once every two days for totally three weeks.During the whole period,skin itch and rash,liver function,subgroups of lymphocytes,and MDSCs and DCs in peripheral blood were investigated.Results In case one,grade Ⅰskin acute GVHD (aGVHD) appeared as early as one week after GM-CSF administration,as well as grade Ⅱ (skin and liver) by the end of the third weeks,and GM-CSF injection was withdrawn.One month later since the start of GM-CSF,the patient showed normal bone marrow morphology and full donor type chimerism. Cyclosporine A (CsA), mycophenolate mofetil and methylprednisolone were administered for two weeks to control GVHD.In the other case,grade Ⅰ aGVHD occurred 9 days after GMCSF administration,and whole blood CsA maintained at 0.134-0.472 μmol/L.Prednisone (30mg per day for 5 days) was used to control grade Ⅱ GVHD from the 11th day after GM-CSF,and grade Ⅰ GVHD continued without any intervention.On the 30th day after GM-CSF treatment,bone marrow aspiration showed complete molecular remission.In both of the two cases,no differences in lymphocytic subtypes were revealed before and after GM-CSF administration,while there were trends of increased DC number and decreased MDSCs in peripheral blood.ConclusionThe administration of GM-CSF as an immunotherapy option for blood malignancy may contribute to the clearance of residual disease after Allo-HSCT.
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P-450-dependent epoxygenase pathway of arachidonic acid and the products of epoxyeicosatrienoic acids (EETs) have been demonstrated to be involved in angiogenesis and tumor progression. This study examined the expression of EETs and the role of the pathway in the angiogenesis of multiple myeloma (MM). MM cell lines of U266 and RPMI8226 were cultured, and the EETs levels (11, 12-EET and 14, 15-EET) in the supernatant were determined by ELISA. Human umbilical vein endothelial cells (HUVECs) were cultured and used for analysis of the angiogenesis activity of the two MM cell lines, which was examined both in vitro and in vivo by employing MTT, chemotaxis, tube formation and matrigel plug assays. 11, 12-EET and 14, 15-EET were found in the supernatant of the cultured MM cells. The levels of the two EETs in the supernatant of U266 cells were significantly higher than those in the RPMI8226 cell supernatant (P<0.05), and the levels paralleled the respective angiogenesis activity of the two different MM cell lines. 17-octadecynoic acid (17-ODYA), as a specific inhibitor of P450 enzyme, suppressed HUVECs proliferation and tube formation induced by MM cells. Furthermore, 17-ODYA decreased the EET levels in the supernatant of MM cells. These results suggest that EETs may play an important role in the angiogenesis of MM, and the inhibitor 17-ODYA suppresses this effect.