Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients.</p><p><b>METHODS</b>Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/mper day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated.</p><p><b>RESULTS</b>Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 10/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%).</p><p><b>CONCLUSION</b>Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.</p>

Protective effects and possible mechanism of 12-O-tetradecanoylophorbol-13-decano-ate against acute intestinal radiation injury of mice / 军事医学

Objective To investigate the effect of 12-O-tetradecanoylophorbol-13-decanoate(TPD)on protection against acute intestinal radiation injury of mice and the possible mechanism.Methods Twenty female BALB/c mice aged 6-8 weeks were divided by random number table method into the control group and TPD groups(25,50,and 100 μg/kg). A radiation-damaged model of mice was irradiated by 10 Gy 60Co γ-rays,while the TPD groups were pretreated for 3 d with caudal vein injection before irradiation.The survival time of 20 days and the number of crypts at 3.5 days after irradiation were detected.Rat intestinal epithelial cells(IEC-6)were treated with 1 nmol/L TPD for 12 h before irradiation with 10 Gy 60Co γ-rays,and CCK-8 was used to detect the capability of cell proliferation at 0,1,2,3 and 4 d after irradiation. Results The mice in the control group survived for an average of 4.2 days,compared to 10 days in the optimal TPD group (100 μg/kg).The average number of crypts in the control group and the best TPD group was 11.0 ±1.3 and 35.1 ±1.9 respectively.The proliferation activity of IEC-6 was measured for four consecutive days.The average D value of the TPD groups was significantly higher than that of control.Conclusion TPD has a protective effect against acute intestinal radiation injury, and its protective mechanism may be achieved by promoting intestinal crypt cell proliferation and increasing the number of crypts in the intestine.

Research Advances in Bacteria-based Microrobot / 中国医学科学院学报

The concept of bacteria-based microrobot has been well recognized. It has shown great advantages and potentials for the early diagnosis and early treatment of malignant tumor and in reducing chemotherapy toxicities. In this article we review the concept,structure,and potential clinical applications of bacteria-based microrobot.

Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC.</p><p><b>METHODS</b>We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell.</p><p><b>RESULTS</b>The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P < 0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.</p><p><b>CONCLUSION</b>MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.</p>

Massive hemoptysis and hemothorax: a rare but fatal complication of intralobar sequestration / 中华医学杂志(英文版)

Intralobar sequestration (ILS) is an uncommon abnormality that accounts for 75% of all pulmonary sequestrations. Over the years there have been several reports of various presenting signs of which hemoptysis was commonly described, however, massive hemoptysis and hemothorax is extremely rare in literature. We present a case of a 45-year-old man who died of fatal complication from an ILS. This case report shows an uncommon presentation of ILS with massive hemoptysis and hemothorax resulting in a dramatic course of disease and a fatal outcome, and for this reason in the absence of trauma or other causes for massive hemoptysis, hemothorax, or lung hematoma, this possibility should be kept in mind so as to avoid misdiagnosis, and resection of the sequestered tissue should be considered in all patients.

Detection and clinical significance of FLT3-ITD gene mutation in patients with acute myeloid leukemia / 中国实验血液学杂志

This study was aimed to evaluate the prevalence of FT3-ITD mutation in patients with acute myeloid leukemia (AML) and its significance for prognosis. The bone marrow of 216 patients with AML were detected by using PCR and R-banding methods. On basis of patients' clinical data the clinical feature and prognosis were analyzed. The results showed that in 216 AML patients incidence of FLT3-ITD mutation was 20.83%. FLT3-ITD mutation was present in 24% patients with normal karyotype while in 12.5% patients with abnormal karyotype. The FLT3-ITD positive patients had more white blood cells in peripheral blood and leukemia cells in bone marrow (P < 0.01). The free-disease survival and overall survival time were shorter in FLT3-ITD positive cases than that in FLT3-ITD negative cases (P < 0.05). It is concluded that FLT3-ITD mutation positive patients have more white blood cells in peripheral blood and leukemia cells in bone marrow. The FLT3-ITD mutation may be a danger factor in the AML patients with normal karyotype. It may be helpful for evaluating prognosis and guiding individual treatment of AML.

Advanced dermatofibrosarcoma protuberans treated with imatinib mesylate / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, side effects and toxicity of imatinib mesylate in the treatment of patients with locally advanced and/or metastatic dermatofibrosarcoma protuberans (DFSP).</p><p><b>METHODS</b>Twenty-four cases of advanced DFSP diagnosed by pathology and treated in our hospital from Nov. 2004 to Oct. 2009 were included in this study. The patients were treated with imatinib mesylate (dosage: 400 mg, po, qd) and carefully observed for treatment efficacy, side effects and survival time. There were 2 patients taking the drug as second line therapy, and other 22 patients as third or more than third line therapy.</p><p><b>RESULTS</b>The 24 patients were evaluable for the efficacy. There were 8 patients (33.3%) with CR, 10 pts (41.7%) PR, 2 patients (8.3%) SD, and 4 patients (16.7%) PD. The disease control rate (DCR = CR+PR+SD) was 83.3%. The median response time in 18 cases with CR and PR was 5.6 months. The median survival time in 20 cases with disease control was 30 months, however, that in nonresponse (PD) cases was only 10 months. Side reactions related to imatinib mesylate included nausea and vomiting (20.8%), neutropenia (12.5%), and edema (8.3%).</p><p><b>CONCLUSIONS</b>Our results are consistent with previous reports in the literature. Imatinib is a safe and effective moleucular target drug used for Chinese. Only mild adverse reactions occur in the treated patients. It is worth using imatinib in the treatment of advanced DFSP patients.</p>

Recent research advances on function of CD4+T lymphocytes / 中国实验血液学杂志

Cellular immunity is an important component of human immune system and plays a crucial role in the fight against tumor cell or invasive pathogens. Researches on cell-based immunotherapy have long been focused on eliciting tumor-specific CD8+ cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. However, the resulting treatments have been surprisingly poor at inducing complete tumor rejection, in both the experimental models and clinical trials. The CD4+ T cells has been studied mainly for their role as helpers for CD8+ CTL, even suggesting that the tumor-specific CD4 T regulatory cells could act as suppressors of antitumor responses. Recent studies indicated that CD4+T cells are not a pure cell lineage with single function, but a cell population with complex functions. Moreover CD4+ T cells may not only be helper cells, but also act as potent effector cells or partners with NK cells that can clear a wide variety of tumors. In a word, the antitumor potential of effector CD4+ T cells might have been underestimated. In this article, the classification and differentiation of CD4+ T cells, the function and secreted cytokines of CD4+ T cells, the CD4+ T cells and tumor immune, the tumor-immuno regulatory effects of CD4+ T cells, and clinical researches of CD4+ T cells are reviewed.

Effect of doxorubicin induced GM-CSF gene expression regulated by Egr-1 promoter on recovery of hematopoietic function in bearing-melanoma mice / 中国实验血液学杂志

This study was purposed to investigate the effect of hematopoietic growth factor expression regulated by Egr-1 promoter on the recovery of hematopoietic function in bearing-melanoma mice after chemotherapy with doxorubicin (ADM). The human GM-CSF cDNA and enhanced green fluorescence protein (GFP) cDNA were linked together with internal ribozyme entry site (IRES) and then were inserted into the expression vector pCI-neo under control of the Egr-1 promoter (Egr-EG). This vector was transduced into human bone marrow stromal cell lines HFCL by lipofectamine and was transfused in severe combined immunodeficiency (SCID) mice. The experimental mice were randomly divided into 4 groups (6 mice in each group): (1) HFCL/EG + ADM group in which the HFCL/EG cells were transplanted intravenously in SCID mice bearing melanoma, ADM was given intraperitoneally after 3 days; (2) HFCL + ADM group in which the HFCL cells were transplanted intravenously, ADM was given intraperitoneally after 3 days; (3) HPCL/EG group in which HFCL/EG cells were transplanted alone; (4) HFCL group in which HFCL cells were transplanted alone. The dynamic change of peripheral blood picture was assayed by hemocytometer; the eGFP(+) human stromal cells were detected by flow cytometry; the expression of GM-CSF mRNA and protein were determined by RT-PCR and Western blot respectively. The results indicated that as compared with HFCL/EG and HFCL groups, the leukocyte count in HFCL/EG + ADM group decreased, but decrease level was weaker than that in HFCL + ADM group, meanwhile the recovery of leukocyte count was earlier than that in HFCL + ADM group. The CFU-GM amount between 4 groups showed no significant difference. The detection results showed that the inhibitory rate of tumor was related to chemotherapy, but not to expression of exogenous gene; the eGFP(+) stromal cells existed in bone marrow of mice treated with ADM. The RT-PCR and Western blot assays revealed enhancement of GM-CSF mRNA and protein. It is concluded that the ADM-inducible GM-CSF gene therapy regulated by Egr-1 promoter may promote the hematopoietic recovery after chemotherapy.

Regulatory effect of Egr-1 promoter sequences induced by doxorubicin in transcriptional targeting on expression of GM-CSF gene / 中国实验血液学杂志

In order to explore the regulatory effects of Egr-1 promoter sequences induced by doxorubicin (ADM) in transcriptional targeting on the expression of hematopoietic growth factor genes. The human GM-CSF cDNA and enhanced green fluorescent protein (eGFP) cDNA were linked together with internal ribozyme entry site (IRES) and then inserted into the expression vector pCIneo under control of the Egr-1 promoter (Egr-EG). The vector was transferred into human bone marrow stromal cell line HFCL by lipofectin. The transfected cell clones (HFCL/EG) were selected by the addition of G418. The cells were exposed to the clinically important anticancer agent doxorubicin. The activity of eGFP in HFCL/EG cells was detected by flow cytometry. The amounts of GM-CSF in HFCL/EG postchemotherapy were confirmed with ELISA. The effect of GM-CSF in HFCL/EG cultural supernatants on expansion of CFU-GM derived from cord blood was also studied. The effect of N-acetylcysteine (a free radical scavenger) on GM-CSF production following exposure to ADM was examined. The results indicated that the activity of eGFP and the amounts of secreted GM-CSF in HFCL/EG cells exposed to ADM increased as compared to non-ADM group. The effect of GM-CSF in HFCL/EG cultural supernatants on expansion of CFU-GM was significantly higher than that of non-ADM group. N-acetylcysteine significantly decreased the concentration of GM-CSF produced by HFCL/EG treated with ADM. It is concluded that these in vitro data provide an experimental basis for the use of gene therapy of hematopoietic growth factor gene regulated by Egr-1 promoter to protect hematopoiesis from ADM-injury.

HER-2 and ER expression in prediction of chemo-sensitivity of taxane for advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer.</p><p><b>METHODS</b>Of 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay.</p><p><b>RESULTS</b>Univariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P < 0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane.</p><p><b>CONCLUSION</b>ER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.</p>

Effect of chemoinducible GM-CSF gene expression regulated by Egr-1 promoter on chemotherapy damage of tumor bearing mice / 中国癌症杂志

Background and purpose:Ionizing radiation(IR) activates the early growth response- I(Egr1) promoter through specific cis-acting sequences termed CArG elements by production of radical oxygen intermediates(ROls).Egr-EG,an expression vector pCIneo containing CArG elements cloned upstream of the cDNA for human recombinant GM-CSF,was used to treat hematopoietic damage due to chemotherapy.Commonly used chemotherapeutic agents can cause tumor cell death by producing DNA damage and generating ROIs.We therefore hypothesized that clinically employed chemotherapeutic agents that increase ROIs could also be employed to activate Egr-EG in a chemoinducible gene therapy strategy.This study was done to explore the chemo-protective effect of the expression of hematopoietic growth factors regulated by Egr-1 promoter on chemotherapy induced damage. Methods:The human GM-CSF cDNA and EGFP cDNA were linked together with internal ribosome entry site(IRES) and then inserted into the eukaryotic expression vector pCI-neo with the Egr-1 promoter(Egr-EG),and was further transduced into human bone marrow stromai cell lines HFCL(HFCL/EG).The HFCL/EG cells were transplanted i.v.into BI6 melanoma in C.B-17 combined immunodeficient(SCID) mice.5-FU was given i.p.on day 3 and 4.The white blood cell amount in peripheral blood,the expression of EGFP and GM-CSF in human stromal cell engrafted in recipient mice were detected by flow cytometry,RT-PCR,Western blot and colony-forming units for granulocytes and macrophages(CFU-GM),respectively.Results:In contrast to the two control groups,HFCL/EG(the Egr-regulatory element-derived expression of GM-CSF gene therapy) resulted in a proportional increase in the number of the white blood cell after chemotherapy,no significant diifferences were found for CFU-GM in bone marrow cells and the inhibition ratio on tumor in recipient mice.Chemotherapy could markedly increase the expression of EGFP and GM- CSF mRNA/protein as compared with that of non-chemotherapy control groups and HFCL group.Conclusion: Chemoinducible GM-CSF gene therapy regulated by Egr-1 promoter can ameliorate the toxic effect on 5-FU chemotherapy-inducible hematopoietic damage.

Relation of dose intensity and efficacy, toxicity in paclitaxel as a single agent for advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the relation of dose intensity and efficacy, toxicity in advanced breast cancer treated with paclitaxel as a single agent.</p><p><b>METHODS</b>Seventy-one patients with advanced breast cancer received paclitaxel as a single agent with different dose intensities. According to the phase I or phase II trial, the standard dose intensity of paclitaxel was defined as 58.3 mg.(m(2))(-1).week(-1). The dose of paclitaxel was 175 mg/m(2) given every three weeks, ranging 33.3 - 70.3 mg.(m(2))(-1).week(-1) [median delivered dose intensity 58.82 mg.(m(2))(-1).week(-1)]. Efficacy and toxicity was evaluated.</p><p><b>RESULTS</b>The overall response rate in this group of advanced breast cancer was 40.8%. Responses were seen in lungs, soft tissue, bone and liver, with the response rates of 52.0%, 38.0%, 12.5%, 7.7%, respectively. When the relative dose intensity (RDI) was > 1.0, 0.9 - 1.0, < 0.9, the response rates were 44.2%, 47.6%, 0, respectively. The difference between the group (RDI >/= 0.9% - 1.0%) in 7 patients and the group (RDI < 0.9) was significant (P < 0.05). Toxicity was well tolerated, with the efficacy decreased as soon as the RDI had been reduced without embarrassing the toxicity.</p><p><b>CONCLUSION</b>Paclitaxel as a single agent therapy with standard dose intensity is effective and well tolerated by patients with advanced breast cancer.</p>