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Di-Jiao Tang,
Qian Niu,
Ting-Ting Zeng,
Neng-Gang Jiang,
Yong-Mei Jin,
Bin Ding,
Qin Zheng,
Qing Shi,
Jiao Chen,
Jiang Yu,
Jun Su, Yong-Qian Jia
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ABSTRACT: This study was purposed to investigate the ratio of Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood of patients with chronic lymphocytic leukemia (CLL) and to explore their roles in the pathogenesis and clinical diagnosis. Based on the number of peripheral lymphocytes and treatment condition, the CLL patients were divided into 2 groups: untreated group (n = 30) and remission group (n = 15), the healthy control group (n = 20) was set up as well. The frequencies of Th17 and Treg cells of all cases were detected by flow cytometry (FCM). The results showed that frequencies of CD3(+)CD4(+)T cells and Th17 cells were significantly higher in untreated group than that in healthy control group (P < 0.05), the frequencies of CD3(+)CD8(+)T cells and Treg cells were significantly lower in untreated group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in untreated group than that in healthy control group (P < 0.05). The frequencies of Th17 were not statistically different between remission and healthy control groups, the frequencies of Treg cells were significantly lower in remission group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in remission group than that in healthy control group (P < 0.05), frequencies of Th17 cells were markedly lower in remission group than that in untreated group (P < 0.05). It is concluded that Th17/Treg imbalance exists in patients with CLL, which may play a key role in pathogenesis and development of CLL.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 03/2013; 21(2):329-33.
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ABSTRACT: The purpose of this study was to detect the minimal residual disease (MRD) in peripheral blood of newly diagnosed patients with acut myeloid leukemia (AML) on day 8 of induction chemotherapy and analyze the correlation between day 8 MRD (D8RD) and therapeutic effectiveness. 29 adult patients (13 males and 16 females, aged 16 - 75 years, median 41 years) with AML diagnosed and treated in West China Hospital from September 2009 to June 2010 were analyzed and followed up in the study. The leukemia-associated aberrant immunophenotype (LAIP) of all the patients were detected by multiparameter flow cytometry (FCM) before therapy. The level of MRD in the peripheral blood at day 8 of induction chemotherapy was detected by FCM based on the LAIP. The overall survival curve was drawn by calculation using Kaplan-Meier method using, and the comparison between different groups was carried out by Log-rank test. The results indicated that after first course therapy, the levels of peripheral D8RD in 7 out of 29 AML cases were lower than 0.01% (negative group), and that in another 22 cases were higher than 0.01% (0.08% - 55%, positive group). The sex, age, WBC, LDH, percentage of bone marrow blasts at diagnosis in these groups were not statistically different. 6 cases achieved CR (86%) in D8RD negative group, and also 6 cases achieved CR (27%) in D8RD positive group, CR rate in D8RD negative group was higher than in D8RD positive group (86% vs 27%, P < 0.05). The median follow-up of 29 cases lasted for 15 months; the 1-year overall survival rate of D8RD negative and D8RD positive groups was 100% and 39.4%, respectively (P < 0.01). It is concluded that MRD level in peripheral blood at day 8 of induction chemotherapy is an early index to predict clinical efficacy of induction therapy in AML.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2013; 21(1):57-61.
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ABSTRACT: Immunophenotypes are critical for diagnosing common B cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic-CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, patient-specific composite leukemia cell populations could provide detailed information concerning the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.
Chinese journal of cancer 07/2012;
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ABSTRACT: Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML).
To study the patterns of FLT3-ITD in Chinese patients with AML.
A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives.
A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML.
Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.
Archives of pathology & laboratory medicine 01/2012; 136(1):84-9. · 2.58 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the influence of immunosuppressive therapy on the expression of TNF-α/IFN-γ in cytoplasm of peripheral blood lymphocytes of patients with aplastic anemia (AA). The expression of TNF-α and IFN-γ in cytoplasm of peripheral CD3(+) lymphocytes were measured by flow cytometry in 25 cases of de novo AA patients and 20 cases of AA after immunosuppressive therapy. The results showed that the positive rates of CD3(+)/TNF-α(+) and CD3(+)/IFN-γ(+) in de novo AA patients were (5.97 ± 6.78)% and (15.20 ± 11.28)% respectively, and (1.56 ± 0.87)% and (1.76 ± 0.87)% in normal controls respectively. There was significant difference between de novo AA patients and normal controls (p < 0.05). The positive rates of CD3(+)/TNF-α(+) and CD3(+)/IFN-γ(+) in immunosuppressive therapy group were (1.67 ± 1.26)% and (4.35 ± 4.33)% respectively. The difference between immunosuppressive therapy group and de novo AA group was statistically significant (p < 0.05). It is concluded that the levels of intracellular TNF-α and IFN-γ in AA patients are higher than those in normal controls. Immunosuppressive therapy significantly reduces the expression of intracellular TNF-α and IFN-γ. Its relationship with the clinical treatment is worth further observing.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 06/2011; 19(3):689-91.
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ABSTRACT: The aim of study was to investigate the immunophenotype characteristics and prognosis of acute leukemia patients with cross-expressing lymphoid and myeloid lineage-associated antigens. The immunophenotypes of leukemic cells were examined by using flow cytometry. All patients were classified into several groups according to FAB subtypes and immunophenotyping. The cross-expressed antigens analyzed for AML included CD2, CD7, CD19, CD56 and other co-expressed lymphoid antigens. The myeloid antigens analyzed for ALL included CD13 and co-expressed CD13/CD33. ALL and AML patients without expression of cross-expressing antigens were selected as control. Complete remission (CR) ratio and relapse-free survival (RFS) of patients in all groups were compared. The results indicated that among 161 patients analyzed, 91 cases of AML with cross-expressing lymphoid and myeloid antigens included that 24 cases of AML expressed lymphoid surface marker-CD7, namely CD7(+) AML, 14 cases of AML only expressed lymphoid surface marker-CD19, namely CD19(+) AML, 8 cases of AML expressed lymphoid surface marker-CD2 (including CD2/CD19 co-expressed), namely CD2(+) AML, 10 cases of AML expressed lymphoid surface marker-CD56 (including CD56/CD19 or CD56/CD2 co-expressed), namely CD56(+) AML, 16 cases of AML expressed two or more lymphoid surface markers, namely Ly ≥ 2(+) AML, 9 cases of ALL expressed myeloid surface markers CD13, namely CD13(+) ALL, 10 cases of ALL expressed myeloid surface markers CD13 and CD33, namely CD13/CD33(+) ALL. 29 cases of ALL did not expressed myeloid surface markers, namely My(-) ALL, and 41 case of AML did not expressed lymphoid surface markers, namely Ly(-) AML. CR ratio and RFS of Ly ≥ 2(+) AML patients were lower than those of Ly(-) AML patients. RFS of CD56(+) AML patients was lower, but CR ratio had no significant difference, when compared with Ly(-) AML patients. CR ratio and RFS of other AML patients with cross-expressing antigens had no significant difference when compared with Ly(-) AML patients. CR ratio and RFS of CD13(+) ALL and CD13/CD33(+) ALL patients had no significant difference when compared with My(-) ALL patients. It is concluded that the importance of cross-expressing antigens for prognosis of patients should be analyzed concretely. CD56(+) AML and Ly ≥ 2(+) AML have bad prognosis, while other cross-expressed lymphoid and myeloid lineage-associated antigens have no impact on prognosis of acute leukemia patients.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 11/2010; 18(6):1405-9.
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ABSTRACT: To evaluate the value of flow cytometric immunophenotyping of cerebrospinal fluid (CSF) cells in the diagnosis of central nervous system leukemia.
Ninety two CSF samples were analyzed with 4-color flow cytometry. Antibody panles CD19/CD34/CD3/CD45, CD117/CD34/CD5/CD45, CD7/CD34/ CD19/CD45, CD7/CD3/HLA-DR/CD45, CD20/CD10/CD3/CD45, and anti-g/anti-lambda/CD19/CD45 were used in determining cell composition and detecting abnormal cells. The results of flow cytometry were compared with conventional cell count and morphology. Flow cytometry analysis was repeated for five samples 48 hours after the initial test.
Abnormal cells were found in 33 out of the 92 (35.9%) samples. Among the 59 samples taken from patients with lymphocyte neoplasm, CD19 + blast cells were found in the CSF in 13 patients with B-cell lymphoblastic leukemia; CD7+ blast cells were found in 4 T-ALL cases; and monoclonal CD19+ cells were found in 6 other types of lymphoma cases. In the 32 patients with clinically diagnosed myeloid leukemia, CD117+ myeloid cells were found in the CSF of 7 patients and B cell blast cells were found in 2 CML cases. The abnormal cells in the CSF detected by immunophenotyping decreased significantly 48 hours after the initial test. Abnormal cells were detected in 25 samples (27.2%) by morphology, less than those detected by immunophenotyping. The cell concentrations of the eight samples in which abnormal cells were only detected by flow cytometry were lower than 10 X 10(6)/L. The immunophenotyping results of two ALL patients were still positive when morphologic results had become negative after chemotherapy.
Flow cytometric analysis of CSF may be helpful in the diagnosis of meningeal leukemia. It has higher positive rate and better accuracy than cytomorphology and cell count.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 07/2010; 41(4):664-8.
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ABSTRACT: To test the effect of Artesunate (ART) on the proliferation of Raji cells, Jurkat cells and acute lymphoblastic leukemia (ALL) primary cells; to determine the synergistic antiproliferation effect between ART and Vincristine (VCR) or Cytarabine(Ara-C) on Raji and Jurkat cells; and to explore the mechanism of ART induced apoptosis of tumor cells in vitro.
MTT assay was performed to detect the inhibition of proliferation of Raji, Jurkat, and ALL primary cells. The cells were exposed to ART at various concentrations with or without VCR or Ara-C. The morphological changes of Raji and Jurkat cells were observed under light microscopy after Wright-Giemsa dyeing and electron transmission microscopy. The mitochondria transmenbrane potential was measured by Rhodamine 123 staining. Colorimetric method was used to measure the activities of caspase-3 in those tumor cells.
ART inhibited the proliferation of Raji cells, Jurkat cells and ALL primary cells. The cytotoxicity of ART on Raji cells and Jurkat cells at a low concentration increased when combined with VCR or Ara-C. Apoptosis in Raji cells and Jurkat cells appeared after exposure to ART. Raji cells and Jurkat cells exposed to ART showed mitochondria transmembrane potential collapse. ART increased the caspase-3 activities of Raji, Jurkat and ALL primary cells.
ART alone or combined with chemotherapy drugs could inhibit the proliferation of B/T lymphocytic tumor cell lines as well ALL primary cells in vitro, probably through the mechanism of apoptosis, which suggest that ART is likely to be a potential drug in the treatment of leukemia/lymphoma.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 11/2009; 40(6):1038-43.
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ABSTRACT: This study was purposed to evaluate the clinical significance of FLT3-ITD of free DNA in plasma from patients with AML. Free DNA in plasma of 235 patients with AML were extracted and identified by globin gene. FLT3 was amplified by PCR and compared with detected results of leukemic cellular DNA (BM or PB). The results indicated that out of total 235 patients, globin gene in plasma free DNA was successfully amplified from 190 cases. In 188 newly diagnosed, replaced and refractory cases, 35 cases showed ITD mutation (19%). And they also showed ITD mutation in leukemic cellular DNA. But in 47 patients in remission, 2 patients with FLT3-ITD mutation of free DNA in plasma had no mutation in cellular DNA, but got relapse early. Compared with patients of FLT3-wt, patients with FLT3-ITD mutation had increased WBC count and expression rate of CD7, CD56 and decreased CR rate. It is concluded that leukemic-specific DNA in plasma can be detected in AML patients and consistent with detected results of leukemic cellular DNA. Furthermore, the free DNA in plasma is more sensitive for MRD monitoring in remitted patients. FLT3-ITD detection plays an important role in evaluation of prognosis and molecular target therapy for AML patients.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 10/2009; 17(5):1144-8.
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ABSTRACT: The mechanisms of human bone marrow mesenchymal stem cells (hBMMSCs)-mediated immunomodulation are still not be completely clarified. In order to investigate the expression of B7-H1 on hBMMSCs and to explore whether B7-H1 mediated signaling pathway (B7-H1/PD-1) involves in the mechanisms of hBMMSCs-mediated immunomodulation, the hBMMSCs were isolated, cultured and identified, the B7-H1 expression on hBMMSCs was detected by flow cytometry, RT-PCR, and Western blot. The inhibitory effect of hBMMSCs on proliferation of T lymphocytes was observed in mixed lymphocyte culture, and then the functional anti-B7-H1 monoclonal antibody (mcAb) was used to block B7-H1, the proliferation of T lymphocytes was detected by using CCK-8. The results indicated that hBMMSCs highly expressed B7-H1 molecule, hBMMSCs effectively inhibited the proliferation of T lymphocytes with a dose-dependent manner, and the inhibitory proliferation of T lymphocytes by hBMMSCs could be partially restored when the anti-B7-H1 mAb was used to block the B7-H1, the inhibitory rate of T lymphocyte proliferation decreased from 64.1% to 38.75%. It is concluded that B7-H1 highly expresses on hBMMSCs, the B7-H1 mediated signaling pathway (B7-H1/PD-1) involves in the mechanisms for hBMMSCs-mediated immunomodulation.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 09/2009; 17(4):990-3.
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ABSTRACT: To explore the MMP-9 expression profile in peritoneal inflammatory macrophages and granulocytes in Mip-1alpha-, CCR1- and CCR5-deficient mice.
In sodium thioglycolate-induced murine peritonitis models, peritoneal macrophages and granulocytes were harvested, identified and purified from WT mice and Mip-1alpha-, CCR1-, CCR5-deficient mice. The RT-PCR was applied to evaluate the expression of MMP-9 in macrophages and granulocytes of different group of mice.
The expressions of MMP-9 of macrophages in Mip-1alpha-, CCR1-, CCR5-deficient mice were significantly lower than that of WT mice (P<0.05); MMP-9 expression of granulocytes in Mip-1alpha-, CCR5-deficient mice were also significantly lower than that of WT mice (P<0.05), while the MMP-9 expression of granulocytes in CCR1-deficient mice was significant higher than that of WT mice.
Deletion of Mip-1alpha and CCR5 could reduce the MMP-9 expression in both macrophages and granulocytes, while deletion of CCR1 could reduce MMP-9 expression in macrophages but increase MMP-9 expression in granulocytes.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 06/2009; 40(3):374-7.
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ABSTRACT: To evaluate the clinical significance of IgH and TCR gamma gene rearrangement in plasma free DNA in patients with non-Hodgkin Lymphoma (NHL).
Plasma free DNA in 74 patients with NHL were extracted and identified by Globin gene. IgH (FR3A/VLJH), TCR gamma (TVG/TJX) clonal rearrangements were amplified by PCR and compared with results of mononuclear cell DNA and pathological biopsy sample DNA.
Plasma free DNAs were successfully obtained from 58 cases (35 B-NHL and 23 T-NHL) of newly diagnostic, refractory and relapsed NHL out of total 74 patients (78.4%), but not found in the rest 16 patients in remission. Of 35 B-NHL cases, 31 showed IgH rearrangement (88.6%), and none with TCR gamma rearrangement; of 23 T-NHL cases, 8 showed TCR gamma rearrangement (34.8%), and 2 with IgH gene rearrangement synchronously. In comparison with the results of IgH and TCR gamma gene rearrangement in biopsy samples in 30 B-NHL cases, 26 cases in plasma free DNA (86.7%) and 24 in biopsy samples (80%) were positive (P > 0.05). In 20 T-NHL patients, 7 cases in plasma cell-free DNA (35%) and 6 cases in biopsy samples (30%) were positive (P >0.05).
Tumor-derived DNA could be detected in plasma from underlying cancer patients. For NHL patients, detecting IgH and TCR gamma gene rearrangement in plasma free DNA has the same clinical significance as in biopsy samples.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 04/2008; 29(4):258-62.
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ABSTRACT: To study the efficiency of polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) in detecting the DNA base mutation and single nucleotide polymorphism (SNP).
By DNA sequencing and PCR-DGGE respectively, mutations in the D-loop of the mitochondrial genome were detected in patients with acute leukemia in period of diagnosis and remission, which was regarded as constitutional DNA. The comparison of results was made for evaluating above two methods. Also, the wild type DNA and mutational DNA were mixed at different proportions to mimic the presence of DNA polymorphism. PCR-DGGE was done to study its sensitivity for SNP.
The specificity and sensitivity of PCR-DGGE in detecting base mutation were 100% and 97.1% respectively. And PCR-DGGE could even detect the presence of polymorphism at rate of 0.5%.
PCR-DGGE has high sensitivity and specificity and can be applied to detection of DNA mutation and SNP, which is better method for checking DNA mutations.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 10/2007; 38(5):882-4.
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ABSTRACT: To investigate the effect of autoreactive T lymphocyte cells on the production of antiplatelet antibody.
The platelet membrane IIb/ IIIa was purified from the affinity chromatography of healthy donors. Peripheral blood mononuclear cells (PBMCs) were isolated from the patients with Immune Thrombocytopenic Purpura (ITP) (experimental group) and the normal people (control group). The PBMCs were stimulated with the purified GP IIb/ IIIa. The cell proliferation was monitored and the level of ILG and anti-GP IIb/ IIIa IgG were measured.
The cell proliferation of the experimental group was faster than that of the control group. The T cells comprised the majority of increased cells in the experimental group. The CD4+ T cells were slightly more in the experimental group than in the control group. The CD28+T and CD25+ T cells were significantly more in the experimental group than in control group. More IL-6 and anti-GP II b/III a IgG were detected in the nine ITP patients than in the control group. The increase of T cell growth of three of the seven ITP patients was not obvious. The three patients also had low levels of IL6 and anti-GP IIb/ IIIa IgG. The proliferation of lymphocyte was also observed in the control group. But very low level of anti-GP IIb/ IIIa IgG antibody was detected in the PBMCs of the control group in vitro.
Autoreactive T lymphocyte GP IIb/ IIIa increases the production of anti-GP IIb/ IIIa IgG antibody. Such increase has a positive effect on the activation of B cells.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 08/2007; 38(4):653-6.
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ABSTRACT: To establish an imatinib resistance cell line and to study its resistant principia.
K562 cells were cultured in imatinib at gradually increased concentrations to generate their resistance cell line. MTT assay, RT-PCR, flow cytometry and HPLC were used to clarify the possible mechanisms of the resistance.
(1) Imatinib resistance cell line K562R was successfully induced by continuous culture in the presence of gradually increasing doses of imatinib up to 5 micromol/L. K562R cells were maintained in the media containing 5 micromol/L imatinib. (2) Proliferation data showed that cell growth of K562R was not inhibited in 5 micromol/ L imatinib, whereas the parental sensitive cell was significantly inhibited by up to 2.0 micromol/L imatinib. (3) The IC50 of K562R was about 7.5 micromol/L which was ten times higher than that of the parental cell. (4) HPLC revealed that the intracellular imatinib concentration of K562R was strikingly lower than that of the parental cells (up to 27. 8-fold). By flow cytometry, P-gp was not detected on K562R cell, indicating that low intracellular imatinib concentration may not be due to P-gp mediated efflux. (5) Sequence analysis of the 374 bp ABL kinase domain showed no mutation in K562R cell.
An imatinib resistance cell line K562R has been successfully established. Low intracellular imatinib concentration is a key link in the chain of cell resistance.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 02/2007; 38(1):22-6.
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Xian-cheng Chen,
Rui Wang,
Xia Zhao,
Yu-quan Wei,
Min Hu,
Yang-sheng Wang,
Xiao-wei Zhang,
Ru Zhang,
Lin Zhang,
Bin Yao, [......],
Ting-ting Zeng,
Jin-liang Yang,
Ling Tian,
Bing Kan,
Xiao-juan Lin,
Song Lei,
Hong-xin Deng,
Yan-jun Wen,
Yong-qiu Mao,
Jiong Li
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ABSTRACT: Mesenchymal stem cells (MSCs) were adenovirally engineered to secrete interleukin-12 (AdIL-12-MSCs) and evaluated for their anticarcinogenesis efficacy against three kinds of unestablished tumor models including B16 melanoma, LLC Lewis lung cancer and HCC hepatoma. Injection of AdIL-12-MSCs into protected mice before tumor inoculation prevented all of 12 mice in B16 preventive groups, 10 out of 12 in LLC lung cancer model and 11 out of 12 mice in HCC hepatoma model from developing tumors, whereas the control groups pre-receiving PBS were validated for 100% carcinogenesis; the tumor formation rates in free-AdIL-12 and vacant MSC groups were unveiled between approximately 83 and 100% even with plentiful angiogenesis and newborn lymphatic vessels, as well as distant metastases. As a novel approach, AdIL-12-MSC has revealed expected preventive effects on carcinogenesis (P<0.01) with low-toxic, broad-spectrum and long-range superiorities. In conclusion, our data indicate that AdIL-12-MSC possess the potential for tropism to preclinical tumor lesions and deprives surviving or hibernating tumor cells, which have escaped from conventional treatments, of revival and recurrence.
Carcinogenesis 12/2006; 27(12):2434-41. · 5.70 Impact Factor
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ABSTRACT: We aim at inducing a potent antitumor immune response via CCL20 expressing in situ tumor.
We constructed a recombinant lentivirus encoding mouse CCL20 cDNA and transduced the mouse mesenchymal stem cells (mMSCs) in vitro, and then selected the transfected cells to get a stable mixed mCCL20-expressing pool (named as lenti-mCCL20-mMSCs) with blasticidin. By the same means, we produced another pool named as lenti-null-mMSCs. The CT26 was mixed with lenti-mCCL20-mMSC and inoculated sc into the left hinder back of BALB/c mouse. And also the CT26 was alone, or mixed with lenti-null-mMSCs or parent mMSCs, and then inoculated sc into BALB/c mice serving as controls.
We got a lenti-mCCL20-mMSCs expression construct. It was shown that mCCL20 increased intratumoral lymphocytes infiltration and facilitated tumor growth in syngeneic murine tumor model.
CCL20 expressing in situ tumor enhances intratumoral lymphocytes infiltration but facilitates tumor growth. However, the mechanism involved remains to be further elucidated.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 10/2006; 37(5):712-6.
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ABSTRACT: Hemophilia A affects male, whereas females are carriers and generally spared from this disease. However, we here reported a 65-year-old female with Hemophilia A while screening the gene mutation of coagulation factor VIII. The female went to hospital because of tripping to lead her right chest to be injured with subcutaneous hematoma. She had historically a hemorrhagic diathesis. The physical examination discovered her hip limited to bend and move, but no discrepancy length between her two legs. The initial laboratory tests showed that the activated partial thromboplastin time (APTT) was 61. 3 seconds (20-40 seconds), and the APTT corrected by mixing with normal plasma was 41.3 s, but the levels of PT, FIB and TT were normal. The plain radiographs revealed the hip joints to suffer from the acetabular dysplasia and osteoarthritis. The level of FVIII:C was 2%, F IX:C 200%, vWF:Ag 120%, vWF:Rcof 100%, vWF:CBA 128%, and the F VIII binding assay to vWF was normal. The primers for exon 14 of F VIII gene were designed according to the NM - 000132 gene sequence. DNA was abstracted from the patient blood. PCR were carried out and the DNA sequence was followed. A new mutation of 4111A-->C was discovered, which caused the amino acid sequence changed (T 1314 P). The mutation of T 1314 P may be the cause of this female patient to get the hemophilia A. This mutation was a novel one which has never been reported before.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 06/2006; 37(3):492-4.
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ABSTRACT: To observe and evaluate the long term survival of patients with chronic myelocytic leukemia transplanted with MCC and BuCy conditioning regimens.
Fourteen cases were treated with MCC regimen (Melphanlan 170 mg/m2 x d x 1, MeCCNU 400 mg/m2 x d x 1, CTX 60 mg/kg x d x 2) and the median follow up time was 6 years; 16 cases were treated with BuCy regimen (Busulfan 4 mg/kg x d x 4, CTX 60 mg/kg x d x 2) and the median follow up time was 4 year.
All the patients were engrafted successfully. 4 of 10 patients examined in MCC group showed mixed chimerism at day 100 after transplantation, whereas only 1 of 12 patients examined in BuCy group showed mixed chimerism. All the patients became complete donor source later without any DLI. The 5-year disease-free survival rate was 71.4% for MCC group and 62.5% for BuCy group. The transplant related mortality and relapse rate were 21% and 7% for MCC group, whereas those were 25% and 12% for BuCy group, respectively. The regimen related toxicity was relatively lower in MCC group and the median duration of hospitalization was 39 days (25-55 days) for patients with MCC regimen, and 55 days (39-90 days) for BuCy regimen.
MCC regimen has a partial ablative effect on CML and the long term disease-free survival is the same as that of BuCy regimen. In regard to the cost-effect efficacy, MCC regimen has a substantial advantage over BuCy regimen.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 04/2006; 37(2):226-9.
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ABSTRACT: To explore the antitumor effect of immunotherapy with recombinant Xenopus laevis vascular endothelial growth factor (xVEGF) as a vaccine combined with adriamycin on lymphoma model in mice.
EL4 lymphoma model was established in C57BL/6 mice. Mice were randomized into four groups: combination therapy, adriamycin alone, xVEGF alone and normal saline (NS) groups, and then were given relevant treatments. The growth of tumor, the survival rate of tumor-bearing mice, and the potential toxicity of regimens above were observed. Anti-VEGF antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. In addition, microvessel density (MVD) of tumor was detected by immunohistochemistry, and tumor cell apoptosis was also detected by TUNEL staining.
The tumor volumes of mice were significantly smaller in combination group than those in other three groups (P < 0.05). Complete regression of tumor was observed in 3 of 10 mice in combination group. Forty-eight days after inoculation of tumor cells, the survival rate of mice was significantly higher in combination group than in NS group (P < 0.01). The anti-VEGF APBC count in combination group or xVEGF group was significantly higher, compared with that in adriamycin group or NS group (P < 0.01). MVD in tumor tissues was significantly lower in combination group than those in other three groups (P < 0.05). Moreover, tumor cell apoptosis was significantly higher in combination group than those in other three groups (P < 0.05).
In this experimental study, the use of xVEGF vaccine and adriamycin as a combination of immunotherapy with chemotherapy has sucessfully produced synergistic antitumor effect on lymphoma in mice.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 09/2005; 36(5):661-4, 675.
