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31.
Tumor necrosis factor alpha enhances the adenoviral transduction of CD34+ hematopoietic progenitor cells 总被引:1,自引:0,他引:1
The purpose of this study was to improve the transduction efficiency of adenoviral vectors (Ad) in human CD34+ hematopoietic progenitor cells. CD34+ cells from cord blood or mobilized peripheral blood were incubated with tumor necrosis factor-alpha (TNF-alpha). After removal of free TNF-alpha, the cells were infected with an Ad encoding green fluorescent protein (GFP). One day later, viable cells were counted and analyzed for GFP and CD34 by flow cytometry. To visualize vectoral trafficking, CD34+ cells were incubated with fluorophore-conjugated Ad. Plating efficiencies of hematopoietic progenitors before and after transduction were evaluated by methylcellulose assays. Pretreatment with TNF-alpha increased the transduction efficiency more than twofold (39.2% versus 15.5%) in a dose-dependent manner and strongly improved the survival of GFP-positive CD34+ cells. Time course experiments showed that TNF-alpha incubation times as short as 10 minutes were still effective. Neutralizing antibodies to TNF receptor II and RGD peptides diminished the TNF-alpha-dependent increase in transduction efficiency. No TNF-alpha-dependent increase in adenoviral receptors (coxsackie-adenovirus receptor, alphavbeta3-integrin) occurred. Analysis of viral binding demonstrated a significantly higher incidence of local concentrations of Ad along the cell surface (caps) in virus-positive cells of the TNF-alpha-treated group. Plating efficiency, especially the formation of granulocyte-macrophage colony forming units, was enhanced by TNF-alpha pretreatment. We conclude that brief incubation with TNF-alpha before addition of the Ad significantly increased the Ad transduction efficiency in CD34+ cells, and improved post-transduction survival of progenitors of the granulocyte-macrophage lineage. This finding correlates with increased Ad capping at the cell surface and suggests an alteration of Ad trafficking. 相似文献
32.
Genome-wide profiling of oral squamous cell carcinoma 总被引:7,自引:0,他引:7
Chen YJ Lin SC Kao T Chang CS Hong PS Shieh TM Chang KW 《The Journal of pathology》2004,204(3):326-332
Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c-Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21-tel; 20q; 11q13; 3q27-29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC. 相似文献
33.
34.
同种异体黑素细胞移植治疗白癜风 总被引:2,自引:2,他引:0
0 引言 白癜风患者免疫紊乱 ,黑素细胞 (melanocyte,MC)异体移植有可能不被排斥 ,治疗如成功将有很大临床前景 [1 ] .探索同种异体黑素细胞移植后的效果很有意义 .1 病例报告 女 ,2 7岁 ,确诊白癜风 (稳定期 ) ,患者皮肤自幼出现色素脱失斑 ,逐渐增多扩大 . 1996年外用“敏白灵”,前2 mo有效 . 1999- 0 7外用补骨酯酊 ,日服 5 g· L- 1 硫酸铜 10m L和中药 1剂 ,转移因子 4m L ,sc,1· 2 d- 1 .皮损缩小 ,4mo后稳定 .用健康男青年环切的包皮培养 MC,第 4代大约80 %融合时 ,用 2 .5 g· L- 1 胰酶消化 5 min,加入含 2 0 0 g·L- 1小… 相似文献
35.
Parenchymal microglia are targets of HIV infection. We, as well as others, have used in vitro microglia culture systems to study the tropism and replication of HIV. Characterization of perivascular and parenchymal microglia surface markers in vivo, in vitro, and ex vivo, has led to the understanding that these cell populations are different, and data from both the HIV and SIV models support the hypothesis that they may play different roles in infection of the CNS. We determined that human adult parenchymal microglia cultured from temporal lobe tissue for use in HIV replication studies, were CD11c+, CD45+, CD68+, CD14- when cultured with standard serum/cytokine-supplemented media. To determine the influence of serum and cytokines on HIV replication in microglia, we designed a new protocol for culturing microglia, and compared the results obtained with this protocol with the standard approach previously described. Microglia cultured in the presence of a 'feeder' layer of glial cells and in the absence of serum and cytokines expressed the same surface markers as pure microglia (>95%) cultured in supplemented media. However, pure microglia cultured in the absence of both serum/cytokines supplements and other glial cells, did not have characteristic microglial morphology and did not support HIV replication to as high a level. Lastly, we determined that unlike monocytes, ex vivo parenchymal microglia were capable of supporting HIV replication. 相似文献
36.
The Notch family of transmembrane receptors has been implicated in the regulation of many developmental processes. In this study, we evaluated the role of Notch4 in immature hematopoietic progenitors by inducing, with retroviral transduction, enforced expression of Int-3, the oncogenic and constitutively active form of mouse Notch4. Int-3-transduced human myeloid leukemia (HL-60) cells demonstrated significantly delayed expression of differentiation markers following retinoic acid and 12-0-tetradecanoylphorbol 13-acetate treatment. Furthermore, HL-60 cells expressing Int-3 displayed a slower growth rate than cells infected with void virus, and accumulation in the G0/G1 phases of cell cycle. Transduction with deletion mutants of Int-3 defined the importance of individual domains of the protein (in particular, the ANK domain and the C-terminal domain) in the inhibition of differentiation and growth arrest of HL-60 cells. When mouse bone marrow enriched for stem cells (5-fluorouracil-resistant, lineage negative) was transduced and cultured for two weeks, the Int-3-transduced population displayed a lower expression of differentiation markers and a three- to five-fold higher frequency of colony-forming cells (CFU-GM/BFU-E) than control cultures. These results strongly support the notion that Notch signaling inhibits differentiation and promotes expansion of hematopoietic stem/progenitor cells. 相似文献
37.
Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung 总被引:1,自引:0,他引:1
Prahalad AK; Ross JA; Nelson GB; Roop BC; King LC; Nesnow S; Mass MJ 《Carcinogenesis》1997,18(10):1955-1963
Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic
hydrocarbon, is the most potent carcinogen ever tested in mouse skin and
rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction,
tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in
strain A/J mouse lung. Groups of mice received a single i.p. injection of
0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment,
DNA adducts were measured at times between 1 and 28 days, while tumors were
counted at 250 days and analyzed for the occurrence of point mutations in
codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung
induced six major and four minor DNA adducts. Maximal levels of adduction
occurred between 5 and 10 days after injection followed by a gradual
decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti-
and syn-11,12- dihydroxy-13,14-epoxy-
11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both
deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed
by cochromatography. The major adduct was identified as a product of the
reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced
significant numbers of lung adenomas in a dose- dependent manner, with the
highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In
tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based
on the administered dose, DB[a,l]P was more active than other environmental
carcinogens including benzo[a]pyrene. As a function of time-integrated DNA
adduct levels, DB[a,l]P induced lung adenomas with about the same potency
as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar
in carcinogenic potency to other PAHs in the strain A/J mouse lung model.
Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors
revealed the predominant mutations to be G-->T transversions in the
first base of codon 12, A-->G transitions in the second base of codon
12, and A-->T transversions in the second or third base of codon 61,
concordant with the DNA adduct profile.
相似文献
38.
Nesnow S; Davis C; Nelson G; Ross JA; Allison J; Adams L; King LC 《Carcinogenesis》1997,18(10):1973-1978
C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study the in
vitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) and
benzo[a]pyrene (B[a]P). The morphological transforming activities of these
rodent carcinogens were compared using replicate concentration- response
studies. In concentration ranges where both polycyclic aromatic
hydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12 times as
potent as B[a]P based on concentration. At lower concentrations DB[a,l]P
was active at 0.10 and 0.20 microM, concentrations where B[a]P was
inactive. This makes DB[a,l]P the most potent non-methylated PAH evaluated
to date in C3H10T1/2 cells. DNA adducts of DB[a,l]P in C3H10T1/2 cells were
analyzed by both TLC and TLC/HPLC 32P-postlabeling methods using
mononucleotide 3'-phosphate adduct standards derived from the reactions of
anti-DB[a,l]P-11,12-diol- 13,14-epoxide (anti-DB[a,l]PDE) and
syn-DB[a,l]P-11,12-diol-13,14- epoxide (syn-DB[a,l]PDE) with deoxyadenosine
3'-monophosphate and deoxyguanosine 3'-monophosphate. All of the DNA
adducts observed in C3H10T1/2 cells treated with DB[a,l]P were identified
as being derived from the metabolism of DB[a,l]P to its fjord region diol
epoxides through DB[a,l]P-11,12-diol. The predominant adduct was identified
as an anti-DB[a,l]PDE-deoxyadenosine adduct. Other major adducts were anti-
DB[a,l]PDE-deoxyguanosine and syn-DB[a,l]PDE-deoxyadenosine adducts with
minor amounts of syn-DB[a,l]PDE-deoxyguanosine adducts. These DNA adduct
data are consistent with similar findings of DB[a,l]PDE- deoxyadenosine
adducts in mouse skin studies and human mammary cells in culture.
相似文献
39.
Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control 总被引:1,自引:0,他引:1
Chang JT; See LC; Liao CT; Chen LH; Leung WM; Chen SW; Chen WC 《Japanese journal of clinical oncology》1998,28(3):207-213
OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the
control of early stage nasopharyngeal carcinoma (NPC) treated with a
combination of external radiotherapy and brachytherapy, MATERIALS &
METHODS: We reviewed the records of 133 patients with early stage
nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who
received definitive radiotherapy in Chang Gung Memorial Hospital from 1979
to 1991. The median follow-up time was 7.1 years with a minimum of 2 years.
All patients were treated with megavoltage external radiotherapy to the
nasopharynx area (63-72 Gy) followed by high dose rate intracavitary
brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks
apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4
Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used
to examine the effect of several variables on prognosis. RESULTS: The
5-year rates were 86.4% for local control, 84.7% for disease free survival,
88.5% for actuarial survival and 84.2% for overall survival. The treatment
group (combination of time and dose of irradiation) was the most important
prognostic factor according to Cox's proportional hazard model. Patients
receiving radiation at a total dose of < or = 75 Gy completed in < 12
weeks showed the best prognosis. CONCLUSION: Treatment time and total
treatment dose are both important factors in treating early stage NPC.
Decreasing the total radiation time to < 12 weeks and not exceeding a
radiation dose of 75 Gy gave the best results.
相似文献
40.