Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

Immunoregulatory Factor Released From a Cell Line Derived From Human Decidual Tissue

ABSTRACT: The culture supernatant of the TTK-1 cell line, established from human decidual tissue, was found to contain a factor that strongly suppressed the mixed lymphocyte reaction (MLR). The mechanism of the MLR-suppressive activity as well as the biochemical characterization of this factor was analyzed. The TTK-1 supernatant suppressed the MLR much more strongly than the culture supernatants of the three other malignant cell lines examined. The molecular weight of this factor was estimated to be between 43 kilodaltons (kd) and 67 kd by gel filtration chromatography. The TTK-1 supernatant also suppressed the proliferation of the interleukin 2 (IL-2)-dependent T cell lines, but did not suppress that of the IL-2-independent T cell lines, suggesting that the TTK-1 supernatant inhibited the action of IL-2 and subsequently suppressed the MLR. The fact that the TTK-1 cell line originated from human decidual tissue might imply the important role of this factor in immunological fetomaternal balance.     

二乙酰二脱水卫矛醇对小鼠白血病L1210细胞增殖的影响

目的　研究二乙酰二脱水卫矛醇 (1 ,2 :5 ,6 dianhydro 3 ,4 diacetylgalactitol,DADAG)的抗脑白血病作用及机制。方法　用小鼠脑内移植瘤模型、MTT法、DNA掺入法、流式细胞仪和Westernblot法 ,观察DADAG对小鼠脑内移植瘤和体外白血病L1 2 1 0 细胞的作用 ,并探讨作用机制。结果　DADAG对DBA/ 2小鼠脑内移植白血病L1 2 1 0 有明显的抑制作用 ;对体外白血病L1 2 1 0 细胞同样有很强的抗增殖作用 ,其IC50 值为 2 4 6mg·L- 1 。DADAG不可逆地抑制L1 2 1 0 细胞内DNA的生物合成。DADAG 2 4mg·L- 1 处理L1 2 1 0 细胞 6h后 ,细胞发生G2 /M周期阻滞 ,2 4h后达最高峰。细胞周期素B1 蛋白水平在DADAG处理 2 4h后开始下降 ,而磷酸化的细胞周期依赖性激酶CDK1在DADAG处理 6h后开始上调 ,并呈时间依赖性。结论　DADAG的抗脑白血病作用与其抑制白血病细胞的增殖密切相关     

rhGM—CSF对小鼠口腔粘膜损伤的防治作用

目的：观察rhGM-CSF对TMX致实验性小鼠口腔粘膜损伤的疗效。方法：按随机分组原则将501只昆明种小白鼠分成8组，分别在相应时间给予不同药物（MTX，CF或rhGM-CSF）的处理因素，于第1－10天光镜下观察小鼠口腔粘膜的病理改变和积分情况。结果：IDMTX致口腔粘膜损伤病变率（45％－63％）和积分率（19．4％－56％）较其它组高，且死亡率很低（小于5％）；IDMTX＋GM0（或GM2）组的口腔粘膜损伤病变率（30．53％和30．99％）和积分率（19．47％和17．25％）比IDMTX组（55．56％和36．31％）明显减少，且溃疡严重程度较轻，二者相差显著（P＜0．01）。结论：IDMTX致小鼠口腔粘膜损伤模型可以用于粘膜损伤的研究；rhGM-CSF可以减少MTX致小鼠口腔粘膜损伤，并促进粘膜损伤恢复。     

Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

The high prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma

BACKGROUND: Although many histopathologic factors in squamous cell carcinoma of the tongue predict the prognosis, the major predictive factors have not been identified clearly. This study analyzed the prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma. METHODS: The clinicopathologic features of 124 consecutive patients seen between January 1985 and December 1999 with previously untreated squamous cell carcinoma of the tongue were reviewed. Their mean age was 58.5 years (range: 23-90) and the male-female ratio was 1.8: 1 (79 men and 45 women). There were 41, 40, 30, and 13 cases at stage I to stage IV, respectively. The clinicopathologic factors, especially the histologic grade at the deep invasive front (invasive front grade, IFG), were analyzed to determine factors predicting prognosis. RESULTS: The 5-year disease-free survival rate of the patients treated with curative aim only was 66.7%. Clinicopathologic factors significantly associated with the prognosis were T classification, tumor size, stage classification, tumor depth, macroscopic appearance, cervical lymph node metastasis (nodal metastasis), microvascular invasion, and IFG. In a multivariate analysis, patients with tumor depth >/=4 mm, IFG >/=8 points, and nodal metastasis had a reduced disease-free survival and IFG >/=11 points had a predictive value for nodal metastasis (odds ratio: 7.34; P = 0.0019). CONCLUSION: This study found that a high IFG malignancy score had a high prognostic value for squamous cell carcinoma of the tongue.     

Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by inter-facial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatial implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamne frr at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-β-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.     

胰腺癌黏蛋白4基因修饰的树突状细胞疫苗构建及对胰腺癌细胞的免疫效应

Objective To obtain the dendritic cells ( DC)-based vaccine modified by adenovirus containing MUC4 gene , and evaluate the anti-tumor efficacy of DC vaccine to pancreatic tumor cells. Meth-ods The mRNA sequence of tumor associated antigen, MUC4, was obtained from NCBI, and MUC4 se-quence was acquired through the restriction enzyme sites and over lap PCR, then subcloned into adenovirus plasmid to create recombinant adenovirus ( rAd-MUC4) . The DCs were infected by rAd-MUC4 virus and then stimulated the lymph cells from the same donor to induce MUC4 specific cytotoxicity T lympbocytes ( CTL) . The efficacy of CTL was analyzed by LDH releasing assay. Elispot was used to detect the IFN-γ release. Results The recombinant adenovirus containing MUC4 ( sv12) gene was obtained. The MUC4-induced CTL could specifically kill the Capan-1 pancreatic tumor cells [ ( 13. 7±6.0)% , ( 21.4± 4. 7)% , (36.1±9. 5)% at ratios of 10: ,20: ,40: ] , higher than MCF-7 and Bxpc-3 cells respectively, P < 0. 05. The spots number of CTL induced by rAd-MUC4 was ( 139.1±23.3) , more than GFP and PBS control group,P<0.05. Conclusion The Muc4 gene modified DC vaccine could induce the proliferation of CTL, which provided a significant cytotoxicity to HLA-matched MUC4 positive tumor cell lines in vitro.