A23187诱导恶性黑色素瘤患者的外周血单核细胞向树突状细胞分化

A23187为一种钙离子载体(calcium ionophore,CI),可提高胞浆内游离钙水平,模拟某些细胞内信号转导事件,导致多基因活化[1-2].我们先前曾探讨了A23187对正常人外周血单核细胞(peripheral monotytes,PBMC)来源的DC的影响[3],最近,我们进行了有关A23187诱导MMe患者的PBMC向DC分化的实验研究.     

dbcAMP诱导的EoL-1分化和凋亡与bcl-2家族的关系

目的:探讨dbcAMP(dbutyryl cyclicAMP)诱导的EoL-1(eosinophilic leukemia cell line)分化和凋亡与bcl-2家族的关系.方法:通过免疫印记和流式细胞仪调查bcl-2家族蛋白在dbcAMP刺激的EoL-1细胞中的表达.结果:EoL-1在正常培养条件下表达高水平的bcl-2、bcl-xL和中等水平的bax,但未表达bcl-xs.dbcAMP诱导了EoL-1细胞下调表达bcl-2和bax及上调表达bcl-xs.结论:dbcAMP诱导EoL-1分化和凋亡与bcl-2的降低以及bcl-xs的升高有关.     

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

PURPOSE: To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). RESULTS: All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). CONCLUSION: There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.     

Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication.

PURPOSE: Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT. EXPERIMENTAL DESIGN: Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years. RESULTS: Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%). CONCLUSIONS: Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control.     

A man with osteoblastic metastasis and hypocalcaemia

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.     

Globotriaosyl Ceramide and Globoside as Major Glycolipid Components of Fibroblasts in Scirrhous Gastric Carcinoma Tissues

Scirrhous gastric cancer is characteristic in that cancer cells proliferate and invade with prominent fibrosis. To search for the expression of specific carbohydrate chains in scirrhous gastric cancer, we have examined the glycosphingolipid composition of scirrhous cancer tissues (n=10) in comparison with that of non-scirrhous cancer tissues (n=10) by means of two-dimensional thin layer chromatography, followed by fast atom bombardment mass spectrometry of the individual glycolipids and immunostaining analysis. The major neutral glycosphingolipids from scirrhous gastric cancer tissues were identified as ceramide monohexoside, ceramide dihexoside, globotriaosyl ceramide (Gb₃) and globoside (Gb₄), while the major acidic glycosphingolipids were II³ Neu-Acα-LacCer, II³ NeuAcα₂-LacCer and sulfatide. Relative concentrations of Gb₃ and Gb₄ in scirrhous gastric cancer tissues (Gb₃+ Gb₄=58%) were two times higher than those in non-scirrhous gastric cancer tissues (29%). Orthotopic fibroblasts cloned from scirrhous gastric cancer tissues showed similar high concentrations of Gb₃ and Gb₄ to scirrhous gastric cancer tissues. Furthermore, immunohistochemical study revealed that Gb₃ and Gb₄ were expressed intensely on the fibroblasts. On the other hand, analysis of glycosphingolipids in four scirrhous gastric cancer cell lines yielded the following results. i) The contents of Gb₃ and Gb₄ were low (6%), compared with orthotopic fibroblasts (62%). ii) Significant amounts of Le^a (pentaglycosylceramide) and Le^b (hexa- and heptaglycosylceramides), which could not be detected in scirrhous cancer tissues, were observed. The results show that the major neutral glycosphingolipids such as Gb₃ and Gb₄ of scirrhous gastric cancer tissues were derived from orthotopic fibroblasts and not from the cancer cells.     

Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States)

Objectives: Because several serum studies of vitamin D metabolites have produced equivocal results on their relation to prostate cancer risk, the purpose of this study is to evaluate this association further.Methods: A nested case-control study in a cohort of 3,737 Japanese-American men examined from 1967 to 1970 was conducted in Hawaii (United States). At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of over 23 years, 136 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 136 matched controls were measured for the following: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, phosphorus, and parathyroid hormone.Results: There were no notable differences between cases and controls in their median serum levels of the five laboratory measurements. Odds ratios (OR) for prostate cancer, based on the quartiles of serum levels in controls, were also determined. The ORs for the highest quartiles relative to the lowest were 0.8 (95 percent confidence interval [CI] = 0.4-1.8) for 25-hydroxyvitamin D and 1.0 (CI = 0.5-2.1) for 1,25-dihydroxyvitamin D.Conclusion: It is possible that the lack of sufficient numbers of study subjects with low vitamin D levels affected the results. Nonetheless, the findings suggest that there is a lack of a strong association between vitamin D and prostate cancer.     

妊娠期接受MRI磁场照射对子代大鼠不同发育期MAPK的影响

【目的】　研究妊娠期接受磁共振 (magneticresonanceimaging ,MRI)复合磁场照射对子代大鼠不同发育期脑部丝裂原活化蛋白激酶 (mitogenactivatedproteinkinase ,MAPK) /细胞外信号调节蛋白激酶 (extracellularsignalregulatedproteinkinase ,ERK )表达的影响。 　【方法】　SD孕鼠妊娠第 12～ 18d给予 0 .3 5TMRI磁场照射 ,雌性子鼠1、2、5月龄时进行大脑切片免疫组化SP方法染色 ,并用图像分析仪进行半定量分析。　【结果】　MAPK/ERK免疫反应在大鼠脑切片上广泛表达 ;随着年龄增长 ,未发现其表达的变化 ;在各年龄段子鼠照射组和对照组间MAPK/ERK的免疫反应表达差异均无显著性 (P >0 .0 5 )。　【结论】　妊娠期MRI磁场照射后并未引起子代大鼠MAPK/ERK免疫反应表达的异常