Prognostic Significance of Vascular Endothelial Growth Factor,Basic Fibroblast Growth Factor,and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery

Background: Hepatocellular carcinoma (HCC) is a hypervascular malignancy. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG) are important angiogenic factors of neoangiogenesis. This study investigated the predictive value of serum VEGF, bFGF, and ANG in tumor recurrence, disease-free survival (DFS), and overall survival (OS) in HCC patients.Methods: Preoperative serum VEGF, bFGF, and ANG were measured in 98 patients with resectable HCC and in 15 healthy controls. The median follow-up time was 43 months.Results: Preoperative serum VEGF was increased in patients with resectable HCC compared with healthy controls (P < .05). Increased serum VEGF was correlated with tumor recurrence (P = .001). Univariate analysis showed that serum VEGF, tumor-node-metastasis stage, tumor size and number, macroscopic portal vein invasion, and microscopic vascular invasion were correlated with OS and DFS. Serum bFGF and ANG were not associated with survival. Multivariate analysis showed that serum VEGF was the most significant predictor of DFS (relative risk, 2.35; 95% confidence interval, 1.26–4.39; P = .007) and OS (relative risk, 3.44; 95% confidence interval, 1.81–6.57; P < .001) in HCC patients after surgical resection.Conclusions:Preoperative serum VEGF is a significant independent predictor of tumor recurrence, DFS, and OS in patients with resectable HCC.     

<Superscript>18</Superscript>F-FDG PET for the lymph node staging of non-small cell lung cancer in a tuberculosis-endemic country: <Emphasis Type="Italic">Is dual time point imaging worth the effort?</Emphasis>

PURPOSE: This study was to compare (18)F-FDG positron emission tomography (PET) with thoracic contrast-enhanced CT (CECT) in the ability of lymph node (LN) staging non-small cell lung cancer (NSCLC) in a tuberculosis-prevalent country. The usefulness of dual time point PET imaging (DTPI) in NSCLC nodal staging was also evaluated. METHODS: We reviewed 96 NSCLC patients (mean age, 65.3 +/- 11.7 years) who had received PET studies before their surgery. DTPI were performed on 37 patients (mean age, 64.8 +/- 12.2 years) who received an additional scan of thorax 3 h after tracer injection. The accuracies of nodal staging by CECT and PET were evaluated according to final histopathology of hilar and mediastinal LN resected by surgery. RESULTS: The accuracy for nodal staging by CECT was 65.6% and that by PET was 82.3% (p < 0.05). Six patients were over-staged and 11 were under-staged by PET. Tuberculosis (n = 3, 50%) were mostly responsible for false-positive, while small tumor foci (n = 7, 63.6%) were mostly accountable for false-negative. For the 37 patients with DTPI, 45 min standardized uptake value (SUV) and 3 h SUV for negative LNs are significantly lower than those for positive LNs (p < 0.0001). Nevertheless, the retention index (RI) showed no significant difference between these two groups. CONCLUSIONS: Our study demonstrates that PET is more accurate than CECT in LN staging NSCLC patients in Taiwan where TB is still prevalent. Semi-quantitative SUV method or DTPI with RI does not result in better diagnostic accuracy than visual analysis of PET images.     

The conditional probabilities of survival in patients with anaplastic astrocytoma or glioblastoma multiforme

BACKGROUND: By the use of conditional probabilities of survival, we studied the yearly survival rates for individual tumor survivors. METHODS: Conditional survival rate was estimated in 114 consecutive patients with anaplastic astrocytoma or glioblastoma multiforme. Conditional probabilities of surviving some years given survival to a specific period of time after craniotomy and 95% confidence intervals were calculated in the individual tumor survivors. RESULTS: The estimated median survival was 30 months for 45 patients with anaplastic astrocytoma and 12 months for 69 patients with glioblastoma multiforme. The conditional probabilities of surviving next one year given survival to 1 year, 2 years, 3 years, 4 years, or 5 years after craniotomy for anaplastic astrocytoma were 86.2%, 75.0%, 85.9%, 77.8%, or 85.7%, respectively; for glioblastoma multiforme 64.8%, 58.7%, 85.7%, 80.0%, or 75.0%, respectively. The conditional probability of surviving to 5 years given survival to 2 years after craniotomy for anaplastic astrocytoma, i.e., surviving an additional 3 years, was 50.1%, which was better than observed 5-year survival rate (28.6%); for glioblastoma multiforme it was 40.2%, which also was better than observed 5-year survival rate (12.4%). CONCLUSIONS: The conditional probability of survival was a good method to clinically predict yearly survival rate for individual tumor survivors. In addition, the method can estimate the probabilities of surviving next some years given survival to a specific period of time after craniotomy. It also showed a more encouraging result than observed survival rate in patients with supratentorial malignant astrocytomas.     

S腺苷蛋氨酸对肝癌细胞中GADD45β基因的表达诱导及其机制研究

目的 初步明确肝癌细胞中特异性表达缺失的GADD45β基因近端启动子活性调控中心,并探讨S腺苷蛋氨酸对肝癌细胞HepG2中GADD45β表达的影响及可能机制.方法 以30～50个碱基的间隔,于体外人工合成GADD45β近端启动子序列(-618～-520),分别插入pGL3 basic荧光素表达质粒的荧光基因上游,以电穿孔法转染HepG2,根据启动子活性强度结合TRANSFAC数据库,分析可能存在的转录调节因子结合位点;实时荧光定量PCR比较S腺苷蛋氨酸作用前后HepG2细胞GADD45β表达,并在此基础上进一步比较S腺苷蛋氨酸对GADD45β启动子活性的诱导作用,探讨其可能作用机制,并为GADD45β近端启动子研究提供功能性证据.结果 GADD45β近端启动子中含有3个NF-kB转录调节因子与启动子结合位点(-602/-593、-581/-572、-537/-528);S腺苷蛋氨酸能明显诱导HepG2中GADD45β的表达,并呈现出剂量一效应的正相关关系,同时其能相应明显诱导NF-kB的启动子活性.结论 S腺苷蛋氨酸能明显诱导肝癌细胞中特异性缺失的GADD45β基因表达,增强转录调节因子NF-kB的活性水平是其可能的作用机制,该研究为S腺苷蛋氨酸的肝脏保护作用提供了新的实验依据.     

Combination of a new composite biocampatible skin graft on the neodermis of artificial skin in an animal model

Introduction: There have been very limited and inconsistent attempts at combining the cultured epidermal autograft (CEA) with the neodermis of artificial skin (Integra). The reasons for this remain unknown. The basement membrane proteins of conventional CEA sheets are easily damaged by the dispase treatment during the harvesting of the CEA from the culture flask. The damage of the basement membrane proteins may affect the anchorage of CEA onto the neodermis of Integra. A new Composite Biocompatible Skin Graft (CBSG) was recently developed. Methods: Composite biocompatible skin graft consists of autologous keratinocytes cultivated on a pliable hyaluronate‐derived membrane (Laserskin) which has been pre‐seeded with allogenic dermal fibroblasts. Basement membrane proteins of CBSG are protected from the dispase treatment because the keratinocytes are directly seeded onto Laserskin. The engraftment of CBSG was evaluated on 20 wounds of 10 rats. Integra was grafted on two freshly excised full‐thickness wounds (3 cm in diameter) in the dorsum of each animal. A polypropylene ring was applied to each wound to prevent the migration of epithelium from the edges. Composite Biocompatible Skin Graft was used to cover the neodermis of Integra after the silicone membrane was removed 14?21 days postgrafting. Results: Fourteen (70%) of 20 skin biopsies taken at day 21 from the centre of the grafted wounds revealed regenerated epithelium. Conclusion: A feasible delivery system of cultured keratinocytes onto the neodermis of Integra is demonstrated in this animal ­experiment.     

Subthalamotomy for advanced Parkinson disease

OBJECT: The aim of this study was to determine if subthalamotomy is effective in treating advanced Parkinson disease (PD). METHODS: The authors performed microelectrode mapping-guided stereotactic surgery on the subthalamic nucleus in eight patients with PD. Lesioning was performed using radiofrequency heat coagulation and confirmed with magnetic resonance imaging. Three patients who underwent unilateral and four with bilateral subthalamotomy were evaluated for up to 18 months according to the Unified PD Rating Scale (UPDRS). One patient who underwent unilateral subthalamotomy died 6 months postsurgery. At 3 months into the "off" period after surgery, there were significant improvements in contralateral bradykinesia (p < 0.0002), rigidity (p < 0.0001), tremor (p < 0.01), axial motor features (p < 0.02), gait (p < 0.03), postural stability (p < 0.03), total UPDRS scores (p < 0.03), and Schwab and England scores (p < 0.04). The benefits were sustained at 6, 12, and 18 months, except for the improvement in tremor. At 12 months into the "on" period, significant benefits were present for motor fluctuation (p < 0.04), on dyskinesia (p < 0.006), off duration (p < 0.05), total UPDRS score (p < 0.02), and contralateral tremor (p < 0.05). Benefits for motor fluctuation, off duration, and off-period tremor were lost after the 18-month follow-up period. The levodopa requirement was reduced by 66% for the unilateral and 38% for the bilaterally treated group. Bilateral subthalamotomy offered more benefits than did unilateral surgery for various parkinsonian features in both the on and off periods. Three patients suffered hemiballismus, two recovered spontaneously, and one died of aspiration pneumonia after discontinuation of levodopa. CONCLUSIONS: These findings indicate that subthalamotomy can ameliorate the cardinal symptoms of PD, reduce the dosage of levodopa, diminish complications of the drug therapy, and improve the quality of life.     

羟基脲对肝癌细胞HepG2中GADD45β表达影响及其可能机制

目的 初步明确肝癌细胞中GADD45β基因近端启动子序列,探索羟基脲对人肝癌细胞HepG2的GADD45β表达影响及可能机制.方法 体外合成GADD45β近端启动子序列群(-618～-314),构建荧光素表达质粒,转染肝癌细胞株HepG2,根据启动子活性强度结合数据库分析存在的转录调节因子结合位点;以实时荧光定量PCR比较羟基脲作用前后HepG2细胞GADD45β表达,并进一步比较羟基脲对GADD45β启动子活性的调控作用、分析羟基脲对HepG2的抑制效应,并通过Caspase-8、Caspase-9和Caspase-3的表达变化测定凋亡的发生和发展.结果 GADD4518近端启动子中含有3个NF-кB(-602/-593、-581/-572、-537/-528)和1个E2F-1(-470/-436)转录调节因子与启动子结合位点;羟基脲能明显诱导HepG2中GADD45β的表达,并呈现出剂量-效应的正相关关系,同时NF-кB和E2F-1启动子均明显增强.羟基脲能够明显抑制HepG2的DNA合成能力和细胞克隆形成能力,同时羟基脲能迅速启动HepG2凋亡的发生和发展.结论 羟基脲能明显诱导肝癌细胞中特异性缺失的GADD45β基因表达,增强转录调节因子的表达水平是其可能的作用机制.