Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia

Increasing the expression of the gamma globin genes is considered a useful therapeutic approach to the beta globin diseases. Because butyrate and alpha-amino-n-butyric acid (ABA) augment gamma globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with beta thalassemia and sickle cell anemia who might benefit from such an effect. Both substances increased fetal hemoglobin (Hb F) expression in Bfu-e from 7% to 30% above levels found in control cultures from the same subjects with sickle cell anemia. The fraction of cultured erythroblasts producing Hb F increased more than 20% with sodium butyrate treatment in 70% of cultures. In most cultures, this produced greater than 20% total Hb F and greater than 70% F cells, levels which have been considered beneficial in ameliorating clinical symptoms. Alpha: non-alpha (alpha-non-alpha) imbalance was decreased by 36% in erythroid progenitors of patients with beta thalassemia cultured in the presence of butyrate compared with control cultures from the same subjects. These data suggest that sodium butyrate may have therapeutic potential for increasing gamma globin expression in the beta globin diseases.     

Immuno- and gene-therapeutic strategies targeted against cancer (mainly focusing on pancreatic cancer)

Current treatment modalities of surgical resection and chemotherapy against cancers have improved survival. However, mortality from tumor recurrence remains high. Immunotherapy and gene therapy are potential additions to the treatment arsenal in the care of cancer patients. These novel therapeutic approaches need further investigation in in vitro and in vivo models as they are developed for potential use in humans. Here we reviewed immunotherapies and gene therapies that included clinical trials against cancers (mainly focusing on pancreatic cancer) suggesting the strong possibility of using these novel approaches.     

National Trends in the Management and Survival of Surgically Managed Gallbladder Adenocarcinoma Over 15 years: A Population-Based Analysis

Introduction  

National Comprehensive Cancer Network (NCCN) guidelines recommend hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA). We sought to evaluate compliance with these recommendations and to assess trends in the management and survival of patients with GBA.     

Pancreatic Resection of Isolated Metastases from Nonpancreatic Primary Cancers

Background  The goal of this study is to report the safety and efficacy of pancreatic resection for isolated metastatic cancers from nonpancreatic primary disease. Methods  We retrospectively identified patients from a single institution’s prospectively gathered pancreaticobiliary database from 1970 to 2007 who underwent a pancreatic resection for metastatic disease. Results  Forty-nine patients were identified with metastatic lesions to the pancreas. Pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy were performed in 31, 14, and 4 patients, respectively. Pathology distribution was as follows: 21 renal cell carcinoma (RCC), 6 gallbladder cancer, 4 lung cancer, 4 ovarian cancer, 4 sarcoma, 3 melanoma, 2 colon cancer, 1 breast cancer, 1 hepatocellular carcinoma, 1 seminoma, 1 Langerhans cell histiocytosis, and 1 nonpancreatic endocrine cancer. Postoperative morbidity was 48%. There were no perioperative deaths. A statistically significant difference in survival was found between cancer types (P = .007) with median survivals ranging from 4.8 years for RCC to .9 years for melanoma. Univariate analysis demonstrated a survival disadvantage for patients with perineural (hazard ratio [HR] = 5.4, P = .004) and vascular invasion (HR = 4.4, P = .002). The most commonly resected metastatic lesion of the pancreas was RCC. Eighteen of the 23 patients with RCC had a metachronous lesion with a median length between initial operation and pancreatic resection of 9.3 years. Metachronous lesions had a survival similar to that of synchronous lesions (HR = 1.0, P = .98). Vascular invasion (HR = 2.4, P = .007) and lymph node metastases (HR = 24.1, P = .01) were associated with greater mortality. Conclusion  Long-term survival can be achieved in patients undergoing resection of isolated metastases to the pancreas. Presented at the Society of Surgical Oncology Annual Cancer Symposium, Chicago, Illinois, March 13–16, 2008.     

Early and late components of error monitoring in violent offenders with psychopathy

BACKGROUND: One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. METHODS: Event-related potentials (ERPs) and behavioral components of error-monitoring processes were investigated in 16 individuals with psychopathy and in 18 healthy subjects. A letter version of the Eriksen flanker task was used in two conditions. The first condition (normal condition) required participants to press one of two buttons depending on the identity of the target stimulus. The second condition (signaling condition) required them to signal each time they had committed an error by making a second press on a signaling button. Early stages of error monitoring were investigated by using the error-related negativity (ERN/Ne) and post-error slowing as indexes. Later stages were explored by examining the error positivity (Pe) and signaling rates. RESULTS: Both groups showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic group exhibited both reduced Pe amplitudes and diminished error-signaling rates compared with the control group. CONCLUSIONS: Individuals with psychopathy show intact early error processing and automatic behavioral adaptation but have deficits in later stages of error processing and controlled behavioral adaptation. This is an indication that individuals with psychopathy are unable to effectively use error information to change their behavior adequately.     

Concurrent chemoradiation for oesophageal cancer: Factors influencing myelotoxicity

Concurrent chemotherapy and radiation (CT/RT) for localized oesophageal cancer can cause life-threatening myelo-suppression. This non-randomized study examines 95 patients from three Australasian centres treated on the Trans-Tasman Radiation Oncology ‘definitivechemoradiation ‘ study. Duration of fluorouracil infusion and patient age were independently predictive of myelotoxicity after the first cycle of CT/RT. Overall rates of grade III and IV neutropaenia were 23% and of thrombocytopaenia 8% following the first cycle of chemotherapy. Five neutropaenic septic episodes followed the first cycle and six the second. All five patients recovered after the first cycle but there were four treatment-related deaths occurring after the second cycle of CT/RT. Recommendations are made concerning initial dosing, dose reductions and delays to minimize adverse patient outcomes from myelosuppression.     

樟叶胡椒中新木脂素成分的研究

自胡椒科胡椒属植物樟叶胡椒(Piper polysyphorum C. DC)中分离到六个新木脂素(neolignans)类化合物,经光谱(UV,IR,MS,¹H-NMR,¹³C-NMR,2D-NMR,CD)分析及衍生物制备,确定Ⅱ为新化合物,即threo-△⁷-7-羟基-3,4,5,3′,5′-五甲氧基-8-O-4′-新木脂素,为一对对映体,命名为樟叶素(polysyphorin),Ⅰ,Ⅲ,Ⅳ为新的对映体,分別为(+)-virolongin,(+)-grandisin及(+)-lancifolin D.化合物Ⅴ为南藤素(wallichinine),Ⅵ为山蒟素D(hancinone D)。血小板活化因子(PAF)受体结合实验及PAF引起的血小板聚集实验证明化合物Ⅰ～Ⅴ具有明显的抑制活性。     

三七中人参三醇甙对羊心浦氏纤维动作电位及延迟整流钾电流的影响

三七中人参三醇甙(PTS)2.5μg/ml及5.0μg/ml均能明显延长羊心浦氏纤维动作电位时程(APD)包括APD_(30),APD_(50),APD_(90),对动作电位幅度(APA)无明显影响。双微电极法电压钳实验证明,PTS能明显抑制羊心浦氏纤维延迟整流钾电流(I_x)的峰值,且此种抑制作用呈时间及剂量依赖性。揭示PTS通过阻滞延迟整流钾通道而延长APD。