<Emphasis Type="Italic">PTTG</Emphasis>/securin activates expression of <Emphasis Type="Italic">p53</Emphasis> and modulates its function

Background  

Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed abundantly in most tumors. Overexpression of PTTG induces cellular transformation and promotes tumor formation in nude mice. PTTG has been implicated in various cellular processes including sister chromatid separation during cell division as well as induction of apoptosis through p53-dependent and p53-independent mechanisms. The relationship between PTTG and p53 remains unclear, however.     

Tolosa–Hunt syndrome: MRI appearances

A review of MRI findings in seven patients with Tolosa–Hunt syndrome was carried out. Seven patients presented with unilateral painful ophthalmoplegia. Magnetic resonance imaging studies were carried out to evaluate the cavernous sinuses and orbits. Coronal fast spin‐echo T2‐weighted images and fat‐saturated T1‐weighted coronal and transverse images with and without contrast enhancement were obtained for the cavernous sinuses and orbits. All patients showed focal‐enhancing masses expanding the ipsilateral cavernous sinus. In one patient the mass was extending to the orbital apex and intraorbitally. All patients recovered on corticosteroid therapy and resolution of the masses was documented on follow‐up MRI studies in five patients. One patient had a relapse of symptoms after discontinuing therapy. Magnetic resonance imaging studies of the cavernous sinus and orbital apex show high sensitivity for the detection and follow up of inflammatory mass lesions in Tolosa–Hunt syndrome. Magnetic resonance imaging should be the initial screening study in these patients.     

Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience

Purpose: Our center contributed 183 patients to the Asian–Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available.

Methods and Materials: Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho’s T3 disease, N2–N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (≤ 3 cm, >3– 6 cm, > 6 cm). Patients were randomized to receive 2–3 cycles of CT with cisplatin 60 mg/m² and epirubicin 110 mg/m² D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan–Meier method and significance of survival curve differences calculated using log–rank test. Analysis was performed based on the intent-to-treat.

Results: The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37 months in the RT arm. The median OAS has not yet been reached for both arms. No significant differences were found for the various endpoints, although there was a trend suggesting better nodal control in the CT arm. The 5-year rates for the various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p = 0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs. 80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no significant difference in the patterns of failure between both arms: in the CT arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44% distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed locoregional and distant.

Conclusion: Induction chemotherapy with the regimen used in the current study did not improve the treatment outcome or alter the failure patterns in patients with locoregionally advanced NPC, although there was a trend suggesting better nodal control in the combined modality arm. Alternative strategies of combining chemotherapy and radiotherapy should be tested and employed instead.     

Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice.

Among numerous gene therapeutic strategies for cancer treatment, gene transfer by conditionally replicative adenovirus (CRAd) of interferon-gamma (IFN-gamma) may be useful because of the possibility that it will yield IFN-gamma-mediated antiangiogenesis, immune responses, and CRAd-mediated oncolysis. In this study, we constructed a human TERT promoter-mediated oncolytic adenovirus targeting telomerase-positive cancers and armed with a mouse or human IFN-gamma gene to generate novel immune gene-viral therapeutic systems, CNHK300-mIFN-gamma and CNHK300-hIFN-gamma, respectively. The systems can specifically target, replicate in, and lyse cancer cells, while sparing normal cells. The advantage of these systems is that the number of transgene copies and their expression increase markedly via viral replication within infected cancer cells, and replicated viral progeny can then infect additional cancer cells within the tumor mass. CNHK300-mIFN-gamma induced regression of xenografts in liver cancer models in both immunodeficient and immunocompetent mice by triplex mechanisms including selective oncolysis, antiangiogenesis, and immune responses. We conclude that combining immune gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and transgene composite antitumor responses.     

Commentary on “Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy.”

Background

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes.

Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p < 0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.     

Characteristics of elderly blood donors

The aging of our society will result in an increased demand for blood components, but it also has the potential to produce a large group of blood donors, the elderly. To study the effects of regular donation by older persons, a randomized, controlled trial is being conducted among 244 healthy, elderly volunteers. This report focuses on the efficacy of the recruiting efforts for that study and describes the resultant population in terms of their demographics, medical status, and donation safety. Of 325 potential subjects, 18 percent were disqualified and 7 percent refused entry into the study. After medical evaluation, only 2 persons were disqualified for conditions not detected by the usual blood services screening protocols. The resultant elderly donor population (n = 244) was well-educated, middle-income, and, for the most part, married. The group reported more past and present medical conditions, past surgical procedures, and current medications than would be expected in a younger donor group. Reactions to donation were infrequent and mild. With current screening and donation procedures, blood donation by the elderly appears to be safe and practical.     

中长跑运动锻炼对机体心肺功能的干预效应

目的:通过对体育学院中长跑运动员和普通大学生进行试验对比,揭示长期耐力性训练对于机体心肺功能所产生的影响。方法:实验于2005-04/05在广西师范大学体育学院生理实验室完成。选择32名男性受试者,在正式试验前进行专项体格检查,均为身体健康者。其中试验组为高等体育院校中长跑运动员(n=16),年龄(20±1)岁,身高(171±3)cm,体质量(65.3±3.7)kg,训练年限(2±1)年,运动员级别2、3级。对照组为普通大学生(n=16),年龄(20±1)岁,身高(171±3)cm,体质量(64.8±5.4)kg,采用列杜诺夫联合机能试验、哈佛台阶试验、最大吸氧量和无氧阈等生理指标,观察16名高等体育院校中长跑运动员和16名普通大学生在安静时、负荷后即刻和恢复期心肺功能变化的情况。结果:纳入32名受试者,均进入实验结果分析。①心功能和哈佛指数的变化:心率以对照组在进行负荷后即刻的值与安静时相比,其变化幅度较试验组大,差异有显著性意义[负荷后即刻:(157±10),(128±6)次/min;安静时:(70±9),(61±4)次/min;P<0.05]。试验组安静时收缩压和舒张压的值都较对照组低,但差异无显著性意义[收缩压:(108±9),(115±10)mmHg(1mmHg=0.133kPa);舒张压:(64±7),(76±9)mmHg]。在定量负荷后的恢复期内,其血压值都较对照低,差异有显著性意义[收缩压:(113±8),(131±12)mmHg;舒张压:(68±6),(83±10)mmHg;P<0.01]。试验组哈佛指数都较对照组相应时相内的值高,差异有显著性意义[安静时:(93±2)%,(68±4)%,P<0.01;负荷后即刻:(77±3)%,(52±3)%,P<0.05;恢复期:(86±3)%,(63±5)%;P<0.05]。②肺活量的变化:安静时试验组的肺活量较大,与对照组相比,差异具有显著性意义[(4664.25±801.47),(3913.77±710.34)mL;P<0.05]。③最大吸氧量和无氧功率的变化:试验组在进行负荷后即刻的最大吸氧量和无氧功率值与对照组相比,差异具有显著性意义[最大吸氧量:(3.04±0.35),(2.25±0.13)L/min;无氧功率:(570.17±100.22),(498.02±112.49)W;P<0.05]。结论:在高等院校进行中长跑运动训练能有效地降低心率和血压的升高幅度,提高哈佛指数和肺通气量的值。