BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标： 背景：我们检查了膀胱癌中P53基因的杂合性（LOH）缺失，并研究了P53基因在乳头状瘤恶性进展中的作用。另外，检查了复发性膀胱癌的克隆性。
方法：分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定，石蜡包埋的组织中提取DNA，在P53基因的3个多态性位点处通过聚合酶链反应（PCR）进行扩增，并通过非放射性同位素单链构象多态性（Non-RI SSCP）分析。
结果：在40个信息量样本中，在13个样本中检测到LOH，其中3个7级中有4个（57％），2个23级中有9个（39％），1个10级中没有10个（10％）。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明，3例（60％）在原发性肿瘤中显示LOH，2例在复发性肿瘤中显示LOH。 ，与LOH在19例（16％）的3例中未显示出恶性进展的情况相反。 4例异时复发表现为LOH。在复发性肿瘤中2个，仅在初始肿瘤中1个，在两个肿​​瘤中1个。
结论：P53基因的改变被认为与肿瘤的分级有关，并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。

BACKGROUND & AIMS: BACKGROUND:Brain tumors (BT) are second only to acute lymphoblastic leukemia as the most prevalent form of pediatric cancer, with BT 5-year survival rates approaching 70%. With increased survival, quality of life has emerged as an essential health outcome. This investigation examines the internal consistency reliability and construct validity of the Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module. METHODS:The PedsQL 4.0 Generic Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Brain Tumor Module were administered to 99 families. The average age of the 56 boys and 43 girls was 9.76 years (range=2-18 years). The sample included children with tumors located in the posterior fossa/brainstem (N=62, 62.6%), supratentorial (N=15, 15.2%), and midline (N=22, 22.2%). Children were on treatment (N=46, 46.5%), off treatment<12 months (N=19, 19.2%), or off treatment>12 months/long-term survivor (N=34, 34.3%). Treatment included radiation (N=61, 61.6%), surgery (N=83, 83.8%), chemotherapy (N=87, 87.9%), and bone marrow transplant (N=5, 5.1%). RESULTS:Internal consistency reliability was demonstrated for the 24-item PedsQL Brain Tumor Module (average alpha=0.78-0.92, parent proxy-report, n=99; average alpha=0.76-0.87, child self-report, n=51). Construct validity for the PedsQL Brain Tumor Module was supported through an analysis of the intercorrelations with the Generic Core Scales and Fatigue Scale. CONCLUSIONS:The findings provide support for the measurement properties of the PedsQL Brain Tumor Module.

背景与目标： 背景：脑肿瘤（BT）仅次于急性淋巴细胞白血病，是儿童癌症的最普遍形式，其BT 5年生存率接近70％。随着生存率的提高，生活质量已成为一种必不可少的健康结果。这项研究检查了儿童生命质量量表（PedsQL）脑肿瘤模块的内部一致性可靠性和构建效度。
方法：将PedsQL 4.0通用核心量表，PedsQL多维疲劳量表和PedsQL脑肿瘤模块应用于99个家庭。 56名男孩和43名女孩的平均年龄为9.76岁（范围= 2-18岁）。样本包括肿瘤位于后颅窝/脑干（N = 62，62.6％），幕上（N = 15，15.2％）和中线（N = 22，22.2％）的儿童。儿童正在接受治疗（N = 46，46.5％），未接受治疗<12个月（N = 19，19.2％）或接受过治疗> 12个月/长期幸存者（N = 34，34.3％）。治疗包括放疗（N = 61，61.6％），手术（N = 83，83.8％），化学疗法（N = 87，87.9％）和骨髓移植（N = 5，5.1％）。
结果：24项PedsQL脑肿瘤模块具有内部一致性可靠性（平均α= 0.78-0.92，父母代理报告，n = 99；平均α= 0.76-0.87，孩子自我报告，n = 51）。通过分析通用核心量表和疲劳量表之间的相互关系，支持了PedsQL脑肿瘤模块的构建效度。
结论：这些发现为PedsQL脑肿瘤模块的测量特性提供了支持。

BACKGROUND & AIMS: :In addition to their role in cellular homeostasis, pathways that regulate autophagy affect both tumorigenesis and tumor response to treatment. Therefore, understanding the regulation of autophagy in treated cancer cells is relevant to the discovery of molecular targets for the development of anti-cancer drugs. Our recent report points to radiation-induced inactivation of the mTOR pathway as an underlying mechanism of radiation-induced autophagy in the human breast cancer cell line MCF-7. Most importantly, radiation-induced inactivation of this pathway was detrimental to cell survival and was associated with reversal of mitochondrial ATPase activity and mitochondrial hyperpolarization, decreased level of eukaryotic initiation factor 4G (eIF4G) and increased phosphorylation of p53. Future analysis of the interrelationship among these events and the role each of them plays in cell survival following radiation will increase our ability to employ the mTOR pathway in anti-cancer therapy.

背景与目标： ：除了在细胞稳态中的作用外，调节自噬的途径还影响肿瘤发生和肿瘤对治疗的反应。因此，了解在治疗的癌细胞中自噬的调控与发现抗癌药物的分子靶标有关。我们最近的报告指出，辐射诱导的mTOR途径失活是人类乳腺癌细胞系MCF-7辐射诱导的自噬的潜在机制。最重要的是，此途径的辐射诱导失活对细胞存活有害，并且与线粒体ATPase活性和线粒体超极化的逆转，真核起始因子4G（eIF4G）的水平降低以及p53磷酸化的增加有关。进一步分析这些事件之间的相互关系以及它们各自在放射后的细胞存活中所起的作用，将提高我们在抗癌治疗中采用mTOR途径的能力。

BACKGROUND & AIMS: BACKGROUND:Transanal resection of benign and selected malignant rectal tumors is a well accepted surgical technique. The use of a stereoscopic microsurgical technique, as originally described by Buess et al in 1984, has been shown to improve the results of standard transanal resection by allowing precise, full thickness resections up to 24 cm from the anal verge. Transanal endoscopic microsurgery (TEM) has failed to gain widespread popularity for two reasons: The proprietary instrument set is expensive and complex ($68,000 and 30 components), and the procedure is difficult to master technically. We present our results with a modification of the TEM instrument that incorporates a standard laparoscope and video camera as well as standard laparoscopic instruments.

METHODS:Four surgeons have been trained to date. Details of the training curriculum are presented. The technique of videoendoscopic transanal tumor resection (VTEM) is described. A prospective data base was maintained of all VTEM cases. This was reviewed for this study to determine indications, operative times, complications and outcomes.

RESULTS:Four surgeons performed 27 VTEM cases between August 1994 and June 1996. The average age was 69 years and the majority (16) of patients were ASA III. Pre-op diagnosis was benign polyp in 25 patients and adenocarcinoma in 2. Average operating time was 127 minutes (49 to 280 minutes), and was longer during a surgeon's first 5 cases and for lesions more than 16 cm from the anal verge. Operative problems were rare (4%) and post-op complications (incontinence 2, late bleeding 1, adenoma recurrence 1) were seen in 15%.

CONCLUSIONS:VTEM can be taught successfully to GI and colorectal surgeons using a format similar to that used for advanced laparoscopic courses. The use of already available laparoscopes and instruments decreases the initial costs of the set-up. Results are good, with low rates of complications and recurrence and a very short hospital stay. The patient benefits from an effective, minimally invasive alternative to open surgery.

背景与目标： 背景：经肛门切除良性和恶性直肠肿瘤是一种广为接受的手术技术。如Buess等人在1984年最初描述的，使用立体显微外科技术已显示可通过允许距肛门边缘长达24 cm的精确，全层切除来改善标准经肛门切除的结果。经肛门内窥镜显微外科手术（TEM）未能获得广泛的普及，其原因有两个：专有的器械套件昂贵且复杂（68,000美元，包含30个组件），并且该过程在技术上难以掌握。我们通过修改TEM仪器（结合标准腹腔镜和摄像机以及标准腹腔镜仪器）展示我们的结果。

方法：到目前为止，已经培训了四名外科医生。介绍了培训课程的详细信息。描述了视频内镜经肛门肿瘤切除术（VTEM）的技术。保留了所有VTEM病例的前瞻性数据库。

结果：1994年8月至1996年6月，四名外科医生进行了27例VTEM病例。平均年龄为69岁。年，大多数（16）患者为ASA III。术前诊断为良性息肉25例，腺癌2例。平均手术时间为127分钟（49至280分钟），在外科医生的前5例中以及距肛门边缘16厘米以上的病变中，手术时间更长。手术中很少有手术问题（4％），术后并发症（尿失禁2，晚期出血1，腺瘤复发1）占15％。

结论：可以教VTEM使用类似于高级腹腔镜课程的格式成功地向胃肠道和结直肠外科医生使用。使用已经可用的腹腔镜和仪器可降低安装的初始成本。结果良好，并发症和复发率低，住院时间很短。患者可以从有效，微创的替代开放手术中受益。