BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.

背景与目标： ：这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯（PDTC）是否会影响SKOV-3人卵巢癌细胞系中核因子-κB（NF-kappaB）的活化及其作用两种药剂对癌细胞的生长和凋亡都有影响。在不同的时间间隔用不同浓度的紫杉醇和/或PDTC处理细胞。处理后，通过2-（2-甲氧基-4-硝基苯基）-3-（4-硝基苯基）-5-（2,4-二磺酰基）-2H-四唑鎓（WST-8）（WST）测定细胞生长和凋亡）分析和流式细胞术。蛋白质印迹法用于确定核p65蛋白和细胞质IkappaB-alpha蛋白。高剂量的PDTC显着抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC联合显示可抑制细胞生长和增加细胞凋亡水平。单独使用紫杉醇的治疗显示核p65蛋白增加，而细胞质IkappaB-α蛋白表达降低，而PDTC的预处理逆转了该功能。 PDTC阻止紫杉醇诱导的NF-κB活化，从而导致对紫杉醇的化学敏感性增加和细胞凋亡增强。抗氧化剂和紫杉醇的组合具有克服紫杉醇耐药性的巨大潜力。

BACKGROUND & AIMS: :It is clear that the optimal clinical outcomes in bladder cancer patients requiring radical cystectomy are related to standard histopathologic variables of tumor grade, stage and lymph node status. However, other less well defined variables are also critical to the successful outcomes of these patients. Patients with muscle invasive bladder cancer and treating physicians should avoid unnecessary and significant treatment delays. In addition, hospital and surgeon-volume/experience are thought to be factors that may too be important components that relate to the clinical outcomes of patients following surgery. Lastly, there is a growing body of literature to support the concept of an appropriate lymphadenectomy at the time of surgery, for both node-positive and node-negative bladder cancer patients. It is becoming more obvious that there are multiple variables involved in the clinical success and outcomes of patients with bladder cancer following radical cystectomy. As treating physicians and surgeons we must be aware of these components to ensure the best outcomes for our patients.

背景与目标： ：很明显，需要根治性膀胱切除术的膀胱癌患者的最佳临床结局与肿瘤分级，分期和淋巴结状态的标准组织病理学变量有关。但是，其他定义欠佳的变量对于这些患者的成功结局也至关重要。患有肌肉浸润性膀胱癌的患者和主治医师应避免不必要和显着的治疗延迟。另外，医院和外科医生的体格/经验被认为是可能也是与手术后患者的临床结果相关的重要组成部分的因素。最后，越来越多的文献支持针对淋巴结阳性和淋巴结阴性的膀胱癌患者在手术时进行适当的淋巴结清扫术的概念。越来越明显的是，根治性膀胱切除术后膀胱癌患者的临床成功和结局涉及多个变量。作为主治医师和外科医生，我们必须意识到这些因素，以确保为我们的患者提供最佳的治疗效果。

BACKGROUND & AIMS: AIM:To investigate the dynamic alteration of telomerase expression during development of hepatocellular carcinoma (HCC) and its diagnostic implications in liver tissues or peripheral blood mononuclear cells for HCC. METHODS:Dynamic expressions of liver telomerase during malignant transformation of hepatocytes were observed in Sprague-Dawly (SD) rats fed with 0.05% of 2-fluoenyacetamide (2-FAA). Total RNA and telomerase were extracted from rat or human liver tissues. The telomerase activities in livers and in circulating blood were detected by a telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA), and its diagnostic value was investigated in patients with benign or malignant liver diseases. RESULTS:The hepatoma model displayed the dynamic expression of hepatic telomerase during HCC development. The telomerase activities were consistent with liver total RNA levels (r = 0.83, P<0.01) at the stages of degeneration, precancerosis, and cancerization of hepatocytes. In HCC patients, the telomerase levels in HCC tissues were significantly higher than in their adjacent non-cancerous tissues, but liver total RNA levels were lower in the former than in the latter. Although the circulating telomerase of HCC patients was abnormally expressed among patients with chronic liver diseases, the telomerase activity was a non-specific marker for HCC diagnosis, because the incidence was 15.7% in normal control, 25% in chronic hepatitis, 45.9% in liver cirrhosis, and 85.2% in HCC, respectively when absorbance value of telomerase activity was more than 0.2. If the value was over 0.6, the incidence was 60% in HCC group and 0% in any of the others (P<0.01) except in two cases with liver cirrhosis. However, the combination of circulating telomerase with serum alpha-fetoprotein level could increase the positive rate and the accuracy (92.6%, 125 of 135) of HCC diagnosis. CONCLUSION:The overexpression of telomerase is associated with HCC development, and its abnormality in liver tissues or in peripheral blood could be a useful marker for diagnosis and prognosis of HCC.

背景与目标： 目的：研究肝细胞癌（HCC）发展过程中端粒酶表达的动态变化及其在肝组织或外周血单核细胞中的诊断意义。
方法：在喂食0.05％2-氟乙酰胺（2-FAA）的Sprague-Dawly（SD）大鼠中观察肝细胞恶性转化过程中肝端粒酶的动态表达。从大鼠或人肝脏组织中提取总RNA和端粒酶。通过端粒重复扩增方案-酶联免疫吸附测定（TRAP-ELISA）检测肝脏和循环血液中的端粒酶活性，并对其在良性或恶性肝病患者中的诊断价值进行研究。
结果：肝癌模型在肝癌发生过程中表现出肝端粒酶的动态表达。在变性，癌前期和肝细胞癌化阶段，端粒酶活性与肝脏总RNA水平一致（r = 0.83，P <0.01）。在HCC患者中，HCC组织中的端粒酶水平显着高于其相邻的非癌组织，但前者的肝脏总RNA水平低于后者。尽管在慢性肝病患者中HCC患者的循环端粒酶异常表达，但端粒酶活性不是HCC诊断的非特异性标志物，因为正常对照组的发生率为15.7％，慢性肝炎为25％，肝为45.9％当端粒酶活性的吸光度值大于0.2时，肝硬化和HCC中的85.2％。如果该值超过0.6，则除两名肝硬化患者外，HCC组的发生率为60％，其他任何一组的发生率为0％（P <0.01）。但是，循环端粒酶与血清甲胎蛋白水平的结合可以提高HCC诊断的阳性率和准确率（92.6％，第125页）。
结论：端粒酶的过表达与肝癌的发生有关，其在肝组织或外周血中的异常可能是诊断和预后的有用标志物。

BACKGROUND & AIMS: :Outside the nasopharynx, undifferentiated carcinomas occur only rarely at other head and neck locations. Although the association between undifferentiated nasopharyngeal carcinoma and Epstein-Barr virus (EBV) is consistent, there is conflicting evidence as to the association of EBV with undifferentiated carcinomas outside the nasopharynx. Here, we report on a case of undifferentiated carcinoma of the tongue base. A 71-year-old male, who had been treated with irradiation for primary unknown right neck metastatic EBV-positive undifferentiated carcinoma 9 years previously, was referred to our clinic with masses at the tongue base and right neck. The lesion at the tongue base was revealed to be an EBV-positive undifferentiated carcinoma. He was treated with resection of tongue base tumor and bilateral-neck dissection, and the defect at the tongue base was reconstructed with a free rectus abdominis myocutaneous flap. Re-irradiation was added post-operatively because of a positive surgical margin at the tongue base. The patient is presently alive without recurrence or distant metastasis 20 months after treatment. Although it is unclear whether our case is recurrent or newly developed EBV-latently infected undifferentiated carcinoma, we propose that EBV-associated tumors should be carefully observed after treatment at least for more than 10 years.

背景与目标： ：在鼻咽以外，未分化癌仅在其他头颈部位置很少发生。尽管未分化的鼻咽癌和爱泼斯坦-巴尔病毒（EBV）之间的关联是一致的，但关于EBV与鼻咽外未分化癌的关联有相互矛盾的证据。在这里，我们报道一例未分化舌基癌。一位71岁的男性在9年前接受过放射治疗，原发性右颈部转移性EBV阳性原发性未分化癌已经接受过放射治疗，现被转诊至我们的诊所，舌根和右颈部有肿块。舌根处的病变显示为EBV阳性未分化癌。对他进行了舌根肿瘤切除术和双侧颈淋巴结清扫术，并用游离的腹直肌肌皮瓣修复了舌根缺损。由于舌根的手术切缘阳性，因此在术后增加了再次照射。治疗后20个月，该患者目前尚无复发或远处转移。尽管尚不清楚我们的病例是复发的还是新发的EBV潜伏感染的未分化癌，但我们建议治疗至少10年后应仔细观察与EBV相关的肿瘤。

BACKGROUND & AIMS: :Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

背景与目标： ：通过免疫组织化学法构建组织微阵列（TMA）以有效表征乳腺中大量非侵袭性上皮病变的方法是一种有吸引力的研究方法，但也带来了技术挑战。我们报告进行的方法学研究，以优化从大型乳腺癌病例对照研究中收集的无创乳腺组织中构建TMA的方法。我们使用直径为2.0毫米针头的手动排列技术，从32位乳腺癌女性的标本中构建了TMA，这些标本包括以下目标：（1）28个末梢小叶单位（TDLU）； （2）28例原位导管癌，（3）23例浸润性癌。通过精心选择目标，我们通过TMA第30节实现了约80％的非侵入性目标的代表，并得到了持续的保护。 TDLU靶标的免疫组织化学染色显示，在30.8％的肾小管中，雌激素受体（ER）阳性染色，在50.0％中，孕激素受体（PR）染色阳性。为了建立一种有效的方法来评估TDLU中的染色结果，我们创建了一个分类评分系统，以估计含有阳性染色细胞的小管的百分比（<10％，10％至5​​0％，>或= 50％），并比较结果与那些通过肾小管计数获得的。两种方法之间的比较表明，ER染色的70.8％和PR染色的79.2％完全吻合，没有两类差异。单个区域中相同组织类型（TDLU或DCIS）的多个（多达4个）非侵入性靶标中的ER / PR表达水平显示出良好的相关性。这些数据表明，尽管精心选择了靶标，但生产无创性乳房结构的TMA是可行的，并且此类核心的免疫染色可允许对肿瘤周围组织进行有效的免疫组织化学表征。需要对该方法进行其他探索。

BACKGROUND & AIMS: :Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.

背景与目标： ：野生型（WT）序列p53肽是广泛应用的癌症疫苗的诱人候选物。这项研究的目的是评估肝细胞癌（HCC）患者基于WT p53的免疫治疗方法的潜力。通过在24 HCC中使用肽/HLA-A2.1四聚体直接在外周血中鉴定出对WT p53（149-157）和WT p53（264-272）HLA-A * 0201限制性表位具有特异性的循环CD8 T细胞耐心。 WT p53肽特异性刺激后的细胞毒性T淋巴细胞（CTL）活性通过使用实时定量聚合酶链反应测定的颗粒酶B和干扰素-γmRNA转录分析来评估。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中p53的状态，主要组织相容性复合体（MHC）的表达和共刺激分子。与健康对照相比，HCC患者表现出明显更高的WT p53特异性记忆CD8 T细胞频率和更强的WT p53特异性CTL活性。 p53特异性CD8 T细胞的频率增加及其活性与选择性HLA-A2等位基因缺失和肿瘤细胞共刺激分子表达降低有关。此外，p53特异性T细胞数量的增加与肿瘤细胞中II类MHC的高表达相吻合，但与肿瘤淋巴结转移分期系统的T状态呈负相关。我们的结果表明，在肝癌患者中存在自然免疫监视和肿瘤免疫逃避，涉及针对WT p53肿瘤抗原的T细胞应答。这些发现可能对癌症疫苗的未来发展具有重要意义。

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: :Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemotherapy and chemoradiotherapy are new alternatives for locally advanced disease, particularly induction chemotherapy for patients with unresectable tumors. In recurrent/metastatic disease and after progression to platin-based regimens, no treatments other than best supportive care are currently available. Most SCCHN tumors overexpress the epidermal growth factor receptor (EGFR). This is a tyrosine kinase membrane receptor and has a clear implication in angiogenesis, tumor progression and resistance to different cancer treatments. Cetuximab is a monoclonal antibody that binds to EGFR and alters the tyrosine kinase-mediated signal transduction pathway. The drug is active in colon cancer and is currently being tested in SCCHN patients. For locally advanced disease, cetuximab/radiotherapy combination has demonstrated a benefit in survival when compared with radiotherapy alone as radical treatment. Cetuximab is an active treatment in platin-refractory patients with recurrent/metastatic disease.

背景与目标： ：外科手术和放射疗法是头颈部鳞状细胞癌（SCCHN）患者的标准治疗选择。化学疗法和放化疗是局部晚期疾病的新选择，特别是对于无法切除的肿瘤患者的诱导化疗。在复发/转移性疾病中，以及发展为以铂为基础的治疗方案之后，除最佳支持治疗外，目前尚无其他治疗方法。大多数SCCHN肿瘤过表达表皮生长因子受体（EGFR）。这是酪氨酸激酶膜受体，在血管生成，肿瘤进展和对不同癌症治疗的抗性中具有明显的含义。西妥昔单抗是与EGFR结合并改变酪氨酸激酶介导的信号转导途径的单克隆抗体。该药物在结肠癌中有活性，目前正在SCCHN患者中进行测试。对于局部晚期疾病，西妥昔单抗/放疗联合治疗与单纯放疗作为根治性治疗相比，已显示出生存获益。西妥昔单抗是铂类难治性复发/转移性疾病患者的积极治疗方法。

BACKGROUND & AIMS: :Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

背景与目标： ：口腔癌是一种具有某些已知原因的肿瘤。增殖基因在其少数致病和预后因素中很重要。钙环蛋白是与细胞周期相关的基因，其功能尚不清楚。为了评估它们在鳞状细胞癌中的致病作用，已经研究了它的表达以及Haras和组蛋白H3的表达。从鳞状细胞癌（SCC）和良性病变的病理和正常粘膜中提取的RNA通过聚合酶链反应（PCR）进行逆转录和扩增。仅在SCC中，病理黏膜中所有三个基因的表达均得到增强。这表明它们可能参与其发病机理，并为区分恶性和良性病变提供了另一个参数。

BACKGROUND & AIMS: :Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma cell line, DDM-1.13. Six patients were enrolled in the phase I trial. Autologous DCs were generated in vitro from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were pulsed with melanoma cell lysate from a cloned and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.

背景与目标： ：免疫疗法已显示出令人兴奋的癌症治疗新观点。我们研究的目的是评估用来自新开发的黑素瘤细胞系DDM-1.13的裂解物脉冲的自体树突状细胞（DC）对晚期结直肠癌患者进行疫苗接种的毒性和可能的​​不良反应。一期试验招募了六名患者。在粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白介素-4（IL-4）的存在下，由外周血单核细胞体外产生自体DC。用来自克隆和选择的黑色素瘤细胞系的黑色素瘤细胞裂解液对DC进行脉冲处理，该黑色素瘤细胞系富含MAGE-A抗原的表达，而黑色素瘤分化抗原（酪氨酸酶，MART-1和gp100）的表达不足。在大腿近端皮内注射疫苗，每两周间隔注射五种给定的疫苗。每种疫苗均包含3-5 x 10（6）个DC。六名患者中有五名接受了全部五种疫苗的治疗。所有患者对治疗的耐受性良好，没有观察到疫苗相关的不良反应。事实证明，使用这种基于DC的癌症疫苗进行治疗是安全且无毒的。

BACKGROUND & AIMS: PURPOSE:The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. EXPERIMENTAL DESIGN:In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. RESULTS:UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. CONCLUSIONS:UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.

背景与目标： 目的：在中国最常见的泌尿生殖系统恶性肿瘤是膀胱移行细胞癌（TCC）。尽早诊断出新发和复发性膀胱癌，然后及时进行治疗，将有助于降低死亡率。目前，临床上尚无令人满意的膀胱癌标记物。迫切需要更好的诊断方法。
实验设计：在这项研究中，我们使用了全面的表达序列标签分析，基因表达的系列分析和微阵列分析，并迅速发现了候选标记尿路上皮癌相关1（UCA1）。对UCA1基因进行了表征，并通过逆转录PCR与尿沉渣一起分析了其作为尿液标记物的性能。这项研究总共包括212位个体，其中94位患有膀胱癌，33位输尿管/盆腔癌以及85位正常和其他泌尿系统疾病对照。
结果：UCA1被鉴定为TCC中上调的新型非编码RNA基因，是迄今鉴定到的最具TCC特异性的基因。全长cDNA为1439 bp，序列分析表明它属于人内源性逆转录病毒H家族。临床测试表明，UCA1检测对膀胱癌的诊断具有高度特异性（91.8％，在78中的78）和非常敏感（80.9％，在76中的76），对于浅表G2-G3患者尤其有价值（敏感性91.1％，41） 45）。在没有TCC的各种泌尿系统疾病中，它表现出出色的鉴别诊断性能。
结论：UCA1是膀胱癌非常敏感和特异的独特标志物。它可能对术后无创性随访产生重要影响。这项研究还突出了通过将计算机隔离方法与基于RNA检测方案的转化临床测试相集成的新癌症诊断测定方法的捷径。

BACKGROUND & AIMS: :Several molecular-targeted therapeutics have been tested in clinical trials for the treatment of head and neck squamous cell carcinoma (HNSCC). Of these, therapeutics targeting the epidermal growth factor receptor (EGFR) have been studied most extensively and some agents have demonstrated measurable clinical effectiveness. However, molecular studies designed to define HNSCC patient subcohorts of likely responders to EGFR-targeted therapy have not identified molecular signatures that correlate with clinical response. Here, the authors summarise the relevant clinical findings and highlight reported molecular correlative studies for EGFR-targeted therapeutics for HNSCC. The authors focus especially on molecular markers evaluated for association with clinical response and include data from EGFR-targeted clinical studies in other cancer sites that they anticipate will be of interest to the head and neck cancer research and treatment communities.

背景与目标： ：几种针对分子的疗法已在临床试验中用于治疗头颈部鳞状细胞癌（HNSCC）。其中，针对表皮生长因子受体（EGFR）的疗法已得到最广泛的研究，某些药物已证明可测量的临床有效性。然而，旨在定义可能对EGFR靶向治疗有反应的HNSCC患者亚组的分子研究尚未发现与临床反应相关的分子标志。在这里，作者总结了相关的临床发现，并着重报道了针对HNSCC的EGFR靶向治疗药物的分子相关研究。作者特别关注评估与临床反应相关的分子标记，并包括来自其他癌症部位针对EGFR的临床研究的数据，他们预计这将是头颈癌研究和治疗界感兴趣的数据。

BACKGROUND & AIMS: OBJECTIVE:To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. METHOD:Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. RESULTS:Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. CONCLUSION:The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors.

背景与目标： 目的：探讨台湾西南部黑脚病（BFD）流行地区低剂量（井水砷水平<150μg/ L）村庄中砷暴露对癌症死亡率的分析作用数据。
方法：对低剂量（<150μg/ L）村庄的砷暴露量（μg/ kg /天）进行膀胱和肺癌死亡的泊松分析，暴露量由村庄的中位数，平均值或最大值定义或没有区域数据。
结果：使用村庄中井水砷中位数作为暴露指标，通过将水平> 500μg/ L的村庄包括在内，引入了分类错误，但是没有使用村庄平均值或最大值。使用平均砷含量或最大砷含量进行的泊松分析表明，对于膀胱癌以及膀胱癌和肺癌的模型，癌症斜率因子显着为负。当模型包含非砷差异的解释变量时，包含台湾西南地区的数据并没有改变结果。只有将比较人群作为一个单独的数据点，并假设饮用水中砷的暴露量为零，并消除非砷危险因素的变量，才能产生正斜率。
结论：BFD地区低剂量（<150μg/ L）村庄的癌症发生率高于台湾西南地区。但是，在BFD地区的低剂量村庄中，癌症风险提示与井水砷水平呈负相关。与区域数据的正差异似乎归因于非砷生态因素。

BACKGROUND & AIMS: :Epidural blood patch (EBP) is an effective procedure for the treatment of spontaneous intracranial hypotension (SIH). Neurological compromise following EBP, although rare, is recognized as a serious potential complication. We describe a 33-year-old female patient in whom long-term bladder and bowel dysfunction developed following a small volume (10 mL) EBP to treat SIH. We also discuss the possible pathophysiological mechanisms related to this complication in the postprocedure setting.

背景与目标： ：硬膜外补血（EBP）是治疗自发性颅内低血压（SIH）的有效方法。 EBP后的神经功能损害虽然很少见，但被认为是严重的潜在并发症。我们描述了一名33岁的女性患者，在该患者中，小剂量（10 mL）EBP治疗SIH后会出现长期的膀胱和肠功能障碍。我们还将讨论与术后并发症相关的可能的病理生理机制。

BACKGROUND & AIMS: BACKGROUND:The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. PATIENTS AND METHODS:One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events). RESULTS:The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). CONCLUSIONS:Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.

背景与目标： 背景：甲氨蝶呤，长春碱，阿霉素，顺铂（Pharmanell，雅典，希腊）（MVAC）或吉西他滨，顺铂（GC）的组合代表了晚期尿路上皮癌（UC）的标准治疗方法。与传统的MVAC相比，剂量密集（DD）-MVAC获得了更长的无进展生存期（PFS）。但是，尚未研究GC强化的作用。我们进行了一项随机III期研究，比较了DD-GC方案与DD-MVAC在晚期UC中的比较。
患者与方法：一百三十名患者被随机分配至DD-MVAC：66（M 30 mg / m（2），V 3 mg / m（2），A 30 mg / m（2），C 70 mg / m（2）q 2周）和DD-GC 64（G 2500 mg / m（2），C 70 mg / m（2）q 2周）。中位随访时间为52.1个月（89事件）。
结果：DD-MVAC的中位总体生存期（OS）和PFS为19和8.5个月，DD-GC的中位总体生存期（OS）和PFS为18和7.8个月（分别为P = 0.98和0.36）。与DD-MVAC相比，DD-GC的中性粒细胞减少感染频率较低（0％对8％）。使用DD-GC的患者更多，至少接受了六个周期的治疗（85％对63％，P = 0.011），DD-GC的停药率较低（3％对13％）。
结论：尽管DD-GC并不优于DD-MVAC，但其耐受性更好。 DD-GC被认为是对该患者人群进行进一步研究的合理治疗选择。临床试验编号ACTRN12610000845033，www.anzctr.org.au。