BACKGROUND & AIMS: The Orphan Annie-eyed clear nucleus, defined as a large, optically clear nucleus, devoid of chromatin strands, with sharp chromatin rim, is a more specific feature than are nuclear grooves or intranuclear cytoplasmic inclusions in papillary thyroid carcinoma. In addition, this characteristic nuclear feature is detectable at low magnification. Although these clear nuclei are routinely seen in paraffin sections, they are inconspicuously seen in conventionally processed touch-imprints and fine-needle aspiration (FNA) smears. Among our two institutions, there have been 148 thyroid cases processed by Ultrafast Papanicolaou stain (UFP), including 43 papillary carcinomas, 38 cellular follicular lesions, and 67 cases of nodular hyperplasia. We observed clear nuclei in all of the cases of UFP-processed FNA and intraoperative smears of papillary carcinoma but not of other thyroid lesions. The clear nuclei are most evident in tumor cells with direct contact to the glass slide and are not seen in tumor cells soaked in cystic fluid. UFP is a valuable way to detect Orphan Annie-eyed clear nuclei of papillary thyroid carcinoma early in the diagnostic evaluation, either at immediate on-site evaluation of FNA or at intraoperative consultation and before the availability of permanent sections.

背景与目标： 孤儿安妮眼透明核，定义为一个大的，光学上透明的核，没有染色质链，具有尖锐的染色质边缘，是比甲状腺乳头状癌中核沟或核内细胞质包涵体更特异的特征。此外，这种特征性核特征在低放大倍率下是可检测到的。尽管这些清晰的核通常在石蜡切片中可见，但在常规处理的触摸印记和细针抽吸 (FNA) 涂片中却不明显。在我们的两个机构中，有148例经超快巴氏染色 (UFP) 处理的甲状腺病例，包括43例乳头状癌，38例细胞滤泡病变和67例结节性增生。我们在所有经UFP处理的FNA病例和乳头状癌的术中涂片中都观察到了清晰的核，但没有观察到其他甲状腺病变。透明的核在与载玻片直接接触的肿瘤细胞中最为明显，在浸泡在囊性液中的肿瘤细胞中未见。UFP是一种有价值的方法，可以在诊断评估的早期，无论是在FNA的现场评估还是在术中咨询以及在永久性切片之前，检测甲状腺乳头状癌的孤儿安妮眼透明核。

BACKGROUND & AIMS: :The objective of this study was to confirm whether hemoglobin (Hb) levels during chemoradiotherapy are associated with survival in patients with locally advanced cervical carcinoma and to assess impact of the Hb level on survival according to lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma patients treated with concurrent chemoradiotherapy was conducted. The stage of disease ranged between FIGO stage IB and stage IVA. Disease-free and overall survivals were evaluated by univariate and multivariate analyses. After median follow-up of 35.7 months, 24 patients developed recurrence of disease and 14 patients died from their disease. Stage, LN metastasis, and squamous cell carcinoma antigen and Hb levels during chemoradiation were correlated significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was associated with better survival (P < 0.05). However, no such benefits were observed in patients with LN metastasis by magnetic resonance imaging (MRI). Multivariate Cox regression hazard model showed that Hb levels during chemoradiation were an independent prognostic factor in patients without LN metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in cervical carcinoma patients without LN metastasis but not with LN metastasis by MRI.

背景与目标： : 本研究的目的是确认放化疗期间血红蛋白 (Hb) 水平是否与局部晚期宫颈癌患者的生存相关，并根据淋巴结 (LN) 转移评估Hb水平对生存的影响。回顾性分析了85例同期放化疗治疗的宫颈癌患者。疾病的阶段介于FIGO IB期和IVA期之间。通过单变量和多变量分析评估无病生存率和总体生存率。中位随访35.7个月后，24例患者出现疾病复发，14例患者死于疾病。分期、LN转移、放化疗期间鳞状细胞癌抗原和Hb水平与生存率显著相关 (P <0.05)。Hb维持在10.0g/dL以上与较好的生存率相关 (P <0.05)。然而，通过磁共振成像 (MRI) 在LN转移患者中未观察到这种益处。多因素Cox回归风险模型显示，放化疗期间的Hb水平是MRI无LN转移患者的独立预后因素。化疗期间维持血红蛋白对无LN转移但无LN转移的宫颈癌患者有好处。

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-κ B (NF-κ B) 的活化以及这两种药物对癌细胞生长和凋亡的影响。在不同的时间间隔用各种浓度的紫杉醇和/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-(2,4-二硫酰基)-2h-四唑 (WST-8) (WST) 测定和流式细胞仪测定细胞生长和凋亡。Western blot测定法用于测定核p65蛋白和细胞质IkappaB-α 蛋白。高剂量的PDTC显著抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC组合显示出对细胞生长的加性抑制和凋亡水平的增加。单独治疗紫杉醇显示核p65蛋白增加，胞质IkappaB-α 蛋白表达降低，而PDTC的预处理逆转了这一功能。PDTC阻断紫杉醇诱导的NF-κ b激活，从而增加对紫杉醇的化学敏感性并增强细胞凋亡。结合抗氧化剂和紫杉醇具有克服紫杉醇耐药性风险的巨大潜力。

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：

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： : 在鼻咽部以外，未分化癌仅在其他头颈部部位很少发生。尽管未分化鼻咽癌与爱泼斯坦-巴尔病毒 (EBV) 之间的关联是一致的，但关于EBV与鼻咽部以外未分化癌的关联的证据却相互矛盾。在这里，我们报告了一例未分化的舌根癌。一名71岁的男性，9年前曾接受过原发性未知的右颈转移性EBV阳性未分化癌的放射治疗，被转诊到我们的诊所，舌根和右颈有肿块。舌根病变被发现是EBV阳性未分化癌。他接受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重建了舌根缺损。由于舌根的手术切缘阳性，术后增加了再照射。治疗后20个月，患者目前还活着，没有复发或远处转移。尽管目前尚不清楚我们的病例是复发还是新开发的EBV潜伏感染的未分化癌，但我们建议在治疗至少10年以上后应仔细观察EBV相关肿瘤。

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： : 通过免疫组织化学构建组织微阵列 (tma) 以有效表征乳房中大量非侵入性上皮病变是一种吸引人的研究方法，但存在技术挑战。我们报告了方法学研究，以优化从大型乳腺癌病例对照研究中收集的非侵入性乳腺组织中构建TMAs的方法。使用具有2.0毫米直径针头的手动排列技术，我们从32名乳腺癌妇女获得的标本中构建了TMAs，这些标本包含以下目标 :( 1) 28个末端导管小叶单位 (TDLUs); (2) 28个原位导管癌和 (3) 23个浸润性癌。通过仔细的靶标选择，我们通过TMAs的第30节获得了约80% 的非侵入性靶标的持续保存。TDLU靶标的免疫组织化学染色显示肾小管30.8% 中的雌激素受体 (ER) 和50.0% 中的孕激素受体 (PR) 呈阳性染色。为了建立一种有效的方法来评估TDLUs中的染色结果，我们创建了一个分类评分系统来近似包含阳性染色细胞 (<10%，10% 至50%，> 或 = 50%) 的小管的百分比，并将结果与通过小管计数获得的结果进行比较。两种方法之间的比较表明，ER的70.8% 和PR染色的79.2% 完全一致，没有两类差异。来自单个块的相同组织类型 (TDLU或DCIS) 的多个 (最多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，尽管仔细选择了靶标，但产生非侵入性乳房结构的tma是可行的，并且此类核心的免疫染色可能允许对瘤周组织进行有效的免疫组织化学表征。需要对这种方法进行进一步的探索。

BACKGROUND & AIMS: Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced only by the epithelial cells of the prostate, has recently been found in 30% of female breast tumours using immunofluorometry. Our aim was to localize PSA immunohistochemically in a selected group of 27 paraffin-embedded breast tissues. A scoring system was developed for the histological assessment of PSA positivity within the breast tissue. One pathologist (DH) scored, classified and graded all tumours. Site-specific PSA staining was noted in the histology slides. Intense staining was identified in apocrine metaplasia and within the lining ductal epithelium of cystically dilated ducts. The epithelium in lesions of sclerosing adenosis was also frequently positive for PSA staining. Hyperplastic ductal epithelium (especially of mild degree) occasionally stained positive, as did normal breast ducts. Better differentiated tumours showed PSA staining [e.g. mucinous carcinoma (colloid)]. If an infiltrating duct carcinoma showed staining for PSA, adjacent intraductal carcinoma was also noted to stain positively, if present.

背景与目标： 前列腺特异性抗原 (PSA) 是一种最初认为仅由前列腺的上皮细胞产生的糖蛋白，最近已在使用免疫荧光法的女性乳腺肿瘤30% 中发现。我们的目标是通过免疫组织化学方法将PSA定位在27个石蜡包埋的乳腺组织的选定组中。开发了一种评分系统，用于对乳腺组织内的PSA阳性进行组织学评估。一位病理学家 (DH) 对所有肿瘤进行评分，分类和分级。在组织学载玻片中发现了位点特异性PSA染色。在顶汗腺化生和膀胱扩张的导管上皮内发现了强烈的染色。硬化性腺病病变中的上皮也经常出现PSA染色阳性。增生的导管上皮 (尤其是轻度) 偶尔呈阳性，正常的乳腺导管也是如此。分化更好的肿瘤显示PSA染色 [例如粘液癌 (胶体)]。如果浸润性导管癌显示PSA染色，则邻近的导管内癌 (如果存在) 也被阳性染色。

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肽是广泛适用的癌症疫苗的有吸引力的候选者。这项研究的目的是评估WT p53-based免疫治疗方法对肝细胞癌 (HCC) 患者的潜力。通过在24例HCC患者中使用肽/HLA-A2.1四聚体，在外周血中直接鉴定了对WT p53(149-157) 和WT p53(264-272) hla-a * 0201限制性表位特异性的循环CD8 + T细胞。使用定量实时聚合酶链反应测定法，通过分析颗粒酶B和干扰素-γ mRNA转录来评估WT p53肽特异性刺激后的细胞毒性T淋巴细胞 (CTL) 活性。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中的p53状态，主要组织相容性复合物 (MHC) 和共刺激分子的表达。与健康对照组相比，HCC患者表现出明显更高的WT p53-specific记忆CD8 + T细胞频率和更强的WT p53-specific CTL活性。p53-specific CD8 + T细胞的频率增加及其活性与肿瘤细胞的选择性HLA-A2等位基因丢失和共刺激分子表达降低相关。此外，p53-specific T细胞数量的增加与肿瘤细胞中高MHC II类表达相吻合，但与肿瘤淋巴结转移分期系统的T状态成反比。我们的结果表明存在自然免疫监视和肿瘤免疫逃避，涉及HCC患者针对WT p53肿瘤抗原的T细胞反应。这些发现可能对癌症疫苗的未来发展具有重要意义。

BACKGROUND & AIMS: :The course of untreated localized prostate cancer after 10 years of follow-up is at large unknown. As curative treatment is usually only offered patients with a life expectancy exceeding 10 Years, the expected course of the disease if left untreated is of the utmost interest. This paper aims to describe the outcome for patients who survive for more than 10 years when treated without curative intent. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50% after 15 years. This is a much higher figure than in reported series on radical prostatectomy. Even if many deaths occur at an old age, prostate cancer death is shown to be associated with a significant morbidity, need for palliative treatment, hospital care and cost. Preventing prostate cancer death is therefore not only a matter of saving year of life but also to prevent suffering caused by the disease. Modern diagnostic tools, such as prostate specific antigen, seem to detect clinically significant cancers in the vast majority of patients. Over diagnosis seems to be uncommon if diagnostic procedures are restricted to patients with a long life expectancy. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.

背景与目标： : 经过10年的随访，未经治疗的局部前列腺癌的病程尚不清楚。由于通常只为预期寿命超过10年的患者提供治愈性治疗，因此，如果不及时治疗，该疾病的预期病程是最大的利益。本文旨在描述无治疗意图治疗后存活10年以上的患者的结果。结果表明，局部前列腺癌患者的癌症特异性死亡率随着时间的推移而稳定增加，并且在15年后约为50%。这比报道的根治性前列腺切除术系列要高得多。即使许多死亡发生在老年，前列腺癌的死亡也被证明与显着的发病率，姑息治疗的需求，医院护理和费用有关。因此，预防前列腺癌死亡不仅是挽救生命的问题，而且还可以防止疾病造成的痛苦。现代诊断工具 (例如前列腺特异性抗原) 似乎可以在绝大多数患者中检测到临床上重要的癌症。如果诊断程序仅限于预期寿命长的患者，则过度诊断似乎并不常见。局限性前列腺癌是一种生长缓慢但进行性的肿瘤性疾病。当被诊断为预期寿命较长的男性时，应该这样处理。

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： : 手术和放疗是头颈部鳞状细胞癌 (SCCHN) 患者的标准治疗选择。化疗和放化疗是局部晚期疾病的新选择，尤其是不可切除肿瘤患者的诱导化疗。在复发/转移性疾病和进展为基于铂的方案后，除了最佳支持治疗外，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)。这是一种酪氨酸激酶膜受体，对血管生成，肿瘤进展和对不同癌症治疗的抵抗力具有明确的意义。西妥昔单抗是一种与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。该药物在结肠癌中具有活性，目前正在SCCHN患者中进行测试。对于局部晚期疾病，与单纯放疗相比，西妥昔单抗/放疗联合治疗在生存方面具有益处。西妥昔单抗是对复发/转移性疾病的铂难治性患者的积极治疗。

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： 口腔癌是一种已知病因的肿瘤。增殖基因在其少数致病和预后因素中具有重要意义。钙周期蛋白是一个与细胞周期相关的基因，其功能尚不清楚。在评估其在鳞状细胞癌中的致病作用时，已研究了其表达以及Haras和histone-H3的表达。从鳞状细胞癌 (SCC) 和良性病变患者的病理和正常粘膜中提取的RNA被逆转录并通过聚合酶链反应 (PCR) 扩增。仅在SCC中，病理粘膜中所有三个基因的表达均增强。这表明它们可能参与其发病机理，并为恶性和良性病变的鉴别提供了另一个参数。

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： : 免疫疗法为癌症治疗展示了新的令人兴奋的观点。我们研究的目的是评估用新开发的黑色素瘤细胞系DDM-1.13的裂解液对自体树突状细胞 (DC) 进行疫苗接种的毒性和可能的不良反应。6名患者参加了I期试验。在存在粒细胞-巨噬细胞集落刺激因子 (gm-csf) 和interleukin-4 (IL-4) 的情况下，从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，该细胞系富含MAGE-a抗原的表达，并且缺乏黑色素瘤分化抗原的表达: 酪氨酸酶，MART-1和gp100。在大腿近端皮内接种疫苗，每隔2周共接种5种疫苗。每种疫苗含有3-5x10(6) dc。六名患者中有五名接受了全部五种疫苗。所有患者的治疗耐受性良好，没有观察到任何与疫苗相关的不良反应。使用这种基于DC的癌症疫苗进行治疗被证明是安全且无毒的。

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：

BACKGROUND & AIMS: A 66-year-old man, admitted to the hospital for prostatic carcinoma, presented with a nodular lesion located on the presternal region and a small nodule (0.5 cm in diameter) simulating a scalp sebaceous cyst located on the scalp. Moreover, an irregular darkbrown lesion was observed on the left side of the abdomen, and a brownish macula was also present on the presternal region. Histologic examination of the two nodular lesions revealed cutaneous metastases from prostatic carcinoma. The pigmented lesion, localized on the abdomen, proved to be a superficial spreading melanoma with a maximal depth of 1.36 mm. Histologic examination of the brownish lesion on the presternal region revealed nevus cell nests within the epidermis and in the dermis. We discuss the propensity of developing a secondary cancer in a patient with a primary malignancy.

背景与目标： 一名66岁的男子因前列腺癌入院，表现为位于胸骨前区的结节状病变和位于头皮上的小结节 (直径0.5厘米)，模拟头皮皮脂腺囊肿。此外，在腹部左侧观察到不规则的深褐色病变，胸骨前区域也出现褐色黄斑。对两个结节性病变的组织学检查显示前列腺癌的皮肤转移。位于腹部的色素性病变被证明是表面扩散的黑色素瘤，最大深度为1.36毫米。对胸骨前区域的褐色病变进行组织学检查，发现表皮和真皮内有痣细胞巢。我们讨论了原发性恶性肿瘤患者发生继发性癌症的倾向。

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： : 几种分子靶向疗法已在治疗头颈部鳞状细胞癌 (HNSCC) 的临床试验中进行了测试。其中，针对表皮生长因子受体 (EGFR) 的疗法已被最广泛地研究，并且一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确定与临床反应相关的分子特征。在这里，作者总结了相关的临床发现，并重点报道了针对HNSCC的EGFR靶向治疗的分子相关研究。作者特别关注评估与临床反应相关的分子标志物，并包括来自其他癌症部位的EGFR靶向临床研究的数据，他们预计这些数据将对头颈癌症研究和治疗社区感兴趣。