Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.

OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.     

Evidence for an S-phase checkpoint regulating DNA replication after heat shock: a review.

Exposure of cells to heat inhibits a number of nuclear activities associated with semi-conservative replication of DNA including the incorporation of radiolabelled precursors into acid-insoluble DNA, the initiation of new replicons, the elongation of the DNA fibre at the replication fork, the synthesis and deposition of new histones into chromatin and the reorganization of nascent DNA into mature chromatin. These effects are likely to underlie the heat sensitivity of S-phase cells and may contribute to the radiosensitization observed in this phase of the cell cycle. While some of these effects may be explained as 'passive' consequences of heat-induced damage on chromatin structures experiments reviewed here point to the activation of a checkpoint as a contributing factor to the observed inhibition of DNA replication. Activation of a heat responsive S-phase checkpoint targets the activity of RPA via interaction with nucleolin. Nucleolin, a major nucleolar protein, is found normally sequestered in the nucleolus. Exposure of cells to heat causes a rapid translocation of nucleolin from the nucleolus into the nucleoplasm that enables RPA/nucleolin interaction. This interaction inhibits functions of RPA associated with the initiation of DNA replication and contributes to the immediate inhibition of DNA synthesis observed after heat shock. The results suggest that the nucleolus serves as a sequestration centre for the temporary inactivation of regulatory molecules, such as nucleolin, capable of regulating essential cellular functions after heat shock. It is speculated that this regulatory process is integrated in the network of responses that determine cell sensitivity to heat and that it may be involved in heat radiosensitization to killing as well.     

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA.

PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.     

普通额镜下鼻内激光泪囊鼻腔造孔术治疗慢性泪囊炎

报告在普通额镜下以YAG激光经鼻腔行泪囊鼻腔造孔术，治疗慢性泪囊炎患者37例（45眼），经3～24个月的随访观察，泪道阻塞均解除，有效率为95．6％，治愈率为88．9％。本手术具有损伤小，操作简便，快捷，术后反应轻，并发症少等优点。并对手术方法及影响疗效的因素进行了探讨。     

Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.     

中药“二黄”滴耳剂治疗急慢性化脓性中耳炎的临床观察(附1000例分析)

本文总结了“二黄”滴耳剂治疗急慢性中耳炎1000例，结果表明总有效率为89％，尤其对急性化脓性中耳炎效果更为明显，与其它抗生素相比具有很多优点。抗菌谱广，对革兰氏阳性菌及革兰氏阴性菌、病毒都有一定作用，低浓度抑菌，高浓度杀菌，不易产生抗药性及过敏反应，对第八对脑神经无毒性，价格低廉应用方便优于任何一种抗生素。     

声门上型喉癌临床N_0病理转移的观察

目的：为探讨喉癌颈淋巴结转移的规律，选择手术方法。方法：采用１１０例临床Ｎ０声门上型喉癌的１６４侧颈廓清术标本淋巴结连续切片方法观察。结果：发现颈淋巴结转移率为３５．５％（３９／１００）。提出临床Ｎ０病理转移的特点：１）转移淋巴结大小大多数介于０．５～１．５之间占８４．２％。２）转移淋巴结大多数为早期侵入期和生长发展期占８６．０％。３）转移淋巴结绝大多数为单发型占７４．４％。４）各个Ｔ分期均有转移淋巴结。结论：在颈淋巴结处理上，我们支持尽可能同期行选择性颈廓清术的观点     

ODC反义寡核苷酸对K562细胞生长抑制作用

鸟氨酸脱羧酶(ornithine decarboxylase,ODC)是催化多胺生物合成的限速酶.过去的研究表明多胺在维持肿瘤恶性表型中起着重要作用.用ODC不可逆抑制剂抑制多胺生物合成不仅能抑制肿瘤细胞的增殖而且还诱导细胞分化.近年我们采用反义技术,以ODC反义RNA转染肿瘤细胞,通过对ODC表达的封闭,成功地使其恶性表型得到了逆转.提示抑制肿瘤细胞的多胺合成可能是抗癌的有效途径.本文用ODC反义寡核苷酸控制肿瘤细胞的多胺生物合成,观察了其对K562细胞生长特性的影响,以期为ODC反义寡核苷酸在肿瘤临床的应用提供实验依据.     

EB病毒VCA-IgA抗体水平与鼻咽癌病人远期疗效关系

目的：分析ＥＢ病毒血清学ＶＣＡ－ＩｇＡ抗体与鼻咽癌病人远期疗效关系，为临床治疗提供参考依据。方法：１９８５年本院病理确诊的５２２例鼻咽癌病人，按治疗前、后ＶＣＡ－ＩｇＡ抗体滴度分为三组：低滴度组（１：５～１：２０）、中滴度组（１：４０～１：８０）和高滴度组（１：１６０以上），随访１０年，比较生存率的异同。结果：治疗前鼻咽癌病人高滴度组１０年生存率低于低滴度组（Ｐ＜０．０５），但和中滴度组差别无显著性（Ｐ＞０．０５）。治疗后三组病人１０年生存率比较，高、中滴度二组差别无显著性（Ｐ＞０．０５），但低于低滴度组。结论：ＥＢ病毒ＶＣＡ－ＩｇＡ抗体水平可以作为估计预后的重要参考依据，与远期疗效有密切关系。     

Intracerebral transportation and cellular localisation of insulin-like growth factor-1 following central administration to rats with hypoxic-ischemic brain injury

Insulin-like growth factor-1 (IGF-1) has been shown to be neuroprotective when administered centrally following hypoxic-ischemic (HI) brain injury. However, the cerebral distribution and site of action of IGF-1 after intracerebroventricular (i.c.v.) administration are not known. A unilateral HI brain injury was induced in adult rats by a modified Levine method. Either 3H-IGF-1 alone, or in combination with unlabelled IGF-1, was administered into the lateral ventricle 2 h after injury. The activity of 3H-IGF-1 signal in the potentially injured cortex was compared between two treatment groups using image analysis. The regional distribution and cellular localisation of 3H-IGF-1 were examined autoradiographically in potentially injured hemispheres at 0.5 and 6 h after administration. Tritiated IGF-1 was detected predominantly in the pia mater, perivascular spaces and subcortical white matter tracts 0.5 h after administration and decreased by 6 h (p<0.05). The signals associated with the perivascular spaces and pia mater were not blocked by unlabelled IGF-1, suggesting non-saturable binding in these brain areas. IGF-1 signal was co-localised with IGF binding protein (IGFBP)-2 immunostaining in the white matter tracts where the signal was blocked by unlabelled IGF-1, suggesting competitive association. IGF-1 signal associated with neurons and glia was maximal in the cerebral cortex and less in the CA1-2 subregion of the hippocampus which were blocked by unlabelled IGF-1 (p<0.05). The signals from cortical neurons did not decrease 6 h after administration, suggesting specific and persistent binding to these cells. Our results indicate that centrally administered IGF-1 can be translocated to neurons and glia via the perivascular circulation and the ependymal cell-white matter tract pathways.