细胞毒性T淋巴细胞相关抗原-4的生物学功能及其在头颈部鳞状细胞癌治疗中的应用

细胞毒性T淋巴细胞(T细胞)相关抗原-4(CTLA-4)是一种白细胞分化抗原,是T细胞上的一种跨膜受体,与CD28竞争性结合B7分子配体。CTLA-4与B7分子结合后发生T细胞无反应性,参与免疫反应负调节,与头颈部鳞状细胞癌的免疫逃逸密切相关。本文就CTLA-4的基本结构、功能与抗CTLA-4免疫疗法在头颈鳞状细胞癌中的应用做一综述。     

Reduced ultraviolet irradiation delays subsequent squamous cell carcinomas in hairless mice

Background: Ultraviolet (UV) radiation induces non-melanoma skin cancer (NMSC), and UV prophylaxis is essential to prevent skin cancer. It is unclear whether patients diagnosed with squamous cell carcinomas (SCC) may benefit from reduced UV exposures in terms of delaying the development of new tumors. The objective was to evaluate the significance of discontinued or reduced UV exposure for the development of subsequent skin tumors.
Methods: Seven groups of mice ( n =175) were irradiated with UV doses of 2 and 4 standard erythema doses (SED) that were continued, reduced or discontinued at the time of appearance of the first skin tumor.
Results: The development of new tumors was delayed, corresponding to the degree of reductions in UV dose in an inversely linear manner. Discontinuation of UV doses delayed the median times to the second tumor by 24 days (2 SED, P =0.0549) and 33.5 days (4 SED, P <0.0001), and when reduced to 1 SED, the median delays were 18 days (2 SED, P =0.0469) and 33 days (4 SED, P <0.0001). The median delay to the third tumor was after UV reduction 47 days (4 SED, P <0.0001) and 35 days (2 SED, P =0.151), and after UV discontinuation 49 days (4 SED, P <0.0001) and 44 days (2 SED, P =0.111).
Conclusion: This suggests that patients with SCC may benefit from reduced UV exposure.     

High sensitive mutation analysis on KRAS gene using LNA/DNA chimeras as PCR amplification blockers of wild-type alleles

The missense mutations at codons 12 and 13 of KRAS gene have been confirmed as a predictor of nonresponse to EGFR-targeted therapy with monoclonal antibodies cetuximab and panitumumab in patients with metastatic colorectal carcinoma (mCRC). Because of the intra-tumor heterogeneity at genetic levels, it is important to develop sensitive and selective assays to detect above KRAS mutation of rare mutated cells in the presence of large excess of wild-type cells. In the present study, wild-type blocking PCR (WTB-PCR) was developed to detect the aforementioned KRAS mutations, in which a chimera composed of locked nucleic acid (LNA) and DNA was used to inhibit with high sensitivity the amplification of wild-type KRAS alleles whereas it allowed the highly selective amplification of mutated KRAS alleles. Using mutated KRAS from HCT-116 as spiking DNA, the results showed that WTB-PCR could detect mutated alleles in a ratio of 1:10,000 (i.e., 0.01%) wild-type alleles and at a single copy level. For its further applications to detect aforementioned KRAS mutations in 20 cases of mCRC patients, the results showed that the detected mutation percentage of WTB-PCR (60%, 12/20) was higher than that of traditional PCR (45%, 9/20). Moreover, two patients respectively having synonymous mutated codons 13 (i.e., c.39C > T) and missense mutated codons 14 (i.e., c.40G > A) could be also only detected by WTB-PCR. In conclusion, the current WTB-PCR was a rapid, simple, and low-cost method to detect a trace amount of mutated KRAS gene.     

Comparison of photodynamic therapy for skin cancers and pre-cancers with δ-aminolevulinic acid

Objective  

The aim of the study was to compare the effects of photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) for patients with different kinds of skin cancers and pre-cancers.     

影响卵巢上皮性癌化疗疗效的临床病理因素分析

目的:探讨影响卵巢上皮性癌预后及化疗疗效的因素。方法:对1985~2004年间我院收治的362例卵巢上皮性癌化疗患者进行回顾性研究。结果:患者1年、2年、3年、4年、5年、10年的累积生存率分别为84.99%、66.57%、57.87%、50.22%、46.70%、35.73%,中位生存期48.75个月。年龄、临床分期、病理类型、分化程度、组织学类型、残余灶的大小、化疗疗程数、化疗间隔时间、紫杉醇剂量强度是影响预后及化疗疗效的因素;Cox模型对上述因素进行多因素分析显示,临床分期、术后残余灶的大小、分化程度、化疗疗程数是影响预后的因素。结论:FIGO分期、首次手术后残余灶大小、细胞分化程度、化疗疗程为卵巢上皮性癌的独立预后因素。因此努力提高卵巢上皮性癌的早诊断,做到早治疗,术后进行正规、足量、足疗程、及时的化疗是改善生存率的必要手段。     

支气管动脉灌注加外照射治疗中晚期肺癌的疗效观察(附36例报告)

目的　探讨同时应用支气管动脉灌注化疗和外放射治疗两种疗法治疗中晚期肺癌的疗效。方法　采用Seldinger’技术 ,经支气管动脉灌注化疗药物 :顺铂 80mg ,阿霉素 5 0mg ,丝裂霉素 10mg或 5 -氟脲嘧啶 10 0 0mg。每 3～ 4周灌注一次 ,3～ 4次为一疗程。放疗于灌注后 10～ 15天进行。放射源为60 Co ,所有病例均行对穿照射。剂量DT2 0 0cGy/次 ,5次 /周 ,总量DT5 0 0 0～ 60 0 0cGy/2 5～ 3 0次 ,共 5～ 6周。结果　CR 8例 ( 2 2 2 % ) ,PR 2 3例 ( 63 6% ) ,S 3例 ( 8 6% ) ,P 2例 ( 5 65 % )。总有效率CR PR为 85 6% ,2年生存率2 7 8%。结论　支气管动脉灌注加外照射治疗肺癌有协同作用 ,是目前治疗中晚期肺癌的一种安全、有效的方法。     

KRAS status and epidermal growth factor receptor expression as determinants for anti-EGFR therapies in salivary gland carcinomas

Salivary gland carcinomas (SGC) are rare cancers with poor prognosis and limited response to conventional chemotherapy. New strategies based on molecular targeted therapy are needed and the EGFR signaling cascade is considered a possible key pathway for therapeutic molecules. We have analyzed 65 SGC of the main histopathological types for the expression of EGFR and and the mutation status of its downstream effector KRAS. EGFR overexpression (+2, +3) has been identified by immunohistochemistry in 75.4%. KRAS mutation analysis was performed by direct genomic sequencing and revealed a KRAS wildtype in 98.5% except of one adenoid cystic carcinoma with a GGT–GAT transition at codon 12 (Gly12Asp). EGFR overexpression and KRAS wildtype are prerequisites for a successful anti-EGFR therapy. The results of this study plead in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies in SGC.     

CD56在肾细胞癌中的表达及其意义

目的研究CD56与肾细胞癌的细胞类型、肿瘤分级、临床分期及预后的关系。方法采用免疫组织化学二步法检测CD56在120例肾细胞癌中的表达，并对肾细胞癌组织进行系统的病理检查和分析。结果CD56的表达与肾细胞癌的病理分级和临床分期均呈正相关。CD56表达者与未表达者术后5年生存率分别为23．8％和92．5％，差异有统计学意义（P〈0.5）结论CD56的表达与肾细胞癌的病理分级和临床分期呈正相关，CD56与临床分期结合能更好地判断肾细胞癌的预后。CD56表达者易发生转移且预后差。     

康艾配合放射治疗100例鼻咽癌的临床观察

目的研究康艾注射液对鼻咽癌放射治疗（简称放疗）的增敏减毒作用。方法将100例Ⅰ、Ⅱ期鼻咽癌患者随机分成综合组与对照组,行前瞻性研究。两组患者均采用加速器6mVX线放疗,常规分割DT70GY。综合组在放疗开始至结束使用康艾注射液;对照组单纯放疗。结果综合组与对照组控制瘤体的完全缓解率分别为96%和76%,治疗后白细胞减少发生率分别为5%和13%,差异均有统计学意义（P＜0.05）。综合组治疗前、后T淋巴细胞亚群差异无统计学意义（P＞0.05）,对照组治疗前、后对比,以及综合组与对照组治疗后相比,T淋巴细胞亚群差异有统计学意义（P＜0.05）。结论对早期鼻咽癌患者放疗时加用康艾注射液能提高治疗效果,减轻不良反应。