Redox-sensitive signaling factors as a novel molecular targets for cancer therapy.

Tumor cells undergoing proliferation, de-differentiation and progression depend on a complex set of respiratory pathways to generate the necessary energy. The metabolites from these pathways produce significant oxidative stress and must be buffered to prevent permanent cell damage and cell death. It is now clear that, in order to cope with and defend against the detrimental effects of oxidative stress, a series of redox-sensitive, pro-survival signaling pathways and factors regulate a complex intracellular redox buffering network. This review develops the hypothesis that tumor cells use these redox-sensitive, pro-survival signaling pathways and factors - up-regulated due to increased tumor cell respiration - to evade the damaging and cytotoxic effects of specific anticancer agents. It further suggests that redox-sensitive, signaling factors may be potential novel targets for drug discovery.     

尺骨鹰嘴骨折三种治疗方法的比较分析

为给临床治疗尺骨鹰嘴骨折选择方法提供依据.对分别采用非手术治疗(A组)、张力带钢丝内固定(B组)、双边外固定器固定(C组)三种方法治疗的112例该病患者的临床资料进行了回顾性分析.依据远期临床功能恢复情况分优、良、可、差4级标准进行疗效评价,结果优良率A组78.25%、B组92.30%、C组94.59%.B组和C组的优良率明显优于A组,B组和C组的优良率接近.认为治疗尺骨鹰嘴骨折张力带钢丝法为有效可靠的选择,双边外固定器固定效果满意,值得推广应用.     

五输穴的临床应用

五输穴是十二经分布在肘膝关节以下的5个重要经穴,分别命名为井、荥、输、经、合,简称"五输".有关五输的记载首见于<灵枢·九针十二原>:"所出为井、所溜为荣、所注为输、所行为经、所入为合",但并未指出具体的穴名和部位.<灵枢·本输>则详细阐明了各经井、荥、输、经、合各穴的名称和具体位置,惟独没有手少阴心经,以后在<针灸甲乙经>中才被补充完备.古人把经气运行的过程用自然界由小到大、由浅到深的水流变化来形容,把五输穴按井、荣、输、经、合的顺序从四肢末端向肘、膝方向依次排列.     

Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival.

PURPOSE: Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS: All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION: Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.     

Concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas: radiation therapy oncology group phase II trial 99-14.

PURPOSE: To investigate the feasibility of combining concomitant boost accelerated radiation regimen (AFX-C) with cisplatin and to assess its toxicity and the relapse pattern and survival in patients with advanced head and neck carcinoma (HNC). PATIENTS AND METHODS: Between April and November of 2000, 84 patients with stage III to IV HNC who met the eligibility criteria were enrolled; 76 of these patients were analyzable. Radiation consisted of 72 Gy in 42 fractions over 6 weeks (daily for 3.5 weeks, then twice a day for 2.5 weeks). Cisplatin dose was 100 mg/m(2) on days 1 and 22. Tumor and clinical status were assessed, and acute late toxicities were graded. RESULTS: Sixty-five patients (86%) received both radiation and chemotherapy per protocol or with minor variations. The estimated 2-year locoregional relapse and distant metastasis rates were 34.7% and 16.1%, respectively. The estimated 2-year overall survival and disease-free survival rates were 71.6% and 53.5%, respectively. Three patients (4%) died of complications, 19 patients (25%) had acute grade 4 toxicity, and 49 patients (64%) had acute grade 3 toxicity. The 2-year cumulative incidence of late grade 3 to 5 toxicities was 51.3%. CONCLUSION: These data showed that it was feasible to combine AFX-C with cisplatin. The compliance to therapy was high, and the locoregional control and survival rates achieved compared favorably with AFX-C alone or other concurrent chemoradiation regimens tested by the Radiation Therapy Oncology Group. A phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin is ongoing to determine whether the use of AFX-C in the concurrent chemoradiation setting further improves outcome.     

The association of XRCC1 haplotypes and chromosomal damage levels in peripheral blood lymphocyte among coke-oven workers.

Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg(194)Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg(280)His, Arg(399)Gln and Gln(632)Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.     

Closed-form solution for the thermal dose delivered during single pulse thermal therapies.

This study provides a closed form, analytical expression for the thermal dose delivered by a single heating pulse. The solution is derived using the effective cooling method and the non-linear Sapareto-Dewey equation to determine the thermal dose delivered by the time-temperature history of a treatment. The analytical solutions are used to determine the optimal treatment conditions, i.e. those that exactly deliver the desired thermal dose at a specified time. For purposes of illustration, this study focuses on a 'conservative' clinical approach in which the desired thermal dose is delivered at the end of the 'cool down' period. The analytical results show that, after a clinical strategy has been chosen (e.g. conservative, aggressive or intermediate), the user can only specify two free variables for such an optimal treatment. Results are presented which suggest that a practical approach would be to specify both (1) the desired thermal dose to be delivered to the target (the clinically relevant outcome) and (2) the peak temperature to be reached (a measurable, clinically useful, patient dependent response variable that can be employed in feedback control systems); and then determine the associated, optimal heating magnitude and duration that need to be used to reach that dose and temperature. The results also reveal that, with a given patient condition and power deposition distribution (together specifying an effective cooling time constant for the treatment) and a specified thermal dose, there is a maximum allowable peak temperature that, if exceeded, will result in 'over-dosing' the heated tissue. The results also show that avoiding such non-optimal 'over-dosing' will be difficult in most high temperature therapies since, when high temperatures are produced in tissues, the temperature decay must be very fast in order to avoid over-dosing during the cooling period. Such rapid cooling can only occur if short effective cooling time constants are present-either as a result of large tissue blood flows in the patient or due to large conduction effects induced by the use of highly localized power deposition sources.     

婴儿双歧杆菌/胞嘧啶脱氨酶肿瘤靶向性基因治疗系统的构建(英文)

目的构建婴儿双歧杆菌/胞嘧啶脱氨酶靶向性基因治疗系统。方法 PCR 扩增 CD 基因,EcoR Ⅰ,BamH Ⅰ对 CD 基因和 pGEX-1LamdaT 质粒同时进行双酶切,获得4.9 kb、1.3 kh 两个 DNA 片段。T4 DNA 连接酶连接这两个片段构建重组的CD/pGEX-1LamdaT 质粒,然后用电穿孔法将重组质粒转染婴儿双歧杆菌。从阳性转染的婴儿双歧杆菌中提取重组质粒,双酶切后检测切取片段长度,采用 Sanger 双脱氧链终止法对提取的重组质粒中的插入片段进行测序。结果从阳性转染的婴儿双歧杆菌中获得了6.2 kb大小的重组质粒,该质粒经双酶切后,得到了4.9 kb 和1.3 kb 两个长度的片段,其长度分别与 pGEX-1LambdaT 及 CD 基因的长度相同。测序结果显示,提取的重组质粒中插入的基因片段全长及核苷酸序列与 CD 基因完全相同。结论外源性 CD 基因被准确插入 pGEX-1LambdaT 质粒并转入婴儿双歧杆菌中,婴儿双歧杆菌/胞嘧啶脱氨酶靶向性基因治疗系统被成功构建。     

Solitary fibrous tumors of the pleura: clinical, radiological, surgical and pathological evaluation.

AIMS: To report a clinicopathological series of cases of solitary fibrous tumor of the pleura from Taiwan. METHODS: Clinical data was collected from a review of medical records and telephone interviewing for follow-up. RESULTS: Eight patients, three men and five women aging from 34 to 71 years, underwent tumor resection and were followed in a period from 7 months to 13.5 years. Six patients underwent standard thoracotomy and two had VATS for tumor excision. Tumors were pathologically benign in seven patients and malignant in one. Patients were all alive with no evidence of tumor recurrence at the time of this report. CONCLUSIONS: One should always consider SFTPs as potentially malignant tumors. Complete resection remains the mainstay of cure. Standard thoracotomy should always be considered when a high suspicion of malignancy is raised, whereas VATS may be a preferred approach for smaller tumors.     

中西医结合治疗输卵管阻塞性不孕症

陈益昀主任中医师是全国第二、三批中医药专家学术经验继承指导老师，临床悬壶五十余载，治学严谨，注重实际。几十年的临床实践加之深厚扎实的理论功底，尤其能够结合现代医学知识，使其在治疗疾病，立法用药上独树一帜。笔者有幸随师学习，获益匪浅，兹将陈老师运用中西医结合治疗输卵管阻塞性不孕症的经验总结介绍如下：