孕烷X受体介导的代谢酶和转运体转录调控及其在化疗药物耐药中的作用

孕烷X受体(PXR,NR1I2)是生物体内药物代谢酶和转运体基因表达的主要调控因子之一.近来研究发现,PXR介导的药物代谢酶和转运体的过表达,与化疗药物多药耐药的产生密切相关.鉴于PXR在药物代谢酶和转运体调控中的重要性和PXR转录调控的多样性,有必要对其导致的多药耐药形成机制进行更深入的研究.本文综述了PXR介导的代谢酶和转运体基因表达调控机制,及其引起化疗药物多药耐药的相关研究进展,为提高化疗药物敏感性、逆转化疗药物的多药耐药提供有效的治疗策略.     

MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism

Resistance to chemotherapeutic agents is one of the distinct features of cancer cells. We evaluate the role of activated MEK-ERK signaling in Camptotecin/irinotecan (CPT-11)-induced cell death using constitutively activated MEK1-transfected normal rat intestinal epithelial cells (IEC-caMEK cells). A CPT-11-induced inhibitory concentration of 50% was determined by WST assay. Apoptosis was evaluated by DNA staining and fragmented DNA analysis. Protein expressions were analyzed by western blotting. We also examined the role of cyclooxygenase-2 in the cell systems. IEC-caMEK cells possessed survival advantages compared to control cells. Apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed increased expression of Bcl-2, Bcl-xL, Mcl-1, and COX-2 and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor ameliorated the antiapoptotic nature of IEC-caMEK cells. MEK activation suppressed CPT-11-induced apoptosis in IEC-caMEK cells via a COX-2- dependent mechanism. Therefore, MEK-ERK signaling may contribute to the drug-resistant nature of cancer cells.     

Percutaneous Radiofrequency Ablation and Transcatheter Arterial Chemoembolization for Hypervascular Hepatocellular Carcinoma: Rate and Risk Factors for Local Recurrence

PURPOSE: To analyze local recurrence-free rates and risk factors for recurrence following percutaneous radiofrequency ablation (RFA) or transcatheter arterial chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC). METHODS: One hundred and nine nodules treated by RFA and 173 nodules treated by TACE were included. Hypovascular nodules were excluded from this study. Overall local recurrence-free rates of each treatment group were calculated using the Kaplan-Meier method. The independent risk factors of local recurrence and the hazard ratios were analyzed using Cox's proportional-hazards regression model. Based on the results of multivariate analyses, we classified HCC nodules into four subgroups: central nodules < or =2 cm or >2 cm and peripheral nodules < or =2 cm or >2 cm. The local recurrence-free rates of these subgroups for each treatment were also calculated. RESULTS: The overall local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p = 0.013). The 24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and 48.9%, respectively. In the RFA group, the only significant risk factor for recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a central location was the only significant risk factor for recurrence. In central nodules that were < or =2 cm, the local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p < 0.001). In the remaining three groups, there was no significant difference in local recurrence-free rate between the two treatment methods. CONCLUSION: A tumor diameter of >2 cm was the only independent risk factor for local recurrence in RFA treatment, and a central location was the only independent risk factor in TACE treatment. Central lesions measuring < or =2 cm should be treated by RFA.     

两种不同静脉输入奥沙利铂对患者的影响

目的比较周围静脉和颈外静脉留置针穿刺,输入奥沙利铂及5-氟尿嘧啶后,对患者造成静脉炎及末梢神经损伤的观察。方法随机分为两组,比较两种方法给药后引起患者静脉炎和末梢神经损伤有无差异。结果颈外静脉留置针输入奥沙利铂,发生静脉炎较周围静脉留置针组明显偏低,其差异有显著意义（P〈0.001）,并且未发生一例末梢神经损伤。结论颈外静脉留置针输入奥沙利铂,对患者造成静脉炎的影响较轻,避免了末梢神经损伤,使患者易于接受,该方法适用于进行化疗的肿瘤患者。     

Synergistic interaction between tetrandrine and chemotherapeutic agents and influence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines

PURPOSE: Tetrandrine (Tet), a bis-benzylisoquinoline alkaloid that was isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known as processing a marked antitumor effect in vitro and in vivo. The aim of this study was to assess the interaction between tetrandrine and chemotherapeutic agents widely used in gastric cancer treatment, and to investigate the influence of tetrandrine on chemotherapeutic agent-associated gene expression and apoptosis. METHODS: Synergistic interaction on human gastric cancer BGC-823 and MKN-28 cells was evaluated using the combination index (CI) method. The double staining with both Annexin-V-FITC and PI was employed to distinguish the apoptotic cells from living cells. Expression of chemotherapeutic agent-associated genes, i.e., excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS), class III beta-tubulin (beta-tubulin III) and tau, of BGC-823 cells with or without tetrandrine treatment were measured by real-time quantitative PCR. RESULTS: Tetrandrine had a synergistic effect on the cytotoxicity of chemotherapeutic agents in both two gastric cancer cell lines. The combination of tetrandrine and chemotherapeutic agents could also induce apoptosis in a synergistic manner. Tetrandrine could suppress the mRNA expression of ERCC1, TS, beta-tubulin III and tau. Most prominently, ERCC1, TS and beta-tubulin III mRNA levels were markedly suppressed at 0.29-, 0.12- and 0.60-fold, respectively, by the presentation of tetrandrine. CONCLUSION: Tetrandrine appears a promising candidate for combining with three chemotherapeutic agents. The possible mechanisms might be the synergistic apoptotic effect and the downregulation of chemotherapeutic agent-associated genes.     

风险管理联合积极心理护理预防PICC置管患者机械性静脉炎风险的价值

目的研究风险管理联合积极心理护理在预防经外周静脉置入中心静脉导管（PICC）置管患者机械性静脉炎风险中的价值。 方法选择2020年5月至2020年10月首都医科大学附属北京世纪坛医院收治的116例PICC置管的肿瘤患者作为研究对象,将其随机分为观察组（58例）和对照组（58例）。对照组按照PICC置管的常规护理方法进行护理,观察组在对照组的基础上使用风险管理联合积极心理护理。记录2组PICC置管时间、一次穿刺成功率、一次置管成功率;记录置管后1周两组机械性静脉炎发生情况。 结果与对照组相比,观察组置管操作时间较短（P＜0.05）;与对照组相比,观察组机械性静脉炎发生率较低,（P＜0.05）。 结论采用风险管理联合积极心理护理的方案对PICC患者进行护理能降低机械性静脉炎的发生率,具有推广价值。     

Nodular granulomatous phlebitis of the skin: a fourth type of tuberculid

We present five cases of granulomatous phlebitis of the skin and compare them with a case of miliary tuber-culosis with granulomatous phlebitis. All five patients were hypersensitive to purified protein derivative, but without active tuberculosis. Although anti-tuberculous drugs were effective, no tubercle bacilli were isolated from the skin. Clinically, subcutaneous nodules were felt along the course of the leg vein. Histologically, epithelioid cell granulomas with Langhans' giant cells were observed within the walls of the cutaneous veins. In a later stage, granulomatous panniculitis was often associated. Using the polymerase chain reaction method, Mycobacterium tuberculosis DNA was detected in four of the five cases of granulomatous phlebitis of the skin. Granulomatous phlebitis of the skin seems to represent a relatively early phase of delayed-type hypersensitivity reactions to Mycobacterium tuberculosis and may represent a distinct entity different from other types of tuberculid—a new tuberculid. Nevertheless, before making the diagnosis, the possibility of true tuberculosis must always be excluded. Nodular granulomatous phlebitis of the skin would be an appropriate name for the newly described condition.     

Identifying Risk Factors for Anthracycline Chemotherapy-induced Phlebitis in Women with Breast Cancer: An Observational Study

AimsAnthracycline chemotherapy administered via a peripheral cannula results in severe anthracycline chemotherapy-induced phlebitis (ACIP) in about 20–30% of patients. Administering chemotherapy via a central venous catheter (CVC) prevents ACIP. However, CVCs are associated with an increased risk of thrombosis and sepsis. Our aim was to identify risk factors associated with severe ACIP and to provide evidence about the individual risk of developing symptoms.Materials and methodsA prospective observational study of 263 women with breast cancer receiving peripheral administration of anthracycline chemotherapy at a UK cancer centre was conducted between May 2016 and January 2018. Data were collected at baseline and every 3 weeks following each chemotherapy treatment, using both healthcare professional- and participant-reported symptom assessments.ResultsAfter three cycles of chemotherapy, 27% of participants experienced severe ACIP. Factors associated with symptom severity were identified as: arm used for chemotherapy administration, epirubicin dose, age, pre-existing hypertension, comorbidity, ethnic group and pain during chemotherapy administration. The sequence of arm used for chemotherapy administration was the single most significant factor (P < 0.001). When alternating arms were used no other risk factor was influential. Where alternating arms were not used, younger age and higher dose were associated with higher-grade symptoms, with age being more influential than dose. The cumulative effect of increasing symptom severity with repeated cycles was also identified (P < 0.001).ConclusionIt is recommended that a CVC is not routinely required for women with breast cancer who have not undergone an axillary node clearance and receive chemotherapy in alternate arms. The need for a CVC for women who are planned to receive all anthracycline chemotherapy cycles in the same arm should be assessed in the light of peripheral venous access assessment and the key risk factors of age, dose and number of cycles.     

南风Ⅰ号外用防治长春瑞宾所致静脉炎的临床研究

目的观察新型中药复方制剂——南风Ⅰ号防治长春瑞宾所致静脉炎的临床疗效.方法选择以长春瑞宾为主的联合化疗方案第1、8天给药的患者,将自身2次化疗同一注射部位分成预防组和对照组,对预防组患者给予中药南风Ⅰ号涂剂;将已发生静脉炎的患者随机分成治疗组和对照组,治疗组给予南风Ⅰ号外敷治疗,对照组给予硫酸镁外敷对照进行临床观察.结果采用STATA 8.0软件进行统计分析,卡方检验比较预防组和对照组之间以及治疗组和对照之间的差异,均具有显著的统计学意义（P＜0.01）.结论新型中药复方制剂——南风Ⅰ号对防治长春瑞宾所致静脉炎具有一定的疗效.     

下肢血栓性浅静脉炎的超声诊断

目的探讨血栓性浅静脉炎的声像图特征。方法回顾性分析下肢血栓性浅静脉炎患者52例,观察病变的位置、范围、形态、边界、回声特点、血流分布等。结果所有患者均表现为局部静脉曲张,管径增宽明显,管壁不均匀增厚,管壁回声增强,腔内可见低、等回声团,探头加压管腔不变形,病变区域内无明显血流信号,皮下组织水肿。结论下肢血栓性浅静脉炎的声像图表现具有一定的特征性,结合临床表现超声易做出正确诊断。