Sister chromatid exchanges in lymphocytes of nurses handling antineoplastic drugs

The effects of handling antineoplastic drugs were examined in a group of 23 nurses working in the hematology and oncology departments of different university hospitals in Ankara and in a group of 50 unexposed controls. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges (SCEs) in circulating lymphocytes which result from the breakage and rejoining of DNA at apparently homologous sites on the 2 chromatids of a single chromosome. A significant increased frequency of SCE is observed in nurses in daily contact with antineoplastics (n = 23, mean SCEs/cell +/- SE 6.5 +/- 0.2) as compared to a group of controls (n = 50, mean SCEs/cell 5.2 +/- 0.2). The nurses who smoked also had a higher SCE frequency (n = 15, mean SCEs/cell 7.0 +/- 0.3) than non-smokers, (n = 8, mean SCEs/cell 5.5 +/- 0.3). A significant increase (P less than 0.001) in the mean number of SCE was found for non-smoking nurses as compared to non-smoking controls (n = 27, mean SCEs/cell 4.1 +/- 0.2).     

Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo

Imipramine and desipramine are two widely used tricyclic antidepressants which have shown conflicting results in regard to their in vitro genotoxic evaluation. The aim of this investigation was to determine the capacity of these compounds to induce in vivo sister-chromatid exchanges (SCEs) in mouse bone marrow cells. For each compound, the animals were organized in five groups constituted by five individuals. They were intraperitoneally (ip) administered with the test substances as follows: a negative control group treated with 0.4 ml of distilled water, a positive control group administered with cyclophosphamide (70 mg/kg), three groups treated with imipramine (7, 20 and 60 mg/kg), and three other groups treated with desipramine (2, 20 and 60 mg/kg). The general procedure included the subcutaneous implantation to each mouse of a 5-bromodesoxyuridine tablet (45 mg), and 1 h later, the administration of the chemicals involved. Twenty-one hours after the tablet implantation, the mice received colchicine, and 3 h later their femoral bone marrow was obtained in KCL, fixed, and stained with the Hoechst-Giemsa method. The results showed that both compounds were SCE inducers, starting from the second tested dose. The response of these compounds was dose-dependent, and showed that the highest tested dose increased about four times the SCE control level. The cellular proliferation kinetics was not affected by the chemicals, and the mitotic indexes were slightly diminished with the highest dose. These results indicate an in vivo genotoxic potential for both chemicals, and suggest that it is pertinent to follow their evaluation in other models.     

Sister chromatid exchanges and micronuclei formations induced by sorbic acid and sorbic acid-nitrite in vivo in mice

The in vivo induction of sister chromatid exchanges and micronuclei formations by acute treatment with different concentrations of sorbic acid and by nitrite, individually and in combination, was studied in bone marrow cells of mice. A significant increase in the frequency of sister chromatid exchanges was only observed with the three higher concentrations of sorbic acid when compared to a distilled water control. Sodium nitrite produced a significant increase at all doses tested. A combination of half the concentration of sorbic acid and of sodium nitrite gave an additive effect over that of sorbic acid or sodium nitrite alone. In the micronucleus assay, the highest dose of sorbic acid (150 mg/kg body weight) produced a significant increase in micronuclei formations compared to the distilled water control. Sodium nitrite alone induced significant numbers of micronuclei at all concentrations tested when compared to the negative control. However, a combination of half the concentration of sorbic acid and of sodium nitrite gave synergistic effects which could possibly be ascribed to the formation of certain genotoxic compounds in vivo.     

不同全身麻醉方式对老年消化道肿瘤患者手术后早期认知功能的影响

目的比较不同全身麻醉方式对老年患者消化道肿瘤手术后早期认知功能的影响。方法随机选择90例无神经精神系统疾病史或服用相应药物的消化道肿瘤患者,美国麻醉医师协会(ASA)Ⅰ～Ⅱ级,年龄60～79岁,采用随机数字表法,将择期行消化道肿瘤手术患者随机分为3组(每组30例):异丙酚全凭静脉组(P组)、七氟醚与异丙酚静吸复合组(SP组)、七氟醚吸入麻醉组(S组)。分别于术前1d、出麻醉恢复室时及术后1、3、7d时,采用简易精神状态评价量表(MMSE)进行认知功能评分。结果与术前1d比较,P组、SP组、S组出麻醉恢复室时、术后1d时MMSE评分降低(P<0.05),出麻醉恢复室时、术后1d时认知功能障碍发生率升高(P<0.05);术后3、7d时MMSE评分有所恢复,虽较术前略下降,但差异无统计学意义(P>0.05);P组、SP组、S组间MMSE评分和术后认知功能障碍发生率差异无统计学意义。结论老年患者全身麻醉术后早期认知功能下降,不同全身麻醉方式早期认知功能障碍发生率差异无统计学意义。     

Urinary 8-hydroxydeoxyguanosine and sister chromatid exchanges in patients with total hip replacements

Ion release from metal implants has been suspected to increase the risk of genotoxic effects in patients wearing orthopedic metal devices. In this study we used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage and the frequency of sister chromatid exchanges in lymphocytes to test a possible relationship between the concentrations of chromium or cobalt and the induction of cytogenetic modifications in 46 patients with total hip replacements. A broad range of individual levels of metals has been observed in these patients: chromium in blood, 1.59-14.11 microg/L; chromium in urine, 0.79-93.80 microg/24 h; cobalt in blood, 0.77-37.80 microg/L; cobalt in urine, 2.59-166.94 microg/24 h. By linear regression analysis, no significant correlation between urinary 8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was found. However, cobalt in blood as well as 8-OHdG in urine were higher in patients with implants 3-4 yr old as compared to patients with implants 1-2 yr old. Smoking significantly increased the frequency of SCE. Our data do not indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or cobalt in patients with total hip replacements.     

乳腺癌患者化疗药物不良反应情况及影响因素分析

目的分析乳腺癌化疗药物所致药物不良反应的影响因素。方法随访调查北京大学第一医院2015-08-10—2017-03-31乳腺癌患者化疗药物不良反应情况,并对化疗患者的年龄、化疗方案等进行统计和分析。结果本研究纳入260例患者进行分析,其中男性1名,女性259名,平均年龄(51.33±10.99)岁;乳腺癌化疗后常见药物不良反应包括恶心(67.69%)、呕吐(36.15%)、白细胞计数减少(66.54%)、中性粒细胞计数减少(66.54%)、贫血(57.69%)、疲劳(53.85%)、味觉障碍(40.77%)等。化疗方案对恶心、呕吐、神经毒性、骨髓抑制等有显著影响(均P<0.05)。结论化疗方案对药物不良反应有显著影响,在化疗方案制定时应注意根据患者发生恶心、呕吐、神经毒性、骨髓抑制等情况风险对治疗方案与剂量做适当调整,做到个体化给药。     

联合放化疗治疗乳腺癌患者的心电变化分析

目的探讨联合放化疗对乳腺癌患者的心脏损伤作用。方法乳腺癌术后患者60例,随机分成单一化疗组（单化组）和联合放化疗组（放化组）,每组30例,单化组接受表阿霉素治疗,放化组接受放射治疗配合表阿霉素化疗,两组患者治疗前后均行动态心电图监测,并对监测结果进行统计学分析,比较两种治疗方法对心肌损伤的作用的大小。结果放化组24 h平均心率（88.7±7.3）次/分明显高于化疗组;出现心律失常7例、ST段改变4例、传导异常6例,共17例、总异常率为56.7%,明显多于单化组30.0%,两组比较差异有统计学意义（P〈0.05）。结论联合放化疗比单一化疗增加乳腺癌患者的心律不齐、传导异常、ST段改变等心电异常例数,有增加心脏损伤作用,治疗时应定期行心电图检查,以策安全。     

乳腺癌患者化疗期护理

目的对乳腺癌患者化疗期护理方法和护理效果进行研究分析,以更好的指导临床应用。方法随机选择我院近三年乳腺癌化疗期患者58名,分成A、B两组,A组23名患者为对照组,给予常规化疗方法治疗;B组35名患者为观察组,在A组基础上加系统的护理方法。结果经统计,B组患者均坚持接受化疗,化疗完成率为100％,高于A组患者,化疗有效率高于A组,患者满意率高于A组患者。结论对乳腺癌患者化疗期进行系统护理,患者化疗完成率较高,化疗效果显著。     

Sister chromatid exchanges, proliferating rate index, and micronuclei in biomonitoring of internal exposure to vinyl chloride monomer in plastic industry workers

The frequency of micronuclei (MN), sister chromatid exchange (SCEs), and the proliferating rate index in peripheral blood lymphocytes from 93 individuals were measured. Fifty-two of the individuals were workers in the plastics industry where they were exposed to vinyl chloride monomer while the remaining 41 individuals served as a control group. In our results, an increase of SCEs and MN, as well as inhibited cell kinetics, was observed in the group of exposed workers. Of the tests used, SCE was found to be the most sensitive endpoint for indicating a biological response. However, since methods for restricting the MN analysis to only cells at risk (i.e., second generation interphase cells) were not used, this statement requires verification.     

High-dose chemotherapy in breast cancer

High-dose chemotherapy is based on the scientific hypothesis that escalating the dose of drug will overcome drug resistance and improve outcome. Autologous bone marrow transplantation and, more recently, peripheral stem cell transplantation used as a means to restore marrow, made this a viable treatment for patients with selected tumours such as haematological malignancies. The role in breast cancer is less certain. Given the known as well as the potential toxicities, the objective of high-dose chemotherapy should be cure as opposed to palliation. However, the natural history of breast cancer can be protracted, with relapses occurring 15-20 years after treatment or within months of curative surgery. In breast cancer there is a positive correlation between recurrence-free and long-term survival. Therefore, the recurrence-free survival can be considered a surrogate endpoint in clinical trials. In patients with metastatic disease where cure is rare, at best, duration of a disease-free state may be a surrogate for overall benefit. Alternatively, time to progression may be another endpoint in the evaluation of treatment for metastatic disease. This is based on the assumption that quality of life is enhanced without progression of disease. Toxicity is the significant issue in the use of high-dose chemotherapy. The most common toxicity is myeloablation, potentially requiring prolonged hospitalisation. The only justification for these toxicities would be evidence of significant and meaningful benefit. A clinically relevant benefit with high-dose chemotherapy has not been seen in major randomised clinical trials of breast cancer in both the adjuvant and metastatic setting. In patients with advanced breast cancer, a small percentage may achieve long-term, disease-free survival, although there is no improvement in overall survival. Nonetheless, some investigators believe that high-dose chemotherapy holds promise, although currently this treatment is not recommended outside of a well designed prospective trial. These studies have provided useful information regarding cancer treatment. However, ongoing study of drug administration intervals, that is, dose-dense therapies, may lead to an approach that allows superior and less toxic treatment for breast cancer.     

佳木斯地区放射工作人员外周血淋巴细胞姊妹染色单体交换频率的研究

本文对佳木斯地区130名放射工作人员外周血淋巴细胞的SCE频率进行了研究。其结果,放射工作人员每个细胞SCE频率平均为5.65±1.4,正常对照组每个细胞SCE频率平均为5.01±1.27,两者之间有显著性差异(t=2.55,p<0.05)。本文还对放射工作人员的工龄和吸烟与SCE频率的相关性进行了分析。为探讨小剂量电离辐射的人体效应,进一步改善卫生防护措施提供依据。     

DCE-MRI对乳腺癌新辅助化疗疗效的评估

目的 探讨动态增强磁共振成像(DCE-MRI)检查对乳腺癌新辅助化疗疗效评价方面的价值.方法 回顾性分析32例乳腺癌患者的临床、病理及影像学资料,所有患者于术前均行新辅助化疗且化疗前后2周内均行DCE-MRI检查,提取患者的MRI资料,由两位高年资影像专业主治医师进行独立评价,最后汇总二者结果,将不一致的结果共同协商并达成一致.结果 DCE-MRI评价32例患者,完全反应7例,部分反应20例,无反应5例,无疾病进展病例;有效的27例全部证实属于病理反应有效;MRI评价新辅助化疗疗效的敏感度为90.0％,特异度为100.0％.结论 DCE-MRI可准确显示新辅助化疗前后病灶的变化,对新辅助化疗疗效的评价准确度较高,有重要临床应用价值.     

Molecular chemotherapy for breast cancer

Gene therapy for breast cancer initially involves local or systemic delivery. Local delivery may be intrapleural or via direct injection to lesions. However, systemic delivery remains the greatest challenge with targeting, although methods using antibodies or growth factor receptor ligands have been demonstrated in preclinical models. This review focuses on the next step of using tissue-specific promoters such as Muc-1, CEA, PSA, HER-2, Myc, L-plastin and secretory leukoproteinase inhibitor promoters. All of these have demonstrated differential upregulation in breast cancer and additional specificity may be obtained by using physiological stimuli that are more frequently expressed in cancers, such as glucose regulated promoters and hypoxia response elements or radiation inducible elements. Amongst the later are the EGR-1, p21 and tissue type plaminogen activator promoters. Potential therapy genes include the prodrug activation system 5-fluorocytosine and other analogues of antimetabolites, but all of these need gap junctions to transfer the phosphorylated metabolites. Other approaches involving more freely diffusible products include cyclophosphamide, ifosfamide and thymidine phosphorylase to activate 5-deoxy-5-fluoruridine to fluorouracil. The bystander effect is important both for cell killing and for immunological and antivascular effects. Breast cancer is one type of tumour where a major clinical research effort is underway using local delivery methods. For prodrug activation systems, the use of human enzymes is desirable to prevent an immunological response that would eventually eliminate cells producing the prodrug activation system. The use of alkylating agents has an advantage over antimetabolites in that they are cytotoxic to cycling and noncycling cells, and the cytotoxic products can diffuse across cell membranes without the need for gap junctions. They also have a much steeper dose response curve than antimetabolites.     

Neoadjuvant chemotherapy of breast cancer

About 80% of patients with breast cancer ultimately die of metastatic disease at 20 years. Distant metastases are more important as a cause of death than local or regional relapses. It is for this reason that adjuvant chemotherapy is necessary, especially in young patients and those with extensive disease. Initial chemotherapy preceding any local or regional treatment is justified on the grounds that both surgery and anaesthesia lead to immunodepression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials by Nissen-Meyer, Bonadonna and Cooper (1-3). In the present study 145 patients, including 67 with inflammatory breast cancer (IBC), were treated with 4-6 weeks of Velbe, thiotepa, methotrexate, fluorouracil and prednisone, with Adriblastin added for patients with IBC, T greater than 7 cm, or N2, N3. Because of tumour regression of greater than 50% observed in 80% of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium), resulting in complete remission in all these cases. Maintenance treatment with the same drugs was prescribed for 6-18 months depending on the initial stage. Tumour regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest being 42 months. Overall survival at 2 years for IBC is 90%, with a disease-free survival of 80%. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.     

Cytogenetic outcomes of adjuvant chemotherapy in non-target cells of breast cancer patients

Spontaneous and chemotherapy-induced sister chromatid exchanges (SCES) and lymphocyte proliferation rate index (PRI) in cultured peripheral lymphocytes were evaluated in 30 patients with diagnosed breast cancer before and after adjuvant chemotherapy and in 30 healthy women with no known familial history of breast cancer. Before chemotherapy, the breast cancer patients had a significantly increased background level of SCE, and lowered PRI as compared with the healthy women. Marked inter-individual variations were observed in both endpoints among the patients. Significantly elevated frequency of SCE and depressed PRI were recorded in blood samples collected after the first cycle of chemotherapy, with high inter-individual variations in the responses to the chemotherapy. FAC (5-fluorouracil, adriamycin and cyclophosphamide) protocol was the most genotoxic of the protocols studied, but also AC (adriamycin, cyclophosphamide) and CMF (cyclophosphamide, methotrexate and 5-fluorouracil) clearly increased SCE. All protocols significantly retarded lymphocyte proliferation in vitro. Our findings indicate that both SCE and PRI may serve as sensitive biomarkers for the routine detection of critical lesions produced by the administration of antineoplastic drugs in the clinical setting, as well as for possible screening of high-risk individuals among patients who have successfully completed chemotherapy.     

阿加曲班预防宫颈癌同步放化疗患者下肢静脉血栓的效果观察

目的 比较阿加曲班和低分子肝素用于预防宫颈癌同步放化疗患者下肢静脉血栓的效果.方法 选取60例宫颈癌放化疗的病例,按随机数表分为阿加曲班组和低分子肝素组两组,每组30例.阿加曲班组采用阿加曲班注射液,低分子肝素组采用低分子肝素钙.用药过程中监测患者活化部分凝血活酶时间(APTT),统计血栓形成、出现不良反应的例数,比较两组患者用药前后症状和体征的变化.结果 用药后,阿加曲班组APTT水平第1d为(39.05±7.51)s,第7d为(38.16±8.55)s,第14 d为(38.67±7.52)s,阿加曲班组活化部分凝血活酶时间显著短于低分子肝素组(P＜0.05),阿加曲班组血栓形成、出现不良反应各1例,显著低于低分子肝素组的3例和6例(P＜0.05).结论 阿加曲班对预防宫颈癌同步放化疗患者下肢静脉血栓的效果优于低分子肝素.     

Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer

The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cyclophosphamide (CTX) and methotrexate (MTX) (CM) have been demonstrated. The authors report results and long-term follow-up for patients with metastatic breast carcinoma who obtained prolonged clinical benefit with CM. Prospectively collected data from two successive clinical trials were evaluated. From July 1997 to October 2003, patients with metastatic breast carcinoma were treated with low-dose oral chemotherapy (MTX 2.5 mg, twice daily on day 1 and day 2 or 4, and CTX 50 mg daily). Patients who achieved prolonged clinical benefit for a duration of 12 months or more (complete remission, partial remission or stabilization of disease) were considered for the analysis. Median follow-up was 23 months. A total of 153 patients were enrolled and are evaluable: Eastern Cooperative Oncology Group performance status 0-1 in 90 patients, two or more sites of metastatic disease in 97 patients, zero regimen for metastatic breast carcinoma in 48 patients. Among 153 patients, five demonstrated complete remission and 25 partial remission. The proportion of patients who achieved prolonged clinical benefit was 15.7% (95% confidence interval 9.9-21.4%). Median time to progression for patients with prolonged clinical benefit was 21 months (range 12-37+ months). One patient maintained complete remission 42 months after therapy discontinuation. At the multivariate analysis endocrine responsiveness and the achievement of an objective response significantly correlated with the achievement of prolonged clinical benefit. Metronomic chemotherapy can induce prolonged clinical benefit in metastatic breast cancer, supporting its role as an additional therapeutic tool in the treatment of patients with metastatic breast carcinoma.     

分子检测在乳腺癌辅助化疗中的应用

目的：分析根据分子检测技术选择的化疗药物的毒副反应及有效性。方法：选择246例乳腺癌术后患者分为检测组150例和常规组96例。检测组采用分子预测法对常用化疗药物进行分子检测,并根据结果选择敏感性高及毒副作用低的药物进行化疗;常规组采用常规化疗。结果：TEC方案化疗的粒细胞减少以及呕吐发生率在检测组明显低于常规组（P＜0.05）,CEF-T/EC-T（H）方案化疗的粒细胞减少发生率在检测组明显低于常规组（P＜0.05）。结论：根据分子检测选择的化疗方案的毒副反应明显低于常规化疗,但药物敏感性是否带来有效性的提高而产生生存获益,尚需更长时间的随访。