诺维本持续静脉输注联合顺铂治疗转移性乳腺癌临床观察

目的 探索诺维本不同用药方法联合顺铂治疗转移性乳腺癌的疗效和不良反应。方法 对６７例转移性乳腺癌采用随机分组，其中４２例予诺维本持续静脉输注联合顺铂（Ａ组），２５例予诺维本常规静脉冲入联合顺铂（Ｂ组）。结果 Ａ组有效率（ＣＲ＋ＰＲ）４７．６２％。Ｂ组有效率（ＣＲ＋ＰＲ）４０．０％，毒副反应Ａ组明显低于Ｂ组。结论 诺维本持续静脉输注较常规静脉冲入联合顺铂治疗转移性乳腺癌疗效有所提高，毒副反应明显减轻。     

诺维本持续静脉输注联合顺铂治疗晚期乳腺癌的临床观察与护理

探讨诺维本（NVB）持续静脉输注（CIV）联合顺铂（PDD）治疗晚期乳腺癌的观察和护理。方法 对16例晚期乳腺癌经锁骨下静脉穿刺置管处行NP方案化疗2个周期。化疗期间除密切观察化疗反应外，重点是锁穿护理和微泵的使用及观察。结果 全组病例总有效率为43．75％，中位 绘解期6个月，中位生存期16个月。白细胞下降占43．75％，无Ⅳ度毒性，静脉炎发生率及严重程度明显下降。结论 诺维本持续静脉输联合顺铂治疗晚期乳腺癌具有疗效好、副作用小的优点，护理措施的改进也给这一新方案的应用带来了方便。     

长春瑞宾联合顺铂二线治疗复发转移性乳腺癌

目的 探索长春瑞宾联合顺铂二线化疗方案对复发转移性乳腺癌的疗效和安全性。方法 采用NP方案即长春瑞宾(NVB)25mg／m^2，iv，d1，8；顺铂(DDP)80mg/m^2，iv，d1；作为二线方案治疗经病理和(或)细胞学诊断的35例晚期乳腺癌，22例曾用含阿霉素方案化疗，经治疗后复发或进展。结果 可评价疗效的35例中，无CR(完全缓解)、PR(部分缓解)22例，SD(稳定)8例，PD(进展)5例，有效率62．8％；中位生存期18个月；1年生存率68．6％。化疗的不良反应主要是血液学毒性，但患者可以耐受。结论 NVB联合DDP用于二线化疗方案治疗复发转移性乳腺癌临床有效，患者耐受性尚可。     

诺维本持续静脉输注联合顺铂治疗转移性乳腺癌临床观察

目的　探索诺维本不同用药方法联合顺铂治疗转移性乳腺癌的疗效和不良反应。方法　对 67例转移性乳腺癌采用随机分组 ,其中 42例予诺维本持续静脉输注联合顺铂 (A组 ) ,2 5例予诺维本常规静脉冲入联合顺铂 (B组 )。结果　A组有效率 (CR PR)47 62 % ,B组有效率 (CR PR) 40 .0 %。毒副反应A组明显低于B组。结论　诺维本持续静脉输注较常规静脉冲入联合顺铂治疗转移性乳腺癌疗效有所提高 ,毒副反应明显减轻。     

长春瑞滨联合顺铂治疗晚期乳腺癌的临床观察

目的：观察长春瑞滨(NVB)和顺铂(DDP)联合化疗治疗晚期乳腺癌的疗效及毒性。方法：40例转移性乳腺癌患者，以往均接受过含阿霉素和氟脲嘧啶的化疗方案。NVB25mg／m^2快速静脉滴入，dl、d8；DDP25-30mg／m^2，静脉滴入，dl、d2、d3，每2ld为l周期，在用2周期后评价疗效。结果：完全缓解3例，部分缓解16例，有效率为47．5％。毒副作用主要为血液学毒性、消化道反应、脱发、静脉炎。白细胞下降为95％，其中Ⅲ—Ⅳ级为55％。结论：NVB联合DDP治疗晚期难治性乳腺癌疗效好，毒副反应可耐受，值得临床进一步推广使用。     

诺维本持续静脉输注联合顺铂治疗晚期乳腺癌的临床观察与护理

目的　探讨诺维本 (NVB)持续静脉输注 (CIV)联合顺铂 (PDD)治疗晚期乳腺癌的观察和护理。方法　对 16例晚期乳腺癌经锁骨下静脉穿刺置管处行NP方案化疗 2个周期 ,化疗期间除密切观察化疗反应外 ,重点是锁穿护理和微泵的使用及观察。结果　全组病例总有效率为 43 75 % ,中位缓解期 6个月 ,中位生存期 16个月。白细胞下降占 43 75 % ,无Ⅳ度毒性 ,静脉炎发生率及严重程度明显下降。结论　诺维本持续静脉输注联合顺铂治疗晚期乳腺癌具有疗效好、副作用小的优点 ,护理措施的改进也给这一新方案的应用带来了方便     

诺维本联合顺铂治疗阿霉素类药物耐药性的晚期乳腺癌的疗效

目的：观察诺维本(Navelbine，NVB)联合顺铂(DDP)治疗阿霉素耐药性的晚期乳腺癌疗效及毒副反应。方法：对36例乳腺癌术后复发转移者，且全部为阿霉素治疗后转移或复发的晚期乳腺癌患者。NVB 25mg／m^2。静脉滴人。d1、d8；DDP30mg／m^2静脉滴入。第d1～d3。21天为1周期，全组化疗共90周期，中位数2．5周期(2～4周期)。结果：36例患者中有效率为61．1％(22／36)，CR4例，PR18例，SD10例。PD4例。主要毒性为骨髓抑制。以白细胞减少为主。其发生率为88．9％。本组绝大多数经锁骨下静脉置管给药，故静脉炎的发生率很低，其他毒性轻微。结论：NVB DDP治疗阿霉素类药物耐药性的晚期乳腺癌疗效较好，且毒性可以耐受，值得临床推广应用。     

去甲长春花碱联合顺铂治疗转移性乳腺癌

目的：观察去甲长春花碱（vinorelbine,NVB)联合顺铂（cisplatin,DDP)治疗转移性乳腺癌的疗效及不良反应,方法：采用NVB25mfg/m^2d1.8DDP30mg/m^2d1-3,每3周重复一次,共用2－4周期。结果：40例患者中有效率45％（18／40）,CR2．5％（1／40）,PR42．5％（17／40）,主要剂量限制不良反应是白细胞减少（Ⅲ、Ⅳ度27．5％）,结论：NVB联合DDP治疗转移性乳腺癌有较好的疗效,且阿霉素和／或泰素治疗失败的患者亦有较好的疗效,不良反应中耐受。     

NP方案时辰化疗治疗晚期恶性肿瘤40例分析

[目的]观察国产长春瑞滨(NVB)联合顺铂(PDD)时辰化疗治疗晚期恶性肿瘤的疗效和毒副反应。[方法]中心静脉置管,NVB10mg加入生理盐水40ml缓慢静脉推注,d1,NVB10mg,22∶00～10∶00持续12h输注,d1～5;PDD20mg,10∶00～22∶00,持续12h输注,d1～5,21d为1个周期,2个周期后评价疗效。[结果]全组40例,CR2例,PR16例,总有效率45.0%;主要毒副反应为骨髓抑制和消化道反应,Ⅲ～Ⅳ度白细胞下降为30.0%,Ⅲ～Ⅳ度消化道反应为25.0%。[结论]NP方案时辰化疗治疗晚期恶性肿瘤近期疗效好,不良反应轻,耐受性好,值得临床进一步研究。     

长春瑞滨联合顺铂治疗晚期乳腺癌

目的：观察长春瑞滨（NVB）联合顺铂（DDP）治疗晚期转移性乳腺癌的疗效及不良反应.方法：41例乳腺癌术后复发转移者,既往接受过术后辅助化疗,化疗采用NVB 25mg/m2,d1,8,DDP 60-80mg/m2,分3天输注d2-4,每3周为1周期,至少用4个周期.结果：41例患者均可评价疗效,有效率（RR）为53.7%（22/41）,疾病控制率（DCR）为73.2%（30/41）,其中CR 2例,PR 20例,SD 8例,PD 11例,TTP 8.6个月,OS 24个月.主要不良反应为骨髓抑制和消化道反应,Ⅲ-Ⅳ度白血胞下降发生率为26.8%,无血小板下降者,Ⅲ-Ⅳ度恶心、呕吐发生率为14.6%,无肾功能损伤者,肝功Ⅱ度异常者9.8%,无Ⅲ-Ⅳ度者.结论：NVB联合DDP治疗晚期转移性乳腺癌有较好疗效,且对蒽环类和/或紫杉类治疗失败的患者亦有较好疗效,不良反应轻,耐受性好,可作为治疗复发转移性乳腺癌的解救方案.     

体内诱导艾氏腹水瘤细胞的耐药性研究

肿瘤细胞耐药性的存在是临床化疗失败的主要原因之一。本实验在小鼠体内用阿霉素（ADR）诱导艾氏腹水瘤细胞（EHR）的耐药性，探讨细胞产生耐药性的机理。HPLC法测定细胞内药物浓度．结果表明耐药细胞─—EHR/ADR细胞内ADR积聚低于EHR细胞，而对ADR外排快于EHR细胞；异博定（VER）增加EHR／ADR细胞对ADR的摄取并阻滞其外排．而对EHR影响不大，揭示EHR／ADR细胞具有MDR特性。     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜癌的临床观察

目的 分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery, CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）治疗腹膜癌（peritoneal carcinoma, PC）的围手术期安全性及疗效。 方法 PC患者行CRS+HIPEC治疗,药物为洛铂50 mg/m2、多西他赛60 mg/m²,加入12 000 ml 0.9%氯化钠溶液加热至（43±0.5）℃持续灌注60 min。记录术后6天体温和心率变化、围手术期不良事件、血常规及血生化指标、术后患者恢复情况及生存结果。结果 90例PC患者行95次CRS+HIPEC,手术时间180~450 min (中位数485 min）;术后6天最高体温、心率分别为36.4℃~38.6℃（中位数37.5℃）、76~124 bpm（中位数100 bpm）,严重不良事件16例,包括围手术期死亡2例。中位生存期20.8月（95%CI: 13.1~25.8月）,1、3、5年生存率分别为75.6%、45.6%、43.3%。 结论 洛铂联合多西他赛进行CRS+HIPEC治疗PC安全性可接受,有助于延长患者生存期。     

两种不同方案治疗晚期非小细胞肺癌的疗效比较(英文)

Objective: The aim of this study was to analyze and compare the recent efficacy and toxicity of a three-drug platinum-based regimen (A regimen): [cisplatin (DDP) + gemcitabine (GEM) + vinorelbine (NVB)] and a two-drug combination without a platinum drug (B regimen): GEM + NVB, which were used to treat 55 advanced non-small cell lung cancer (NSCLC) patients, in a bid to provide a guidance for clinical treatment. Methods: Twenty-four cases of advanced NSCLC (stage III-IV) patients were treated with A regimen ...     

参麦注射液对阿霉素所致大鼠心肌损伤保护作用的实验研究

目的　观察参麦注射液 (SMI)对阿霉素 (ADM )诱导大鼠心肌损伤的保护作用和抗氧化作用。方法　选用ADM诱导大鼠心肌损伤模型。SD大鼠 60只 ,随机分为 3个组 ,每组 2 0只 ,分别为正常组、治疗组、对照组。正常组 :实验第 1～ 9天注射生理盐水 ,每天 3ml/kg ,1次 /天。治疗组 :实验第 1～ 9天注射参麦注射液 ,每天 3ml/kg ,1次 /天 ,第 4天注射阿霉素 ,隔天 1次 ,连用 3次 ,用生理盐水配置成 1mg/ml,每次 3mg/kg。对照组实验 1～ 9天注射生理盐水 ,每天 3ml/kg ,1次 /天。第 4天注射阿霉素 ,以后隔天 1次 ,连用 3次 ,用生理盐水配置成 1mg/ml,每次 3mg/kg。到期测定血丙二醛 (MDA )含量和超氧化物歧化酶(SOD )活性 ,并进行心肌病理检查。结果　对照组MDA水平明显高于治疗组 ,对照组SOD水平则显著低于治疗组 ,即加用SMI可提高SOD活性 ,降低MDA含量。SMI能明显减轻大鼠心肌损伤 ,对照组与治疗组比较 ,治疗组心肌损伤明显减轻 ,治疗组与正常组比较无显著性差异。参麦注射液有抗氧化作用 ,与对照组比较 ,血SOD水平升高 ,MDA水平降低 ,心肌病理计分下降。结论参麦注射液有抗氧化作用和对阿霉素所引起的心脏毒性具有保护作用 ,为临床寻找有效的阿霉素所致心肌损伤保护药物提供良好的客观依据 ,值得临床推广应用     

Suppression of NAD(P)H-quinone oxidoreductase 1 enhanced the susceptibility of cholangiocarcinoma cells to chemotherapeutic agents

Background

Cholangiocarcinoma (CCA) is highly resistant to most of the known chemotherapeutic treatments. NAD(P)H-quinone oxidoreductase 1 (NQO1) is an antioxidant/detoxifying enzyme recently recognized as an important contributor to chemoresistance in some human cancers. However, the contribution of NQO1 to chemotherapy resistance in CCA is unknown.

Methods

Two CCA cell lines, KKU-100 and KKU-M214, with high and low NQO1 expression levels, respectively, were used to evaluate the sensitivity to chemotherapeutic agents; 5-fluorouracil (5-FU), doxorubicin (Doxo), and gemcitabine (Gem). NQO1 and/or p53 expression in KKU-100 cells were knocked down by siRNA. NQO1 was over-expressed in KKU-M214 cells by transfection with pCMV6-XL5-NQO1 expression vector. CCA cells with modulated NQO1 and/or p53 expression were treated with chemotherapeutic agents, and the cytotoxicity was assessed by SRB assay. The mechanism of enhanced chemosensitivity was evaluated by Western blot analysis.

Results

When NQO1 was knocked down, KKU-100 cells became more susceptible to all chemotherapeutic agents. Conversely, with over-expression of NQO1 made KKU-M214 cells more resistant to chemotherapeutic agents. Western blot analysis suggested that enhanced chemosensitivity was probably due to the activation of p53-mediated cell death. Enhanced susceptibility to chemotherapeutic agents by NQO1 silencing was abolished by knockdown of p53.

Conclusions

These results suggest that inhibition of NQO1 could enhance the susceptibility of CCA to an array of chemotherapeutic agents.     

鼻咽癌患者放射性骨坏死引起的正电子显像假阳性结果1例及文献复习

目的:探讨鼻咽癌(NPC)患者放射性骨坏死(osteoradionecrosis,ORN)引起正电子假阳性结果的原因及避免因此引发诊断错误的方法。方法:回顾性分析1例放疗后的鼻咽癌患者,行鼻咽部MRI及正电子显像后,再行组织病理学检查,对三种结果进行分析、比较。结果:MRI及正电子显像均诊断患者颅底区域肿瘤复发,组织病理学结果则显示鼻咽部病灶为放射性骨坏死。因此正电子扫描结果为假阳性结果。结论:鼻咽癌患者放疗后所致的放射性骨坏死容易引起正电子显像假阳性结果并可能引发不必要的治疗,因此NPC患者的正电子图像,对于可能的局限性肿瘤复发诊断,应该非常慎重。     

Proficiency of DNA repair genes and microsatellite instability in operated colorectal cancer patients with clinical suspicion of lynch syndrome

Background

Lynch syndrome (LS) diagnosis is underestimated, and most of the patients remain undetected after colorectal resections. The study aims to assess the frequency of LS in patients undergoing surgical treatment for colorectal cancer (CRC).

Methods

A total of 458 CRC patients were operated from January 2005 to December 2008. Positive CRC family history (FH) was present in 118 (25.8%) patients. Histologic sections were reviewed for microsatellite instability (MSI) criteria (Bethesda guidelines), immunohistochemical (IHC) analysis for MLH1, MSH2, MSH6, PMS2 proteins, through the avidin-biotin-peroxidase complex, MSI (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) and BRAF somatic mutation.

Results

Of the 118 patients with FH, 61 (51.69%) met at least one of the revised Bethesda criteria. IHC was abnormal in 8 (13.1%) and MSI in 12 patients (20%). BRAF was negative in all cases. MSI histopathological included: intratumoral lymphocytes (47.5%), expansive tumors (29.5%) mucinous component (27.8%) and Crohn’s like reaction in (14.7%). There was an association between the revised Bethesda criteria with: sex, mucinous histology and Crohn’s like reaction; MSI and IHC with PMS2 and MLH1. Revised Bethesda criteria 4 had 10.6 increased chances to display positive MSI. We have proposed a score to contribute as a practical tool in the diagnosis of LS.

Conclusions

The frequence of LS in resected CRC patients was 2.6%. The criterion 4 Revised Bethesda was associated more strongly with the presence of MSI.     

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.     

Marked radiosensitization of cells in culture to X ray by 5-chlorodeoxycytidine coadministered with tetrahydrouridine, and inhibitors of pyrimidine biosynthesis

Our approach to overcome the problem of rapid catabolism and general toxicity encountered with 5-halogenated analogues of deoxyuridine (5-bromo, chloro or iododeoxyuridine), which has limited their use as tumor radiosensitizers, is to utilize 5-chlorodeoxycytidine (CldC) with tetrahydrouridine (H4U). We propose that CldC, coadministered with H4U, is metabolized in the following manner: CldC----CldCMP----CldUMP---- ----CldUTP----DNA. All the enzymes of this pathway are elevated in many human malignant tumors and in HEp-2 cells. In X irradiation studies with HEp-2 cells, limited to 1 or 2 radiation doses, we have obtained 3.0 to 3.8 apparent dose enhancement ratios (these represent upper limits) when cells are preincubated with inhibitors of pyrimidine biosynthesis: N-(Phosphonacetyl)-L-aspartate (PALA) and 5-fluorodeoxyuridine (FdU) or 5-fluorodeoxycytidine (FdC) + H4U. Optimum conditions for radiosensitization are: PALA (0.1 mg/ml) 18-20 hr prior to FdU (0.1 microM) or FdC (0.02 microM) + H4U (0.1 mM) followed 6 hr later by CldC (0.1-0.2 mM) + H4U (0.1 mM) for 56-68 hr. Viabilities of 10 +/- 4% to 15 +/- 1% (+/- S.E.) were obtained for drug-treated unirradiated cells. Enzymatic studies indicate that this toxicity may be tumor selective. CldC + H4U alone (at these concentrations) results in 20% substitution of CldU for thymidine in DNA (determined by HPLC analysis). Preliminary toxicity studies indicate that mice will tolerate treatment protocols involving a single dose of PALA (200 mg/kg) followed by a dose of FdU (50 mg/kg) and 3 cycles of CldC (500 mg/kg) + H4U (100 mg/kg) at 10 hour intervals, with marginal weight loss (4%). In this approach we seek to obtain preferential conversion of CldC to CldUTP at the tumor site by taking advantage of quantitative differences in enzyme levels between tumors and normal tissues.     

蛋白激酶C的下调与KBV200细胞多药耐药性的关系

目的　探讨蛋白激酶C (PKC)在肿瘤多药耐药 (MDR)中的作用。方法　3 2 P掺入法测定PKC的活性 ;Westernblot法检测KBV2 0 0细胞株PKC亚型的表达和亚细胞分布 ;实验组用十字孢碱 (SP)预孵育KBV2 0 0细胞 ;MTT法检测耐药株KBV2 0 0细胞的耐药性。结果　SP可下调膜组分和浆组分的PKC活性及总活性 ;使PKCα膜组分和浆组分的表达均降低 ,PKCβ的膜组分消失 ,浆组分PKCβ的表达稍增强 ,PKCε的膜组分和浆组分表达无变化 ;SP可降低VCR、ADR对KBV2 0 0细胞的IC50 值 (P <0 0 1)。结论　SP使KBV2 0 0细胞耐药性降低 ,可能与下调PKC有关。