不同化疗方案对MCF-7乳腺癌荷瘤裸鼠的抑瘤作用及对PCNA表达的影响

背景与目的：随着规范化化疗在临床推广，化疗疗效正稳步提高，但仍无法实现真正意义上的个体化化疗。本研究通过研究不同化疗方案对乳腺癌荷瘤裸鼠的抑瘤作用及瘤组织中增殖细胞核抗原（PCNA）表达的影响，探讨PCNA在评价乳腺癌化疗效果及选择化疗方案的意义。方法：①制备MCF-7细胞系移植性乳腺癌裸鼠模型；②不同化疗方案化疗后监测裸鼠体重和肿瘤体积的变化情况，计算抑瘤率；③观察肿瘤病理组织学变化，并用免疫组化和流式细胞术检测PCNA表达情况。结果：①荷瘤裸鼠体重、瘤重和抑瘤率：2／3LD10剂量各化疗组裸鼠体重和瘤重均显著低于对照组（P〈0．05），抑瘤率分别为83．1％、75。5％、84。6％、87．9％、91．0％。提示2／3LD10剂量化疗组可较准确反应化疗药物的联合作用和对裸鼠的影响，故选择2／3LD10剂量化疗组进入后续的研究。②PCNA表达：免疫组化：各化疗组PCNA表达均显著低于对照组（P〈0．05），且NP组显著低于CMF、CAF、TP和Xeloda组（P〈0．05），TP、Xeloda组显著低于CMF、CAF组（P〈0．05）；流式细胞术：各化疗组PCNA表达较对照组显著下降（P〈0．05），且TP和Xeloda组显著低于cMF、CAF组（P〈0．05），NP组显著低于cMF组（P〈0．05）。③PCNA表达与病理学疗效分级呈显著正相关（r=0．540，P〈0．05）。结论：联合化疗对荷瘤裸鼠的抑瘤作用明显，并可降低乳腺癌组织中的PCNA表达；PCNA表达水平可作为判断乳腺癌化疗效果的评价指标，且可为临床制定方案提供参考。     

可手术乳腺癌新辅助化疗364例临床分析

目的：探讨新辅助化疗对可手术乳腺癌的治疗作用、方案、周期数以及生物学指标与疗效的关系。方法：364例新辅助化疗的乳腺癌患者，治疗前肿瘤穿刺活检或术后标本均检测生物学指标ER、PR、C-erbB-2、Ki-67、p53。患者采用FAC、TE、NP方案化疗，每3～4周1次，共1～4个周期，化疗结束后10～14天手术。疗效按UICC实体瘤疗效评定标准进行评价，并统计患者5年生存率。结果：TE方案有效率及病理缓解率高于FAC方案及NP方案（P〈0．05），其5年生存率也高于后两方案（P〈0．05）；新辅助化疗2周期以上的有效率高于2个周期（P〈0．05），但平均生存时间无显著差异（P〉0．05）；C-erbB-2阴性、p53阳性、ER／PR阴性患者的有效率高（P〈0．05）；Ki-67表达结果不影响治疗的有效率（P〉0．05）；以上生物学指标表达的不同情况5年生存率之间无显著差异（P〉0．05）。结论：可手术乳腺癌术前应给予2个周期以上TE方案化疗；生物学指标中C-erbB-2阴性、p53阳性、ER／PR阴性的患者有效率高。     

乳腺癌的TECIA法药敏试验及其临床应用价值

目的探讨组织培养-终点染色计算机图像分析（TECIA）法体外肿瘤药敏试验对乳腺癌化疗的临床应用价值。方法选取2005年9月至2008年9月本院手术的46例乳腺癌标本,采用TECIA法进行化疗药物敏感性的体外检测。所测药物为乳腺癌常用化疗药物紫杉醇（PTX）、诺维本（NVB）、多柔比星（ADM）、氨甲喋呤（MTX）、5-氟脲嘧啶（5-FU）、顺铂（DDP）及联合化疗TA（PTX＋ADM）、NP（NVB＋DDP）、CAF（CTX＋ADM＋5-FU）、CMF（CTx＋MTX＋5-FU）方案。化疗药物敏感性差异的比较,采用多个样本率的χ^2检验。结果46例乳腺癌对化疗药物的敏感性为：PTX60．9％（28／46）、NVB58．7％（27／46）、ADM56．5％（27／46）、MTX37．0％（17／46）、5-FU 34．8％（16／46）、DDP26．1％（12／46）;PTX、NVB、ADM、MTX之间及5-FU和DDP之间比较,敏感率差异均无统计学意义（χ^2=6．724,P=0．081;χ^2=0．821,P=0．365）,PTX、NVB比5-FU、DDP的敏感率高,其差异有统计学意义（P〈0．003）;TA、NP、CAF和CMF方案的敏感率分别为71．7％（33／46）、67．4％（31／46）、45．7%（21／46）、39．1％（18／46）,但TA与NP方案、CAF与CMF方案比较,差异无统计学意义（P〉0．007）;TA和NP方案比CAF和CMF方案的敏感率高,其差异有统计学意义（P〈0．007）。PTX、NVB及含有此类药物的联合化疗方案的敏感性较高,化疗药物敏感性存在个体差异。结论TECIA法体外肿瘤药敏试验在乳腺癌的化疗用药方面具有指导意义。     

SODD和Bcl-2蛋白表达在儿童急性白血病中的意义及相关性探讨

目的：探讨儿童急性白血病（AL）骨髓细胞中SODD、Bcl-2蛋白的表达及其与AL的分型、临床特征、疗效、预后的关系。方法：采用免疫组化SABC法检测86例AL患儿骨髓细胞SODD、Bcl-2蛋白表达情况。结果：初治组、难治复发组及完全缓解组SODD与Bcl-2蛋白阳性表达率明显高于对照组，差异有显著性（P〈0．05）。SODD、Bcl-2蛋白表达在ALL与ANLL间无显著差异（t=1．874，t=1．583．P〉0．05）；经化疗，完全缓解组SODD、Bcl-2阳性表达率均低于初治组，差异有显著性（t=2．054，t=2．703，P〈0．05）；难治复发组SODD蛋白表达显著高于初治组（t=-1．081，P〈0．05），Bcl-2蛋白在初治组及难治复发组均高表达，差异无显著性（t=-1．196，P〉0．05），但难治复发组Bcl-2阳性细胞百分率（45％-87％）显著高于初治组（5％-62％）；等级相关分析显示SODD和Bcl-2蛋白表达呈显著正相关（P〈0．01．r=-0．726），经统计学分析，SODD及Bcl-2阴性表达者完全缓解率均高于阳性表达者，差异有显著性（P〈0．05）。结论：SODD、Bcl-2均与AL的发生、发展、疗效及预后密切相关、且两者在AL的发生、发展过程有一定的协同作用。     

环磷酰胺、阿霉素、5-氟尿嘧啶方案与紫杉醇、顺铂方案治疗晚期乳腺癌的疗效比较

背景及目的：环磷酰胺、阿霉素、5－氟尿嘧啶方案（CAF方案）和紫杉醇、顺铂方案（TP方案）均是治疗晚期乳腺癌的有效方案,但TP方案给药复杂,我们对两组晚期乳腺癌病例进行回顾性分析。比较CAF方案及TP方案治疗晚期乳腺癌的客观疗效和不良反应。方法：经病理检查证实的晚期乳腺癌患者117例,按不同治疗方案分为CAF组和TP组,两组病例特征具可比性（P＞0．05）,CAF组（66例）：环磷酰胺600mg/m^2,静脉推注,第1天;5－氟尿嘧啶600mg/m^2,静脉滴注,第1、8天,阿霉素60mg/m^2,静脉推注,第1天,TP组（51例）,紫杉醇135mg/m^2,静脉滴注3h,第1天,顺铂60mg/m^2,静脉滴注,第2、3天,两组均以3周为1个疗程,至少接受2个疗程化疗。结果：CAF组初治病例有效率54．8％（17／31）,复治病例有效率31．4％（11／35）,总有效率42．4％（28／66）,TP组分别为62．5％（15／24）,59．3％（16／27）,60．8％（31／51）。两组初治病例有效率差异无统计学意义（P＞0．05,X2检测）,复治病例有效率及总有效率差异有统计学意义（P＜0．05,X2检验）,CAF组中位无进展时间7．8个月（95％可信区间（confidence interval,VI)为5．3－10．8个月）,中位生存时间17．8个月（95％CI为13．3－22．5个月）TP组分别为8．6个月（95％CI为6．5－12个月）和19个月,（95％CI为15－25．5个月）,两组差异均无统计学意义（P＞0．05,Log-rank检验）。腹泻的发生率在CAF组明显高于TP组,而肌痛,皮疹及周围神经毒性等不良反应的发生率在TP组则明显高于CAF组,差异均有统计学意义（P＜0．05）,秩和检验）,其余不良反应的发生率相近,所有不良反应均能耐受。结论：CAF方案疗效较好,可作为晚期乳腺癌首选治疗方案在临床应用。     

局部晚期乳腺癌新辅助化疗疗效观察

目的比较3组不同化疗方案在局部晚期乳腺癌新辅助化疗中的疗效及毒副反应。方法90例Ⅱ、Ⅲ期乳腺癌随机分为2组，每组45例。A组应用CAF方案（环磷酰胺＋吡柔比星＋5-氟脲嘧啶），B组用TA方案（多西他赛＋吡柔比星）新辅助化疗。完成2个周期新辅助化疗后评价疗效。结果A组总有效率为55．6％，B组的总有效率为82．3％，差异有统计学意义（P〈0．05）。2组胃肠反应相似，A组发生率为84．4％，B组发生率为88．9％，差异无统计学意义（P〉0．05）。B组骨髓抑制和脱发发生率分别为92．3％和84．4％，明显高于A组的73．3％和53．3％，差异有统计学意义（P〈0．05）。结论2组新辅助化疗方案对乳腺癌治疗均有效，毒副反应均可耐受。TA组疗效及毒副反应均高于CAF组。     

乳腺癌新辅助化疗中MCM7和C—erbB-2的表达及其临床意义

目的：探讨乳腺癌新辅助化疗前后MCM7和C—erbB-2蛋白的表达状况,分析其与化疗疗效的关系。方法：采用免疫组化法检测55例乳腺癌新辅助化疗前后标本中MCM7和C—erbB-2的表达。结果：新辅助化疗有效率为76．4％。化疗前MCM7蛋白阳性表达显著高于化疗后（P〈0．01）,而化疗前后C—erbB-2蛋白阳性表达差异无显著性（P〉0．05）。化疗有效组（42例）MCM7蛋白阳性表达显著高于无效组（13例）（P〈0．01）,而化疗有效组C—erbB-2蛋白阳性表达显著低于无效组（P〈0．01）。结论：ET方案新辅助化疗有较好的疗效,可能通过抑制MCM7蛋白表达来阻止乳腺癌细胞的增殖。MCM7高表达,C—erbB-2阴性者化疗更为敏感,二者可作为临床指导乳腺癌化疗并预测化疗敏感性的分子生物学指标。     

化学治疗对乳腺癌转移患者疼痛的治疗效果

目的探讨化学治疗对乳腺癌转移患者疼痛的治疗效果。方法对37例伴有中度和重度疼痛的乳腺癌转移患者分别采用CMF、CAF或TA（泰素、阿霉素）等方案化疗并评价镇痛疗效。结果37例中21例（56．8％）疼痛完全缓解，16例（43．2％）疼痛部分缓解，总疼痛缓解率100．0％。肿瘤PR13例中疼痛完全缓解11例（84．6％），而肿瘤SD24例中10例疼痛完全缓解（41．7％），肿瘤PR与肿瘤SD者的疼痛完全缓解率比较有显著差异（x^2=6．33，P〈0．05）。结论化疗对乳腺癌转移患者的疼痛治疗有显著疗效，化疗镇痛作用与肿瘤客观疗效密切相关，化疗应成为乳腺癌转移患者疼痛的首选治疗。     

红霉素逆转乳腺癌多药耐药的临床研究

目的：研究红霉素逆转乳腺癌多药耐药（MDR）的临床疗效，方法：采用免疫组化SP法检测乳腺癌P－糖蛋白（P-gp)表达，将P-gp表达阳性者随机分两组：红霉素加化疗组（试验组）28例，单纯化疗组（对照组）14例，采用CAF方案化疗，结果：试验组CR＋PR 19例（67．9％），对照组4例（28．6％），两组比较差异有显著性（P＜0．05），结论：红霉素对逆转乳腺癌MDR具有一定的作用。     

术前化疗与乳腺癌多药耐药的关系

目的：了解可手术的乳腺癌对术前化疗的反应性以及与多药耐药的关系，探讨其机制。方法：将80例Ⅱ期乳腺癌患者随机分为2组，即术前未化疗组和CMF方案化疗组；分别观察其多药耐药基因蛋白（P－gp)的表达情况及与化疗反应的关系，并观察肿瘤体外药敏试验的耐药情况。结果：本组化疗部分缓解和轻度缓解分别为12／40（30．0％）、21／40（52．5％）；未化疗组P－gp表达率为22．5％，经化疗后表达率明显升高（P＜0．05）；对化疗有较好反应的肿瘤，其P－gp多为阳性表达。体外药敏试验显示化疗后肿瘤细胞对长春碱类及蒽环类的耐药比率明显增加（P＜0．05）。结论：术前CMF方案化疗有一定疗效，经化疗后残留癌细胞的P－gp表达增加，可能出现交叉耐药性，术后可参考药敏试验选择化疗药物。     

不同化疗方案对MCF-7乳腺癌荷瘤裸鼠的抑瘤作用及对PCNA表达的影响

Objective: To investigate the antitumor activity of different combination regimens to human breast cancer xenograft (MCF-7) transplanted in nude mice and the effects on the expression of PCNA, and to evaluate the value of PCNA as predictive factor for the response of chemotherapy and individualized treatment. Methods: (1) 88 nude mice models of human breast cancer xenograft (MCF-7) were established, and then were randomly divided into control group and 10 chemotherapy groups (each group, n = 8). Among them, the mice of 5 chemotherapy groups were treated intraperitoneally/orally by 5 combination chemotherapy regimens (CMF, CAF, NP, TP, Xeloda) respectively at 1/3 LD10 dosage schedule (dose lethal to 10%of the mice), and that in another 5 chemotherapy groups were treated at 2/3 LD10 dosage schedule. Control animals were administered intraperitoneally with normal saline. (2) The body weight of nude mice and transplanted tumor growth were observed and recorded, then inhibition rate of tumor growth was calculated. (3) The pathological features of transplanted tumor were studied under microscope. The expression of proliferating cell nuclear antigen (PCNA) was comparatively studied in chemotherapy group and control group by SP immunohistochemical method and flow cytometry analysis. Results: (1) Body weight, tumor weight and inhibition rate of tumor growth of athymic mice bearing cancer: Body weights and tumor weights of nude mice in every 2/3 LD10 chemotherapy group were significantly lower than those of the control group (P ＜ 0.05), and the inhibition rates of tumor growth were 83.1%, 75.5%, 84.6%, 87.9% and 91.0%, respectively. Body weights of athymic mice in every 1/3 LD10 chemotherapy group were lower than that of the control (P ＜ 0.05). The results showed that the 2/3 LD10chemotherapy groups could reflect the effect of combination chemotherapy on the nude mice and the clinical dependability was better. So the data of 2/3 LD10 chemotherapy groups were appropriated for successive study. (2) Immunohistochemical studies: The expressions of PCNA in every chemotherapy group were significantly lower than that of the control (P ＜ 0.05).Moreover, the expression of PCNA in NP group was significantly lower than those of CMF, CAF, TP and Xeloda groups (P ＜0.05), while the expressions of TP and Xeloda groups were significantly lower than those of CMF and CAF groups (P ＜ 0.05).(3) FCM analysis: FI values of PCNA in every chemotherapy group were significantly lower than that of the control (P ＜ 0.05).FI values of PCNA in TP and Xeloda groups were significantly lower than those of CMF and CAF groups (P ＜ 0.05), while the value of NP group was significantly lower than that of CMF group (P ＜ 0.05). (4) Relationship between PCNA expression and pathologic response: The expression of PCNA was significantly correlated with pathological therapeutic response of transplanted breast carcinoma (P = 0.001). Conclusion: In vivo chemosensitivity testing with 2/3 LD10 dosage combinations in nude mice bearing cancer can reflect the effects of chemotherapeutics and affects of organism exactly. Various chemotherapy regimens all can decrease the expression of PCNA in breast cancer. The PCNA can be regarded as the factor to judge the response to chemotherapy, and it become possibly one of the prospective factors in the selection of chemotherapy regimen and play a rule in individualized therapy in the clinic.     

Bcl-2、C-erbB2和PCNA表达与乳腺癌新辅助治疗疗效关系的研究

目的探讨Bcl-2、C-erbB2和PCNA作为浸润性乳腺癌新辅助治疗预后指标的可行性。方法选择55例接受新辅助治疗的乳腺癌病例,空芯针穿刺标本及化疗后根治标本分别行S-P法免疫组织化学染色。所有病例均接受3~4周期含蒽环类化疗药的联合化疗,肿瘤缩小率用彩色多谱勒超声评估。结果术前化疗有效率(CR PR)为61.8%(34/55),完全缓解率(CR)为9.1%(5/55)。C-erbB2在分化较差、受体阴性病例中高表达(P<0.05)。CerbB2阴性病例肿瘤缩小明显,与C-erbB2表达阳性病例相比,差异有显著性(P<0.01)。PCNA在组织学高分级肿瘤中表达增高(P<0.05),化疗后PCNA表达减弱。Bcl-2表达在化疗前后及与各临床病理因素间比较中差异无显著性(P>0.05)。结论C-erbB2与PCNA可作为预测乳腺癌化疗疗效的有价值的指标。     

Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer--a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group. Danish Breast Cancer Cooperative Group (DBCG)

To evaluate the substitution of methotrexate with doxorubicin (Dox) in CMF-(cyclophosphamide, methotrexate, 5-fluorouracil) containing regimen for advanced breast cancer, 415 postmenopausal patients below the age of 66 years, na?ve to chemotherapy, were accrued from 1980 to 1984 and followed-up until 1995. They received tamoxifen 30 mg daily orally and by randomisation either 400 mg/m2, cyclophosphamide, 25 mg/m2 doxorubicin and 500 mg/m2 5-fluorouracil (CAF) or 40 mg/m2 methotrexate instead of Dox (CMF) intravenously (i.v.) days 1 + 8 repeated every 4 weeks. Dox was substituted by methotrexate at a cumulative dose of 550 mg/m2. Among 341 eligible patients the response rate and median time to progression was significantly in favour of CAF: 53% CAF versus 36% CMF (P = 0.002) and 11.8 months CAF versus 6.5 months CMF (P = 0.001). Median duration of response was 19.5 CAF versus 18.0 CMF months, and survival 20.8 CAF versus 17.4 CMF months (non-significant). The two regimens were equimyelotoxic. There were no treatment-related fatalities but 1 patient with congestive heart failure on CAF was reported. Nausea/vomiting, stomatitis and infections were modest in both groups, whilst alopecia was more common with CAF. Regression analysis showed that long recurrence free interval, good performance status, and no visceral involvement was significantly related to long-term survival, whilst the treatment regimen was not. It is concluded that in chemotherapy-na?ve patients with advanced breast cancer Dox-containing regimens are superior and remain the first choice of chemotherapy, especially in patients with visceral metastases, until newer drugs and combinations have been proven to be superior.     

长春瑞滨或紫杉醇联合顺铂治疗晚期乳腺癌的临床观察

目的观察长春瑞滨或紫杉醇联合顺铂治疗晚期乳腺癌的疗效和毒副反应。方法将200例晚期乳腺癌患者随机分为NP方案组和TP方案组2组,每组100例。NP方案组:长春瑞滨50 mg.d-1,d1,8;顺铂30 mg·m-2,d1～5。TP方案组:紫杉醇110～140 mg·m-2,d2;顺铂30 mg·m-2,d1～5。结果 NP方案组总有效率为61%,中位生存期为7.5个月;TP方案组总有效率为55%,中位生存期为7.2个月,比较差异均无统计学意义(P均>0.05)。结论 NP与TP方案治疗晚期乳腺癌疗效相当。     

Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. Cancer and Leukemia Group B

Three combination chemotherapy regimens each with or without the methanol-extracted residue of bacillus Calmette-Guérin (BCG) (MER) were compared for efficacy. After stratification for disease-free interval and dominant sites of disease, patients were randomized to either CMF (cyclophosphamide [CYC], 100 mg/m2 orally, days 1 through 14; methotrexate [MTX], 40 mg intravenously [IV], days 1 and 8; 5-fluorouracil [5-FU], 500 mg/m2 IV, days 1 and 8), or CAF (CYC, 100 mg/m2 orally, days 1 through 14; doxorubicin [DOX], 25 mg/m2 IV, days 1 and 8; 5-FU, 500 mg/m2 IV, days 1 and 8), or CAFVP (CAF as above plus vincristine [VCR], 1.0 mg/m2 IV, days 1 and 8; and prednisone [PRED], 40 mg/m2 orally, days 1 through 14). Nonspecific immunotherapy with MER was administered in five sites at 100 micrograms or at the lowest tenfold dilution that produced a 1-cm indurated lesion. A total of 432 patients were entered, but 37 were disqualified, leaving 395 evaluable for treatment results and toxicities. One hundred thirty-five evaluable patients were randomized to chemoimmunotherapy until October 28, 1978. One hundred twenty-six evaluable patients were randomized to chemotherapy alone in the same time period. For the entire study, a total of 260 evaluable patients were randomized to chemotherapy. Chemoimmunotherapy patients were compared with the initial 126 chemotherapy patients. Chemotherapy regimens were compared among all 260 patients. Patient characteristics were similar between regimens and between chemotherapy and chemoimmunotherapy treatment groups. For patients on chemotherapy plus MER, there was no significant differences between the regimens for response frequencies: 43%, 41%, and 32%, respectively for CMF, CAF, and CAFVP. The comparable chemotherapy alone group had 36%, 58%, and 63% response, respectively. The response rates, adjusted for chemotherapy regimen, were 52% and 38% (P = .02) for chemotherapy and chemoimmunotherapy, respectively. MER was associated with painful ulcers and fevers. Thus, MER produced toxicity without response or survival benefit and further randomization after October 28, 1978 was to chemotherapy alone. For 260 evaluable patients on chemotherapy alone, the complete (CR) and partial responses (PR) were 37%, 55%, and 58%, respectively for CMF, CAF, and CAFVP. These response rates for CAF and CAFVP were significantly better than CMF (P = .01 and P less than .01, respectively). These comparisons were consistent within subgroupings such as dominant sites of disease.(ABSTRACT TRUNCATED AT 400 WORDS)     

子宫内膜样腺癌中eIF3a的表达及意义

目的:检测子宫内膜样腺癌中翻译起始因子3a（eIF3a）的表达,分析其与细胞增殖、凋亡和K-ras基因突变的关系。方法:选择子宫内膜样腺癌患者共55例作为观察组,选择增生期子宫内膜组织55例作为对照组。应用免疫组化方法检测两组中eIF3a的表达以及观察组中Ki67、Bcl-2和BAX的表达。应用Western Blot法检测观察组中PCNA的表达。应用实时荧光定量PCR法检测观察组中K-ras基因突变的情况。结果:观察组中eIF3a 表达的阳性率明显高于对照组（P<0.05）,观察组中eIF3a 表达的阳性率在不同肿瘤最大径、不同浸润深度、有无淋巴脉管浸润、有无淋巴结转移和不同FIGO分期的分组中差别有统计学意义（P<0.05）,而与年龄、分化程度、是否宫颈间质浸润无明显相关性（P>0.05）。eIF3a表达的阳性率与生存时间有关（P<0.05）。相关分析显示eIF3a 与Ki67（r=0.52,P<0.05）、eIF3a与Bcl-2（r=0.47,P<0.05）、eIF3a与PCNA（r=0.59,P<0.05）均呈正相关性,eIF3a与BAX呈负相关性（r=-0.48,P<0.05）。eIF3a在不同K-ras基因突变的表达中差别有统计学意义（P<0.05）。结论:子宫内膜样腺癌中eIF3a 高表达是肿瘤形成的重要分子事件,参与病变的进展,eIF3a 可能对细胞增殖和细胞凋亡有一定的调控作用。eIF3a 的表达与K-ras基因突变有关。检测eIF3a的表达与子宫内膜样腺癌的预后有关。     

MAP2K6-FP和紫杉醇对上皮性卵巢癌裸鼠移植瘤的抑制作用

目的:研究靶向融合肽MAP2K6-FP（mitogen-activated protein kinase kinase 6-fusion protein)、紫杉醇单独和两者联合对上皮性卵巢癌裸鼠移植瘤的抑制作用。方法:建立卵巢癌HO8910细胞的裸鼠皮下移植瘤模型,分为空白对照组（予生理盐水 5 ml/kg腹腔注射治疗）、MAP2K6-FP组（予0.25 mg/kg MAP2K6-FP腹腔注射治疗）、紫杉醇组（予15 mg/kg 紫杉醇腹腔注射治疗）、联合用药组（予0.25 mg/kg MAP2K6-FP+15 mg/kg 紫杉醇腹腔注射治疗）,比较4组裸鼠的移植瘤生长速度、体积、裸鼠体质量;TUNEL法、免疫组织化学法和蛋白印迹法分别检测移植瘤中细胞凋亡情况、血管内皮生长因子（vascular endothelial growth factor,VEGF）、增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）的表达以及Bcl-2、Beclin 1蛋白的表达。结果:联合用药组裸鼠移植瘤体积（90 mm3）,小于MAP2K6-FP组（324 mm3）、紫杉醇组（215 mm3）和空白对照组（804 mm3）（P<0.05）。联合用药组肿瘤细胞的凋亡指数（apoptosis index,AI）(28.88±2.03)%,高于MAP2K6-FP组(14.36±0.56)%、紫杉醇组(15.78±0.87)%以及空白对照组(4.78±0.87)%（P<0.05）。联合用药组VEGF蛋白表达水平(0.14±0.06),低于MAP2K6-FP组(0.32±0.10)、紫杉醇组(0.29±0.08)及空白对照组(0.78±0.14）（P<0.01);联合用药组PCNA表达水平(18.4%),低于MAP2K6-FP组(32.3%)、紫杉醇组(29.8%)及空白对照组(81.4%）（P<0.05）。联合用药组Beclin 1/Bcl-2比例较单一用药组高(P<0.05)。结论:MAP2K6-FP联合紫杉醇能够显著抑制卵巢癌裸鼠移植瘤的生长,其机制可能与促进细胞凋亡有关。     

紫杉醇和顺铂方案与长春瑞滨和顺铂方案治疗晚期乳腺癌的疗效比较

为了观察紫杉醇和顺铂(DDP)方案(TP方案)与长春瑞滨和DDP方案(NP方案)治疗晚期乳腺癌的疗效和毒副反应,将98例晚期乳腺癌患者分为两组。TP方案组46例,PTX135～150mg/m2,d1;DDP25mg/m2,d1～d3。NP方案组52例,NVB40mg/d,d1、d8;DDP25mg/m2,d1～d3。结果:TP方案有效率54.3%(25/46),中位缓解期7.8个月;NP方案有效率48.1%(25/52),中位缓解期6.5个月。组间疗效及缓解期差异无统计学意义,P>0.05。主要毒副反应为骨髓抑制、消化道反应。脱发及关节肌肉疼痛在紫杉醇组明显,静脉炎在长春瑞滨组多见。初步研究结果提示,TP方案与NP方案对晚期乳腺癌疗效确切,毒副作用可耐受,组间疗效差异无统计学意义,均可作为晚期乳腺癌一线方案应用。     

CAF方案新辅助化疗对乳腺癌组织BCSG1蛋白表达的影响(英文)

目的探讨CAF联合化疗方案的新辅助化疗对乳腺癌组织BCSG1蛋白表达的影响。方法采用免疫组化SP法分别检测34例行CAF联合方案新辅助化疗患者(新辅助化疗组)和同期110例未行新辅助化疗患者(对照组)手术切除的乳腺癌组织BCSG1蛋白表达。同时对新辅助化疗组疗效进行病理形态学评价,并分析BCSG1蛋白表达与病理形态学变化的关系。结果新辅助化疗组化疗总有效率为79．4％。新辅助化疗组BCSG1蛋白高表达率明显低于对照组(29．4％比64．5％,P<0．01),化疗后部分缓解(Ⅱ级)病例BCSG1蛋白高表达水平明显低于无效(Ⅲ级)病病(P=0．002)。结论采用CAF方案新辅助化疗近期疗效明显,可抑制乳腺癌BCSG1蛋白的表达。     

Effect of Neoadjuvant CAF Regimen on the Expression of BCSG1 in Breast Cancer

Objective： To evaluate the efficacy of neoadjuvant chemotherapy and explore a sensitive and objective way in the evaluation of neoadjuvant chemotherapy, the pathological changes and BCSG1 expression were studied by pathological and immunohistochemical method in breast cancer patients with CAF neoadjuvant chemotherapy （Cyclophosphamide, Adriamycin and Fluorouracil, CAF） and those without at the same period. Methods： Specimens were obtained from 34 breast cancer patients receiving neoadjuvant CAF regimen chemotherapy （CAF group） and 110 breast cancer patients not receiving neoadjuvant chemotherapy （control group）. The BCSG1 expression was detected by SP immunohistochemistry. Correlation between BCSG1 expression and pathological response to CAF neoadjuvant chemotherapy was analyzed. Results： Overall response rate to neoadjuvant chemotherapy was 79.4%. The strong cytoplasm expression of BCSG1 was significantly lower in CAF group than in control group （29.4% vs. 64.5%, P〈0.01）. In CAF group, the positive cytoplasm expression in partial response （PR） （grade Ⅱ） cases was significantly lower than that in no response （NR） （grade Ⅲ） cases （P=0.002）. Conclusion： Neoadjuvant chemotherapy of CAF regimen could decrease the nuclear expression of BSCG1 in breast cancer.