人膀胱癌原代培养体外药敏试验的研究

目的:探讨用ATP生物荧光肿瘤体外药敏检测技术(ATP-TCA)研究膀胱癌药敏的异质性和个体化疗的可行性。方法:用ATP-TCA检测来自45例初发和6例复发膀胱癌患者的手术标本对4种化疗药物的敏感程度。结果:51例标本中有49例获得药敏结果,可评价率为96·0%。最有活性的药物是吡柔比星,有43·8%(21/48)的标本对它表现强敏感;28·6%(14/49)的标本无强敏感药物;69·4%(34/49)的标本无耐药药物。结论:膀胱癌对抗癌药物的敏感程度存在着异质性。ATP生物荧光肿瘤药敏检测技术可用于为膀胱癌选择合适的化疗药物。     

In vitro chemosensitivity testing of leukemic cells: development of a semiautomated colorimetric assay

A rapid chemosensitivity assay was developed, employing the human continuous leukemic cell lines HL 60, K 562, FLG 29.1. This automated colorimetric assay is based on the characteristic of viable, metabolically active cells to cleave p-iodonitrotetrazolium violet (INT) into a red formazan derivative, whose optical density is readable at 492 nm by an automated microtiter-plate reader photometer. A linear relationship was found between the viable cell number and the optical density of INT cleaved by the cellular samples. Dead cells did not reduce INT and did not interfere with the formazan derivative generation and the photometric reading. Leukemic cell lines were also tested for INT formazan derivative generation after exposure to antileukemic drugs at various concentrations, representative of plasma levels obtainable in vivo. A dose-dependent inhibition was detected, with different sensitivity patterns, related both to the drugs and to the different cell lines. A significant correlation between the viable cell number and the amount of tetrazolium salt cleaved was also demonstrated after drug exposure. INT assay allows the processing of a great number of samples and gives the opportunity to screen several drugs, saving time and yielding fully reliable results.     

Sequential chemotherapy and radiotherapy as sandwich therapy for the treatment of high risk endometrial cancer

Objective

The purpose of this retrospective study was to assess the tolerability and efficacy of sequential chemotherapy and radiotherapy for the treatment of high risk endometrial cancer.

Methods

We conducted a retrospective study of previously untreated high risk endometrial cancer patients who received sequential chemotherapy and radiotherapy in accordance with the sandwich approach from June 2008 until June 2011. High risk endometrial cancer patients underwent complete surgical staging followed by adjuvant therapy encompassing sequential chemotherapy, radiation therapy and consolidation chemotherapy.

Results

The study analysis comprised 32 endometrial cancer patients. All subjects were treated with carboplatin and paclitaxel chemotherapy; currently, 186 cycles have been administered and 94% of patients have completed the planned number of cycles. Grade 3 neutropenia developed in 1 (3.1%) patient; there was no incidence of grade 4 neutropenia. Moreover, we observed grade 3 anemia in four (12.5%) patients and grade 4 anemia in one (3.1%) patient. One (3.1%) patient developed grade 3 thrombocytopenia; grade 4 thrombocytopenia was not observed. Five patients exhibited progressive disease, three of whom have since expired; mean progression free survival and follow-up were 17.4 months and 18.9 months, respectively.

Conclusion

The preliminary results from our study suggest that the sandwich approach to treating high risk endometrial cancer patients is feasible. Hematologic toxicity was well tolerated and non-hematologic toxicity was mild and easily managed. Further study of this novel regimen in a larger patient population with extended follow-up is necessary.     

人乳腺癌细胞原代培养体外药敏试验研究

目的:探讨用ATP生物荧光肿瘤体外药敏检测技术(ATP-TCA)研究乳腺癌药物敏感性的异质性以及个体化治疗的可行性。方法:用ATP-TCA检测114例乳腺癌标本对13种单药或联合用药的敏感性。结果:个体之间的药物敏感性存在着明显的异质性。单药中有效的药物为紫杉醇、长春瑞滨、表阿霉素、丝裂霉素和阿霉素,敏感率分别为73·3%、64·1%、62·3%、49·9%和40·0%。联合用药(紫杉醇 表阿霉素,环磷酰胺 表阿霉素 氟尿嘧啶)的敏感率高于单药。结论:乳腺癌对抗癌药物的敏感程度存在着异质性。ATP生物荧光肿瘤药敏检测技术可用于为乳腺癌选择合适的化疗药物。     

In vitro chemosensitivity testing of leukemic cells: prediction of response to chemotherapy in patients with acute non-lymphocytic leukemia

The in vitro chemosensitivity to daunorubicin and cytosine arabinoside of blast cells derived from 35 patients affected by acute non-lymphocytic leukemia was assessed by a semiautomated tetrazolium-based colorimetric assay, by the use of p-iodonitrotetrazolium violet. The results of the in vitro testing were then compared a posteriori to clinical outcome of patients, who followed a schedule of therapy which always included the drugs tested in vitro. Three dosages of drugs were employed to allow the determination of a dose-response curve, which was obtained for all the patients. The data collected in INT assay correlated with the clinical sensitivity of patients, evaluated in terms of achievement of complete remission. For the dosage of ARA-C 500 ng/ml it was possible to establish a significant cutoff between responders and non-responders to therapy, while an acceptable distribution of sensitivity/resistance prediction was found for DNR 500 ng/ml and 5 micrograms/ml. Present results, together with rapid and easy execution of the test, encourage the use of INT assay in screening leukemic patients' sensitivity to antiblastic drugs before treatment or, in case of resistance to classical chemotherapy, in detecting individual sensitivity to alternative drugs.     

Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer

Background The purpose of this study was to evaluate the toxicity profile of weekly low-dose paclitaxel and carboplatin in patients with gynecologic malignancies. Methods Patients had measurable disease defined by clinical examination or radiographic studies. Each cycle of treatment consisted of carboplatin at an AUC of 2 and paclitaxel at 80 mg/m² on days 1, 8, and 15 of a 28-day cycle. Results Twenty-eight patients with advanced or recurrent cervical and endometrial cancers were included in this study. The overall response rate (ORR) was 39% (2 CR, 9 PR). Among the 15 cervical cancers the ORR was 20%, while the 13 endometrial cancers had a 62% ORR. Median time to progression and overall survival was 3.4 and 7.6 months for those with cervical cancer and 5.5 and 15.4 months for those with endometrial cancer. Grade 3 or 4 hematologic toxicity was uncommon (7% grade 3 anemia, 21% grade 3 or 4 neutropenia, 7% grade 3 or 4 thrombocytopenia). Conclusion A regimen of weekly low-dose paclitaxel and carboplatin has an acceptable toxicity profile that is easily managed by dose adjustment and the use of erythropoietic therapy. This regimen appears to have activity in advanced or recurrent endometrial cancer which warrants further evaluation.     

人乳腺癌细胞MTT药敏试验评价标准的研究

目的：建立人乳腺癌细胞体外药敏评价标准,预测乳癌病人的化疗疗效,方法：应用ＭＴＴ试验,检测１７５例原代乳腺癌细胞对８种化疗药物的敏感性,采用Ｌｏｇｉｓｔｉｃ程序对药物敏感性的指标进行分析。结果：如果ＩｍａｘＴ〉（瘤群Ｉｍａｘ％均数＋标准差）说明药物的抑制作用较弱,临床不能应用该药,如果Ｉｍａｘ％≤瘤群Ｉｍａｘ％均数＋标准差）药物的抑制作用较纱,可以进一步考证其ＩＣ５０,ＩＣ５０≤Ｑ５０,即小于本组     

ATP生物荧光肿瘤药敏检测技术在乳腺癌化疗中的应用研究

目的 探讨ATP生物荧光肿瘤药敏检测技术(ATP-TCA)在乳腺癌化疗中的应用价值。方法 取40例乳腺癌改良根治术、淋巴结活检和胸腔积液标本进行ATP-TCA药敏检测。结果 ATP-TCA肿瘤药敏检测技术在乳腺癌标本中的可评价率为90％(36/40);化疗药物对乳腺癌的杀伤作用具有较强的个体差异性;10种化疗药物的敏感率分别为:氟尿嘧啶(5-Fu)33.3％、顺铂(DDP)37.5％、环磷酰胺(CTX)29.2％、足叶乙苷(VP-16)16.7％、丝裂霉素(MMC)22.0％、表阿霉素(EPI)41.7％、诺维本(NVB)45.8％、阿霉素(ADM)41.70k、泰素(PTX)54.2％、羟基喜树碱(HCPT)25.0％。初步研究表明ATP-TCA体外检测结果与实际临床疗效具有良好的相关性。结论 ATP-TCA检测技术是一种准确、可靠的肿瘤药敏检测技术。该技术检测结果与临床实际疗效具有较好的相关性,可用于指导乳腺癌化疗和化疗药物的新适应证研究。     

ＭＴＴ法抗肿瘤药敏试验影响因素的探讨

目的：对于采用ＭＴＴ法进行抗肿瘤药物敏感试验过程中的多种影响因素进行分析,观察抗肿瘤药物包被板的稳定性。方法：分离人外周血单个核细胞（ＰＢＭＣ）,用ＭＴＴ法测定抗肿瘤药物敏感性,观察红细胞、血小板、３种ＤＭＳＯ及不同浓度ＭＴＴ对实验结果的影响;监测肿瘤药物包被板的稳定性。结果：一定浓度范围的红细胞和血小板均可影响实验结果;进口和国产分析纯的ＤＭＳＯ与ＭＴＴ的呈色反应是一致的,吸光度（Ａ值）与ＭＴＴ呈浓度依赖性;冷冻干燥的抗肿瘤药物包被板的稳定性优于未经冷冻干燥的药物包被板。结论：明确实验过程中多种影响因素,有助于规范ＭＴＴ法体外抗肿瘤药敏试验。     

三磷酸腺苷-肿瘤体外药敏检测在晚期卵巢上皮癌化疗中的成本-效果评价

目的 评价三磷酸腺苷-肿瘤体外药敏检测(adenosine triphosphate-tumor chemosensitivity assay,ATP-TCA)在晚期卵巢上皮癌化疗中的应用价值,以及对该技术应用的成本-效果进行评价.方法 回顾性分析158例在我院例行ATP-TCA检测的晚期卵巢上皮癌病例,其中原发67例...     

MTT法体外药敏实验预测宫颈癌细胞药物敏感性的初步探讨

背景与目的:近年来,宫颈癌新辅助化疗逐渐受到重视,应用广泛,但不同个体对不同化疗药物敏感性不同.本研究通过宫颈癌体外药敏实验来预测肿瘤细胞对化疗药物的敏感性,为临床筛选对宫颈癌相对敏感的化疗药物提供参考依据.方法:采用MTT法测定9种药物对32例宫颈癌患者的原代培养癌细胞的抑制水平.结果:①宫颈癌细胞对9种药物的敏感性依次为:力扑素＞泰素＞卡铂＞异环磷酰胺＞鬼臼乙叉甙＞氟尿嘧啶＞顺铂＞博来霉素＞环磷酰胺,力扑素、泰素和卡铂对肿瘤细胞的平均抑制率(IR)较高,分别为56.56%、55.66%和46.81%,与其它药物相比,差异有显著性(P＜0.05).②对Ⅰ b1期宫颈癌细胞,泰素、力扑素和卡铂IR值较其它药物高,分别为58.71%、53.00%和49.25%;对Ⅰ b2期宫颈癌细胞,力扑素和泰素的IR值较其它药物高,分别为65.26%和50.06%.③对于宫颈中分化鳞癌细胞,泰素、力扑素和卡铂IR值较其它药物高,分别为52.01%、49.21%和40.24%;对低分化鳞癌细胞,力扑素、泰素和卡铂的IR值较其它药物高,分别为61.16%、60.62%和48.75%.结论:①MTT法作为一种应用广泛的药敏实验方法,对宫颈癌新辅助化疗筛选敏感药物、选择临床化疗方案有一定的参考价值.②力扑素、泰素和卡铂对宫颈癌细胞较其它药物敏感.     

Evaluation of in vitro chemosensitivity of antitumor drugs using the MTT assay in fresh human breast cancer

Practical criteria were developed in this paper for the purpose of evaluating chemosensitivity of fresh human breast cancer by the MTT assay. The survival rates at maximum inhibition (Imax %) and the concentrations of drugs which caused fifty percent reduction in absorbance compared to baseline values (IC₅₀) of 175 samples of 10 anti-tumor drugs were evaluated by logistic analyses of the dose-response curves. Distributions of Imax% appeared as normal curves, while those of the IC₅₀ significantly deviated from normal distribution (p < 0.0001). We assessed the in vitro chemosensitivity by comparing the Imax % of each drug on individual samples with the mean Imax % + SD which was obtained from the Imax% of 175 samples. If the individual Imax % > mean Imax % + SD, we thought the tumor sample was resistant to this drug. If the Imax % mean Imax % + SD, we would compare its IC₅₀ with Q₅₀ which was used as a cutoff point for in vitro chemosensitivity of anti-tumor drugs. The in vitro chemosensitivity could be graded as sensitive (Q₁–Q₂₅), intermediate (Q₂₆–Q₇₅), and resistant (Q₇₆–Q₁₀₀) by means of percentile method. If the individual IC₅₀ Q₇₆, the tumor sample would be defined as resistant. If the individual IC₅₀ Q₂₅, it would be defined as sensitive. In the range of Q₂₆–Q₇₅, we used Q₅₀ as a cutoff point between relative sensitivity and relative resistance. Preliminary results showed that the in vitro chemosensitivity to different anti-tumor drugs determined by these criteria were consistent with the clinical response in 83 advanced breast cancer patients.     

ＡＴＰ生物荧光法检测非小细胞肺癌胸水癌细胞对化疗的敏感性

目的　探讨ＡＴＰ生物荧光法（ＡＴＰ-ＴＣＡ）体外药敏试验预测非小细胞肺癌（ＮＳＣＬＣ）胸水治疗药物敏感性的可行性。方法　采用ＡＴＰ-ＴＣＡ检测２４例ＮＳＣＬＣ患者胸水标本,对４种含铂类二药联合方案及培美曲塞单药的敏感性。结果　２４例胸水标本的可评价率为９５.８％（２３／２４）,其中ＧＰ方案的敏感率最高,为６０.９％,其次为ＴＣ、ＴＰ及ＮＰ方案,敏感率分别为４３.５％、３９.１％和３４.８％。８例培美曲塞单药二线治疗标本的敏感率为５０.０％。在敏感检测标本中,不同方案对不同病理类型的敏感度亦不同。结论　ＮＳＣＬＣ对抗癌药物的敏感程度存在着异质性,ＡＴＰ-ＴＣＡ体外药物敏感性检测技术是一种重要的体外药物筛选方法,可以辅助选择ＮＳＣＬＣ合适的化疗药物。     

Endometrial carcinoma in a single horn of a bicornuate uterus: A case report

We discuss the diagnosis and the management of endometrial carcinoma in a single horn of bicornuate uterus in a 64-year-old woman as a case report. The case underwent laparoscopic radical hysterectomy and bilateral iliac lymphadenectomy.The gross examination of the uterus revealed a bicornuate uterus with a greater horn of 12?×?9?×?8?cm and a smaller horn of 10?×?3?cm. The cavity of the greater horn showed a neoplastic growth of 10?cm with infiltration of about 1,8 cm of the myometrium from whole thickness of 1.9?cm. while the other horn was free of tumor tissue.The microscopic examination of the uterus revealed G2 endometrioid adenocarcinoma of the endometrium of the greater horn with infiltration of more than 50% of the myometrium.In the presence of bicornuate uterus, a bilateral endometrial biopsy should be performed in order to reduce the risk of delayed or missed diagnosis.The management of a case of bicornuate unicollis uterus with endometrial carcinoma in only one horn is the same as patients with endometrial cancer in single uterus and depends mainly on stage and histological grade of the tumor.The possibility of existence of a separate uterine cavity should always be considered when endometrial cancer is clinically suspected but pathology fails to confirm the diagnosis. This points out the importance of a careful physical examination and radiographic evaluation in such cases.     

多西紫杉醇为主的联合方案治疗转移性乳腺癌

目的:探讨多西紫杉醇为主的联合化疗方案治疗转移性乳腺癌的疗效及毒副反应。方法:49例转移性乳腺癌患者中,22例既往使用蒽环类治疗失败,予多西紫杉醇联合顺铂或希罗达治疗;27例既往未曾采用蒽环类治疗,予多西紫杉醇联合阿霉素治疗。21天为1周期,2周期后评价疗效,有效者化疗4周期以上。结果:49例患者中,治疗后完全缓解(CR)11例,部分缓解(PR)23例,稳定(SD)8例,进展(PD)7例,有效率为69·3%(34/49)。中位疾病进展时间为8·5个月,中位生存时间为18·3个月。主要毒副反应为白细胞减少,其中Ⅲ~Ⅳ度占51·0%。结论:多西紫杉醇为主的联合化疗方案治疗转移性乳腺癌疗效确切,毒性反应可耐受。     

Significant pelvic recurrence in high-risk pathologic stage I--IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy

To evaluate the risk of pelvic recurrence (PVR) in high-risk pathologic Stage I–IV endometrial carcinoma patients after adjuvant chemotherapy alone.

Between 1992 and 1998, 43 high-risk endometrial cancer patients received adjuvant chemotherapy. All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patients received preoperative radiation therapy (RT). Regional lymph nodes and peritoneal cytology were sampled in 62.8% and 83.7% of cases, respectively. Most patients had Stage III–IV disease (83.7%) or unfavorable histology tumors (74.4%). None had evidence of extra-abdominal disease. All patients received 4–6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. Recurrent disease sites were divided into pelvic (vaginal, nonvaginal) and extrapelvic (para-aortic, upper abdomen, liver, and extra-abdominal). Median follow-up was 27 months (range, 2–96 months).

Twenty-nine women (67.4%) relapsed. Seventeen (39.5%) recurred in the pelvis and 23 (55.5%) in extrapelvic sites. The 3-year actuarial PVR rate was 46.5%. The most significant factors correlated with PVR were cervical involvement (CI) (p = 0.01) and adnexal (p = 0.05) involvement. Of the 17 women who developed a PVR, 8 relapsed in the vagina, 3 in the nonvaginal pelvis, and 6 in both. The 3-year vaginal and nonvaginal PVR rates were 37.8% and 26%, respectively. The most significant factor correlated with vaginal PVR was CI (p = 0.0007). Deep myometrial invasion (p = 0.02) and lymph nodal involvement (p = 0.03) were both correlated with nonvaginal PVR. Nine of the 29 relapsed patients (31%) developed PVR as their only (6) or first site (3) of recurrence. Factors associated with a higher rate of PVR (as the first or only site) were CI and Stage I–II disease.

PVR is common in high-risk pathologic Stage I–IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy. Further studies are needed to test the addition of chemotherapy to locoregional RT.     

Endometrial carcinoma: a review of chemotherapy, drug resistance, and the search for new agents

Adenocarcinoma of the endometrium represents the most common gynecologic malignancy in developed countries. Although early-stage cancers are effectively treated surgically, commonly without adjuvant therapy, the treatment of high-risk and advanced disease is more complex. Chemotherapy has evolved into an important modality in high-risk early-stage and advanced-stage disease, and in recurrent endometrial cancer. Taxane-based therapy consistently demonstrates the highest response rates in the first-line and salvage settings of endometrial cancer. Unfortunately, response to chemotherapy is modest and strategies are needed to predict chemotherapy-responsive and chemotherapy-resistant populations. Chemotherapy resistance mediated by overexpression of drug efflux pump proteins and mutations in β-tubulin isoforms in both primary and recurrent disease represent unique treatment challenges and highlight the need for new agents that are less susceptible to these known resistance pathways. Epothilone B analogs are novel cytotoxic agents with activity in solid tumors, including advanced/recurrent endometrial carcinoma, and may have unique properties that can overcome resistance in some settings. These agents alone and in combination represent a new therapeutic opportunity in endometrial carcinoma.     

Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST)

Purpose In the present study, we prospectively evaluated the clinical feasibility and efficacy of collagen gel droplet embedded culture drug sensitivity test (CD-DST) in unresectable non-small cell lung cancer (NSCLC) without previous treatment. Experimental design Eighty patients with unresectable NSCLC, aged less than 81 years old, PS 0–1, and with evaluable tumor lesions, entered the study. If the patient had CD-DST active drugs, more than three cycles of chemotherapy containing these drugs were administered. If the patient did not have CD-DST active drugs, the patient could choose any treatment including best supportive care. Results Of the 80 patients in this study, CD-DST yielded results successfully in 49 patients (61.3%). CD-DST active drugs were present in 22 patients, and significantly more female patients had in vitro active anticancer agents than male (P = 0.0008). All of the patients with CD-DST active agents received chemotherapy including these agents. In these patients, the response rate was 72.7%, and median survival was 15.0 months. In the patients without CD-DST active agents, 11 patients received standard, empirical chemotherapy. In these patients, response rate was 0%, and median survival was 6.0 months. Conclusions The results show that CD-DST is capable of selecting the responders and the respective optimal regimens, and also delineating the patients less likely benefit from treatment.     

Paclitaxel chemotherapy for the treatment of gastric cancer

A comprehensive review of phase I and phase II clinical trials of paclitaxel and paclitaxel-containing chemotherapy regimens for advanced gastric cancer was performed. Response rates, median progression-free survivals, and median overall survivals were examined, together with the treatment regimens and the numbers of patients registered in each trial. Although paclitaxel monotherapy produced considerable improvement in tumor response and prognosis, combination doublet or triplet chemotherapy with fluoropyrimidines and/or platinum compounds showed better results than the paclitaxel monotherapy. With regard to the schedule of paclitaxel administration, weekly injection seemed to show less toxicity and better results than administration every 3 weeks. Adjuvant therapies, chemoradiation therapies, and paclitaxel treatment for gastric ascites were also investigated and are discussed.