Hormone receptor status and chemosensitivity in breast cancer

In order to investigate the response of breast cancer cells to anticancer drugs as a function of hormone receptors, 69 specimens obtained from the primary tumor of invasive breast cancer patients were cultivated using the human tumor clonogenic assay. Successful growth in vitro (≥ 30 colonies per plate) was obtained in 50 (72.5%) of the 69 viable samples, with a median cloning efficiency of 0.17%. Five drugs (adriamycin, vincristine, 5-fluorouracil, carmustine, methotrexate) were tested for each specimen resulting in 250 drug assays. The overall drug sensitivity was 47.2%. Of these, 5-fluorouracil had the greatest effect in vitro with a sensitivity of 68.0%. There was no significant correlation between hormone receptor status and response to anticancer drugs either overall or for agents analyzed individually. It is concluded that hormone receptors of breast cancer have no predictive value for response to chemotherapy.     

Chemotherapy testing for human ovarian cancer using in vitro colony assay

The in vitro evaluation of anticancer drug efficacy was performed using the human tumor clonogenic assay developed by Hamburger and Salmon, and correlation between the in vitro and clinical efficacy was analyzed retrospectively. The in vitro colony assay method used in this study was a minor modification of the above method. Thirty-two out of forty-eight samples from patients with ovarian cancer formed more than five colonies per plate on in vitro colony assay. The median plating efficiency was 0.06% (range 0.02-1.3%) and the median colony count per plate was 279 (range: 8-4,000). With regard to colony formation of ovarian cancer according to the source of the specimen, the colony-forming rate of solid tumor was high (72%) as compared with 63% for ascites and 43% for pleural effusion. In vitro chemosensitivity was defined as more than a 50% decrease in colony formation and the rates for standard drugs on ovarian cancer were as follows: adriamycin (0.04 micrograms/ml) 29%, bleomycin (0.1 micrograms/ml) 24% cisplatin (0.2 micrograms/ml) 31%, 5-FU (1.0 micrograms/ml) 22%, hexamethylmelamine (1.0 micrograms/ml) 19%, L-PAM (0.4 micrograms/ml) 44%, mitomycin C (0.1 micrograms/ml) 38% and THP-adriamycin (0.5 micrograms/ml) 36%. A group of patients who had not been exposed to any anticancer drug showed higher sensitivity in vitro as compared with a group of patients who had received prior chemotherapy (35% vs 22%, p less than 0.05). Correlation between in vitro drug sensitivity and clinical responses in patients treated with the same drugs were analysed retrospectively. In all twenty cases, two were true positive cases (29%), while in ten cases, the results were true negative (77%), The overall predictive accuracy was 60%. In conclusion, ovarian cancer cells can form colonies well when the soft agar method is used and this assay method is suitable for the evaluation of various anticancer drugs in vitro.     

The role of urinary cytology for detection of bladder cancer.

PURPOSE: The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p<0.05). RESULTS: In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p<0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. CONCLUSIONS: Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.     

Development of an agar-methyl cellulose clonogenic assay for cells in transitional cell carcinoma of the human bladder.

We report the development of a clonogenic assay for progenitor cells in transitional cell carcinoma of the bladder. Colony growth has been demonstrated from cells obtained both from surgical biopsies and from bladder barbotages. Electron microscopic and karyotypic evidence supports the contention that these progenitors represent a part of the population maintaining the tumor in vivo. Colony growth occurred in 9 of 11 surgical biopsy samples and in 6 of 6 bladder barbotage samples. Plating efficiency ranged up to 0.7%, and colony size was in some instances greater than 1000 cells. The assay appears potentially useful for analysis of the biology of human transitional cell carcinoma.     

Colony formation in vitro as a prognostic indicator for primary breast cancer

Cells from some, but not all, tumor biopsy samples form colonies when cultured in semi-solid media. The possibility that colony formation by progenitor cells in these tumors may reflect a more "aggressive" phenotype bearing clinical implications was examined in a series of 61 patients with primary breast cancer. Tumor cells from 32 samples formed colonies in vitro. There was no correlation between colony formation and any of the standard clinical parameters such as tumor size, nodal status, metastatic spread, or hormone receptor levels. Eighteen patients had inflammatory, locally advanced and/or detectable metastatic breast cancer at the time of surgery. Sixteen of these patients have progressed and 15 have died, with no relationship between colony formation and survival. For the 43 remaining patients, 23 had a tissue sample that gave rise to colonies in vitro; 14 of these have relapsed, with a median relapse-free survival (RFS) of 37.6 months, and eight have died with a median survival time of 46.8 months. This is compared with four relapses (median RFS not reached, P = .0043, Peto-Pike), and four deaths (median not reached, P = .1175) in the group without growth of the tumor specimen. These results indicate that colony formation is an independent prognostic parameter for breast cancer, which may be useful for selecting patients who would benefit from more intensive therapy.     

Preliminary correlations of clinical outcome with in vitro chemosensitivity of second passage human breast cancer cells

These studies describe the clinical correlations of 63 in vitro chemosensitivity assays on breast cancer cells after short-term monolayer culture. Forty-five of the assays were single agent correlations. Based on cut-off values determined empirically, the test accurately predicted resistance for 36 of 41 patients (88%) who did not respond to the drug. It also predicted sensitivity with a high degree of accuracy: 21 of 22 patients (95%) who responded to the drug tested had a sensitive assay. In five cases, two biopsies were evaluated from the same patient. Whenever assays were performed before and after treatment with a given drug, tumor cells from the second biopsy were more resistant in vitro if the patient failed on therapy. If the patient did not fail, but stopped therapy for other reasons, or if there was no intervening therapy with the tested drug, the two biopsies remained similar in drug sensitivity. These results suggest that in vitro chemosensitivity assays which accurately predict both sensitivity and resistance can be obtained with breast cancer cells after short-term culture and that further prospective trials are warranted.     

Chemosensitivity of adriamycin, mitomycin C, and bleomycin with in vitro colony assay

In vitro colony assay was used to examine the sensitivities of adriamycin (ADM), mitomycin C (MMC), and bleomycin (BLM), and the effects of a prior chemotherapy on in vitro chemosensitivities of the drugs. One hundred forty-seven tumor specimens from 106 patients with various malignancies were placed in culture. Seventy tumors (56.0%) from 125 evaluable specimens which had histologically or cytologically confirmed to be malignant, and were plated at 5 x 10(5) cells/plate formed more than 30 colonies/plate enough for sensitivity assays. The results of in vitro sensitivities of the drugs were nearly similar to those reported in the clinical trials. The in vitro antitumor activity of BLM was noted in 3 (21.4%) of 14 patients with ovarian cancer, therefore the results suggest that the assay is useful to select effective drugs against tumors in which phase II study has never been performed. In vitro sensitivity of BLM was markedly reduced by a prior chemotherapy containing the same drug (p less than 0.05), and prior therapeutic ADM exposure also reduced in vitro activity of the drug, whereas there was no significant influence on in vitro activity of MMC. These results indicate the usefulness of the in vitro colony assay for predicting clinical antitumor activities of ADM, MMC, and BLM.     

胃癌组织中ERCC1、TS和TUBB3与化疗药物体外药敏相关性的实验研究

目的:分析体外胃癌细胞中ERCC1与顺铂、TS与5-氟尿嘧啶及TUBB3与紫杉醇化疗药物敏感性的相关性。方法:选择经外科手术的胃癌患者的新鲜标本48例,每份癌组织标本均分成两份:一份用于原代培养细胞,ATP-TCA法检测体外化疗药物的敏感性;另一份用于免疫组化检测ERCC1、TS和TUBB3蛋白的表达。结果:45例有效的胃癌组织中,ERCC1高表达21例(46.67%),低表达24例(53.33%)。21例ERCC1高表达组敏感例数7例(33.33%),24例低表达组敏感例数17例(70.83%),ERCC1高表达者对顺铂的敏感有效率要明显低于低表达者。TS高表达19例(42.22%),低表达26例(57.78%)。19例TS高表达组敏感例数5例(26.32%),26例低表达组敏感例数18例(69.23%),TS高表达者对5-氟尿嘧啶的敏感有效率要明显低于低表达者。TUBB3高表达22例(48.89%),低表达23例(51.11%)。22例TUBB3高表达组敏感例数5例(22.73%),23例低表达组敏感例数16例(69.57%),TUBB3高表达者对紫杉醇的敏感有效率要明显低于低表达者,以上差异均具有统计学意义(P＜0.05)。结论:体外实验证实ERCC1、TS和TUBB3的表达与化疗药物耐药具有一定的相关性,低表达组的耐药发生率低于高表达组。ERCC1、TS和TUBB3有望成为判断胃癌患者化疗疗效及预后的分子标志物。     

三维组织药敏法在肿瘤个体化精准医疗中的应用

目前恶性肿瘤的化疗方案大多采用美国国立综合癌症网络(National comprehensive cancer network,NCCN)临床实践指南推荐的标准化疗方案,因忽略了肿瘤内在固有的异质性,导致有效率低、毒副作用大、费用高等问题。因此,实现肿瘤“个体化精准医疗”是大势所趋。肿瘤患者进行化疗药物敏感性筛查,以期达到个体化精准给药,是“个体化精准医疗”的主要内容之一。三维组织药敏法(Histoculture drug response assay,HDRA)是将手术切除或活检获取的活性肿瘤组织块经体外培养后,进行药物敏感性检测的方法,不仅实验周期短,而且还保持了肿瘤组织的结构、异型性和微环境,与临床一致性较好,是一种比较有前景的肿瘤药敏检测技术。因此,本文就HDRA的发展历程、临床应用以及未来的发展趋势做一综述。     

The human tumor clonogenic assay in human breast cancer

The human tumor clonogenic assay (HTCA) was evaluated in 407 fresh samples of breast cancer from 288 patients. Seventy samples were inadequate for testing. Adequate in vitro growth for drug testing (greater than 30 colonies/plate) was obtained in 91 (27%) of the 337 viable samples, inadequate growth for drug evaluation (5 to 30 colonies/plate) in 17%, and no colony formation (less than 5 colonies/plate) in 56%. Operationally defining a greater than or equal to 50% inhibition of colony formation as in vitro drug sensitivity, the in vitro response rates to 12 anticancer drugs tested against ten to 36 different cancers (arranged in decreasing order according to the number of tests performed) were as follows: doxorubicin (14%), bisantrene (54%), vinblastine (33%), mitomycin (36%), interferon clone A (23%), 5-fluorouracil (20%), methotrexate (17%), leukocyte interferon (33%), mitoxantrone (42%), cyclophosphamide (25%), m-AMSA (16%), and melphalan (10%). Among 25 patients receiving single-agent therapy, there were ten (59%) of 17 with in vitro sensitivity who responded; resistance was correctly predicted in nine patients (100%), P = .01. Among 34 patients treated with combination chemotherapy, seven (50%) of 14 with in vitro sensitivity responded, and resistance was predicted in 13 (65%) of 20 patients. Difficulties in using the HTCA in breast cancer (including small specimen size, difficulties in disaggregation, and inadequacy of growth) will require additional research. Nonetheless, the assay appears to detect in vitro activity as well as resistance of a variety of anticancer agents and appears to predict clinical responsiveness to standard as well as some investigational single agents.     

Human tumor clonogenic assay in human breast cancer

The human tumor clonogenic assay (HTCA) developed by Hamburger and Salmon was evaluated in 135 fresh samples of breast cancer. Successful tumor colony growth (greater than or equal to 5 colonies/plate) was obtained in 100 (74%) of the 135 samples, and adequate growth for drug testing (greater than or equal to 30 colonies/plate) in 75 (56%). With regard to the success rates of growing colonies categorized by specimen source, tumor sites, histology, prior chemotherapy and estrogen receptor (ER), specimens from solid tumors and primary tumors showed higher success rates than those from pleural effusions and metastatic tumors. The effects of prior chemotherapy, histology type and ER status on the success rate of colony formation were not significant. The overall median plating efficiency was 0.012%. Higher plating efficiencies were found in pleural effusion, metastatic tumors and samples from patients with prior chemotherapy. These findings appeared to indicate that aggressiveness of disease might be related to plating efficiency. Defining a greater than or equal to 50% inhibition of colony formation (ICF) as in vitro drug sensitivity, the in vitro response rates to anticancer drugs tested were as follows: adriamycin 33%, mitomycin C 39%, 5-fluorouracil 32%, methotrexate 42%, L-PAM 31%, cisplatin 38%, vincristine 32%, vinblastine 54%. The group of patients without prior chemotherapy showed higher sensitivity in vitro compared with the group of patients who had prior chemotherapy (38% vs. 27%). Correlation between in vitro drug sensitivity (greater than or equal to 70% ICF) and clinical response in 12 patients treated with the same drugs were analyzed retrospectively. The predictive accuracy was 0% (0/1) for true positive and 91% (10/11) for resistance. Thus, overall predictive accuracy was 83%. Based on these results, HTCA appeared to be useful chemosensitivity test for evaluation of antitumor drugs for human cancers in vitro and prediction of the chemotherapeutic effect in clinical use.     

Simultaneous soft agar cloning of ascites and solid tumor specimens from patients with ovarian cancer

Concurrent Cloning Efficiencies (CE) of both ascites and solid tumor samples from 36 patients with ovarian carcinoma were studied using the soft agar assay. The CE of both were highly variable (range, 0-1.234% and 0-0.802%, respectively). There was marked intrapatient and interpatient heterogeneity in the CE. Of the 36 tested, comparative CE were evaluable in 29. CE was 0 in both solid tumor and ascites in one patient. CE was 0 in four other ascites samples from four patients. In other 24, the relative CE of solid tumor/ascites from each patient ranged from 0.066 to 435. In the 29 patients with samples of ascites and a solid tumor evaluable for concurrent CE, the median colony counts of solid tumors was more than tenfold higher than ascites. The solid tumors obtained from 31 patients had a significantly higher CE than tumor cells obtained from ascites samples from 32 patients. Solid tumors were significantly better than ascites for in vitro testing based on the data that 75% (27/36) of solid tumors and only 31% (11/36) of ascites formed greater than or equal to 30 colonies. The drug sensitivity profiles of tumor cells from a solid tumor and ascites of the same patient appear similar. Based on these observations, it may be more cost and labor effective to do soft agar in vitro chemotherapy assays using a solid tumor than ascites in ovarian carcinoma.     

膀胱肿瘤组织及尿液标本中TWIST1基因的甲基化水平研究

背景与目的：众多遗传学及表观遗传性的改变引发癌基因的激活剂抑癌基因的失活是膀胱肿瘤发生、发展的重要原因,本研究旨在揭示膀胱肿瘤患者肿瘤组织及尿液标本TWIST1基因的甲基化模式。方法：78例经病理确诊的膀胱肿瘤标本、癌旁正常组织及配对75例尿液标本组成实验组,75例年龄及性别比例匹配的非肿瘤个体组成对照组。从肿瘤、癌旁及尿液标本提取DNA,甲基化特异性聚合酶链反应(methylationspecificpolymerase chain reaction,MSP)检测肿瘤组织、癌旁组织及尿液标本中TWIST1基因的甲基化水平,检测结果与尿细胞学检测结果进行对比,比较两种检测方法的灵敏度及特异度。结果：甲基化检测结果显示,88.5%的肿瘤标本及84.0%的尿液标本出现TWIST1基因的甲基化,11.5%的癌旁正常组织及5.3%的对照尿液标本出现甲基化。尿细胞学检测结果显示,49.3%的肿瘤患者尿液标本检测出瘤细胞,17.3%的对照者被诊断为肿瘤或疑似肿瘤。尿液标本甲基化检测灵敏度及特异度显著高于尿细胞学检测方法。针对低级别肿瘤,TWIST1基因甲基化检测灵敏度为66.7%,高于尿细胞学检测(33.3%)。结论：TWIST1基因甲基化水平检测可作为一种简单、非侵入、敏感及特异的方法应用于早期膀胱肿瘤诊断筛查。     

Soluble Fas--a promising novel urinary marker for the detection of recurrent superficial bladder cancer

BACKGROUND: The objective of this study was to test the hypothesis that elevated urinary levels of soluble Fas (sFas) would aid in the surveillance of patients with a past history of nonmuscle-invasive transitional cell carcinoma (TCC) of the urinary bladder. METHODS: sFas levels were determined in cell lysates and supernatants from 2 human bladder cancer cell lines (T24 and TCC-SUP) and in voided urine from 188 consecutive patients who were at risk for TCC recurrence, 31 patients who had noncancerous urologic conditions, and 10 healthy individuals. The authors also obtained barbotage cytology and voided nuclear matrix protein 22 (NMP22) levels. sFas was analyzed continuously and categorically on the basis of its quintile distribution. RESULTS: sFas was present in cell lysates and conditioned media from both cell lines. sFas levels were found to be higher in the TCC group (n = 122 patients) compared with the control group (P < .001). Higher levels of sFas were associated with positive cytology assay results (P < .001), higher NMP22 levels (P < .001), NMP22 levels > 10 U/mL (P < .001), and tumor stage > or = T1 (P < .001). The areas under the receiver operating characteristics (ROC) curves of sFas and NMP22 for bladder cancer detection were 0.757 (95% confidence interval, 0.694-0.819) and 0.704 (95% confidence interval, 0.637-0.772), respectively. In the > 75% sensitivity region of the ROC curves, sFas was consistently more specific than NMP22. In multivariate analyses, sFas, NMP22, and cytology all were found to be associated with the presence of bladder cancer (P values < or = .009), but only sFas and cytology were associated with tumor stage > or = T1 (P values < or = .026). CONCLUSIONS: sFas was produced and released by bladder TCC cells. Urine sFas was an independent predictor of bladder cancer recurrence and invasiveness in patients who had a past history of nonmuscle invasive bladder TCC, and it outperformed NMP22.     

Noninvasive diagnosis of bladder carcinoma by enzyme-linked immunosorbent assay detection of CD44 isoforms in exfoliated urothelia.

The expression of variant isoforms of the adhesion molecule CD44 is correlated with the onset of neoplasia in many carcinomas. We have previously shown that noninvasive detection of bladder carcinoma is possible by analysis of anomalous CD44 expression in exfoliated urothelia. Although the sensitivity and specificity values obtained for the detection of bladder tumors using RT-PCR and Western blotting methods were superior to those obtained using urine cytology, the application of such techniques is inconvenient for routine diagnostic use. We now report the design and development of a sandwich-ELISA system for the reliable detection of CD44 protein extracted from sedimented urothelial cells in voided urine. Naturally micturated urine samples were obtained from 53 patients with newly diagnosed bladder cancer and from 65 subjects with no evidence of disease; patients with gross hematuria were excluded because of interference with the assay. To demonstrate the diagnostic potential of the system, a "gate" was imposed at N (max), i.e., the highest absorbance value obtained from a sample known to be tumor free. All values above this value were assumed to be indicative of the presence of a tumor. Using this parameter, 42 of 53 (81.1%) patients with histologically confirmed bladder tumors were correctly diagnosed. Correspondingly, under these conditions, the assay is 100% specific for tumor detection, with a sensitivity of 81.1%, which equates to a positive predictive value of 100% and a negative predictive value of 81.1%. A further 54 patients who had previously received treatment for bladder cancer but were currently clinically disease-free were also investigated. Of these, 47 of 54 (87%) were correctly diagnosed to be tumor-free, which in this group equates to a positive predictive value of 87% and a negative predictive value of 100%. The data presented demonstrate that the rapid and accurate detection of elevated levels of CD44 protein isoforms in exfoliated urothelial cells is applicable to the identification and monitoring of primary and recurrent bladder cancer.     

应用荧光原位杂交技术检测膀胱癌的研究

目的应用荧光原位杂交((fluorescence in situ hybridization,FISH)技术检测膀胱癌患者尿液脱落细胞中染色体异常,评估FISH在中国人群中诊断膀胱癌的作用。方法2007年1月至2008年8月,随机留取20例良性前列腺增生症患者的新鲜尿液,用3号和7号、17号及p16位两组混合探针,通过在尿液脱落细胞标本上进行FISH检测,建立正常人群的阈值;其后随机留取30例门诊膀胱镜活检证实的膀胱癌患者的尿液,同时进行尿液脱落细胞的细胞形态学分析及FISH检测,对比检查结果。结果3号、7号和17号染色体非整倍性改变及p16位点异常正常阈值分别为8.5%、7.1%、6.8%和9.2%,FISH与细胞学检查总敏感性分别为76.6%和43.3%(P<0.05)。T_(is)及T_a、T_1患者FISH检测的敏感性分别为80.0%和64.2%,脱落细胞组织学检测显示敏感性分别为40.0%和35.7%;T_(2-3)患者FISH的敏感性为90.9%,而脱落细胞组织学检测为54.7%(P<0.05),低级别尿路上皮癌FISH及细胞学敏感性分别为68.4%和31.6%;高级别分别为90.9%和63.6%。结论与尿液脱落细胞组织学检测相比,对尿液脱落细胞进行FISH检测可以提高膀胱癌的诊断率,FISH可以作为诊断膀胱癌的一种无创伤的新方法。     

Aphidicolin markedly increases the platinum sensitivity of cells from primary ovarian tumours.

Enhanced DNA repair has been observed in cisplatin-resistant ovarian cancer cell lines. This resistance can be modulated, on co-incubation with aphidicolin in established cell lines and animal tumour models, by inhibiting DNA polymerases. We describe a study of the in vitro modulation effect of aphidicolin on cisplatin and carboplatin using fresh cells harvested from biopsy samples or ascitic fluids from 25 patients with ovarian adenocarcinoma. The MTT assay was used to measure cell survival after drug exposure. Aphidicolin (up to 30 microM) showed no cytotoxicity when tested alone. Forty-seven comparisons were made between drug with and without aphidicolin, and 37 (79%) cases demonstrated a significant increase in sensitivity to the platinum agents on co-incubation. Overall, there was a median 10-fold (range 1.64- to 58.5-fold) increase in sensitivity. When patients were grouped according to in vitro sensitivity to platinum, aphidicolin had a significantly greater effect in the "resistant'' group, causing a median 13.5-fold increase in sensitivity compared with 2.4-fold in the "sensitive'' group. Furthermore, a positive correlation between the LC50 for platinum and the corresponding fold increase in sensitivity suggests that aphidicolin overcomes platinum resistance in fresh cells from primary tumours. These results encourage the further development of this interesting compound.     

膀胱肿瘤化疗药物敏感性试验对个体化治疗的指导作用

目的探讨药物敏感性试验对膀胱肿瘤灌注化疗药物选择的指导价值。方法将82例非肌层浸润膀胱尿路上皮癌患者非随机分为两组，药敏组34例行膀胱肿瘤细胞原代培养＋药物敏感性试验（MTT法），并根据药物敏感结果选择化疗药物行膀胱灌注，对照组48例按经验选择药物行灌注化疗。结果药物敏感试验结果显示对表柔比星敏感19例，敏感率59．4％；吡柔比星16例，敏感率47．6％；丝裂霉素20例，敏感率41．2％；羟基喜树碱30例，敏感率88．2％；平均随访22．3个月，药敏组复发率为11．7％（4／34），对照组复发率为31．2％（15／48），两组相比差异有统计学意义（P〈0．05）。结论膀胱肿瘤药物敏感性试验可以有效指导膀胱灌注用药，降低非肌层浸润膀胱尿路上皮癌远期复发率。     

Hematuria Screening Test for Urinary Bladder Mucosal Infiltration in Cervical Cancer

Objective: To determine the diagnostic performance of hematuria as a screening test for urinary bladderinfiltration in cervical cancer patients with a prospective study design. Materials and Methods: Newly diagnosedcervical cancer patients at Srinagarind hospital from 14 June 2011 to 30 April 2012 were enrolled in this study.We collected midstream urine samples for urinalysis from every patient before routine cystoscopic exam forclinical staging. The presence of 3 or more red blood cells (RBCs) per high power field was defined as positivefor hematuria. A two-by-two table was used to determine the diagnostic performance of hematuria to detecturinary bladder mucosal infiltration using cystoscopy and biopsy as the gold standard. Result: A total of 130 werepatients included, 54 of which (41.5%) had hematuria. Of these, four patients (3.08%) had pathological reportfrom cystoscopic biopsy confirmed metastatic squamous cell carcinoma. The sensitivity, specificity, PPV, NPV,and accuracy of hematuria as a screening test to detect urinary bladder mucosal infiltration of cervical cancerwere 100%, 60.3%, 7.4%, 100%, and 61.5%, respectively. There was no single case of urinary bladder mucosalinfiltration in patients initially staged less than stage III. Conclusions: Hematuria can be used as a screening testto detect urinary bladder mucosal infiltration of cervical cancer. This can reduce the number of cervical cancerpatients who really need to undergo cystoscopy as a staging procedure to less than half and to less than 20% ifstage III or more were included without missing a single case of urinary bladder mucosal infiltration.     

In vitro antitumor activity of teniposide against carcinoma of the lung in human tumor clonogenic assay

The antitumor activity of teniposide (VM26) on carcinoma of the lung was tested by comparing it with its congener, etoposide (VP16) in an in vitro soft agar clonogenic assay system (HTCA). Of 56 tumor biopsies placed in culture, 40 tumors were evaluable for drug sensitivity information (i.e., greater than or equal to 30 colonies in the control plate). The overall in vitro response rate (defined as less than or equal to 50% survival of TCFU) at the standard dose (10% peak plasma concentration) was 35%, which is higher than that of VP16 (28%). In cell lines derived from human carcinoma of the lung, VM26 showed 50% inhibition against colony formation of PC-7 cells at 0.45 microgram/ml which is less than that of VP16. A superior antitumor activity of VM26 on PC-9 cells was also observed. VM26 was observed to act faster than VP16 thus indicating its possible superior antitumor activity in vivo.