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M Untch

Publications and source records attributed to M Untch.

At least 91 records · Page 5Linked to original sources
PubMed1994

Evaluation of paclitaxel (taxol), cisplatin, and the combination paclitaxel-cisplatin in ovarian cancer in vitro with the ATP cell viability assay.

This study evaluates the in vitro sensitivities of 42 ovarian cancer specimens to the new anticancer agent Paclitaxel (taxol, Tx), cisplatin (DDP), and the combination Tx-DDP with the adenosine triphosphate cell viability assay (ATP-CVA). In vitro response is defined by > or = 50% ATP decrease compared to untreated controls 6-7 days after drug treatment with 20% of the peak plasma concentration (PPC). Response rates were 12% to Tx, 19% to DDP, and 27% to Tx + DDP. The mean IC50's of Tx, DDP, and the combination Tx-DDP were (2.6x, 1.0x, and 0.38x PPC, respectively). The mean inhibition of cell viability was significantly greater with drug combinations compared to single drugs. In 7/11 tumors synergistic effects and in 2/11 additive effects were found between Tx and DDP. We conclude that based on ATP-CVA in vitro results, Tx-DDP shows significantly better activity compared to each of the single drugs in ovarian cancer.

Adenosine Triphosphate↗
PubMed1994

Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up.

We examined bone marrow aspirates from 100 metastasis-free primary breast cancer patients. In 38/100 patients (38%), tumour cells were detected in the marrow using an immunocytochemical technique with a cocktail of two monoclonal antibodies: anti-EMA and anti-cytokeratin. Median follow-up was 34 months: 15/38 (39%) tumour cell-positive patients have since relapsed, but only 9/62 (15%) tumour cell-negative patients. The median interval between tumour cell detection and relapse was 11.4 months. No statistically significant correlation existed between tumour cell presence and 'established' prognostic factors. However, relapse-free survival was significantly shorter in tumour cell-positive patients. Multivariate analysis showed tumour cell presence as a strong, significant prognostic factor for relapse-free as well as overall survival. We conclude that screening for tumour cells in bone marrow of primary breast cancer patients identifies high-risk patients for early relapse. In particular, patients with node-negative tumours who have tumour cells in their bone marrow may require subsequent systemic therapy.

Adult↗
PubMed1994

Comparison of paclitaxel and docetaxel (Taxotere) in gynecologic and breast cancer cell lines with the ATP-cell viability assay.

The in vitro effects of paclitaxel (Tx) and docetaxel (Taxotere, Txt) are compared in this study using the adenosine triphosphate cell viability assay (ATP-CVA) in 14 cancer cell lines. Eleven cell lines were sensitive and three were partially sensitive to paclitaxel. Nine cell lines were sensitive, three were partially sensitive and two were resistant to docetaxel. Mean IC50s were 3.7-660 ng/ml paclitaxel and 5.4-540 ng/ml docetaxel. In five sensitive cancer cell lines docetaxel was more active than paclitaxel, and in six sensitive cell lines paclitaxel was more active than docetaxel on a concentration basis. Two cell lines were sensitive to paclitaxel and resistant to docetaxel. In one cell line the two compounds had similar activities. In the ATP-CVA, paclitaxel and docetaxel are very active and are partially non-cross-resistant.

Adenocarcinoma↗
PubMed1994

Contrast-enhanced MR imaging of the breast: comparison of two different doses of gadopentetate dimeglumine.

PURPOSE: To optimize detection and diagnosis of breast lesions with contrast-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: A three-dimensional fast low-angle shot pulse sequence was used for a group comparison consisting of 76 high-dose (0.16 mmol gadopentetate dimeglumine per kilogram of body weight) and 76 low-dose (0.1 mmol/kg) examinations. Intraindividual comparisons were possible in a subgroup of 20 patients. RESULTS: Enhancement with the high dose was about 1.5 times higher for benign and malignant tissues. With the lower dose, no false-positive findings could be avoided and definition of a threshold that excluded false-negative findings was problematic. Conspicuity of malignant lesions was much improved with the higher dose (a good to excellent rating in 81% vs 26% with the lower dose). Three small foci were visible only with the higher dose. CONCLUSION: The higher dose of contrast material allowed much better results. Dose comparison studies are also recommended for other techniques.

Breast↗
PubMed1994

Flow cytometric DNA analysis of breast cancer by two colour method using cytokeratin labeling for identification of tumour cells.

Flow cytometric assessment of DNA-ploidy and S-phase fraction in breast cancer is compromised by the heterogeneity of cell subpopulations derived from the malignant and surrounding connective tissue, e.g. tumour, stromal and inflammatory cells. To identify tumour cell subpopulations, epithelial cells were labeled by a FITC-conjugated cytokeratin antibody (CK6, CK18) prior to flow cytometric cell cycle analysis in 205 fresh specimens of primary breast cancer. We found 158/205 (77%) DNA-aneuploid tumours compared to 127/205 (62%) without identification of cytokeratin positive cells (P < 0.001). In addition, the number of detected DNA-multiploid tumours rose from 31 (15%) to 51 (25%) after gating for cytokeratin positive cells. In DNA-diploid tumours, S-phase and G2M-phase fractions were significantly higher in cytokeratin positive (tumour) cells compared to total cell populations (4.4% and 5.8% vs. 3.2% and 4.4%; P < 0.001). Cytokeratin negative cells were found in all tumours and can be used as internal standard for calculation of ploidy and for quality control (CV, linearity) of each individual sample. We conclude that at least 20% of DNA-aneuploid tumours would not have been diagnosed without cytokeratin labeling. In addition, influence of non-tumourous cell elements on cell cycle analysis can be markedly reduced. Therefore, both determination of DNA-ploidy and cell cycle analysis can be optimized by cytokeratin labeling.

Breast Neoplasms↗
PubMed1993

In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines.

BACKGROUND: This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. METHODS: Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. RESULTS: The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. CONCLUSIONS: Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations.

Carcinoma, Squamous Cell↗
PubMed1993

Enhancement of progesterone receptor levels by interferons in AE-7 endometrial cancer cells.

BACKGROUND: Interferon (IFN) has been reported to increase hormone receptor expression in breast cancer cells and to sensitize them to antiproliferative hormones. Endometrial cancer cells with high progesterone receptor (PR) level respond better to progesterone therapy than cells with either low or absent PR level. The effect of four different interferons (alpha and beta, both natural [n] and recombinant [r]) on cell proliferation and steroid receptor levels was investigated in the PR positive AE-7 human endometrial cancer cell line over a period of 12 days. METHODS: Cells were exposed to 10,100 and 1000 IU/ml of each IFN either for 3 days or continuously for 12 days. Hormone receptors were determined by the monoclonal enzyme immunoassay. Chemosensitivity was evaluated with the adenosine triphosphate-cell viability assay. RESULTS: AE-7 has a low level of estrogen receptors, which was not significantly affected by IFN exposure. The four IFN showed significantly enhanced PR levels over 12 days in both the 3-day and continuous-exposure experiments. No significant difference of PR enhancement was observed between 3 days and continuous exposure to IFN. This increase of receptors did not appear to be dose related. IFN enhanced PR level to a maximum level of about two times control cells. IFN did not produce significant cytotoxicity. Antiproliferative activity was observed with nIFN beta and rIFN beta at 1000 IU/ml dose in continuous-exposure experiments, which showed survival values of 79% and 69% respectively, compared with control at day 12. CONCLUSIONS: These preliminary data on PR expression modulation support other studies, which have shown that IFN modulate hormone receptor expression and, therefore, may play a role in the treatment of endometrial cancer.

Adenosine Triphosphate↗
PubMed1993

Characteristics of the combination paclitaxel plus doxorubicin in breast cancer cell lines analyzed with the ATP-cell viability assay.

Preliminary clinical data show promising activity regarding the combination of paclitaxel (Taxol) (TAX) and doxorubicin (Adriamycin) (ADR) in the treatment of breast cancer. This combination needs both further preclinical and clinical investigations to better understand the drug interaction, and to optimize the dose and schedule of these drugs. This study was done to evaluate the combination effect of TAX and ADR in three human breast cancer cell lines. The ATP-Cell-Viability Assay was used to evaluate the chemosensitivity profiles and to obtain dose response curves. For quantitation of synergism and antagonism the median-effect principle was applied and the corresponding combination index values were calculated. Drug synergism/antagonism was shown to be dose-related; synergism was enhanced at higher fractions affected. From this preclinical data, we have concluded that TAX-ADR is highly effective and partly synergistic in vitro. In spite of severe initial toxicities in early clinical trials in metastatic breast cancer patients, further clinical studies appear to be justified in order to define a tolerable dosage.

Adenosine Triphosphate↗
PubMed1993

[Adenocarcinoma and adenosis of the vagina. On the histogenesis, diagnosis and therapy of a rare genital neoplasms].

In the United States, vaginal adenosis and clear-cell carcinoma of the vagina were frequently observed in young women, who had been exposed to the synthetic estrogen diethyl-stilbestrol (DES) during their embryonic development. In Germany, obviously, no such exposure occurred. Clearly, such diseases also develop without the context of intrauterine exposure to certain substances. Our own case of such a partly exophytic, partly endophytic adeno-carcinoma of the vagina with multifocal vaginal adenosis, demonstrates the histogenesis, symptoms, diagnostic procedures and therapy of this rare disease. Since young women during their reproductive years are mostly affected, the possibility of fertility-conserving surgery is discussed despite the current practice of radical cancer surgery (with and without radiation). In the 25-year-old patient, we conducted a colpectomy whilst leaving the uterus and ovaries, and replaced the vaginal defect by a sigmoid transplant anastomosed to the cervix. The patient has regular menstrual cycles, should, however, not become pregnant for 1 to 2 years for oncological reasons.

Adenocarcinoma↗
PubMed1993

In vitro evaluation of the novel chemotherapeutic agents U-73,975, U-77,779, and U-80,244 in gynecologic cancer cell lines.

U-73,975 (U-73), U-77,779 (U-77), and U-80,244 (U-80) are analogs of the potent antitumor compound CC-1065. This class of drugs act as alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study was designed to compare the potencies of U-73, U-77, and U-80 with cisplatin (DDP) or adriamycin (DXR) in 10 gynecologic cancer cell lines. The mean IC50s were: U-73, 0.173 +/- 0.115 ng/ml; U-77, 0.650 +/- 0.209 ng/ml; U-80, 3.0 +/- 3.0 ng/ml; DDP, 4.40 +/- 2.83 micrograms/ml; and DXR, 0.286 +/- 0.040 micrograms/ml. U-73 appears the most potent analog, being 10(3) to 10(4) times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 10(2) to 10(3) greater potency than DDP and DXR. All the cervical, endometrial, and ovarian cell lines were sensitive to U-73, with decreasing sensitivity to U-77, U-80, DXR, and DDP in that order. U-73 as well as the other analogs appear promising chemotherapeutic agents.

Adenosine Triphosphate↗
PubMed1992

Chemosensitivity to the new anthracycline pirarubicin and other chemotherapeutic agents in primary and recurrent ovarian tumors in vitro.

We analysed the in vitro sensitivity of 50 fresh gynecologic cancer specimens to the new anthracycline-analogue pirarubicin (Pira). Nine endometrial and cervical tumors were excluded from the evaluation in this study. The in vitro sensitivities of 41 ovarian cancer specimens to Pira were evaluated with the adenosine triphosphate chemosensitivity assay (ATP-CSA). The results were compared to the sensitivity of drugs used in gynecologic oncology: Adriamycin, cisplatin, and the metabolite of cyclophosphamide, 4-hydroxycyclophosphamide (4-HC). Sensitivity (S) is defined as > or = 70%, partial sensitivity as 50-69% ATP decrease compared to controls at 20% of the peak plasma concentration. In vitro response is defined as S + PS. Twenty-two primary ovarian tumors were assayed, with 77% response to Pira, 12% to Adriamycin, 29% to cisplatin, and 38% to 4-HC. In 19 recurrent ovarian tumors, Pira showed 53% response; Adriamycin, 25%; cisplatin, 8%; and 4-HC, 67%. The in vitro data are partly consistent with reported data from the literature. Pira reveals a significantly higher degree of cytotoxicity compared to the three drugs listed above. The IC50 of Pira is less than 20% of the peak plasma concentration achievable in patients and is significantly lower compared with the IC50s of other drugs. We conclude from our in vitro data that Pira is more active than Adriamycin, cisplatin, and 4-HC.

Adenosine Triphosphate↗
PubMed1992

Comparison of U-73,975 and cisplatin cytotoxicity in fresh cervical and ovarian carcinoma specimens with the ATP-chemosensitivity assay.

U-73,975 (U-73), a closely related synthetic analogue of the antitumor agent CC-1065, acts by binding tightly in the minor groove of DNA. A comparison was made between the cytotoxicity of U-73 and cisplatin (DDP) on 11 fresh cervical and 7 fresh ovarian carcinoma specimens. The ATP-chemosensitivity assay as previously described (Sevin et al. Gynecol. Oncol. 31, 191-204, 1988) was used to determine the cytotoxic effect of U-73 and DDP. IC 50s were calculated using regression analysis. The mean IC 50s for U-73 and DDP were 519 pg/ml and 2918 ng/ml, respectively, for the cervical carcinoma specimens and 324 pg/ml and 2649 ng/ml, respectively, for the ovarian carcinoma specimens. Significance comparing U-73 and DDP for cervical and ovarian tissue was demonstrated with P < 0.001. U-73 was 4000 times as cytotoxic per unit of mass as DDP on cervical carcinoma compared to over 8000 times for ovarian carcinoma. Based on these in vitro data, U-73 appears to be a very promising antitumor agent for cervical and ovarian carcinoma.

Adenosine Triphosphate↗
PubMed1992

Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines.

Pirarubicin (PIRA) has been shown to have improved potency with less cardiac toxicity in several phase I and II clinical trials in Japan and Europe. Since Adriamycin (DXR) remains one of the most potent drugs in treatment of gynecologic cancers, this derivative has the potential to become an important chemotherapeutic agent. In this study, we compared the performance of these two drugs against a panel of 10 gynecologic cancer cell lines. The ATP chemosensitivity assays were used to determine dose-response curves. Flow cytometry was used to study cell kinetic response to both drugs. Using an IC50 value of 0.2 micrograms/ml as a cutoff for drug sensitivity, 4 cell lines, ECC1, HEC1B, BG1, and SKOV3, were considered resistant to DXR. By comparing IC50s, PIRA was 3.4 +/- 0.4 times more potent than DXR (P = 0.05). The other 6 cell lines, AN3, AE7, HEC1A, CAOV3, SKUT1B, and ME180, were considered sensitive to DXR. In this group of cell lines, PIRA was 1.6 +/- 0.3 times more potent than DXR (P = 0.5). Both PIRA and DXR elicited a spectrum of cell kinetics. By comparing the magnitude of G2 blocks at 0.1 micrograms/ml, PIRA was approximately 2-5 times more potent than DXR in SKUT1B, HEC1A, and BG1 cell lines. PIRA also displayed a reverse dose-response pattern of G2 block so that at high dose, cell cycle kinetics would mirror those of untreated controls. This observation supports the presence of a resistant tumor subpopulation and the concept of tumor heterogeneity.

Antibiotics, Antineoplastic↗