Biomedical subjects

A Steren

Publications and source records attributed to A Steren.

15 recordsLinked to original sources

PubMed1995

In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.

This is the first report on the ATP cell viability assay as a chemosensitivity test system for gestational trophoblastic neoplasms (GTN). We obtained chemosensitivity profiles in two established trophoblastic cell lines and four fresh tumors. Ten drugs were tested in vitro in the two cell lines JAR and JEG-3. The IC50 values of the 10 chemotherapeutic agents tested were very similar for both cell lines. The three most active drugs in these cell lines were VP-16, paclitaxel and vincristine. This is the first report on the activity of paclitaxel in trophoblastic cell lines. We furthermore evaluated this assay for chemosensitivity testing in four fresh malignant GTN tumors: one placental site trophoblastic tumor, one chorocarcinoma and two invasive moles. The placental site trophoblastic tumor specimen revealed to be rather chemoresistant in vitro whereas the other three tumors were chemosensitive. From our cell line data we conclude that the ATP cell viability assay is a practicable assay for chemosensitivity testing of GTN cell lines and gives repeatable results. However, the value of this assay for fresh GTN chemosensitivity testing needs to be defined.

Adenosine Triphosphate↗

PubMed1994

National survey of ovarian carcinoma. IV: Patterns of care and related survival for older patients.

BACKGROUND: An analysis was conducted by the American College of Surgeons Cancer Commission evaluating the patterns of care of ovarian cancer patients diagnosed in 1983 and 1988. The purpose of this study was to investigate whether there was a difference in the care patterns of elderly ovarian cancer patients and its impact on survival. METHODS: Data were collected from 25 consecutive patients whose disease was diagnosed initially at 904 participating hospitals with cancer programs in 1983 and 1988. The survival and care of patients greater than or equal to 80 years of age were compared to those less than 80 years of age. RESULTS: Of the 12,316 patients evaluated, 1,115 were 80 years or older. A significant reduction in survival was noted among patients 80 years and older as compared to their younger counterparts (P = 0.03-0.00001). The 5-year survivals were: stage I, 89% versus 79%; stage II, 58% versus 40%; stage III, 25% versus 11%; and stage IV, 13% versus 3%, respectively, for those less than 80 years old as compared to those greater than or equal to 80 years old. Most elderly ovarian cancer patients were cared for by nononcologists such as general surgeons (31%) and obstetricians/gynecologists (29%). As a group, older patients had fewer total abdominal hysterectomies, bilateral salpingo-oophorectomies, and omentectomies than their younger counterpart (P < 0.00001). As further evidence for a less aggressive surgical approach, the optimal tumor debulking rates of women greater than or equal to 80 years were significantly less than those of younger patients (P < 0.001). There was no significant increase in anesthesia complications between age groups. Generally, older patients are less likely to receive adjuvant chemotherapy than younger patients (42% versus 69%, P < 0.0001). CONCLUSION: It appears that conservative treatments contributed to the decreased survival of older ovarian cancer patients.

Age Factors↗

PubMed1993

National survey of ovarian carcinoma. Part V. The impact of physician's specialty on patients' survival.

BACKGROUND: Data analysis of the recent National Survey of Ovarian Carcinoma revealed significant differences in patterns of care among various physician specialists. The goal of this study was to determine if different care patterns led to differences in patient survival. METHODS: Data were collected from 25 consecutive patients with ovarian cancer diagnosed in 1983 and 1988 from 1230 hospitals with cancer programs across the United States. RESULTS: A total of 12,316 patients from 904 hospitals were registered, of whom 20.8% were cared for by gynecologic oncologists (GYO), 45.0% by obstetrician-gynecologists (OBG), and 21.1% by general surgeons (GS). GYO preferred the upper-lower midline incision in 44.1% of patients, whereas both OBG and GS chose the low midline approach in 44-45%. GYO performed more hysterectomies, oophorectomies, omentectomies, and lymph node and peritoneal biopsies than did other specialists. Although the rates of surgery of the small intestine were comparable between GYO and GS, the latter performed significantly more colostomies and resections of the large intestine. The optimal debulking rates were: GYO, 42-45%; OBG, 40-44%; and GS 25%. There was no significant survival difference between patients cared for by GYO and those cared for by OBG for all stage divisions. However, with the exception of patients with Stage I disease, patients cared for by GS had significantly reduced survival than did those cared for by GYO and OBG (P < 0.004). CONCLUSION: Efforts must be made to ensure that more patients with ovarian cancer are cared for by physicians in the appropriate specialties.

Female↗

PubMed1993

National survey of ovarian carcinoma. VI. Critical assessment of current International Federation of Gynecology and Obstetrics staging system.

BACKGROUND: The Commission on Cancer of the American College of Surgeons recently completed a national survey of patients with ovarian cancer. From the large database, the prognostic value of current International Federation of Gynecology and Obstetrics (FIGO) staging system for ovarian carcinoma was re-examined. METHODS: Data was collected from 25 consecutive ovarian carcinomas diagnosed in 1983 and 1988 at 904 hospitals with cancer programs. Among a total of 12,316 cases, 5156 patients had long-term survival data. RESULTS: The overall 5-year survivals were 88.9 +/- 0.9%; 57.1 +/- 2.4%; 23.8 +/- 1.3%; and 11.6 +/- 0.9% for Stages I, II, III, and IV, respectively. Pairwise survival comparisons using Lee-Desu statistic confirmed the prognostic value of current staging system (P < 0.00001). When survival data was substratified further to substage division, the 5-year survivals were: IA, 92.1 +/- 0.9%; IB, 84.9 +/- 3.4%; IC, 82.4 +/- 2.0%; IIA, 69.0 +/- 4.3%; IIB, 56.4 +/- 3.6%; IIC, 51.4 +/- 4.5%; IIIA, 39.3 +/- 2.8%; IIIB, 25.5 +/- 2.6%; IIIC, 17.1 +/- 1.4%; and IV, 11.6 +/- 0.9%. As the disease process becomes more advanced, patients' survival reduces proportionally. However, the survival reduction is relatively small between IB-IC and IIB-IIC divisions. Survival comparisons revealed significant prognostic value for most substage divisions (P = 0.03-0.0002) except for IB-IC and IIB-IIC combinations (P > 0.33). Further analyses revealed no significant differences between IB-IC and IIB-IIC patients in several prognostic parameters such as age, histologic grade, cell type, and amount of residual disease. CONCLUSIONS: These data support the current FIGO staging system. However, Substages IB-IC and IIB-IIC should be combined to respective single substages.

Adult↗

PubMed1993

Screening in gynecologic cancers.

Gynecologic malignancies account for approximately 13% of cancers in women. Ovarian and uterine cancer are among the five most common causes of cancer deaths in women, exceeded in incidence only by cancers of the breast, colon, and lung. Improved survival in patients with genital cancers predominantly reflects early diagnosis and not improved treatments. Even cancers for which there are effective screening and satisfactory treatments are seen more often than is acceptable. It is paramount that those entrusted with the health of women be knowledgeable about all cancer screening techniques and be able to identify the patient at risk for gynecologic malignancy. The provider's obligation to be vigilant about the signs and symptoms of cancer must be matched by the patients' responsibility to her own health. Regular gynecologic examinations, Papanicolaou (Pap) tests, and immediate reporting of unusual signs and symptoms are requirements that cannot be dismissed by patients. Education directed toward patients and health care providers can optimize survival. The Pap test for cervical cancer remains a universally accepted screening procedure. Human papillomavirus (HPV) DNA typing, cervicography, loop electrosurgical excision procedure (LEEP), transvaginal ultrasonography, color flow doppler, endometrial sampling, and serum CA 125 measurements are some of the newer techniques being investigation as potential screening tools. Although additional prospective studies are needed to establish the value of these modalities, there is little doubt that prognostic information obtained from these modalities will influence the clinical care of patients in the near future.

Antigens, Tumor-Associated, Carbohydrate↗

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

Taxol sensitizes human ovarian cancer cells to radiation.

Taxol is an exciting antineoplastic agent with a novel mechanism of action. This study was designed to explore the potential use of taxol as a radiation sensitizer. Three human ovarian cancer cell lines were used: BG-1, SKOV-3, and OVCAR-3. These cell lines were treated in the proliferative and confluent state with taxol doses of 0.0001X, 0.0005X, 0.001X, 0.005X, and 0.01X peak plasma concentration of taxol for 90 min and then irradiated either 24 or 48 hr later. Doses of cobalt60 were 0, 2, 5, 8, and 10 Gy. ATP bioluminescence assays were performed on Day 7 after irradiation. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test and analysis of variance was performed. Taxol was found to have a significant radiosensitizing effect on all cell lines. Proliferating cells were more sensitive to taxol, radiation, and the combination than confluent cells. Treatment of proliferating cells with taxol 48 hr prior to irradiation had a greater radiosensitizing effect than treatment 24 hr prior to irradiation. In summary, taxol is a potent radiosensitizer in ovarian cancer cell lines and should be considered for further study.

Adenosine Triphosphate↗

PubMed1993

Radical hysterectomy for stage IB adenocarcinoma of the cervix: the University of Miami experience.

The treatment of adenocarcinoma of the cervix has traditionally followed that of squamous cancer. A 25-year review of 88 radical hysterectomies for Stage IB adenocarcinoma of the cervix at the University of Miami/Jackson Medical Center (UM) is compared to over 1600 cases reported in the literature. Adenocarcinoma represented 10.4% of 978 radical hysterectomies performed at UM from July 1965 to December 1990. In a survey of the literature, patients with Stage IB cervical adenocarcinoma treated by radical surgery alone had a statistically better 5-year survival than those treated by radiation alone (79% vs 67%, respectively; P < or = 0.05). Furthermore, no additional benefit was achieved by combining the two therapeutic modalities. The corrected 5-year survival at UM is 81% for Stage IB adenocarcinoma of the cervix treated with radical hysterectomy, a number consistent with the cumulative data base. Radical surgery is an acceptable primary therapy in Stage IB adenocarcinoma of the cervix.

Adenocarcinoma↗

PubMed1993

Taxol as a radiation sensitizer: a flow cytometric study.

Taxol is an exciting antineoplastic agent with a novel mechanism of action. Taxol has been shown to prolong the G2/M phase of the cell cycle. This cell cycle perturbation has been the explanation given for the radiation-sensitizing effects seen with taxol in vitro. The aim of this study is to evaluate the cell kinetics of the BG-1 human ovarian cancer cell line after treatment with nontoxic doses of taxol and radiation (RT). This cell line was treated in the proliferative state for 90 min with 5 nM taxol and then irradiated 48 hr later with 2 Gy of Cobalt60. Flow cytometric evaluations of cell cycle perturbations were performed at 24-hr intervals from 0 through 216 hr. ATP cell viability assay was performed in parallel to obtain survival data. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. At this nontoxic dose of taxol no cell cycle perturbations as compared to control were seen. Radiation sensitization was still found. Sensitizer enhancement ratio was 2.3 at 10% survival. The RT-related G2/M block peaked at 24 h after RT and then resolved. The combination of taxol and radiation resulted in a large prolonged block in G2/M that did not resolve through the duration of the experiment. In summary, taxol sensitized cells to radiation at a dose that was not cytotoxic and that did not cause cell cycle perturbations.

Cell Survival↗

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↗

PubMed1992

Rationale of combining radiation and interferon for the treatment of cervical cancer.

The recent surge of interest in the mechanisms of action of biomodulators, also known as biological response modifiers, offers a new avenue of approach in the treatment of cancer. The in vitro antitumor activities of these agents, such as interferons, when combined with chemo- or radiotherapy, have generated enthusiasm among clinicians for developing clinical trials. In recent years many antineoplastic agents have been investigated as neoadjuvant or adjuvant therapy for patients with cervical cancer in an attempt to improve local control and to decrease incidence of metastasis. Normal tissue tolerance limits the potential combinations of standard cytotoxic chemotherapeutic agents with radiation. Interferon used as a radiomodulator has been studied mainly for the treatment of lung cancer with promising results. In this paper we report the rationale of combining interferon and radiation for the treatment of patients with cervical cancer.

Animals↗

PubMed1982

Formation and resealing of intercalator-induced DNA strand breaks in permeabilized L1210 cells without the stimulated synthesis of poly(ADP-ribose).

DNA strand breaks produced by damaging agents such as x-ray generally stimulate poly(adenosine diphosphoribose) (ADP-R) synthesis in mammalian cells. DNA intercalating agents induce the formation of strand breaks which are unusual in that they are associated with tightly or covalently bound protein. In order to determine whether the intercalator-induced strand breaks are associated with poly-(ADP-R) synthesis, L1210 cells were treated with the intercalating agent, 4'-(9-acridinylamino)methanesulfon-m-anisidide. Poly(ADP-R) synthesis, measured by [3H]NAD incorporation following cell permeabilization, was enhanced in x-irradiated cells, but not in cells exposed to 4'-(9-acridinylamino)methanesulfon-m-anisidide at doses which produced equivalent strand breaks frequencies. The permeabilized cell system did not support DNA synthesis and x-ray-induced strand breaks did not reseal. The intercalator-induced strand breaks, however, resealed within 10 min. Hence, the strand breaks observed in intercalator-treated cells may not constitute DNA damage in the usual sense. The resealing of intercalator-induced DNA breaks in the absence of DNA or poly(ADP-R) synthesis is unique among chemical or physical agents which produce DNA scissions.

Aminacrine↗

PubMedDate not supplied

Growth characteristics of nonmalignant cells in the ATP cell viability assay.

Over the last 5 years, the ATP cell viability assay (ATP-CVA) has been used to study the in vitro response of cell lines and fresh gynecologic human tumors to a variety of antineoplastic agents including chemotherapeutic agents, hormones and biological response modifiers. This assay measures light production as intracellular ATP interacts with the luciferin-luciferase complex. Quantitation of the light produced has been shown to directly correspond with the number of viable cells. A past criticism is that in the ATP-CVA, when applied to fresh tumor tissue, normal cells (fibroblasts, macrophages and lymphocytes) also produce ATP, and if present in sufficient numbers, could lead to errors in chemosensitivity testing results. This study was designed to evaluate the growth characteristics of various benign cells found in fresh tumors. The cells were studied under multiple plating conditions to show the relative increase or decrease of fractional ATP measured at different time points. We found that agar/McCoy underlayer and agarose-coated wells do not permit the growth of nonmalignant cells. In the culture conditions of the ATP-CVA, non-malignant cells do not contribute relevant ATP levels when treated samples are compared to controls on day 6. Therefore, results of the ATP-CVA in fresh tumors should not be affected.

Adenosine Triphosphate↗

PubMedDate not supplied

Comparative chemosensitivity profiles in three human breast cancer cell lines with the ATP-cell viability assay.

In this study the dose-response curves for doxorubicin, pirarubicin, 5-fluorouracil, 4-hydroperoxy-cyclophosphamide and taxol were obtained in three breast cancer cell lines (MCF-7, T47D and BT-20). The ATP cell viability assay was chosen to evaluate the chemosensitivity profiles and was a reproducible, practicable method to assess drug response in breast cancer cell lines. The IC50 values were calculated on the median effect principle and indicated that taxol was the most active drug tested in this study with a mean IC50 value of 0.02 microM. This in vitro effect correlated well with clinical observations in metastatic breast cancer where taxol proved to be a vary active drug. Pirarubicin was the second most active drug tested with an IC50 value 10 times less compared to that of doxorubicin. The results obtained with the ATP cell viability assay are promising, therefore further testing with drug combination chemotherapy and fresh human breast cancer tumor testing are warranted and ongoing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗