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R Angioli

Publications and source records attributed to R Angioli.

52 records · Page 3Linked to original sources
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

The role of DNA index as a prognostic factor in early cervical carcinoma.

The value of DNA index as a prognostic factor in early cervical cancers was investigated. A total of 124 patients who underwent radical hysterectomy for stages IB-IA cervical cancers from 1/1982 to 12/1985 were included. Paraffin blocks were available in only 98 patients for the analysis. After dewaxing, rehydrating, and enzyme disaggregation, cells were subjected to dual parameter flow cytometry. Tumor DNA index was calculated and the results were correlated with 5-year survival, stage, grade, tumor size, nodal metastasis, surgical margins, and lymphovascular invasion. There were 1% hypoploid, 7.3% diploid, 72.9% aneuploid, 16.7% tetraploid, and 2.1% hyperploid. At the end of 5 years, there were 69 alive and 27 dead patients with mean DNA indices of 1.50 +/- 0.3 and 1.70 +/- 0.3, respectively. t Test analysis revealed that mean DNA index of deceased patients was significantly higher than that of alive ones (P = 0.008). Survival analysis demonstrated the prognostic significance of DNA index 1.70 (P = 0.017). Median survival of patients with DNA index of 1.70 or greater was 36 months in contrast to 73.5 months for those with DNA index less than 1.70. Multivariate analysis subsequently confirmed DNA index of 1.70 as an independent prognostic indicator with a hazard ratio of 2.05.

Carcinoma↗
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↗
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

Determination of hormonal response in uterine cancer cell lines by the ATP bioluminescence assay and flow cytometry.

Although progesterone receptor status has been shown to correlate with response to hormonal therapy, not all progesterone receptor-positive patients respond to this treatment and additional biologic assays are needed to help better predict clinical response to hormonal therapy. This study explored the potential of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response. Five uterine cancer cell lines were used: AE7, ECC-1, HEC1A, AN3, and SKUT1B. Cells were exposed to Provera or tamoxifen at 0.1, 0.2, 0.5, 1, 2, and 5X (X equal to peak plasma concentrations: 1.0 micrograms/ml Provera and 0.1 micrograms/ml tamoxifen). For correlation, estrogen and progesterone receptors were determined by the standard dextran-coated charcoal method. Only AE7 and ECC-1 were positive for progesterone receptors (501 fmol/mg AE7, 194 fmol/mg ECC-1) and the rest were negative (less than 8 fmol/mg). Tamoxifen exerted no inhibition to the above cell lines. Meanwhile, Provera exerted dose-response inhibition on both AE7 and ECC-1 cell lines. The effects of accumulation of G0-G1 phase and reduction of S, G2 cells (P less than 0.05), but not on the HEC1A cell line (P = 0.4). These changes confirmed the antiproliferative property of Provera. Further studies are needed to establish the role of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response.

Adenocarcinoma↗
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↗
PubMedDate not supplied

Surgical management of advanced and recurrent cervical cancer.

Since the early 1940s, the incidence of cervical cancer has dramatically decreased due in large part to the work of Papanicolaou and Traut. Successful treatment can now be done using simple or radical surgical intervention for early invasive lesions and radiation therapy for more advanced lesions. However, despite current advances in screening and early treatment, local recurrences still happen and are difficult to treat. The natural history of cervical cancers is that of a slowly growing, locally invasive tumor. As such, it lends itself to radical surgical resection in selected patients prior to distant metastasis. Current advances in intraoperative and postoperative monitoring, as well as improved surgical techniques and devices, have decreased the morbidity and mortality of radical surgical procedures to acceptable levels. Current data associated with these procedures for advanced or recurrent cervical cancer are described.

Combined Modality Therapy↗
PubMedDate not supplied

Gynecological cancers in developing countries: the challenge of chemotherapy in low-resources setting.

The epidemiologic pattern of cancers in developing countries differs in many aspects from that of industrialized nations. Cancer natural history, microbiologic environment, patient's immune system, and drug availability may differ as well. Four of five new cases of cervical cancer and most of cervical cancer deaths occur in developing countries. Where chemoradiation and supportive care facilities are unavailable, it would be logical to consider an inexpensive effective drug. In locally advanced cases, neoadjuvant chemotherapy followed by surgery should be considered the treatment of choice. For ovarian cancer, it may be reasonable to maintain a secure supply of platinum and/or taxanes. For endometrial cancer, platinum compounds are proved active chemotherapic single agents. Oral medroxyprogesterone acetate (MPA) may represent a good chance for treating an advanced or recurrent disease. For vulvar/vaginal cancer, the role of chemotherapy alone is currently considered limited, and it is mostly used as palliative treatment in advanced or recurrent cases. Whenever possible, standard western chemotherapic regimens should be applied in developing countries as well. When standard therapies are unavailable, drugs of choice should be easily accessible, inexpensive, and effective. The most commonly used drugs are cisplatin, cyclophosphamide, and MPA.

Antineoplastic Agents↗
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↗