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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 235 records · Page 13Linked to original sources
PubMed1995

[Italian study on the chemoprevention of breast cancer with tamoxifen].

There is currently a large breast cancer chemoprevention trial in Italy. The trial is based on the use of the antioestrogen tamoxifen, which is one of the most successful and most studied anticancer drugs. There is a strong evidence that this drug can prevent the growing of controlateral cancer in women previously operated for breast cancer. The chemoprevention trial using tamoxifen includes healthy women, aged 35 to 70 and hysterectomised. The participants are taking either 20 mg/day of tamoxifen or placebo for 5 years, in double blind; then they are followed-up clinically and instrumentally every 6 months for the further 5 years. The main end-point of the study is to verify the reduction of incidence and mortality from breast cancer. It was decided to recruit only hysterectomised women on the consideration that, according to some studies, tamoxifen could give an additional risk of endometrial cancer: the Italian study was especially designed with the intention of avoiding this unjustified risk.

Adult↗
PubMed1995

Oncogenic transformation of C3H 10T1/2 cells exposed to alpha particles: sensitivity through the cell cycle.

Oncogenic transformation of synchronized C3H 10T1/2 cells was determined after exposure to 4.3 MeV alpha particles (LET = 101 keV/microns). Two synchronization techniques were tested using basic and modified protocols: one based on the release of cells from contact inhibition and the second on the mitotic shake-off method. Progression of cells through the cycle was followed as a function of time by flow cytometric analysis, DNA labeling for passage through S phase, the growth curve for the cell number and mitotic index measurements. The conclusion is that, although the release of cells from confluence provides higher yields of synchronized cells, mitotic shake-off proved to be the best way of collecting a synchronized population of minimally perturbed cells. Cells synchronized by mitotic shake-off were irradiated with 0.30 Gy in the interval between 2 and 10 h corresponding to G1 and early S phases. For comparison asynchronous populations were irradiated in parallel. Oncogenic transformation frequency, corrected for background, in mid-G1 phase was (18 +/- 4) x 10(-5) (average values of frequencies at 4 and 6 h) compared with the value of (8 +/- 4) x 10(-5) for the asynchronous population. While these data are suggestive of a trend toward a slightly increased sensitivity in mid-G1 phase, it is not statistically significant. The surviving fraction is constant in G1 phase.

3T3 Cells↗
PubMed1995

[The study of the modification of the natural resonance of the external ear following tympanoplasty].

The shape, position and amplitude of the natural resonance curve of external ear is related to sensation evoked in a subject by sound coming from the external environment. The involution of this curve varies from individual and is the sum of the effects provoked on the incident sound by the head, auricle and the conformation of canal (EEE = External Ear Effect). Natural amplification supplied by the system allows the individual to distinguish natural sound, whose being natural make them pleasant to hear. Any interventions that modifies the anatomy of the auricle and/or the canal activity alternates the REUR (Real Ear Unaided Response) to some degree. Restoration of basic anatomical conditions are choice of interventions which displace the curve only slightly allows a physiological sensation of sound to be maintained. Surgeon often neglect this little studied aspect preferring to evaluate this work in terms of quantity thus rather ignoring the quality of sound achieved.

Ear↗
PubMed1994

Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide.

Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized in the United States in the late 1960s. This retinoid shows a preferential accumulation in breast instead of liver, is effective in the inhibition of chemically induced mammary carcinoma in rats, and has proved to be less toxic than many other vitamin A analogues. The Milan Cancer Institute has put a particular effort in this molecule in both the experimental and clinical fields. We have demonstrated, in animals and humans, that fenretinide induces a rapid reduction of retinol plasma concentration, that its blood levels remain constant during administration for as long as 5 years, and that the drug is able to accumulate in the human breast. To date, 2969 stage I breast cancer patients have been randomized to evaluate the efficacy of this retinoid to prevent contralateral new primaries, 709 subjects have been accrued in a prevention trial of basal cell carcinoma of the head and neck, and 153 patients entered a study the preliminary results of which already show the capability of fenretinide to prevent recurrences and new localizations of oral leukoplakia. Further studies on fenretinide will be aimed at evaluating its preventive efficacy in superficial bladder and prostate cancers and at exploring possible synergism with tamoxifen and interferons in breast cancer and skin cancer, respectively.

Anticarcinogenic Agents↗
PubMed1994

Successful topical treatment of oral lichen planus and leukoplakias with fenretinide (4-HPR).

Eight patients with diffuse (non-operable) pre-cancerous lesions (oral lichen or leukoplakias) were treated with fenretinidec (4-HPR) applied topically twice daily. After one month of therapy two patients had complete remission and the other six had a greater than 75% response. 4-HPR was well tolerated, and no local or distant side effects were observed. Topical treatment may be combined with oral administration at lower doses to obtain therapeutic results with less toxicity than observed with oral administration alone. A study to further evaluate the efficacy of topical treatment is in progress at our institute.

Administration, Oral↗
PubMed1994

Effect of the synthetic retinoid fenretinide on dark adaptation and the ocular surface.

BACKGROUND: Fenretinide, a synthetic derivative of retinoic acid, is under study in clinical trials for the prevention of breast, skin basal cell, bladder, and oral cancer in patients at risk. Although fenretinide is well tolerated even after prolonged use, it does lower plasma retinol levels and thus may affect night vision. PURPOSE: The purpose of this study was to measure changes in dark adaptation resulting from fenretinide administration, to compare the measured results with the patient's subjective perception, to define the association with plasma retinol levels, to assess the reversibility of alterations in night vision, and to assess the effects of fenretinide on the surface of the eye. METHODS: The study involved 65 women who had been operated on for stage I breast cancer. Of the study group, 34 received 200 mg daily of fenretinide for a median of 32 months, while 31 control subjects did not. Dark adaptation was studied with the Goldmann-Weekers adaptometer and with a subjective questionnaire. Plasma retinol levels were measured at each test of dark adaptation. Effects of fenretinide on the ocular surface were evaluated through conjunctival impression cytology. RESULTS: Of the patients on fenretinide, eight (23.5%) showed mild and nine (26.5%) showed moderate alterations of measured dark adaptability, compared with just two controls (6.5%) with mild alterations (cumulative odds ratio = 15.4; P = .0008). A significant inverse correlation exists between the final sensitivity threshold of dark-adaptometry and plasma retinol levels, with mild alterations arising below 16 micrograms/dL and moderate alterations below 10 micrograms/dL. Abnormal rod function improved significantly after 7 days and normalized 1 month after use of fenretinide was stopped or vitamin A supplementation was begun, while the conventional 3-day drug suspension, or drug half dose, did not allow sufficient recovery. Alterations of conjunctival cytology were slightly higher in patients receiving fenretinide, but no clinical disorders of the ocular surface were observed. CONCLUSIONS: The women treated with 200 mg fenretinide daily showed a relatively high incidence of mild-to-moderate alterations of dark-adaptometry as measured with the Goldmann-Weekers adaptometer. However, the real-life implication of the measurements is an open question, for the questionnaire shows that 50% of the patients with altered dark adaptometry were asymptomatic.

Breast Neoplasms↗
PubMed1994

Visualization of the endogenous NF-kappa B p50 subunit in the nucleus of follicular dendritic cells in germinal centers.

NF-kappa B, a 50 kDa/65 kDa (p50/p65) heterodimer, is a ubiquitous transcription factor involved in the positive regulation of various immune genes. The aim of this study was to determine whether NF-kappa B is related to a particular cell type and/or differentiation step during immunopoiesis. Using in situ hybridization on sections from non HIV hyperplastic lymph nodes, we found that the gene of the 105 kDa precursor of p50 was overexpressed in the light zone of germinal centers, with a network aspect, which suggested the involvement of follicular dendritic cells (FDC). By immunohistochemistry, p50 protein was detected in the cytoplasm and nucleus of FDC, confirming the involvement of FDC. Furthermore, p50 protein was detected in the cytoplasm of all lymphocytes. Thus, we focused our study on isolated FDC clusters from normal tonsils. As showed on tissue sections, we detected the p50 in both cytoplasm and nucleus of FDC. Nuclei of lymphocytes from FDC clusters were negative. We next studied p65 and c-Rel protein expression in FDC clusters. p65 was detected in the cytoplasm of FDC, whereas nuclei were negative. Furthermore, p65 was detected in the nuclei of some lymphocytes. c-Rel protein was detected only in the cytoplasm of lymphocytes and not in the nucleus and cytoplasm of FDC. Our results indicated that, in the context of T cell-dependent B cell immunopoiesis occurring in FDC clusters, p50 is mainly related to FDC with a massive overexpression in the nuclei, whereas p65 is expressed in a scattered manner in the nuclei of lymphocytes and c-Rel protein exclusively in the cytoplasm of lymphocytes from FDC clusters. These results suggested that the two subunits of NF-kappa B and the c-Rel protein have different roles in different cell types during B cell immunopoiesis.

Adolescent↗
PubMed1994

Cell kinetics of colorectal liver metastases.

PURPOSE: Liver metastases are the main cause of death in patients with colorectal cancer. We defined the proliferative activity of a metastatic liver cell population to investigate its potential role as an indicator of clinical outcome in patients with metastatic disease of the colorectum. METHODS: The S-phase cell fraction, evaluated as in vitro [3H]thymidine-labeling index, was determined on liver metastases of primary colorectal cancers from 75 patients. RESULTS: Cell proliferation was not related to the degree of liver involvement, the site of the primary cancer, or the time of presentation of liver metastases. Survival at 2 years was statistically different for patients with slowly proliferating (78 percent) or rapidly proliferating liver metastases (47 percent) (P = 0.024). The risk of death for patients with high [3H]thymidine-labeling index lesions was consistently threefold that of patients with low [3H]thymidine-labeling index lesions throughout the observation period. Bivariate analysis showed that cell proliferation was a further prognostic discriminant within the subsets characterized by a different degree of liver involvement. CONCLUSIONS: These results indicate that cell proliferation is a good prognostic marker even in patients with liver metastases from colorectal cancer. The clinical implications of the marker could be further potentiated by considering it in association with some clinical aspects of known prognostic relevance.

Autoradiography↗
PubMed1994

In vitro effect of lonidamine on the cytotoxicity of mitomycin C and BCNU in human colon adenocarcinoma cells.

The ability of lonidamine (LND), an energolytic derivative of indazole carboxylic acid, to modulate the cytotoxic activity of mitomycin C (MMC) and 1,3,bis(2-chloroethyl)-1-nitrosourea (BCNU) was investigated in two human adenocarcinoma cell lines (LoVo and HT29) expressing different sensitivity profiles to the drugs. After a 1-h treatment with MMC or BCNU, cells were postincubated for 24 h with 150-225 microM LND. In the LoVo cells, a synergistic interaction between LND and MMC or BCNU was observed at both LND concentrations. In HT29 cells, only additive effects of the drugs given in sequence were seen. Flow cytometric analysis indicated that LND was generally able to stabilise the cell cycle perturbations induced by MMC and BCNU in the two cell lines. The ability of LND to potentiate anticancer drug activity, and the consideration that LND causes side-effects different from those of conventional antitumour drugs, make this compound an attractive candidate for multidrug combination therapy in colon cancer.

Adenocarcinoma↗
PubMed1994

Fibrin sealant in laparoscopic adhesion prevention in the rabbit uterine horn model.

OBJECTIVE: To assess the effects of fibrin sealant on adhesions after laparoscopic surgery. DESIGN: Standardized surgical trauma was induced in 60 female rabbits. The animals were randomized in three groups for different adhesion prevention treatment. SETTING: University research laboratory. INTERVENTIONS: After standardized trauma was induced, group 1 (n = 20) received no treatment, group 2 animals (n = 20) were injected in the abdominal cavity with 60 mL of Ringer's lactate, and human fibrin sealant was applied on the surgical lesions under laparoscopic vision in group 3 (n = 20). MAIN OUTCOME MEASURES: Five weeks after laparoscopy, a laparotomy was performed, and the adhesions were scored. RESULTS: Fourteen of 20 rabbits in the control group (70%) presented postoperative adhesions, 11 of 20 (55%) in the Ringer's group, and 5 of 20 (25%) in the fibrin sealant group. High-score adhesions were seen in 15% of cases in control and Ringer's group and in 5% of cases in the fibrin sealant group. CONCLUSIONS: When used during laparoscopic surgery, fibrin sealant has a preventive effect on de novo postsurgical adhesions. To assess the efficacy in reproductive surgery, a trial on recurrent postsurgical adhesions is required.

Animals↗
PubMed1994

Lack of a correlation between micronucleus formation and radiosensitivity in established and primary cultures of human tumours.

The radiation-induced genotoxic damage in three established cell lines and 15 primary cultures of human malignant melanoma and ovarian carcinoma showing different radiosensitivity was tested by the cytokinesis-block micronucleus assay. A dose-related increase in micronucleus frequency was observed in all the cell systems. The mean number of micronuclei per Gy of ionising radiation per binucleated cell was respectively 0.44 +/- 0.0075 and 0.43 +/- 0.04 for M14 and JR8 malignant melanoma cell lines and 0.19 +/- 0.013 for the A2780 ovarian cancer cell line. The number of micronuclei did not rank the cell lines in the same order of radiosensitivity as clonogenic cell survival, which showed a surviving fraction at 2 Gy of 0.38 +/- 0.02 for JR8, 0.34 +/- 0.05 for M14 and 0.22 +/- 0.007 for A2780. As regards primary tumour cultures, no correlation was observed between micronucleus induction and surviving fraction at 2 Gy. In conclusion, the discrepancy we observed between micronucleus formation and cell death raises doubts about the potential of the micronucleus assay as a preclinical means to predict radiosensitivity.

Carcinoma↗