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Biomedical subjects

G Sica

Publications and source records attributed to G Sica.

100 records · Page 6Linked to original sources

Direct antiproliferative effect of triptorelin on human breast cancer cells.

We investigated the effect of Triptorelin (Decapeptyl, DEC) alone or combined with Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) in human breast cancer cells. DEC did not affect the growth of estrogen-insensitive MDA-MB-231 cells, while it inhibited the estrogen-stimulated proliferation of MCF-7 and CG-5 cells. No amplification of growth inhibition induced by TAM or MPA was determined by DEC. Progesterone receptor levels of CG-5 cells were significantly enhanced by DEC in the presence of 17 beta-estradiol (E2) with respect to those in control and E2-treated cells.

Antineoplastic Combined Chemotherapy Protocols↗

Morphological and biochemical features of a medroxyprogesterone acetate (MPA)-resistant MCF-7 breast cancer cell line.

An MCF-7 human breast cancer line variant (MCF-7/MPA), resistant to medroxyprogesterone-acetate (MPA), was obtained by continuous exposure in vitro to the drug. MCF-7/MPA cells were grown in the presence of 12.5 x 10(-6) M MPA and were selected by increasing the concentration of the drug in the growth medium in a stepwise manner from 0.025 x 10(-6) M up to 12.5 x 10(-6) M. Comparative studies of cellular morphology, cytosolic steroid receptor content and P-Glycoprotein expression were performed on both MCF-7 parental line and MCF-7/MPA variant. MCF-7/MPA cells, when compared to the parental line, exhibit a different morphology in terms of membrane alterations, reduced content of cytosolic progesterone receptor, increased expression of P-glycoprotein along with reduction of Doxorubicin (Dx) activity on the growth of MCF-7/MPA resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced breast cancer.

Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high response rates in selected postmenopausal women with advanced breast cancer (ABC). Nevertheless, even in responders, invariably resistance to hormones is developed. In a previous paper we reported that in a subset of patients (pts) with metastatic breast cancer the resistance to the antiestrogen could be overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the association of nIFN-beta and T. In the present study we adopted a treatment schedule employing nIFN-beta (3 x 10(6) IU/day im three times a week) and T (60 mg/day) concurrently in 30 pts with ABC progressive to previous treatment with T (30 mg/day). We obtained a 13% response rate with a median duration of response of 8 months (range 4-16 m). All the responses occurred in pts whose disease progressed after an initial response to T. Stabilisation of disease was observed in 37%. Toxicity was mild. In our opinion the use of the combination T plus nIFN-beta in the treatment of breast cancer remains investigational and the optimal scheduling still undetermined.

Aged↗

Effects of interferon-beta on steroid receptors, prostaglandins and enzymatic activities in human endometrial cancer.

Steroid receptors, prostaglandin output and enzymatic activities were determined in explants derived from human endometrium exposed to natural interferon-beta (IFN-beta). Receptors and cell metabolism were evaluated before culturing the tissue fragments and after a 3-day treatment with varying concentrations of IFN-beta. Total steroid receptor levels were unchanged when explants were set up, but there was a redistribution of both estrogen and progesterone receptors (ER and PR). A decrease in cytoplasmic receptors corresponded to an increase in receptor molecules within the nucleus. Treatment with low concentrations of IFN-beta caused a significant enhancement (p < 0.05) of ER and PR in neoplastic endometrium. In basal conditions the ratio between prostaglandin F2 alpha (Pgf2 alpha) and prostaglandin E2 (PgE2) was higher in normal than in neoplastic endometrium. The addition of low concentrations of IFN-beta to the culture medium determined a significant increase (p < 0.02) in PgF2 alpha and a parallel increase in the above ratio in neoplastic tissue, while no variation was found in normal endometrium. Analysis of the results concerning the variations in hormone-related enzymatic activities due to IFN-B revealed a significant increase (p < 0.05) in 17 beta-hydroxy-steroid-dehydrogenase (17 beta-HSD) activity. The data presented here indicate that treatment with IFN-beta modifies those biological characteristics of neoplastic cells which are involved in hormone-responsiveness.

17-Hydroxysteroid Dehydrogenases↗

Interferons inhibit EGF-stimulated cell growth and reduce EGF binding in human breast cancer cells.

CG-5 estrogen-sensitive human breast cancer cells contain specific Epidermal Growth Factor receptors (EGF-R, Kd = 0.09-0.17 nM) and respond to the mitogenic effect of EGF. The increase in cell proliferation has been observed starting with very low concentrations of EGF (10-12M) and was statistically significant at all doses. Nevertheless, cell growth stimulation was emphasized when cells were grown under stringent culture conditions. When cells were exposed to 100 IU/ml of natural beta-interferon (n beta-IFN) the binding of EGF to the cell membrane was reduced after 72 hours of treatment, while the exposure of CG-5 cells to 1000 IU/ml of n beta-IFN resulted in an EGF-R reduction which started after 48 hours and became statistically significant after 72-120 hours. If CG-5 cells were treated with 1000 IU/ml of recombinant alpha 2b-interferon (ra2b-IFN) this reduction was observed after 168 hours of exposure to the drug. Both the IFNs abolished EGF-stimulated cell growth. Our results indicate that IFN treatment down-regulates EGF-R in estrogen-sensitive breast cancer cells and suggests that this down-regulation may be involved in the inhibitory action of IFN on cell growth.

Breast Neoplasms↗

Effectiveness and safety of combined epidural and general anesthesia for laparoscopic cholecystectomy.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the efficacy and safety of two anesthesia techniques, combined epidural/general anesthesia (CEGA) versus total intravenous anesthesia (TIVA), for laparoscopic cholecystectomy. METHODS: Forty patients were randomly assigned to one of two different groups: group A received TIVA and group B received CEGA. At preset times during the operation, systolic and diastolic arterial pressure, heart rate, oxygen saturation (SaO2) and end-tidal carbon dioxide (Etco2) were monitored. Postoperatively, recovery (Steward's test) and analgesia (visual analog scale [VAS] pain scores) were assessed, as well as the incidence of adverse effects. RESULTS: The groups were comparable as to demographic data and duration of surgery and of anesthesia. Intraoperative parameters also showed no statistical differences. Both groups had a rapid recovery (Steward score of 6 within 12 minutes), but group B showed better recovery scores at 4 minutes. Postoperative pain was well controlled in both groups, but group B exhibited better scores at postoperative hour 2. The incidence of postoperative side effects was low in both groups. CONCLUSIONS: The use of CEGA for laparoscopic cholecystectomy seems to be effective and safe and to offer some advantages as compared to TIVA alone. CEGA can control pain due to CO2-induced peritoneal irritation, providing excellent intra- and postoperative analgesia. CEGA does not require the use of intraoperative intravenous opioids and shortens recovery time, without increasing the incidence of side effects.

Adult↗

[Paget disease of the jaws. Review of the subject. Clinical-therapeutic considerations].

Clinical and diagnostic findings of Paget's disease of the jaws are reported; up to date etiological and pathogenical hypotheses are presented. Laboratory data of increased P.A. as a marker of disease evolution is pointed out, particularly the relationship increasing hydroxyprolinuria, because the increase of a malignant transformation. Surgery, always modeling, is limited to cases of severe facial dysmorphosis associated or not with the local disturbance due to compression; in any case it is suggested to perform the surgery in the phases of inactivity of disease, to avoid local complications, such as hemorrhage a infection.

Adolescent↗

Combined chemotherapy and differentiation therapy in the treatment of advanced non-small-cell lung cancer.

BACKGROUND: In this phase-II pilot study a cisplatin-based treatment was combined with biological agents capable of inducing differentiation in non-small-cell lung cancer (NSCLC) cells with the aim of ameliorating response to chemotherapy. PATIENTS AND METHODS: Forty patients (PTS) with inoperable stage III-B or IV NSCLC were treated with cisplatin (CDDP) 24 mg/m2 on days 1 to 5, 5-fluorouracil (5-FU) 500 mg/m2, by continuous infusion on days 1 to 5 and vindesine (VDS) 3 mg/m2 on days 1 and 5. Beta-interferon (beta-IFN) 1 x 10(6) IU/m2 subcutaneously 3 times a week and retinyl palmitate (R) 50,000 IU orally BID were administered between chemotherapy cycles. Responders were maintained with the same dose of beta-IFN plus R 15,000 IU BID. Half of the PTS had an ECOG performance status of 0-1, 62% of tumours were of squamous histology and 77.5% of PTS had stage IV disease. A median of four courses of chemotherapy per PT was delivered. RESULTS: Forty PTS were evaluable. Seventeen PTS responded, (RR 42%, 95% C.I. 27%-57%). Of the 17 responders 13 had squamous histology. The median response duration was 5.1 months. The median overall survival was 9.1 months. Gastrointestinal toxicity occurred in 58% of PTS, anaemia in 20%, leukopenia in 30%. CONCLUSIONS: The association of CDDP, VDS, 5-FU, beta-IFN and R shows activity in NSCLC, particularly in tumours with squamous histology, with a substantial toxicity.

Aged↗

[Role of p53 gene in colorectal neoplasms].

A prospective study on the role of the p53 gene in sporadic colorectal neoplasms is presented and the level of mutant p53 protein was measured in the tissue removed during colonoscopy from: patients previously operated for colorectal malignant neoplasms, patients with active neoplasms, first degree relatives and during regular checks. 72% of patients with an active tumour showed a positive p53 and 38% in follow-up checks. Longer follow-up periods and a major number of patients are necessary to assess the prognostic importance of the p53 protein.

Colorectal Neoplasms↗

Beta-interferon, retinoids and tamoxifen combination in advanced breast cancer.

PURPOSE: To investigate, in patients with metastatic breast cancer (MBC), a combination of retinoids, beta-interferon (beta-IFN) and tamoxifen (TAM). PATIENTS AND METHODS: This trial was conducted from January 1987 to June 1992 in 85 consecutive patients with MBC. All patients had been treated for metastatic disease: 43 patients received chemotherapy, 35 received hormone therapy and 7 received both. Forty-nine patients, with a better prognosis, and a longer disease-free survival (DFS) were treated with beta-IFN 1 x 10(6) IU/m2 subcutaneously three times a week, TAM 10 mg TID, retinyl palmitate (R) 50,000 IU BID. Thirty-six patients with shorter DFS, were first treated with 8 courses of chemotherapy followed, in responders, by beta-IFN, R and TAM. RESULTS: With a median follow-up of 7 years (minimum 4 years) 59% of 85 evaluable patients responded, 20% had stabilization of disease and 21% progressed. Median response duration was 43 months. Median survival was 28 months and 25% of patients were alive after 9 years. Toxicity of biological therapy was moderate. CONCLUSIONS: Our data show that beta-IFN, TAM and R combination is effective as salvage therapy in patients with MBC.

Adult↗