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Biomedical subjects

G Sica

Publications and source records attributed to G Sica.

At least 55 records · Page 3Linked to original sources

Effect of recombinant human interferon-alpha/2b on epidermal-growth-factor-, estrogen- and progesterone-receptor expression in primary cervical cancer.

The effects of a short period of in vivo systemic rh-IFN-alpha/2b treatment on epidermal-growth-factor(EGFR)-, estrogen(ER)- and progesterone(PR)-receptor content in 11 primary human cervical tumors was investigated by the radioreceptorial technique. EGFR levels were found to be significantly higher in cervical tumors after rh-IFN-alpha/2b treatment with respect to basal levels. In 2 cases, immunohistochemical and cytofluorimetric analysis showed that rh-IFN-alpha/2b treatment induces an increase in EGFR immunoreactivity and in the fraction of EGFR-positive cells. No difference in ER and PR levels in cervical tumors before and after rh-IFN-alpha/2b treatment was observed. Our results suggest that rh-IFN-alpha/2b up-regulates EGFR in primary human cervical tumors in vivo.

Aged↗

Androgen receptors and hormone sensitivity of a human prostatic cancer cell line (PC-3) are modulated by natural beta-interferon.

Androgen receptors are expressed at a low level in the cell line PC-3, which does not respond to either androgens or antiandrogens. If these cells are exposed to natural beta-interferon (beta-IFN) a reduction in cell growth and an increase in androgen receptors, evaluated by both biochemical and immunocytochemical techniques, occur. This increase seems not to be related to a selective block of PC-3 in any phase of the cell cycle. Pretreatment with beta-IFN determines in PC-3 cells a partial responsiveness to the androgen dihydrotestosterone as reflected by the increase in cell number. Moreover, the antiandrogen hydroxyflutamide shows agonistic properties by increasing the cell number of PC-3 cells pre-exposed to beta-IFN. When the antiandrogen is tested in combination with interferon, it produces a reduction in the beta-IFN-induced inhibition of cell growth. It is not known whether these unexpected effects are due to the increase in androgen receptors or to other mechanisms.

Androgen Antagonists↗

Combined effects of estradiol, leuprorelin, tamoxifen and medroxyprogesterone acetate on cell growth and steroid hormone receptors in breast cancer cells.

Both tamoxifen and medroxyprogesterone acetate have a direct antitumor effect and are widely used in breast cancer therapy. Luteinizing-hormone-releasing hormone analogs inhibit the growth of breast cancer cells and could represent an alternative treatment for patients affected by breast cancer. Our study was carried out to investigate the effect of leuprorelin (TAP-144) alone or combined with tamoxifen or medroxyprogesterone acetate in human breast cancer cells. Ineffective when used in the absence of estrogens, TAP-144 inhibited the estrogen-stimulated growth of MCF-7, CG-5 and ZR-75-1 cells cultured in medium supplemented with charcoal-treated serum. The growth of estrogen-unresponsive MDA-MB-231 cells was not affected by TAP-144. The combination of TAP-144 with tamoxifen in CG-5 cells did not determine any enhancement of inhibition of cell growth, whereas in both CG-5 and MCF-7 cells, when 1 microM TAP-144 was associated with 0.1 microM medroxyprogesterone acetate, cell growth inhibition was increased, resulting in a subadditive effect. Progesterone receptor levels of CG-5 cells were significantly increased by TAP-144 in the presence of 17 beta-estradiol with respect to those present in control and 17 beta-estradiol-treated cells.

Breast Neoplasms↗

Monitoring steatorrhoea in cystic fibrosis.

The aim of the study was the evaluation of the relationship between chemical fat analysis and some more rapid tests proposed to estimate steatorrhoea. Stool collections (72 h) were obtained on 32 occasions in 22 patients with cystic fibrosis and in seven healthy children. A very close relationship was found between faecal fat, as measured by standard chemical methods, and faecal energy (r = 0.95, P < 0.001). We conclude that the determination of faecal energy, easier to measure than faecal fat, can provide reliable information about the extent of steatorrhoea in cystic fibrosis.

Adolescent↗

[Comparison between balanced anesthesia and total intravenous anesthesia in videolaparocholecystectomy].

The aim of this work was to assess which anaesthetic technique is more suitable to the performance of videolaparocholecystectomy (VLC), particularly seeking for a faster and more comfortable recovery, although saving the maximum safety of the patient. A comparative investigation between two different anaesthetic techniques was carried out in 40 patients scheduled for VLC; the procedure's average length was 110.3 +/- 32.8 minutes and pneu- moperitoneum was obtained with 12-15 mmHg of CO2. Patients (32 females and 8 males, average age 52.3 +/- 8 years and ASA class 1, 2, 3, were randomized in two groups. The first group was administered total intravenous anaesthesia (TIVA): propofol+ fentanyl+pancuronio bromide; the second one received balanced narcosis:TPS+ Isoflurane+Pancuronio bromide. The following parameters were monitored at set times: SAP, DAP, HR and EtCO2; statistical analysis was performed by analysis of variance. The quality of recovery was assessed by Steward's test and analyzed by Student's "t" test. The data obtained from analysis of the intraoperative parameters showed no significant differences between the two groups; on the contrary a statistically significant difference was found with regard to the quality of recovery (p > 0.5 at 5' from the extubation). Thus, the comparative study showed the efficacy and safety of both techniques, but TIVA allowed a faster and more comfortable awakening with shorter time to recovery of consciousness. This, together with the reduced requirements of analgesic drugs in the postoperative period and the lack of air pollution, seems to suggest that TIVA is to be preferred for laparoscopic surgery.

Anesthesia, General↗

Prognostic indicators in patients with cirrhosis and hepatocellular carcinoma undergoing surgical resection.

A retrospective study was performed in order to identify factors significantly associated with operative mortality and post-operative complications in 114 patients with liver cirrhosis who underwent resection surgery for single hepatocarcinoma nodules (diameter < or = 7 cm) from 1980 to 1992. Vascular thrombosis, extrahepatic spread of the tumor, ascites, advanced cirrhosis, severe cardio-pulmonary disease, and renal failure were exclusion criteria. Forty-one pre-operative (demographic, clinical, laboratory, and histopathological features) and two peri-operative variables (amount of blood transfused and duration of operation) were cross tabulated using chi 2 test with operative mortality and post-operative complications, which were taken as end-point variables. Stepwise logistic regression analysis was then employed in order to define factors independently associated with end-point variables. Only partial thromboplastin time abnormality was significantly (P = 0.003) and independently associated with operative mortality. The length of the operation and the period during which surgery was carried out (1980-1986 and 1987-1992) were significantly (P < 0.001) and independently associated with the occurrence of at least one post-operative complication. The results suggest that the use of more restrictive selection criteria do not make it possible to lower operative mortality, although the coagulative status should be better assessed. Minimizing surgical stress and optimizing post-operative medical care are crucial for preventing post-operative complications.

Adult↗

Natural interferon-beta treatment and steroid hormone receptors in primary endometrial cancer.

Forty-three patients with primary endometrial carcinoma were treated with natural interferon-beta (IFN-beta) at two different dose levels (2 x 10(6) IU or 6 x 10(6) IU im 3 times/week for 1 week). IFN-beta increased receptors for estrogens (ER) and progesterone (PR) in a high percentage of the 40 evaluable patients, without modifying the receptor affinity. The ER and PR enhancement, which was simultaneous in at least 50% of patients, and the increase of over 100 fmol/mg protein observed in some cases suggest that IFN-beta exerts a profound influence on receptor expression and, probably, on the hormone sensitivity of the tumor.

Adenocarcinoma↗

Steroid receptor enhancement by natural interferon-beta in advanced breast cancer.

In the current study we investigated the effect of two different doses of natural interferon-beta (IFN-beta) on steroid hormone receptors in 45 patients with advanced breast cancer. IFN-beta seems to regulate the receptor mechanisms, inducing in cutaneous metastases an increase of oestrogen and progesterone receptors. Moreover, using IFN-beta and tamoxifen as a combined therapy in 23 receptor-positive patients, no negative interference of the two drugs was observed and no relevant side-effects due to the treatment were noticed. The modulation of steroid receptor content by IFN-beta in advanced breast cancer might represent an interesting way to ameliorate the clinical responsiveness to anti-oestrogens.

Aged↗

[Totally implantable systems for long-term chemotherapeutic treatment].

The authors report their own experience with completely implantable systems for the long-term chemotherapeutic treatment, compared with a review of modern literature. The experience even if low demonstrates a good methodology in reducing the number of complications associated with the use of percutaneous catheters.

Antineoplastic Combined Chemotherapy Protocols↗

Recombinant interferon-alpha 2b affects proliferation, steroid receptors and sensitivity to tamoxifen of cultured breast cancer cells (CG-5).

Exposure of CG-5 human breast cancer cells to recombinant interferon (IFN)-alpha 2b results in a significative inhibition of cell proliferation; this is observed when cells are cultured in their standard conditions and is not modified if serum concentration present in the culture medium is lowered. Estrogen receptors are increased in CG-5 cells following a 5 day treatment with concentrations of IFN-alpha 2b ranging from 10 to 1000 IU/ml of culture medium. Progesterone receptors seem to be more influenced by a longer treatment with the drug (7 days). The Kd of both receptors is not modified by the exposure of cells to IFN-alpha 2b. Finally, the antiproliferative effect of tamoxifen on CG-5 cells is amplified by the simultaneous addition to culture medium of IFN-alpha 2b even at very low concentrations.

Breast Neoplasms↗

Antiproliferative effect of leuprorelin acetate, alone or combined with tamoxifen or medroxyprogesterone acetate, on human breast cancer cell lines.

We have investigated the antiproliferative action of leuprorelin acetate (TAP-144) on human breast cancer cells, cultured in medium supplemented with charcoal-treated fetal calf serum. The analogue had no effect on cell growth of oestrogen receptor-negative MDA-MB-231 cells. Although ineffective when used alone, TAP-144 inhibited in a dose-dependent fashion the oestradiol-induced cell growth in oestrogen receptor-positive and oestrogen-sensitive MCF-7, ZR-75-1 and CG-5 cells. TAP-144 did not modify the growth inhibitory activity of tamoxifen on CG-5 cells. A high concentration of TAP-144 (10(-6) M) seemed to increase the antioestrogenic effect of medroxyprogesterone acetate (MPA) (10(-7) M) in the same model. The data reported indicate that, in our culture conditions, TAP-144 has a direct antitumour effect on breast tumour cells. Our findings concerning the promotion of the antiproliferative effect of MPA merit further investigation.

Antineoplastic Agents↗

Effect of recombinant human interferon-alpha 2b on receptors for steroid hormones and epidermal growth factor in patients with endometrial cancer.

Interferons (IFNs) may modulate oestrogen (ER), progesterone (PR) and epidermal growth factor (EGFR) receptor expression in vitro. ER, PR and EGFR levels in tumour specimens taken from 13 patients with endometrial adenocarcinomas before and after 5 days' intramuscular treatment with 5 x 10(6) U per recombinant human leucocyte interferon-alpha 2b (rh IFN-alpha 2b). After treatment, ER (P less than 0.01) and PR (P less than 0.05) levels were significantly increased with a simultaneous reduction of EGFR content (P less than 0.05). Since the expression of ER and PR characterises more differentiated hormono-sensitive tumours, while EGFR are preferentially expressed in less differentiated tumours, the increase of steroid hormone receptor levels with the reduction of EGFR expression suggests that rh IFN-alpha 2b may induce endometrial cancer cell differentiation. Moreover, the decrease of EGFR levels may explain the antiproliferative effect of IFNs.

Adenocarcinoma↗

Natural beta-interferon and androgen receptors in prostatic cancer cells.

Both PC-3 and DU-145 cell lines are androgen-insensitive, but, in our experience, they contain androgen receptors (AR). Treatment of these cells with natural beta-interferon at a concentration of 1,000 IU/ml of culture medium determines an increase of AR (evaluated by a whole-cell assay), statistically significant with respect to control. Androgen unresponsiveness of our cells could be due to an AR level which is lower than that present in hormone-sensitive prostatic cancer cell lines, such as LNCaP cells. For this reason, interferon-promoted AR increase merits further investigation, even if other defects in receptor mechanism, responsible for hormone insensitivity, cannot be excluded.

Cell Line↗

Effects of natural beta-interferon and recombinant alpha-2B-interferon on proliferation, glucocorticoid receptor content, and antigen expression in cultured HL-60 cells.

In the current study, we investigated the effects of natural beta-interferon (beta-IFN) and recombinant alpha-2b-interferon (alpha-IFN) on the growth of the HL-60 cell line. Cells cultured in a medium that contains various concentrations (from 10 to 1000 IU/ml) of interferons showed a growth inhibition, which reaches the maximum after a 6-day treatment, at the highest dose used. Furthermore, we studied the effect of both beta-IFN and alpha-IFN on the level of glucocorticoid receptors. This was enhanced more than 30% with respect to control in HL-60 cells exposed for 24 hours to concentrations of beta-IFN that ranged from 100 to 1000 IU/ml. The increase of the receptor amount was seen even if cells were treated for 5 days, and was not accompanied by a modification of antigen expression of HL-60 cells. alpha-IFN did not modify the glucocorticoid receptor level substantially in our experimental conditions. Our data indicate that both beta-IFN and alpha-IFN regulate HL-60 cell proliferation. Additional studies are required to clarify if modifications of the receptor level induced by beta-IFN could be related to the modulation of hormone-sensitivity in this model.

Antigens↗

Pathophysiologic and endocrine aspects.

Androgens regulate development and functional maturation of the prostate. A lack of androgens at puberty impairs normal prostate growth and causes regression and atrophy of the gland in adults. Orchidectomy or indirect androgen suppression by hypophysectomy or administration of oestrogens reduces prostatic weight and secretion. As far as prostatic cancer is concerned, significant improvement occurs in the clinical conditions of patients affected by advanced neoplasia subjected to castration or oestrogen administration. Recently, other endocrine manipulations have been proposed, but the response to these treatments strictly depends on the composition of the neoplastic population. Prostatic cancer consists of cells that are sensitive to or dependent on hormones and others that are hormone-independent. Biological activity of hormones, particularly androgens, is mediated via intracellular receptors, which are not easy to measure in prostatic tissue. Androgen receptor level can be modulated in prostatic cancer cells by natural interferon-beta, opening new perspectives in the therapy of prostatic cancer.

Androgens↗

Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors.

Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone.

Adult↗