[The surgical therapy of ulcerative rectocolitis. Our experience].
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Colectomy↗
Biomedical subjects
G Sica
Publications and source records attributed to G Sica.
[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↗
Interferon and hormone-sensitivity of prostatic cancer cells.
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Cell Division↗
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↗
Antiproliferative effect of interferons on human prostate carcinoma cell lines.
The effect of purified human fibroblast beta-interferon (B-IFN) and recombinant alpha-2b-interferon (A-IFN) on cell proliferation was investigated in two human prostate carcinoma cell lines, named PC-3 and DU-145. Both cell lines respond to the antiproliferative action of interferon, B-IFN being more effective than A-IFN. PC-3 is more sensitive than DU-145 cell line, showing 95% inhibition of cell proliferation at the highest concentration of B-IFN. As interferons, besides reducing cell growth, are able to modify steroid receptor content in different hormone-sensitive human tumours, our results may be of some relevance as these drugs might be used to regulate both cell proliferation and hormone-sensitivity in prostate cancer.
Cell Division↗
Hormonal modulation of brain tumour growth: a cell culture study.
Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.
Aged↗
Morphometry of in vitro systems. An image analysis of two human prostate cancer cell lines (PC3 and DU-145).
Morphometric analysis on two human prostate cancer cell lines (PC3 and DU-145) was carried out to better characterize these cells and to approach some problems concerning their polymorphism. In our hands, these cells appear to differ either in their ability to oxidize testosterone or in their androgen receptor content. Morphometric evaluation was performed by means of an Interactive Image Analysis System (IBAS 1), which computes several parameters related to the whole cell and to the nucleus. Our results clearly indicate that nuclear parameters alone may discriminate PC3 from DU-145 cells. Particularly, the Nuclear Roundness Factor appeared important, since it quantifies changes in nuclear shape. Nevertheless, the value of this parameter for "in vitro" morphometry may be overshadowed by the polymorphism common to the cultured cells. However, morphometric evaluation of PC3 and DU-145 cells is relevant to a better understanding and definition of the biologic nature of these cells, even if polymorphism, heterogeneity and genetic instability, specially of PC3, require further investigations.
Cell Nucleus↗
In vitro effects of beta-interferon on steroid receptors and prostaglandin output in human endometrial adenocarcinoma.
The effect of natural beta-interferon (beta-IFN) on steroid receptor levels and output of prostaglandins (PGs) was investigated in human endometrial cancer. beta-IFN determines in endometrial adenocarcinoma explants an increase of cytosolic estradiol (ER) and progesterone (PR) receptors at concentrations ranging from 10 to 1000 IU/ml of culture medium. Only cases in which there was an enhancement of at least 50% with respect to control values were considered. Low concentrations of beta-IFN (10 IU/ml of culture medium) produce an enhancement of ER in 60% and of PR in 42% of cases, while higher concentrations of beta-IFN (1000 IU/ml of culture medium) produce an enhancement of ER in 32%, and of PR in 82% of cases. Since PGs are involved in proliferation control in a large variety of tumors, we evaluated the ratio between PGF2-alpha and PGE2 levels in culture medium. This ratio increased, in our experimental model, after treatment with 10 and 1000 IU/ml of beta-IFN in 38% and 58% of cases respectively. Our data suggest that beta-IFN could affect cellular hormone sensitivity through a modification of ER and PR and it can also determine a variation of PG output in human endometrial cancer.
Adenocarcinoma↗
Effect of natural beta-interferon on cell proliferation and steroid receptor level in human breast cancer cells.
The effect of natural beta-interferon (beta-IFN) on cell proliferation and steroid receptor level was investigated in CG-5 human breast cancer cell line. beta-interferon determines an appreciable diminution of cell growth, at concentrations ranging from 100 to 1000 IU/ml, which is enhanced when serum content of the culture medium is lowered. Low concentrations of beta-IFN (10-100 IU/ml) produce, after a 5-day treatment, an increase in estrogen receptors (ER) and progesterone receptors (PR). No variation of ER and PR levels is observed when beta-IFN is added directly to the cell homogenate before the assay. Our data suggest that beta-IFN could affect hormone sensitivity through a modification of ER and PR in neoplastic mammary cells.
Breast Neoplasms↗
Modulation of estrogen receptor and cell proliferation in human breast cancer cells by interferons.
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Breast Neoplasms↗
Malignant fibrous histiocytoma. Report of a case and review of the literature.
Malignant Fibrous Histiocytoma is a sarcoma characterized by two different principal cell types, which has its origin in mesenchymal undifferentiated clones. So it must be included in the differential diagnosis of the very rare primary breast tumors with stromal origin. The review of available literature allows us to define the histopathological and biological peculiarities of this kind of tumor and it confirms the extreme malignity and rarity of the case we observed.
Breast Neoplasms↗
Binding of (3H)R5020 to progesterone receptor and serum contaminants in human endometrium.
The binding of [3H]R5020 to cytosol from human endometrium was utilized to evaluate the concentration of progesterone receptor by means of agar gel electrophoresis, using D-norgestrel as cold competitor. It was observed that radioligand binds predominantly to the receptor, and that serum contaminants such as albumin and corticosteroid-binding globulin do not interfere in the assay procedure.
Binding, Competitive↗