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Biomedical subjects

L Fazzuoli

Publications and source records attributed to L Fazzuoli.

30 records · Page 2Linked to original sources

Thyroid and steroid receptors.

Estradiol and progesterone receptor proteins (ER, PgR) have been demonstrated in neoplastic and non-neoplastic human thyroid. The aim of this study was to determine the sexual steroid receptor content of pathological non-malignant thyroid (solitary adenoma, simple nontoxic goiter), and the adjacent normal tissue of the thyroid. The results show the presence of ER and PgR (cytosolic and/or nuclear) in most of examined tissues both pathological and normal. Low levels of steroid receptors are found in the cytosol fraction, whereas the receptor content is higher in the nuclear fraction. No correlation could be found between receptor levels and patients' age, menstrual state in females, and sexual steroid circulating hormones. A significant difference has been observed between adenomas and simple goiters (p less than 0.001) in the nuclear ER, and between normal tissue surrounding adenoma and normal tissue in goiters (p less than 0.05). This result suggests that estradiol and progesterone receptors are present in thyroid tissue and may have a physiological function.

Adult↗

Estrogen and progesterone receptors in uterine leiomyomas.

The purpose of our study was to evaluate the contrasting data between estrogen receptors (ER) and progesterone receptors (PgR) in uterine leiomyomas, endometrium and myometrium. Uteri were obtained from 30 women undergoing hysterectomy for uterine leiomyomas (24 premenopausal and 6 postmenopausal patients). Cytosolic and nuclear ER and PgR were analysed in uterine tissues by the method of single saturation point assay at a final concentration 5 nM of [3H-17 beta]estradiol and [3H]ORG-2058. Our results confirm that leiomyomas undergo changes similar to those observed in other uterine tissues during the menstrual cycle. The ER levels show decreased values during the postovulatory phase. After subdividing leiomyomas according to their topographic criteria, as submucous or subserosal, we observed that ER and PgR are significantly more numerous in submucous than in subserosal myomas, both in proliferative and in the secretive phase of the cycle. These results agree with the hypothesis that leiomyomas have a different etiology and may explain why some myomas decrease after progestin therapy (submucous), while others (subserosal) remain unchanged.

Adult↗

Cytosolic and nuclear androgen receptor activity in the cancer of the larynx.

It is well known that the larynx is a target organ for androgens and the cancer of larynx is more frequent in male subjects. We have evaluated the androgen receptors (AR) in the cytosol (ACR) and in salt extractable (ANR) and salt resistant nuclear fraction (AMR) in a group of 24 male patients with cancer of the larynx surgically removed. In addition specimens obtained from the normal mucosa of the same subjects were analyzed. In 5 patients estrogen (ER) and progesterone (PgR) receptors were also assayed. In all subjects blood samples were taken before surgery for the assay of the following hormones: LH, FSH, estradiol, testosterone, dihydrotestosterone, delta 4-androstenedione, dehydroepiandrosterone sulfate, cortisol. The results observed showed that 18 out of 24 normal larynx mucosa specimens and 17 out of 24 larynx cancer specimens were positive for ACR or ANR or AMR. The 5 samples of normal and cancer tissues analyzed for ER and PgR were negative. In conclusion there is no significant correlation between AR positivity from one size, histology, degree of differentiation and invasivity of the cancer, age of patients and hormonal blood levels from the other. The high ANR and AMR positivity (normal hormonal translocation and binding on DNA acceptors) confirm that the normal and cancer larynx are target tissue for androgens and establish the hormone dependence of this cancer. Hormonal therapy could be envisaged as an alternative or a complementary therapy for this type of cancer at least in the cases in which the analysis of hormone receptors will prove to be positive.

Adult↗

Estradiol and progesterone receptors in normal and pathologic colonic mucosa in humans.

The presence of estradiol (E) and progesterone (Pg) receptors (R) has been demonstrated also in normal and neoplastic tissues known to be hormone-independent and in particular in primitive colonic cancer, and, possibly, in healthy colonic mucosa. In this study endoscopic and surgical colonic mucosa specimens from 55 subjects were analyzed and divided as follows: 21 samples from healthy subjects, 12 normal mucosa samples from subjects affected with colonic cancer, 8 adenomatous polyps specimens, 5 samples from ulcerative colitis drawn on areas showing macroscopic lesions and 9 colonic cancer specimens. In the control group we have observed 6 cases positive for ER (28.6%) and 2 positive for PgR (14.3%). Six normal mucosa specimens from subjects affected with colonic cancer were found to be positive for ER (50%) and 2 for PgR (16.7%). Five colonic cancers resulted ER positive (55.5%) and 4 PgR positive (44.4%). Four polyps were ER positive (50%) and 3 PgR positive (37.5%); in this group only one subject showed positive binding in the surrounding normal tissue. These data confirm the presence of ER and PgR in colonic cancer and colonic adenomas (so-called precancerous disease); in these subjects the finding of steroid receptors also in normal mucosa suggests that the presence of steroid binding could be considered as a marker of a precancerous condition.

Adenocarcinoma↗

Responsiveness to hormone, growth factor and drug treatment of a human breast cancer cell line: comparison between early and late cultures.

Growth rate, morphology, and responsiveness to mitogenic stimuli and pharmacological treatments were evaluated in early and late cell passages derived from the same clone of the widely used MCF-7 human breast adenocarcinoma cell line. Our results indicate dissimilarities between early (E) and late (L) passages for some of the parameters analyzed. The cells that underwent many subcultivations grew faster than the others; both appeared homogeneous in size and shape. The E cells, subcultured for almost 1 yr, displayed higher sensitivity to the mitogenic action of both estradiol, according to the level of estrogen receptor, and insulin-like growth factor-I than did the L cells, kept in culture for more than 10 yr. Cell responsiveness to two drugs, a novel steroid antiestrogen and a polysulfonated distamycin A derivative, was more pronounced in the early cultures only at the longer time of exposure to the higher concentration of the estrogen antagonist. In addition, a drug-induced inhibition of insulin-like growth factor-I binding to its receptor was shown in both E and L cells, the latter being less sensitive than the former when exposed to the antiestrogen. Finally, MCF-7 E and L cells showed similar behavior when drug-induced apoptosis was tested.

Apoptosis↗

LH-RH analogue treatment in adenocarcinoma of the pancreas: a phase II study. Gruppo Ligure per lo Studio del Pancreas.

In this phase II study, we treated 7 patients, all males, with stage III or IV pancreatic cancer with goserelin (an LH-RH analogue). Goserelin was administered at a dose of 3.6 mg every 4 weeks. The tumour response was assessed by measuring lesions with US- or CT-scan studies, according to WHO criteria. No response was observed. The median survival was 8 months in locally unresectable tumours and 4 months in advanced disease. The accrual was actually stopped at 7 cases because there were no responses in either of our series or in those published during our study. The authors conclude that the treatment with LH-RH analogue alone cannot be recommended for further studies.

Adenocarcinoma↗

Cytosolic and nuclear androgen receptors in colorectal adenomas.

The aim of this study was to verify the presence of androgen receptors (AR) in human colorectal adenomas and in normal adjacent mucosa, and to determine whether there is any difference in AR tissue content between females and males. Our data show higher levels of nuclear AR in normal mucosa than in adenomas (p less than 0.001). A significant difference was also present in males between normal and pathological tissue both in cytosolic (p less than 0.05) and nuclear receptors (p less than 0.01). In female subjects this difference was also evident, but not significant. Our results seem to support the hypothesis of protective effects of androgens in colonic mucosa.

Adenoma↗

Manipulation of the growth rate of human breast cancer cells by antiandrogen followed by chemotherapy.

The effects induced by the antiandrogen Cyproterone Acetate (CPA) on the proliferation of EVSA-T human breast cancer cells endowed with androgen receptors were studied. Kinetic analyses were carried out by two autoradiographic techniques measuring the percentage of cells in S-phase and the growth fraction (GF). The exposure of the cultures to CPA for 24 h caused a marked inhibition on S-phase cells without significantly affecting the CF. The accumulation of cells in G1-phase, confirmed by cytometric analysis, was rescued to the S compartment by replacing the culture medium 24 h after CPA administration. Exposure of EVSA-T to Doxorubicin or Methotrexate after CPA and medium change at the time of maximal proliferative recruitment, led to an enhancement of cytotoxicity as demonstrated by colony survival assay.

Androgen Antagonists↗

Relationship between PRL levels and steroid receptors in breast cancer.

The role of PRL in human breast cancer is still debated. We examined 259 women undergoing surgery for breast cancer (K = 183) and for other diseases (n = 76). In all subjects blood samples were taken for the RIA assay of PRL, during the preanaesthesia. In the breast cancer specimens, estrogen (ER) and progesterone (PGR) receptors were assayed and T.N.M. was evaluated. PRL mean values were assayed and T.N.M. was evaluated. PRL mean values were found to be above the normal range in both groups. PRL values in ER+ and PGR+ were lower than in ER- and PGR-. We also divided the patients into two groups (PRL values greater than 50 or less than 50 ng/ml). The difference between the two groups was significant for ER (p less than 0.005) and PGR (p less than 0.05), using Student's unpaired t-test. Besides this, we observed a significant negative linear correlation between PRL values and receptor values. The finding of this correlation suggests that high PRL values could be associated with unfavourable prognosis in breast cancer.

Biomarkers, Tumor↗