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Biomedical subjects

G Sica

Publications and source records attributed to G Sica.

At least 91 records · Page 5Linked to original sources

Levels of estrogen and progesterone receptor in human endometrium during the menstrual cycle.

Receptors for estrogens and progesterone have been assayed in 24 samples of normal human endometria at different phases of the menstrual cycle. In the proliferative endometrium the concentration of estrogen binding sites was significantly higher than that of progesterone receptor while, in the secretive endometrium, the concentration of estrogen receptor was low, compared to that of progesterone receptor. The highest concentration of both receptors was observed during the periovulatory period. From the correlation observed between estrogen and progesterone receptors and the levels of the respective steroids in the plasma, it is suggested that the levels of plasma estradiol or its own tissue receptor determine the synthesis of progesterone receptors in the periovulatory period.

Cytosol↗

Glucocorticoid receptors in human fetal lung.

A specific dexamethasone binding protein of human fetal lung is described. Characterization of the receptor by sucrose density gradient centrifugation showed a sedimentation coefficient of approximately 7S (low ionic strength) and 4S (high ionic strength). Competition studies showed high specificity for glucocorticoids since binding of radioactive dexamethasone was inhibited by cortisol and corticosterone but not by testosterone and 17 beta-estradiol. Uptake of radioactive steroid by isolated lung nuclei required the presence of cytosol and was temperature dependent. The KCl-extractable nuclear complex sedimented at approximately 5S. Thus the dexamethasone binding components of the human fetal lung have properties similar to those described for steroid receptors present in target tissues. The concentration of receptor remained fairly constant between 15 and 28 weeks of gestation.

Binding, Competitive↗

Chemo-immunotherapy in advanced head and neck cancer.

BACKGROUND: Patients with advanced squamous cell carcinoma of the head and neck (SCC) have a depressed immune system whose function is worsened by chemotherapy. In a pilot phase II study, in order to improve the immune function during chemotherapy, we combined to cisplatin (CDDP) and 5-fluorouracil (5-FU) two biological response modifiers, retinyl palmitate (R) and Thymopentin (TP-5) for the treatment of SCC. PATIENTS AND METHODS: Fifty patients with recurrent or metastatic SCC of the head and neck were treated with Cisplatin 24 mg/m2 from day 1 to 5 and 5-FU 1,000 mg/m2 by a 120 hour continuous infusion. Retinyl palmitate was administered orally 50,000 i.u. b.i.d and Thymopentin 50 mg subcutaneously 3 times a week. RESULTS: Chemotherapy treatment was well tolerated with G3 hematological toxicity in 30% of patients and G2 gastrointestinal toxicity in 20% of patients. 16 patients (32%) had a complete response (CR), 13 patients had partial response (PR) (26%), (response rate 58%, 95% c.i. 43%-72%); stable disease (SD) was observed in 7 patients (14%), while 14 patients progressed (PD) (28%). Median time to progression was 12 months (range 2.8-94.5). Median overall survival was 13.5 months (range 2-104). CONCLUSIONS: The association of CDDP and 5-FU with Retinyl Palmitate and TP5 has a major activity in the treatment of advanced head and neck cancer and a relatively well tolerated toxicity.

Adjuvants, Immunologic↗

The growth of malignant and nonmalignant human cells is modulated by a human placental extract.

BACKGROUND: In the present paper, malignant and nonmalignant human cells were compared in their response to a fraction (fraction D, FD) of a human placental extract. MATERIALS AND METHODS: The activity of FD was tested on cell proliferation both in the absence and in the presence of 5%, 10% and 15% fetal bovine serum (FBS). For cells growing in monolayers, the medium was renewed with fresh medium containing FD 24 hours after plating and 3 days after the first exposure. In breast cancer cells only, it was also changed after 6 days. For leukemic cells, which grow in suspension, FD was added directly to the medium the day of the seeding and then after 3 and 6 days. RESULTS: In normal fibroblasts, when plated at a low density, a strong inhibitory effect on cell growth was seen with the highest FD dose. This effect was observed in the presence of 5% and 10% FBS, while it disappeared with 15% FBS. In endothelial cells, FD, in the presence of 5% or 10% FBS, produced a modest but constant inhibition of cell proliferation, which was evident after a short treatment and with almost every dose of FD. Breast cancer and leukemic cell lines, plated at a standard density, were markedly inhibited by FD, but this effect was reversed in serum-free conditions, at least in mammary cells. In leukemic cells, after an initial stimulatory effect, FD was not able to counterbalance the absence of serum. CONCLUSIONS: Our data seem to suggest that in FD both stimulating and inhibitory growth-factors coexist, the activity of which are greatly influenced by the culture conditions used.

Cell Division↗

Cisplatin, vindesine, mitomycin-C and 13-cis retinoic acid in the treatment of advanced non small cell lung cancer. A phase II pilot study.

BACKGROUND: Thirteen-cis retinoic acid (RA) has been shown to have growth-inhibitory and differentiative activity on non-small cell lung cancer (NSCLC) cells in vitro. This promoted the rationale for combining RA with three active drugs, cisplatin (CDDP) vindesine (VDS) and mitomycin-c (MMC) in the treatment of advanced NSCLC. PATIENTS AND METHODS: Patients with a histologically confirmed non-resectable NSCLC, measurable lesion, performance status < or = 3, and informed consent were enrolled. The chemotherapy schedule included cisplatin 60 mg/m2 and mitomycin-c 10 mg/m2 day 1 and vindesine 3 mg/m2 on days 1 and 5, every 4 weeks. RA was administered orally, at a dose of 0.5 mg/kg, 5 days per week, during chemotherapeutic intervals and to responding patients until disease progression was observed. RESULTS: Thirty patients, receiving a total of 163 chemotherapy courses, were evaluated for response and toxicity. Objective responses included complete response in 2 patients (7%), partial response in 10 patients (33%), stable disease in 9 patients (30%) and progressive disease in 9 patients (30%), (response rate 40%: Confidence interval 95% 22.7% to 59.4%). Median time to progression was 8.6 months (range 3.9-45+). Median overall survival was 11.3 months (range 1-45+). The 1-year survival rate was 47%. Toxicity (WHO) included nausea and vomiting grade 2 in 6 patients, transient ileus in 3 patients and grade 3-4 leukopenia in 5 patients. Two patients underwent surgical resection of residual disease and remain in CR. CONCLUSIONS: The addition of RA to cisplatin, vindesine and mitomycin-c is feasible and shows some activity in the treatment of NSCLC, with manageable toxicity.

Adult↗

Effect of natural beta-interferon on estrogen receptor mRNA of breast cancer cells.

We have demonstrated that natural beta-interferon (beta-IFN) enhances estrogen receptor (ER) mRNA of a human breast cancer cell line, CG-5. Cells were sensitive to the effect of beta-IFN at concentrations ranging from 10 to 100 IU/ml. The increase of ER mRNA was seen after 48 hr of treatment in at least three separate experiments. Our results are in agreement with the previously observed enhancement of receptor protein. In addition, they suggest that the IFN-induced promotion of the antiproliferative activity of drugs which act via ER may be due, in part, to increased receptor synthesis.

Blotting, Northern↗

Combination of beta-interferon and tamoxifen as a new way to overcome clinical resistance to tamoxifen in advanced breast cancer.

This paper shows that the response to tamoxifen (T) can be improved and the resistance to the antiestrogen can be overcome, in advanced breast cancer, by a pretreatment with natural beta-interferon (nIFN-beta) followed by the association of nIFN-beta with T. Forty-three patients with advanced breast cancer, both progressive (group A) and stable or partially responsive (group B) to previous treatment with T received nIFN-beta i.m. 3 x 10(6) IU/day for 14 days and, subsequently, T30 mg/day and nIFN-beta once a week. The overall objective response rate was 26% (95% Confidence Interval = 13-39) with 8 PR obtained in group A and 3 CR in group B. The median duration of response was 6 months (range 3-12+). Stabilization of disease was observed in 44% of cases. Toxicity was mild.

Aged↗

Apoptosis-related gene expression in benign prostatic hyperplasia and prostate carcinoma.

BACKGROUND: The aim of this study was to examine the expressions of the bcl-2, bax, fas and c-myc apoptosis-related genes in benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) to determine whether significant differences exist within each disease and between the two groups of patients. The correlation between gene expression and tumour diameter, stage, Gleason score and serum PSA was also investigated. PATIENTS AND METHODS: Tissue specimens from 51 cases of BPH and 27 cases of CaP were examined for bcl-2, bax, fas and c-myc expression by reverse transcriptase-PCR (RT-PCR). RESULTS: In BPH, bcl-2 and bax gave the weakest signals (p < 0.001). In CaP, bcl-2 was the least expressed gene (p < 0.001). In both patient groups, fas and c-myc were the most highly expressed genes (p < 0.05). Both bcl-2 and bax were expressed at higher levels in CaP than in BPH (p < 0.02). The bcl-2/bax ratio was lower in CaP than in BPH (p < 0.001). Bcl-2 was more highly expressed in high Gleason grade (> 7) tumours (p < 0.05). In the BPH group, bax showed a positive relationship with fas (p < 0.01), while the bcl-2 level inversely correlated with that of c-myc (p < 0.05). CONCLUSION: Our data showed that all the apoptosis-related genes were expressed in both BPH and CaP. The stronger expression of bax and the lower bcl-2/bax ratio observed in CaP may suggest a pro-apoptotic stimulus, while the higher bcl-2 levels appear to counterbalance the tendency to cell death.

Aged↗

Antitumor effect of lonidamine alone or combined with tamoxifen or medroxyprogesterone acetate in breast cancer cells.

The effect of Lonidamine (LND) alone or combined with the antiestrogen Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) on cell proliferation and steroid hormone receptor content of a human estrogen sensitive breast cancer cell line was investigated. LND has a direct growth inhibitory action, even if used at relatively low concentrations (10(-7) M), and shows the maximum effect at 10(-4) M. The combination of LND with the antiestrogen does not produce a potentiation of the TAM-induced reduction of cell number, while the association of the drug with MPA seems more effective with respect to MPA alone, at least at certain concentrations. The negative interference observed between LND and TAM may be due to the LND-induced decrease of estrogen receptor levels.

Antineoplastic Combined Chemotherapy Protocols↗

Antiproliferative effect of lonidamine on a human glioblastoma multiforme cell line.

Recent data from phase II trials have shown that lonidamine (LND) is effective in the treatment of tumors of various histogenesis, including gliomas. In the present work, we tested the antiproliferative effect of LND on a human glioblastoma cell line (LI) in different culture conditions. When LI are cultured in their standard conditions, a reduction of cell growth is seen after 3 days of treatment with 10(-4) M LND. It reaches 70% with respect to control after 6 days and is statistically significant. LND is ineffective at the other concentrations tested. In more stringent culture conditions, 10(-4) M LND determines a higher inhibition of cell proliferation both after 3 and 6 days of exposure, while other doses of LND are unable to affect cell growth.

Antineoplastic Agents↗

[A case of carcinoma of the cervical esophagus treated with interposition of an intestinal loop revascularized using a microsurgical technique].

The Authors present a case of hypopharyngeal tumor in which digestive continuity was assured by a jejunal autotransplant. Tumoral exeresis and jejunal preparation were carried out at the same time by two surgical teams. The use of microsurgical techniques assures the revascularization of the neck transplant by implementing the superior thyroid artery and the internal jugular vein. Digestive anastomoses complete the operation.

Esophageal Neoplasms↗

Some differences in steroid receptors between meningeal and neuroepithelial tumors.

In our study we evaluated the presence of steroid hormone receptors in a large series of endocranial tumors and investigated the possible correlations between receptor presence and levels and patient's age and sex. Our data indicate that steroid receptor behavior in the neoplasias considered is quite different from that observed in endocrine-related tumors, such as breast and endometrial cancer. Moreover, in neuroepithelial tumors an interesting difference between male and female subjects has been found regarding the receptor distribution in poor differentiated neoplasias.

Adolescent↗