F. Di Carlo

Enhancement of pentobarbital narcosis by drugs competing on the serum protein binding

Abstract Prior subcutaneous administration of sulfaethylthiazole (SET), sulfamethazine (SMZ), sulfanilamide (SNA), salicylic acid (SA), doxycycline (DOXI), p -amino-salicylic acid (PAS) is able to enhance the intraperitoneal pentobarbital (PB) narcosis in mice. Such narcosis enhancement seems to be connected with competition between these drugs and PB for serum proteins, which results in an increase of the unbound PB and consequently a higher PB cerebral concentration. This higher concentration may be attributed to competition for serum protein binding, since the PB metabolism is unaffected by SET, SMZ, SNA, SA, DOXI and PAS.

Effects of a β2-agonist (clenbuterol) on cultured human (CG-5) breast cancer cells

Abstract In order to gain further knowledge about the possible oestrogen-like activities of clenbuterol (a gb2-adrenergic drug illegally used as partitioning agent in food producing animals), we treated a hormone dependent human breast cancer cell line (CG-5) with different concentrations of the drug (10 −3 M to 10 −8 M). The effects of clenbuterol and oestradiol on cell proliferation were compared. Both oestradiol and clenbuterol, at low concentrations (10 −7 M and 10 −8 M) stimulated cell proliferation, but the effects of clenbuterol were less marked and significant. Probably clenbuterol elicited cell proliferation through a different mechanism, since it did not affect the cellular oestrogen receptor concentration. Clenbuterol failed in binding to the high affinity oestrogen receptors present in the CG-5 cells. As the β-adrenergic receptors and the susceptibility to their stimulation have been recently demonstrated in vivo and in vitro in many tumour and normal cells, it is reasonable to suppose that clenbuterol may induce cell proliferation through β-adrenergic stimulation.

Anti-HER-2 DNA vaccine protects Syrian hamsters against squamous cell carcinomas.

This paper illustrates the efficacy of DNA vaccination through electroporation in the prevention of oral transplantable carcinoma in Syrian hamsters. At 21 and 7 days before tumour challenge, 19 hamsters were vaccinated with plasmids coding for the extracellular and transmembrane domains of rat HER-2 receptor (EC-TM plasmids), whereas 19 control hamsters were injected intramuscularly with the empty plasmid. Immediately following plasmid injection, hamsters of both groups received two square-wave 25 ms, 375 V cm−1 electric pulses via two electrodes placed on the skin of the injection area. At day 0, all hamsters were challenged in the submucosa of the right cheek pouch with HER-2-positive HCPC I cells established in vitro from an 7,12-dimethylbenz[a]anthracene-induced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) vaccinated hamsters. In addition, the vaccinated hamsters displayed both a stronger proliferative and cytotoxic response than the controls and a significant anti-HER-2 antibody response. Most of the hamsters that rejected the challenge displayed the highest antibody titres. These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.

Hypothalamic H1 and H2 receptors: A tool to investigate the neuroendocrine role of histamine*

Summary The interaction between sexual or adrenal steroids and histamine receptors in rat hyothalamus was studied. The hypothalamic histamine-sensitive adenylate cyclase was stimulated by both estradiol and 2-hydroxy-estradiol, but not by progesterone or methyl-testosterone. Estrogens inhibited the histamine induced stimulation; on the contrary progesterone and methyl-testosterone were unable to antagonize the histamine stimulating effect. Aldosterone and hydrocortisone also stimulated the hypothalamic histamine-sensitive adenylate cyclase. Aldosterone inhibited the 4-methyl-histamine induced stimulation. on the other hand hydrocortisone inhibited the 2-(2-pyridyl) ethylamine induced stimulation. Such results seem to confirm an interaction between sexual or adrenal steroids and histamine receptors. Moreover the hypothalamic H 1 and H 2 receptors may represent the sites where histamine partecipates in a feed back mechanism regulating gonadotropin, prolactin and vasopressin secretion.

Perchloric acid-soluble proteins from goat liver inhibit chemical carcinogenesis of Syrian hamster cheek-pouch carcinoma

SummaryChemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette–Guérin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.

Prognostic significance of prolactin receptor on overall survival of patients with early breast cancer: a long-term retrospective analysis

Abstract The value of prolactin receptor (PRLR) determination in predicting overall survival has been retrospectively evaluated in a group of 170 women bearing primary breast cancer stage I, II and IIIA. All patients underwent surgery (radical or modified mastectomy or quadrantectomy and axillary dissection followed by radiotherapy according to TNM stage) between January 1977 and December 1986. In all patients, oestrogen and progesterone receptors concentrations were also determined. Overall actuarial survival was higher in patients having PRLR positive tumours when compared to patients having PRLR negative tumours (p = 0.0126). No difference in survival was observed between oestrogen or progesterone receptor positive or negative patients. Using Coxs multivariate analysis on 164 patients, stage and PRLR status were the only significant prognostic factors affecting survival (p

Interferences of Radiotherapy and Chemotherapy on the Binding of 3H-17β-Oestradiol with Its Specific Receptors

A clearly lower number of hormone-dependent tumours in the metastatic breast cancers submitted to radiotherapy was observed in our laboratory (see table 1).