Cloning and functional expression of a human heparanase gene.

We have cloned a gene (HSE1) from a human placental cDNA library that encodes a novel protein exhibiting heparanase activity. The cDNA was identified through peptide sequences derived from purified heparanase isolated from human SK-HEP-1 hepatoma cells. HSE1 contains an open reading frame encoding a predicted polypeptide of 543 amino acids and possesses a putative signal sequence at its amino terminus. Northern blot analysis suggested strong expression of HSE1 in placenta and spleen. Transient transfection of HSE1 in COS7 cells resulted in the expression of a protein with an apparent molecular mass of 67-72 kDa. HSE1 protein was detectable in conditioned media but was also associated with the membrane fraction following cell lysis. The HSE1 gene product was shown to exhibit heparanase activity by specifically cleaving a labeled heparan sulfate substrate in a similar manner as purified native protein.

The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma.

For prostate cancer, a correlation exists between overexpression of the epidermal growth factor receptor (EGFR) and poor clinical prognosis. In addition, late-stage metastatic disease is characterized by a change from a paracrine to an autocrine mode of expression for TGF-alpha, the ligand for the EGFR. These observations suggest that activation of the EGFR may be important for the growth of prostatic carcinoma in situ, and blockade of the receptor-ligand interaction may offer a means of therapeutic intervention for this disease. We describe the biologic effects of a chimeric anti-EGFR monoclonal antibody, C225, on several human prostate tumor cell lines in culture and the tumor inhibitory properties of the antibody for the treatment of human prostate carcinoma xenografts in nude mice. In vitro analysis of the EGFR from androgen-responsive and independent prostatic carcinoma cell lines revealed that C225 blocked EGF-induced receptor activation and induced internalization of the receptor. In vivo, a treatment regimen of C225 alone or antibody plus doxorubicin significantly inhibited tumor progression of well-established DU145 and PC-3 xenografts in nude mice. These results suggest that C225 may have utility for the treatment of human prostate carcinoma in a clinical setting.

[Intravenous amiodarone in the therapy of paroxysmal supraventricular tachycardias]. / L'amiodarone endovena nella terapia delle tachiaritmie parossistiche sopraventricolari.

The Authors evaluated the effectiveness and the tolerance of intravenous Amiodarone in 50 cases of recent onset paroxysmal supraventricular tachyarrhythmias. Fifty consecutive patients, aged 17 to 84 (mean 52 years), presenting with paroxysmal supraventricular tachycardia (PSVT, 33 cases) or atrial flutter (11 cases) or atrial fibrillation (6 cases), were given 300 mg of Amiodarone intravenously within 2 min, followed in 4 patients by 150 mg after 15 min. All patients were monitored for 1 hour; ECG and blood pressure were recorded at fixed times. Within 15 min sinus rhythm was restored in 88% of PSVT, in 27% of atrial flutter and in 17% of atrial fibrillation cases; the other cases of atrial flutter and fibrillation always showed a 48-81% reduction of the average heart rate within 15 min. We have evidenced neither significant modifications of blood pressure and ECG parameters (P-Q, QRS and Q-T duration) nor particular side effects, except for 2 cases in which brief hot flushes were reported. The Authors believe Amiodarone to be an effective and well tolerated drug for the above mentioned arrhythmias, particularly promptly acting in PSVT cases, in whom sinus rhythm was restored within 15 min in 88% and within 1 hour in 100% of the cases.