trelstar and Carcinoma--Squamous-Cell

Squamous cell carcinoma of the prostate is rare and represents 0.5% to 1% of prostatic carcinomas. Transformation of prostatic adenocarcinoma into squamous cell carcinoma after LH-RH agonist intake has been reported in only 8 cases in the literature. To our knowledge, our case is the second pure squamous cell carcinoma observed after hormonotherapy and radiotherapy. We reported a case of a patient with prostatic adenocarcinoma treated by radical prostatectomy followed by radiotherapy. Eleven years later, he had a vesical recurrence of prostatic adenocarcinoma. Our patient had an endoscopic resection followed by injections of Triptorelin. Six months later, he developed a local recurrence of a squamous cell carcinoma.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Carcinoma, Squamous Cell; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Recurrence, Local; Prostatectomy; Prostatic Neoplasms; Triptorelin Pamoate

The purpose of this study was to investigate the effects of a potent LHRH agonist, [D-Trp(6)]LHRH on the basal and EGF-induced cell proliferation and the metastasis-associated properties in A431 human epidermoid carcinoma. [D-Trp(6)]LHRH time-dependently inhibited the basal and EGF-stimulated growth of A431 cancer cells. It is assumed that phosphorylation/dephosphorylation of cellular proteins is highly related to cell growth. This study demonstrates that [D-Trp(6)]LHRH decreased the basal and EGF-induced total cellular kinase activity, particularly the tyrosine phosphorylation of several cellular proteins including the EGFR. In contrast, [D-Trp(6)]LHRH did not cause detectable changes in basal and EGF-stimulated serine/threonine phosphorylation of A431 cellular proteins. The inhibitory effect of [D-Trp(6)]LHRH on A431 cell proliferation was associated with apoptosis as evidenced by the cell morphology and DNA integrity (ladder pattern), the expression of interleukin 1beta-converting enzyme (ICE) and activation of caspase. Furthermore, EGF could rescue the remaining attached A431 cells following [D-Trp(6)]LHRH treatment for 48 hr, which suggests that limited exposure to [D-Trp(6)]LHRH did not channel all cells to irreversible apoptotic process. We also determined the effects of [D-Trp(6)]LHRH on metastasis-associated properties in A431 cells. [D-Trp(6)]LHRH reduced both basal and EGF-stimulated secretion of MMP-9 and MMP-2. In addition, [D-Trp(6)]LHRH suppressed the basal and EGF-induced invasive activity of A431 cells based on an in vitro invasion assay. In conclusion, this study indicates that [D-Trp(6)]LHRH may act partly through activating tyrosine phosphatase activity to inhibit cell proliferation and the metastasis-associated properties of A431 cancer cells. Our work suggests that [D-Trp(6)]LHRH may be therapeutically useful in limiting the tumor growth and metastasis of some neoplasms.

Topics: Antineoplastic Agents, Hormonal; Carcinoma, Squamous Cell; Caspases; Cell Division; DNA Fragmentation; Enzyme Activation; Epidermal Growth Factor; Gonadotropin-Releasing Hormone; Humans; Immunoblotting; Matrix Metalloproteinases; Neoplasm Invasiveness; Phosphorylation; Precipitin Tests; Protein Tyrosine Phosphatases; Serine; Threonine; Time Factors; Triptorelin Pamoate; Tumor Cells, Cultured