Efficacy of vaccination with plasmid DNA encoding for HER2/neu or HER2/neu-eGFP fusion protein against prostate cancer in rats.

Despite early diagnosis and improved therapy, 31,500 men will die from prostate cancer (PC) this year. The HER2/neu oncoprotein is an important effector of cell growth found in the majority of high-grade prostatic tumors and is capable of rendering immunogenicity. The antigenicity of this oncoprotein might prove useful in the development of PC vaccines. Our goal is to prove the principle that a single DNA vaccine can provide reliable immunity against PC in the MatLyLu (MLL) translational tumor model. The parental rat MatLyLu PC cell line expresses low to moderate levels of the rat neu protein. To simulate in vivo human PC, MatLyLu cells were transfected with a truncated sequence of human HER2/neu cDNA cloned into the pCI-neo vector. This HER2/neu cDNA sequence encodes the first 433 amino acids of the extracellular domain (ECD). MatLyLu cells were also transfected with the same HER2/neu cDNA sequence cloned into the N1-terminal sequence of EGFP reporter gene to produce a fusion protein. The partial ECD sequence of HER2/neu includes five rat major histocompatibility (MHC)-II-restricted peptides with complete human-to-rat cross-species homology. The HER2/neu protein overexpression was documented by Western Blot analysis, and the expression of fusion protein was monitored by confocal microscopy and fluorimetry. Vaccination with a single injection of HER2/neu cDNA protected 50% of animals against HER2/neu-MatLyLu tumors (P < 0.01). When the tumor cells were engineered to express HER2/neu-EGFP fusion protein, the antitumor immunity was enhanced, as following vaccination with HER2/neu-EGFP cDNA, 80% of these rats rejected HER2/neu-EGFP-MatLyLu (P<0.001). Both vaccines induced HER2/neu-specific antibody titers. Rats vaccinated with EGFP-cDNA rejected 80% of EGFP-MatLyLu tumors and, interestingly, 40% of HER2/neu-MatLyLu tumors. None of the cDNA vaccines induced immunity against parental MatLyLu cells. Our data clearly demonstrate that a single injection of HER2/neu-EGFP cDNA is a very effective vaccine against PC tumors expressing the cognate tumor-associated antigen (TA). The antitumor immunity is significantly more pronounced if the tumors express xenogeneic HER2/neu-EGFP fusion protein as opposed to only the syngeneic HER2/neu oncoprotein. Our data suggests that the HER2/neu-EGFP-MatLyLu tumor is a potential animal tumor model for investigating therapeutic vaccine strategies against PC in vivo and demonstrates the limitations of a cDNA vaccine only encoding for MHC-II-restricted HER2/neu-ECD sequence peptides.

The treatment challenge of hormone-refractory prostate cancer.

BACKGROUND: Both the demographics and treatment of hormone-refractory prostate cancer (HRPC) are changing. Patients are younger and healthier, with fewer comorbidities. The "no treatment until symptoms" approach is disappearing. Chemotherapy is increasingly being utilized. METHODS: The authors review the steps involved in hormone management before chemotherapy is considered. The roles for chemotherapy in current clinical trials are examined. RESULTS: Effective hormonal management of the prostate cancer patient incorporates an understanding of the stages of hormone sensitivity and prescribing additional interventions beyond simple castration. Once hormone refractoriness is established, the combination of mitoxantrone and prednisone has become a standard chemotherapeutic approach. New agents such as docetaxel are being tested in phase III trials against mitoxantrone plus prednisone. CONCLUSIONS: HRPC is now regarded as a chemotherapy-sensitive tumor. The goals of chemotherapy in HRPC are to decrease PSA level and improve quality of life. New agents and combinations are needed to improve survival.

Radical prostatectomy in the management of clinically localized prostate cancer.

BACKGROUND: Several management options are available when prostate cancer is diagnosed at an early stage. However, the optimal treatment for localized prostate cancer is unknown, and reports in the literature are controversial regarding the best treatment modality for this early presentation. METHODS: The authors review improvements in surgical technique that have decreased complications, and they address long-term outcomes of surgery related to cancer control. RESULTS: Improvements in surgical techniques allow for decreased intraoperative complications. The incidence of long-term complications such as incontinence and impotency is also reduced. The 5- and 10-year progression-free survival with radical prostatectomy has improved. CONCLUSIONS: Surgery today is safer with improvements in techniques. The long-term outcomes with surgery are excellent and, in several series, better than outcomes achieved with other treatment modalities.

Successful in utero endoscopic ablation of posterior urethral valves: a new dimension in fetal urology.

Fetal lower urinary tract obstructive uropathy, when associated with oligohydramnios, is usually associated with a poor outcome. We present a case of successful in utero endoscopic ablation of posterior urethral valves in which the infant survived the neonatal period without evidence of renal dysplasia. The role, indications, and potential benefits of this novel technique are discussed.