Publications by authors named "Ralph Highshaw"

Purpose: We evaluated the antitumor effects of vitamins C and K3 for human urothelial carcinoma and the potential use of the combination of vitamins C plus K3 as a sensitizing agent for conventional chemotherapy for urothelial carcinoma.

Materials And Methods: The antiproliferative and apoptotic effects of vitamin C alone, vitamin K3 alone, vitamins C plus K3, gemcitabine alone and gemcitabine plus vitamins C plus K3 were assessed in vitro by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, propidium iodide staining and flow cytometry. For in vivo studies we implanted UMUC-14 tumorigenic urothelial carcinoma cells into the subcutis of nude mice.

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The proteasome inhibitor bortezomib (formerly known as PS-341) recently received Food and Drug Administration approval for the treatment of multiple myeloma, and its activity is currently being evaluated in solid tumors. Bortezomib triggers apoptosis in pancreatic cancer cells, but the mechanisms involved have not been fully elucidated. Here, we show that pancreatic cancer cells exposed to bortezomib formed aggregates of ubiquitin-conjugated proteins ("aggresomes") in vitro and in vivo.

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Objectives: To compare treatment-related outcomes of immediate and staged urethrectomy in patients at high risk of urethral recurrence.

Methods: We retrospectively identified 76 male patients with cystectomy for transitional cell carcinoma of the bladder who had undergone urethrectomy in the absence of established urethral recurrence. Concomitant cystoprostatectomy and urethrectomy was performed in 57 patients and staged urethrectomy in 19 patients.

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Bortezomib (PS-341, Velcade) is a potent and selective inhibitor of the proteasome that is currently under investigation for the treatment of solid malignancies. We have shown previously that bortezomib has activity in pancreatic cancer models and that the drug induces endoplasmic reticulum (ER) stress but also suppresses the unfolded protein response (UPR). Because the UPR is an important cytoprotective mechanism, we hypothesized that bortezomib would sensitize pancreatic cancer cells to ER stress-mediated apoptosis.

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Objective: Several surgical and technical mechanisms have been proposed for the development of port-site metastasis, but the influence of tumor and host biologic factors has not been emphasized. We present a case of a pelvic chordoma that metastasized to a prior laparoscopic radical nephrectomy port-site.

Methods: A 62-year-old woman underwent laparoscopic radical nephrectomy (LRN) for a pT1b grade 3 renal cell carcinoma, followed 6 weeks later by resection of a sacral chordoma.

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Purpose Of Review: To review the progress of the genitourinary SPORE (Specialized Program of Research Excellence) in bladder cancer.

Recent Findings: The optimal management of bladder cancer depends on the accurate assessment of the biological potential of the disease. Methotrexate, vincristine, adriamycin and cisplatin (M-VAC) chemotherapy has been the standard of therapy for over a decade.

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The standard of practice set by the SWOG investigation of BCG therapy for superficial bladder cancer has been to evaluate response at 3 months with cystoscopy and bladder biopsy. This study is to determine if all patients require a biopsy post therapy at 3 or 6 months. We reviewed the charts of 43 patients who had received a 6-weekly course of BCG (Connaught strain) for high grade or recurrent Ta, T1, or Tis transitional cell carcinoma of the bladder.

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Detection and functional evaluation of mutant p53 alleles using a yeast assay could yield significant information for predicting the prognosis of patients with prostate cancer (CaP). Since the current version of this yeast assay is not applicable to archival tissues, we developed a modified assay for use on formalin-fixed, paraffin-embedded tissue and have applied it to the study of patient samples. Using this modified assay, we examined archival CaP samples from 10 patients for mutations in exons 5-8 of p53 gene.

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Although long-term survival of a functional allograft requiring long-term immunosuppressive therapy is responsible for higher incidence of non-urothelial cancers in renal allograft recipients than in normal population, the incidence of bladder cancer is uncommon and carcinoma of the bladder in the setting of combined kidney-pancreas transplantation has not been reported to date. We herein report a case of poorly differentiated invasive adeno-squamous cell carcinoma of the bladder following renal and bladder-drained pancreatic transplantation in a 44-yr-old lady with long-standing insulin dependent diabetes mellitus, which necessitated radical extirpation. Management implications are reviewed.

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