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Myb, a cellular progenitor of v-Myb oncogenes, is amplified in prostate cancer and exhibits greater amplification frequency in hormone-refractory disease. Here, we have investigated the functional significance of Myb in prostate cancer. Our studies demonstrate Myb expression in all prostate cancer cell lines (LNCaP, C4-2, PC3 and DU145) examined, whereas it is negligibly expressed in normal/benign prostate epithelial cells (RWPE1 and RWPE2). Notably, Myb is significantly upregulated, both at transcript (>60-fold) and protein (>15-fold) levels, in castration-resistant (C4-2) cells as compared with androgen-dependent (LNCaP) prostate cancer cells of the same genotypic lineage. Using loss and gain of function approaches, we demonstrate that Myb promotes and sustains cell cycle progression and survival under androgen-supplemented and -deprived conditions, respectively, through induction of cyclins (A1, D1 and E1), Bcl-xL and Bcl2 and downregulation of p27 and Bax. Interestingly, Myb overexpression is also associated with enhanced prostate-specific antigen expression. Furthermore, our data show a role of Myb in enhanced motility and invasion and decreased homotypic interactions of prostate cancer cells. Myb overexpression is also associated with actin reorganization leading to the formation of filopodia-like cellular protrusions. Immunoblot analyses demonstrate gain of mesenchymal and loss of epithelial markers and vice versa, in Myb-overexpressing LNCaP and -silenced C4-2 cells, respectively, indicating a role of Myb in epithelial to mesenchymal transition. Altogether, our studies provide first experimental evidence for a functional role of Myb in growth and malignant behavior of prostate cancer cells and suggest a novel mechanism for castration resistance. [ABSTRACT FROM PUBLISHER]

Objectives β-Elemene, a natural compound extracted from over 50 different Chinese medicinal herbs and plants, has been effective in the treatment of hyperplastic and proliferative disorders such as prostatic hypertrophy, hysteromyoma and neoplasms. Our previous studies have demonstrated that β-elemene exhibits strong inhibitory activity in ovarian cancer cells. The aim of the present study was to assess the effect of β-elemene on prostate cancer cells as well as other types of tumour cells and to determine whether the effect of β-elemene on prostate cancer cell death was mediated through the induction of apoptosis. Methods The MTT assay was used to evaluate the ability of β-elemene to inhibit cellular proliferation in cancer cells. Cellular apoptosis was assessed by annexin V binding, TUNEL and ELISA-based assays. Caspase activity was measured using a caspases assay kit. The protein levels of Bcl-2, caspases, cytochrome c and poly(ADP-ribose) polymerase (PARP) were analysed by Western blotting. Key findings Here, we showed that β-elemene had an antiproliferative effect on androgen-insensitive prostate carcinoma DU145 and PC-3 cells. Treatment with β-elemene also inhibited the growth of brain, breast, cervical, colon and lung carcinoma cells. The effect of β-elemene on cancer cells was dose dependent, with IC50 values ranging from 47 to 95 µg/ml (230-465 µ m). TUNEL assay and flow cytometric analysis using annxin V/propidium iodide staining revealed that the percentage of apoptotic prostate cancer cells was increased by β-elemene in a dose- and time-dependent manner. Moreover, β-elemene exposure resulted in a decreased Bcl-2 protein level, increased cytochrome c release, and activated PARP and caspase-3, -7, -9, and -10 in prostate cancer cells. Conclusions Overall, these findings suggest that β-elemene exerts broad-spectrum antitumour activity against many types of solid carcinoma and supports a proposal of β-elemene as a new potentially therapeutic drug for castration-resistant prostate cancer and other solid tumours. [ABSTRACT FROM AUTHOR]

The androgen receptor plays a major role in the development and function of normal and malignant prostate cells. Due to the relationship of the androgen receptor and prostatic growth, it has been proposed that polymorphisms within the androgen receptor may play a role in an individual’s susceptibility to developing prostate cancer. An inverse relationship has been established between a highly polymorphic trinucleotide repeat located in the first exon of the androgen receptor and the transactivaton function of the receptor. Serum samples were collected from 131 patients with histologically confirmed adenocarcinoma of the prostate, DNA was isolated, and the polymorphic CAG repeat was amplified by PCR and sequenced. The CAG repeat lengths were then compared with age at diagnosis, age at time of study, baseline log[sub 10] PSA, Gleason score, time from diagnosis to initiation of hormonal therapy, time to progression after androgen ablation, and overall survival time. No correlation was found between CAG length and time to progression or overall survival time, but a significant correlation was found between Gleason score and CAG length suggesting that shorter CAG lengths may predict a higher histological grade of prostate cancer.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Leptomeningeal involvement of metastatic prostate cancer is a rare clinical entity. We report such a case, along with a summary of three previous cases where detailed clinical information is available. Seven additional cases (for a total of 10 cases) have been reported previously in the literature. It seems that this syndrome is associated with changes in mentation, specifically without cranial nerve findings on physical exam. The physician should be alerted to the possibility of this clinical circumstance in metastatic prostate cancer patients with altered mental status. [ABSTRACT FROM AUTHOR]

Introduction: Due to in vitro data suggesting antitumor activity with gallium nitrate, we sought to evaluate the safety and activity in patients with androgen-independent prostate cancer. Method: Patients were eligible for this study if they had an ECOG performance status of ≤2, stage D2 metastatic prostate cancer that was progressing following combined androgen ablation (medical or surgical castration plus antiandrogen) and had failed antiandrogen withdrawal. Therapy consisted of gallium nitrate (200 mg/m[sup 2] /day) as a continuous infusion for 7 days, administered every 21 days, with hydration (100 ml/m[sup 2] /h). Individuals that had previously received suramin were treated at a dose of 150 mg/m[sup 2] /day of gallium nitrate. Results: Eight patients were enrolled: 4 patients at the 200 mg/m[sup 2] /day dose level and 4 patients at the lower dosage (150 mg/m[sup 2] /day). One of 8 patients had a >75% decline in prostate-specific antigen (PSA), 3 patients had stable PSA values for 17, 18 and 22 weeks, and 4 patients had progression by PSA (>50% increase over baseline). Anemia requiring transfusion occurred in 5 of 8 patients (63%). Two patients (25%) developed grade 4 toxicity: 1 patient developed complete blindness with partial reversal over 12 months, and another patient had pulmonary infiltrates, hypoxemia, and fever. Serious adverse events were not correlated to prior suramin exposure, or gallium plasma concentrations (total or free), but appeared to be related to cumulative cycles of gallium nitrate. Remaining adverse events were grade 1 or 2. No patients developed renal or neurological toxicity. Conclusion: This trial was prematurely terminated because repeated administration of gallium nitrate was poorly tolerated in an elderly population with androgen-independent prostate cancer. Gallium had modest clinical activity in this disease.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective. To present a patient with metastatic pros tate cancer who has experienced an extended re sponse to the withdrawal of flutamide and the con comitant initiation of aminoglutethimide.Case Summary. A 73-year-old male was diagnosed with advanced metastatic prostate cancer. He received treatment with suramin, leuprolide, and flutamide. After progressing on this regimen his flutamide was discon tinued and aminoglutethimide was initiated. His re sponse to this treatment has reached almost 3 years, with no evidence of progression.Discussion. The response to the withdrawal of flutamide is thought to arise from a mutated androgen receptor that recognizes hydroxyflutamide, the active metabolites of flutamide, as an agonist. The receptor continues to recognize endogenous steroids as agonists. The addition of the adrenal steroid synthesis inhibitor, aminoglutethimide may play a role in enhancing this response phenomenon.Conclusions. This patient is progression free for approximately 3 years following the withdrawal of flutamide. This maneuver has been found to have activity in a subset of patients who have been treated for metastatic prostate cancer with combined andro gen blockade. [ABSTRACT FROM PUBLISHER]