[A Case of General Fatigue Caused by Enzalutamide that was Evaluated Using the Cancer Fatigue Scale and Overcome by Switching to Nighttime Treatment].

An 81-year-old man with castration-resistant prostate cancer experienced general fatigue while receiving enzalutamide treatment. In some patients we encountered the enzalutamide treatment had to be interrupted or the dose decreased because of this adverse effect. We evaluated the patient's general fatigue using the Cancer Fatigue Scale (CFS) score and clarified the quantitative information about his general fatigue. In order to maintain the optimal dose, we advised the patient to take enzalutamide at night. This alleviated the adverse effect, and he could maintain the optimal dose of this medicine. We compared the CFS score before and after switching to nighttime treatment and found improvement. This is the first report of a CFS-based evaluation of the improvement in general fatigue caused by enzalutamide by switching to nighttime treatment.

Silodosin versus naftopidil in the treatment of premature ejaculation: A prospective multicenter trial.

OBJECTIVES: To determine the efficacy of two α1-adrenoceptor antagonists with different affinities for α1-adrenoceptor subtypes, silodosin and naftopidil, in the treatment of premature ejaculation. METHODS: This was a prospective, open-label, multicenter trial. A total of 26 patients with untreated acquired premature ejaculation were enrolled. Premature ejaculation was defined based on the International Society for Sexual Medicine recommendation. Patients self-administered on demand silodosin 4 mg or naftopidil 25 mg 1 h before intercourse, alternating drugs at least three times each. Clinical global impression change for premature ejaculation, premature ejaculation profile, and intravaginal ejaculation latency time were evaluated at baseline and during treatment. RESULTS: Due to clinical global impression change, 24 patients (92%) and 12 patients (46%) reported improvement in their own premature ejaculation problems under silodosin and nafitopidil administration, respectively. Silodosin treatment produced a significantly higher improvement rate compared with naftopidil (P = 0.0002). Objectively, silodosin significantly prolonged intravaginal ejaculation latency time compared with baseline and naftopidil (P < 0.01). Mean intravaginal ejaculation latency times were 1.9, 4.1, and 7.6 min at baseline, control and with silodosin, respectively. The rate of reduced semen volume during silodosin treatment was higher than during naftopidil treatment. There were no adverse systemic effects in either group. CONCLUSIONS: Silodosin, a highly selective α1A-adrenoceptor antagonist, produces greater improvements in premature ejaculation profiles and related symptoms along with intravaginal ejaculation latency time in acquired premature ejaculation patients with or without erectile dysfunction. This result supports the clinical use of silodosin as an alternative treatment for premature ejaculation.

Simple and reliable predictor of urinary continence after radical prostatectomy: serial measurement of urine loss ratio after catheter removal.

OBJECTIVES: To evaluate urine loss ratio after catheter removal as a predictive factor of urinary continence after radical prostatectomy. METHODS: A total of 190 patients who had undergone retropubic radical prostatectomy were evaluated. Urine loss ratio was measured using the 24-h pad test during 7 consecutive days after removal of urethral catheters. Continence rates at 1, 3, 6 and 12 months after operation were evaluated with the urinary function domain of the University of California, Los Angeles Prostate Cancer Index. The desirable urine loss ratio for continent condition at 12 months after the operation was calculated. As desirable target urine loss ratio continence at 12 months was determined by using logistic analysis. RESULTS: Continence rates of all patients at 1, 3, 6 and 12 months after surgery were 13%, 37.8%, 58.9%, and 85.8%, respectively. Continence rates of patients who achieved ≤1% of urine loss ratio within 7 days or ≤5% urine loss ratio within 3 days after catheter removal was 100% at 12 months. Logistic regression analysis proved these urine loss ratio values were significant predictors of continence at 12 months. CONCLUSIONS: Urine loss ratio after catheter removal within 7 days is a significant determinant of urinary continence after radical prostatectomy. This parameter could have clinical usefulness to estimate future recovery of urinary continence.

Hypoxia-inducible factor (HIF)-independent expression mechanism and novel function of HIF prolyl hydroxylase-3 in renal cell carcinoma.

PURPOSE: We previously found that hypoxia-inducible factor (HIF) prolyl hydroxylase-3 (PHD3) was frequently overexpressed in renal cell carcinomas (RCCs), unlike in normal tissues, and therefore, we studied the mechanism and role of PHD3 expression in RCC. METHODS: The von Hippel-Lindau (VHL)-gene-mutant RCC cell lines SMKT-R2 and SMKT-R3 and wild-type VHL cell lines Caki-1 and ACHN were used. Associations of the expression of PHD3 with HIF-α proteins and signal transduction pathways were evaluated under normoxic conditions. The effect of PHD3 on cell proliferation was also examined by small interference RNA and cDNA transfection. Moreover, the prognostic impact of PHD3 expression in clear cell RCC (CCRCC) was evaluated using primary cancer tissues. RESULTS: In SMKT-R2 and SMKT-R3, HIF-α proteins were expressed and PHD3 was highly expressed. On the other hand, ACHN had low expression of HIF-α proteins and PHD3. However, Caki-1 had high expression of PHD3 even though there was no distinct expression of HIF-α proteins. PHD3 expression was inhibited by blockade of Akt and mammalian target of rapamycin (mTOR), but not by HIF-1α and HIF-2α double knockdown. In addition, PHD3 knockdown resulted in the promotion of cell proliferation in SMKT-R2, SMKT-R3 and Caki-1. On the other hand, forced expression of PHD3 reduced cell proliferation in ACHN. In immunohistochemistry, PHD3 expression was a significant factor for better recurrence-free survival in patients with CCRCC. CONCLUSIONS: PHD3 expression can be induced by the phosphatidylinositol-3 kinase/Akt/mTOR pathway in RCC independently of HIF proteins. Furthermore, PHD3 has an antiproliferative function independent of HIF protein status in RCC, indicating a novel expression mechanism and function of PHD3.

[Masturbation device (EGG) as a new penile rehabilitation tool: a pilot study].

Erectile dysfunction following radical prostatectomy (RP) is still a significant burden as a post-operative morbidity, despite advances in nerve-sparing techniques and penile (erectile function) rehabilitation (PR) programs. We assessed the effects of stimulation with the masturbation device "EGG" on enhancement of erectile response along with administration of phospho diesterase type 5 inhibitor. We also studied the change of self-esteem and motivation for continuation of PR after stimulation with EGG. Eight nonresponders for PDE5-I who underwent retropubic RP were enrolled. Patients' median age was 71.5 years old. No patients received adjuvant therapy for prostate cancer. The patients' erectile response in the penile rehabilitation session (masturbation) with PDE5-I＋manual stimulation and PDE5-I＋stimulation with EGG were evaluated by erection hardness score (EHS). Changes of self-esteem and motivation for penile rehabilitation were assessed by the self-esteem subscale of the Self-Esteem and Relationship (SEAR) questionnaire and one original question, respectively. PDE5-I ＋ stimulation with EGG significantly enhanced EHS compared to PDE5-I＋manual stimulation in the eight patients (p＝0.027). Transformed score of self-esteem subscale score of SEAR questionnaire was significantly increased in the PR session with EGG compared to the PR session with manual stimulation (p＝0.043). Six patients who showed a better erectile response with EGG retained motivation for continuation of PR. PDE5-I＋stimulation with EGG improved the erectile response in post-RP patients. EGG as a masturbation device may have a potential for contribution to successful PR.

Dissociation between patients and their partners in expectations for sexual life after radical prostatectomy.

OBJECTIVE: To analyze expectations for sexual life after radical prostatectomy in patients and their partners, and its influence on sexual motivation and bothers in the postoperative period. METHODS: A total of 162 patients who underwent retropubic radical prostatectomy and their partners were evaluated. The patients' sexual function, sexual bother and expectations for postoperative sexual life were assessed prospectively at baseline, and at 1, 3, 6 and 12 months after radical prostatectomy. The partner was asked questions about postoperative sexual life before the operation. Sexual function and sexual bother were evaluated by the University of California Los Angeles Prostate Cancer Index. Expectations for postoperative sexual life were studied using three ad hoc questions. RESULTS: The rate of having sexual intercourse and adequate penile rigidity for vaginal penetration at baseline was 29.0% and 21.6%, respectively. A significantly higher rate of patients considered "sexual life is important" (patient 35.2%, partner 13.0%), hoped for "preservation of erectile function" (patient 66.0%, partner 33.3%) and accepted "use of phosphodiesterase type 5 inhibitor" (patient 65.4%, partner 43.2%) compared with their partners (P < 0.001). Patients who had partners with a negative sexual attitude lost sexual motivation 1 year after operation. However, patients with cooperative partners maintained sexual motivation, although they felt greater sexual bother 1 year after radical prostatectomy. CONCLUSIONS: There was a significant dissociation in perspectives of postoperative sexual life between patients undergoing radical prostatectomy and their partners. Partners' low expectations are associated with patients' low sexual bother and motivation. Partners' cooperative attitude might contribute to maintaining patients' sexual desire and motivation.

[Follow-up method for patients with non-muscle-invasive bladder cancer who remained recurrence-free for a long time].

To determine the follow-up schedule in patients with non-muscle-invasive bladder cancer who had remained recurrence-free for 5 or more years, we retrospectively reviewed 258 patients with Ta and T1 bladder cancer who had been free of recurrence for at least 5 years. Of these 258 patients, subsequent recurrences developed in 100 patients. In spite of our recommendation that cystoscopic follow-up be done at 12-month intervals for patients who remained recurrence-free for more than 5 years, 45 had been followed at intervals of more than 12 months (range, 13-77 months) when the recurrences were found. Of 100 recurrent tumors, 20 (20.0%) showed bladder muscle invasion. Muscle-invasive cancer was identified more often in the patients with cytoscopic intervals of more than 12 months than in those of less than 12 months (35.6% versus 7.3%). Therefore, we recommend that cystoscopy be performed at intervals of less than 12 months in patients with non-muscle invasive bladder cancer for recurrence detection before tumors become muscle invasive, even when patients remain free of recurrence for a long period.

Silodosin and its potential for treating premature ejaculation: a preliminary report.

Premature ejaculation is a common sexual problem, as is erectile dysfunction. We evaluated silodosin, a highly selective α1A-adrenoceptor antagonist, as a new treatment option for premature ejaculation. α1-Adrenoceptor antagonists are widely used for lower urinary tract symptoms, and clinical studies on silodosin have shown excellent clinical efficacy for lower urinary tract symptoms. However, compared with other α1-adrenoceptor antagonists, silodosin appeared to suppress ejaculation in a relatively higher percent of trial participants. This suppression of ejaculation by silodosin suggested its potential for treating premature ejaculation. Consequently, we evaluated the feasibility of off-label silodosin as a new treatment option for premature ejaculation. Eight patients suffering premature ejaculation were treated with silodosin. Silodosin (4 mg) was given 2 h before sexual intercourse. Intravaginal ejaculatory latency time, premature ejaculation profile item, clinical global impression change in premature ejaculation and systemic adverse events were recorded. Intravaginal ejaculatory latency time was significantly prolonged (from 3.4 min to 10.1 min, P = 0.003). All patients answered better (much better) or slightly better for their own premature ejaculation problem compared with pretreatment condition in the clinical global impression change. Premature ejaculation profile also significantly improved. Two (25%), three (37.5%) and seven patients (87.5%) experienced anejaculation, reduced semen volume and discomfort during orgasm, respectively. However, these problems were not of major concern for the participants. No systemic adverse effects were reported. The current results support the possible use of silodosin as a new treatment option for premature ejaculation, and suggest that a placebo controlled study assessing its clinical usefulness would be worthwhile.

Isolated ACTH deficiency in self referred patients for LOH syndrome: two case reports.

We experienced two cases of isolated ACTH deficiency (IAD) in patients self referred for late-onset hypogonadism (LOH) syndrome. IAD is secondary adrenal insufficiency due to lack of secretion of ACTH and delayed diagnosis of this rare condition may be life-threatening. The predominant symptoms of IAD, such as general malaise and weakness, resemble those of LOH syndrome creating the possibility that IAD may be referred as LOH syndrome. Two middle aged men with severe general malaise visited our clinic requesting evaluation for LOH syndrome. Previous treatments had been ineffective and based on varying incorrect diagnoses by previous doctors. The patients self referred themselves for LOH syndrome. Some of their symptoms were consistent with LOH syndrome but others were atypical, in particular, the severity of malaise and appetite loss. Hormonal assays were compatible with adrenal insufficiency secondary to ACTH deficiency. Steroid replacement dramatically improved their symptoms. The clinical course of our two patients and points of differential diagnosis between IAD and LOH syndrome are reported here.

Clinical outcomes of patients with pT0 bladder cancer after radical cystectomy: a single-institute experience.

OBJECTIVE: To investigate the clinical outcomes of patients who underwent radical cystectomy for bladder cancer at a single institution and compare those who had pT0 specimens with those who had residual cancer. METHODS: From January 1990 to December 2006, 186 patients underwent radical cystectomy with or without neoadjuvant chemotherapy for cT2 or higher stage urothelial carcinoma in the bladder in our hospital. We estimated the 5-year disease-free survival, cancer-specific survival and overall survival by the pathological stage. RESULTS: The median follow-up of the 186 patients was 38.5 months (0-194). Of these, 51 received neoadjuvant chemotherapy. For all subjects, the 5-year disease-free survival was 54.9%, cancer-specific survival 61.0% and overall survival 57.1%. Of the 186 patients, 24 (12.9%) had no residual cancer in the bladder specimen at radical cystectomy. Of the 24 patients with pT0, only 1 (4.2%) died of bladder cancer. The 5-year disease-free survival, cancer-specific survival and overall survival rates in patients with pT0 were ∼96.0%. We found pT0 histology in 11 of the 51 patients (21.6%) with neoadjuvant chemotherapy and in 13 of the 135 patients (9.6%) with radical cystectomy alone (P = 0.047). CONCLUSIONS: We demonstrated that the outcomes of patients who underwent radical cystectomy were similar to those in previous reports. Patients with pT0 showed favorable outcomes for disease-free survival, cancer-specific survival and overall survival in our study. However, they should be periodically followed up because pT0 does not always mean cure.

Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer.

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL)-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs) and determined HLA-A24-restricted CTL epitopes.RT-PCR and immunohistochemical analysis revealed that AMACR was strongly expressed in prostate cancer cell lines and tissues as compared with benign or normal prostate tissues. Four AMACR-derived peptides carrying the HLA-A24-binding motif were synthesized from the amino acid sequence of this protein and analyzed to determine their binding affinities to HLA-A24. By stimulating patient's PBMCs with the peptides, specific CTLs were successfully induced in 6 of 11 patients. The peptide-specific CTLs exerted significant cytotoxic activity against AMACR-expressing prostate cancer cells in the context of HLA-A24. Our study demonstrates that AMACR could become a target antigen for prostate cancer immunotherapy, and that the AMACR-derived peptides might be good peptide vaccine candidates for HLA-A24-positive AMACR-expressing cancer patients.

[Prognosis of local recurrence after radical cystectomy for bladder cancer].

The clinical outcome is poor for patients who have local recurrence after radical cystectomy for bladder cancer. We investigated clinical outcomes of patients with isolated local recurrence and with both local recurrence and distant metastasis. From 1990 to 2006, 299 patients who had bladder cancer without distant metastasis underwent radical cystectomy in our hospital. We included 200 patients who had a negative surgical margin at radical cystectomy and urothelial carcinoma, and who had not had upper urinary tract cancer or other active cancer. Fifteen (7.5%) had isolated local recurrence (isolated group) and 18 (9.0%) had local recurrence and distant metastasis simultaneously (simultaneous group). The median overall survival time and that for survival after recurrence were 24 and 13 months, respectively, in the isolated group, and 18 and 5 months, respectively, in the simultaneous group. Although we did not find a significant difference in overall survival (p = 0.314), there was one for survival after recurrence (p = 0.001) between the two groups. In the isolated group, 13 died of cancer, 1 of another cause and 1 was alive without cancer. All patients in the simultaneous group died of cancer. Three patients in the isolated group underwent surgery for residual tumors after systemic chemotherapy, and 2 of the 3 survived for more than 2 years after recurrence. Some patients with isolated local recurrence benefited from multimodal therapies. In these patients, surgery for the residual tumor after systemic chemotherapy was likely to be effective if a negative margin was achieved in surgical specimens.

Phase I clinical study of anti-apoptosis protein survivin-derived peptide vaccination for patients with advanced or recurrent urothelial cancer.

Survivin, a member of the inhibitor of apoptosis protein family, is expressed in many malignant tumors including urothelial cancer but is hardly detectable in normal, differentiated adult tissues. Previously we reported CD8-positive cytotoxic T-lymphocytes (CTLs) were successfully induced by stimulation with survivin-2B80-88 peptide in vitro. We started a phase I clinical study of survivin-2B80-88 peptide vaccination for advanced urothelial cancer patients to assess the safety and efficacy of this vaccination. Nine patients were received vaccination and were evaluated for immunological evaluation, adverse events, and clinical responses. A total of 46 vaccinations were carried out. There was no severe adverse event. HLA-A24/survivin-2B80-88 peptide tetramer analysis revealed a significant increase in the peptide-specific CTL frequency after the vaccination in five patients. Slight reduction of the tumor volume was observed in one patient. Survivin-2B80-88 peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in urothelial cancer patients.

Identification of an immunogenic CTL epitope of HIFPH3 for immunotherapy of renal cell carcinoma.

PURPOSE: CD8(+) CTLs have an essential role in immune response against tumor. Although tumor-associated antigens have been identified in renal cell carcinoma (RCC), few of these are commonly shared and investigated as therapeutic targets in the clinical medicine. In this report, we show that HIFPH3, a member of prolyl hydroxylases that function as oxygen sensor, is a novel tumor antigen and HIFPH3-specific CTLs are induced from peripheral blood lymphocytes of RCC patients. EXPERIMENTAL DESIGN: Expression of HIFPH3 was examined by reverse transcription-PCR and immunostaining with anti-HIFPH3 antibody. To identify HLA-A24-restricted T-cell epitopes of HIFPH3, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. Peptide-specific CTLs were induced by stimulating peripheral blood lymphocytes of HLA-A24-positive RCC patients with these peptides in vitro. HLA-A24-restricted cytotoxicity of the CTLs against HIFPH3(+) RCC lines was assessed by chromium release assay. RESULTS: HIFPH3 was overexpressed in many RCC cell lines and primary RCC tissues, whereas it was not detectable in normal adult tissues by reverse transcription-PCR. Of the eight peptides that contained HLA-A24-binding motif, HIFPH3-8 peptide (amino acid sequence, RYAMTVWYF) could induce the peptide-specific CTLs from 3 of 6 patients with HIFPH3-positive RCC. Furthermore, HIFPH3-8 peptide-specific CTLs showed cytotoxicity against HIFPH3(+) RCC cell lines in a HLA-A24-restricted manner. CONCLUSIONS: HIFPH3 may be a target antigen in immunotherapy for RCC and HIFPH3-8 peptide could be used as a peptide vaccine for HLA-A*2402(+)/HIFPH3(+) RCC patients.

[Early postoperative complications of radical cystectomy and urinary diversion in elderly patients].

Clinical and operative features and early postoperative complications were reviewed in 26 patients 75 years old and older who were treated with radical cystectomy including pelvic lymphadenectomy and urinary diversion in our hospital from 1994 to 2005. These findings were compared with those in 170 patients younger than 75 years old who received the same surgery and in 26 patients 75 years old and older who were not surgically treated. Early postoperative complications were found in 9 elderly patients (34%), but there were no deaths in the preoperative and early postoperative periods. There was no significant difference in the rate of early postoperative complications between patients 75 years old and older and those younger than 75. Preoperative performance status (PS) and the American Society of Anesthesiologists Score (ASA score) were significantly better in elderly patients with the surgery than those without surgery. Therefore, evaluation with PS and the ASA score may allow urologists to appropriately select elderly candidates for radical cystectomy and urinary diversion. Chronological age alone is not a determinant for indicating the surgery.

Expression of livin in renal cell carcinoma and detection of anti-livin autoantibody in patients.

OBJECTIVES: To assess the expression of livin, a member of the inhibitor of apoptosis protein family, in renal cell carcinoma (RCC) and to determine its prognostic relevance. METHODS: Immunohistochemical staining for livin was performed using paraffin-embedded tissues from 45 cases of RCC. Then we assessed anti-livin antibodies (Abs) in patient sera by enzyme-linked immunosorbent assay and Western blotting. Disease-specific survival of patients was assessed, and differences between the immunohistologically livin-positive and livin-negative groups and between the anti-livin Ab-positive and anti-livin Ab-negative groups were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. RESULTS: Of the 45 RCC specimens, 26 (57.8%) showed positive staining of livin immunohistochemically. In the RCC patients, anti-livin antibodies were detected and their levels were significantly higher than those in healthy volunteers. However, there was no difference in disease-specific survival between the livin-positive and livin-negative patients or between the anti-livin-positive and anti-livin-negative patients. CONCLUSIONS: Although livin expression may not provide predictive information, it may be recognized as a tumor antigen by the immune system in RCC patients.

Effects of a new immunosuppressive agent, beta-SQAG9, in swine kidney transplantation.

We previously reported that 1,2-di-O-acyl-3-O-(-D-sulfoquinovosyl)-glyceride with two stearic acids (beta-SQAG9) bound to L-selectin on the cell surface of the CD62L(+) T-cell subset and inhibited T-cell migration into lymph nodes in a rat skin allograft model. The aim of this study was to verify the efficacy of beta-SQAG9 for kidney allograft survival in miniature swine. Recipient swine underwent bilateral nephrectomy and then received renal allograft transplantation from a swine leukocyte antigen-mismatched donor. Swine were divided into 4 experimental groups. The control (n=2), 25-SQ (n=3), FK (n=3) and 10-SQ/FK (n=2) groups were treated with no immunosuppressant, 25 mg/kg beta-SQAG9, 0.1 mg/kg FK506, and a combination of 10 mg/kg beta-SQAG9 and 0.1 mg/kg FK506, respectively, for 14 days. All recipients were autopsied on the day of death to evaluate the cause of death histopathologically. In the control group, the grafts survived for 12 and 15 days. By comparison with the control, beta-SQAG9 alone did not contribute to prolongation of graft survival (9, 10 and 24 days), whereas the FK group had significantly longer graft survival (19, 20 and 68 days, p=0.0289). The 10-SQ/FK pigs died of lethal visceral hemorrhage, although the grafts were still functioning. In conclusion, our results suggest that beta-SQAG9 possesses an insufficient immunosuppressive effect for kidney allografts in miniature swine, and may affect blood coagulation and fibrinolysis. In addition, the combination of beta-SQAG9 and FK506 can potentially cause severe hemorrhagic complications.

Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition.

PURPOSE: HLA class I down-regulation in cancer cells confers immunological escape from cytotoxic T lymphocytes. We assessed the frequency of down-regulation of HLA class I antigens in a large series of prostate cancer tissues and determined the mechanism of up-regulation by investigating prostate cancer cell lines. MATERIALS AND METHODS: Immunohistochemical staining for HLA class I was done in specimens of 419 prostate cancers. We also investigated clinicopathological parameters, and the relationships between HLA class I down-regulation and the parameters. Furthermore, we examined whether HLA down-regulation was caused by epigenetic changes in vitro. RESULTS: HLA class I was down-regulated in 311 prostate cancers (74.2%) and it significantly correlated with beta2-microglobulin down-regulation and a higher clinical stage. Flow cytometric analysis revealed a low level of HLA class I in LNCaP cells, which was up-regulated by the histone deacetylase inhibitor trichostatin A (Sigma). Trichostatin A up-regulated LNCaP beta2-microglobulin at the protein level. Furthermore, chromatin immunoprecipitation assay using an anti-acetylated histone H3 antibody provided direct evidence that trichostatin A up-regulated beta2-microglobulin by modulating the acetylation status of the promoter region in LNCaP cells. CONCLUSIONS: The current study shows that the prevalence of HLA class I down-regulation is high in prostate cancer but histone deacetylase inhibitors can up-regulate HLA class I in LNCaP cells by up-regulating beta2-microglobulin. We suggest that the combination of an immunotherapeutic approach and histone deacetylase inhibition would accentuate the effects of current immunotherapies for prostate cancer.