One hundred cases of Rezum water vapor thermal therapy for benign prostatic hyperplasia: Real-world data at a single institution in Japan.

OBJECTIVE: The objective of our study was to assess the efficacy of Rezum, a minimally invasive surgical treatment, for patients with lower urinary tract symptoms related to benign prostatic hyperplasia (BPH) in real-world clinical practice at a single institution in Japan. MATERIALS AND METHODS: We conducted a prospective study involving 100 patients who underwent the Rezum procedure between October 2022 and February 2024. We analyzed patient backgrounds that are compliant with Japanese regulations and assessed descriptive outcomes such as symptom scores, peak flow in uroflowmetry, post-void residual (PVR) volume, and prostate volume (PVol). These data were collected at 1 and/or 3 months postoperatively. RESULTS: On average, 4.7 water vapor injections were administered during the Rezum procedures, with a mean operative time of 6.3 min. Patients experienced significant relief in symptoms, with reductions of 55% in International Prostate Symptom Score, 53% in quality of life score, and 30% in Overactive Bladder Symptom Score. There was also a significant decrease in mean PVR volume (50% reduction) and PVol (27% reduction). Among the subgroup of 23 pre-interventional catheter-dependent patients, 91% achieved catheter independence. CONCLUSION: Our single-center analysis demonstrates that Rezum is an effective and safe minimally invasive therapeutic option for patients with BPH. This promising novel technique can be particularly beneficial for patients at an augmented risk of bleeding or those considered high risk for anesthesia.

[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 as second-line α-blocker monotherapy in patients with benign prostatic hyperplasia: A prospective observational study.

OBJECTIVE: To assess the efficacy of silodosin as second-line α-blocker monotherapy in patients with lower urinary tract symptoms as a result of benign prostatic hyperplasia. METHODS: Men who were given an α-blocker other than silodosin for ≥8 weeks, aged ≥50 years, had a total International Prostate Symptom Score ≥13 and quality of life index ≥4 were enrolled. After treatment with 8 mg/day silodosin for 8 weeks, symptoms and treatment satisfaction were assessed. If the patients still complained and hoped for readministration of the first-line α-blocker, the previous medication was administered again for 8 weeks in the case of persisting symptoms, and efficacy was again evaluated. RESULTS: A total of 73 patients were enrolled and analyzed at 8 weeks. Silodosin administration significantly improved the International Prostate Symptom Score and Overactive Bladder Symptom Score. The quality of life index was improved by at least 1 point in 49.3% patients, and its mean change was significantly greater in the group with previous naftopidil treatment than in those with tamsulosin. A total of 59 patients hoped to continue silodosin, and 13 requested administration of the first-line α-blocker. Previously taking naftopidil and having a shorter duration of prior α-blocker treatment at baseline were associated with silodosin continuation. Although prior α-blocker readministration in the 13 patients did not show significant efficacy, six preferred to continue the previous α-blocker. CONCLUSIONS: Silodosin represents an effective second-line α-blocker monotherapy, even in those who still have moderate lower urinary tract symptoms.

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.

Mucosal gene therapy using a pseudotyped lentivirus vector encoding murine interleukin-10 (mIL-10) suppresses the development and relapse of experimental murine colitis.

BACKGROUND: Therapeutic gene transfer is currently being evaluated as a potential therapy for inflammatory bowel disease. This study investigates the safety and therapeutic benefit of a locally administered lentiviral vector encoding murine interleukin-10 in altering the onset and relapse of dextran sodium sulfate induced murine colitis. METHODS: Lentiviral vectors encoding the reporter genes firefly-luciferase and murine interleukin-10 were administered by intrarectal instillation, either once or twice following an ethanol enema to facilitate mucosal uptake, on Days 3 and 20 in Balb/c mice with acute and relapsing colitis induced with dextran sulfate sodium (DSS). DSS colitis was characterized using clinical disease activity, macroscopic, and microscopic scores. Bioluminescence optical imaging analysis was employed to examine mucosal lentiviral vector uptake and transgene expression. Levels of tumor necrosis factor-α and interleukin-6 in homogenates of rectal tissue were measured by ELISA. Biodistribution of the lentiviral vector to other organs was evaluated by real time quantitative PCR. RESULTS: Mucosal delivery of lentiviral vector resulted in significant transduction of colorectal mucosa, as shown by bioluminescence imaging analysis. Lentiviral vector-mediated local expression of interleukin-10 resulted in significantly increased levels of this cytokine, as well as reduced levels of tumor necrosis factor-α and interleukin-6, and significantly reduced the clinical disease activity, macroscopic, and microscopic scores of DSS colitis. Systemic biodistribution of locally instilled lentiviral vector to other organs was not detected. CONCLUSIONS: Topically-delivered lentiviral vectors encoding interleukin-10 safely penetrated local mucosal tissue and had therapeutic benefit in this DSS model of murine colitis.

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.

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.

[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.

Adenovirus-retrovirus hybrid vectors achieve highly enhanced tumor transduction and antitumor efficacy in vivo.

Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ, which not only accelerates subsequent vector spread and progressive tumor transduction, but can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug activator gene therapy.

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.

[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.

[OPEN SURGICAL HEMOSTASIS FOLLOWING TRANSARTERIAL EMBOLIZATION (TAE) FOR RENAL INJURY AFTER EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY (ESWL): A CASE REPORT].

We report a case of open surgical hemostasis following transarterial embolization (TAE) that failed to stabilize the hemodynamics for renal injury after extracorporeal shock wave lithotripsy (ESWL). A 48-year-old man presented with severe left renal colic pain 1 day after ESWL for a left renal stone. Computed tomography revealed arterial bleeding from the lower pole of the left kidney and retroperitoneal hematoma. TAE was successfully performed for the lower poler bleeding. However, we were unable to complete the procedure for bleeding from an aberrant artery to the lower pole of the kidney that was supplied directly from the aorta. Therefore, an emergency laparotomy was performed and the injury in the aberrant artery was manually ligated. Hemostasis was obtained after the direct surgical ligation and he had a good postoperative recovery. Open surgical hemostasis is a treatment modality that should be considered following TAE that fails to control arterial bleeding after ESWL.

Effective in vivo and ex vivo gene transfer to intestinal mucosa by VSV-G-pseudotyped lentiviral vectors.

BACKGROUND: Gene transfer to the gastrointestinal (GI) mucosa is a therapeutic strategy which could prove particularly advantageous for treatment of various hereditary and acquired intestinal disorders, including inflammatory bowel disease (IBD), GI infections, and cancer. METHODS: We evaluated vesicular stomatitis virus glycoprotein envelope (VSV-G)-pseudotyped lentiviral vectors (LV) for efficacy of gene transfer to both murine rectosigmoid colon in vivo and human colon explants ex vivo. LV encoding beta-galactosidase (LV-beta-Gal) or firefly-luciferase (LV-fLuc) reporter genes were administered by intrarectal instillation in mice, or applied topically for ex vivo transduction of human colorectal explant tissues from normal individuals. Macroscopic and histological evaluations were performed to assess any tissue damage or inflammation. Transduction efficiency and systemic biodistribution were evaluated by real-time quantitative PCR. LV-fLuc expression was evaluated by ex vivo bioluminescence imaging. LV-beta-Gal expression and identity of transduced cell types were examined by histochemical and immunofluorescence staining. RESULTS: Imaging studies showed positive fLuc signals in murine distal colon; beta-Gal-positive cells were found in both murine and human intestinal tissue. In the murine model, beta-Gal-positive epithelial and lamina propria cells were found to express cytokeratin, CD45, and CD4. LV-transduced beta-Gal-positive cells were also seen in human colorectal explants, consisting mainly of CD45, CD4, and CD11c-positive cells confined to the LP. CONCLUSIONS: We have demonstrated the feasibility of LV-mediated gene transfer into colonic mucosa. We also identified differential patterns of mucosal gene transfer dependent on whether murine or human tissue was used. Within the limitations of the study, the LV did not appear to induce mucosal damage and were not distributed beyond the distal colon.

[Primary testicular leiomyosarcoma].

Leiomyosarcoma is a malignant soft-tissue cancer arising from tissues containing smooth muscle. It commonly occurs in the gastrointestinal system and retroperitoneum, but is rare in the genito-urinary system. We experienced a case of primary testicular leiomyosarcoma. A 71-year-old man presented with painless swelling of the right scrotal contents for 4 months. A high orchiectomy was performed. Histological examination revealed primary testicular leiomyosarcoma. The patient did not receive any adjuvant therapy. Seven months after the operation, there has been no recurrence. Cases of primary intratesticular leiomyosarcoma are rare. To the best of our knowledge, only sixteen cases have been reported in the literature.

PTEN knockout prostate cancer as a model for experimental immunotherapy.

PURPOSE: Testing immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer. MATERIALS AND METHODS: PTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging. RESULTS: Vaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-gamma secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo. CONCLUSIONS: The PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.

Therapeutic efficacy of replication-competent retrovirus vector-mediated suicide gene therapy in a multifocal colorectal cancer metastasis model.

Replication-competent retrovirus (RCR) vectors are intrinsically incapable of infecting quiescent cells and have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. However, i.v. delivery of RCR vectors expressing therapeutic genes has never previously been tested, particularly in an immunocompetent tumor model. Therefore, in the present study, we sought to test the therapeutic effect of an RCR vector (ACE-CD) carrying the yeast cytosine deaminase (CD) gene, which converts the nontoxic prodrug 5-fluorocytosine (5FC) into the chemotoxin 5-fluorouracil, after delivery by infusion into the locoregional circulation in a multifocal hepatic metastasis model of colon cancer. After confirmation of suicide gene cytotoxicity in vitro, multifocal hepatic tumors were established in syngeneic mice with murine CT26 colorectal cancer cells expressing firefly luciferase (CT26-Luc), and the ACE-CD vector was infused via intrasplenic injection into the portal circulation. Fourteen days after locoregional infusion, systemic administration of 5FC resulted in significant inhibition of bioluminescent signals in mice whose tumors had been infected with RCR but not in control mice. Notably, there was no detectable RCR vector spread to normal liver or bone marrow by quantitative PCR analysis. Our results thus show that locoregional delivery of a suicide gene by RCR vectors infused into the portal circulation results in progressive transduction of multiple tumor foci in the liver, without evidence of spread to adjacent normal parenchyma or extrahepatic tissues, and can achieve significant tumor growth inhibition.

Long-term follow-up of penile glans necrosis due to paraphimosis.

INTRODUCTION: Paraphimosis is a urologic emergency in which the foreskin of the penis becomes trapped behind the coronal sulcus and forms a tight band of constricting tissue. Surgical or conservative release of this constriction is required for the treatment. Delayed treatment will cause devastating outcomes, such as penile glans necrosis. A few studies have reported penile glans necrosis/gangrene, but long-term follow-up of the recovery from glans necrosis due to paraphimosis has not been previously reported. CASE PRESENTATION: A 25-year-old man who experienced glans necrosis following paraphimosis was not treated promptly with circumcision. The patient underwent conservative treatment with debridement of necrotic tissue and cystostomy for urethral meatal necrosis. We were able to prevent partial penectomy. His penile glans was covered with healthy epithelium and retained its natural shape and voiding and erectile functions were normal 2 years after the treatment. CONCLUSION: We report successful conservative management of penile glans necrosis.

Reduction of HLA class I expression by ribonucleic acid interference mitigates allogenicity of human primary and Immortalized cells.

Unmatched human leukocyte antigens (HLA) expressed by allogeneic donor cells are the major target for immunological rejection. In order to reduce the immunogenicity of allograft cells, we have developed lentiviral vectors for delivery of short hairpin ribonucleic acid (shRNA) against Class I HLA. This approach was evaluated in both an established human embryonic kidney cell line and primary human CD34+ hematopoietic stem/progenitor cells. Target cells transduced with lentiviral vectors expressing either HLA-A*0201 allele-specific or HLA-A, -B, -C consensus sequence-specific shRNA showed effective knockdown of cell surface HLA expression. Mixed lymphocyte-target cell reactions showed significantly reduced interferon-gamma production from alloreactive cytotoxic T lymphocytes and significantly reduced levels of target cell apoptosis after shRNA-mediated knockdown of HLA expression and target cell survival correlated with vector transduction efficiency. Furthermore, increasing resistance to complement-dependent cytotoxicity mediated by anti-HLA antibodies was observed to correlate with increasing levels of shRNA vector transduction in primary human CD34+ cells. Notably, non-HLA restricted killing by lymphokine-activated killer cells was not incurred after HLA knockdown. These data demonstrate the potential for genetic engineering strategies targeting incompatible HLA alleles to reduce both cellular and humoral responses and enable graft survival after transplantation of allogeneic cells and tissues.