Efficacy of tadalafil on symptom-specific bother in men with lower urinary tract symptoms.

INTRODUCTION: This multicenter and prospective study was performed to evaluate the efficacy of tadalafil on patient-reported bother for each symptom in men with lower urinary tract symptoms (LUTS). METHODS: Men with LUTS received 5 mg of tadalafil daily for 4 weeks. We assessed change in symptom severity using both international prostate symptom score (IPSS), and overactive bladder symptom score (OABSS), as well as patient-reported quality of life (QOL: bother or satisfaction) for each symptoms using IPSS-visual analog scale (IPSS-VAS) and OABSS-VAS. RESULTS: We found significant improvements in total IPSS (P < 0.001), including voiding symptoms (P < 0.001), storage symptoms (P < 0.001), and QOL (P < 0.001). All VAS measures corresponding to symptoms in IPSS and OABSS also significantly improved (P < 0.001). The most bothersome symptoms for each patient at baseline evaluated by VAS measures significantly improved (P < 0.001). Patients whose most bothersome symptoms at baseline included IPSS-Q7 (nocturia) showed significantly smaller improvement of VAS measure after treatment than those without it (P = 0.024). CONCLUSIONS: Daily tadalafil significantly improved not only symptom severity of LUTS but also patient-reported QOL on each symptom.

Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA.

OBJECTIVES: To evaluate the impact of morphometric magnetic resonance imaging (MRI) analysis of the prostate zonal anatomy on aging, prostatic hypertrophy and lower urinary tract symptoms in patients from Japan and the USA. SUBJECTS AND METHODS: A retrospective analysis of 307 men, including 156 men from Japan and 151 from the USA, who consecutively underwent 3-Tesla MRI and International Prostate Symptom Score (IPSS) assessment because of elevated PSA levels. Using Synapse-Vincent (Fujifilm), the prostatic zones were segmented in each axial step-section of the T2-weighted MRI to reconstruct a three-dimensional model of the prostate, which was used to calculate: zonal volumes (whole-gland prostate, transition zone and peripheral zone volumes); the presumed circle area ratio (PCAR); and PZ thickness. Bivariate associations were quantified using Spearman's rank correlation coefficients. RESULTS: The USA subgroup had a greater prostate volume (49 vs 42 mL; P = 0.003) and TZ volume (26 vs 20 mL; P < 0.001) than the Japan subgroup, with no difference in PZ volume (19 vs 20 mL; P = 0.2). There was no age-related increase in PZ volume in either of the subgroups or in the entire cohort (P = 0.9, P = 0.2, P = 0.3, respectively). PZ thickness had a significant negative correlation with PCAR (P < 0.001) and TZ volume (P < 0.001). The greater the increase in the TZ volume with the increase in PCAR, which probably correlates with obstructive pressure, the thinner the PZ became. PCAR had a significant positive correlation with IPSS (P = 0.003) and obstructive symptoms (P = 0.007), while PZ thickness had a significant negative correlation (P = 0.018). CONCLUSIONS: No age-related increases and no differences between the Japanese and the US subgroups were found with regard to PZ volume. The more TZ volume increased, the higher the obstructive pressure and the thinner the PZ became; these changes were associated with increased obstructive symptoms. MRI analysis of prostate zonal anatomy enhanced our understanding of age-related changes in morphology and urinary symptoms.

CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53.

Renal cell carcinoma (RCC) is the most common type of kidney cancer. However, the mechanisms underlying the progression of the disease are not well understood. The data in this report suggest that canopy FGF signaling regulator 2 (CNPY2) is a promoter of RCC progression. We found that CNPY2 significantly promoted growth of RCC cells and upregulated TP53 gene expression. Although TP53 is widely known as a tumor suppressor, in RCC TP53 promoted tumor cell growth. A typical p53 target gene, CDKN1A, was upregulated by both p53 and CNPY2 in RCC cells, suggesting that CNPY2 increased the expression level of TP53. Consistent with these results, CNPY2 and TP53 expression levels were positively correlated in RCC patients. These findings suggested that CNPY2 promoted cancer cell growth in RCC through regulating TP53 gene expression.

Androgen suppresses testicular cancer cell growth in vitro and in vivo.

Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model. Tryptophan hydroxylase 1 (TPH1), the rate limit enzyme in serotonin synthesis, was one of the genes which expression was reduced in DHT-treated SE cells. TPH1 was highly expressed in SE cancer tissues compared with adjacent normal tissues. Activation of androgen/AR signaling in SE cells reduced the expression of TPH1 in SE cells, followed by the reduction of serotonin secretion in cell culture supernatant. These results suggested that silencing of androgen/AR signaling may cause initiation and progression of SE through increase in TPH1 gene expression level.

A novel technique using three-dimensionally documented biopsy mapping allows precise re-visiting of prostate cancer foci with serial surveillance of cell cycle progression gene panel.

BACKGROUND: Conventional systematic biopsy has the shortcoming of sampling error and reveals "no evidence of cancer" with a rate of >50% on active surveillance (AS). The objective of this study is to report our initial experience of applying a 3D-documented biopsy-mapping technology to precisely re-visit geographically documented low-risk prostate cancer and to perform serial analysis of cell-cycle-progression (CCP) gene-panel. METHODS: Over a period of 40 months (1/2010-4/2013), the 3D-biopsy-mapping technique, in which the spatial location of biopsy-trajectory was digitally recorded (Koelis), was carried out. A pair of diagnostic (1st-look) and surveillance (2nd-look) biopsy were performed per subject (n = 25), with median interval of 12 months. The documented biopsy-trajectory was used as a target to guide the re-visiting biopsy from the documented cancer focus, as well as the targeted field-biopsy from the un-sampled prostatic field adjacent to negative diagnostic biopsies. The accuracy of re-visiting biopsy and biopsy-derived CCP signatures were evaluated in the pair of the serial biopsy-cores. RESULTS: The 1st-look-biopsy revealed a total of 43 cancer lesions (1.7 per patient). The accuracy of re-visiting cancer was 86% (37/43) per lesion, 76% (65/86) per core, and 80% (20/25) per patient. This technology also provided an opportunity for 3D-targeted field-biopsy in order to potentially minimize sampling errors. The CCP gene-panel of the 1st-look (-0.59) versus 2nd-look (-0.37) samples had no significant difference (P = 0.4); which suggested consistency in the molecular signature of the known cancer foci during the short-time interval of median 12 months. Any change in CCP of the same cancer foci would be likely due to change in sampling location from the less to more significant portion in the cancer foci rather than true molecular progression. The study limitations include a small number of the patients. CONCLUSION: The 3D-documented biopsy-mapping technology achieved an encouraging re-sampling accuracy of 86% from the known prostate cancer foci, allowing the serial analysis of biopsy-derived CCP signatures.

Evaluation of autonomic malfunction in idiopathic normal pressure hydrocephalus.

OBJECTIVE: The autonomic nervous system plays an important role in urinary disturbance which is one of the main symptoms of idiopathic normal pressure hydrocephalus (iNPH); thus, the focus of the present study was to identify the autonomic function parameters that would be useful as clinical indicators of iNPH. METHODS: The subjects consisted of 18 iNPH patients (group N) and 31 normal controls (group C). Before and after a lumbar puncture test, they were examined for CVR-R and total heart rate. A power spectral analysis of R-R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Urinary incontinence was evaluated using the overactive bladder symptom score (OABSS) questionnaire and bladder capacity. Correlations between the above indicators and clinical indicators of iNPH, such as the mini-mental state examination and the Evans index, were examined. RESULTS: The HF values (ms(2)) were 190.3 in group C and 237.2 in group N; the difference was statistically significant. In group N, the HF value after the lumbar puncture test was lower (160.3) than the value before the lumbar puncture test, confirming that the increased parasympathetic state returned to a near normal level after CSF drainage. A significant positive correlation was noted only between the pre-lumbar puncture HF value and the OABSS. CONCLUSION: iNPH is associated with increased parasympathetic activity, and the lumbar puncture test and shunt surgery may correct this autonomic imbalance to near normal levels.

A comparison of cooling methods for laparoscopic partial nephrectomy.

OBJECTIVES: To evaluate appropriate cooling methods in laparoscopic partial nephrectomy. METHODS: Under general anesthesia, 21 porcine kidneys were exposed retroperitoneoscopically. Ice slush (500 g) was put into the retroperitoneal cavity after renal vascular clamping. Renal parenchymal temperature was measured by a thermometer. Seven kidneys were cooled only by ice slush (group I). In seven kidneys, 200 mL of 4 degrees C saline was infused around the kidney 45 minutes after vascular clamping (group II). In seven kidneys, 4 degrees C saline was irrigated continuously through a 5F ureteral catheter, which was inserted into the ureter (group III). RESULTS: In group I, 21 minutes after vascular clamping, the lowest temperature achieved was 13.2 degrees C, and at 47 minutes the temperature exceeded 20 degrees C. In group II, the lowest temperature achieved was 13.0 degrees C 23 minutes after vascular clamping, and at 59 minutes the temperature exceeded 20 degrees C. In group III, the lowest temperature of 10.6 degrees C was achieved at 27 minutes, and at 79 minutes the temperature exceeded 20 degrees C. CONCLUSIONS: In complicated cases of laparoscopic partial nephrectomy, cooling with both ice slush and ureteral catheter irrigation was thought to be effective. When the renal collecting system is opened, an additional infusion of cooled water may also be effective.

Localization of increased insulin-like growth factor binding protein-3 in diabetic rat penis: implications for erectile dysfunction.

OBJECTIVES: Diabetes-induced erectile dysfunction (ED) is assumed to result from neurovascular abnormalities. However, the entire picture of the molecular mechanisms underlying ED has not yet been clarified. To elucidate the possible elements involved in ED in diabetes mellitus, we performed broad-scale gene expression profiling using cDNA array in the penis of streptozotocin-induced diabetic rats. METHODS: Northern blot analysis was performed to examine the course of the mRNA expression encoded by the identified gene. Immunohistochemistry was performed to identify the cellular localization of the encoded protein. RESULTS: Of the genes investigated, the expression level of insulin-like growth factor binding protein 3 (IGFBP-3) was greatly increased at 12 weeks after streptozotocin treatment. The levels of ErbB3 epidermal growth factor receptor-related proto-oncogene, G1/S-specific cyclin D2, hepatic neutral cholesteryl ester hydrolase precursor, UDP-galactose ceramide galactosyltransferase, and serine protease RNK-Met-1 were markedly decreased. Increased levels of IGFBP-3 mRNA were demonstrated as early as 2 weeks after induction of hyperglycemia. Increased IGFBP-3 protein was localized to the epithelium of the urethra, penile endothelium, and smooth muscle in the corpus cavernosum. Significant depletion of the smooth muscle density relative to the connective tissue was first observed in the penis of the 8-week diabetic rats, and a significant reduction in the intracavernous pressure was demonstrated only at 12 weeks after the induction of hyperglycemia. CONCLUSIONS: These results suggest that the increased expression of IGFBP-3 during hyperglycemia might play an important role in the development of ED.

Gene therapy with TRAIL against renal cell carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells. However, TRAIL is not toxic against most normal cells. We have accordingly examined by in vivo electroporation whether TRAIL induces apoptosis in renal cell carcinoma. In addition, combination treatment with TRAIL and 5-fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65 renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into the NC65 tumors in the right flanks of severe combined immunodeficient mice. Tumors were pulsed with the CUY21 electroporator. Electroporation was done once on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal deoxyribonucleotide transferase-mediated nick-end labeling assay. When TRAIL gene therapy using in vivo i.t. electroporation was done once only, the growth of NC65 tumors was not inhibited. However, when TRAIL gene therapy was done thrice, growth suppression of the NC65 tumors was observed. Transfection of the TRAIL gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells were treated with TRAIL gene therapy in combination with 5-FU, stronger growth suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in severe combined immunodeficient mice. This study shows that TRAIL gene therapy induced growth suppression and apoptosis in NC65 tumors without severe side effects, and that combination treatment of NC65 cells with TRAIL gene therapy and 5-FU resulted in higher antitumor activity. These findings suggest that TRAIL gene therapy and/or 5-FU may be effective against renal cell carcinoma without harmful toxic effects.

Significant relationship of time-dependent uroflowmetric parameters to lower urinary tract symptoms as measured by the International Prostate Symptom Score.

AIMS: The aim of the present paper is to elucidate the possible involvement of time-dependent parameters as obtained by uroflowmetry in the manifestation of lower urinary tract symptoms (LUTS) in elderly patients. METHODS: Using simple and multiple regression analyses, the correlation of the International Prostate Symptom Score (IPSS) with objective parameters including age, postvoid residual, uroflowmetry and transrectal ultrasonic measurements of the prostate was analyzed in 206 male patients (average age of 68.0 +/- 7.4 years) who visited our outpatient clinic complaining of LUTS. RESULTS: In the 206 patients, the mean maximum flow rate was 12.2 mL/s (13.7 mL/s in mild, 11.9 mL/s in moderate, and 11.2 mL/s in severe IPSS total score) and average flow rate was 4.4 mL/s (5.4 mL/s in mild, 4.3 mL/s in moderate, and 3.5 mL/s in severe IPSS total score). Simple regression analyses demonstrated that age, voiding time, and average and maximum flow rates correlate significantly with symptom scores. In particular, relatively strong relationships were found between average flow rate and scores of intermittency, weak stream and total and voiding symptoms scores. Serum prostate specific antigen level, postvoid residual and prostatic ultrasonic measurements did not show a significant correlation with symptom scores. Multiple regression analyses revealed age and average flow rate to be independent determinants for symptom scores. These results suggest that the time-dependent function in micturition interferes in the manifestation of LUTS in elderly men who have borderline or pathologic maximum flow rate. When evaluating uro flowmetry in elderly male patients with LUTS, attention should be paid to time-dependent parameters such as voiding time and average flow rate.

Visual analog scale questionnaire to assess quality of life specific to each symptom of the International Prostate Symptom Score.

PURPOSE: We assessed patient quality of life specific to each of the 7 items on the International Prostate Symptom Score, as evaluated with a novel visual analog scale questionnaire. MATERIALS AND METHODS: A total of 246 male patients with a chief complaint of lower urinary tract symptom were asked to complete the International Prostate Symptom Score and visual analog scale questionnaires to assess bother or satisfaction regarding patient quality of life specific to each of the 7 items on the International Prostate Symptom Score. RESULTS: An item with the maximum visual analog scale measure matched the chief complaint in 169 patients (69%). In contrast, the chief complaint failed to match to an item with the most severe International Prostate Symptom Score in 104 patients (42%) (p = 0.012). Multiple regression analysis to define the best predictor of International Prostate Symptom Score quality of life score of the 14 items, including International Prostate Symptom Score and visual analog scale, revealed that the best predictor was the visual analog scale measure for nocturia (p = 0.0003), followed by visual analog scale measures for frequency (p = 0.0004) and incomplete emptying (p = 0.01). After alpha-blocker treatment improvement in the visual analog scale measure for the chief complaint correlated better with improvement in the International Prostate Symptom Score quality of life score than the change in International Prostate Symptom Score. The overall test-retest correlation for the visual analog scale questionnaire in 55 healthy elderly men and 44 patients with lower urinary tract symptoms was 0.772 and 0.742, respectively (p <0.00001). CONCLUSIONS: The novel visual analog scale measure of quality of life specific to each of the 7 items on the International Prostate Symptom Score has a significant impact on identifying the patient chief complaint as well as on patient specific quality of life. Our study supports the concomitant use of the International Prostate Symptom Score and visual analog scale questionnaires.

Four-dimensional ultrasonography for dynamic bladder shape visualization and analysis during voiding.

OBJECTIVE: The purpose of this study was to describe initial applications of 4-dimensional ultrasonography (4DUS) for visualizing dynamic change in 3-dimensional (3D) bladder shape as well as for analyzing intravesical volume and diameters during voiding. METHODS: In 15 healthy volunteers and 5 patients with lower urinary tract symptoms, 4DUS images of the bladder during voiding were obtained by transabdominal 4DUS and compared with the outcome of uroflowmetry. Changes of intravesical volume as well as diameters in axial, coronal, and sagittal planes were measured and analyzed in comparison with uroflow data. RESULTS: Dynamic 3D visualization of the bladder shape was feasible in all 20 men. Multiplanar display of 4DUS showed dynamic 3D images of the bladder during voiding to be simultaneously visualized in the axial, coronal, and sagittal planes. The change and decrease rate in intravesical volume calculated by 4DUS data had significant correlation with the average flow rate (P = .02) and the maximum flow rate (P = .04), respectively. Among the 3 diameters, the change of coronal diameter was significantly most correlated with change of the intravesical volume (P < .0001). The change in coronal diameter, which was observed in patients with urinary disturbance, had a significant difference compared with those observed in control subjects (P = .01). CONCLUSIONS: Monitoring of voiding with 4DUS was feasible in healthy men and patients with lower urinary tract symptoms. Four-dimensional ultrasonography has the potential to be a novel noninvasive urodynamic modality to visualize dynamically the lower urinary tract during voiding and to improve pathophysiologic understanding of voiding.

Possible contribution of prostatic anterior fibromuscular stroma to age-related urinary disturbance in reference to pressure-flow study.

Recently, we reported that the anterior fibromuscular stroma (AFMS) of the prostate has significant different innervation compared with the other glandular regions of the prostate. In healthy volunteers (n = 12) using transrectal ultrasound (US), or TRUS, monitoring during voiding, we observed dynamic change (p < 0.0001) of the thickness of the AFMS during voiding. The aim of this study was to reveal the possible functional contribution of the AFMS to micturition, as well as the age-related voiding dysfunction. In the patients (n = 56) with voiding dysfunction who underwent both pressure-flow study (PFS) for determining obstruction and TRUS monitoring during voiding, we measured the ultrasonic dynamic change of the lower urinary tract during voiding. In old men with voiding dysfunction, ultrasonic measurements of dynamic change in the AFMS (p < 0.01) as well as the opening urethra (p < 0.05) could contribute to diagnosing of the anatomical localization of obstructive lesions. The poor movement of AFMS could account for the age-related urinary disturbance in the patients without benign prostatic enlargement and without bladder neck obstruction.

Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis.

In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.

Neuroselective current perception threshold evaluation of bladder mucosal sensory function.

OBJECTIVE: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders. METHODS: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three different CPTs were obtained from each test site using a constant alternating current sinusoid waveform electrical stimulus presented at 2000Hz, 250Hz and 5Hz stimulation frequencies, which could selectively reflect the functions of the large myelinated fibers (A-beta-fiber), the small myelinated fibers (A-delta-fiber), and the unmyelinated fibers (C-fiber), respectively. RESULTS: As the determination of CPT values on the finger skin, the CPT values in the bladder could be determined using the neuroselective measures in all patients but three who had no sensory response (absence of sensation) caused by complete spinal injury. In the 8 patients with detrusor hyperreflexia due to incomplete spinal cord injury (supra-sacral lesion), the bladder CPT value (4.0+/-1.9) at 5Hz was significantly lower (p<0.01) than that in the controls (26.2+/-17.7). In the neurogenic bladders determined to be underactive (n=11, including post pelvic surgery, post infra-sacral level spinal cord injury and diabetes patients), the higher CPT values of bladder mucosal sensory functions were found at 5Hz (p<0.05), 250Hz (p=0.07), and 2000Hz (p<0.05) compared to the controls. CONCLUSIONS: Quantitative neuroselective measurement of CPT values in the human bladder mucosal function was feasible. Hypersensitivity or hyposensitivity of the urinary sensory function could be determined using the CPT values in comparison to control. The quantitative neuroselective estimation of the bladder sensory functions in different types of sensory peripheral nerve fibers may contribute to the appropriate selection of therapeutic strategy in patients with urinary sensory dysfunction.

Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk.

OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia. METHODS: Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20-53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3-6 months and an evaluation of metastasis was performed every 6 months. RESULTS: At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma. CONCLUSION: Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.

Human testis specific protein: a new member of aldo-keto reductase superfamily.

Human testis specific protein, HTSP, was identified initially by the search of the Expressed Sequence Tag database, followed by the screening of human testis cDNA library. Among various organs examined, the HTSP transcripts were detected only in the testis, not in other reproductive organs such as vas deferens and prostate. No cross-hybridizing signal was detected in the testis of mouse or rat, indicating that this gene is specifically expressed in the human testis. We isolated four isoforms, HTSP1, 2, 3 and 4. Screening of the high throughput genomic sequence database indicated the localization of the HTSP gene in chromosome 10. Thus, HTSP isoforms were generated by alternative splicing of a single gene. HTSP4, the longest gene product, was composed of 307 amino acids and shared 56% identity to mouse vas deferens protein as well as human aldose reductase in amino acid levels. Bacterially expressed recombinant HTSP protein showed small but significant activity towards 9,10-phenanthrenequinone among the putative substrates so far tested. Accordingly, HTSP is a new member of the aldo-keto reductase superfamily with as yet unidentified function.