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Biomedical subjects

Tsuguru Usui

Publications and source records attributed to Tsuguru Usui.

At least 19 recordsLinked to original sources
PubMed2007

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer.

The retinoblastoma protein-interacting zinc finger gene, RIZ1, is thought to be a tumor suppressor gene. RIZ1 is inactivated by mutation, deletion and DNA methylation in several human cancers. In the present study, the relationship between DNA methylation of RIZ1 and mutation of p53 was investigated in prostate cancer (PCa). In total, 47 cases of node-negative PCa (stages I-III) were analyzed. DNA methylation of the RIZ1 gene was detected in 20 (42.6%) of the 47 PCa tissues by methylation-specific polymerase chain reaction. DNA methylation of the RIZ1 gene was not associated with clinicopathological features. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score (16/30, 53.3%) than in those with a low Gleason score (4/17, 23.5%); however, this tendency was not statistically significant (P = 0.0675). Nuclear accumulation of p53 was observed in four (8.5%) of 47 PCa specimens by immunostaining. All four PCa specimens with nuclear accumulation of p53 were stage III disease and showed DNA methylation of RIZ1. However, of the remaining 43 cancers without nuclear accumulation of p53, DNA methylation of RIZ1 was observed in only 16 (37.2%) specimens (P = 0.0272). Of the three PCa cell lines, only the PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis. Genetic alterations are likely associated with epigenetic alterations in PCa.

Aged↗
PubMed2006

Women's perception of male erectile dysfunction drugs in the general population.

OBJECTIVE: The aim of this study is to investigate trends in women's perception of male erectile dysfunction (ED) drugs in the general population. METHODS: We designed an online questionnaire survey and randomly invited an initial total of 2370 women to respond to it from a database population that included 450,000 men and women recruited through an Internet-based market research company. The 17 items of the questionnaire comprised 9 items related to socio-cultural background and 8 items related to the perception of ED drugs, ED itself, and sexual relations. RESULTS: A total of 1262 women (53.2% of those initially invited), ranging in age from 20 to 77 years, participated. Among the participants, 83.3% were aware of the existence of ED drugs, but only 12.0% showed some interest in them, 46.4% and 43.2% of the participants claimed to have an unfavorable image of ED drugs, and of men using ED drugs, respectively. Among the participants, 45.2% stated that if their partners suffered from ED at present or in the future, they would not desire their partners to use ED drugs, and 25.5% stated that they would not accept it. Multiple logistic regression analysis revealed that higher age had a negative impact on knowledge, interest and image of ED drugs, the image of men using ED drugs, and the importance of sexual relations. CONCLUSIONS: Our findings reveal that a high proportion of women have a negative perception of ED drugs and associated issues in Japan.

Adult↗
PubMed2006

Transurethral ethanol injection for prostatic obstruction: an excellent treatment strategy for persistent urinary retention.

OBJECTIVES: To evaluate the efficacy of transurethral ethanol injection into the prostate (TUEIP) for patients with persistent urinary retention resulting from benign prostatic hyperplasia or advanced prostate cancer. METHODS: Twenty-one Japanese men (elderly or at high risk anesthesiologically) who had developed persistent urinary retention because of benign prostatic hyperplasia or advanced prostate cancer were treated with TUEIP from January 2001 to January 2005. Patient age and preoperative prostate volume was 64 to 92 years (median 84) and 24.1 to 125 cm3 (mean 57.6), respectively. Under sacral or lumbar anesthesia, 6 to 14 mL (mean 10.6) of dehydrated ethanol (mean ratio for prostate volume 22.7%) was injected into the prostate under endoscopic guidance, followed by placement of an indwelling catheter. RESULTS: Of the 16 patients with benign prostatic hyperplasia and 5 with advanced prostate cancer, 14 (87.5%) and 3 (60%), respectively, were able to void spontaneously after catheter removal. The catheter had been left in place for 7 to 37 days (mean 12.4) after surgery. No additional treatment was required during the 2 to 24 months (mean 16) of follow-up. The postoperative residual urine volume of these 17 patients was 20 to 150 mL (mean 60) and their mean prostate volume had decreased from 52.7 to 37.9 cm3 (28.1% reduction) at 6 months postoperatively (P <0.001). No major complication was experienced. CONCLUSIONS: In patients with persistent urinary retention due to prostatic obstruction without severe complications, TUEIP removes the need for catheterization and allows spontaneous voiding. TUEIP may be an alternative to transurethral resection of the prostate for high-risk or elderly patients who cannot tolerate surgery.

Aged↗
PubMed2006

Nocturnal enuresis and overactive bladder in children: an epidemiological study.

AIMS: To investigate the prevalence and characteristics of nocturnal enuresis (NE) and to examine the prevalence of overactive bladder (OAB) symptoms in primary schoolchildren. METHODS: After conducting an anonymous questionnaire survey about voiding habits and bowel habits in primary schoolchildren, a total of 6917 schoolchildren belonging to 11 primary schools were randomly enrolled in the survey. According to the International Continence Society, we defined NE as any involuntary loss of urine during sleep, occurring more frequently than once per month. Children with NE were subdivided into two groups, monosymptomatic NE (MNE) and enuretic syndrome (ES). To evaluate the characteristic differences of MNE and ES, we assessed the relationships between NE and voiding habits, and episodes of cystitis and constipation. Overactive bladder was defined as increased daytime frequency and/or urge urinary incontinence, and its prevalence was investigated. RESULTS: The response rate to the questionnaire was 76.4%. The prevalence of NE was 5.9% and was inversely related to increasing age. Monosymptomatic NE comprised 59.4% of NE cases. The annual spontaneous resolution rate of MNE was higher than that of ES. Increased daytime frequency, a history of cystitis and infrequent bowel habits were not related to MNE, but were significantly related to ES. The prevalence of OAB was 17.8%. Children with a history of cystitis had a significantly higher rate of OAB than children without it. CONCLUSIONS: Overall, NE and OAB were detected in 5.9% and 17.8% of primary schoolchildren, respectively. The link between NE and OAB symptoms, urinary tract infections and constipation deserves more attention.

Child↗
PubMed2006

Lower urinary tract symptoms and risk of prostate cancer in Japanese men.

Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer. A total of 3511 men aged 50-79 years who underwent mass screening for prostate cancer between 2002 and 2004 for the first time, and completed the International Prostate Symptom Score (IPSS) questionnaire at the time of the prostate specific antigen (PSA) test, were enrolled in the present study. All men with PSA values greater than 4.0 ng/mL were advised and encouraged to undergo transrectal systematic sextant biopsy. The number of cancers subsequently detected was compared between men with IPSS scores of 0-7 and 8-35. Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL, 178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer. Although the PSA positivity rate for men with IPSS scores of 8-35 was significantly higher than that in the 0-7 group, there were no significant intergroup differences in the cancer detection rates for biopsied men and for total screened subjects. Multivariate logistic regression analysis revealed that prostate volume was the dominant predictor for the detection of prostate cancer, followed by PSA level, but the IPSS made no significant contribution. No significant difference was noted in the IPSS scores between men with cancer and the others of the same age group. Symptomatic Japanese men are not at higher risk of prostate cancer despite their higher PSA values compared with asymptomatic men of the same age group.

Aged↗
PubMed2006

The prevalence of overactive bladder and nocturnal enuresis in Japanese early adolescents: a questionnaire survey.

To assess the prevalence of overactive bladder (OAB) and nocturnal enuresis (NE) in early adolescents, we distributed an anonymous questionnaire about urinary symptoms to 624 middle school students aged 13 and 15 years. The questionnaire included items regarding age, gender, past and present diseases, urinary symptoms and bowel habits. OAB was defined as symptoms of increased daytime frequency occurring more than eight times during the daytime and/or urge incontinence occurring at least once a month. The overall response rate to the questionnaire was 32.4%, and the mean age +/- SD of all respondents was 13.9 +/- 0.89 years. The prevalence of OAB was 15.3% of all respondents (95% CI, 10.4-20.3%; 4.2-16.1% of boys and 12.5-28.3% of girls). The prevalence of OAB decreased with age from 17.6% of respondents aged 13-year-olds to 11.8% of 15-year-olds. The mean daytime frequency was 5.0 +/- 2.2 times. Increased daytime frequency was found in 10.4% (95% CI, 6.2-14.6%; 2.7-13.5% of boys and 6.1-19.0% of girls) and nocturia in 4.0% (95% CI, 1.3-6.7%). The prevalence of NE was 3.0% (95% CI, 0.65-5.4%; three boys and three girls). The results of this study demonstrate that some early adolescents had OAB or NE. Further large-scale studies would be required to investigate the prevalence and natural history of OAB and NE.

Adolescent↗
PubMed2006

Transrectal ultrasound-guided 10-core biopsy of the prostate for Japanese patients.

To determine the utility of transrectal ultrasound (TRUS)-guided 10-core prostate biopsy (sextant plus 4 far lateral cores) for Japanese patients, we compared it with the standard sextant for detection of prostate cancer. The study patients were 564 consecutive Japanese men (median age 71 years) who underwent 10-core biopsy because of PSA values of > or = 2.0 ng/ml at Hiroshima University Hospital between March 2000 and December 2004. The overall cancer detection rate for the 10-core biopsy was 42.6% (240/564), which was significantly higher than the 36.3% (205/564) for the standard sextant biopsy (P=0.0330), with a 14.6% (35/240) improvement. The 10-core biopsy also detected a significant number of additional cancers in the sub-groups of patients with PSA values of 2 to approximately 10 ng/ml (P=0.0275), a prostate volume of > 20 cc (P=0.0440), or normal findings of digital rectal examination (P=0.0304). The 10-core biopsy scheme detected 9.6% and 2.1 to approximately 8.3% more cancers than the lateral sextant (apex, lateral mid portion, and lateral base) and the probable different combinations of 8-core biopsy designs, respectively. Compared to the standard sextant biopsy, the 10-core biopsy did not detect an increased proportion of clinically insignificant cancers. There was no severe morbidity, and only 2 patients (0.4%) were briefly hospitalized due to high fever. These results show that the TRUS-guided 10-core biopsy yields a better prostate cancer detection rate than the 6-core or 8-core protocol without severe complications. Therefore, it seems to be practicable for Japanese patients.

Adult↗
PubMed2005

Urological retroperitoneoscopic surgery for patients with prior intra-abdominal surgery.

OBJECTIVE: To determine whether previous intra-abdominal surgery is associated with surgical outcome in patients undergoing urological retroperitoneoscopic surgery. PATIENTS AND METHODS: One hundred seventeen cases of urological retroperitoneoscopic surgery, including 78 cases of retroperitoneoscopic radical nephrectomy (RN) for localized renal tumor and 39 cases of retroperitoneoscope-assisted radical nephroureterectomy (RNU) for upper urinary tract cancer, were evaluated. Thirty (38.5%) of the 78 patients who underwent RN and 13 (33.3%) of the 39 patients who underwent RNU had a history of intra-abdominal surgery. The patients were divided into two groups: those who had undergone prior intra-abdominal surgery (OP+) and those who had not (OP-). Patients' backgrounds, degree of surgical invasiveness, and period of convalescence were compared between the OP+ and OP- groups. RESULTS: There was no significant difference between the OP+ and OP- groups in terms of background, surgical invasiveness or convalescence, except for age in the patients who had undergone RN. Complications in the studied cases were unrelated to any history of intra-abdominal surgery. CONCLUSION: Previous intra-abdominal surgery is not associated with a negative outcome of urological retroperitoneoscopic surgery in patients with localized renal tumors and those with upper urinary tract cancer.

Abdomen↗
PubMed2005

Cloning and characterization of the 5'-flanking region of the rat estrogen receptor beta gene.

In the rat, estrogen receptor (ER) beta is preferentially expressed in the ovary and the prostate gland where it is transcriptionally regulated by testosterone. A single 5'-end of rERbeta cDNA was identified in these tissues by the 5'-RACE analysis in the present study. The transcription starting site was predicted at -335 from the translation starting signal (ATG), and a 640bp section of the 5'-flanking region of the gene was cloned. Luciferase reporter assays revealed this region to be responsible for cell-specific promoter activity and successive deletion analyses indicated that only 98bp were sufficient for basic promoter activity as well as for testosterone-dependent transcription. The sequence of the determined region found to demonstrate high homology with the mouse ERbeta promoter with more than 80% identity between positions -1 and -550. The rat region of -30/-110 also showed good homology with 69% identity to corresponding section of the human promoter. Putative cis-acting elements, USF/Arnt and AML1a, were found in common in the promoter regions of three species. The present study thus demonstrated the 5'-flanking region of the rERbeta gene to be a functional promoter.

5' Untranslated Regions↗
PubMed2005

Laparoscopic nephron-sparing surgery: preoperative assessment with three-dimensional computed tomography.

OBJECTIVE: For retroperitoneal laparoscopic nephron-sparing surgery using a microwave tissue coagulator, it is helpful to know the relationship between the tumour, collecting system and vessels to prevent urinary leakage and vascular damage. We assessed the efficacy of multiplanar reformation and three-dimensional (3D) CT with the renal collecting system filled with contrast medium. METHODS: Fifteen patients with small renal tumours of less than 3 cm in diameter underwent dynamic CT examination ten minutes after injection of contrast medium of 30 ml. Multiplanar reformation, volume-rendered and maximum intensity projection images were created for determining operative approaches and for planning the operation. RESULTS: In all cases, the distance between the tumour and collecting system was measured on the multiplanar reformation. Accordingly, five cases were indicated for retroperitoneal laparoscopic nephron-sparing surgery using a microwave tissue coagulator. The remaining ten cases, due to the short distance (less than 10mm), were not considered good candidates for this procedure. The relationship between the tumour, collecting system and vessels was well shown on the volume-rendered and maximum intensity projection images. CONCLUSIONS: Multiplanar reformation and 3D-CT are able to give us an understanding of the surrounding structures. They are helpful in defining the indications for retroperitoneal laparoscopic nephron-sparing surgery using a microwave tissue coagulator and preoperative planning of nephron-sparing surgery.

Aged↗
PubMed2005

Proteome analysis of gelatin-bound urinary proteins from patients with bladder cancers.

OBJECTIVES: Proteome analysis with protein separation by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and mass spectrometric measurement is utilized for comprehensive identification of proteins in various biological samples. However, this technique has not been widely applied for the analysis of body fluid for clinical assessments, because large amounts of proteins in fluid such as albumin and globulin hinder the detection of small amounts of proteins with high clinical values. The aim of the present study is to develop a method of proteomic analysis for urine of patients with bladder cancers. MATERIALS AND METHODS: Urine samples collected from 40 patients with bladder cancers, 32 healthy volunteers, and 7 old volunteers with benign prostate hypertrophy were treated with gelatin-beads as a group-specific affinity carrier. The gelatin-bound proteins were subjected to the proteome analysis. RESULTS: Various amounts of matrix metalloproteinase-2 (MMP-2), -9 (MMP-9), fibronectin (FN), and their fragments were identified on 2-D PAGE gels from cancer-bearing patients, but not from normal individuals. Importantly, not only total amounts of these proteins, but also patterns of their distributions on the gels were well matched with the extent of invasion diagnosed with histopathological examinations. Thus, the score including such qualitative patterning of these proteins predicts pathological stages of the cancer. CONCLUSION: The proteomic analysis with gelatin-affinity purification of urine samples is useful not only for the diagnosis of bladder cancers, but also for estimating the extent of tumor invasion.

Biomarkers, Tumor↗
PubMed2005

Local anesthesia during 10 core biopsy of the prostate: comparison of 2 methods.

PURPOSE: We investigated the effectiveness of a new method, intraprostatic administration of local anesthesia vs traditional periprostatic injection for decreasing the discomfort caused by transrectal ultrasound guided, 10 core biopsy of the prostate. MATERIALS AND METHODS: We studied 71 patients who received intraprostatic anesthesia between October 2002 and March 2003, and 99 who received periprostatic anesthesia between October 2001 and September 2002 before prostate biopsy. After biopsy patients were given a questionnaire, which consisted of 5 questions about pain and 3 about morbidity, and were asked to complete it and mail it to our department. RESULTS: The mean score +/- SD for the degree of pain during biopsy in the periprostatic groups was 2.6 +/- 1.1 and that in the intraprostatic group was 1.9 +/- 1.1, which was significantly different (p <0.001). Other items, including the degree of pain after biopsy, duration and location of pain, and medicine intake for pain, were not significantly different between the 2 groups. There was no significant difference in morbidity, including hematuria, hemospermia and rectal bleeding, between the 2 groups. CONCLUSIONS: Intraprostatic administration of local anesthesia significantly decreases the pain associated with prostate biopsy compared with periprostatic nerve block. It is a simple, safe and rapid technique that should be considered in all patients undergoing transrectal ultrasound guided prostate biopsy.

Aged↗
PubMed2005

Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient.

AIMS: To report a pharmacokinetic interaction between valproic acid (VPA) and anticancer agents observed in an epileptic patient. METHODS: A 34-year old male epileptic patient receiving VPA underwent cisplatin-based chemotherapy for the treatment of a testicular tumour. The first chemotherapeutic cycle decreased the serum VPA concentration and caused severe generalized tonic-clonic seizures. Thus, thereafter, the serum VPA concentration was monitored along with the chemotherapy. RESULTS: In a patient receiving VPA daily, severe seizures were observed 7 weeks after the first chemotherapeutic cycle, at which the serum VPA concentration was found to be reduced by approximately 50% of the initial level (90-100 microg ml(-1)). The following cycles (six cycles over a 7-month period) also caused seizures in association with decreased serum VPA concentrations. In contrast, the serum concentration of phenytoin, which was given daily after the second chemotherapeutic cycle, remained at a therapeutic concentration (10-20 microg ml(-1)). After the completion of chemotherapy, the serum concentration of a tumour marker, hCGbeta, decreased to 1.2 ng ml(-1) from more than 120 ng ml(-1) prior to the chemotherapy in this patient. CONCLUSIONS: Careful monitoring of VPA concentrations are necessary during cisplatin-based chemotherapy because anticancer agents can reduce the serum concentration and antiepileptic activity of VPA.

Adult↗
PubMed2005

Impact of radical perineal prostatectomy on urinary continence and quality of life: a longitudinal study of Japanese patients.

AIM: We used self-completed questionnaires to obtain a longitudinal assessment of urinary continence and urinary, bowel, and sexual domain-related quality of life (QOL) in Japanese patients undergoing radical perineal prostatectomy (RPP). METHODS: A total of 41 Japanese patients with a median age of 69 years who underwent RPP between February 2002 and February 2004 were included in the study. We measured QOL by the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and assessed urinary continence on the basis of three different definitions of continence. The International Prostate Symptom Score (I-PSS) was also included to evaluate lower urinary tract symptoms (LUTS). RESULTS: When urinary continence was de fi ned as none, one, or two protective pads per day, 100%, 73%, 94%, 97%, or 100% of the patients were continent before, and 1, 3, 6, and 12 months after, RPP, respectively. When it was de fi ned as total control or occasional dribbling, the corresponding values were 97%, 70%, 84%, 94%, and 97%. Urinary function returned to the preoperative baseline level by 6 months postoperatively and scores for urinary bother had significantly surpassed the baseline by 12 months (P = 0.043). The I-PSS was significantly improved (P = 0.014), with a mean 4.7-unit decrease. Sexual function worsened significantly after surgery, and its recovery was less favorable. No significant change was observed in scores for bowel function or bowel bother. CONCLUSIONS: The majority of patients who undergo RPP rapidly regain urinary continence and QOL within 3-6 months. RPP has a favorable impact on LUTS.

Age Factors↗
PubMed2005

[Measurement of salivary testosterone by a simple enzyme immunoassay procedure].

PURPOSE: The level of serum free testosterone (Se free T) is thought to affect personal emotion and behavior. On the other hand, salivary testosterone (Sa-T) exists mainly in an unbound state and its measurement is noninvasive and repeatable. The aim of this study was to evaluate whether Sa-T can be measured in a clinical setting using a simple enzyme immunoassay kit, and to evaluate whether the level of Sa-T obtained by a simple procedure can be used as a substitute for the level of Se free T by comparing the values obtained with those of Se free T. PATIENTS AND METHODS: Seventy-six volunteers from among patients who visited our outpatient clinic. They were 74 male and 2 female patients between the ages of 28 and 90 (mean 67.2 +/- 12.7 years, median 70 years). Sixteen of 74 male patients were treated with hormone therapy for prostate cancer. All of 76 patients were scheduled for blood examinations because of urological diseases, and gave full informed consent to participate in this study. Saliva and serum samples were collected between 06.00 and 11.00 h. Sa-T, Se free T and the concentration of transferine in saliva was measured with a Salivary Testosterone Enzyme Immunoassay Kit, a Coat-A-Count Free Testosterone and a Blood Contamination Enzyme Immunoassay Kit, respectively. The average of duplicate values was used. Bioavailable testosterone (BT) was assayed by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry. Average intraassay coefficient of variations of all assays were within 15%. RESULTS: Eleven out of 76 salivary samples were disqualified as unsuitable because of possible blood contamination or falling outside the range of the assay sensitivity. The ranges of Sa-T, Se free T and the transferrin concentration in saliva were 32 to 360 pg/ml (n = 65, mean 176.8 +/- 96.6 pg/ml, median 168.0 pg/ml), 0.15 to 21.0 pg/ml (n = 76, mean 6.6 +/- 4.2 pg/ml, median 7.0 pg/ml), and 0.08 to 6.0 mg/dl (n = 76, mean 0.66 +/- 0.89 pg/ml median 0.42 mg/dl), respectively. In 10 participants randomized chosen out of all, there was significantly correlation between Se free T and BT (r = 0.964, p < 0.01) . There was significant correlation between Se free T and Sa-T (n = 65, r = 0.592, p < 0.01) and estimated Se free T value can be calculated based on the Sa-T level. CONCLUSION: Though disqualified samples accounted for 14.5% of the total number of saliva samples, Sa-T can be used as a substitute parameter for biologically active testosterone.

Adult↗
PubMed2005

[Comparison of endoscopic versus open radical nephrectomy for stage T1 and T2 renal cancer].

The aim of this study was to compare the efficacy, efficiency and patient well-being of endoscopic radical nephrectomy (ERN) with those of open radical nephrectomy (ORN) in patients with stage T1 and stage T2 renal cell carcinoma during the period from 1995 to 2003. Eighty-four patients including 53 patients receiving ERN and 31 patients receiving ORN were evaluated. The two groups were analyzed for sex, side of tumor, clinical stage, age, tumor diameter, operative time, operative blood loss, postoperative time to oral intake and ambulation. There was no difference in patient background between the ERN and ORN groups. Although the mean operative times between the ORN and ERN group were not different (mean 240 versus 267 min. in ERN group, P N .S.), ERN patients had significantly less operative blood loss (mean 123 versus 469 ml. in ERN group, P < 0.01), significantly shorter time to start the oral intake of rice gruel (mean 1.4 versus 4.6 days. in ERN group, P < 0.01) and significantly shorter time to ambulation (mean 1.2 versus 3.1 days. in ERN group, P < 0.01). These findings revealed that endoscopic radical nephrectomy for the patients with stage T1 and T2 renal cell carcinoma appears to be associated with less morbidity and faster recovery rather than open radical nephrectomy.

Adolescent↗
PubMed2004

Restoration of fibroblast growth factor receptor2 suppresses growth and tumorigenicity of malignant human prostate carcinoma PC-3 cells.

BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) expedite stromal-epithelial communication in development and homeostasis of the human prostate. Loss of resident epithelial cell FGFR2IIIb that responds to stromal FGF7 and FGF10 accompanies malignant progression of both model animal and human prostate tumors. METHODS: We examined whether restoration of FGFR2IIIb by transfection in the malignant human prostate tumor PC-3 cell line restored cellular properties associated with less malignant tumors. Cell proliferation, apoptosis, and tumor cell implants were used to monitor malignant properties. Activity of FGFR2IIIb was assessed by immunoblot of FRS2 and p44/42 MAP kinase. Immunochemical analysis of pancytokeratin and lactoferrin expression was utilized to assess changes in cellular differentiation. RESULTS: Expression of FGFR2IIIb in PC-3 cells by transfection resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis. CONCLUSIONS: The results indicate that restoration of FGFR2IIIb to the malignant human prostate epithelial cell prototype PC-3 restores properties associated with nonmalignant tumors and normal cells. This further suggests that epithelial cell resident, homeostasis-promoting FGFR2 may be involved in suppression of malignancy and that restoration may be a candidate for gene therapy of hormone-refractory prostate cancer.

Apoptosis↗