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J W Moul

Publications and source records attributed to J W Moul.

At least 19 recordsLinked to original sources
PubMed2001

Quantitative expression profile of androgen-regulated genes in prostate cancer cells and identification of prostate-specific genes.

Quantitative expression profile of androgen-regulated genes (ARGs) was evaluated in the hormone-responsive prostate cancer cell line LNCaP by serial analysis of gene expression (SAGE). A total of 83,489 SAGE tags representing 23,448 known genes or expressed sequence tags (ESTs) and 1,655 potentially novel sequences have unraveled the transcriptome of LNCaP cells, the most common cell line used in prostate cancer research. Comparison of transcripts between control and R1881-treated LNCaP cells revealed the induction of 136 genes and repression of 215 genes in response to androgen (p < 0.05). Strikingly, a high fraction ( approximately 90%) of ARGs identified in our study has not been described as ARGs previously. A number of prostate-specific transcription factors were among the ARGs identified here. Classification of the ARGs on the basis of biochemical functions revealed that a great majority of ARGs identified in our experimental system appear to be involved in regulation of transcription, splicing, ribosomal biogenesis, mitogenesis, bioenergetics and redox processes. One of the novel aspects of androgen signaling included androgen regulation of genes involved in DNA repair/recombination process. By comparing our LNCaP-C and LNCaP-T SAGE libraries with SAGE tag libraries available at the NCBI-SAGE website, we have identified >200 potential prostate specific/abundant transcripts. The discovery of new prostate-specific genes and ARGs provides a unique opportunity to determine the role of these genes in prostate cell growth, differentiation and tumorigenesis.

Androgens↗
PubMed2001

Prostate-specific antigen-enhanced testing and risk stratification for chemoprevention trials.

Prostate-specific antigen (PSA) testing could be used to identify men who are at higher future risk of developing clinical prostate cancer or to diagnose prostate cancer earlier in high-risk groups, such as black men or those with a family history of the disease. These cohorts then could be offered chemopreventive clinical trial participation opportunities. The Physicians' Health Study and other longitudinal studies have shown that even between a PSA level of 1.0 and 4.0 ng/mL, the risk of future prostate cancer is incrementally increased. Department of Defense Studies of young men between 15 and 45 show that normal men have very low PSA values. Using a threshold PSA even as low as 1.5 ng/mL for men in their fifth decade is well beyond the 95th percentile of "normal" PSA. Young black men between 40 and 49 years old have a higher risk of prostate cancer than white men and should be pursued for chemoprevention studies. PSA is not perfect. Benign prostatic hyperplasia and inflammation (and, perhaps, other factors) can confound the use of PSA thresholds to identify men for chemoprevention or early detection. Certain chemopreventive agents may affect PSA physiology without affecting the disease process itself creating a meaningless epiphenomenon. Young black men may not generally be receptive to PSA testing or chemopreventive trials.

Adult↗
PubMed2001

A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group.

OBJECTIVE: To review and compare the outcome of patients undergoing radical retropubic prostatectomy (RRP) or radical perineal prostatectomy (RPP) for clinically localized prostate cancer. PATIENTS AND METHODS: From 1988 to 1997, 1382 men who were treated by RRP and 316 by RPP were identified from databases of the Uniformed Services Urology Research Group. The following variables were assessed; age, race, prostate-specific antigen (PSA) level before surgery, clinical stage, biopsy Gleason sum, estimated blood loss (EBL), margin-positive rate, pathological stage, biochemical recurrence rate, short and long-term complication rates, impotence and incontinence rates. To eliminate selection bias, the analysis was concentrated on pairs of patients matched by race, preoperative PSA level, clinical stage and biopsy Gleason sum. RESULTS: In the 190 matched patients there were no significant differences between the RRP and RPP groups in either organ-confined (57% vs 55%), margin-positive (39% vs 43%), or biochemical recurrence rates (12.9% vs 17.6% at a mean follow-up of 47.1 vs 42.9 months), respectively. The mean EBL was 1575 mL in the RRP group and 802 mL in the RPP group (P < 0.001). The only significant difference in complication rates was a higher incidence of rectal injury in the RPP group (4.9%) than in the RRP group (none, P < 0.05). CONCLUSIONS: In similar populations of patients, RPP offers equivalent organ-confined, margin-positive and biochemical recurrence rates to RRP, while causing significantly less blood loss.

Adult↗
PubMed2001

The development of erectile dysfunction in men treated for prostate cancer.

PURPOSE: Erectile dysfunction is a common side effect in men treated for prostate cancer. Previously published studies document the incidence of erectile dysfunction in men treated for prostate cancer to be between 20% and 88%. To our knowledge a prospective evaluation focused on the development of erectile dysfunction in men treated for prostate cancer has not elucidated components of its chronology or risk factors. MATERIALS AND METHODS: A centralized prospective database of 2,956 patients diagnosed with prostate cancer at a single institution was studied in regard to pretreatment and posttreatment erectile dysfunction. Of these 2,956 patients 802 had sufficient information regarding erectile function and comprise our study population. Factors analyzed in regard to treatment and erectile dysfunction include treatment modality, that is radical prostatectomy, external beam radiation therapy and watchful waiting, and ethnicity, patient age, clinical stage and tumor histological grade. RESULTS: No significant difference was noted in the posttreatment erectile function between patients treated with radical prostatectomy or external beam radiation (10% versus 15%). Patients selecting watchful waiting had the lowest risk of erectile dysfunction. Clinical stage and race were significant predictors for the development of erectile dysfunction in the watchful waiting and external beam radiation treatment groups. CONCLUSIONS: Erectile dysfunction develops in greater than 80% of patients treated for prostate cancer. External beam radiation has the same risk for erectile dysfunction as radical prostatectomy.

Adult↗
PubMed2000

Impact of socioeconomic status and race on clinical parameters of patients undergoing radical prostatectomy in an equal access health care system.

OBJECTIVES: To analyze the relationships among socioeconomic status (SES), race, and the clinical parameters of patients undergoing radical prostatectomy (RP) in an equal access health care system. METHODS: The Department of Defense Center for Prostate Disease Research longitudinal prostate cancer database from multiple military institutions was used to analyze the clinical, pathologic, and outcome data of 1058 patients with localized (Stage T2c or lower) prostate cancer and a preoperative prostate-specific antigen (PSA) level of 20 ng/mL or less who underwent RP between January 1987 and December 1997. Military rank (officer versus enlisted) was used as a surrogate measure of SES. RESULTS: The percentage of patients with pathologic Gleason grade 7 or greater prostate cancer was higher in enlisted (45%) than in officer (37%) patients (P = 0. 021). However, no difference was found between these groups with respect to pathologic stage or biochemical recurrence rates. African Americans presented at a younger age (P = 0.003), with a higher pretreatment PSA level (P = 0.001), and demonstrated higher biochemical recurrence rates than other ethnic groups (P = 0.037). The Cox proportional hazards analysis showed that a lower SES (P = 0.010) but not African American race (P = 0.696) was an independent predictor of a higher grade (Gleason grade 7 or higher) cancer. However, biochemical progression was more common in African American men (P = 0.035) and was not related to SES (P = 0.883). CONCLUSIONS: In an equal access health care system, patients of lower SES presented with higher grade prostate cancer at the time of RP. However, only African American race predicted biochemical progression after RP.

Age Factors↗
PubMed2000

PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer.

PSGR, a new prostate tissue-specific gene with homology to the G protein-coupled odorant receptor gene family, has been identified. Here we report the characteristics of the predicted protein sequence of PSGR and its prostate tissue specificity and expression profile in human prostate cancer and matched normal tissues. Using multiple tissue Northern blots from over 50 different tissues, PSGR expression was restricted to human prostate tissues. Paired normal and tumor specimens from 52 primary prostate cancers, obtained by laser capture microdissection or manual microdissection, were analyzed for PSGR expression by semiquantitative and real-time PCR assays. The differential expression of PSGR between normal and tumor tissues was highly significant (P < 0.001), and 32 of 52 (62%) matched prostate specimens exhibited tumor-associated overexpression of PSGR. Of note, there was very little or no expression of PSGR in many normal specimens in comparison with the generally high expression of PSGR seen in matched tumor specimens. In situ hybridization assays showed restricted PSGR expression in the epithelial cells of the normal and tumor tissue sections. Restricted expression of PSGR in prostatic epithelial cells, overexpression of the PSGR in a significant percentage of prostate cancers, and the predicted protein sequence of PSGR with seven transmembrane domains provide a foundation for future studies evaluating the potential of PSGR as a prostate cancer gene expression marker and the utility of PSGR protein as a novel target for developing immunotherapeutic strategies for prostate cancer.

Amino Acid Sequence↗
PubMed2000

Prostate-specific antigen levels in young white and black men 20 to 45 years old.

OBJECTIVES: To determine the prostate-specific antigen (PSA) levels and PSA change over time in young white and black men 20 to 45 years old. METHODS: The Department of Defense Serum Repository, a serum bank that stores all residual serum from the military human immunodeficiency virus screening program at -25 degrees C, was sampled to obtain a total of 588 black and 588 white subjects 20 to 45 years old. This was a retrospective study with only demographic data available on the studied subjects. The samples used for this study were collected between June 24, 1988 and June 12, 1996. Individuals with a history of prostate disease were excluded by query of a centralized Department of Defense diagnosis database. Three serum specimens evenly distributed over a mean of 6 years were selected for each individual to determine the free and total PSA levels and PSA velocity. The Hybritech Tandem-E PSA assay was used for the total PSA measurement, and the Hybritech Tandem-R assay was used for the free PSA measurement. RESULTS: The baseline serum PSA levels differed by race (P = 0.04). The median (25th, 75th percentile) baseline serum PSA levels for black men 20 to 29, 30 to 39, and 40 to 45 were 0.38 ng/mL (0.26, 0.61), 0.45 ng/mL (0.32, 0. 67), and 0.52 ng/mL (0.37, 0.73), respectively. The median baseline serum PSA levels for the same decade groups in white men were 0.38 ng/mL (0.27, 0.57), 0.45 ng/mL (0.28, 0.68), and 0.40 ng/mL (0.26, 0. 64), respectively. The PSA velocity was higher in white men than in black men (mean 2.8%/yr and 1.6%/yr, respectively, P = 0.032). CONCLUSIONS: These results suggest that although black men 20 to 45 years old have higher baseline serum PSA levels than white men of the same age, the PSA velocity is greater in young white than in young black men. Additional work is needed to determine the clinical significance of these findings.

Adult↗
PubMed2000

PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer.

A prostate-specific gene, PCGEM1, was identified by differential display analysis of paired normal and prostate cancer tissues. Multiple tissue Northern blot analysis revealed that PCGEM1 was expressed exclusively in human prostate tissue. Analysis of PCGEM1 expression in matched normal and primary tumor specimens revealed tumor-associated overexpression in 84% of patients with prostate cancer by in situ hybridization assay and in 56% of patients by reverse transcription-PCR assay. Among various prostate cancer cell lines analyzed, PCGEM1 expression was detected only in the androgen receptor-positive cell line LNCaP. Extensive DNA sequence analysis of the PCGEM1 cDNA and genomic DNA revealed that PCGEM1 lacks protein-coding capacity and suggests that it may belong to an emerging class of noncoding RNAs, also called "riboregulators." The PCGEM1 locus was mapped to chromosome 2q32. Taken together, the remarkable prostate-tissue specificity and androgen-dependent expression of PCGEM1 as well as its elevated expression in a significant percentage of tumor tissues suggest specific functions of PCGEM1 in the biology and tumorigenesis of the prostate gland.

Androgens↗
PubMed2000

A novel androgen-regulated gene, PMEPA1, located on chromosome 20q13 exhibits high level expression in prostate.

Biologic effects of androgen on target cells are mediated in part by transcriptional regulation of androgen-regulated genes (ARGs) by androgen receptor. Using serial analysis of gene expression (SAGE), we have identified a comprehensive repertoire of ARGs in LNCaP cells. One of the SAGE-derived tags exhibiting homology to an expressed sequence tag was maximally induced in response to synthetic androgen R1881 treatment. The open reading frame of the androgen-induced RNA (PMEPA1) was characterized as a 759-bp nucleotide sequence coding for a 252-amino-acid protein. The analysis of PMEPA1 protein sequence indicated the existence of a type Ib transmembrane domain between residues 9 and 25. Analysis of multiple-tissue Northern blots revealed the highest level of PMEPA1 expression in prostate tissue. PMEPA1 expression was predominately detected in glandular epithelial cells of prostate by in situ hybridization analysis. The expression of PMEPA1 in LNCaP cells was induced by androgen in a time- and dose-specific manner. Evaluation of PMEPA1 expression in androgen-dependent/independent tumors of the CWR22 xenograft model revealed that PMEPA1 was overexpressed in three of four androgen-independent tumor tissues. These observations define PMEPA1 as a novel androgen-regulated gene exhibiting abundant expression in prostate tissue. The increased expression of PMEPA1 in relapsed tumors of the CWR22 model suggests activation of androgen signaling in hormone refractory disease. PMEPA1, along with other highly androgen-induced prostate-specific genes, has potential to serve as an androgen signaling read-out biomarker in prostate tissue.

Androgens↗
PubMed2000

p53 regulates the expression of the tumor suppressor gene maspin.

Maspin has been shown to inhibit tumor cell invasion and metastasis in breast tumor cells. Maspin expression was detected in normal breast and prostate epithelial cells, whereas tumor cells exhibited reduced or no expression. However, the regulatory mechanism of maspin expression remains unknown. We report here a rapid and robust induction of maspin expression in prostate cancer cells (LNCaP, DU145, and PC3) and breast tumor cells (MCF7) following wild type p53 expression from an adenovirus p53 expression vector (AdWTp53). p53 activates the maspin promoter by binding directly to the p53 consensus-binding site present in the maspin promoter. DNA-damaging agents and cytotoxic drugs induced endogenous maspin expression in cells containing the wild type p53. Maspin expression was refractory to the DNA-damaging agents in cells containing mutant p53. These results, combined with recent studies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inhibitor 1 (PAI1), define a new category of molecular targets of p53 that have the potential to negatively regulate tumor invasion and/or metastasis.

Adenoviridae↗
PubMed2000

Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database.

PURPOSE: Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS: We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS: There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Adenocarcinoma↗
PubMed2000

Molecular genetic parameters in pathogenesis and prognosis of testicular germ cell tumors.

Aim of this review article was to critically analyze the recently described cytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosme i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromosomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies the percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in the research for prgnosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it will also define new approaches to classification and management of germ cell tumors

Carrier Proteins↗
PubMed2000

Aneuploidy of chromosome 9 and the tumor suppressor genes p16(INK4) and p15(INK4B) detected by in situ hybridization in locally advanced prostate cancer.

INTRODUCTION AND OBJECTIVES: The linked p16(INK4)/MTS1 and p15(INK4B)/MTS2 genes on chromosome 9p21 encode proteins that inhibit the cyclinD dependent kinases CDK4/6. Biallelic homozygous deletions involving this locus have been identified in a wide range of tumor cell lines, but in a lower frequency of primary tumors. As PCR based approaches analyzing for homozygous deletions could be confounded by unavoidable contributions of normal cells in microdissected tissue, we performed in situ hybridization (ISH) on primary prostate carcinomas to accurately evaluate p16 and p15 copy numbers on a cell-by-cell basis. MATERIAL AND METHODS: p16 and p15 loci were evaluated in 28 pT3N0M0 prostate cancer specimens. Of 28 patients, 15 (53%) were ascertained showing no recurrence (mean follow-up 61+/-17 months), 13 (47%) developed recurrences within 27+/-19 months. Tissues were provided for ISH analysis in a blinded fashion. Isolated DNA derived from P1 clone 1063 compromising p16 and p15 as well as a centromeric probe for chromosome 9 were used for hybridization. Signals were enumerated within 300 interphase nuclei per tumor specimen, and in 100 nuclei derived from 18 benign prostate tissues and 7 adjacent PIN regions. RESULTS: ISH detected aneuploid tumors in 12/13 (92%) patients with recurrence and in 5/15 (33%) without recurrence (p<0.0014). Whereas 3/7 PIN specimens associated with nonrecurrent PCA demonstrated euploidy, all 4/7 PIN associated with recurrent disease demonstrated the same aneuploidy for chr9 as the primary tumor. All benign tissues evaluated exhibited euploidy for chr9, p16 and p15. None of the PCA and PIN samples revealed homozygous deletions for p16(INK4)/MTS1/p15(INK4B)/MTS2; 2/28 (7.1%) PCA exhibited partial deletion for p16(INK4)/MTS1/p15(INK4B)/MTS2 and aneuploidy for chr9; both PCA derived from the recurrent group. CONCLUSIONS: Deletion of 9p21 was rare and therefore such genetic alterations may not play an important role in the pathogenesis of PCA. Analysis of the limited number of PCA examined suggest a strong association between chr9 aneuploidy and recurrenct disease. Aneuploidy in both PIN and PCA suggests that the clinical outcome of PCA might already be determined in the preinvasive PIN.

Aneuploidy↗
PubMed2000

Inflammatory infiltrate (prostatitis) in whole mounted radical prostatectomy specimens from black and white patients is not an etiology for racial difference in prostate specific antigen.

PURPOSE: Although black men with and without prostatic carcinoma in general have higher levels of prostate specific antigen (PSA) than other racial groups, the cause is unknown. Previous studies have shown that black men produce greater PSA per cc of benign gland volume. We determined whether prostatic inflammation varied by race and could account for the racial difference in PSA among prostate cancer patients. MATERIALS AND METHODS: Between April 1993 and February 1997, 238 patients underwent radical prostatectomy for clinically localized prostate cancer at Walter Reed Army Medical Center and whole mounted specimens were processed at the Armed Forces Institute of Pathology. Cases were reviewed by 2 pathologists (W. Z. and I. A. S.) blinded to clinical information, and scored for inflammation as 0--rare; 1--mild, 10 to 15 small foci; 2--moderate, greater than 15 foci with a large area or greater than 20 small foci; 3--marked, greater than 20 small foci with a large area, and 4--diffuse, multiple large areas. The extent of inflammation was correlated to pretreatment PSA and other variables. RESULTS: A total of 181 white and 57 black men were evaluated. Of the patients 28 were excluded from analysis due to prior hormonal therapy. The percentage of patients with inflammation scores from 1 to 4 was higher among white (113 of 161, 70.2%) than black (30 of 49, 61.2%) men but this difference was not significant (p = 0.299) and the extent of inflammation was not significantly related to racial variation in serum PSA. CONCLUSIONS: To our knowledge no significant racial difference exists in the extent of inflammatory infiltrate, and inflammation was not the etiology of the racial difference in serum PSA levels in this clinically localized prostate cancer cohort.

Aged↗
PubMed2000

Multicenter patient self-reporting questionnaire on impotence, incontinence and stricture after radical prostatectomy.

PURPOSE: We determined the incidence of patient self-reported post-prostatectomy incontinence, impotence, bladder neck contracture and/or urethral stricture, sexual function satisfaction, quality of life and willingness to undergo treatment again in a large multicenter group of men who underwent radical prostatectomy. We also determined whether the morbidities of sexual function satisfaction, quality of life and bladder neck contracture and/or urethral stricture are predictable from demographic and postoperative prostate cancer factors. MATERIALS AND METHODS: A self-reporting questionnaire was completed and returned by 1,069 of 1,396 eligible patients (77%) who underwent radical prostatectomy between 1962 and 1997. Of the respondents 868 (85.7%) underwent surgery after 1990 and in all prostatectomy had been done a minimum of 6 months previously. Questionnaire results were independently analyzed by a third party for morbidity tabulation and the association of patient reported satisfaction. RESULTS: The patient self-reported incidence of any degree of post-prostatectomy incontinence, impotence and bladder neck contracture or urethral stricture was 65.6%, 88.4% and 20.5%, respectively. The incidence of incontinence requiring protection was 33% and only 2.8% of respondents had persistent bladder neck contracture or urethral stricture. Although incontinence and impotence significantly affected self-reported sexual function satisfaction, quality of life and willingness to undergo treatment again (p = 0.001), 77.5% of patients would elect surgery again. This finding remained true even after adjusting for demographic variables, and the time between surgery and the survey by multiple logistic regression. CONCLUSIONS: Although radical prostatectomy morbidity is common and affects self-reported overall quality of life, most patients would elect the same treatment again. Impotence and post-prostatectomy incontinence were significantly associated with sexual function satisfaction, quality of life and willingness to undergo treatment again. Bladder neck contracture and/or urethral stricture was associated with willingness to undergo treatment again after adjusting for demographic variables and time from surgery to the survey.

Adult↗
PubMed2000

Expression profile of an androgen regulated prostate specific homeobox gene NKX3.1 in primary prostate cancer.

PURPOSE: NKX3.1, a member of the family of homeobox genes, exhibits prostate tissue specific expression and appears to play a role in mouse prostate development. Rapid induction of NKX3.1 gene expression in response to androgens has also been described. On the basis of the established role of androgens in prostatic growth and differentiation and studies showing an association of aberrant homeobox gene expression with the neoplastic process, we hypothesize that alterations of NKX3.1 gene expression play a role in prostate tumorigenesis. MATERIALS AND METHODS: NKX3.1 expression was analyzed in matched, microdissected normal and tumor tissues from 52 primary prostate cancer specimens from radical prostatectomy by semiquantitative RT-PCR and in situ hybridization and correlated with the clinicopathologic features. NKX3.1 expression was quantified as differential expression between matched tumor and normal tissues and was grouped as overexpression in tumor tissue, reduced expression in tumor tissue and no change between tumor and normal tissues. Androgen regulation of NKX3.1 expression was also studied in LNCaP cells. Androgen receptor (AR) expression in prostate tumor and normal tissue was correlated with NKX3.1 expression. RESULTS: Comparison of NKX3.1 expression between normal and tumor tissues revealed overexpression in 31% tumor specimens (16 of 52), decreased expression in 21% tumor specimens (11 of 52) and no change in 48% specimens (25 of 52). When these expression patterns were stratified by organ confined and non-organ-confined tumor, a higher percentage of patients exhibited NKX3.1 overexpression in non-organ confined tumor (40%) versus organ confined tumor (22%). Elevated NKX3.1 expression significantly correlated with tumor volume and serum prostate specific antigen (PSA) level in the NKX3.1 overexpression group (p<0.05). Metastatic prostate cancer cell lines did not exhibit mutations in the protein coding sequence of NKX3.1. Additionally, the NKX3.1 expression correlated with AR expression (p<0.01) in vivo in human prostate tissues. Comparison of PSA and NKX3.1 expression in response to androgen revealed a rapid androgen mediated induction of NKX3.1 expression in LNCaP cells. In situ hybridization analysis of representative specimens confirmed RT-PCR observations. CONCLUSIONS: These results suggest an association of NKX3.1 with a more aggressive phenotype of carcinoma of the prostate. Correlation of AR expression with NKX3.1 in human prostate tissues underscores the androgen regulation of NKX3.1 in the physiologic context of human prostate tissues.

Androgens↗
PubMed2000

Prostate specific antigen only progression of prostate cancer.

PURPOSE: Introduction of the prostate specific antigen (PSA) serum marker for prostate cancer and the subsequent PSA era from 1988 to the present have dramatically altered the diagnosis of the disease. The early to mid 1990s diagnosis boom resulted in a huge increase in clinically localized and early stage disease treatments. Radical prostatectomy rates increased from 17.4 to 54.6/100,000 between 1988 and 1992, and age adjusted rates increased 2 to 4-fold for men in the fifth and sixth decades of life. Since the late 1990s clinicians have been seeing the effects of this diagnosis and localized treatment boom, in that many men each year are experiencing PSA only disease recurrence. Given that the majority are relatively young and otherwise healthy, treatment of PSA only recurrence requires approaches that not only improve survival, but also preserve quality of life. A comprehensive overview of the definition of PSA only recurrence, staging controversies and the wide variety of treatments to be considered is provided. MATERIALS AND METHODS: A literature review and overview of the topic of PSA only recurrence after prior clinically localized prostate cancer treatment were performed. RESULTS: For radical prostatectomy cases PSA only recurrence is broadly defined as any elevation of PSA postoperatively. For radiation treated patients the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify 3 consecutive elevations of PSA after posttreatment PSA nadir is achieved. As localized treatment series in the PSA era have matured, and database and statistical support have improved, a number of useful models to predict PSA only recurrence have emerged. These models are based on traditional prognostic markers, such as pretreatment PSA, and grade and stage of disease as well as emerging molecular and cellular biomarkers. Although bone scans and pelvic computerized tomography are commonly used for re-staging at PSA only recurrence, recent study suggests that their value is limited unless PSA recurrence exceeds 30 to 40 ng./ml. 111Indium capromab pendetide radionuclide scan, which has been approved for radical prostatectomy PSA only recurrence, may be helpful to determine cases best suited for salvage radiotherapy versus systemic hormonal therapy, although more study is needed. Treatment of PSA only recurrence is divided into 2 main categories of salvage local treatments and systemic therapy. The principal dilemma is the inability to determine definitively whether PSA only recurrence is solely due to local progression or distant micrometastases. External beam radiation is the main local salvage treatment for radical prostatectomy recurrence, and cryotherapy, salvage prostatectomy and salvage brachytherapy are options for radiation recurrence. Proper patient selection is critical to the success of all salvage local treatments. Traditional hormonal therapy is the mainstay of systemic treatment for PSA only recurrence, although nontraditional approaches, such as intermittent and low dose hormonal therapy, are under study. Emerging chemopreventive agents, such as vitamins, minerals and other supplements, may have a future role in treatment. CONCLUSIONS: PSA only recurrence after prior local prostate cancer treatment remains a common problem facing clinicians.

Brachytherapy↗