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D G McLeod

Publications and source records attributed to D G McLeod.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lateral biopsies added to the traditional sextant prostate biopsy pattern increases the detection rate of prostate cancer.

Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error and data based upon whole-mounted step-sectioned radical prostatectomy specimens using a three-dimensional computer-assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. The simulated 10-core biopsy pattern (traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland) was shown to be superior to the traditional sextant biopsy. The objective of this pilot study was to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in patients. We reviewed data on 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients being diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3, 43-46

Journal Article↗
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

3-D computer visualization and interactive prostate biopsy simulation leads to an improved systematic technique for the detection of prostate cancer: clinical correlation.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. Recent data based upon whole-mounted step-sectioned radical prostatectomy specimens using a 3-D computer assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was shown to be superior to the traditional sextant biopsy. This pattern includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in a small cohort of patients. METHODS: We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. RESULTS: Of the 35 patients diagnosed with prostate cancer, 54.3% (19/35) were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7% (16/35) of patients were diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. CONCLUSIONS: Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the apex and mid portion of the gland are the most important.

Biopsy, Needle↗
PubMed2000

Investigating 3D tumor distribution for optimized diagnosis of prostate cancer.

Transrectal Ultrasonography (TRUS) based systematic needle biopsy of the prostate has been widely used clinically in the diagnosis of prostate carcinoma. Current protocols for prostate biopsy, such as the Sextant Protocol, however, have been proven to be insufficient in cancer detection since these protocols were built without having accurate information on 3D distribution of prostate cancers. In this research, our goal is to optimize prostate biopsy protocols by statistically investigating spatial distributions of prostate cancers. Based on the low-resolution nature of ultrasound imaging and the current clinical conventions, we propose to divide each individual prostate gland into different zones that are can be recognized and accessed by the urologists with ultrasound images during biopsy. By calculating cancer appearance inside each of these zones using a large number of prostate samples, we get the overall distributions of prostate cancers based on which an optimal biopsy protocol can be developed.

Biopsy, Needle↗
PubMed2000

Comparative study of the clinical efficacy of two dosing regimens of flutamide.

PURPOSE: We performed a randomized trial to compare the efficacy and toxicity of a new dose of flutamide (500 mg QD) with the currently recommended dose (250 mg q8h) in the treatment of advanced prostate cancer. The primary endpoints were percent of patients having normalization of prostate specific antigen (PSA), time to normalization, and percent change from baseline. Secondary endpoints were quality of life and toxicity. PATIENTS: Altogether, 440 men aged 46 to 94 years (mean 71 years) with confirmed stage M(1) disease, documented PSA rise >0.2 ng/mL, ECOG status 0 to 2, no second neoplasm, no liver function tests > or = 1.5-fold normal values, and no previous treatment for metastatic disease were entered in the trial. RESULTS: The PSA normalized by week 12 in 71% of the patients receiving 500-mg dose and 75% of those receiving the standard dose. The percent change in PSA was 89% and 96%, respectively. The treatment groups were not significantly different with respect to the incidence of adverse events: 71% v 68% in the 500-mg and 250-mg arms, respectively (P = 0.337). CONCLUSIONS: When combined with castration, 500 mg of flutamide appears to be equally effective in lowering serum PSA and is not significantly more toxic than conventional dosing. The use of 500 mg QD instead of the standard 250 mg q8h would result in a cost savings of 30%.

Aged↗
PubMed1999

Exploratory analysis on the effect of race on clinical outcome in patients with advanced prostate cancer receiving bicalutamide or flutamide, each in combination with LHRH analogues. The Casodex Combination Study Group.

BACKGROUND: Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB). METHODS: Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.6 mg, or leuprolide acetate 7.5 mg) in 813 patients with stage D(2) prostate cancer (median follow-up, 160 weeks). Patients were analyzed according to race (African American [AA], white, or other). The primary clinical events were disease progression and survival. RESULTS: Four hundred and four patients received bicalutamide/LHRHa and 409 received flutamide/LHRHa. Although treatment with bicalutamide/LHRHa resulted in slightly longer time to progression and survival time in white and AA males than treatment with flutamide/LHRHa, the differences between the treatment groups were not statistically significant. CONCLUSIONS: No marked effect of race on clinical outcome was observed regardless of antiandrogen, suggesting that similar treatment benefits are to be expected in either race.

Adenocarcinoma↗
PubMed1999

Allelic loss on chromosome 6Q in primary prostate cancer.

Molecular genetic analyses of human prostate cancer (CaP) has revealed frequent loss of specific chromosome regions suggesting the presence of putative tumor suppressor gene(s) (TSG) on these chromosome loci whose inactivation may play a role in prostate tumorigenesis. To understand the role of 6q alterations in CaP, we have undertaken a comprehensive analysis of proximal 6q. Genomic DNA from tumor and normal prostate tissues from radical prostatectomy specimens of 38 patients were analyzed by polymerase chain reaction (PCR) for 13 polymorphic microsatellite loci on 6q. Allelic losses of 1 or more polymorphic loci were detected in 11 of 38 patients (29%). Six of 11 tumors showing any 6q deletion were found to have allelic losses at D6S1056 and D6S300 loci. Our results revealed a 1.5 megabase interval between D6S1056 and D6S300 at 6q16.3-21 as the minimal region of deletion, which may contain the putative TSG involved in prostate tumorigenesis. One of the tumor samples demonstrated homozygous deletion at a distal location D6S314 (6q23-24), suggesting another locus potentially associated with CaP. Although the relationship of 6q loss of heterozygosity (LOH) with various clinico-pathologic variables, i.e., cancer recurrence or pathologic stage, did not reveal a statistically significant association, the risk for 6q LOH to non-organ confined (pT3) disease was 5-fold higher than for organ confined disease.

Adult↗
PubMed1999

Prostate-specific antigen to predict outcome of external beam radiation for prostate cancer: Walter Reed Army Medical Center experience, 1988-1995.

OBJECTIVES: To assess the ability of pretreatment and post-treatment prostate-specific antigen (PSA) measurements, clinical tumor stage, tumor grade, Gleason sum, race, age, and radiation dose to predict the recurrence of prostate cancer following external beam radiation therapy (XRT) since the introduction of PSA as a tumor marker at one tertiary care center. METHODS: The recurrence of prostate cancer among 371 evaluable patients of 389 patients treated with XRT at Walter Reed Army Medical Center was analyzed using Kaplan-Meier survival methodology and Cox multivariable regression models. Serologic (PSA) recurrence was determined using three consecutive rises in PSA after a nadir value. Clinical recurrence was defined as local recurrence (palpable or positive biopsy) and/or distant (radiographically evident) recurrence. Mean and median follow-up is 40.2 and 39.4 months, respectively (range 3.0 to 89.5), and minimum follow-up is 18 months for patients who were alive at the time of analysis. No patient received adjuvant hormonal therapy. Potential prognostic factors evaluated are pretreatment PSA, PSA nadir, age, race, clinical tumor stage, tumor grade, Gleason sum, and radiation dose. RESULTS: Of the 371 evaluable patients, 125 had disease recurrence. The Kaplan-Meier 5-year disease-free survival (DFS) rates for significant pretreatment variables in univariate analyses are as follows: pretreatment PSA less than 4 (79%), 4.1 to 10 (67%), 10.1 to 20 (57%), 20.1 to 50 (27%), and more than 50 (0%); for clinical tumor Stage T1a-T1c (84%), T2a-T2c (51 %), and T3-T4 (29%); for tumor grade well (58%), moderate (58%), and poor (30%). Four-year DFS rates for Gleason sum are 2 to 4 (82%), 5 (72%), 6 (56%), and 7 to 10 (48%). In multivariable Cox regression analysis with backward elimination of nonsignificant variables, age, race, tumor grade, and radiation dose were eliminated, leaving pretreatment PSA, clinical tumor stage, and Gleason sum as significant prognostic factors. Analysis of a Cox model that included nadir PSA as a time-dependent variable showed it to be the strongest prognostic factor variable in the analysis. CONCLUSIONS: XRT remains a suitable treatment modality for patients with pretreatment PSA less than 20.0, clinical tumor Stages T1-T2, and Gleason sum 2 to 6 prostate cancer. Patients achieving a nadir value less than 0.5 have more durable treatment outcomes.

Aged↗
PubMed1999

Blinded evaluation of reverse transcriptase-polymerase chain reaction prostate-specific antigen peripheral blood assay for molecular staging of prostate cancer.

OBJECTIVES: The reverse transcriptase-polymerase chain reaction (RT-PCR)-prostate-specific antigen (PSA) assay to detect presumed occult micrometastatic prostate cancer has been controversial, and this molecular staging has been thought to be clinically useful by some groups but not others. METHODS: We used a sensitive nested RT-PCR assay with specific primers derived from the PSA sequence and a very stringent two-step PCR protocol with denaturing temperature of 94 degrees C annealing and extension temperature of 68 degrees C. This method enabled us to detect PSA-expressing LNCaP prostate cancer (PC) cells as low as one cell of 10 million lymphocytes (1/10(7)). Ninety-six patients with PC were studied, including 85 before radical prostatectomy (RP), and 22 controls, including healthy men and women and men with benign prostatic hyperplasia. RESULTS: In 85 patients undergoing RP, a minimum of two independent RT-PCR-PSA assays detected circulating prostate cells preoperatively in 27 patients (31.8%). Of 12 patients with locally advanced or advanced stage cancer, RT-PCR-PSA was positive in 5 (41.7%); of the 22 controls, no patient was RT-PCR-PSA positive. In 10 randomly selected cases, the RT-PCR product was confirmed as PSA by DNA sequencing. Of the 27 patients undergoing RP who were RT-PCR positive, 11 (40.7%) had non-organ-confined disease (pT3a or greater), and of the 58 patients who were RT-PCR negative, 32 (55.2%) had non-organ-confined disease. Patients with RT-PCR positive results also had lower margin positivity (9 of 27, 33.3%) than did patients with RT-PCR negative results (21 of 58, 36.2%). Finally, at a mean follow-up of 25.7 months, 5 (18.5%) of 27 RT-PCR positive patients had recurrence (PSA) compared with 14 (24.1%) of 58 RT-PCR negative patients. CONCLUSIONS: On the basis of this blinded study, RT-PCR for PSA-expressing cells in 85 patients before RP is not related to clinical stage, age, race, grade, Gleason sum, serum PSA or prostatic acid phosphatase, tumor volume, or tumor multifocality. RT-PCR positivity did not predict pathologic stage or early PSA recurrence. A standardized RT-PCR assay needs to be developed to account for interlaboratory discrepancies.

Aged↗
PubMed1999

Detection of circulating prostate specific antigen expressing prostatic cells in the bone marrow of radical prostatectomy patients by sensitive reverse transcriptase polymerase chain reaction.

PURPOSE: The reverse transcriptase polymerase chain reaction (RT-PCR) assay for prostate specific antigen (PSA) expressing cells in the blood circulation has been under intense investigation since 1992. Although it has been suggested that this technology could be used as molecular staging for occult prostatic hematogenous metastases, we have been unable to confirm RT-PCR PSA positivity of peripheral blood to predict stage or recurrence in radical prostatectomy cases. We performed bone marrow RT-PCR PSA assay on a large cohort of radical prostatectomy cases and evaluate the use of this assay in improving prostate cancer staging and detecting early recurrence. MATERIALS AND METHODS: Unilateral anterior iliac crest bone marrow aspirates were performed on 116 patients immediately before radical prostatectomy between February 1995 and September 1997. Radical prostatectomy specimens were processed as whole mounts. A sensitive nested RT-PCR assay with specific primers derived from the PSA sequence was used, which enabled us to detect PSA expressing LNCaP prostate cancer cells at the sensitivity of 1 cancer cell per 10 million lymphocytes (1/10(7)). A minimum of 3 RT-PCR PSA reactions were performed on all patients and at least 2 positive tests were required to define positivity. Patients were followed for PSA recurrence (mean followup 14.7 months). RESULTS: PSA expressing cells were detected in bone marrow of 51 of 116 patients (44.0%) when at least 2 of 3 RT-PCR PSA assays per patient were positive. A much higher rate of RT-PCR PSA positivity was noted (77/116 patients, 66.3%) when any RT-PCR PSA positivity was considered. In 10 randomly selected cases the RT-PCR product was confirmed as PSA by deoxyribonucleic acid sequencing. Of 51 bone marrow RT-PCR positive cases 25 (49%) had organ confined disease and 26 (51%) had nonorgan confined disease. Similarly, bone marrow RT-PCR PSA was not associated with age, race, grade, pretreatment PSA or prostatic acid phosphatase value, clinical stage or margin status. However, the 2-year disease-free survival was 96.6% in RT-PCR negative patients versus 77.5% in RT-PCR positive patients (p = 0.054), and bone marrow RT-PCR PSA was an independent prognostic factor in multivariate analysis including PSA, Gleason grade and pathological stage. CONCLUSIONS: Bone marrow RT-PCR PSA positivity in this study did not predict pathological stage, grade or margin positivity as determined from whole mount prostate cancer specimens. Furthermore, no relationship with age, grade or serum markers and bone marrow RT-PCR PSA positivity was noted. However, bone marrow RT-PCR PSA was associated with early disease recurrence. Further studies and longer followup are warranted to define the metastatic potential of the PSA expressing cells in the bone marrow of prostate cancer patients.

Aged↗
PubMed1999

Racial differences in tumor volume and prostate specific antigen among radical prostatectomy patients.

PURPOSE: Black men with and without prostate cancer in general have higher prostate specific antigen (PSA) before screening and treatment than other racial groups. A preliminary study suggested that higher PSA levels may be primarily due to greater tumor burden. We compared PSA and 3-dimensional (D) tumor volume in a consecutive cohort of black and white radical prostatectomy patients in an equal access military health care setting to determine racial differences in these parameters. MATERIALS AND METHODS: Prospective data collection, 2.25 mm. step section whole mount specimen processing and 3-D tumor volume assessment were performed in 226 patients with clinical stage T1-T3 prostate cancer undergoing radical prostatectomy at our center between April 1993 and March 1997. Of the patients 25 were excluded from further analysis because of neoadjuvant hormone treatment, T3 disease or Asian race. A total of 155 white and 46 black patients were compared. RESULTS: There was no significant racial difference in the distribution of patients by age, clinical stage, pathological stage, Gleason sum or benign prostate gland volume. A significant racial difference was noted for pretreatment PSA and 3-D tumor volume. PSA values were higher in black men than in white men, and the racial difference remained statistically significant in multivariate analysis adjusting for 3-D tumor volume, benign gland volume, age, stage and Gleason sum. CONCLUSIONS: Racial difference in PSA persists, despite rigorous covariate adjustment, and further study is needed to explain this PSA difference.

Adult↗
PubMed1998

Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.

BACKGROUND: Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy. METHODS: We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status. RESULTS: Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall, the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease. CONCLUSIONS: The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.

Adenocarcinoma↗
PubMed1998

Perineal seeding of prostate cancer as the only evidence of clinical recurrence 14 years after needle biopsy and radical prostatectomy: molecular correlation.

Perineal needle tract seeding of prostate cancer is an unusual complication of perineal prostate biopsy. We report a case with the longest known interval from biopsy to perineal recurrence--14 years. The prostate-specific antigen did not become detectable until 12 years after biopsy and no other metastases were apparent, suggesting that the patient's perineal disease was an isolated recurrence. Immunohistochemical staining of the perineal recurrence and the original biopsy and prostate for the p53 tumor suppressor gene and bcl-2 oncogene proteins revealed rare/absent p53 expression but marked increased bcl-2 expression. This unusual molecular pedigree may help to explain this rare clinical scenario.

Aged↗
PubMed1998

Hepatic subcapsular extension of pelvic lymphocele after radical retropubic prostatectomy.

Lymphoceles are a rare symptomatic complication after radical prostatectomy occurring in less than 5% of cases. We present a case of a symptomatic lymphocele that occurred after a radical retropubic prostatectomy and obturator lymphadenectomy. The lymphocele dissected along the retroperitoneum and extended into the hepatic subcapsular space and became secondarily infected with Candida albicans.

Candidiasis↗
PubMed1998

Measurement of serum prostate-specific membrane antigen, a new prognostic marker for prostate cancer.

OBJECTIVES: To describe current results with Western blot assay for prostate specific membrane antigen (PSMA) using 7E11.C5 antibody and the development of an additional antibody measurement for PSMA by a new sandwich immunoassay. METHODS: A population of patients from a screening group, from a difficult diagnostic group, from a pre- and postoperative radical prostatectomy group, and from a group with metastatic disease followed for a serial period, provided the serum values for a prospective assessment of PSMA by Western blot assay. A new monoclonal antibody was sought, reacting to the C-terminal region of PSMA in order to develop a sandwich radioimmunoassay. RESULTS: PSMA values in screened patients correlate with the more advanced stage of the cancers determined. In postprostatectomy patients, the PSMA value corresponds more with preoperative values and with the values of those with a poor clinical course. In difficult diagnostic cases, the PSMA value is increased, specifically in hormone-refractory cases and particularly in those cases judged by other criteria, such as the National Prostatic Cancer Project, to be in clinical progression compared with those judged to be in clinical remission. The level of PSMA value appears to be independent of homogeneous tumor volume and to be more related to that of prior hormone treatment, or to where prostate cancer cells can be documented to be outside the prostate. A new monoclonal antibody, 3F5.4G6, reacts with the extracellular domain of PSMA near the C-terminal region. This is in contrast to the previously measured antibody 7E11.C5, which reacts with an N-terminal epitope. 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5. The epitopes are essentially at opposite ends of the molecule. The 3F5.4G6 antibody reacts with the LNCaP line but not with DU145, or PC3. These two antibodies to PSMA are well suited for use in a new sandwich immunoassay. CONCLUSIONS: PSMA provides a prostatic cancer serum test by using Western blot, which suggests a clinical prognostic value not seen with other markers. New antibodies, such as 3F5.4G6, reacting with the extracellular domain of PSMA combined with 7E11.C5, appear to offer an opportunity for a new sandwich immunoassay.

Antibodies, Monoclonal↗
PubMed1998

Significance of familial history of prostate cancer to traditional prognostic variables, genetic biomarkers, and recurrence after radical prostatectomy.

OBJECTIVES: Prostate cancer (PCa) has a familial predisposition imparting an increased risk of developing the disease in those with a family history. The pathologic characteristics are similar to sporadic cases; however, the disease-free survival rates of hereditary PCa have recently been disputed, with one major study suggesting that familial cases have higher recurrence rates. Our study seeks to support or refute this association and to evaluate the genetic biomarkers p53, bcl-2, Ki-67, and neovascularity between familial and sporadic disease. METHODS: We retrospectively reviewed data of 573 patients who underwent radical prostatectomy over an 11-year period. Of these, 474 patients had known family history data. Univariable statistical analysis using the Pearson chi-square test and Kaplan-Meier disease-free survival analysis was performed to identify any correlation between the tested variables and family history. Smaller subsets of this cohort that had available archival material for immunohistochemical staining and family history data were analyzed in a similar manner. RESULTS: The preoperative variables (prostate-specific antigen, prostatic acid phosphatase, clinical stage, highest biopsy Gleason sum, and glandular differentiation) and postoperative variables (stage, highest Gleason sum, and glandular differentiation) did not correlate with family history. Kaplan-Meier disease-free survival analysis revealed no differences between sporadic and familial cases. The analysis of p53, bcl-2, Ki-67, and angiogenesis revealed that only increasing p53 expression and positive family history of PCa approached significance (P = 0.057). CONCLUSIONS: Prognostic variables routinely used in PCa and selected genetic biomarker immunostaining abnormalities are not significantly different in men with and without a family history of PCa. Disease-free survival after radical prostatectomy is also unaffected by family history.

Aged↗
PubMed1998

Efficacy of multiple administrations of a recombinant adenovirus expressing wild-type p53 in an immune-competent mouse tumor model.

Infection of Renca cells in vitro with a recombinant adenovirus expressing a marker gene beta-galactosidase resulted in high level of the transgene expression. Renca tumors grown in Balb/C mice were also infectable with this recombinant adenovirus. The transgene expression in the tumors lasted for about 7 days, however, administration of another dose of Ad-beta gal, on day 7 produced beta-galactosidase expression. To investigate the effect of antibodies to adenovirus, animals were injected with multiple doses of adenovirus to produce neutralizing antibodies. To these animals Renca cells were injected and tumors formed. Interestingly, when Ad beta-gal was administered into these tumors, a high level of transgene expression was still observed. We next explored the utility of a recombinant adenovirus expressing p53 (AdWTp53) in the Renca tumor model. Renca cells when exposed to an adenovirus expressing p53 (AdWTp53) produced a high level of p53 protein, a p53-inducible gene p21/WAF1/Cip1 and underwent apoptosis. A single injection of AdWTp53 (10(9) plaque forming units) resulted in significant inhibition of tumor growth. However, multiple administrations (four doses of 2.5 x 10(8) plaque forming units) of AdWTp53 were needed for tumor cures. Mixing uninfected and AdWTp53-infected cells showed a bystander effect of AdWTp53-infected Renca cells. Based on these results we believe that an appropriate dose scheduling of AdWTp53 can be efficacious for cancer gene therapy in immune-competent tumor-bearing animals.

Adenoviridae↗