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Mark Frydenberg

Publications and source records attributed to Mark Frydenberg.

9 recordsLinked to original sources
PubMed2003

Outcome, morbidity, and prognostic factors in post-prostatectomy radiotherapy: an Australian multicenter study.

OBJECTIVES: To report the outcome and morbidity data for patients treated with post-prostatectomy radiotherapy (PPRT) in a multicenter collaboration. METHODS: The case records of all patients treated with PPRT from 1996 to 1998 were reviewed. Survival was calculated using Kaplan-Meier methods. Potential prognostic factors were evaluated using the Cox proportional hazards regression model. Prostate-specific antigen (PSA) remission was defined as a PSA level of 0.2 ng/mL or less. Acute and late morbidities were documented. RESULTS: We reviewed the data of 115 patients, with a median follow-up from the start of PPRT of 28.7 months. Patients were treated with adjuvant intent (n = 23), for local recurrence (n = 27), or for a detectable PSA level (n = 65). The overall and cause-specific survival rate at 5 years was 73.7% and 81.4%, respectively. The biochemical disease-free survival rate was 69.6% at 2 years and 50% at 5 years. Factors predicting for subsequent relapse on multivariate analysis were pre-PPRT PSA (P = 0.013) and post-PPRT nadir (P <0.0001). Patients with a PSA greater than 1 ng/mL fared significantly worse than those with lower levels (P <0.0001). For patients with a pretreatment PSA of less than 1 ng/mL and an operative Gleason score of 7 or less, the 5-year projected biochemical disease-free survival rate was 71%. One case of grade 3 late proctitis was recorded, and 4 patients had continued grade 3 late urinary incontinence. CONCLUSIONS: Early use of PPRT is effective and well tolerated in patients at risk of, or with proven, local recurrence.

Aged↗
PubMed2003

PSA testing.

Explore the source record for details and available documents.

Aged↗
PubMed2002

Poor prognosis germ-cell tumors: An unresolved challenge.

The prognostic classification developed by the International Germ Cell Consensus group (IGCCC) enables appropriate choice of initial treatment, and provides consistent eligibility criteria for clinical trials and more accurate assessment of published results. The standard therapy for IGCCC poor- and intermediate-prognosis germ-cell tumors is 4 cycles of bleomycin, etoposide, and cisplatin chemotherapy followed by surgical resection of residual masses, if the serum tumor markers have returned to normal. Improved outcomes are achieved by centers that treat a larger number of cases. The unsatisfactory results achieved with current therapy warrant entry of these patients into appropriate clinical trials. Future improvements in therapy are likely to require a better understanding of the molecular mechanisms of resistance and the development of novel therapeutic approaches that target these mechanisms.

Germinoma↗
PubMed2002

Investigations with FDG-PET scanning in prostate cancer show limited value for clinical practice.

The aim of this study was to investigate FDG-PET (fluorodeoxyglucose positron emission tomography) imaging in the management of prostate cancer. Twenty-two patients were studied during different disease phases of prostate cancer, for staging or restaging to clarify specific clinical questions. FDG-PET was performed encompassing the thorax, abdomen and pelvis using the Penn PET 300H scanner. Scanning was begun 60 min after 18F fluorodeoxyglucose marker. Patients were catheterized and administered diuretics to minimize urinary activity. Information obtained with FDG-PET was concordant with findings from other investigations in 7/22 (32%) patients, discordant in 15/22 (68%) patients and equivalent in one patient (4%). PET indicated progressive disease in five patients with prostate-specific antigen (PSA) < 4 ng/L. The impact on management of the patients was high in 46% of cases, low in 41% and for 14% there was no impact on management. The accuracy of FDG-PET was 72% (95% CI 50-89) as confirmed by invasive diagnostics/follow-up. FDG-PET can provide useful information and improve the clinician's decision on further management procedures in selected patients with low PSA and bone or lymph node changes. A negative PET scan in prostate cancer should be interpreted with caution.

Adenocarcinoma↗
PubMed2002

Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men.

Testosterone (T) treatment suppresses gonadotropin levels and sperm counts in normal men, but the addition of a progestin may improve the efficacy of hormonal contraception. This study aimed to investigate the speed and extent of suppression of testicular germ cell number induced by T plus or minus progestin treatment and correlate these changes with serum gonadotropins and inhibin B levels, testicular androgens, and sperm output. Thirty normal fertile men (31-46 yr) received either testosterone enanthate (TE, 200 mg im weekly) alone or TE plus depot medroxyprogesterone acetate (DMPA, 300 mg im once) for 2, 6, or 12 wk (n = 5 per group) before vasectomy and testis biopsy. Five men (controls) proceeded directly to surgery. The inclusion of DMPA led to a more rapid fall in serum FSH/LH levels (time to 10% baseline: FSH; 12.6 +/- 2.6 vs. 7.9 +/- 1.4 d; LH, 9.9 +/- 3.4 vs. 3.4 +/- 1.7 d, TE vs. TE+DMPA, respectively, mean +/- SD, both P < 0.0001), yet the mean time to reach a sperm count 10% of baseline was not different (23.7 +/- 7.3 vs. 25.3 +/- 13.9 d, NS). The maximum extent of FSH/LH suppression was identical at 12 wk (mean serum FSH 1.2 and 1.6%, and mean LH 0.3 and 0.2% of baseline: TE vs. TE+ DMPA, respectively) as was sperm count suppression (5 of 5 and 4 of 5 men, respectively, with sperm counts < or =0.1 x 10(6)/ml). Serum inhibin decreased to 55% control at 12 wk in the TE+DMPA group (P < 0.05) but was unchanged by TE treatment (86% control, NS). Testicular T levels declined to approximately 2% of control levels, but testicular dihydrotestosterone and 5alpha-androstane-3alpha,17beta-diol (Adiol) levels were not different to control. Germ cell numbers as determined by stereological methods did not differ between TE and TE+DMPA except at 2 wk when type B spermatogonia and early spermatocytes were significantly lower in the TE+DMPA group (P < 0.05). In all groups, a marked inhibition of Apale-->B spermatogonial maturation was seen along with a striking inhibition of spermiation. We conclude that: 1) the addition of DMPA hastens the onset of FSH/LH suppression, correlating with a more rapid impairment of spermatogonial development, but in the longer term, neither germ cell number nor sperm count differed; 2) testicular dihydrotestosterone and Adiol levels are maintained during FSH/LH suppression despite markedly reduced T levels suggesting up-regulation of testicular 5alpha-reductase activity; and 3) spermatogonial inhibition is a consistent feature, but spermiation inhibition is also striking and is an important determinant of sperm output.

Adult↗
PubMed2002

Hypermethylation of the inhibin alpha-subunit gene in prostate carcinoma.

Inhibin is composed of an alpha- and a beta-subunit. Transgenic studies assigned a tumor-suppressive role to the inhibin alpha-subunit, and in human prostate cancer inhibin alpha-subunit gene expression was down-regulated. This study examined the inhibin alpha-subunit gene promoter and gene locus to determine whether promoter hypermethylation or LOH occurred in DNA from prostate cancer. The 5'-untranslated region of the human inhibin alpha-subunit gene was sequenced and shown to be highly homologous to the bovine, rat, and mouse inhibin alpha-subunit promoter sequences. A 135-bp region of the human promoter sequence that continued a cluster of CpG sites was analyzed for hypermethylation. Significant (P < 0.001) hypermethylation of the inhibin alpha-subunit gene promoter occurred in DNA from Gleason pattern 3, 4, and 5 carcinomas compared with nonmalignant tissue samples. A subset of the carcinomas with a cribriform pattern were unmethylated. LOH at 2q32-36, the chromosomal region harboring the inhibin alpha-subunit gene, was observed in 42% of prostate carcinomas. These data provide the first demonstration that promoter hypermethylation and LOH are associated with the inhibin alpha-subunit gene and gene locus in prostate cancer.

5' Untranslated Regions↗
PubMed2002

Induction of apoptosis in low to moderate-grade human prostate carcinoma by red clover-derived dietary isoflavones.

Epidemiological evidence suggests a geographical basis for the incidence of prostate cancer and dietary factors, including isoflavone consumption, may be linked to this phenomenon. This paper reports a nonrandomized, nonblinded trial with historically matched controls from archival tissue designed to determine the effects of acute exposure to a dietary supplement of isoflavones in men with clinically significant prostate cancer before radical prostatectomy. Thirty-eight patients were recruited to the study upon diagnosis of prostate cancer. Before surgery, 20 men consumed 160 mg/day of red clover-derived dietary isoflavones, containing a mixture of genistein, daidzein, formononetin, and biochanin A. Serum PSA, testosterone, and biochemical factors were measured, and clinical and pathological parameters were recorded. The incidence of apoptosis in prostate tumor cells from radical prostatectomy specimens was compared between 18 treated and 18 untreated control tissues. There were no significant differences between pre- and posttreatment serum PSA, Gleason score, serum testosterone, or biochemical factors in the treated patients (P > 0.05). Apoptosis in radical prostatectomy specimens from treated patients was significantly higher than in control subjects (P = 0.0018), specifically in regions of low to moderate-grade cancer (Gleason grade 1-3). No adverse events related to the treatment were reported. This report suggests that dietary isoflavones may halt the progression of prostate cancer by inducing apoptosis in low to moderate-grade tumors, potentially contributing to the lower incidence of clinically significant disease in Asian men. The assessment of new prostatic therapies aimed at increasing apoptosis should control for intake of dietary isoflavones.

Adenocarcinoma↗