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C Seitz

Publications and source records attributed to C Seitz.

At least 19 recordsLinked to original sources
PubMed2004

[Chemoprevention of prostate cancer].

Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, i.e., the administration of agents that inhibit one or more steps in the natural course of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe. Published studies were identified in a search of MEDLINE. Information about ongoing studies was provided by author access to protocols. A variety of chemoprevention studies have focused on the role of dietary factors, vitamins, and trace elements in prostate cancer. Some of these studies have been prospective, randomized, and double-blinded, while others have used retrospective or epidemiological approaches. Large-scale randomized studies are also evaluating the role of 5alpha-reductase inhibitors, which inhibit the conversion of testosterone to the more potent androgen dihydrotestosterone. Robust evidence is lacking for the value of chemopreventive agents in prostate cancer. Current evidence does suggest that vitamin E and selenium may have a role in prostate cancer chemoprevention. Data from two studies, one examining the type 1 5alpha-reductase selective inhibitor finasteride and the other using the dual 5a-reductase inhibitor dutasteride, will determine the benefits of androgen inhibition strategies for prostate cancer chemoprevention.

Anticarcinogenic Agents↗
PubMed2003

Can total and transition zone volume of the prostate determine whether to perform a repeat biopsy?

OBJECTIVES: To compare the ability of total prostate (TP) and transition zone (TZ) volume to predict the outcome of a repeat prostate biopsy in patients with serum prostate-specific antigen (PSA) levels of 4 to 10 ng/mL. METHODS: A total of 1137 patients were included and underwent transrectal ultrasound-guided needle sextant and two transition zone biopsies of the prostate. All patients with a prior negative biopsy (benign prostatic tissue) underwent a repeat biopsy after 6 weeks. The TP and TZ volumes of the prostate were measured by transrectal ultrasonography. RESULTS: Of the 1137 patients, prostate cancer was diagnosed in 364 (32%), in 276 (24.2%) after the first biopsy and in 88 (7.7%) after the repeated biopsy. The TP and TZ volumes were larger in the patients with prostate cancer detected on the repeated biopsy (P <0.0001). Using a cutoff for TP volume of less than 20 cm3 and greater than 80 cm3 and for TZ volume of less than 9 cm3 and greater than 41 cm3 would have spared 7.1% and 10% of repeated biopsies, respectively. CONCLUSIONS: The probability for a positive repeat prostate biopsy increases in a logarithmic function for larger prostates, as well as for larger TP and, especially, for larger TZ volumes. The probability of finding prostate cancer on a repeat biopsy in prostates with small (less than 20 cm3) and large (greater than 79 cm3) TP, as well as in small (less than 9.3 cm3) and large (greater than 41 cm3) TZ volumes, was very low. Therefore, a repeat prostate biopsy within 6 weeks is unnecessary. These patients should be followed up by serial PSA determination.

Aged↗
PubMed2003

Heat versus drugs in the treatment of benign prostatic hyperplasia.

The improvement in symptoms and voiding function is greater with transurethral microwave thermotherapy than with drug therapy, and the associated morbidity is low. Transient urinary retention necessitating catheterization is of short duration after targeted microwave thermotherapy. The short-term effect of microwave thermotherapy can be improved by neoadjuvant and adjuvant alpha-blockade. Microwave treatment offers greater versatility than drug therapy, allowing patients with severe baseline symptoms and small prostates to be treated successfully. Medical management improves symptoms to a more modest extent than does microwave treatment. Finasteride gives comparatively small symptom and flow rate improvements and requires several months for the maximum responses. With alpha-blockers the onset of action is fast and side-effects reversible, although they limit their utility. Finasteride or alpha-blockers must be continued indefinitely to maintain improvements in patients with BPH, but they have a favourable safety and tolerability profile.

5-alpha Reductase Inhibitors↗
PubMed2003

Prostate biopsy.

Transrectal ultrasound guided (TRUS) prostate biopsies is the standard method in the diagnosis of prostate cancer. The use of prostate specific antigen (PSA) and digital rectal examination for prostate cancer screening has led to a dramatic increase in the number of TRUS guided biopsies. Frequently urologists are faced with the dilemma of treating a patient with a high suspicion of prostate cancer, but an initial set of negative biopsies. In this review we focus on the current knowledge of prostate biopsies, the indication to perform a biopsy, the impact of prostate volume in the number of cores taken, the technique of an initial and repeat biopsies and when to stop.

Biopsy, Needle↗
PubMed2001

A novel p75TNF receptor isoform mediating NFkappa B activation.

We report the identification of a novel p75TNF receptor isoform termed icp75TNFR, which is generated by the use of an alternative transcriptional start site within the p75TNFR gene and characterized by regulated intracellular expression. The icp75TNFR protein has an apparent molecular mass of approximately 50 kDa and is recognized by antibodies generated against the transmembrane form of p75TNFR. The icp75TNFR binds the tumor necrosis factor(TNF) and mediates intracellular signaling. Overexpression of the icp75TNFR cDNA results in TNF-induced activation of NFkappaB in a TNF receptor-associated factor 2 (TRAF2)-dependent manner. Thus, our results provide an example for intracellular cytokine receptor activation.

Alternative Splicing↗
PubMed2001

Insulin-like growth factors and prostate cancer.

Prostate cancer is one of the most common malignant tumors in Western countries. The etiology of prostate cancer is currently unknown, but it has been suggested that growth factor abnormalities may be involved in initiation and progression of this disease. Insulin-like growth factors (IGFs), including IGF-1 and IGF-2, are mitogenic peptides involved in the regulation of cell proliferation, differentiation and apoptosis. Studies have shown that IGFs are potent mitogens for a variety of cancer cells including prostate cancer since they stimulate cancer cell growth and suppress programmed cell death. This review outlines elements of IGF pathophysiology, reviews recent evidence that circulating IGF-1 levels are related to prostate cancer risk and discusses the clinical implications of these lines of research with respect to prevention and treatment.

Humans↗
PubMed2001

Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months.

OBJECTIVES: To compare directly the efficacy, safety, and durability of targeted transurethral microwave thermotherapy with that of alpha-blocker treatment for lower urinary tract symptoms of benign prostatic hyperplasia. METHODS: In a randomized, controlled clinical trial, 52 patients with lower urinary tract symptoms due to benign prostatic hyperplasia received terazosin treatment and 51 underwent microwave treatment under topical anesthesia. The patient evaluation included the International Prostate Symptom Score, peak flow rate, and quality-of-life score before microwave treatment or initiation of terazosin treatment and at periodic intervals thereafter up to 18 months. RESULTS: The mean International Prostate Symptom Score, peak flow rate, and quality-of-life score all improved significantly in both groups by 6 months. However, the magnitude of improvement was significantly greater in the microwave group than in the terazosin group. The significant between-group differences observed at 6 months in the mean International Prostate Symptom Score, peak flow rate, and quality-of-life score were fully maintained at 18 months, at which time the improvements in these three outcome measures were significantly greater (P <0.0005), by 35%, 22%, and 43%, respectively, in the microwave group than in the terazosin group. The actuarial rate of treatment failure at 18 months was significantly greater by sevenfold in the terazosin group. Adverse events were generally infrequent and readily manageable in both groups. CONCLUSIONS: Although the initial onset of terazosin action was more rapid, the longer term clinical outcomes of targeted microwave treatment were markedly superior. The more favorable results in patients who underwent microwave treatment were maintained for at least 18 months.

Adrenergic alpha-Antagonists↗
PubMed2001

Hypoxic upregulation of TNF receptor type 2 expression involves NF-IL-6 and is independent of HIF-1 or HIF-2.

Tumor necrosis factor (TNF) exerts its biologic activity via two distinct membrane receptors, TNF receptor type 1 (p55TNFR) and TNF receptor type 2 (p75TNFR). Whereas the p55TNFR gene is rather constitutively expressed, transcription of p75TNFR is strongly modulated by a number of stimulatory agents. Experimental evidence suggested the involvement of p75TNFR in endothelial cell activation. Therefore, we have tested the transcriptional activity of p75TNFR under conditions of hypoxia and reoxygenation. Northern blot analysis revealed that p75TNFR mRNA is upregulated in NIH3T3 cells under hypoxia and reoxygenation. This observation directly originates from transcriptional activation of the p75TNFR gene, as shown by reporter gene analysis. Cotransfection experiments clearly showed that the transcriptional induction of the p75TNFR gene is independent of the hypoxia-induced factors, HIF-1alpha and HIF-2alpha. Using deletion mutants of the 5'-flanking region of the p75TNFR gene, we were able to identify a putative DNA binding site for the transcription factor nuclear factor-interleukin-6 (NF-IL-6) to be responsible for the transcriptional upregulation of the p75TNFR gene under conditions of hypoxia and reoxygenation.

3T3 Cells↗
PubMed2001

Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study.

PURPOSE: We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. MATERIALS AND METHODS: In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. RESULTS: Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. CONCLUSIONS: Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

Aged↗
PubMed2001

Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop?

PURPOSE: We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate biopsy 1. MATERIALS AND METHODS: In this prospective European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies. All patients in whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localized cancer underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Overall, of the patients with clinically localized disease, which was 67% of cancers detected, 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectively. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, there were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), respectively. CONCLUSIONS: Despite differences in location and multifocality, pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar, suggesting comparable biological behaviors. Cancer detected on biopsies 3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.

Aged↗
PubMed2000

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.

Adolescent↗
PubMed2000

Pretreatment prostate-specific antigen as an outcome predictor of targeted transurethral microwave thermotherapy.

OBJECTIVES: To evaluate pretreatment serum prostate-specific antigen (PSA) as an outcome predictor of targeted microwave thermotherapy. METHODS: Seventy-one patients with lower urinary tract symptoms of benign prostatic hyperplasia underwent targeted transurethral microwave thermotherapy using the Targis system. Outcomes 12 months after treatment were evaluated by the International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and quality-of-life (QOL) score. The ability of PSA to predict outcomes was evaluated by linear and logistic regression and receiver operating characteristic curve analysis. RESULTS: Higher pretreatment PSA levels were significantly predictive of an absolute IPSS change of -7.5 or less for patients with moderate baseline symptoms or - 15 or less for those with severe baseline symptoms; an absolute Qmax change of 5 mL/s or greater; an absolute QOL score change of -3 or less; an IPSS at 12 months of 7 or less; a Qmax at 12 months of greater than 12 mL/s; and a QOL score at 12 months of 1 or less. Nevertheless, even without taking pretreatment PSA into account, most patients benefitted substantially from targeted microwave thermotherapy. Thus, 74%, 71%, and 79% of all eligible patients improved 50% or more in IPSS, Qmax, and QOL score, respectively, at 12 months compared with baseline. No significant association between PSA and either prostate or transition zone volume could be demonstrated. CONCLUSIONS: Most patients benefit substantially from targeted microwave thermotherapy. However, higher PSA levels are significantly predictive of more favorable outcomes. This association may reflect patient-to-patient differences in the relative abundance of PSA-producing epithelial cells in the transition zone of the prostate.

Aged↗
PubMed2000

Structurally diverse forms of HLA-B27 molecules are displayed in vivo in a cell type-dependent manner.

The formation of a trimeric complex, composed of heavy chain (HC), beta(2)-microglobulin (beta(2)m) and antigenic peptide, is generally believed to be a prerequisite for the expression of HLA class I molecules at the cell surface in vivo. Therefore, a possible role in immunological processes for HC/beta(2)m complexes devoid of peptide has not been seriously considered. Using a novel HLA-B*2705-transgenic rat model and monoclonal antibodies that distinguish between structurally different forms of HLA-B27 molecules, we demonstrate here that class I molecules which appear to lack antigenic peptides are expressed in abundance on a variety of cell types in lymphoid organs. These results imply a role for structurally diverse, possibly empty, MHC molecules in physiological T cell selection which has so far not been sufficiently appreciated.

Amino Acid Sequence↗
PubMed1999

Elastin gene expression in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly a stromal process, showing an increased ratio of stromal to epithelial elements, a collagen type III downregulation, and a collagen types I and IV upregulation. Little is known about elastin gene expression in BPH tissues due to difficulties related to extensive alternative splicing of the elastin gene. Therefore, we analyzed and quantified elastin gene expression in BPH. METHODS: A competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR) quantitative technique was used, and a quantitative elastin mRNA analysis with normal (n = 10) and BPH (n = 12) tissues was performed with two newly designed elastin primers. Small tissue samples (4-8 mg) were homogenized and sonicated, and cDNA was synthesized from mRNA using a RT reaction. Various target (wild-type) elastin cDNAs with unknown concentrations were competitively coamplified with known serial dilutions of the control mutant template, differing from the target cDNA by a short deletion. Gel fractions and computerized densitometry, were performed and cDNA concentration was calculated by linear regression. RESULTS: The primers identified in our study (BOB-1 and BOB-2) accurately amplified a consistent length of the elastin cDNA, avoiding areas of alternative splicing. The average elastin mRNA concentration in BPH tissues was 53 attomole/mg +/- 11.6 vs. 140.6 attomole/mg +/- 19.6 in normal prostatic tissue (P = 0.019). The variation within every sample was less than 10%. CONCLUSIONS: Our observations suggest a significant downregulation (70%) of the elastin mRNA gene in the transition zone of BPH patients.

Aged↗
PubMed1999

Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial.

OBJECTIVES: Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS: In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS: Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS: Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.

Adrenergic alpha-Antagonists↗
PubMed1999

High-energy transurethral microwave thermotherapy in patients with acute urinary retention due to benign prostatic hyperplasia.

OBJECTIVES: To evaluate the efficacy and safety of targeted high-energy transurethral microwave thermotherapy (HE-TUMT) in the treatment of acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH). METHODS: In this prospective cohort study, 31 patients with painful AUR due to BPH underwent HE-TUMT. Patient evaluation before treatment and during a 12-week follow-up interval included determination of International Prostate Symptom Score (IPSS), quality of life (QOL) score, peak flow rate (Qmax) by uroflowmetry, and postvoid residual urine. Patients also underwent urodynamic evaluation before treatment and at 16 weeks. RESULTS: By 4 weeks after HE-TUMT, 29 (94%) of 31 patients had regained the ability to void spontaneously. The actuarial median time for restoration of spontaneous voiding was 3.0 weeks (95% confidence interval [CI] 2.2 to 3.8). At 12 weeks, the mean IPSS (9.4; 95% CI 8.3 to 10.5) was 50% below (P <0.0005) that before retention (18.9; 95% CI 18.2 to 19.6). Improvements in the mean QOL score were similar in pattern and relative magnitude to those in the mean IPSS. A 69% increase in mean Qmax (P <0.0005) determined by uroflowmetry was observed by 12 weeks versus 1 week after HE-TUMT. Complications were infrequent. CONCLUSIONS: This study provides preliminary evidence that HE-TUMT may potentially afford a novel and useful option for the patient with AUR who is not a suitable candidate for surgery.

Acute Disease↗