Udo Dunzendorfer

Polyamines, hydrolases (PAP, LAP, SDH, plasmin) TSH, T3, T4 and C-peptide in benign hyperplasia of the prostate

SummaryHigh concentrations of polyamines have been found in the normal human prostate. The profile of these amines appeared significantly changes in benign hypertrophy of the prostate. An increase of spermine and a fall of putrescine were always found in patients with a hypertrophied prostate weighing more than 30 g. Alterations of plasmin in these tissues seemed to reflect changes in the matrix; abnormalities of thyroid and pancreatic function documented by changes in the serum levels of TSH and c-peptide which are thought to be further evidence of a mesenchymal-epithelial interaction in the pathogenesis of benign prostate hypertrophy.

13,14-Dihydro-15-keto-prostaglandin F2α in Patients with Urogenital Tumors

13,14-Dihydro-15-keto-prostaglandin F2α (13,14-DHK-PGF2α) represents a stable product of degradation after pulmonary flow and it is shown to be reliably measured by radioimmunoassay. In patients with urogenital tumors, serum levels of 13,14-DHK-PGF2α are distinctly elevated when compared to a control group. The rate of synthesis of this compound in urogenital tumors, however, appears to be different.

New Results on the Pharmacokinetics of Fosfestrol

For more than 30 years Fosfestrol (Honvan®) has been used as an estrogen for successful palliative therapy of prostatic carcinoma, but the pharmacokinetics of this compound were unknown due to the lack of analytical methods. Over the last few years we have developed a special extraction process for Fosfestrol and its metabolites from plasma with recovery yields > 90%. The simultaneous measurement of the most important compounds after intravenous and oral administration was achieved by high-performance liquid chromatography, either with the UV detector (236 nm) or with an electrochemical detector (+ 1 V). The working electrode is a carbon paste electrode constructed in this laboratory; the counter electrode is an Au and the reference electrode an Ag/AgCl electrode. The electrode processes have been clarified. Fosfestrol and its monophosphate exist only for a short time in small amounts in the circulating blood after intravenous administration, whilst after oral administration, not even traces of the phosphates could be detected in the plasma. The most important influence on plasma levels of Fosfestrol and its metabolites is due to the extraction function of the liver. Diethylstilbestrol conjugates enter into the enterohepatic circle, thus forming a possible source of DES available over more than 24 h. Only DES glucuronide and DES glucuronide-sulphate are renally eliminated and could be detected after administration over 3 days.

Polyamine, Polyaminantimetaboliten und urogenitale Tumoren

The polyamine metabolism is pathologically changed in tumor tissues, and especially putrescine and spermidine demonstrate abnormally high values in kidney, bladder, and prostate cancer. The inductive processes which activate the biosynthetic polyamine enzymes in cancer are completely unknown. Of therapeutic interest is the fact that increased enzyme activities through irreversible inhibitors become significantly reduced, which consequently slows the tumor growth. Experimental therapy, especially in transplantable bladder and prostate cancer, displayed a 50% tumor destruction. In clinical studies using inhibitors of the polyamine biosynthesis, the dose had to be significantly reduced because of expressed toxicity. Additional investigations which tried a combination of reversible and irreversible inhibitors proved a similar antitumor activity, but less severe side effects.

The Effect of Alpha-Difluoromethyl-Ornithine on Tumor Growth, Acute Phase Reactants, Beta-2-Microglobulin and Hydroxyproline in Kidney and Bladder Carcinomas

Multiple oral doses of alpha-difluoromethyl-ornithine (alpha-DFMO), 18-24 g/day for up to 2 months, were administered to 2 patients with invasive and metastatic carcinoma of the bladder and to 3 patients with metastatic renal cancer in an open study. The moderate antigrowth effect of alpha-DFMO in these patients was concluded from the results of serial kidney, liver and bone scintigrams, from the low frequency of a local recurrence of bladder carcinoma and from the survival rate of 4 of 5 patients after 12 months. Increased excretion of hydroxyproline and beta2-microglobulin were measured 1 month following alpha-DFMO treatment suggesting initial tumor necrosis and degradation. Treatment was poorly tolerated with gastrointestinal side effects (e.g. gastritis, vomiting, diarrhea) in all subjects, erythropenia in 2 subjects (associated with thrombocytopenia and leucopenia in 1 subject each), and audiovestibular symptoms in 2 patients. All side effects were reversible and normal function returned 2-4 months after stopping therapy.

Diethylstilbestrol-Diphosphate, Fosfestrol ‘Reevaluated’

Primary therapy of metastatic prostate cancer (stage D2, pT3N1M1, GII/III) consists either of orchiectomy/1.0 g/m2 diethylstilbestrol-diphosphate

Quantification of Alpha-Fetoprotein and Beta-HCG in Testis Tumor Patients

Patients with testis tumor were investigated for serum and tissue levels of alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG). The tissue immune peroxidase-antiperoxidase staining for the tumor marker was quantitated by computer-assisted immunohistophotometry and immuno-gamma ray histospectrometry. The results supported the general view that mostly polynuclear giant cells produce beta-HCG in 66% of nonseminoma cancer. This finding qualifies beta-HCG as relatively unspecific in the absence of chorioepithelial cells in the tumor. Discrepancies of tissue and serum beta-HCG values may be caused by deglycolysation of beta-HCG while penetrating the perivascular tissues. Alpha-fetoprotein (AFP) appears helpfully to discriminate the true seminoma cancer, which is constantly negative. Histologically pure seminoma which reacts for AFP therefore suggests sclerotic teratoma compartments. A constant finding is the significantly reduced synthesis rate of tumor markers in metastasis compared to primary tumor.

Therapie des Prostatakarzinoms mit Polyaminsyntheseinhibitoren

The therapeutic concept of irreversible inhibition of both ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) by alpha-difluoromethylornithine (DFMO) and methylglyoxal bis-gu

Prolactin, LH, TSH, T3 and T4 in patients with urogenital carcinomas.

Serum level of peptide hormones LH, FSH, TSH and prolactin have been measured in patients with urogenital tumor. In this randomized study we found a frequent elevation of TSH and prolactin, which did not correlate. Increased serum level of TSH was confirmed to be without any elevation of serum T3 and T4. In some of these patients ectopic production of peptides may account for this abnormality. Systemic change of peptides in elderly patients, however, must be taken into consideration as well.