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Immune evaluation with skin testing. A study of testicular, prostatic, and bladder neoplasms.

Fifty patients with testicular carcinoma, 45 with prostatic neoplasm, 84 with bladder carcinoma, and 13 with benign bladder papilloma were evaluated for skin reactivity to DNCB and other intradermal antigens. Correlation between pathologic staging and skin-test reactivity was sought. Reaction to DNCB among patients with testis tumors was more significantly depressed by chemotherapy than by the extent of retroperitoneal or distant metastatic disease indicating that skin testing as a means of following the course of disease or of predicting survival may be limited by alterations caused by chemotherapy. DNCB reactivity did not correlate with the prognosis for the different stages of disease, but follow-up studies of individual patient survival are needed for substantiation. Depression of DNCB reactivity exists among patients with prostatic carcinoma whether the disease is localized or widely metastatic. Only lengthy follow-up will determine if there is any correlation of reactivity with survival in individual patients. DNCB reactivity among patients with bladder tumors shows progressive reduction with increasing stage disease and lends support to the evidence suggesting immune deficiency in patients with bladder neoplasm.

Adolescent↗

Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: role in vasculogenic mimicry.

BACKGROUND: Tumor cell plasticity represents a significant clinical challenge in that the fate and function of tumor cells can be elusive until a tumor mass is evident. A remarkable example of plasticity is tumor cell vasculogenic mimicry, recently described in aggressive uveal and cutaneous melanoma, in addition to ovarian carcinoma, whereby tumor cells express endothelial-associated genes and form de novo vasculogenic-like networks in three-dimensional (3-D) culture. In the current investigation, we examined whether there is evidence for vasculogenic mimicry in heterogeneous prostatic neoplasms. METHODS: Dunning rat and human prostate cancer cell lines (comprised of epithelial- and fibroblastic-like tumor subpopulations) were tested for their ability to express selected endothelial-associated genes, laminin, the alpha6beta1 laminin-binding integrin, and for their potential to form perfusable tubular networks in 3-D culture. Simultaneous morphological analysis of tumor-lined channels in rat and human tumors was also performed. RESULTS: Green fluorescent protein labeling of prostatic clonal subpopulations revealed unique cooperative interactions of epithelial- and fibroblastic-like tumor cells in the formation of perfusable vasculogenic-like networks. Furthermore, while these cell lines were shown to express various vascular markers, prostatic tumor cell-lined channels were also detected in vivo in high grade tumors, and occurred in some cases in close proximity to conventional endothelial-lined vasculature. CONCLUSIONS: A multidisciplinary approach to assess vasculogenic mimicry by prostatic tumor cells has revealed supportive evidence that it occurs in invasive, heterogeneous prostate cancer cell lines, and circumstantially in aggressive rat and human tumors. These results reflect the plasticity of aggressive prostatic tumor cells and may provide new prognostic markers for clinical diagnosis and new therapeutic intervention strategies.

Animals↗

Prostatic and laryngeal malignancies: common or uncommon multiple occurrence?

The presence of multiple primary malignancies involving the head and neck has been well documented. The majority of second primaries appear within the respiratory system. Few reports exist describing multiple primary malignancies involving the larynx and the prostate. This paper reports on four cases of primary laryngeal and prostatic neoplasms. Physical findings and laboratory work-up necessary for diagnosis of these lesions are reviewed. The dilemma of the proper therapeutic course based on the histological grading and pathological staging is presented. Suggestions for treatment based on the prognosis of the disease that is present are offered.

Adenocarcinoma↗

Lack of modifying effects of 4-ter t-octylphenol and benzyl butyl phthalate on 3,2-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in rats.

The modifying effects of dietary feeding of two estrogenic compounds, 4-tert-octylphenol (tOP) and benzyl butyl phthalate (BBP), on 3,2-dimethyl-4-aminobiphenol (DMAB)-induced prostatic carcinogenesis were investigated in male F344 rats. We also assessed the effects of the test compounds on the proliferating cell nuclear antigen (PCNA) index in induced neoplasms, prostatic intra-epithelial neoplasm (PIN), and non-lesional glands in the prostate. To induce prostatic neoplasms, rats were given subcutaneous injections of DMAB (25 mg/kg body weight) every other week, 10 times in total. They also received the experimental diet containing 10 or 100 ppm tOP and BBP for 40 weeks, starting 1 week after the last dosing of DMAB. DMAB exposure produced prostatic adenocarcinoma with an incidence of 41.2% at the end of the study (week 60). Dietary administration of tOP and BBP did not affect the incidence of prostatic adenocarcinoma: 43.8% in the DMAB --> 10 ppm tOP group; 25.0% in the DMAB --> 100 ppm tOP group; 43.8% in the DMAB --> 10 ppm BBP group; and 43.8% in the DMAB --> 100 ppm BBP group. The PCNA indices in adenocarcinomas, PIN, and non-lesional glands in rats treated with DMAB and tOP or BBP were slightly lower than that of the DMAB alone group, but the differences were not statistically significant. These results might suggest that dietary feeding of the estrogenic compounds tOP and BBP did not modulate DMAB-induced prostatic carcinogenesis in rats.

Adenocarcinoma↗

[The role of prostate specific antigen and its derivatives (age-specific PSA, PSA density, velocity, free/total PSA) in the diagnosis of prostate cancer].

PSA is the most useful tumor marker for the diagnosis and treatment of prostate cancer. Its clinical use, however, still lacks the necessary sensitivity and specificity to be considered as ideal. In fact PSA is not specific for adenocarcinoma of the prostate: an elevated serum level of the marker does not necessarily mean malignant growth and normal levels too often hide an occult and potentially lethal cancer. With the discovery of different molecular PSA forms in the serum, an improved discrimination between benign prostate hyperplasia (BPH) and prostate cancer appears possible. This may be particularly useful in cases with equivocal PSA values and unpalpable prostate neoplasm to reduce the number of unnecessary prostate biopsies and increase the number of biopsies in cases without palpable or ultrasonic visible anomalies. The clinical use of PSA age-referenced levels is discussed. Their use is invaluable in screening programs where the routine adoption of age-specific values can help to pick-up younger patients with potentially curable prostate cancer and older patients with BPH where additional tests would be unnecessary. The role of PSA velocity (PASAV) s also discussed. An elevation rate of PSA of 0.75 ng/ml over 18 months on 3 serial samples appears to be the best cut-off to distinguish BPH from prostate cancer. However, the use of PSAV seems to be less useful in patients with elevated PSA levels and negative biopsy results. Free to total PSA ratio is probably the best parameter to reduce the number of unnecessary biopsies in men with a serum total PSA of 4 to 10 ng/ml. The advantages and limitations for different levels of cut-off are shown. A flow chart illustrating the role of various PSA "derivatives" in screening and subsequent evaluation of men over 50 years of age is also presented.

Age Factors↗

Zinc concentration in human prostatic fluid: normal, chronic prostatitis, adenoma and cancer.

Radionuclide induced energy dispersive X-ray fluorescence was used to estimate zinc content in prostatic fluid in normal, chronic prostatitis, adenoma and cancer cases, Groups of patients suffering from chronic prostatitis, adenoma and malignant tumours consisting of 28, 28 and 13 men, respectively, were examined. The control group included 22 healthy volunteers. Expressed prostatic fluid was obtained by digital rectal massage. The zinc concentration of intact prostatic fluid was 590 +/- 45 (SE) micrograms/ml. Almost no difference was found between the zinc concentration for chronic prostatitis and for adenoma, and those for normal levels being 455 +/- 60 (SE) and 540 +/- 50 (SE) micrograms/ml, respectively. Prostatic neoplasm resulted in a significant decrease of zinc secretion, with the concentration averaging 34.7 +/- 9.6 micrograms/ml, p < 0.000001.

Adult↗

Access of tumor-derived macromolecules and cells to the blood: an electron microscopical study of structural barriers in microvessel clusters in highly malignant primary prostate carcinomas.

BACKGROUND: The neo-angiogenetic microvessels forming a major reactive stromal element in highly malignant prostate neoplasms may exhibit fine-structural features relevant to our understanding of the passage of macromolecules from tumor to blood, on the one hand, and of events facilitating the metastatic cascade, on the other hand. METHODS: Ensuring rapid, optimal fixation in buffered glutaraldehyde was a foremost concern. Thin parings from radical prostatectomy specimens of Gleason scores (GS) 5-9 were taken from the tumor and from the contralateral side of the gland, glutaraldehyde-fixed, diced to smaller than 1 mm(3), postfixed in osmium tetroxide, embedded in Epon, ultrathin-sectioned, contrasted with lead and uranyl salts, and viewed in a transmission electron microscope. RESULTS: In dysplastic tissue areas, intraductal microvessels located in gland ducts were occasionally observed, and found to be aggressively invasive and highly active in producing neo-angiogenetic sprouts. Closely spaced microvessel clusters contained almost exclusively neo-angiogenetic microvessels, which were in cell-cell contact with numerous ameboid migratory cells, some of which were likely to be tumor cells. In these microvessel clusters, all structural barriers hindering passage of tumor-derived molecules or cells to the blood were eliminated. CONCLUSION: In microvessel clusters, the ultrastructural equivalent of microvascular hotspots, tumor invasion of microvessels is facilitated, but equally microvessels are observed invading the gland duct epithelial walls. This reciprocal invasivity of tumor cells and microvascular endothelial cells generates ideal conditions for tumor products and metastatic cells to enter the blood.

Aged↗

Paneth cell-like change and small cell carcinoma of the prostate. Two divergent forms of prostatic neuroendocrine differentiation.

Paneth cell-like change of the prostate refers to collections of prostatic cells with eosinophilic cytoplasmic granules that bear a striking histological resemblance to normal intestinal Paneth cells. Paneth cell-like change in malignant prostatic epithelium usually represent neuroendocrine differentiation, with neuroendocrine granules confirmed by immunohistochemical and ultrastructural studies. We report the histopathological, immunohistochemical, and electron microscopic findings in a mixed adenocarcinoma with Paneth cell-like change and small cell undifferentiated carcinoma. This case illustrates two divergent forms of neuroendocrine differentiation occurring in a single prostatic neoplasm. The spectrum of neuroendocrine differentiation in the prostate should be expanded to include tumors with Paneth cell-like change in addition to carcinoid tumors and small cell undifferentiated carcinoma. These three distinct forms of prostatic neuroendocrine neoplasia appear to correlate with three size ranges of neuroendocrine granules seen by electron microscopy.

Adenocarcinoma↗

CYTOLOGY OF THE PROSTATE.

A series of prostates has been studied cytologically by making smears directly from surgically excised glands. The cytological findings in these smears are described. Benign conditions of the prostate can be readily diagnosed by this means but it is not a satisfactory method for finding latent carcinomas. In addition, the cells in the smears obtained from the excised glands were compared with the cells found in smears obtained by prostatic massage from a series of patients attending with prostatic disorders. It was found that direct smears from prostatectomy specimens give a useful indication of the types of benign cells which may be found in smears obtained by massage. They provide help in the differentiation of malignant from benign epithelium in the massage specimens although they give little indication of the appearances of the malignant cells themselves.

Cytodiagnosis↗

Melengestrol acetate and megestrol acetate are prostatic tumor inhibiting agents.

We had previously reported that 6-methylene progesterone, an inhibitor of 5 alpha-reductase, the enzyme which converts testosterone to dihydrotestosterone, markedly inhibited growth of the androgen-dependent Dunning R3327-H rat prostatic tumors. We now find that the progesterone derivatives melengestrol acetate (MGA) and megestrol acetate (MA) inhibit both the androgen-dependent (Dunning R3327-H) and the androgen-independent (Dunning R3327-AT3) prostatic tumors. Growth of the AT3 tumors was suppressed by approximately 53% after 9 days of daily s.c. injections with MGA at 10 mg/kg body weight. MGA also caused a 54% weight reduction of the ventral prostate and a 53% reduction of the seminal vesicles. Adrenal weights were reduced by 42%. A 24-day oral treatment with MGA (at approximately 15-17 mg/(kg.day)) inhibited AT3 tumor growth by 59% and caused a weight reduction in the following tissues: prostate (46%), seminal vesicles (19%), testes (12%), and adrenals (52%). Under the same protocol, MA inhibited AT3 tumor growth by 32% and reduced the weight of the ventral prostate by 49% and the weight of the adrenals by 18%, but had no effect on the seminal vesicles and testes. The extent of the MGA-induced prostatic regression was accompanied by cytological changes similar to those effected by 6-methylene progesterone, i.e., shrinking of the acinar epithelium. The AT3 tumors in MGA-treated rats displayed a limited degree of apoptosis. Atrophy of the adrenal cortex and lowered plasma levels of corticosterone and dihydroepiandrosterone were also observed. A therapeutic role for MGA and MA against androgen-independent prostatic neoplasms in man is forecast by these observations.

Adrenal Glands↗