Psma-Psa clones drived by full akt phosphorylation [t308+,s473+] recapitulate molecular features of human prostate cancer

Background: [PSMA+,PSA+] and [PSMA+,PSA-] are the two most individual clones that we have previously identified during prostate cancer [PC] progression. However, molecular signatures associated with these distinct PSMA-PSA prostate clones and their specific correlation with disease outcome is yet to be defined

Aim: Since Akt is a major pathway involved in the critical activating events that leads to malignant form of the disease, we studied the involvement of full Akt activation [T308+,S473+] connected with serum PSA levels, tissue PSMA expression and angiogenic activity on the emergence of [PSMA+,PSA+] and [PSMA+,PSA-] PC clones

Methods: The study was carried out in 6 normal prostate, 25 benign prostate hyperplasia [BPH] and 23 [PC]. Immunohistochemical analysis was performed to study the expression of PSMA, PSA, pAkt[T308], pAkt[S473] and CD34 in prostate tissues. The evaluation of angiogenesis was made by CD34 immune marker. Serum levels of PSA were assayed by Immulite autoanalyser

Results:The most relevant result showed that, among PC patients with pAkt [T308+,S473+] profile, patients that exhibit the [PSMA+,PSA+] clone have higher serum PSA levels, tissue PSMA expression and angiogenic activity than those with [PSMA+,PSA-] clone. Although have the same [PSMA+,PSA+] prostate clone, BPH patients have distinct molecular-biological features compared to PC patients among pAkt [T308+,S473+] profile. In fact, among patients with maximal Akt activation, the [PSMA+,PSA+] PC clone is characterized by higher serum PSA levels, tissue PSMA production and intensive angiogenic activity than [PSMA+,PSA+] BPH clone

Conclusion: These findings emphasize the potential role of the full Akt activation [T308+,S473+] in expansion of several PSMA-PSA prostate clones capable of driving both human PC initiation as well as progression to a metastatic phenotype. Pinpoint patients according to PSMA-PSA clones could recapitulate the histological and molecular features of human PC and may offer a novel approach for controlling metastasis

Cellular distribution and heterogeneity of PSA and PSMA expression in normal, hyperplasia and human prostate cancer

As promising targets for in vivo diagnostic, prognostic and therapeutic approaches, the distribution and staining pattern of prostate specific antigen [PSA] and prostate specific membrane antigen [PSMA] in tumors are of significant interest. To compare the cellular distribution and heterogeneity of PSA and PSMA expression in normal prostate [NP], benign prostatic hyperplasia [BPH] and primary prostatic tumors and to analyze their relation with the angiogenic activity according to Gleason grade [low, medium and high] in primary PC. The study was carried out in 6 NP, 44 BPH and 39 PC. Immunohistochemical analysis was performed. Monoclonal antibodies 3E6 and ER-PR8 were used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis was made by CD34 immune marker. In our study we noticed differences in the intracellular localization of the PSMA immunostaining which seem to be related to the normal and pathological context. A significant number of primary tumors presented with apical pattern of PSMA [28/39]; whereas a relevant part of NP samples and BPH samples showed cytoplasmic localization [4/6 and 30/44, respectively] in luminal epithelial cells. Compared to PSMA, PSA was preferentially localized in cytoplasmic compartment in all type of prostate. A direct correlation between histological grade, PSMA expression and angiogenic activity could be demonstrated in primary PC. Simultaneous stains with PSA and PSMA in individual prostate tissue will greatly improve the detection rate and identify a high risk PC that could progress to metastatic phenotype. Our findings clearly support the feasibility but also direct the potential of PSMA-targeted in vivo therapeutic approaches in PC patients rather than PSA especially those with poorly differentiated adenocarcinoma

Hydrated sodium calcium aluminsilicate protects against genotoxic effects in zeralenone-treated balb/C mice

Zearalenone [ZEN] is a potent estrogenic metabolite mycotoxin produced by some Fusarium species. Few studies have been successfully employed to get rid of the ZEN contamination in foods. This study was conducted to evaluate the ability of hydrated sodium calcium aluminsilicate [HSCAS] to protect Balb/c mice against cytotoxicity and genotoxicity induced by ZEN. Mice were divided into nine experimental groups [12 mice/group] included the control group, the olive oil group, the groups treated orally with a single dose of HSCAS at doses level of 400, 600 and 800 mg/kg b.w, the group treated orally with a single dose of ZEN [40 mg/kg b.w], the group treated with ZEN plus HSCAS [400 mg/kg b.w], the group received Colchicin [4 mg/kg bw] as a positive control for micronucleus assay and the group treated with mitomycin C [1 mg/kg bw] as a positive control for chromosome aberrations assay. Forty eight hours after treatment, the femur and tibia were dissected out and bone marrow was obtained for different assays. The results showed that ZEN was cytotoxic and genotoxic to Balb/c mice as indicated by the increase in frequencies of polychromatic erythrocytes micronucleated [PCEMN] and chromosomal aberrations in bone marrow cells. The simultaneous administration of HSCAS with ZEN resulted in a decrease of PCEMN number and chromosomal aberrations frequency and increased the polychromatic erythrocytes [PCE] in bone marrow cells compared with the ZEN alone group. It could be concluded that HSCAS itself was safe at different tested doses and efficient in the prevention of ZEN induced clastogenicity in mice at a dose level as low as 400 mg/kg b.w