Rat Prostate Research Articles

Histological and Histochemical Changes Induced by Human Chorionic Gonadotropin on Prostate of Adult albino Rats

Aims of the study: To evaluate the histological and histochemical changes induced by human chorionic gonadotropin (hCG) on the adult prostate and to correlate the changes with the levels of testosterone. Materials and Methods: eighty adult male albino rats were divided into 4 groups; 3 treated and 1 control. The treated groups were received 10, 50 or 100 IU/kg BW of hCG, while the controls received normal saline. The doses were given twice weekly for 3 months via subcutaneous injections. Subsequently, on day 1, 30, 60 and 90 post therapy, blood samples and the prostate glands were obtained for evaluation. Results: All the doses of hCG caused accumulation of secretory products within the prostate, which resulted in dilatation of the acinar lumens, reduction of the mucosal folds, and non dose dependent diminution in height of the lining epithelial cells. Moreover, foci of hyperplasic cells were observed in the prostate. The therapy increased the collagen fibers of the gland. The general distribution of the Periodic Acid-Sciff (PAS) +ve material was not altered. Most of these changes were reversible within 3 months. Conclusions: Treatment with hCG causes accumulation of secretory products within the prostate and in turn affects the structure of the prostate.

Endogenous hydrogen sulfide can function as a relaxation factor in the bladder and prostate of male rats

Endogenous hydrogen sulfide can function as a relaxation factor in the bladder and prostate of male rats

Histological analysis of rat prostate under exogenous testosterone and low dose of oral selenium administration

Objective: to verify selenium effectiveness in maintenance of prostate tissue architecture. Method: experimental study using 20 adult male rats, 90 days old, were divided in followed groups: TG, 05 animals that received testosterone administration; TSG, 05 animals that received testosterone administration and doses of selenium by gavage; CG1, 05 intact animals; CG2, 05 animals that received saline injection, and saline by gavage. Results: characteristic architecture was found in tissue samples from animals of CG with cubic/prismatic secretory epithelium surrounded by fibro-muscular stroma. Animals of TG showed an increase in prostatic epithelium height, increase in the number of blood vessels in stroma and presence of proliferative lesions. Proliferative lesions were also found in tissue samples from animals of TSG, besides having improve in epithelial height, as seen in TG. Conclusion: it is concluded that selenium at this concentration has no effectiveness in modulating morphology of prostatic tissue of adult rats.

Cancer pain and neuropathic pain are associated with A β sensory neuronal plasticity in dorsal root ganglia and abnormal sprouting in lumbar spinal cord.

Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aβ sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. Neuropathic pain model rats were induced with a polyethylene cuff implanted around a sciatic nerve. Cancer-induced pain model rats were induced with mammary rat metastasis tumour-1 rat breast cancer or MATLyLu rat prostate cancer cells implanted into the distal epiphysis of a femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Aβ-fibre low threshold mechanoreceptor neurons in both cancer-induced pain and neuropathic pain models exhibited slower dynamics of action potential genesis, including a wider action potential duration and lower action potential amplitude compared to those in control animals. Enhanced excitability of Aβ-fibre low threshold mechanoreceptor neurons was also observed in cancer-induced pain and neuropathic pain models. Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.

Prostate tumors downregulate microseminoprotein-beta (MSMB) in the surrounding benign prostate epithelium and this response is associated with tumor aggressiveness.

Microseminoprotein-beta (MSMB) is a major secretory product from prostate epithelial cells. MSMB synthesis is decreased in prostate tumors in relation to tumor grade. MSMB levels are also reduced in the circulation and MSMB is therefore used as a serum biomarker for prostate cancer. We hypothesized that cancers induce a reduction in MSMB synthesis also in the benign parts of the prostate, and that the magnitude of this response is related to tumor aggressiveness. Reduced levels of MSMB in the circulation could therefore be a consequence of reduced MSMB expression not only in tumor tissue but also in the benign prostate tissue. MSMB expression was analyzed in prostatectomy specimens from 36 patients using immunohistochemistry and qRT-PCR. MSMB expression in the benign prostate tissue was analyzed in relation to Gleason score, tumor stage, and distance to the tumor. Furthermore, Dunning rat prostate tumors with different aggressiveness were implanted into the prostate of Copenhagen rats to study if this affected the MSMB expression in the tumor-adjacent benign rat prostate tissue. In prostatectomy specimens, MSMB expression was reduced in prostate tumors but also in the tumor-adjacent benign parts of the prostate. The reduction in tumor MSMB was related to tumor grade and stage, and the reduction in the benign parts of the prostate to tumor grade, stage, and distance to the tumor. Implantation of Dunning cancer cells into the rat prostate resulted in reduced MSMB protein levels in the tumor-adjacent benign prostate tissue. Rapidly growing and metastatic MatLyLu tumors had a more pronounced effect than slow-growing non-metastatic G tumors. Our data suggest that aggressive prostate tumors suppress MSMB synthesis in the benign prostate and that this could explain why serum levels of MSMB are decreased in prostate cancer patients. This study suggests that markers for aggressive cancer can be found among factors altered in parallel in prostate tumors and in the adjacent benign tissue.

Influence of postnatal prolactin modulation on the development and maturation of ventral prostate in young rats.

Besides androgenic dependence, other hormones also influence the prostate biology. Prolactin has been described as an important hormone associated with maintenance of prostatic morphophysiology; however, there is a lack of information on the involvement of prolactin during prostate development and growth. This study aimed to evaluate whether perinatal prolactin modulation interferes with rat ventral prostate (VP) development and maturation. Therefore, prolactin or bromocriptine (an inhibitor of prolactin release from the pituitary) were administered to Sprague Dawley rats from postnatal Day (PND) 12 to PND 21 or 35. Animals were then killed and serum hormonal quantification, VP morphological-stereological and immunohistochemical analyses and western blotting reactions were employed. Our results demonstrate that prolactin blockage increased serum testosterone on PND 21, which reflected an increase in anogenital distance. Although prolactin modulation did not interfere with VP weight, it modified VP morphology by dilating the acinar lumen and reducing epithelial cell height. Prolactin activated the signal transducer and activator of transcription (STAT) downstream pathway, increased androgen receptor expression and epithelial proliferation. In addition, prolactin and bromocriptine also increased expression of cytokeratin 18, a marker of luminal-differentiated cells. In conclusion, the VP responds to prolactin modulation through a mechanism of increasing the epithelial proliferative response and dynamics of cell differentiation, especially in animals treated for a more prolonged period.

Atrazine affects the morphophysiology, tissue homeostasis and aromatase expression in the efferent ductules of adult rats with mild alterations in the ventral prostate

The widely used herbicide atrazine is a potent endocrine disruptor known to cause increased aromatase expression and transient increase in testicular weight followed by remarkable testis atrophy. However, whether the effects of atrazine on the testes are primary or secondary to dysfunctions in other components of male reproductive tract remains unknown. Given the high sensitivity of the efferent ductules to estrogen imbalance and the similarity to alterations previously described for other disruptors of these ductules function, and the testicular alterations observed after atrazine exposure, we hypothesized that the efferent ductules could be a target for atrazine. Herein we characterized the efferent ductules and the ventral prostate of adult Wistar rats treated with 200 mg/kg/day of atrazine for 7, 15, and 40 days. Additionally, we evaluated if the effects of atrazine in these organs could be reduced after discontinuation of the treatment. Atrazine exposure resulted in mild effects on the ventral prostate, but remarkable alterations on the efferent ductules, including luminal dilation, reduced epithelial height, and disruption of the epithelial homeostasis, which coincides with increased aromatase expression. Together with our previous data, these results suggest that at least part of the testicular effects of atrazine may be secondary to the alterations in the efferent ductules.

Serotonin regulates prostate growth through androgen receptor modulation

Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT’s inhibitory mechanism is also present in human cells of normal prostate and BPH, namely in cell lines expressing AR when treated with testosterone. In both models, 5-HT’s inhibitory mechanism was replicated by specific agonists of 5-Htr1a and 5-Htr1b. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type, whereas 5-HT treatment restored the prostate weight and AR levels. As 5-HT is decreased in BPH, we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a new therapeutic target for BPH.

Carbon ion radiotherapy: impact of tumor differentiation on local control in experimental prostate carcinomas

BackgroundTo summarize the research activities of the “clinical research group heavy ion therapy”, funded by the German Research Foundation (DFG, KFO 214), on the impact of intrinsic tumor characteristics (grading, hypoxia) on local tumor control after carbon (12C-) ion- and photon irradiations.MethodsThree sublines of syngeneic rat prostate tumors (R3327) with various differentiation levels (highly (-H), moderately (-HI) or anaplastic (-AT1), (diameter 10 mm) were irradiated with 1, 2 and 6 fractions of either 12C-ions or 6 MV photons using increasing dose levels. Primary endpoint was local tumor control at 300 days. The relative biological effectiveness (RBE) of 12C-ions was calculated from TCD50-values (dose at 50% tumor control probability) of photons and 12C-ions and correlated with intrinsic tumor parameters. For the HI-subline, larger tumors (diameter 18 mm) were irradiated with either carbon ions, oxygen ions or photons under ambient as well as hypoxic conditions to determine the variability of the RBE under different oxygenation levels. In addition, imaging, histology and molecular analyses were performed to decipher the underlying mechanisms.ResultsExperimental results revealed (i) a smaller variation of the TCD50-values between the three tumor sublines for 12C-ions (23.6 - 32.9 Gy) than for photons (38.2 - 75.7 Gy), (ii) steeper dose-response curves for 12C-ions, and (iii) an RBE that increased with tumor grading (1.62 ± 0.11 (H) vs 2.08 ± 0.13 (HI) vs 2.30 ± 0.08 (AT1)). Large HI-tumors resulted in a marked increase of TCD50, which was increased further by 15% under hypoxic relative to oxic conditions. Noninvasive imaging, histology and molecular analyses identified hypoxia as an important radioresistance factor in photon therapy.ConclusionsThe dose-response studies revealed a higher efficacy of 12C-ions relative to photon therapy in the investigated syngeneic tumor model. Hypoxia turned out to be at least one important radioresistance factor, which can be partly overridden by high-LET ion beams. This might be used to increase treatment effectiveness also in patients. The results of this project served as a starting point for several ongoing research projects.

Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs.

9P - Anti-metastatic effect of riluzole on Mat-LyLu rat prostate cancer cell line

9P - Anti-metastatic effect of riluzole on Mat-LyLu rat prostate cancer cell line

32 - Protection of rat prostate and erectile function from radiation-induced damage by novel Mn(III) N- substituted pyridylporphyrin and ascorbate

Prostate cancer is the most common cancer in American men, with approximately 30-50% of men developing loss of erectile function after definitive radiotherapy (RT). Currently, no treatment is available that preserves erectile function. Therefore there is a significant reduction of the quality of life of survivors which incurs considerable healthcare costs. Hence, there is an imminent need to protect normal tissues during prostate cancer RT. We have developed Mn porphyrin-based SOD mimics and demonstrated that they radioprotect normal tissues such as brain, salivary glands and mouth mucosa while radio- and chemosensitizing tumors, such as brain, breast and lymphoma. We have also demonstrated and explained the reasoning behind the significant enhancement of tumor radiosensitization by Mn porphyrins when combined with ascorbate (Asc). A lead drug, BMX-001 is now in two Phase I/II clinical trials as a normal tissue radioprotector with glioma and head&neck cancer patients. Herein we have explored the radioprotection of a lower pelvic region by a member of the new class of powerful Mn porphyrin-based SOD mimics – Mn(III) meso-tetrakis(5',5',5'-trifluoropentylpyridinium-2-yl)porphyrin, MnF3Pen. The SOD-like activity given by log kcat(O2.-) is 7.45, and the reduction potential of the Mn site, E1/2 is +288 mV vs NHE. In this study we also aimed to show that the addition of Asc would not diminish radioprotection of a normal tissue by MnF3Pen. The rat toxicity and pharmacokinetic studies of MnF3Pen/Asc system showed that MnF3Pen reached ~100 to 500 nM levels at targeted sites (penis, prostate, bladder, testes and rectum) within few hours after single subcutaneous (sc) 1 mg/kg injection. We subsequently performed the efficacy study. Single radiation dose of 20 Gy was delivered stereotactically to the prostate of Sprague-Dawley 8 week old rats using image-guided small animal irradiator. MnF3Pen was given sc at 0.5 mg/kg/day for four weeks and continued twice weekly for the next 5 weeks. Ascorbate was given intraperitoneally at 1 g/kg/day for first 3 days and then twice weekly for the rest of 9 weeks. We showed that MnF3Pen/Asc treatment prevented erectile dysfunction observed in RT-treated group. We further showed that MnF3Pen/Asc treatment greatly suppressed RT-induced damage to prostate as evaluated by H&E staining.

Highly aggressive rat prostate tumors rapidly precondition regional lymph nodes for subsequent metastatic growth.

The aim of this study was to examine in what ways MatLyLu (MLL) rat prostate tumors with high metastatic capacity influence regional lymph nodes prior to metastatic establishment compared to AT1 rat prostate tumors with low metastatic potential. MLL or AT1 tumor cells were injected into the ventral prostate of immunocompetent rats. Tumor and lymph node morphology, and lymph node mRNA expression of macrophage associated markers, T-cell associated markers, and cytokines were examined over time until the first microscopic signs of metastases (at day 14 for MLL- and at day 28 for AT1-tumors). Already at day 3 after tumor cell injection, when the tumors were extremely small and occupied less than 1% of the prostate volume, MLL- and AT1-tumors provoked different immune responses in both the prostate and the regional lymph nodes. MLL-tumors induced expression of immunosuppressive cytokines, suppressed T-cell accumulation, and directed T-cells towards an immunosuppressive phenotype. AT1-tumors caused a response more similar to that in vehicle-injected animals, with accumulation of T-cells in tumors and regional lymph nodes. Prostate tumors with high metastatic potential were able to precondition regional lymph nodes to subsequent metastatic growth in ways different from tumors with less metastatic potential. This may indicate the existence of a time-window when pre-metastatic changes in regional lymph nodes can aid in the prognostication of locally aggressive and potentially metastatic prostate cancer.

Experimental evaluation of the influence of gold nanoparticles and cerium dioxide on normal and malignant cells and tissues.

The results of experimental studies of the effect of gold nanoparticles ( AuNPs ) on the organs of the reproductive system of male rats, cells and tissues of androgen-dependent prostate cancer (PCa) are presented, as well as the effect of cerium dioxide nanoparticles (CeO 2 NPs ) on the testes and fertility of aging male rats. Addition of polydisperse colloidal solution of AuNPs (10-50 nm) to the culture medium in a final concentration of 10 μg/ml inhibited the growth of the LNCaP culture, PCa cells, while monodisperse solution of AuNPs (20 nm) caused no effect. The polydisperse colloidal solution of AuNPs arrested the growth of PCa xenografts in mice, when administered parenterally at a dose range of 0.64-6.4 μg/kg body weight. The selectivity of the drug effect on the malignant epithelium is confirmed by signs of its destruction and decrease in the epithelial stromal ratio on histological preparations of xenografts. There was no significant damaging effect of poly- and monodisperse AuNPs solutions on the organs of the reproductive system of male rats when administered for up to two weeks. The stimulating effect of a low dose of CeO 2 NPs (1 mg/kg b.w.) administered orally on hormonal function of testes and spermatogenesis, proliferative and secretory processes in the prostate of aging male rats was established. However, fertility of animals was reduced in comparison with the control group due to immaturity of the part of spermatozoa. Thus, metal nanoparticles and their salts can have both a stimulating and destructive effect on organs and tissues, which should be taken into consideration when studying their therapeutic potential and in toxicology.

The expression and functional activities of smooth muscle myosin and non-muscle myosin isoforms in rat prostate.

Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and volume. SM myosin (SMM) and non‐muscle myosin (NMM) play important roles in mediating SM tone and cell proliferation, but these molecules have been less studied in the prostate. Rat prostate and cultured primary human prostate SM and epithelial cells were utilized. In vitro organ bath studies were performed to explore contractility of rat prostate. SMM isoforms, including SM myosin heavy chain (MHC) isoforms (SM1/2 and SM‐A/B) and myosin light chain 17 isoforms (LC 17a/b), and isoform ratios were determined via competitive RT‐PCR. SM MHC and NM MHC isoforms (NMMHC‐A, NMMHC‐B and NMMHC‐C) were further analysed via Western blotting and immunofluorescence microscopy. Prostatic SM generated significant force induced by phenylephrine with an intermediate tonicity between phasic bladder and tonic aorta type contractility. Correlating with this kind of intermediate tonicity, rat prostate mainly expressed LC 17a and SM1 but with relatively equal expression of SM‐A/SM‐B at the mRNA level. Meanwhile, isoforms of NMMHC‐A, B, C were also abundantly present in rat prostate with SMM present only in the stroma, while NMMHC‐A, B, C were present both in the stroma and endothelial. Additionally, the SMM selective inhibitor blebbistatin could potently relax phenylephrine pre‐contracted prostate SM. In conclusion, our novel data demonstrated the expression and functional activities of SMM and NMM isoforms in the rat prostate. It is suggested that the isoforms of SMM and NMM could play important roles in BPH development and bladder outlet obstruction.

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis.

ABSTRACTPurpose:To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation.Materials and Methods:24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy.Results:Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood.Conclusion:Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations.

Methyl jasmonate reduces testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats

BackgroundPhytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. MethodsBPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days. ResultsThe weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax were seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory indices and induced apoptotic parameters in BPH rats. ConclusionMeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme.

The effect of thick burdock extracts on development of model hyperplasia of the prostate gland in rats

The effect of thick burdock extracts on development of model hyperplasia of the prostate gland in rats

Reduced number of CD169+ macrophages in pre-metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients.

BackgroundTumor‐derived antigens are captured by CD169+ (SIGLEC1+) sinus macrophages in regional lymph nodes (LNs), and are presented to effector cells inducing an anti‐tumor immune response. Reduced CD169 expression in pre‐metastatic regional LNs is associated with subsequent metastatic disease and a poor outcome in several tumor types, but if this is the case in prostate cancer has not been explored.MethodsCD169 expression was measured with immunohistochemistry in metastasis‐free regional LNs from 109 prostate cancer patients treated with prostatectomy (January 1996 to April 2002). Possible associations of CD169 expression with PSA‐relapse, prostate cancer death, Gleason score, and other clinical data were assessed using Kaplan‐Meier survival‐ and Cox regression analysis. In addition, the Dunning rat prostate tumor model was used to examine CD169 expression in pre‐metastatic LNs draining either highly metastatic MatLyLu‐ or poorly metastatic AT1‐tumors.ResultsIn patients with low CD169 immunostaining in metastasis‐free regional LNs, 8 of the 27 patients died from prostate cancer compared with only three of the 82 patients with high immunostaining (P < 0.001). CD169 expression in regional LNs was not associated with PSA‐relapse. Rats with highly metastatic tumors had decreased CD169 immunoreactivity in pre‐metastatic regional LNs compared with rats with poorly metastatic tumors.ConclusionLow expression of CD169 in metastasis‐free regional LNs indicates a reduced anti‐tumor immune response. If verified in other studies, CD169 expression in regional LNs could, in combination with other factors, potentially be used as a marker of prostate cancer aggressiveness.

Nano-sized titanium dioxide toxicity in rat prostate and testis: Possible ameliorative effect of morin

This study investigated the effect of short-term oral exposure to nano-sized titanium dioxide (nTiO2) on Wistar rat prostate and testis, and the associating reproductive-related alterations. The study also evaluated the potential ameliorative effect of the natural flavonoid, morin, on nTiO2-induced aberrations. Intragastric administration of nTiO2 (50mg/kg/day for 1, 2 and 3weeks) increased testicular gamma-glutamyltransferase (γ-GT) activity and decreased testicular steroidogenic acute regulatory protein (StAR) and c-kit gene expression, serum testosterone level and sperm count. nTiO2-treated rats also exhibited prostatic and testicular altered glutathione levels, elevated TNF-α levels, up-regulated Fas, Bax and caspase-3 gene expression, down-regulated Bcl-2 gene expression and enhanced prostatic lipid peroxidation. Sperm malformation and elevated testicular acid phosphatase (ACP) activity and malondialdehyde level, serum prostatic acid phosphatase activity, prostate specific antigen (PSA), gonadotrophin and estradiol levels occurred after the 2 and 3week regimens. Morin (30mg/kg/day administered intragastrically for 5weeks) mitigated nTiO2-induced prostatic and testicular injury as evidenced by lowering serum PSA level, testicular γ-GT and ACP activities and TNF-α level, along with hampering both intrinsic and extrinsic apoptotic pathways. Moreover, morin alleviated prostatic lipid peroxidation, raised prostatic glutathione level, and relieved testicular reductive stress. Additionally, morin increased testicular StAR and c-kit mRNA expression, raised the sperm count, reduced sperm deformities and modified the altered hormone profile. Histopathological evaluation supported the biochemical findings. In conclusion, morin could ameliorate nTiO2-induced prostatic and testicular injury and the corresponding reproductive-related aberrations via redox regulatory, anti-inflammatory and anti-apoptotic mechanisms, promoting steroidogenesis and spermatogenesis, and improving sperm count and morphology.