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Background Serine-arginine protein kinase 1 (SRPK1) has been implicated in prostate cancer (PCa) progression. However, its prognostic value and association with ERG and PTEN expression, two of the most common genetic alterations, have not been explored fully. Objective We assessed the prognostic value of SRPK1 in association with ERG and PTEN in a cohort of patients managed nonsurgically by androgen deprivation therapy (ADT) for advanced disease. Design, setting, and participants The study cohort consisted of men diagnosed with PCa by transurethral resection of the prostate (TURP; n = 480). The patients were divided into three main groups: incidental (patients with Gleason score [GS] ≤7 with no prior ADT), advanced (patients with GS ≥8 with no prior ADT), and castrate-resistant PCa (patients with prior ADT). Outcome measurements and statistical analysis A total of 480 TURP samples were assessed by immunohistochemistry for SRPK1, ERG, and PTEN, and results were correlated with Gleason grade group (GG), overall survival (OS), and PCa-specific mortality (PCSM). Results and limitations High SRPK1 expression was noted in 105/455 (23%) available patient cores. Expression of SRPK1 was associated with Gleason grade grouping (p, Take Home Message The expression of serine-arginine protein kinase 1 (SRPK1) is associated with prostate cancer progression, overall survival, and cause-specific mortality. Assessing combined status of SRPK1 and PTEN is of added prognostic significance compared with either marker alone. Patients with high SRPK expression/PTEN loss show the highest prognostic value among all combinations.

Background: Garlic has a wide range of actions, including antibacterial, antiviral, antifungal, antiprotozoal and antihelminthic actions. This antiparasitic activity has been attributed to allicin, which is the main constituent of garlic. The aim: is to evaluate the potential therapeutic and/or prophylactic effects of allicin on S. mansoni. Method: Swiss albino mice strain CD1were infected with S. mansoni cercariae and sacrificed 40 days later to acquire the adult worms. These worms were collected by perfusion and placed in RPMI medium 1640 at 37°C before transferring to RPMI media containing 0 (control), 5, 10 and 100µg/ml of allicin, where they were incubated for 48h and monitored during this time to evaluate motility and mortality rate by means of stereomicroscope. Twenty male Swiss albino mice strain CD1were divided into two groups. One group was infected with S. mansoni cercariae and treated with allicin one week post infection. The second group was (control). Results: In vitro incubation of S. mansoni adult worms with allicin, showed a statistically high significant difference in comparison with control non-treated group. All worms showed slow movement after 48 h of incubation at concentration of 100µg/ml. No effect was noticed at allicin concentrations of 10 and 5 µg/ml at the end of the experiment. Administration of allicin to the infected mice had non- significant effect on the worm burden. Conclusion: allicin was effective against adult S. mansoni worms in vitro, but with no significant effect in vivo.

To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western population. Immunohistochemistry for ERG, PTEN and SPINK1 was performed in a cohort of localized PCA (n = 340). The data were correlated to pathological and clinical outcomes and compared to Western populations. ERG expression and PTEN loss were noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression was assessed in a subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in the lower grade groups (1–3 vs 4–5; p = 0.04). In contrast to the Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI 1.10–726, p = 0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI 0.98–7.33, p = 0.05), after adjusting for GG, path stage and surgical margin. This study documents significant differences in key molecular events in PCA in Middle Eastern population compared to Western populations that could explain differences in PCA incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest risk for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCA and add further insight to understanding PCA molecular pathways.

Trefoil Factor 3 (TFF3) has been implicated in Prostate Cancer (PCa) progression. However, its prognostic value and association with other biomarkers have not been fully explored. We assessed the combined value of TFF3 and PTEN in two cohorts: one is managed surgically for localized PCa and the second is managed non-surgically by androgen deprivation therapy for advanced disease. 228 radical prostatectomies (RP) and 318 transurethral resection of prostate (TURP) samples were assessed by immunohistochemistry (IHC) for TFF3 and by IHC and fluorescent in situ hybridization (FISH) for PTEN. Results of biomarkers expression were correlated with various pathological and clinical outcome parameters including biochemical recurrence (BCR) in the RP cohort and cancer-specific mortality (PCSM) and overall survival (OS) in the TURP cohort. TFF3 expression was detected in 131/226 (57.9%) RP samples and 148/318 (46.5%) of TURP cases. In general, TFF3 positivity was less frequently observed with advanced Gleason Groups. TFF3 expression was also assessed in relation to PTEN expression. Only 15–16% of TFF3-expressed cases were present in association with complete loss of PTEN expression in the TURP and localized cohorts, respectively. Loss of TFF3 expression was not related to BCR after RP, but was prognostic in the non-surgical cohort and associated with decrease OS and PCSM (HR 2.31, CI: 1.67–3.18, p

Healthcare facilities are complex and complicated structures that affect their inhabitants heavily. The effects may become both physical and psychological and address patients, users, and visitors. However, recent studies have shown that “coming back to nature” affects hospital stays significantly. Patients that are given access to nature and continuous connection to family, friends, and specialized social workers may eventually recover faster and become dismissed earlier. This research is based on an analytical overview of previous literature in relevance to the promotion of health and healing in healthcare facilities which have higher access to daylight and natural views. It accentuates previous research and emphasizes the importance of these factors as well as exterior connectivity for patients and their essentiality in accelerating the healing process. The research also presents the design indicators and criteria that future hospitals should follow to enhance the productivity of these institutions and promote wellness for patients. The results of this research came out as a group of indicators that address the effect of design factors on overall building and interior design of healthcare facilities.

ISL1 serves as a biomarker of metastasis and neuroendocrine neoplasia in multiple tumors. However, the expression and relation of ISL1 to other biomarkers in prostate cancer have not been fully elucidated. Here, we characterize the expression of ISL1 and its partners in PCa and document its association to disease progression and post castration resistance neuroendocrine differentiation. The expression of ISL1 was interrogated in > 6000 primary samples from the Decipher GRID registry and 250 mCRPC samples to assess its prognostic value and relation to neuroendocrine differentiation. ISL1 was highly correlated to MEIS genes and other genes related to cell motility. ISL1 down-regulation in PCa was associated with cancer progression, aggressive primary tumors, and metastatic outcome. We found that ISL1 is highly correlated to MEIS genes across multiple primary PCa and mCRPC cohorts. The expression of ISL1 and MEIS genes were significantly and inversely related to metastasis-free survival and lethal disease, and were downregulated in CRPC and hormone naive metastatic tumors but showed upregulation in neuroendocrine tumors. Co-immunoprecipitation showed MEIS2 and ISL1 interacting with each supporting their role in modulating transcriptional regulation and nominating this complex for potential targeted therapy. ISL1 complex with MEIS2 serves a critical role in prostate tumor progression and its upregulation in mCRPC/NE provides a rationale for assessing the role of ISL1 and its associated protein in treatment resistance.

Abstact Background Many men diagnosed with prostate cancer are active surveillance (AS) candidates. However, AS may be associated with increased risk of disease progression and metastasis due to delayed therapy. Genomic classifiers, e.g., Decipher, may allow better risk-stratify newly diagnosed prostate cancers for AS. Methods Decipher was initially assessed in a prospective cohort of prostatectomies to explore the correlation with clinically meaningful biologic characteristics and then assessed in diagnostic biopsies from a retrospective multicenter cohort of 266 men with National Comprehensive Cancer Network (NCCN) very low/low and favorable-intermediate risk prostate cancer. Decipher and Cancer of the Prostate Risk Assessment (CAPRA) were compared as predictors of adverse pathology (AP) for which there is universal agreement that patients with long life-expectancy are not suitable candidates for AS (primary pattern 4 or 5, advanced local stage [pT3b or greater] or lymph node involvement). Results Decipher from prostatectomies was significantly associated with adverse pathologic features (p-values

The chemical drugs are safe and effective being the main tool in controlling schistosomiasis. Referring to the possibility of appearance of drug resistant parasites especially with retreatment regimens in endemic areas, search for new schistosomicidal is essential. Nigella sativa has been extensively studied for its biological activities and therapeutic potentials and shown to possess wide spectrum of activities including antihelminthic and antiprotozoal activities. The present report aimed to investigate the prophylactic and therapeutic effect of Nigella sativa oil in treatment of Schistosoma mansoni. Nigella sativa oil was administrated orally to S. mansoni infected mice in two different doses, a prophylactic dose (1.14g/kg) every day for 2 weeks before infection and a therapeutic dose (1.14g/kg) daily for 4 weeks starting from 2nd day post infection aiming to investigate its potential therapeutic role. Therapeutic treatment with Nigella sativa oil had a high significant effect on mature worm burden, as the reduction percentage was (57.5%). Nigella sativa oil in prophylactic and therapeutic doses significantly increased the mean number of dead ova (14.75±6.5) and (21.43±3.64) respectively in comparison to control (5.25±1.71). Nigella sativa oil therapeutic dose had a high reduction effect on ova count in intestinal tissue (81.45%) and a moderate reduction on ova count in hepatic tissue (57.86%). Prophylactic dose gave a high reduction effect (78.76%) on ova count in intestinal tissue. As regard the size of hepatic granuloma, Nigella sativa oil treated group had the highest significant reduction on mean granuloma diameter; the reduction was 26.69% with marked improvement of hepatic pathology. N. sativa oil treated group showed obvious improvement of liver pathology with mild hydrobic degeneration and small sized fibrocellular granuloma accompanied by multiple malformations in both S. mansoni adult worms. These results showed that N. sativa oil has remarkable effect on mature S. mansoni which could be helpful for potentiating Praziquantel effect and thus reducing development of resistance.

To validate a previously characterized 10-gene signature in prostate cancer with implication to distinguish aggressive and indolent disease within low and intermediate patients’ risk groups. A case–control study design used to select 545 patients from the Mayo clinic tumor registry who underwent radical prostatectomy. A training set from this cohort (n = 359) was used to build a 10-gene model, based on high-dimensional discriminant analysis (HDDA10) to predict several endpoints of clinical patients’ outcome. An independent set (n = 219) from the same institution was used as validation set. HDDA10 showed significant performance for predicting metastasis (Mets) (AUC 0.68, p = 6.4E – 6) and biochemical recurrence (BCR) (AUC = 0.65, p = 0.003) in the validation set outperforming Gleason grade grouping (GG) for BCR (AUC 0.57, p = 0.03) and with comparable performance for Mets endpoint (GG AUC 0.66, p = 8.1E – 5). HDDA10 prognostic significance was superior to any clinical–pathological parameter within GG2 + 3 (GS7) patients achieving an AUC of 0.74 (p = 0.0037) for BCR compared to Gleason pattern 4 (AUC 0.64) (p = 0.015) and AUC for Mets of 0.68 versus AUC of 0.65 for Gleason pattern 4 (p = 0.01). HDDA10 remained significant for both BCR and Mets in multivariate analysis, suggesting that it can be used to increase accuracy in stratifying patients eligible for active surveillance. HDDA10 is of added value to GG and other clinical–pathological parameters in predicting BCR and Mets endpoint, especially in the low to intermediate patients’ risk groups. HDDA10 prognostic value should be further validated prospectively in stratifying patients specifically in low to intermediate GS (GG1-2), such as active surveillance programs.

The aim of the present study was to assess the frequency of intestinal parasitic infection among patients with gastrointestinal tract disorders from the Greater Cairo region, Egypt. In addition, a comparison was made of the accuracy of direct thin and thick smear, formol-ether sedimentation (FEC), centrifugal flotation (CF), and mini-FLOTAC techniques in the diagnosis of infection. Out of 100 patients, the overall prevalence of parasitic infection was 51%. Only 6% had dual infection. Giardia lamblia was the most common parasite (26%), followed by Hymenolepis nana (20%), Entamoeba coli (8%), and Enterobius vermicularis (3%). Except the statistically significant association between E. vermicularis infection and perianal itching and insomnia (P < 0.001), age, gender, and complaints of the examined individuals had no association with prevalence of parasitic infection. Both FEC and CF were equally the most accurate techniques (accuracy = 98.2%, confidence interval [CI] = 0.95–1.0, and κ index = 0.962), whereas the Kato-Katz method was the least accurate (accuracy = 67.5%, CI = 0.57–0.78, and κ index = 0.333). However, mini-FLOTAC-ZnSO4 was the most accurate for diagnosis of helminthic infection, and FEC was more accurate for diagnosis of protozoal infection (accuracy = 100%, CI = 1.0–1.0, and κ index = 1).

The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.

The process of "Site Analysis" in the "architectural design process" methodology is considered as a categorical and critical process in many design decisions that affect the final product. This product will be completely adequate with the qualitative and quantitative surrounding, both environmental and man-made ones. The problem is the possibility of design completion and prepare a project that will look presentable in appearance, without the evaluation of the objective criteria that related to site elements, which eventually lead to operation and interaction problems. Therefore, it is essential to highlight on the site analysis process goals in an integrated and comprehensive method. In order to achieve the goals that reflect the architectural design decisions, the site analysis method process should be done on three stages: The first stage: Site Data Monitoring, The Second stage: Explanation Site Phenomena and The third stage: Deduction of Design Decision Directives. This paper has provided the chance for deep understanding for the importance of site analysis in its positive, negative and neutral phenomena to make design decision. In conclusion, the paper presents design decisions directives which coming throw site analysis and guideline that allows to more design decisions that affect the design project.

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) has been recently described as a unique and indolent renal neoplasm, found in female patients with and without tuberous sclerosis complex. Although ESC RCC has a distinct morphology and frequent CK20 reactivity, its molecular karyotype has been previously studied only in few cases. We identified 19 ESC RCC from multiple institutions; all patients were female individuals without clinical features of tuberous sclerosis complex. Molecular karyotyping was performed in 13 cases (12 with informative result). The median age was 55 years (range: 32 to 79 y). The tumors were yellow-gray with a median size of 31 mm (range: 12 to 135 mm) and showed solid and cystic gross appearance. All tumors demonstrated typical microscopic features with solid areas admixed with variably sized macrocysts and microcysts. The cells showed eosinophilic cytoplasm with granular cytoplasmic stippling and round-to-oval nuclei. CK20 was positive in 14/19 (74%) cases. Stage pT1 was found in 17/19 (89%) patients (pT1a in 12, pT1b in 5); 1 patient each had pT2a and pT3a. A total of 15/16 patients with available follow-up were alive and without evidence of disease progression, after 1 to 169 months (median: 44 mo; mean: 49.6 mo); 3 died of other causes. The most common copy number gains were 16p13.3-16q23.1 (33% to 67%), 7p21.2-7q36.2 (42% to 50%), 13q14.2 (33%), and 19p12 (33%). The most common copy number losses included Xp11.21 (42%) and 22q11.23 (33%). Loss of heterozygosity was most frequently found at 16p11.2-11.1 (75%), Xq11.1-13.1 (75%), Xq13.1-21.1 (33%), 11p11.2-11.11 (33%), 9q21.1-22.2 (33%), and 9q33.1 (33%). ESC RCC demonstrates common molecular karyotype alterations, which further support its distinct nature.

The objective of this study was to determine the effects of dietary supplementation with different betaine , choline and methionine levels on productive performance, egg quality and some blood parameters of laying hens under high ambient temperature. Two hundred and thirty one birds (210 pullts +21cocks ) at 24 weeks -old from Inshas developed strain were divided into seven groups of 30 pullets in three replicats ( 10 pulles and one cock ). The frist group was fed the basal diet without supplementation (control 0 % ) ,the second and the third groups were fed the same diet with betaine (0.1 and 0.2 % ,respectively). Choline and methionine were also supplemented at 0.2 % and 0.4 % for choline and 0.1 % and 0.2% for methionine in group 4 to 7 . Birds of each group were housed in open floor pen . Results showed that ,body weight change (g/day) increased and feed conversion ( g feed / g egg) improved significantly by dietary supplementation of methionine (0.2% ) during the period from 24 to 36 wks of age . Rectal temperature and respiratory rate were decreased significantly with supplementation of betaine ( 0.1%) and methionine (0.1%) in diet as compared to control group, and no significant effect on egg quality traits except egg weight . It is concluded that supplemental dietary betaine, choline and mithionine enhanced growth performance and reduced respiration rate and rectal temperature and improved some blood parameters forInshas strain subjected to heat stress.

Background. Human ficolin 2 (encoded by FCN2) and mannose-binding lectin (encoded by MBL2) bind to specific pathogen-associated molecular patterns, activate the complement lectin cascade in a similar manner, and are associated with several infectious diseases. Our recently published study established certain FCN2 promoter variants and ficolin-2 serum levels as protective factors against schistosomiasis. Methods. We used the Nigerian cohort from our recently published study, which included 163 Schistosoma haematobium–infected individuals and 183 matched healthy subjects, and investigated whether MBL deficiency and MBL2 polymorphisms are associated with schistosomiasis. Results. MBL serum levels were significantly higher in controls and were associated with protection (P < .0001). The −550H minor allele was significantly associated with protection (P = .03), and the heterozygous genotypes −550HL were observed to confer protection (P = .03). The MBL2*HYPA haplotype was significantly associated with protection (P = .03), with significantly higher serum MBL levels in controls (P = .00073). The heterozygous 6-bp deletion in the promoter was observed to be a susceptibility factor in schistosomiasis (P = .03). Conclusions. In agreement with findings from our recently published study, the findings reported here support the observation that MBL is also associated with protection in schistosomiasis.

Preventive chemotherapy with praziquantel is the mainstay of schistosomiasis control. However, drug resistance is an imminent threat, particularly with large-scale administration of praziquantel, in addition to much less efficacy against young schistosomes. Several biological activities of limonin have been explored such as insecticidal, insect antifeedant, and growth-regulating activity on insects as well as antimalarial, antiviral, anticancer, cholesterol-lowering, and antioxidant activities. This study investigates limonin as an alternative antischistosomal compound using two novel, single, oral dose regimens. In the current work, the therapeutic efficacy of different limonin dosing protocols was evaluated in experimentally infected mice harboring Schistosoma mansoni (Egyptian strain) juvenile or adult stages. Oral administration of limonin in a single dose of 50 or 100 mg/kg on day 21 post-infection (p.i.) resulted in a significant worm burden reduction of 70.0 and 83.33 %, respectively. The same dose given on day 56 p.i. reduced total worm burdens by 41.09 and 60.27 %, respectively. In addition, significant reductions of 34.90 and 47.16 % in the hepatic and 46.67 and 56.1 % in the intestinal tissue egg loads, respectively, associated with significant alterations in the oogram pattern with elevated dead egg levels. Limonin produced ameliorations of hepatic pathology with reduction in dimensions and number of granulomas. Limonin also produced a variety of tegumental alterations in treated worms including tubercular disruption, edema, blebbing, and ulcerations. Results obtained by this work elucidated promising limonin bioactivity against S. mansoni juvenile and adult stages and provided a basis for subsequent experimental and clinical trials.

Background. Human ficolin-2 (L-ficolins) encoded by the FCN2 gene are pattern-recognition proteins involved in innate immunity and are associated with several infectious diseases. Methods. A Nigerian cohort of 168 Schistosoma haematobium–infected individuals and 192 healthy controls were examined for functional single-nucleotide polymorphisms in the promoter region (−986G>A, −602G>A, −4A>G) and in exon 8 (+6424G>T) using real-time polymerase chain reaction. Results. The FCN2 −986A and −4G alleles were significantly associated with the occurrence of schistosomiasis (P = .0004 for −986G>A; P= .0001 for −4A>G). The heterozygous genotypes (P= .0006 for −986G>A; P = .0002 for −4A>G) were observed to be a risk factor for susceptibility to schistosomiasis, whereas the homozygous genotypes of major alleles (P = .0002 for −986G>A; P= .0001 for −4A>G) were observed to shield against schistosomiasis. The haplotype AGGG (P = .0002) was observed to be a risk factor for susceptibility to schistosomiasis compared with controls, and the haplotype GGAG (P= .04) was observed to confer protection compared with patients. Ficolin-2 serum level was significantly higher in controls (P A and −4A>G) influence ficolin-2 serum levels and susceptibility to schistosomiasis. Schistosomiasis is a major human parasitic disease that is caused by different species of trematode of the genus Schistosoma in sub-Saharan Africa. The most prevalent species in sub-Saharan Africa is S. haema

71 Background: The Decipher 22-feature genomic classifier (GC) has been validated to predict metastasis and prostate cancer specific mortality in needle biopsy (Bx) tissue of men with intermediate and high-risk prostate cancer. We validate GC in diagnostic Bx specimens for the prediction of high-grade/stage (HGS) disease at radical prostatectomy (RP) in men with low and favorable-intermediate (fav-int) NCCN risk group disease. Methods: We identified 176 men diagnosed with low or fav-int NCCN risk group disease who had available Bx GC scores and pathological information after RP from Cedars-Sinai, University of Calgary, Cleveland Clinic, MD Anderson, and Johns Hopkins. The GC score was calculated based on a locked random forest model. Scores range from 0-1 with cut points for GC low, intermediate and high risk groups as 0.6, respectively. The primary endpoint was HGS (Gleason group 3-5 or pT3b or lymph node invasion (LNI)). Univariable (UVA) and multivariable (MVA) logistic regression models were used to evaluate GC and CAPRA. Results: Median age of the cohort was 62 years, 87% and 13% had Bx grade group (GG) 1 or 2 disease. 76% and 24% were NCCN low and fav-int risk, respectively. CAPRA classified 70% as low (0-2) and 30% as average risk (3-5). GC classified 80% low, 16% intermediate and 4% high genomic risk. After RP, 41% had RP GG 1, 46% GG 2 and 13% had GG 3-5 disease. pT3b or positive lymph nodes were observed in 7 men (4%), overall 27 (15%) of men had HGS at RP. In the UVA and MVA, GC was the only significant predictor of HGS with odds ratio (OR) of 1.38 and 1.34 per 10% unit increase, before and after adjusting for CAPRA (p=0.011, 0.027). A low risk score (GC

Ankyrin G (ANK3) is a member of the Ankyrin family, which functions to provide cellular stability by anchoring the cytoskeleton to the plasma membrane. Deregulation of ANK3 expression has been observed in multiple human cancers but its mechanism remains unknown. ANK3 expression in relation to disease progression and patients' outcome was investigated in two cohorts of prostate cancer (PCA). Mechanistic studies were carried out in vitro and in vivo using several PCA cell lines and the avian embryo model. Silencing ANK3 resulted in significant reduction of cell proliferation through an AR-independent mechanism. Decreased ANK3 expression delayed S phase to G2/M cell cycle transition and reduced the expression of cyclins A and B. However, cells with knocked-down ANK3 exhibited significant increase in cell invasion through an AR-dependent mechanism. Furthermore, we found that ANK3 is a regulator of AR protein stability. ANK3 knockdown also promoted cancer cell invasion and extravasations in vivo using the avian embryo model (p 0.01). In human samples, ANK3 expression was dramatically upregulated in high grade intraepithelial neoplasia (HGPIN) and localized PCA (p 0.0001). However, it was downregulated castration resistant stage (p 0.0001) and showed inverse relation to Gleason score (p 0.0001). In addition, increased expression of ANK3 in cancer tissues was correlated with better cancer-specific survival of PCA patients (p = 0.012).Silencing ANK3 results in significant reduction of cell proliferation through an AR-independent mechanism. ANK3 knockdown results in significant increase in cell invasion through an AR-dependent mechanism. ANK3 is a regulator of AR protein stability. ANK3 knockdown also promotes cancer cell invasion and extravasation in vivo using the avian embryo model.

The inhibitor of growth family member 3 (ING3) is a member of the ING tumor suppressor family. Although its expression has been reported in various types of cancers, the role of ING3 and its prognostic value in prostate cancer (PCa) has not been investigated. ING3 expression and prognostic value was assessed in a cohort of PCa patients (n = 312) treated with transurethral resection of prostate using immumoflourescent automated quantitative analysis (AQUA) system. In vitro studies were carried out in conjunction to investigate its expression in various PCa cell lines. ING3 knockdown was also carried out in DU145 cell lines to assess for any changes in invasion and migration. ING3 expression was highest in benign prostate tissues (mean 3.2 ± 0.54) compared to PCa (mean 2.5 ± 0.26) (p = 0.437), advanced prostate cancer (AdvPCa) (mean 1.5 ± 0.32) (p = 0.004), and castration-resistant prostate cancer (CRPC) (mean 2.28 ± 0.32) (p = 0.285). ING3 expression was inversely correlated to Gleason score (p = 0.039) and ETS-related gene (ERG) expression (p = 0.019). Higher ING3 expression was marginally associated with lethal disease (p = 0.052), and this was more pronounced in patients with ERG-negative status (p = 0.018). Inhibition of ING3 in DU145 PCa cells using small interfering RNA (siRNA) was associated with decreased cell invasion (p = 0.0016) and cell migration compared to control cells. ING3 is significantly associated with PCa disease progression and cancer-specific mortality. To our knowledge, this is the first report suggesting an oncogenic function of ING3, previously well known as a tumor suppressor protein. Further studies should investigate potential-related pathways in association to ING3.