High D-dimer levels are associated with prostate cancer

RESUMO OBJETIVO O câncer de próstata é uma das neoplasias mais comuns em homens. Os principais fatores de risco para a ativação da coagulação e trombose são malignidade e idade mais avançada. O risco de trombose pode estar associado ao aumento do nível dos marcadores de coagulação, tais como o fibrinogênio e D-dímero. O objetivo deste estudo é avaliar a relação entre os marcadores de coagulação e o câncer de próstata. METODOLOGIA Este estudo prospectivo incluiu os pacientes que foram submetidos à biópsia de próstata transretal guiada por ultrassonografia e que passaram por cirurgia da próstata entre janeiro de 2015 e janeiro de 2016. Os níveis no plasma de antígeno prostático específico (PSA), PSA livre (fPSA), porcentagem de fPSA, D-dímero e fibrinogênio foram medidos antes dos procedimentos. Os pacientes foram divididos em dois grupos de acordo com os resultados de patologia. Os pacientes com hiperplasia benigna da próstata foram colocados no grupo 1 e os pacientes com câncer de próstata no grupo 2. RESULTADOS No total, 76 pacientes foram incluídos neste estudo. Houve um total de 53 pacientes no grupo 1 e 23 pacientes no grupo 2. A idade média dos pacientes e os níveis de PSA, fPSA, fibrinogênio e D-dímero foram, respectivamente, 65.33 ± 7.47 anos, 8.21 ± 4.59, 1.41 ± 0.74 ng/ml, 309.75 ± 80.46 mg/dl e 0.42 ± 0.39 µg/ml no grupo 1. No grupo 2, a idade média dos pacientes e os níveis de PSA, fPSA, fibrinogênio e D-dímero foram, respectivamente, 66.08 ± 6.7 anos, 145.69 ± 509.35, 7.32 ± 15 ng/ml, 312.16 ± 69.48 mg/dl, 1.09 ± 2.11 µg/ml. Biópsia da próstata e cirurgia transuretal foram realizadas em 64 (%84,21) e 12 (%15,79) pacientes, respectivamente. CONCLUSÃO O presente estudo demonstrou que os níveis de D-dímero no plasma foram maiores em pacientes com câncer de próstata. Novos estudos com um maior número de pacientes são necessários para definir a relação entre câncer de próstata e distúrbios de coagulação.

Discovery of the ARP2 protein as a determining molecule in tumor cell death

Cancer is a multifactorial disease that constitutes a serious public health problem worldwide. Prostate cancer advanced stages are associated with the development of androgen-independent tumors and an apoptosis-resistant phenotype that progresses to metastasis. By studying androgen-independent lymphoid nodule carcinoma of the prostate (LNCaP) cells induced to apoptosis by serum elimination, we identified the activation of a non-selective cationic channel of 23pS conductance that promotes incoming Ca2+ currents, as well as apoptosis final stages. arp2cDNA was isolated and identified to be of the same cell type, and mRNA was expressed in Xenopus laevis oocytes, which was found to be associated with the activation of incoming Ca2+ currents and induction to apoptosis. cDNA, which encodes the ARP2 protein, was overexpressed in LNCaP cells and Chinese hamster ovary cells, which induced apoptosis. Our evidence suggests that protein ARP2 overexpression and transit to the cell membrane allows an increased Ca2+ incoming current that initiates the apoptosis process in epithelial-type cells whose phenotype shows resistance to programmed cell death.

Can expressed prostatic secretions affect prostate biopsy decision of urologist?

ABSTRACT Objectives: To evaluate the frequency of NIH category IV prostatitis, and the use of expressed prostatic secretions tests in an effort to improve the reliability of prostate specific antigen as an indicator, to avoid unnecessary prostate biopsy. Materials and Methods: 178 expressed prostatic secretion positive patients with serum prostate specific antigen levels of ≥ 2.5 ng / mL were included in present prospective study. The diagnostic evaluation included detailed history and physical examination, digital rectal examination, urine analysis, urine culture, and expressed prostatic secretions tests. Transrectal ultrasonography was used both to measure prostate volume and conduct 12 core prostate biopsy. Results: The prevalence of NIH category IV prostatitis was 36.9% (178 / 482) in our population of men. In our study patients (n: 178) prostate biopsy results were classified as; 66 prostatitis, 81 BPH, and 31 Pca. In asymptomatic prostatitis group, expressed prostatic secretion mean leucocyte ratio was higher compared to other two groups (p < 0.0001). The relation between number of expressed prostatic secretion leucocytes and prostatitis, benign prostate hyperplasia, and prostate cancer is analyzed. If 16 is taken as the cut of number for leucocyte presence, its sensitivity is 0.92 (AUC = 0.78 p = 0.01). Conclusions: The number of leucocytes in expressed prostatic secretion is higher in the chronic prostatitis group. If the leukocyte presence of 16 and above is taken as the cut off point, the sensitivity becomes 0.92 (AUC = 0.78). We firmly believe that our new cut off value may be used as to aid prostate specific antigen and derivates while giving biopsy decision.

Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

PTEN is the most commonly inactivated tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes. ERG rearrangement is a genomic alteration frequently found in PCa and its prognostic significance has yielded mixed results. Although the association of PTEN and ERG biomarkers has potential impact on clinical outcomes, studies examining the two genes simultaneously are scarce in Brazilian populations. In this study, we retrospectively examined the relationship between ERG expression and PTEN loss in 119 surgically treated prostate cancer patients from Northeastern Brazil through immunohistochemical analysis. ERG expression was found in 41.0% (48/117) of cases and the loss of PTEN detected in 38.1% (40/105) of samples. ERG-positive cases were significantly associated with lower prostate weight; ERG negatively correlated with Gleason score above 6. The lack of associations for PTEN loss alone in this cohort is counter to the literature, which shows that PTEN loss is usually associated with more aggressive disease. The overlapping of the two biomarkers revealed that samples with positive ERG expression without PTEN loss were associated with lower Gleason and lower Grade group. This study contributes with the discussion about the development of the molecular profiling of prostate cancer. The further development of similar studies could help in stratifying specific risk groups, leading to a more personalized therapeutic decision for prostate cancer treatment.

The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy

ABSTRACT Objectives The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). Materials and Methods A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Results Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Conclusion Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted.

Metabolic syndrome and prostatic disease: potentially role of polyphenols in preventive strategies. A review

ABSTRACT Benign prostatic hyperplasia and prostate cancer are two common urological diseases of the elderly. Scientific community has always looked for a link that could explain the correlation between the two diseases and the role of chronic inflammation in the pathogenesis of BPH and PCa. As shown by the reports of the two diseases relationship with oxidative stress and metabolic syndrome, the use of compounds with antioxidant action could therefore affect both the symptoms and their onset. Polyphenols appear to act not only against oxidative stress but also at different levels. The aim of this review is to evaluate the role of the most important polyphenols on these two urological diseases. As antioxidants these compounds seems to have a direct action on the cell cycle and hormone function, important for both prostate cancer and BPH. Despite a large number of articles about the relationship of the polyphenols with prostate cancer, very little evidence exists for BPH. Additional clinical trials or meta-analysis are necessary on this topic.

Arterial blood and end-tidal concentrations of sevoflurane during the emergence from anesthesia in gynecologic patients

OBJECTIVE: The end-tidal concentration of inhalation anesthetics is a clinical indicator for predicting the emergence from anesthesia. This study was conducted to assess the relationship between arterial blood and end-tidal sevoflurane concentrations during emergence. METHODS: Thirty-two female American Society of Anesthesiologists physical status I-II patients receiving general anesthesia for elective gynecologic surgery were included. A fixed dose of 3.5% inspiratory sevoflurane in 6 L min-1 oxygen was maintained until the end of surgery. At 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuing sevoflurane, as well as at the time of eye opening by verbal command, defined as awakening, 1 ml arterial blood was obtained to measure its sevoflurane concentration by gas chromatography. Simultaneous inspiratory and end-tidal concentrations of sevoflurane were detected by an infrared analyzer and tested by Bland-Altman agreement analysis. RESULTS: The arterial blood concentrations of sevoflurane were similar to the simultaneous end-tidal concentrations during emergence: 0.36% (0.10) and 0.36% (0.08) sevoflurane at awakening, respectively. The mean time from discontinuing sevoflurane to eye opening was 15.8 minutes (SD 2.9, range 10-26) and was significantly correlated with the duration of anesthesia (52-192 minutes) (P = 0.006) but not with the body mass index or total fentanyl dose. CONCLUSION: The mean awakening arterial blood concentration of sevoflurane was 0.36%. The time to awakening was prolonged in accordance with the anesthetic duration within 3 hours. With well-assisted ventilation during emergence, the sevoflurane end-tidal concentration was nearly equal to its arterial blood concentration, which could be a feasible predictor for awakening. .

Napping during the night shift and recovery after work among hospital nurses / Cochilo durante o plantão noturno e a recuperação após o trabalho entre enfermeiros de hospitais / Siesta durante la guardia nocturna y la recuperación tras el trabajo entre enfermeros de hospitales

OBJECTIVE: To analyze the association between the length of napping during the night shift and the recovery after work among nurses. METHOD: Cross-sectional epidemiological study involving 1940 nurses from 18 public hospitals in the City of Rio de Janeiro. A multidimensional and self-applied questionnaire was used with information about health, sociodemographic and occupational characteristics, health-related behaviors and housework. Multiple logistic regression was applied to identify the association, adjusted for confounding variables. RESULTS: The gross analyses showed 44%, 127% and 66% higher chances of a high level of recovery after work for nurses who sleep up to two hours, between 2.1 and 3 hours and 3.1 hours or more, respectively, when compared to the nurses who do not sleep. After adjusting for confounding variables, the association only continues significant for the group that sleeps 2.1 to 3 hours during the night shift (OR=1.79; 95%CI=1.33-2.41). CONCLUSION: The association between the length of napping and the high level of recovery after work, confirmed in the present results, can be included in the studies that aim to support more appropriate policies aimed at improving the workers' work, life and health conditions, not only in nursing, but night-shift workers in general. .

OBJETIVO: analisar a associação entre duração do cochilo durante o plantão noturno e recuperação após o trabalho, entre enfermeiros. MÉTODO: estudo epidemiológico seccional com 1940 enfermeiros, de 18 hospitais públicos, do Município do Rio de Janeiro. Utilizou-se questionário multidimensional e autopreenchível com informações sobre saúde, características sociodemográficas, ocupacionais, comportamentos relacionados à saúde e trabalho doméstico. Utilizou-se a regressão logística múltipla, buscando identificar a associação ajustada por variáveis de confundimento. RESULTADOS: as análises brutas mostraram chances 44%, 127% e 66% mais elevadas de alta recuperação após o trabalho, para aqueles que dormem até 2 horas, de 2,1 a 3 horas e de 3,1 horas ou mais, respectivamente, comparados aos que não dormem. Após o ajuste por variáveis de confundimento, a associação permanece significativa apenas para o grupo que dorme de 2,1 a 3 horas durante o plantão noturno (OR=1,79; IC95%=1,33-2,41). CONCLUSÃO: a associação entre tempo de cochilo e alta recuperação após o trabalho, confirmada nos resultados, pode compor os estudos que buscam subsidiar políticas mais adequadas voltadas à melhoria das condições de trabalho, de vida e saúde dos trabalhadores, não apenas da enfermagem, mas trabalhadores noturnos de forma geral. .

OBJETIVO: Analizar la asociación entre la duración de la siesta durante la guardia nocturna y la recuperación tras el trabajo entre enfermeros. MÉTODO: Estudio epidemiológico seccional con 1940 enfermeros de dieciocho hospitales públicos del Municipio de Rio de Janeiro. Fue utilizado cuestionario tipo multidimensional y autollenado con informaciones sobre salud, características sociodemográficas, ocupacionales, comportamientos relacionados a la salud y trabajo doméstico. Fue utilizada la regresión logística múltipla, buscando identificar la asociación ajustada por variables de confusión. RESULTADOS: Los análisis brutos mostraron posibilidades 44%, 127% y 66% más elevadas de alta recuperación tras el trabajo, para aquellos que duermen hasta 2 horas, de 2,1 a 3 horas y de 3,1 horas o más, respectivamente, comparados a aquellos que no duermen. Tras el ajuste por variables de confusión, la asociación sigue significativa solamente para el grupo que duerme de 2,1 a 3 horas durante la guardia nocturna (OR=1,79; IC95%=1,33-2,41). CONCLUSIÓN: La asociación entre el tiempo de siesta y la alta recuperación tras el trabajo, confirmada en nuestros resultados, puede componer los estudios con objeto de subsidiar políticas más adecuadas dirigidas a la mejora de las condiciones de trabajo, de vida y salud de los trabajadores, no solamente enfermeros, pero trabajadores nocturnos de manera general. .

Expression levels of heat shock protein 27 and cellular FLICE-like inhibitory protein in prostate cancer correlate with Gleason score sum and pathologic stage

PURPOSE: Heat shock protein (HSP) 27 protects the cell by controlling apoptosis and immune reactions, and c-FLIP (cellular-FLICE inhibitory protein) inhibits apoptosis by inhibiting caspase-8 activity. We investigated the relationship of HSP27 and c-FLIP expression to prostate-specific antigen, Gleason score sum (GSS), and pathologic stage. MATERIALS AND METHODS: Samples from 163 patients between May 2004 and April 2010 were analyzed: 83 from patients that had underwent a radical prostatectomy, and 80 from those that underwent transurethral resection of the prostate to alleviate urinary symptoms from benign prostate hyperplasia. c-FLIP and HSP27 expression were observed by immunohistochemistry staining. Samples with less than 5% expression-positive cells were scored as 1, with 5%-50% were scored as 2, and with more than 50% were scored as 3. Local reactions were identified as 0.5 and evaluated. RESULTS: Both the presence of HSP27 within the tumor and the number of cancer cells positive for HSP27 were significantly correlated to GSS and pathologic stage (p<0.001, p=0.001, p<0.001, p<0.001). The same was true for c-FLIP expression (p<0.001). GSS was more highly correlated to HSP27 expression than to c-FLIP expression (r=0.814 for HSP27, r=0.776 for c-FLIP), as was pathologic stage (r=0.592 for HSP27, r=0.554 for c-FLIP). CONCLUSIONS: In prostate cancer, higher GSS and a more advanced pathologic stage were associated with a higher likelihood of having a HSP27-positive tumor and more HSP27-positive tumor cells. HSP27 expression was correlated with GSS and prostate cancer stage. A more advanced pathologic stage corresponded to a higher likelihood of having a c-FLIP-positive tumor and more c-FLIP-positive tumor cells. HSP27 expression had a higher correlation with prostate cancer stage and GSS than c-FLIP expression did.

Expression of Peroxisome Proliferato Activated Receptor gamma in Prostatic Adenocarcinoma

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-gamma ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-gamma expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-gamma antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-gamma and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-gamma except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-gamma was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-gamma mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-gamma mRNA expression between low (7) Gleason score groups. There was no association of PPAR-gamma mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-gamma. Further studies are needed to assess the functional role of PPAR-gamma and to validate its therapeutic implication in prostate cancer.

A systematic review of the nutritional adequacy of the diet in the Central Andes / Revisión sistemática de la adecuación nutricional del régimen alimentario en los Andes centrales

OBJECTIVE:To examine dietary adequacy in the Andean area, including macro- and micronutrient intakes, with a particular focus on rural communities; to highlight nutrition priorities in the Andes; and to identify opportunities for improvement. METHODS: A comprehensive literature search was conducted, identifying published and grey literature in English and Spanish related to diet in the central Andean countries of Bolivia, Colombia, Ecuador, and Peru. Articles reporting data from dietary surveys or nutrition interventions were included. Thirty-four papers or reports published in 1969-2011 were included in the final review. The mean and variation in intakes by sex and age group of all presented nutrients were collated and the mean of means were calculated. RESULTS: Thiamin, niacin, and vitamin C intakes were usually adequate. Intakes of most other micronutrients, including iron, zinc, vitamin A, riboflavin, vitamin B12, folate, and zinc were low, likely resulting in high levels of inadequacy. Energy intakes were lower than requirements, but it is unlikely to be a common problem, rather, this result was probably due to the known tendency of most dietary survey tools to underreport intake. However, energy from fat intakes was very low, usually less than 20% of the total, and in some settings, less than 10%. CONCLUSIONS: The inadequate intake of some micronutrients is common in many developing countries, but the extremely low intake of dietary fat found in the central Andes is not. Increased consumption of animal-source foods would increase fat intakes, while addressing micronutrient deficiencies; however, the impact on the fragile ecosystem of the Andes needs considering. Indigenous crops, such as lupine bean, quinoa, and amaranth are also rich in fat or micronutrients.

OBJETIVO: Analizar la adecuación del régimen alimentario en la zona andina, incluidas las ingestas de macro y micronutrientes, prestando especial atención a las comunidades rurales; señalar las prioridades nutricionales en los Andes; y establecer las oportunidades de mejora. MÉTODOS: Se llevó a cabo una exhaustiva búsqueda bibliográfica, en la que se seleccionaron documentos publicados y procedentes de la literatura gris, en inglés y español, relacionados con el régimen alimentario en los países andinos centrales de Bolivia, Colombia, Ecuador y Perú. Se incluyeron artículos que aportaran datos de encuestas alimentarias o intervenciones nutricionales. En el análisis final, se incluyeron 34 artículos o informes publicados desde 1969 a 2011. Se recopilaron las medias y las variaciones de las ingestas de todos los nutrientes presentados según el sexo y el grupo de edad, y se calculó la correspondiente media de las medias. RESULTADOS: Las ingestas de tiamina, niacina y vitamina C eran generalmente adecuadas. Las ingestas de la mayor parte de los restantes micronutrientes, incluidos el hierro, el cinc, la vitamina A, la riboflavina, la vitamina B12 y el folato, eran bajas, lo que probablemente ocasionaba altos niveles de inadecuación. Los aportes energéticos eran inferiores a los requeridos, aunque es poco probable que ello constituya un problema frecuente; más bien, este resultado podría deberse a la tendencia conocida de notificar insuficientemente la ingesta en la mayor parte de las encuestas alimentarias. Sin embargo, el aporte energético procedente del consumo de grasas era muy reducido, generalmente por debajo del 20% del total, y en algunos lugares, por debajo del 10%. CONCLUSIONES: La ingesta inadecuada de algunos micronutrientes es frecuente en muchos países en desarrollo, aunque no es tan frecuente la ingesta extremadamente baja de grasa alimentaria observada en los Andes centrales. Un mayor consumo de alimentos de origen animal aumentaría la ingesta de grasas, al tiempo que abordaría las carencias en micronutrientes; sin embargo, debe tenerse en cuenta su posible repercusión sobre el frágil ecosistema de los Andes. Los cultivos autóctonos, como el frijol de altramuz, la quinoa y el amaranto, son también ricos en grasas o micronutrientes.

Evaluation of target mRNA cleavage by Aurorakinase B specific siRNA in prostate and hepatic cancer cells and its therapeutic potential in mouse models of liver cancer.

The anti proliferative potential of siRNA26, targeted to Aurora kinase B, in prostate cancer cells is known from a previous study from our laboratory. Here we first show that siRNA26 cleaves at the same position of the target mRNA in the prostate cancer and hepatocellular carcinoma cell lines, PC3 and HepG2 respectively. Aurorakinase B specific siRNA, but not a control siRNA, inhibited PC3 and HepG2 cell proliferation and cell migration. These effects correlated to RNA silencing of Aurorakinase B in both the cell lines. Intra-tumoral administration of HiPerfect complexed siRNA26 inhibited the growth of HepG2 xenografts in SCID mice. In an orthotopic setting, intravenous administration of HiPerfect encapsulated siRNA26 appeared to reduce the severity of multifocal lesions.

Inflamación y cáncer de próstata: implicaciones biológicas y posible utilidad clínica / Inflammation and prostate cancer: Biological implications and clinical usefulness

El cáncer de próstata es la neoplasia no cutánea que afecta con mayor frecuencia a los hombres en todo el mundo. Existe evidencia que señala un papel de la inflamación crónica en el desarrollo de distintas neoplasias en humanos, entre ellas el cáncer de próstata. Esta asociación fue sugerida hace mucho tiempo por la observación de infiltrados en muestras de tejido prostático de pacientes con cáncer y, más recientemente, por los altos niveles de citocinas proinflamatorias en el suero de pacientes con esta enfermedad. Muchos estudios han determinado la asociación de ciertos polimorfismos de base única en genes asociados a inflamación con el riesgo de desarrollar cáncer de próstata. En los últimos años se han descrito los efectos de moléculas inflamatorias sobre el comportamiento biológico de esta neoplasia; se destacan entre ellos el potencial de inducir la proliferación de células cancerígenas y la des-diferenciación de células del estroma. La influencia de la inflamación en el desarrollo y avance del cáncer de próstata se ha convertido en un asunto de interés debido al potencial diagnóstico y terapéutico de su uso. Se espera que en el futuro una mejor comprensión biológica de esta asociación lleve a una explotación práctica de su utilidad clínica.

Worldwide, prostate cancer is the non-cutaneous neoplasm that most frequently affects men. Recent evidence demonstrates a role for chronic inflammation in the development of different cancer types in humans, including prostate cancer. This association was suggested long ago by the observation of inflammatory infiltrates in tissue samples from patients with prostate cancer. More recently it has been supported by high levels of circulating pro-inflammatory cytokines in serum of patients with this disease. Multiple studies have found association between certain single nucleotide polymorphisms in genes associated with inflammation, and the risk of developing prostate cancer. In the last few years, the effects of inflammatory molecules on the behavior of this disease have been described; among them, the potential to induce cancer cell proliferation and dedifferentiation of stromal cells. The influence of inflammation in the development and progression of prostatic cancer has become a topic of interest because of the potential use in diagnosis and therapy. It is expected that a better biological understanding of the mechanisms underlying this association may lead to a practical exploitation of its clinical usefulness.

Leptin and leptin receptor expressions in prostate tumors may predict disease aggressiveness?

PURPOSE: The aim of this study was to evaluate the expression of leptin and its receptor in histological sections of prostate tumors, and their association with prognostic factors. METHODS: A total of 532 surgical specimens from prostate cancer were studied. After histopathological diagnosis, the samples were included in tissue microarrays containing cores from tumor and non-tumor (benign prostatic hyperplasia) areas. These were immunostained with anti-leptin and anti-leptin-receptor antibodies. Objective and subjective analyses were performed. Student's-t-test and ANOVA were used to compare mean values, and linear regression was used to evaluate the correlation between histological results and prognostic indicators. RESULTS: Leptin receptor expression was reduced in tumors with a positive surgical margin, urethral margin involvement, and seminal vesicles invasion. Further, there was a negative correlation between the expression of leptin receptor in tumor areas and the sum of prognostic factors, suggesting that leptin receptor may predict the aggressiveness of disease. CONCLUSION: Our findings suggest that leptin receptor expression is a potential prognostic factor for PCa. Further investigation is needed to support the use of leptin receptor as a novel biomarker, although leptin itself does not seem to predict the aggressiveness of prostate cancer. .

What Is the Ideal Core Number for Ultrasound-Guided Prostate Biopsy?

PURPOSE: We evaluated the utility of 10-, 12-, and 16-core prostate biopsies for detecting prostate cancer (PCa) and correlated the results with prostate-specific antigen (PSA) levels, prostate volumes, Gleason scores, and detection rates of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP). MATERIALS AND METHODS: A prospective controlled study was conducted in 354 consecutive patients with various indications for prostate biopsy. Sixteen-core biopsy specimens were obtained from 351 patients. The first 10-core biopsy specimens were obtained bilaterally from the base, middle third, apex, medial, and latero-lateral regions. Afterward, six additional punctures were performed bilaterally in the areas more lateral to the base, middle third, and apex regions, yielding a total of 16-core biopsy specimens. The detection rate of carcinoma in the initial 10-core specimens was compared with that in the 12- and 16-core specimens. RESULTS: No significant differences in the cancer detection rate were found between the three biopsy protocols. PCa was found in 102 patients (29.06%) using the 10-core protocol, in 99 patients (28.21%) using the 12-core protocol, and in 107 patients (30.48%) using the 16-core protocol (p=0.798). The 10-, 12-, and 16-core protocols were compared with stratified PSA levels, stratified prostate volumes, Gleason scores, and detection rates of HGPIN and ASAP; no significant differences were found. CONCLUSIONS: Cancer positivity with the 10-core protocol was not significantly different from that with the 12- and 16-core protocols, which indicates that the 10-core protocol is acceptable for performing a first biopsy.

MicroRNA 100: a context dependent miRNA in prostate cancer

OBJECTIVE: MicroRNAs are noncoding RNA molecules involved in the development and progression of tumors. We have found that miRNA-100 is underexpressed in metastatic prostate cancer compared to localized disease. Conversely higher levels of miR-100 are related to biochemical recurrence after surgery. This suggests that miR-100 may be a context-dependent miRNA, acting as oncogene or tumor suppressor miRNA. Our aim is to demonstrate the role of miR-100 in the control of predicted target genes in prostate cancer cell lines. METHODS: Cell lines DU145 and PC3 were transfected with miR-100, antimiR-100 and after 24 h and 48 h of exposure, qRT-PCR and western blot were performed for mTOR, FGFR3, THAP2, SMARCA5 and BAZ2A. RESULTS: There was reduction in mTOR (p = 0.025), THAP2 (p = 0.038), SMARCA5 (p = 0.001) and BAZ2A (p = 0.006) mRNA expression in DU145 cells after exposure to miR-100. In PC3 cells, mTOR expression was decreased by miR-100 (p = 0.01). There was a reduction in the expression levels of proteins encoded by studied genes, ranging from 34% to 69%. CONCLUSIONS: We demonstrate that miR-100 is a context-dependent miRNA controlling BAZ2, mTOR, FGFR3, SMARCA5 and THAP2 that might be involved in PC progression. The elucidation of the roles of miRNAs in tumors is important because they can be used as therapeutic targets in the future. .

The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer

OBJECTIVE: The aim of this study is to verify the expression of proteins that are controlled by miR-let7c, 100 and 218 using immunohistochemistry in tissue microarray representative of localized and metastasized the lymph nodes and bone prostate cancer. METHODS: To verify the expression of proteins that are controlled by miR-let7c (C-MYC, BUB1, RAS) 100 (SMARCA5, RB) and 218 (LAMB3) and cell proliferation (Ki-67) we used immunohistochemistry and computerized image system ImageJ MacBiophotonics in three tissue microarrays representative of localized prostate cancer and lymph node and bone metastases. miRNA expression was evaluated by qRT-PCR using 60 paraffin blocks to construct the tissue microarray representative of localized disease. RESULTS: RAS expression was increased in localized prostate cancer and bone metastases compared to the lymph nodes (p=0.017). RB showed an increase in expression from localized prostate cancer to lymph node and bone metastasis (p=0.036). LAMB3 was highly expressed in localized and lymph node metastases (p<0.001). Cell proliferation evaluated by Ki-67 showed an increase from localized prostate cancer to metastases (p<0.001). We did not found any relationship between C-MYC (p=0.253), BUB1 (p=0.649) and SMARCA5 (p=0.315) protein expression with prognosis or tumor behavior. CONCLUSION: We found that the expression of RAS, RB, LAMB3 and Ki-67 changed in the different stages of prostate cancer. Furthermore, we confirmed the overexpression of the miRNAs let7c, 100 and 218 in localized prostate cancer but failed to show the control of protein expression by the putative controller miRNAs using immunohistochemistry. .

RNAi-mediated knockdown of pituitary tumor- transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells

Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.

Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm²) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm²). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo.