Aptamers as Theragnostic Tools in Prostate Cancer.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

Índice de Salud Prostática (phi) / Prostate Health Index (phi)

El antígeno específico de próstata (PSA, del inglés, Prostate Specific Antigen) es una glicoproteína producida por la próstata, y es el marcador tumoral de mayor uso. Sin embargo, su baja especificidad para diferenciar entre cáncer de próstata y otras alteraciones no malignas, como la hipertrofia benigna de la próstata (HBP) y la prostatitis aguda, limitan su utilidad diagnóstica

Prostate Specific Antigen (PSA) is a glycoprotein produced by the prostate and is the most widely used tumor marker. However, its low specificity to differentiate between prostate cancer and other non-malignant conditions, such as benign prostate hypertrophy (BPH) and acute prostatitis, limits its diagnostic utility

Antígeno prostático específico (PSA) relacionado al perfil antropométrico en pacientes del Hospital II Huamanga Carlos Tuppia García-Godos, EsSalud. Ayacucho

Objetivo: Determinar la asociación del nivel de antígeno prostático específico (PSA) plasmático y PSA masa según riesgo de padecer enfermedades prostáticas con el perfil antropométrico. Materiales y métodos: Estudio correlacional, de enfoque cuantitativo de dimensión transversal y retrospectiva. La muestra estuvo constituida por 156 historias clínicas de pacientes varones, con pruebas de PSA y datos antropométricos. Para el análisis de la relación de las variables se utilizó la prueba Rho de Spearman, con un nivel de confianza de 95 %. Resultados: La edad promedio de los pacientes fue 67,85±10,83 años y presentaron un valor medio de PSA de 3,57±7,30 ng/mL. El 9,60 % (15 pacientes) tuvo un riesgo bajo de padecer enfermedades prostáticas (PSA = 4,1-9,90 ng/mL); el 5,10 % (8 individuos) mostró riesgo intermedio (PSA= 10-19,90 ng/mL); y el 3, 80 %(6 pacientes) tuvo un riesgo alto (PSA ≥20 ng/mL). El promedio del índice de masa corporal (IMC) fue 26,37±3,81 kg/m2 : 85 pacientes (54,50 %) tenían sobrepeso; y 18 (11,50 %), obesidad. La media de PSA masa fue14,89±30,50 μg; la superficie corporal (SC) se calculó en 3,93± 2,72 m2; y el volumen plasmático fue 4,18± 0,21 L. Se evidenció una correlación positiva muy baja entre el PSA plasmático y la edad (rho = 0,184; p = 0,022), así como con entre la PSA masa y la edad (rho = 0,176; p = 0,028). Se obtuvo una asociación positiva moderada entre el PSA plasmático y la superficie corporal (SC) (rho = 0,456; p = 0,000); y entre el PSA masa y SC (rho = 0,463; p = 0,000). No se encontró relación entre el IMC y el PSA. Conclusiones: Se evidenció la asociación entre el valor de PSA plasmático y PSA masa con el perfil antropométrico, según el riesgo de padecer enfermedades prostáticas, que fue mayor con la superficie corporal y la edad.

Objective: To determine the association between plasma and mass prostate-specific antigen (PSA) levels and the anthropometric profile, taking into account the risk of prostate pathologies. Materials and methods: A correlational, quantitative, cross-sectional and retrospective study conducted with a sample of 156 medical records of male patients with PSA tests and anthropometric data. Spearman's Rho with a 95 % confidence level was used to analyze the relationship between the variables. Results: The average age of the patients was 67.85 ± 10.83 years and their mean PSA value was 3.57 ± 7.30 ng/mL. Fifteen (15) patients (9.60 %) had a low risk (PSA = 4.1 - 9.90 ng/mL), eight (5.10 %) a medium risk (PSA = 10 - 19.90 ng/mL) and six (3.80 %) a high risk (PSA ≥ 20 ng/mL) of developing prostate pathologies. The mean body mass index (BMI) was 26.37 ± 3.81 kg/m2: 85 patients (54.50 %) were overweight and 18 (11.50 %) were obese. The mean mass PSA was 14.89 ± 30.50 μg, the body surface area (BSA) was 3.93 ± 2.72 m2 and the plasma volume was 4.18 ± 0.21 L. A very low positive correlation was evidenced between plasma PSA and age (rho = 0.184; p = 0.022) and between mass PSA and age (rho = 0.176; p = 0.028). There was a moderate positive association between plasma PSA and BSA (rho = 0.456; p = 0.000) and between mass PSA and BSA (rho = 0.463; p = 0.000). No relationship was found between BMI and PSA. Conclusions: The association between plasma and mass PSA levels and the anthropometric profile was demonstrated, taking into account the risk of prostate pathologies, which increased with BSA and age.

Is there an association between prostate-specific antigen and androgen levels in 46, XX patients with congenital adrenal hyperplasia?

INTRODUCTION: Congenital adrenal hyperplasia (CAH), a genetic disease characterized by defective cortisol synthesis and excessive levels of sex hormones, can cause precocious puberty in both sexes in untreated individuals and virilization in female patients with a 46, XX karyotype. The female paraurethral (Skene's) gland has been reported as prostate analogous. Growth of prostate tissue is associated with androgen production; therefore, prostate-specific antigen (PSA) levels may represent a marker of virilization in 46, XX patients with CAH. OBJECTIVES: To describe PSA levels in 46, XX patients and evaluate whether higher PSA levels are associated with androgenization and the severity of the disease. STUDY DESIGN: Sixty-six patients with CAH and a 46, XX karyotype were included, irrespective of age. Serum PSA, testosterone, 17-hydroxyprogesterone (17-OHP) and androstenedione levels were measured. Patients' age, age at diagnosis, forms of the disease, Prader classification, bone age assessment, sex of rearing, surgery, and the presence of clinical complications were obtained from their medical records. RESULTS: The mean age of patients was 11.45 ± 10.74 years. Forty-three patients (65%) were diagnosed neonatally at a median of 0.08 years (mean 1.47 ± 2.34 years), with registers of 17-OHP measurements (Guthrie test) being available in 51%. Testosterone, 17-OHP and androstenedione were significantly high. PSA was detectable in 25% of cases (levels >0.01 ng/ml), with a mean of 0.03 ± 0.09 ng/ml, and only in patients over five years of age. A correlation was found between PSA and age (p < 0.001), age at diagnosis (p = 0.002), testosterone (p = 0.001) and androstenedione (p = 0.023). There was no correlation between PSA and the forms of CAH or Prader classification. A sub-analysis of the patients over five years of age in whom PSA was detectable also showed that there was a correlation between PSA (p < 0.05) and age at analysis, age at diagnosis, testosterone and androstenedione levels. DISCUSSION: Limitations of this study include the small sample size due to the rareness of the disease, its retrospective nature, the absence of a control group, the fact that the sample was selected at two referral centers, which could have resulted in a selection bias, and the use of different reference values in the different laboratories conducting the PSA tests. CONCLUSIONS: PSA is detectable in 25% of 46, XX patients with CAH, only after five years of age. PSA level increases significantly with age, age at diagnosis, and testosterone and androstenedione levels, confirming a correlation between PSA levels and elevated androgen levels.

Impacto de la obesidad en la agresividad del cáncer de próstata / Impact of obesity on the aggressiveness of prostate cancer / Impacto da obesidade na agressividade do câncer de próstata

RESUMEN El cáncer de próstata suele diagnosticarse tardíamente en obesos debido a que el exceso de tejido adiposo dificulta la detección del tumor al interferir en la exploración física (dificultad para realizar el tacto rectal) y en la confiabilidad de exámenes de diagnóstico complementarios como el Antígeno Prostático Específico (PSA, por sus siglas en inglés), retardando de esta forma la realización de la biopsia prostática. Con el objetivo de identificar la relación entre la obesidad y la agresividad del cáncer de próstata al momento de su diagnóstico, se realizó un estudio transversal, analítico en 136 pacientes diagnosticados con cáncer de próstata mediante biopsia transrectal, en el Hospital Provincial "Carlos Manuel de Céspedes", de Bayamo, Granma, Cuba, desde el 1ro de enero de 2018 hasta el 31 de diciembre de 2020. El análisis de asociación entre las variables (Índice de Masa Corporal [IMC], PSA, Suma de Gleason y Estadio Clínico) se realizó a través de la prueba de Tukey y la U de Mann-Whitney. La edad promedio de los pacientes fue de 66,1 años. No se encontró asociación significativa entre el PSA y el IMC (p > 0,05), sin embargo, el valor del PSA mostró una tendencia a disminuir en la medida que aumentó el IMC. La suma de Gleason y el Estadio Clínico mostraron una asociación directa con el IMC, (p<0,003) y (p=0.000) respectivamente. Los pacientes con sobrepeso y obesidad fueron más propensos a presentar valores de PSA más bajos y mayor Gleason, manifestándose en estos un mayor riesgo de cáncer de próstata agresivo al momento del diagnóstico.

ABSTRACT Prostate cancer is often diagnosed late in obese because excess adipose tissue makes it difficult to detect the tumor by interfering with physical examination (difficulty performing rectal touch) and the reliability of complementary diagnostic tests such as Psa, the delaying prostate biopsy. In order to identify the relationship between obesity and the aggressiveness of prostate cancer at the time of diagnosis, a cross-sectional, analytical study was conducted in 136 patients diagnosed with prostate cancer by transrectal biopsy, at the Provincial Hospital "Carlos Manuel de Céspedes", Bayamo, Granma, Cuba, from January 1, 2018 to December 31, 2020. The association analysis between the variables (Body Mass Index [BMI], PSA, Gleason Sum and Clinical Stage) was performed through the Mann-Whitney Tukey and U test. The average age of patients was 66.1 years. No significant association was found between PSA and BMI (p > 0.05), however, the psa value showed a tendency to decrease as BMI increased. The sum of Gleason and the Clinical Stadium showed a direct association with BMI, (p<0.003) and (p-0.000) respectively. Overweight and obese patients were more likely to develop lower PSA and higher Gleason values, with an increased risk of aggressive prostate cancer at the time of diagnosis.

RESUMO O câncer de próstata é frequentemente diagnosticado tardiamente em obesidade porque o excesso de tecido adiposo dificulta a detecção do tumor interferindo no exame físico (dificuldade em realizar o toque retal) e a confiabilidade de exames diagnósticos complementares como psa, a biópsia da próstata retardando. Como objetivo de identificar a relação entre obesidade e agressividade do câncer de próstata no momento do diagnóstico, foi realizado umestudo transversal e analítico em 136 pacientes diagnosticados comcâncer de próstata por biópsiatransretal, no Hospital Provincial "Carlos Manuel de Céspedes", bayamo, Granma, Cuba, de 1º de janeiro de 2018 a 31 de dezembro de 2020. A análise de associação entre as variáveis (Índice de Massa Corporal [IMC], PSA, Gleason Sum e Estágio Clínico) foi realizada através do teste Mann-WhitneyTukey e U. A idademédia dos pacientes foi de 66,1 anos. Nãofoi encontrada associação significativa entre PSA e IMC (p > 0,05), porém, o valor do PSA apresentou tendência a diminuir à medida que o IMC aumentou. A soma de Gleason e do Estádio Clínico mostrou associação direta com o IMC, (p<0.003) e (p-0,000), respectivamente. Pacientes com sobrepeso e obesidade foram mais propensos a desenvolver menores valores de PSA e Gleason mais elevados, commaior risco de câncer agressivo de próstata no momento do diagnóstico.

Importance of prostate-specific antigen (PSA) as a predictive factor for concordance between the Gleason scores of prostate biopsies and RADICAL prostatectomy specimens

OBJECTIVE: To evaluate the concordance between the Gleason scores of prostate biopsies and radical prostatectomy specimens, thereby highlighting the importance of the prostate-specific antigen (PSA) level as a predictive factor of concordance. METHODS: We retrospectively analyzed 253 radical prostatectomy cases performed between 2006 and 2011. The patients were divided into 4 groups for the data analysis and dichotomized according to the preoperative PSA, <10 ng/mL and ≥10 ng/mL. A p-score <0.05 was considered significant. RESULTS: The average patient age was 63.3±7.8 years. The median PSA level was 9.3±4.9 ng/mL. The overall concordance between the Gleason scores was 52%. Patients presented preoperative PSA levels <10 ng/mL in 153 of 235 cases (65%) and ≥10 ng/mL in 82 of 235 cases (35%). The Gleason scores were identical in 86 of 153 cases (56%) in the <10 ng/mL group and 36 of 82 (44%) cases in the ≥10 ng/mL group (p = 0.017). The biopsy underestimated the Gleason score in 45 (30%) patients in the <10 ng/mL group and 38 (46%) patients in the ≥10 ng/mL (p = 0.243). Specifically, the patients with Gleason 3 + 3 scores according to the biopsies demonstrated global concordance in 56 of 110 cases (51%). In this group, the patients with preoperative PSA levels <10 ng/dL had higher concordance than those with preoperative PSA levels ≥10 ng/dL (61% x 23%, p = 0.023), which resulted in 77% upgrading after surgery in those patients with PSA levels ≥10 ng/dl. CONCLUSION: The Gleason scores of needle prostate biopsies and those of the surgical specimens were concordant in approximately half of the global sample. The preoperative PSA level was a strong predictor of discrepancy and might improve the identification of those patients who tended to be upgraded after surgery, particularly ...

Prostate cancer risk prediction in a urology clinic in Mexico.

OBJECTIVES: To evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score ≥ 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). METHODS AND MATERIALS: From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC. RESULTS: Rates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13). CONCLUSIONS: Lack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics.

Prostatic tissue markers in the dog / iptcadores de tecido prostático no cão

Although prostatic diseases are common in older dogs, diagnosis can be difficult due to the presence of concurrent alterations. The routine evaluation of the prostate is not common in veterinary practice, and thus the diagnosis of prostate disease is often late, and the prognosis very poor. The study of other diagnostic methods, such as prostate tissue markers, can help to improve the success rate of treatments.

As enfermidades prostáticas são comuns em cães idosos, sendo o diagnóstico dificultado pela presença de concomitantes alterações. Contudo, a avaliação rotineira da próstata não é muito comum na prática veterinária. Dessa forma, o diagnóstico é realizado tardiamente e o prognóstico toma-se reservado. O estudo de outros métodos de diagnóstico, como os marcadores de tecido prostático, contribuirá para obtenção de maior sucesso no tratamento.

Prostatic tissue markers in the dog / iptcadores de tecido prostático no cão

Although prostatic diseases are common in older dogs, diagnosis can be difficult due to the presence of concurrent alterations. The routine evaluation of the prostate is not common in veterinary practice, and thus the diagnosis of prostate disease is often late, and the prognosis very poor. The study of other diagnostic methods, such as prostate tissue markers, can help to improve the success rate of treatments.

As enfermidades prostáticas são comuns em cães idosos, sendo o diagnóstico dificultado pela presença de concomitantes alterações. Contudo, a avaliação rotineira da próstata não é muito comum na prática veterinária. Dessa forma, o diagnóstico é realizado tardiamente e o prognóstico toma-se reservado. O estudo de outros métodos de diagnóstico, como os marcadores de tecido prostático, contribuirá para obtenção de maior sucesso no tratamento.