Prostatic Neoplasia Research Articles

In Vitro Cytotoxic Activity and In Vivo Antiproliferative Activity of Ethyl Acetate Fraction of Bunium bulbocastanum Seed Against Prostatic Neoplasia

AbstractSeveral in vitro investigations of the therapeutic characteristics of B. bulbocastanum have shown that it has cytotoxic, antifungal, and antibacterial effects. It also exhibits antioxidant and anticancer effects. When the ethyl acetate fraction of B. bulbocastanum was examined for its phytochemical composition, it was found to be rich in phenolic compounds and had significant cytotoxic effects on PC-3 cell lines. The prostate length-to-weight ratio was significantly higher in vivo in the ethyl acetate fraction-treated group. Compared to the disease control group, histopathological examination of the ethyl acetate-treated group revealed a reduction in inflammation and malignant lesions, confirming its antiproliferative efficacy. According to serum biochemistry, acid phosphatase and PSA levels in the ethyl acetate fraction treatment group were significantly lower than those in the disease control group. When compared to the disease control group, malondialdehyde levels in the ethyl acetate fraction treatment group were likewise reduced dramatically. However, in the group treated with the ethyl acetate fraction, glutathione levels increased considerably. The ethyl acetate fraction of B. bulbocastanum may have cytotoxic and antiproliferative potential, both in vitro and in vivo.

Intraprostatic hormone dosage: Validation of a novel prostate biopsy technique

BackgroundAdvances in chromatography and mass spectrometry have allowed us to develop a novel technique for measuring intraprostatic hormone concentrations directly on prostate needle biopsies, rather than using traditional punch excision. This has significant clinical implications as intraprostatic dihydrotestosterone and testosterone levels could help monitor prostate growth, neoplasia and castration resistance. MethodsPatients undergoing radical cystoprostatectomy for bladder cancer were prospectively included. Each prostate specimen received one 90mg punch excision and six needle biopsies. Intraprostatic hormones were dosed through gas chromatography-mass spectrometry. ResultsWe included twenty patients, of which eleven were incidentally diagnosed with prostate cancer; four had ISUP 1 (20%) and seven had ISUP 2 (35%). The prostate biopsy technique was unable to obtain measures for testosterone, Delta-4-androsterone and androstenedione. Tissue concentrations of DHEA, DHT, E1 and E2 can be obtained with no significant difference from the reference established on a punch from a single biopsy core sample. ConclusionsOur study demonstrates that intraprostatic concentrations of DHEA, DHT, E1 and E2 can be measured without significant difference from the reference established on a single punch excision. This finding opens the way to research on the interactions between endocrinology and prostate oncogenesis and particularly on the mechanisms of resistance to hormone therapies in vivo. Level of evidence2

Incidental Myocardial Uptake in Patients with Prostate Cancer: A Challenging Subject

Background: Countless confounding factors have been described in the interpretation of incidental myocardial uptakes. Among them, prostate cancer is probably the most important. While some authors may defend the benign etiology of these uptakes, others propose a further study to rule out amyloid cardiomyopathy. Objective: Our aim is to investigate the clinical relevance of incidental myocardial uptakes in bone scans requested to evaluate prostatic neoplasia, assessing the possibility that the described uptakes correspond to cardiac amyloidosis (CA). Methods: Retrospective revision of 997 patients, 20 of which showed incidental myocardial uptake. We performed a cardiological study in these 20 patients in order to indicate whether the myocardial uptake is just attributable to prostate cancer or data suggesting CA. Results: By analysing clinical, biochemical and imaging data, 11 out of 20 of the patients had two or more Red-Flags of transthyretin amyloid cardiomyopathy (ATTR-c). In the other four cases, there was one Red-Flag suggestive of ATTR-c. Conclusions: When myocardial uptake is detected incidentally in patients with prostate cancer, it cannot be attributed to the neoplasm itself before ruling out cardiac amyloidosis. Therefore, a cardiological study must be carried out following current protocols for the diagnosis of transthyretin amyloid heart disease.

Discovery of PSMA in the prostate of the common marmoset (Callithrix jacchus).

Prostate-specific membrane antigen (PSMA) is a biomarker and therapeutic target of high relevance in prostate cancer. Although upregulated PSMA expression is a well-documented feature of prostatic neoplasia in both humans and canids, to date humans are the only species known to express PSMA basally in the prostate. Thus, traditional laboratory animal species have limited utility for studying PSMA biology in the prostate or for predicting efficacy or toxicity of PSMA-targeted agents. PSMA expression in human, macaque, and marmoset prostates was determined by immunohistochemistry, employing an antibody with validated cross-species reactivity in a PSMA-positive control tissue; kidney. We newly discover that the common marmoset endogenously expresses PSMA in non-diseased prostate, similar to humans, and thus may be a valuable preclinical model for researchers studying PSMA.

Canine Prostate Cancer: Current Treatments and the Role of Interventional Oncology.

Prostate carcinoma is one of the most common cancers worldwide in men, with over 3 million men currently living with prostate carcinoma. In men, routine screening and successful treatment schemes, including radiation, prostatectomy, or hormone therapy, have allowed for high survivability. Dogs are recognized as one of the only mammals to spontaneously develop prostate neoplasia and are an important translational model. Within veterinary medicine, treatment options have historically been limited in efficacy or paired with high morbidity. Recently, less invasive treatment modalities have been investigated in dogs and people and demonstrated promise. Below, current treatment options available in dogs and people are reviewed, as well as a discussion of current and future trends within interventional treatment for canine PC.

Digital postprocessing analysis of prostatic perfusion in neutered dogs.

B-mode ultrasound is routinely performed to evaluate the prostate gland in neutered dogs, although, the detection of malignancies may be challenging. Contrast-enhanced ultrasound (CEUS) has shown to be useful for the assessment of prostatic perfusion in normal and diseased dogs, although the interpretation of contrast ultrasonographic features may still be subjective. A quantitative tool for evaluating prostatic perfusion might improve the reliability of the results in terms of early detection of prostate neoplasia in neutered dogs. The present study aimed to evaluate the applicability of a postprocessing analysis tool to CEUS of the prostate in healthy neutered dogs, to provide quantitative measurements, and to study the influence of individual characteristics on prostatic regression. Twenty-three neutered dogs underwent a B-mode and CEUS examination of the prostate to acquire data about prostatic morphology and microcirculation. The prostate was imaged using a 5-7.5MHz linear transducer and contrast was administered intravenously. Videoclips were analyzed by using Qontrast software and a postprocessing digital analysis tool (ImageJ) to measure perfusion peak intensity, time to peak, and vascularization ratio at the moment of the peak, which were then related to body weight, age, and time elapsed since orchiectomy. Correlation tests revealed higher vascularization in younger compared with older dogs (P<.05) and in smaller compared with larger dogs (P<.05). Time elapsed since orchiectomy (P>.05) did not affect prostatic perfusion. Contrast-enhanced ultrasound and the postprocessing analysis tool ImageJ allowed analysis of vascular perfusion in all dogs and have the potential to improve the diagnostic possibilities for andrological examination.

Prostate cancer mortality temporal trend in Brazil

Prostate cancer (CaP) is the second most common malignant tumor among men in Brazil and represents a significant factor in mortality when diagnosed late. Studies on mortality are relevant sources for understanding the epidemiological profile and measuring the importance of PCa as a public health problem. The objective was to describe the distribution and temporal trends of the mortality rate in different age groups (30 to 80 years or more) in Brazil between the years 2011 - 2020. The research has a quantitative and analytical character, through the collection of mortality data in the Mortality Information System (SIM) of the Ministry of Health (SIM/MS/DATASUS). The mortality rate due to malignant prostate neoplasia was calculated annually, considering age range, and then arranged in simple dispersion data. According to the analyses, it was observed that the incidence of prostate cancer was 95.17% in individuals over 60 years of age, highlighting the age group of 80 years or more in which it was 44%. Furthermore, the mortality rate prevailed in white ethnic groups, with low education and married people. Among the years analyzed, the period with the peak in mortality was in 2017, representing 29.25%. Furthermore, a linear decline in PCa mortality rates was evidenced in all age groups between 2011 and 2020. However, there was a higher prevalence of deaths from the sixth decade of life onwards, with emphasis on the population over 80 years. And, it was possible to observe a lower number of deaths among individuals aged 30 to 59 years.

Periprostatic adipose tissue thromboinflammation triggers prostatic neoplasia in early metabolic impairment: Interruption by rivaroxaban

AimsProstate cancer is among the highest incidence malignancies in men with a prevalence rate increasing in parallel to the rising global trends in metabolic disorders. Whereas a sizeable body of evidence links metabolic impairment to negative prognosis of prostate cancer, the molecular mechanism underlying this connection has not been thoroughly examined. Our previous work showed that localized adipose tissue inflammation occurring in select adipose depots in early metabolic derangement instigated significant molecular, structural, and functional alterations in neighboring tissues underlying the complications observed at this stage. In this context, the periprostatic adipose tissue (PPAT) constitutes an understudied microenvironment with potential influence on the prostatic milieu. Main methods and resultsWe show that PPAT inflammation occurs in early prediabetes with signs of increased thrombogenic activity including enhanced expression and function of Factor X. This was mirrored by early neoplastic alterations in the prostate with fibrosis, increased epithelial thickness with marked luminal cellular proliferation and enhanced formation of intraepithelial neoplasia. Significantly, interruption of the procoagulant state in PPAT by a 10-day anticoagulant rivaroxaban treatment not only mitigated PPAT inflammation, but also reduced signs of prostatic neoplastic changes. Moreover, rivaroxaban decreased the murine PLum-AD epithelial prostatic cell viability, proliferation, migration, and colony forming capacity, while increasing oxidative stress. A protease-activated receptor-2 agonist reversed some of these effects. SignificanceWe provide some evidence of a molecular framework for the crosstalk between PPAT and prostatic tissue leading to early neoplastic changes in metabolic impairment mediated by upregulation of PPAT thromboinflammation.

Diagnostic Utility of PSMA 18F-DCFPyL PET/TC in Occult Biochemical Recurrence of Prostate Carcinoma with PSA Values

To analyze the diagnostic capability of PET-PSMA in clinical practice in patients with occult biochemical recurrence of prostate carcinoma with PSA values less than 2ng/ml. The first 116 patients who underwent PSMA 18F-DCFPyL PET/TC at the centers participating in the study for occult biochemical recurrence of prostatic neoplasia were selected. All patients had low PSA values (<2ng/ml). The studies were visually assessed by two experts in Nuclear Medicine, and classified dichotomously as positive or negative/inconclusive. The diagnostic capacity of the test was determined according to the PSA values, as well as the densities by groups. Descriptive statistical analysis was performed. The AUC was evaluated, determining the optimal cut-off point and its precision parameters. The retrospective analysis showed that 66/116 patients (56.9%) were positive, with statistically significant differences in the medians of the positive group (AUC 0.77) and 50/116 (43.1%) patients were negative (AUC 0.42). The study of densities by group showed a marked clustering of the negative/ inconclusive studies in PSA values less than 0.5 ng/ml. Correlation was observed between the PSA values and the detection capability of the test (AUC: 0,74). The optimal cut-off point calculated was 0,55 which showed a sensitivity of 0,75 and specificity of 0,68. PET-PSMA shows excellent diagnostic capability even in strictly selected patients with PSA values < 2ng/ml. Its indication with values < 0.5ng/mL should be assessed according to individual risk. In 56.9% of the patients in the study the positive result could influence changes in therapeutic strategy.

Probing the Relationship Between the Human Gut Microbiome and Prospects of Prostate Cancer: A Systematic Review.

Prostate neoplasia is one of the most commonly occurring neoplasias in males and has a high mortality rate. Prostate cancer (PCA) risk factors include tall stature, male sex, known family history, obesity, high blood pressure, lack of fitness, higher levels of testosterone for a long time, increasing age, and ethnicity are well known. The association and role of the gut microbiota in different diseases in our body have been highlighted recently. Therefore, finding the influence of gut microbiota on the prostatic cells can be useful for preventing prostatic neoplasia and/or reducing its severity. We aimed to assess its impact on PCA risk. We thoroughly searched databases for the relevant literature for our systematic review. The final research papers analyzed how bacteria played a role in the risk of PCA, either through inflammation or the production of metabolites that increase/decrease the risk of PCA. Based on the studies reviewed, we found that some gut bacteria play a role in the formation of PCA. In contrast, some bacteria can help prevent PCA, but the metabolism of the dietary components is the major factor for PCA.

The impacts of exposure to bisphenol A in the adult female prostate Meriones unguiculatus

The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-β estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERβ, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate.

Surgical Management of Canine Prostatic Neoplasia: - A Case Report

Surgical Management of Canine Prostatic Neoplasia: - A Case Report

ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer.

The mechanisms underlying ETS-driven prostate cancer initiation and progression remain poorly understood due to a lack of model systems that recapitulate this phenotype. We generated a genetically engineered mouse with prostate-specific expression of the ETS factor, ETV4, at lower and higher protein dosage through mutation of its degron. Lower-level expression of ETV4 caused mild luminal cell expansion without histologic abnormalities, and higher-level expression of stabilized ETV4 caused prostatic intraepithelial neoplasia (mPIN) with 100% penetrance within 1 week. Tumor progression was limited by p53-mediated senescence and Trp53 deletion cooperated with stabilized ETV4. The neoplastic cells expressed differentiation markers such as Nkx3.1 recapitulating luminal gene expression features of untreated human prostate cancer. Single-cell and bulk RNA sequencing showed that stabilized ETV4 induced a previously unidentified luminal-derived expression cluster with signatures of cell cycle, senescence, and epithelial-to-mesenchymal transition. These data suggest that ETS overexpression alone, at sufficient dosage, can initiate prostate neoplasia.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

What is your diagnosis? Perineal swelling in a dog.

What is your diagnosis? Perineal swelling in a dog.

Robotic-Assisted Pelvic Surgery: Early Outcomes in a Single Institution.

Introduction: This article reports the authors' experience with their first 50 consecutive robotic pelvic procedures, aiming to determine the feasibility and safety of adopting robotic pelvic surgery. Robotic surgery offers several benefits for minimally invasive surgery, but its applicability is hindered by cost and limited regional experience. This study aimed to evaluate the feasibility and safety of robotic pelvic surgery. Material and Methods: This is a retrospective review of our initial experience with robotic surgery for colorectal, prostate, and gynaecologic neoplasia, between June and December 2022. The surgical outcomes were evaluated in terms of perioperative data, such as operative time, estimated blood loss, and length of hospital stay. Intraoperative complications were recorded, and postoperative complications were evaluated at 30 days and 60 days after surgery. The feasibility of the roboticassisted surgery was assessed by measuring the conversion rate to laparotomy. The safety of the surgery was evaluated by recording the incidence of intraoperative and postoperative complications. Results: Fifty robotic surgeries were performed over 6 months, including 21 interventions for digestive neoplasia, 14 gynaecologic cases, and 15 prostatic cancers. Operative time ranged from 90 to 420 minutes, with two minor complications and two grade II Clavien-Dindo complications. One patient required prolonged hospitalization and an end-colostomy, deriving from an anastomotic leakage requiring reintervention. No thirty-day mortality or readmissions were reported. Conclusion: The study found that robotic-assisted pelvic surgery is safe and has a low rate of transfer to open surgery, making it a suitable addition to conventional laparoscopy.

Benign prostatic hyperplasia in the dog

In small animal practice, prostatic diseases are increasingly encountered. All dogs may experience prostatic disease, but there should be particular attention to breeding dogs, as prostatic disease may decrease semen quality and fertility. The most common prostatic disease is benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the gland affecting intact adult dogs, part of an aging process, including both an increase in cell numbers (hyperplasia) and in cell size (hypertrophy). Acute and chronic prostatitis, prostatic abscess, prostatic neoplasia and prostate squamous metaplasia also occur in dogs, in order of frequency. These diseases often lack pathognomonic clinical signs; therefore, a thorough clinical examination and a correct diagnostic protocol are essential to determine the most appropriate treatment or prophylaxis. Frequently dogs with BPH are asymptomatic, but when clinical signs are present, the most common is a serous to sanguineous urethral discharge. BPH therapy includes various options and is usually recommended when mild-severe signs are present or if clinical signs disturb the dog. In most dogs with this disorder, it is possible to maintain fertility by avoiding castration and choosing alternative therapeutic approaches.

Prospective comparison of prostatic aspirate culture and cystocentesis urine culture for detection of bacterial infection in dogs with prostatic neoplasia.

The purpose of this study was to determine whether prostatic aspirate culture is a superior method to detect infection compared to culture of urine collected by cystocentesis in dogs with prostatic neoplasia. A prospective study was conducted and dogs with suspected or confirmed prostatic neoplasia were enrolled. Urinalysis was done and culture and antimicrobial susceptibility testing was performed on paired urine and prostatic aspirate samples collected at a single timepoint. Ten dogs with prostatic neoplasia were enrolled. All dogs had one or more clinical sign consistent with lower urinary tract disease. One dog (10%) had a positive urine culture, but negative prostatic aspirate culture, one dog (10%) had a positive prostatic aspirate culture, but negative urine culture, and one dog (10%) had both positive urine and prostatic aspirate cultures. Using prostatic aspirate culture as the reference standard, urine culture had a sensitivity for detecting infection of 87.5% (95% confidence interval 52.9 to 99.4) and specificity of 50% (92.6 to 97.4) in this population of dogs. Positive cultures were uncommon with both culture collection methods. Study results did not identify prostatic aspirate culture to be a more sensitive method of detecting prostatic infection than urine culture collected by cystocentesis in these dogs with prostatic neoplasia.

Differential impact of PI3K/AKT/mTOR signaling on tumor initiation and progression in animal models of prostate cancer.

The PI3K/AKT/mTOR signaling pathway is essential for initiation and progression of prostate cancer. However, there has been no a comprehensive comparison for the role of these signaling nodes in prostate tumor initiation and progression. With genetically engineered animal models, we compared the impact of prostate-specific deletions of Pten, Tsc1, and Tsc2 and activation of Akt1 on tumor initiation and progression. Also, we assessed the expression and genetic alterations of PTEN, AKT1, TSC1, and TSC2 in human primary prostate cancers. For the genetically engineered mice, prostate conditional knockout (cKO) of Pten, Tsc1, and Tsc2 led to initiation and progression of mouse prostatic neoplasia hyperplasia (mPIN). Akt1 transgenic mice developed more aggressive mPINs than mice with Tsc1 or Tsc2 single-cKO, but the effect was more moderate than that for Pten single-cKO or Tsc1/Tsc2 double-cKO mice. Functional analyses showed that Pten single-cKO, AKT1 activation, and Tsc1/Tsc2 double-cKO induced cell proliferation more than Tsc1 or Tsc2 single-cKO, but only Pten single-cKO and AKT1 activation reduced epithelial adhesion. All cKO or AKT1 activation enhanced the phosphorylation of p-S6 (S235/236) but only Pten single-cKO and Tsc1/Tsc2 double-cKO enhanced the phosphorylation of p-AKT (S473) and p-4EBP1 (T37/46/70). In human prostate cancers, PTEN, but not AKT1, TSC1, or TSC2 had frequent genetic alterations. However, as key signaling nodes, AKT1, TSC1, and TSC2 may be responsible for PTEN loss-mediated tumor initiation and progression. Our results for genetically engineered mouse models suggest a differential role of the PI3K/AKT/mTOR signaling nodes in prostate cancer initiation and progression, but the underlying molecular mechanisms remain unaddressed.

MRI characteristics of canine prostatic neoplasia.

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics. The most consistent characteristics were heterogeneous hyperintensity of the tumor on T2-weighted images (10/10) and short tau inversion recovery images (10/10), prostatic capsular margin distortion by the tumor (10/10), cavitations (10/10), complete effacement of the prostatic architecture (9/10), neurovascular bundle (NVB) compression or invasion (9/10), heterogeneous isointensity of the tumor on T1-weighted images (9/10), and strong contrast enhancement of the tumor (8/10). Additional features included an overlying pattern of distorted radiating striations (7/10), regional lymphadenomegaly (5/10), mineralization within the mass (5/10), urinary bladder trigone involvement (6/10), and post-prostatic urethral involvement (7/10). These findings supported the use of MRI as an adjunct imaging modality for diagnosis and therapeutic planning of prostatic neoplasia and including prostatic neoplasia as a likely differential diagnosis for dogs with these MRI characteristics.