Computed tomographic features of canine prostatic carcinoma.

Canine prostatic carcinoma (PC) has incompletely defined CT features. The purpose of this multicenter retrospective case series was to assess prostatic, regional, and distant findings of PC. Thirty dogs were enrolled. Consistent prostatic features included postcontrast heterogeneity with hypoattenuating, nonenhancing areas (30/30), capsular distortion (29/30), prostatic urethral effacement, displacement, or invasion (28/30), precontrast heterogeneity (27/30), and mineralization (24/30) which was always within or at the margin of the hypoattenuating areas. Consistent extraprostatic features included medial iliac lymph node enlargement (20/30), internal iliac lymph node enlargement (15/30), and periprostatic fat streaking or fluid (15/29). In a minority of dogs, there was lymph node mineralization, bladder trigone invasion, ureteral dilation, ductus deferens invasion, and bony changes consistent with hypertrophic osteopathy. Strongly suspected and potential bony metastases were noted infrequently (8/26), all in vertebrae regional to the prostate. In conclusion, these findings provide guidance on the expected CT features of canine PC.

Anti-tumour effects of lapatinib on HER2-positive canine prostatic carcinoma cell lines.

Background: Canine prostatic carcinoma (cPC) is a urogenital tumour with a poor prognosis, for which no effective treatment has been established. Recently, it has been shown that human epidermal growth factor receptor type 2 (HER2) is overexpressed in cPC cells; however, the efficacy of HER2-targeted therapy remains unclear. Aim: Investigate the anti-tumour effect of lapatinib on HER2-positive cPC cell lines. Methods: Two cell lines (muPC and bePC) were established from two dogs with cPC and the effects of lapatinib treatment on cell proliferation, apoptosis, and HER2 downstream signalling were investigated. Furthermore, muPC was used to generate tumour-bearing mice, and the anti-tumour effects of lapatinib were examined in vivo. Results: Lapatinib treatment inhibited the proliferation and phosphorylation of Erk1/2 and Akt, which are downstream signals of HER2. Furthermore, the TUNEL assay showed that lapatinib induced apoptosis in both cell lines. The muPC-engrafted nude mouse model showed that lapatinib significantly inhibited tumour growth and increased the area of necrotic tumour tissue compared to the vehicle-treated groups. Conclusion: Lapatinib exerts anti-tumour effects on cPC cells by inhibiting HER-2 signalling.

Effective detection of BRAFV595E mutation in canine urothelial and prostate carcinomas using immunohistochemistry.

Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E-specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600-specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost-efficient test for large-scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate / Associação entre diminuição da expressão dos receptores de estrógeno alfa e andrógeno, e imunoexpressão de fosfatase e tensina homóloga na próstata canina

Canine prostate gland is a hormonal dependent organ and its imbalance of estrogen and androgen receptor expressions are directly associated with the development of different diseases. Due to the lack of information regarding the behavior of the aforementioned receptors in canine prostate cancer (PC), this study aimed to identify estrogen receptor alpha (ERα), androgen receptor (AR), Ki67 and phosphatase and tensin homolog (PTEN) protein expressions in canine PC by immunohistochemistry. We found nuclear expression of ERα and AR in the epithelial cells of normal canine samples and a loss of protein expression in PC samples. Normal samples showed Ki67 expression in a few basal cells and the PC samples showed the highest mean of positive cells (253.1). Canine prostate cancer showed a high proliferative index, which was associated with independence of hormonal actuation. PTEN showed positive nuclear and cytoplasmic expression in normal canine samples and a loss in PC. Loss of ERα, AR and PTEN indicated that canine PC exhibits the same immunohistochemical phenotype as in human patients with PC resistant to hormonal therapy. Therefore, canine PC should be considered as a model to study human PC resistant to hormonal therapy.(AU)

A glândula prostática canina é um órgão dependente de hormônio, e o desequilíbrio na expressão dos receptores de estrógeno e andrógeno estão diretamente associados com o desenvolvimento de diferentes doenças. Devido à falta de informação sobre o comportamento desses receptores no câncer prostático canino (PC), este estudo tem por objetivo identificar a expressão proteica através da técnica de imuno-histoquímica do receptor de estrógeno alfa (REα), receptor de andrógeno (RA), Ki67 e fosfatase e tensina homóloga (PTEN). Foi encontrado nas células epiteliais prostáticas normais caninas a expressão nuclear de REα e RA, e perda de expressão proteica nas amostras de PC. As amostras normais apresentaram expressão de Ki67 em poucas células basais e as amostras de PC apresentaram a maior média de células positivas (253,1). O câncer de próstata canino apresentou uma taxa alta de proliferação, o qual foi associado com a atuação independente de hormônio. As amostras de próstatas caninas normais revelaram marcação nuclear e citoplasmática da proteína PTEN e perda nas amostras de PC. A perda de REα, RA e PTEN indicam que as amostras de PC exibem o mesmo fenótipo imuno-histoquímico de pacientes humanos com câncer prostático resistente a terapia hormonal. Sendo assim, o PC canino deve ser considerado um modelo para estudos de câncer prostático humano resistente a terapia hormonal.(AU)

Vías relacionadas con IGF-1 (Insulin-like growth factor-1) y promoción de dieta alta en grasas en la progresión del cáncer de próstata en ratones TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) / Insulin-Like growth factor 1 related pathways and high-fat diet promotion of transgenic adenocarcinoma mouse prostate (TRAMP) cancer progression

Introducción: Nuestro objetivo fue investigar el papel de las vías relacionadas con IGF-1 en la promoción de dieta alta en grasas (DAG) de la progesión del cáncer de próstata en ratones TRAMP. Métodos: Los ratones TRAMP fueron divididos aleatoriamente en 2 grupos: el grupo DAG y el grupo de dieta normal. Los ratones TRAMP de ambos grupos fueron sacrificados y se tomaron muestras en las semanas 20, 24 y 28, respectivamente. Los niveles séricos de insulina, IGF-1 e IGF-2 se probaron mediante ELISA. El tejido prostático de los ratones TRAMP se utilizó tanto para tinción H-E como para tinción inmunohistoquímica de proteínas de la vía relacionadas con IGF-1, incluyendo IGF-1Rα, IGF-1Rβ, IGFBPs y AKT. Resultados: La mortalidad de los ratones TRAMP del grupo DAG fue significativamente más alta que la del grupo de dieta normal (23,81% y 7,14%, p = 0,035). La incidencia de tumores de los ratones TRAMP de DAG a la semana 20 fue significativamente mayor que en el grupo de dieta normal (78,57% y 35,71%, p = 0,022). El nivel sérico de IGF-1 de los ratones TRAMP de DAG fue significativamente mayor que el de los ratones TRAMP de dieta normal. El nivel sérico de IGF-1 tendió a aumentar con la edad de los ratones TRAMP de DAG. Los ratones TRAMP de DAG tenían una tasa de tinción positiva más elevada de IGF-1Rα, IGF-1Rβ, IGFBP3 y AKT que los ratones TRAMP de dieta normal. Conclusiones: La vía relacionada con IGF-1 ejerció un papel importante en la promoción de la dieta de alto contenido en grasa del desarrollo y la progresión del CaP de ratón TRAMP

Introduction: We aimed to investigate the role of IGF-1 related pathway in high-fat diet (HFD) promotion of TRAMP mouse PCa progression. Methods: TRAMP mice were randomly divided into two groups: HFD group and normal diet group. TRAMP mice of both groups were sacrificed and sampled on the 20th, 24th and 28th week respectively. Serum levels of insulin, IGF-1 and IGF-2 were tested by ELISA. Prostate tissue of TRAMP mice was used for both HE staining and immunohistochemical staining of IGF-1 related pathway proteins, including IGF-1Rα, IGF -1Rβ, IGFBPs and AKT. Results: The mortality of TRAMP mice from HFD group was significantly higher than that of normal diet group (23.81% and 7.14%, p = .035). The tumor incidence of HFD TRAMP mice at 20th week was significantly higher than normal diet group (78.57% and 35.71%, p = .022). Serum IGF-1 level of HFD TRAMP mice was significantly higher than that of normal diet TRAMP mice. Serum IGF-1 level tended to increase with HFD TRAMP mice's age. HFD TRAMP mice had higher positive staining rate of IGF-1Rα, IGF-1Rβ, IGFBP3 and Akt than normal diet TRAMP mice. Conclusions: IGF-1 related pathway played an important role in high-fat diet promotion of TRAMP mouse PCa development and progression

Aberrant expression of UCA1 in gastric cancer and its clinical significance

Long noncoding RNAs (lncRNAs) have been shown to regulate tumor biology and might be used for cancer diagnosis, prognosis and potential therapeutic targets. Although up-regulation of lncRNA UCA1 (urothelial carcinoma-associated 1) in several cancers has been found, its role in gastric cancer remains elusive. The aim of this study was to detect the expression of lncRNA UCA1 in gastric cancer and its clinical association. The expression of UCA1 was detected in 112 pairs of tumorous and adjacent normal tissues from patients with gastric cancer, as well as in four gastric cancer cell lines and a human normal gastric epithelium cell line using RT-qPCR. Results showed that UCA1 expression was remarkably increased in gastric cancer tissues and cell lines compared with that in the normal control. Clinicopathologic analysis revealed that high UCA1 expression correlated with worse differentiation, tumor size, invasion depth and TNM stage in gastric cancer. Kaplan–Meier analysis showed that increased UCA1 expression contributed to poor overall survival (p = 0.017) and disease-free survival (p = 0.024) of patients. A multivariate survival analysis also indicated that UCA1 could be an independent prognostic marker. The levels of UCA1 in gastric juice from gastric patients were significantly higher than those from normal subjects (p = 0.016). Moreover, validation analysis showed that UCA1 levels were robust in differentiating gastric cancer patients from control subjects [area under the curve (AUC) = 0.721; 95 % confidence interval (CI) = 0.655–0.788, p < 0.01]. These results suggested that UCA1 might serve as a promising biomarker for early detection and prognosis prediction of gastric cancer (AU)

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CMTM3 is reduced in prostate cancer and inhibits migration, invasion and growth of LNCaP cells

Purpose. A novel tumor suppressor gene CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) is reduced or undetectable in many kinds of cancers and relates tumor malignant features. We detected its role in prostate cancer for possibility of target therapy as accumulating evidence has shown that CMTM3 is a promising tumor suppressor gene (TSG) for gene therapy. Methods. The expression of CMTM3 detected in prostate tissue microarray, specimens and cell lines were evaluated by immunohistochemistry and semi-quantitative PCR and Western blot, respectively. After being transfected with CMTM3 adenovirus or vector (mock), the proliferation and migration and invasion of LNCaP cells were detected by transwell assay and matrigel assay, respectively. Furthermore, the effects of CMTM3 on tumor growth were performed in nude mice xenograft in vivo. Results. We found CMTM3 was reduced in PCa tissues and cells compared with BPH tissues, and its expression in PCa tissues was related to the Gleason score. Moreover, after being transfected with adenovirus, ectopic expression of CMTM3 in LNCaP cells led to significant inhibition of cell proliferation and migration and invasion compared with the control (P < 0.05), which may be attributed to decreased Erk1/2 activity as p-Erk1/2 was remarkably reduced when CMTM3 was overexpressed. Finally, restoration of CMTM3 significantly suppressed xenograft tumor growth in vivo (P < 0.01) (AU)

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