scholarly journals Study of gene expression changes in primary prostate cancer of mice treated with Urtica dioica L

Background: The role of tumor suppressor genes in the development of prostate cancer is well known. Decrease or lack of expression of these genes causes the tumor to spread through metastasis to other tissues of the body. Since nettle has anti-cancer effects, the aim of this study was to investigate the effects of hydroalcoholic extract of nettle stem and root on the expression changes of PTEN, MAGI-2 and SMAD-2 genes in mouse prostate induced tumor. Materials and Methods: In this experimental study, hydroalcoholic extract of nettle was prepared by Soxhlet apparatus. The mice were injected subcutaneously for 28 days after injection of DMBA carcinoma with doses of 75 and 250 mg/kg, respectively. Also, the control group received no drug and the sham group received only the extract. The expression changes of the target genes were analyzed by Real Time PCR and the results were analyzed statistically. Results: The results showed that PTEN gene expression was increased in treatment with 250 root extract compared to day 14 turmeric. Expression of MAGI-2 gene was increased in treatment with root extract of 75 dose on day 28 compared to day 28 tumor. Evaluation of SMAD-2 gene expression showed that expression of this gene in treatment group with 250 root extract increased on day 21 compared to day 21 tumor. Conclusion: According to studies on PTEN, MAGI-2 and SMAD-2 have revealed that inactivation of these three genes is considered a risk for cancer progression.

2020 ◽  
Vol 247 (3) ◽  
pp. 225-238
Author(s):  
Ana Sánchez-Tusie ◽  
Carlos Montes de Oca ◽  
Julia Rodríguez-Castelán ◽  
Evangelina Delgado-González ◽  
Zamira Ortiz ◽  
...  

Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasion of tumors. In vitro, in the LNCaP prostate cancer cell line, we found that both T3 and T4 increased the number of viable cells (Trypan blue assay), and only T4 response was fully blocked in the presence of an integrin-binding inhibitor peptide (RGD, arginine-glycine-aspartate). In summary, our data show that the prostate was highly sensitive to physiological T3 doses and suggest that in vivo, an increase in the T3/T4 ratio could be associated with the reduced weight of prostate tumors. Longitudinal studies are required to understand the role of thyroid hormones in prostate cancer progression.


Author(s):  
Nikita Sushentsev ◽  
Leonardo Rundo ◽  
Oleg Blyuss ◽  
Tatiana Nazarenko ◽  
Aleksandr Suvorov ◽  
...  

Abstract Objectives To compare the performance of the PRECISE scoring system against several MRI-derived delta-radiomics models for predicting histopathological prostate cancer (PCa) progression in patients on active surveillance (AS). Methods The study included AS patients with biopsy-proven PCa with a minimum follow-up of 2 years and at least one repeat targeted biopsy. Histopathological progression was defined as grade group progression from diagnostic biopsy. The control group included patients with both radiologically and histopathologically stable disease. PRECISE scores were applied prospectively by four uro-radiologists with 5–16 years’ experience. T2WI- and ADC-derived delta-radiomics features were computed using baseline and latest available MRI scans, with the predictive modelling performed using the parenclitic networks (PN), least absolute shrinkage and selection operator (LASSO) logistic regression, and random forests (RF) algorithms. Standard measures of discrimination and areas under the ROC curve (AUCs) were calculated, with AUCs compared using DeLong’s test. Results The study included 64 patients (27 progressors and 37 non-progressors) with a median follow-up of 46 months. PRECISE scores had the highest specificity (94.7%) and positive predictive value (90.9%), whilst RF had the highest sensitivity (92.6%) and negative predictive value (92.6%) for predicting disease progression. The AUC for PRECISE (84.4%) was non-significantly higher than AUCs of 81.5%, 78.0%, and 80.9% for PN, LASSO regression, and RF, respectively (p = 0.64, 0.43, and 0.57, respectively). No significant differences were observed between AUCs of the three delta-radiomics models (p-value range 0.34–0.77). Conclusions PRECISE and delta-radiomics models achieved comparably good performance for predicting PCa progression in AS patients. Key Points • The observed high specificity and PPV of PRECISE are complemented by the high sensitivity and NPV of delta-radiomics, suggesting a possible synergy between the two image assessment approaches. • The comparable performance of delta-radiomics to PRECISE scores applied by expert readers highlights the prospective use of the former as an objective and standardisable quantitative tool for MRI-guided AS follow-up. • The marginally superior performance of parenclitic networks compared to conventional machine learning algorithms warrants its further use in radiomics research.


2018 ◽  
Vol 40 (7) ◽  
pp. 893-902 ◽  
Author(s):  
Teresa T Liu ◽  
Jonathan A Ewald ◽  
Emily A Ricke ◽  
Robert Bell ◽  
Colin Collins ◽  
...  

Abstract Detailed mechanisms involved in prostate cancer (CaP) development and progression are not well understood. Current experimental models used to study CaP are not well suited to address this issue. Previously, we have described the hormonal progression of non-tumorigenic human prostate epithelial cells (BPH1) into malignant cells via tissue recombination. Here, we describe a method to derive human cell lines from distinct stages of CaP that parallel cellular, genetic and epigenetic changes found in patients with cancers. This BPH1-derived Cancer Progression (BCaP) model represents different stages of cancer. Using diverse analytical strategies, we show that the BCaP model reproduces molecular characteristics of CaP in human patients. Furthermore, we demonstrate that BCaP cells have altered gene expression of shared pathways with human and transgenic mouse CaP data, as well as, increasing genomic instability with TMPRSS2–ERG fusion in advanced tumor cells. Together, these cell lines represent a unique model of human CaP progression providing a novel tool that will allow the discovery and experimental validation of mechanisms regulating human CaP development and progression. This BPH1-derived Cancer Progression (BCaP) model represents different stages of cancer. The BCaP model reproduces molecular characteristics of prostate cancer. The cells have altered gene expression with TMPRSS2-ERG fusion representing a unique model for prostate cancer progression.


2020 ◽  
Author(s):  
Boris Shorning ◽  
Neil Trent ◽  
David Griffiths ◽  
Thomas Worzfeld ◽  
Stefan Offermanns ◽  
...  

AbstractProstate cancer mortality is associated with the metastatic spread of tumour cells. A better understanding of the mechanisms which allow a locally advanced tumour to disseminate around the body will identify new therapeutic targets to block this process. One of set of genes implicated in metastasis are plexins, which can promote or suppress tumour progression depending on cancer type and cellular context. We have taken a mouse genetics approach to gain insight into the role of Plexin-B1 in prostate cancer progression in vivo.We show here that genetic deletion of Plexin-B1 in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mouse prostate cancer models significantly decreased metastasis. High levels of prostate epithelial cell-specific expression of wild-type Plexin-B1 in knock-in mice with a PbCre+Ptenfl/flKrasG12V background also significantly decreased metastasis. In contrast, expression of a Plexin-B1 mutant (P1597L; identified from metastatic deposits in prostate cancer patients) in prostate epithelial cells in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mice significantly increased metastasis, in particular metastasis to distant sites. In line with these findings, both deletion and overexpression of wild-type Plexin-B1 reduced invasion of tumour cells into the prostate stroma, while overexpression of mutant Plexin-B1 significantly increased invasion, suggesting that Plexin-B1 has a role in the initial stages of metastasis. Invasion and metastasis also correlated with phosphorylation of myosin light chain, suggesting that Plexin-B1 signals via the Rho/ROCK pathway to promote metastasis.Our results demonstrate that mutant Plexin-B1 promotes metastasis in prostate cancer and represents a new therapeutic target to suppress tumour spread.


2015 ◽  
Vol 86 (10) ◽  
Author(s):  
Marcin Feldo ◽  
Janusz Kocki ◽  
Jan Feldo ◽  
Sylwia Łukasik ◽  
Jacek Bogucki ◽  
...  

Abstractgene and the genes of LRP group play a key role in the regulation of the body weight and lipid metabolism in mammals.was to define the role of. The study group consisted of 38 subjects, including 27 men and 11 women qualified for endovascular aneurysm repair (EVAR). The subjects with abdominal aortic aneurysm were enrolled in the study group, depending on the body mass index (BMI); in obese patients (BMI > 30). The control group (n = 16) included subjects without lipid disorders. One-step isolation of RNA from lymphocytes and adipose tissue cells was performed using the modified TRI method by Chomc-zynski and Sacchi, and then the gene expression was tested by real-time PCR.. The highest mean relative of the gene expression for. Due to the important role of the


2018 ◽  
Vol 47 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Chunhua Lin ◽  
Fengchun Wan ◽  
Youyi Lu ◽  
Guojun Li ◽  
Luxin Yu ◽  
...  

Objective To determine the value of an enhanced recovery after surgery (ERAS) protocol for prostate cancer patients undergoing laparoscopic radical prostatectomy (LRP). Methods We conducted a retrospective cohort study using clinical data for 288 patients who underwent LRP in our hospital from June 2010 to December 2016. A total of 124 patients underwent ERAS (ERAS group) and the remaining 164 patients were allocated to the control group. ERAS comprised prehabilitation exercise, carbohydrate fluid loading, targeted intraoperative fluid resuscitation and keeping the body warm, avoiding drain use, early mobilization, and early postoperative drinking and eating. Results The times from LRP to first water intake, first ambulation, first anal exhaust, first defecation, pelvic drainage-tube removal, and length of hospital stay (LOS) were all significantly shorter, and hospitalization costs and the incidence of postoperative complications were significantly lower in the ERAS group compared with the control group. No deaths or reoperations occurred in either group, and there were no readmissions in the ERAS group, within 90 days after surgery. Conclusion ERAS protocols may effectively accelerate patient rehabilitation and reduce LOS and hospitalization costs in patients undergoing LRP.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Viswanathan Saraswathi ◽  
Curtis Perriotte-Olson ◽  
Robert D Heineman ◽  
Cyrus V Desouza

Introduction: Dyslipidemia is a prevalent condition in obesity and type 2 diabetes. Although fish oil rich in omega-3 fatty acids (ω-3) is a widely used hypolipidemic agent, it is often required at high doses. At high doses, these fatty acids can induce oxidative stress or endothelial activation and therefore, strategies to improve their beneficial effects are needed. We previously reported that fish oil in combination with cyclooxygenase (COX) inhibitors exerts enhanced hypolipidemic and anti-inflammatory effects in low density lipoprotein receptor knock-out mice. Here, we sought to determine the effects of ω-3 fatty acids in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in subcutaneous adipose tissue (scAT) in humans. Methods: Obese dyslipidemic patients were randomly assigned to receive one of these interventions (n=8/group) for 12 wk: 1) Standard nutrition counseling (control), 2) ω-3 (2 g twice daily), 3) NX (220 mg twice daily), and 4) ω-3 (2 g twice daily) + NX (220 mg twice daily). Results: The body mass index, HOMA-IR, and plasma total, LDL, and HDL cholesterol levels were not altered significantly in any of the groups. The percent change in plasma triglycerides (TG) from baseline was 75% ( P <0.1) and 68% ( P <0.05) in ω-3 and ω3 + NX-treated subjects, respectively. Notably, 25% of subjects who received ω-3s alone did not show a reduction in TG whereas all the patients that received ω-3 + NX showed a reduction in TG. Realtime PCR analysis of scAT showed that the expression of glucose transporter 4 (GLUT-4), a marker of glucose uptake and a key regulator of glucose homeostasis was significantly reduced in ω-3 compared to control group ( P <0.01). However, combining NX with ω-3 abolished this effect. Moreover, the expression of MCP-1 and VCAM-1, markers of inflammatory response or endothelial activation, was significantly increased in ω-3 but not in ω-3 + NX group. The plasma levels of MCP-1 and E-selectin did not vary significantly in any of the groups. Conclusions: Our data reveal previously unrecognized effects of fish oil in scAT. Our data suggest that combining NX with ω-3 fatty acids will increase their effectiveness in reducing plasma TG and improve the benefits of ω-3 supplements by favorably altering gene expression in scAT.


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