scholarly journals Differential Effects of Leptin on the Invasive Potential of Androgen-Dependent and -Independent Prostate Carcinoma Cells

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Dayanand D. Deo ◽  
Ashwin P. Rao ◽  
Saideep S. Bose ◽  
Allal Ouhtit ◽  
Surendra B. Baliga ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Carcinoma ◽  
Intracellular Signaling ◽  
Cellular Proliferation ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Free Oxygen Radicals ◽  
Lncap Cells ◽  
Increased Risk ◽  
The Impact

Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP) cells as well as androgen-insensitive (PC-3 and DU-145) cells. At a concentration of 200_nm, LNCaP cells showed a significant increase (20% above control;P<.0001) in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P<.01toP<.0001) dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates theinvasivepotential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.

scholarly journals Cytokine Effects on Cell Viability and Death of Prostate Carcinoma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Georgios Chondrogiannis ◽  
Michalis Kastamoulas ◽  
Panagiotis Kanavaros ◽  
Georgios Vartholomatos ◽  
Maria Bai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cell Viability ◽  
Prostate Carcinoma ◽  
Lncap Cell ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Lncap Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Active Caspase

We analyzed the effects of IL-13, IFN-γ, and IL-1βon cell viability and death of LNCaP and PC-3 cells and major signaling pathways involved in these effects. Significant increase of LNCaP cell death (apoptotic and necrotic) and increased levels of active caspase 3 were observed in cells treated with inhibitors of ERK 1/2 (UO126) and p38 (SB203580) prior to IL-1βtreatment in comparison to cells treated with UO126, SB203580, or IL-1βalone. Significant increase of LNCaP but not PC-3 cell death was detected after treatment with LY-294002 (inhibitor of phosphatidylinositol 3-kinase). No significant increase of LNCaP and PC-3 cell death was observed after treatment with SP600125 (inhibitor of JNK), SB203580 (inhibitor of p38), UO126 (inhibitor of ERK 1/2), or BAY 11-7082 (inhibitor of NF-κB). Reduced c-FLIPLexpression was observed in LNCaP cells treated with LY-294002. The significant potentiation of LNCaP cell death by inhibition of ERK 1/2, p38, and PI3-K pathways may provide a rationale for therapeutic approach in androgen-dependent prostate cancer.

scholarly journals Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone

2008 ◽  
Vol 105 (40) ◽  
pp. 15541-15546 ◽  
Author(s):  
Akihiro Yano ◽  
Shinji Tsutsumi ◽  
Shiro Soga ◽  
Min-Jung Lee ◽  
Jane Trepel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Carcinoma ◽  
Hsp90 Inhibitor ◽  
Carcinoma Cells ◽  
Hsp90 Inhibitors ◽  
Hsp90 Inhibition ◽  
Normal Tissues ◽  
The Impact

Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.

scholarly journals In VitroProtective Effects ofLycium barbarumBerries Cultivated in Umbria (Italy) on Human Hepatocellular Carcinoma Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
M. R. Ceccarini ◽  
S. Vannini ◽  
S. Cataldi ◽  
M. Moretti ◽  
M. Villarini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Migration And Invasion ◽  
Total Phenolic ◽  
Lycium Barbarum ◽  
Hepatocellular Carcinoma Cells ◽  
Umbria Region ◽  
Increased Risk ◽  
Human Hepatocellular Carcinoma Cells

Lycium barbarumis a famous plant in the traditional Chinese medicine. The plant is known to have health-promoting bioactive components. The properties ofLycium barbarumberries cultivated in Umbria (Italy) and their effect on human hepatocellular carcinoma cells (HepG2) have been investigated in this work. The obtained results demonstrated that theLycium barbarumberries from Umbria region display high antioxidant properties evaluated by total phenolic content and ORAC method, on hydrophilic and lipophilic fractions. Moreover, on HepG2 cell lineLycium barbarumberries extract did not change cell viability analyzed by MTT and Trypan blue exclusion assay and did not induce genotoxic effect analyzed by comet assay. Furthermore, it was demonstrated, for the first time, that the berries extract showed a protective effect on DNA damage, expressed as antigenotoxic activityin vitro. Finally,Lycium barbarumberries extract was able to modulate the expression of genes involved in oxidative stress, proliferation, apoptosis, and cancer. In particular, downexpression of genes involved in tumor migration and invasion (CCL5), in increased risk of metastasis and antiapoptotic signal (DUSP1), and in carcinogenesis (GPx-3 and PTGS1), together with overexpression of tumor suppressor gene (MT3), suggested that UmbrianLycium barbarumberries could play a protective role against hepatocellular carcinoma.

Is BMI a risk factor for active surveillance progression in patients with prostate cancer diagnosed by MRI-Trus fusion biopsy?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 124-124 ◽  
Author(s):  
Kareem Rayn ◽  
Samuel Gold ◽  
Graham R. Hale ◽  
Joey Baiocco ◽  
Jonathan Bloom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factor ◽  
Active Surveillance ◽  
Progression Free Survival ◽  
Normal Weight ◽  
Fusion Biopsy ◽  
Patient Demographics ◽  
Increased Risk ◽  
Risk Of Progression ◽  
The Impact

124 Background: MRI−TRUS fusion biopsy (FBx) use in the diagnosis of prostate cancer (PCa) results in a more accurate assessment of disease burden and has increasingly been incorporated into urologic practice. In addition, with more men choosing active surveillance (AS) and the reports of increased PCa aggressiveness with obesity, we wanted to study the impact of obesity on the risk of PCa progression in men on AS diagnosed and followed by MRI and MRI−TRUS FBx. Methods: A retrospective review was performed on a prospectively maintained database of all men who underwent MRI−TRUS FBx at our institution from January 2007 to May 2015. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients who enrolled on AS were stratified by BMI into normal weight (BMI 18.5−24.9), overweight (BMI 25.0−29.9), and obese (BMI ≥ 30.0). Statistical analysis was performed using SPSS software. Results: 204 men were enrolled in AS. Within the AS cohort, 51 (25%) had a normal weight, 101 (49.5%) were overweight, and 52 (25.5%) were obese. Age, BMI, PSA and mean estimated progression free survival time are described for each of these groups in Table 1. The overall rate of progression was 32.8%. Of the patients who progressed, 18 (26.9%) were normal weight, 32 (15.7%) were overweight and 17 (25.4%) were obese. On multivariate analysis, BMI was not a risk factor for AS progression, HR = 1.00 (p = 0.99, 95% CI = 0.95−1.06). Conclusions: There is evidence of increased risk of aggressive PCa specific death in obese patients. However, we demonstrate that in patients diagnosed by FBx, obesity does not confer an additional risk of progression on AS. This may be due to the improved characterization of cancer volume and grade by MRI−TRUS fusion biopsy. Further study is required to determine risk factors for AS progression in patients undergoing FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Medical Research Scholars Program.

scholarly journals Circular RNA circANKS1B as the Sponge of miR-152-3p Promotes Prostate Cancer Progression by up-Regulating TGF-α Expression

2020 ◽  
Author(s):  
Liangjun Tao ◽  
Xinyuan Pan ◽  
Jiawei Wang ◽  
Li Zhang ◽  
Lingsong Tao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Cancer Progression ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
And Function ◽  
The Impact

Abstract Background: Growing studies indicate that circRNAs play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aims to investigate the expression and function of circANKS1B in prostate cancer (PC).Methods: The expression of circANKS1B and miRNA-152-3p were determined by real-time qRT-PCR. The cell migration and invasion were measured by transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by dual-luciferase reporter gene assay. Rescue experiments were conducted to demonstrate whether circANKS1B regulated the migration and invasion of PC cells by the circANKS1B-miR-152-3p-TGF-α pathway.Results: The expression of circANKS1B was dramatically up-regulated both in PC cells and tissues. Moreover, high circANKS1B expression was associated with a poor prognosis of PC patients. Dual-luciferase reporter assay indicated that circABKS1B directly bound to miRNA-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B remarkably suppressed PC cells invasion and TGF-α expression, while the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on PC cell invasion was also abrogated by TGF-α deficiency. In all, circANKS1B as the sponge of miR-152-3p promotes prostate cancer progression by up-regulating TGF-α expression.Conclusion: Our findings reveal that circANKS1B could be a potential prognostic biomarker and therapeutic target of PC.

scholarly journals The impact of prostate cancer upgrading and upstaging on biochemical recurrence and cancer-specific survival

2019 ◽  
Author(s):  
Arnas Bakavicius ◽  
Mingaile Drevinskaite ◽  
Kristina Daniunaite ◽  
Marija Barisiene ◽  
Sonata Jarmalaite ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Cancer Specific Survival ◽  
Increased Risk ◽  
Definitive Therapy ◽  
Treatment Naïve ◽  
The Impact ◽  
Mean Time

Abstract Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes.Methods Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging.Results Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5-times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1-times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p < 0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p < 0.001). Grade and stage increase after RP were associated with inferior ten-year CSS rates: 78% vs. 96% for upgrading (p = 0.002) and 77% vs. 95% for upstaging (p = 0.001).Conclusions Currently used risk stratification models are associated with a substantial number of misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, what should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

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