Prostate cancer 2000

Tong

Clinical Cancer Research

et al. 2018

Inflammatory infiltration plays important roles in both carcinogenesis and metastasis. We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer. By using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer. Treating TRAMP mice with metformin delays prostate cancer progression from low-grade prostatic intraepithelial neoplasia to high-grade PIN, undifferentiated to well-differentiated, and PIN to adenocarcinoma with concurrent inhibition of inflammatory infiltration evidenced by reduced recruitment of macrophages. Furthermore, metformin is capable of inhibiting the following processes: inflammatory infiltration after androgen deprivation therapy (ADT) induced by surgically castration in mice, bicalutamide treatment in patients, and hormone deprivation in LNCaP cells. Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells. Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment. .

Section: Introductionmentioning

confidence: 99%

Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration

Tong

Clinical Cancer Research

et al. 2018

BioMed Research International

“…Before transgenic mouse of PCa was widely used, some in vivo studies on human PCa cell transplanted rodent models also suggested that HFD acted as a promoter in PCa development and progression [ 6 – 8 ]. Transgenic adenocarcinoma mouse prostate (TRAMP) animal is one of the most widely used mouse model for PCa, which successfully resembles the human PCa development and progression [ 9 ]. We have shown TRAMP mouse as a good in vivo model to study the association between HFD and PCa in our previous research [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory Cytokines in Prostate Cancer Development and Progression Promoted by High-Fat Diet

Bai

et al. 2015

Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa) development and progression promoted by high-fat diet (HFD). Methods. TRAMP (transgenic adenocarcinoma mouse prostate) mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33%) were from the normal diet group and 10 (27.78%) from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P = 0.032). Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P = 0.045). Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

“…Transgenic adenocarcinoma mouse prostate (TRAMP) animal is the best characterized model for PCa and closely resembles the progression of PCa in human [15]. The TRAMP model was generated using the minimal probasin (PB) -426/+28 regulatory sequence to restrict SV40 early gene (T and t antigens; Tag) expression in the prostatic epithelium [16-17].…”

mentioning

confidence: 99%

Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice

et al. 2013

Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer.