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Molecular characterization of the prostate after hormonal and antiangiogenic therapies in senile mice (FVB) and in transgenic adenocarcinoma of mice prostate (Tramp) model

Abstract

Senescence is related to structural imbalance of the prostate due to androgen level ablation and accumulation of senescent cells, leading to microenvironment in favour of glandular lesions which are similar to reactivy stroma found in cancer with tissue remodelation and angiogenic process. In the prostate, the angiogenic process is regulated by androgens and contributes in the stromal reaction during carcinogenesis. Thus, angiogenic and androgen inhibitors such as TNP470, SU5416 and finasteride are hopeful alternatives in the cancer treatment. The herewith aim is to characterize the dorsolateral prostate stroma of senile mice and of senile mice submitted to antiangiogenic and hormonal therapies, relating to the results found in the stromal reaction in the prostatic malignant lesions. 60 mice (FVB and TRAMP) will be divided into control and senile groups (6 mice/per group). The control group will receive 5mL/kg/day dose of physiological solution (0,9%) subcutaneously (s.c.): a) and b) Young controls groups (JV8) and (JV18): 8 and 18 week old FVB mice; c)NIP group: 8 week old Tramp mice; d) Cancer group (CP):18 week old Tramp mice. All animals in the senile groups will be 52 week old FVB mice: Senile group (SNL): similar to the other control groups; f) Senile+TNP470 group (ST): 15mg/kg/day dose of TNP470(s.c.); g) Senile+ SU5416 group (SSU): 6mg/kg/day dose of SU5416 (s.c.); h) Senile+Finasteride group (SFI):20mg/kg/day dose of finasteride (S.c.); i) Senile+TNP470+SU5416 group (STSU): similar to the ST and SSU groups; j) Senile+TNP470+SU5416+Finasteride (STSF) group: similar to the ST, SSU, SFI groups. After 21 days of treatment, the samples from dorsolateral prostate will be collected to morphological, immunohistochemistry, microdissection, Western Blotting analyses, in addition to microvessels density. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MONTICO, FABIO; KIDO, LARISSA AKEMI; MARTIN, REBECA SAN; ROWLEY, DAVID R.; CAGNON, VALERIA H. A. Reactive stroma in the prostate during late life: The role of microvasculature and antiangiogenic therapy influences. PROSTATE, v. 75, n. 14, p. 1643-1661, OCT 1 2015. Web of Science Citations: 8.
MONTICO, FABIO; KIDO, LARISSA AKEMI; HETZL, AMANDA CIA; ALVES CAGNON, VALERIA HELENA. Prostatic Angiogenic Responses in Late Life: Antiangiogenic Therapy Influences and Relation With the Glandular Microenvironment in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model. PROSTATE, v. 75, n. 5, p. 484-499, APR 1 2015. Web of Science Citations: 10.
MONTICO, FABIO; KIDO, LARISSA AKEMI; HETZL, AMANDA CIA; LORENCINI, RAISA MISTIERI; CANDIDO, EDUARDO MARCELO; ALVES CAGNON, VALERIA HELENA. Antiangiogenic therapy effects on age-associated matrix metalloproteinase-9 (MMP-9) and insulin-like growth factor receptor-1 (IGFR-1) responses: a comparative study of prostate disorders in aged and TRAMP mice. Histochemistry and Cell Biology, v. 142, n. 3, p. 269-284, SEP 2014. Web of Science Citations: 9.
KIDO, LARISSA AKEMI; HETZL, AMANDA CIA; CANDIDO, EDUARDO MARCELO; MONTICO, FABIO; LORENCINI, RAISA MISTIERI; ALVES CAGNON, VALERIA HELENA. Antiangiogenic and finasteride therapies: Responses of the prostate microenvironment in elderly mice. Life Sciences, v. 106, n. 1-2, p. 58-70, JUN 13 2014. Web of Science Citations: 4.

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