Limits...
Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment.

Iuliani M, Pantano F, Buttigliero C, Fioramonti M, Bertaglia V, Vincenzi B, Zoccoli A, Ribelli G, Tucci M, Vignani F, Berruti A, Scagliotti GV, Tonini G, Santini D - Oncotarget (2015)

Bottom Line: These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment.To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs).Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.

View Article: PubMed Central - PubMed

Affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.

ABSTRACT
Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.

No MeSH data available.


Related in: MedlinePlus

Comparison between ALP at baseline and after three, six and nine months
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494955&req=5

Figure 5: Comparison between ALP at baseline and after three, six and nine months

Mentions: ALP did not show a significant increase, median 123 U/L (95%CI: 126-261) and 190 U/L (95%CI 172-344) at baseline and nine months (p = 0.28), respectively. However, the comparison between ALP at baseline and after 3 months showed a significant increase (p = 0.010) (Table 2, Fig. 5). Compared to median value at baseline an ALP increase by 16.3%, 2.4% and 54.5% was observed at three, six and nine months, respectively.


Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment.

Iuliani M, Pantano F, Buttigliero C, Fioramonti M, Bertaglia V, Vincenzi B, Zoccoli A, Ribelli G, Tucci M, Vignani F, Berruti A, Scagliotti GV, Tonini G, Santini D - Oncotarget (2015)

Comparison between ALP at baseline and after three, six and nine months
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494955&req=5

Figure 5: Comparison between ALP at baseline and after three, six and nine months
Mentions: ALP did not show a significant increase, median 123 U/L (95%CI: 126-261) and 190 U/L (95%CI 172-344) at baseline and nine months (p = 0.28), respectively. However, the comparison between ALP at baseline and after 3 months showed a significant increase (p = 0.010) (Table 2, Fig. 5). Compared to median value at baseline an ALP increase by 16.3%, 2.4% and 54.5% was observed at three, six and nine months, respectively.

Bottom Line: These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment.To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs).Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.

View Article: PubMed Central - PubMed

Affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.

ABSTRACT
Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.

No MeSH data available.


Related in: MedlinePlus