English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Bortezomib is a proteasome inhibitor currently studied in clinical trials of childhood cancers. So far, no side effects on bone growth have been reported in treated children. However, bortezomib was recently found to induce apoptosis in growth plate chondrocytes and impair linear bone growth in treated mice. We hypothesize that [Gly(14)]-humanin (HNG), a 24-amino acid synthetic antiapoptotic peptide, can prevent bortezomib-induced bone growth impairment.Mice with human neuroblastoma or medulloblastoma tumor xenografts (9-13 animals/group) received one 2-week cycle (2 injections/week) of bortezomib (0.8 mg/kg or 1.0mg/kg), or HNG (1 µg/mouse), or the combination of HNG/bortezomib, or vehicle. Cultures of human growth plate cartilage, chondrogenic- and cancer cell lines, and immunohistochemistry for detection of proapoptotic proteins were also used. Statistical significance was evaluated by two-sided Mann-Whitney U test or by parametric or nonparametric analysis of variance.Bortezomib efficiently blocked the proteasome and induced pronounced impairment of linear bone growth from day 0 to day 13 (0.09 mm/day, 95% confidence interval [CI] = 0.07 to 0.11 mm/day; vs 0.19 mm/day, 95% CI = 0.15 to 0.23 mm/day in vehicle; P < .001), an effect significantly prevented by the addition of HNG (0.15 mm growth/day, 95% CI = 0.14 to 0.16 mm/day; P < .001 vs bortezomib only; P = 0.03 vs vehicle). Bortezomib was highly toxic when added to cultures of human growth plate cartilage, with markedly increased apoptosis compared with control (P < .001). However, when combining with HNG, bortezomib-induced apoptosis was entirely prevented, as was Bax and PARP activation. Bortezomib delayed tumor growth, and HNG did not interfere with the anticancer effect when studied in human tumor xenografts or cell lines.HNG prevents bortezomib-induced bone growth impairment without interfering with bortezomib's desired anticancer effects.

Protective Role of Humanin on Bortezomib-Induced Bone Growth Impairment in Anticancer Treatment