Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.Aims
Methods
Avascular necrosis (AVN) is a serious complication
of high-dose chemotherapy for haematological malignancy in childhood.
In order to describe its incidence and main risk factors and to
evaluate the current treatment options, we reviewed 105 children
with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic
or acute myeloid leukaemia, or a non-Hodgkin’s lymphoma. Overall,
eight children (7.6%) developed AVN after a mean of 16.8 months (8
to 49). There were four boys and four girls with a mean age of 14.4
years (9.8 to 16.8) and a total of 18 involved sites, 12 of which
were in the femoral head. All these children were aged >
nine years
(p <
0.001). All had received steroid treatment with a mean cumulative
dose of prednisone of 5967 mg (4425 to 9599) compared with a mean
of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No
difference existed between genders and no thrombophilic disorders
were identified. Their initial treatment included 11 core decompressions
and two bipolar hip replacements. Later, two salvage osteotomies
were done and three patients (four hips) eventually needed a total
joint replacement. We conclude that AVN mostly affects the weight-bearing
epiphyses. Its risk increases with age and higher steroid doses.
These high-risk patients may benefit from early screening for AVN. Cite this article:
