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
Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.Aims
Methods
Pigmented villonodular synovitis (PVNS) is a
rare proliferative process of the synovium which most commonly affects
the knee and occurs in either a localised (LPVNS) or a diffuse form
(DPVNS). The effect of different methods of surgical synovectomy
and adjuvant radiotherapy on the rate of recurrence is unclear.
We conducted a systematic review and identified 35 observational
studies in English which reported the use of surgical synovectomy
to treat PVNS of the knee. A meta-analysis included 630 patients, 137 (21.8%) of whom had
a recurrence after synovectomy. For patients with DPVNS, low-quality
evidence found that the rate of recurrence was reduced by both open
synovectomy (odds ration (OR) = 0.47; 95% CI 0.25 to 0.90; p = 0.024)
and combined open and arthroscopic synovectomy (OR = 0.19, 95% CI
= 0.06 to 0.58; p = 0.003) compared with arthroscopic surgery. Very
low-quality evidence found that the rate of recurrence of DPVNS
was reduced by peri-operative radiotherapy (OR = 0.31, 95% CI 0.14
to 0.70; p = 0.01). Very low-quality evidence suggested that the
rate of recurrence of LPVNS was not related to the surgical approach. This meta-analysis suggests that open synovectomy or synovectomy
combined with peri-operative radiotherapy for DPVNS is associated
with a reduced rate of recurrence. Large long-term prospective multicentre
observational studies, with a focus on both rate of recurrence and
function, are required to confirm these findings. Cite this article:
Giant cell tumours (GCT) of the synovium and
tendon sheath can be classified into two forms: localised (giant
cell tumour of the tendon sheath, or nodular tenosynovitis) and
diffuse (diffuse-type giant cell tumour or pigmented villonodular
synovitis). The former principally affects the small joints. It
presents as a solitary slow-growing tumour with a characteristic
appearance on MRI and is treated by surgical excision. There is
a significant risk of multiple recurrences with aggressive diffuse
disease. A multidisciplinary approach with dedicated MRI, histological assessment
and planned surgery with either adjuvant radiotherapy or systemic
targeted therapy is required to improve outcomes in recurrent and
refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has
been advocated as an alternative to arthrotomy, there is a significant
risk of inadequate excision and recurrence, particularly in the
posterior compartment of the knee. For local disease partial arthroscopic
synovectomy may be sufficient, at the risk of recurrence. For both
local and diffuse intra-articular disease open surgery is advised
for recurrent disease. Marginal excision with focal disease will
suffice, not dissimilar to the treatment of GCT of tendon sheath.
For recurrent and extra-articular soft-tissue disease adjuvant therapy,
including intra-articular radioactive colloid or moderate-dose external
beam radiotherapy, should be considered.