Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.Aims
Methods
Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.Aims
Methods
Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.Aims
Methods
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
Massive endoprostheses rely on extra-cortical bone bridging (ECBB)
to enhance fixation. The aim of this study was to investigate the
role of selective laser sintered (SLS) porous collars in augmenting
the osseointegration of these prostheses. The two novel designs of porous SLS collars, one with small pores
(Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared
in an ovine tibial diaphyseal model. Osseointegration of these collars
was compared with that of a clinically used solid, grooved design
(G). At six months post-operatively, the ovine tibias were retrieved and
underwent radiological and histological analysis.Aims
Materials and Methods
Monostotic fibrous dysplasia of the proximal
femur has a variable clinical course, despite its reported limited tendency
to progress. We investigated the natural history and predisposing factors
for progression of dysplasia in a group of 76 patients with a mean
follow-up of 8.5 years (2.0 to 15.2). Of these, 31 (41%) presented
with an asymptomatic incidental lesion while 45 (59%) presented
with pain or a pathological fracture. A group of 23 patients (30%)
underwent early operative treatment for pain (19: 25%) or pathological
fracture (4: 5%). Of the 53 patients who were initially treated non-operatively,
45 (85%) remained asymptomatic but eight (15%) needed surgery because
of pain or fracture. The progression-free survival of the observation
group was 81% ( The risk of experiencing pain or pathological fracture is considerable
in monostotic fibrous dysplasia of the proximal femur. Patients
presenting with pain, a limp or radiological evidence of microfracture
have a high chance of needing surgical treatment. Cite this article:
The pre-operative differentiation between enchondroma,
low-grade chondrosarcoma and high-grade chondrosarcoma remains a
diagnostic challenge. We reviewed the accuracy and safety of the
radiological grading of cartilaginous tumours through the assessment
of, first, pre-operative radiological and post-operative histological agreement,
and second the rate of recurrence in lesions confirmed as high-grade
on histology. We performed a retrospective review of major long
bone cartilaginous tumours managed by curettage as low grade between
2001 and 2012. A total of 53 patients with a mean age of 47.6 years
(8 to 71) were included. There were 23 men and 30 women. The tumours
involved the femur (n = 20), humerus (n = 18), tibia (n = 9), fibula
(n = 3), radius (n = 2) and ulna (n = 1). Pre-operative diagnoses
resulted from multidisciplinary consensus following radiological
review alone for 35 tumours, or with the addition of pre-operative
image guided needle biopsy for 18. The histologically confirmed diagnosis
was enchondroma for two (3.7%), low-grade chondrosarcoma for 49
(92.6%) and high-grade chondrosarcoma for two (3.7%). Three patients
with a low-grade tumour developed a local recurrence at a mean of 15
months (12 to 17) post-operatively. A single high-grade recurrence
(grade II) was treated with tibial diaphyseal replacement. The overall
recurrence rate was 7.5% at a mean follow-up of 4.7 years (1.2 to
12.3). Cartilaginous tumours identified as low-grade on pre-operative
imaging with or without additional image-guided needle biopsy can
safely be managed as low-grade without pre-operative histological
diagnosis. A few tumours may demonstrate high-grade features histologically,
but the rates of recurrence are not affected. Cite this article:
Local recurrence along the biopsy track is a
known complication of percutaneous needle biopsy of malignant musculoskeletal
tumours. In order to completely excise the track with the tumour
its identification is essential, but this becomes increasingly difficult
over time. In an initial prospective study, 22 of 45 patients (48.8%)
identified over a three-month period, treated by resection of a
musculoskeletal tumour, had an unidentifiable biopsy site at operation,
with identification statistically more difficult after 50 days.
We therefore introduced the practice of marking the biopsy site
with India ink. In all 55 patients undergoing this procedure, the
biopsy track was identified pre-operatively (100%); this difference
was statistically significant. We recommend this technique as a
safe, easy and accurate means of ensuring adequate excision of the
biopsy track.
Cite this article:
The most appropriate protocol for the biopsy of musculoskeletal tumours is controversial, with some authors advocating CT-guided core biopsy. At our hospital the initial biopsies of most musculoskeletal tumours has been by operative core biopsy with evaluation by frozen section which determines whether diagnostic tissue has been obtained and, if possible, gives the definitive diagnosis. In order to determine the accuracy and cost-effectiveness of this protocol we have undertaken a retrospective audit of biopsies of musculoskeletal tumours performed over a period of two years. A total of 104 patients had biopsies according to this regime. All gave the diagnosis apart from one minor error which did not alter the management of the patient. There was no requirement for re-biopsy. This protocol was more labour-intensive and 38% more costly than CT-guided core biopsy (AU$1804
