ABSTRACT
Objective Synovial chondromatosis is a rare benign proliferative disorder of synovium characterized by the formation of cartilaginous bodies in a joint. The condition typically affects one single large joint. The development of synovial chondromatosis in the joints of hand and wrist is extremely rare. Case description In this report, we present a case of synovial chondromatosis arising from the midcarpal joint and the arthroscopic treatment thereof. Literature review Owing to its rarity, literature on synovial chondromatosis occurring in the hand and wrist is extremely limited. To our knowledge, no report has been published describing the arthroscopic treatment of an isolated synovial chondromatosis of the midcarpal joint. Clinical relevance As synovial chondromatosis of the hand and wrist is extremely rare, and clinical and radiological findings can be nonspecific, the diagnosis might be overlooked initially. The condition does, however, require surgical treatment and thorough follow-up. Thus, awareness of this possible diagnosis among treating physicians is important.
ABSTRACT
Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Despite aggressive therapy, survival outcomes remain unsatisfactory, especially for patients with metastatic disease or patients with a poor chemotherapy response. Chemoresistance contributes to treatment failure. To increase the efficacy of conventional chemotherapy, essential survival pathways should be targeted concomitantly. Here, we performed a loss-of-function siRNA screen of the human kinome in SaOS-2 cells to identify critical survival kinases after doxorubicin treatment. Gene silencing of JNK-interacting-protein-1 (JIP1) elicited the most potent sensitisation to doxorubicin. This candidate was further explored as potential target for chemosensitisation in OS. A panel of OS cell lines and human primary osteoblasts was examined for sensitisation to doxorubicin using small molecule JIP1-inhibitor BI-78D3. JIP1 expression and JIP1-inhibitor effects on JNK-signalling were investigated by Western blot analysis. JIP1 expression in human OS tumours was assessed by immunohistochemistry on tissue micro arrays. BI-78D3 blocked JNK-signalling and sensitised three out of four tested OS cell lines, but not healthy osteoblasts, to treatment with doxorubicin. Combination treatment increased the induction of apoptosis. JIP1 was found to be expressed in two-thirds of human primary OS tissue samples. Patients with JIP1 positive tumours showed a trend to inferior overall survival. Collectively, JIP1 appears a clinically relevant novel target in OS to enhance the efficacy of doxorubicin treatment by means of RNA interference or pharmacological inhibition.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Bone Neoplasms/drug therapy , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/genetics , Osteosarcoma/drug therapy , RNA, Small Interfering/genetics , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/genetics , Adolescent , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Blotting, Western , Bone Neoplasms/genetics , Bone Neoplasms/mortality , Case-Control Studies , Cell Line, Tumor , Humans , Immunoenzyme Techniques , Immunoprecipitation , Neoplasm Staging , Osteoblasts/metabolism , Osteoblasts/pathology , Osteosarcoma/genetics , Osteosarcoma/mortality , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Tissue Array AnalysisABSTRACT
The reconstruction of massive structural acetabular defects after revision arthroplasty presents a unique challenge to the orthopedic surgeon. This report describes such a salvage procedure where an autologous vascularized distal femur was used to reconstruct acetabular bone stock with subsequent implantation of a total femoral endoprosthetic replacement that uses a constrained cup and a hinged total knee system. At 2 years of follow-up, there is a good functional result with full incorporation of the graft.
Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip , Femur/transplantation , Female , Humans , Middle Aged , ReoperationABSTRACT
BACKGROUND: The use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G(2) cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G(2) arrest and could sensitize OS cells to irradiation induced cell death. METHODS: WEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot. RESULTS: WEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G(2) arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment. CONCLUSION: We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G(2) checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS.
Subject(s)
Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/genetics , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/genetics , Radiation Tolerance/genetics , Apoptosis/drug effects , Apoptosis/genetics , Apoptosis/radiation effects , Bone Neoplasms/physiopathology , CDC2 Protein Kinase , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Cycle/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Cell Survival/radiation effects , Cyclin B/metabolism , Cyclin-Dependent Kinases , DNA Damage/drug effects , DNA Damage/radiation effects , Gamma Rays , Gene Expression Profiling , Humans , Osteosarcoma/physiopathology , Phosphorylation/drug effects , Phosphorylation/radiation effects , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Radiation-Sensitizing Agents/pharmacologyABSTRACT
This report describes the radiological and histological findings of a small cell osteosarcoma of a toe phalanx in a 38 year old man. This man presented with pain, swelling and redness of the left third toe. Medical history revealed an osteomyelitis of this toe eight years prior. Based on clinical findings and medical history the lesion was diagnosed as an osteomyelitis. However, peroperatively the lesion had a malignant aspect. Histological examination revealed a small cell osteosarcoma of the proximal phalanx.Osteosarcoma of the foot and especially of the tubular bones is rare. Moreover small cell osteosarcoma is a rare subtype of osteosarcoma. This case demonstrates that medical history and clinical examination can be misleading. In patients with apparent bone destruction, a malignancy must always be excluded prior to treatment. It emphasises the care that should be taken in the process of formulating a diagnosis.
