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Article: Synovial Chondromatosis of the Midcarpal Joint: A Case Report and Brief Review of Literature.

PosthumaDeBoer, Jantine / Torrekens, Marieke / Nuffel, Maarten Van

2021 Volume 11, Issue 2, Page(s) 177–180

Abstract: ... ...

Abstract	Objective
Language	English
Publishing date	2021-03-24
Publishing country	United States
Document type	Case Reports
ZDB-ID	2678060-4
ISSN	2163-3924 ; 2163-3916
ISSN (online)	2163-3924
ISSN	2163-3916
DOI	10.1055/s-0041-1726405
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Article: Synovial Chondromatosis of the Midcarpal Joint: A Case Report and Brief Review of Literature

PosthumaDeBoer, Jantine / Torrekens, Marieke / Nuffel, Maarten Van

Journal of Wrist Surgery

2021 Volume 11, Issue 02, Page(s) 177–180

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 ... ...

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.
Keywords	wrist arthroscopy ; synovial chondromatosis ; imaging ; histology
Language	English
Publishing date	2021-03-24
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2678060-4
ISSN	2163-3924 ; 2163-3916 ; 2163-3924
ISSN (online)	2163-3924
ISSN	2163-3916 ; 2163-3924
DOI	10.1055/s-0041-1726405
Database	Thieme publisher's database

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Article ; Online: Small cell osteosarcoma of a toe phalanx: a case report and review of literature.

Posthumadeboer, Jantine / Graat, Harm Ca / Bras, Johannes / Saouti, Rachid

Journal of orthopaedic surgery and research

2010 Volume 5, Page(s) 36

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2010-06-03
Publishing country	England
Document type	Journal Article
ISSN	1749-799X
ISSN (online)	1749-799X
DOI	10.1186/1749-799X-5-36
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Article ; Online: Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature.

PosthumaDeBoer, J / Witlox, M A / Kaspers, G J L / van Royen, B J

Clinical & experimental metastasis

2011 Volume 28, Issue 5, Page(s) 493–503

Abstract: Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific ... ...

Abstract	Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Bone Neoplasms/drug therapy ; Bone Neoplasms/pathology ; Humans ; Molecular Targeted Therapy ; Neoplasm Metastasis/drug therapy ; Neoplasm Metastasis/pathology ; Osteosarcoma/drug therapy ; Osteosarcoma/pathology
Language	English
Publishing date	2011-04-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604952-7
ISSN	1573-7276 ; 0262-0898
ISSN (online)	1573-7276
ISSN	0262-0898
DOI	10.1007/s10585-011-9384-x
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Article ; Online: Pelvic reconstruction with a free vascularized distal femur for revision total hip arthroplasty.

Van de Kerkhove, Maarten-Paul / PosthumaDeBoer, Jantine / Jiya, Timothy U / Winters, Hay A / Saouti, Rachid

The Journal of arthroplasty

2012 Volume 27, Issue 3, Page(s) 493.e19–22

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Acetabulum/surgery ; Arthroplasty, Replacement, Hip ; Female ; Femur/transplantation ; Humans ; Middle Aged ; Reoperation
Language	English
Publishing date	2012-03
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2011.03.049
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Article ; Online: Targeting JNK-interacting-protein-1 (JIP1) sensitises osteosarcoma to doxorubicin.

Posthumadeboer, Jantine / van Egmond, Pim W / Helder, Marco N / de Menezes, Renée X / Cleton-Jansen, Anne-Marie / Beliën, Jeroen A M / Verheul, Henk M W / van Royen, Barend J / Kaspers, Gert-Jan J L / van Beusechem, Victor W

Oncotarget

2012 Volume 3, Issue 10, Page(s) 1169–1181

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 ... ...

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.
MeSH term(s)	Adaptor Proteins, Signal Transducing/antagonists & inhibitors ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adolescent ; Antibiotics, Antineoplastic/pharmacology ; Apoptosis/drug effects ; Blotting, Western ; Bone Neoplasms/drug therapy ; Bone Neoplasms/genetics ; Bone Neoplasms/mortality ; Case-Control Studies ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm/genetics ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Neoplasm Staging ; Osteoblasts/metabolism ; Osteoblasts/pathology ; Osteosarcoma/drug therapy ; Osteosarcoma/genetics ; Osteosarcoma/mortality ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Tissue Array Analysis
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antibiotics, Antineoplastic ; MAPK8IP1 protein, human ; RNA, Messenger ; RNA, Small Interfering ; Doxorubicin (80168379AG)
Language	English
Publishing date	2012-10-08
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.600
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Article ; Online: Surface proteomic analysis of osteosarcoma identifies EPHA2 as receptor for targeted drug delivery.

Posthumadeboer, J / Piersma, S R / Pham, T V / van Egmond, P W / Knol, J C / Cleton-Jansen, A M / van Geer, M A / van Beusechem, V W / Kaspers, G J L / van Royen, B J / Jiménez, C R / Helder, M N

British journal of cancer

2013 Volume 109, Issue 8, Page(s) 2142–2154

Abstract: Background: Osteosarcoma (OS) is the most common bone tumour in children and adolescents. Despite aggressive therapy regimens, treatment outcomes are unsatisfactory. Targeted delivery of drugs can provide higher effective doses at the site of the tumour, ...

Abstract	Background: Osteosarcoma (OS) is the most common bone tumour in children and adolescents. Despite aggressive therapy regimens, treatment outcomes are unsatisfactory. Targeted delivery of drugs can provide higher effective doses at the site of the tumour, ultimately improving the efficacy of existing therapy. Identification of suitable receptors for drug targeting is an essential step in the design of targeted therapy for OS. Methods: We conducted a comparative analysis of the surface proteome of human OS cells and osteoblasts using cell surface biotinylation combined with nano-liquid chromatography - tandem mass spectrometry-based proteomics to identify surface proteins specifically upregulated on OS cells. This approach generated an extensive data set from which we selected a candidate to study for its suitability as receptor for targeted treatment delivery to OS. First, surface expression of the ephrin type-A receptor 2 (EPHA2) receptor was confirmed using FACS analysis. Ephrin type-A receptor 2 expression in human tumour tissue was tested using immunohistochemistry. Receptor targeting and internalisation studies were conducted to assess intracellular uptake of targeted modalities via EPHA2. Finally, tissue micro arrays containing cores of human OS tissue were stained using immunohistochemistry and EPHA2 staining was correlated to clinical outcome measures. Results: Using mass spectrometry, a total of 2841 proteins were identified of which 156 were surface proteins significantly upregulated on OS cells compared with human primary osteoblasts. Ephrin type-A receptor 2 was highly upregulated and the most abundant surface protein on OS cells. In addition, EPHA2 was expressed in a vast majority of human OS samples. Ephrin type-A receptor 2 effectively mediates internalisation of targeted adenoviral vectors into OS cells. Patients with EPHA2-positive tumours showed a trend toward inferior overall survival. Conclusion: The results presented here suggest that the EPHA2 receptor can be considered an attractive candidate receptor for targeted delivery of therapeutics to OS.
MeSH term(s)	Bone Neoplasms/chemistry ; Bone Neoplasms/drug therapy ; Bone Neoplasms/metabolism ; Cell Line, Tumor ; Chromatography, Liquid/methods ; Data Mining ; Female ; Flow Cytometry/methods ; Humans ; Male ; Membrane Proteins/analysis ; Membrane Proteins/metabolism ; Middle Aged ; Molecular Targeted Therapy ; Osteosarcoma/chemistry ; Osteosarcoma/drug therapy ; Osteosarcoma/metabolism ; Prognosis ; Proteome/analysis ; Proteome/metabolism ; Proteomics/methods ; Receptor, EphA2/analysis ; Receptor, EphA2/metabolism ; Tandem Mass Spectrometry/methods ; Up-Regulation
Chemical Substances	Membrane Proteins ; Proteome ; Receptor, EphA2 (EC 2.7.10.1)
Language	English
Publishing date	2013-09-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/bjc.2013.578
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Article ; Online: WEE1 inhibition sensitizes osteosarcoma to radiotherapy.

PosthumaDeBoer, Jantine / Würdinger, Thomas / Graat, Harm C A / van Beusechem, Victor W / Helder, Marco N / van Royen, Barend J / Kaspers, Gertjan J L

BMC cancer

2011 Volume 11, Page(s) 156

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	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 Cycle Proteins/antagonists & inhibitors ; Cell Cycle Proteins/genetics ; 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 ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/genetics ; Osteosarcoma/physiopathology ; Phosphorylation/drug effects ; Phosphorylation/radiation effects ; Protein Kinase Inhibitors/pharmacology ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Protein-Tyrosine Kinases/genetics ; Pyrimidines/pharmacology ; Radiation Tolerance/genetics ; Radiation-Sensitizing Agents/pharmacology
Chemical Substances	Cell Cycle Proteins ; Cyclin B ; Nuclear Proteins ; PD 0166285 ; Protein Kinase Inhibitors ; Pyrimidines ; Radiation-Sensitizing Agents ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; WEE1 protein, human (EC 2.7.10.2) ; CDC2 Protein Kinase (EC 2.7.11.22) ; CDK1 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinases (EC 2.7.11.22)
Language	English
Publishing date	2011-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/1471-2407-11-156
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Article ; Online: WEE1 inhibition sensitizes osteosarcoma to radiotherapy

Helder Marco N / van Beusechem Victor W / Graat Harm CA / Würdinger Thomas / PosthumaDeBoer Jantine / van Royen Barend J / Kaspers Gertjan JL

BMC Cancer, Vol 11, Iss 1, p

2011 Volume 156

Abstract: Abstract 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 ... ...

Abstract	Abstract 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.
Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	616
Language	English
Publishing date	2011-04-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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