Prostate cancer is one of the most common cancers among males worldwide and a common cause of cancer related mortality in males. Bone metastasis from prostate cancer is common in advanced stage disease leading to majo...Prostate cancer is one of the most common cancers among males worldwide and a common cause of cancer related mortality in males. Bone metastasis from prostate cancer is common in advanced stage disease leading to major complications including severe bone pain and fractures. Here, we present a case of 79-year-old male newly diagnosed metastatic prostate cancer, with metastasis to the lungs, liver and lymph nodes, and a solitary osteolytic bone metastasis seen in bone scan. It is well known that osseous metastasis from prostate cancer is primarily sclerotic, although lytic bone metastasis is rare, but it can also be seen as in our case.展开更多
Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond ...Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients.Thus,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments.The microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were determined.Methods:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2/gc/male mice.Results:Bone lesions formed only in femurs of mice injected with PCSD1 cells.Bone volume(BV)was significantly decreased at the proximal and distal ends of the femurs(p<0.01)whereas BV(p<0.05)and bone shaft diameter(p<0.01)were significantly increased along the femur shaft.Conclusion:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur shaft.Therefore,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion.Our approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments.展开更多
Background: Elderly patients with primary intracranial osteolytic and externally growing atypical meningiomas are rare and easy to be misdiagnosed. Recently, a patient with an atypical meningioma was treated in our de...Background: Elderly patients with primary intracranial osteolytic and externally growing atypical meningiomas are rare and easy to be misdiagnosed. Recently, a patient with an atypical meningioma was treated in our department and analyzed the case by reviewing the historical literature.Case presentation: We describe a 63-year-old female with primary intracranial osteolytic atypical meningioma at our neurosurgery department, and retrospectively reviewed previous literatures about its diagnosis, surgical treatment,pathological results, and clinical outcome. Simpson grade I resection was accomplished through a pterional approach.First-stage skull reconstruction was performed, and the patient underwent an uneventful recovery.Conclusions: The final diagnosis of the primary osteolytic atypical meningioma is dependent on a pathological examination. First-stage skull reconstruction could avoid a secondary lesion and improve the patient's quality of life.展开更多
Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bid...Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecu- lar components and mechanisms that are responsible for those interactions.展开更多
Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-presse...Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.展开更多
A 56-year-old male visited our hospital for evaluation of an occipital mass.Contrast computed tomography showed hypervascular enhancement with osteolytic change in the skull and a huge enhanced mass in the liver.Magne...A 56-year-old male visited our hospital for evaluation of an occipital mass.Contrast computed tomography showed hypervascular enhancement with osteolytic change in the skull and a huge enhanced mass in the liver.Magnetic resonance imaging showed bone metastasis in the thoracic vertebrae.Assays for hepatitis B surface antigen and hepatitis B core antibody were positive and his liver condition was Child-Pugh grade A.Our diagnosis was hepatocellular carcinoma(HCC) with skull and vertebrae metastases on chronic hepatitis B.He was treated with radiation therapy for bone metastases and transcatheter arterial chemoembolization for HCC.But he developed acute respiratory failure because of aspiration pneumonia,congestion and oedema with haemorrhage of the lungs and died.Dissection showed HCC with multiple bone metastases.The liver tumor was categorized as well-differentiated HCC,Edmondson classification Ⅰ,trabecular type and pseudoglandular type.In the liver mild infiltration of lymphocytes was seen in Glisson's capsules which were signif icantly enlarged with well preserved limiting plates.Piecemeal necrosis was not obvious.No fibrosis was noted.An 8 cm × 7 cm × 3 cm metastatic lesion had formed in the left occipitotemporal part of the cranial bone.The lesion was osteolytic and showed invasion into the dura mater.Neither the subdural cavity nor the brain showed involvement from the metastatic tumor.However,skull metastasis from HCC is very rare and it affects the patient's prognosis and the quality of life.Therefore,it is very important to make an early diagnosis and carry out proper management of skull metastasis from HCC.展开更多
Erdheim-Chester disease(ECD) is an uncommon, nonfamilial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic fe...Erdheim-Chester disease(ECD) is an uncommon, nonfamilial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic features include bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal parts of the long bones, or bilateral symmetrically abnormal intense 99 mTechnetium labelling of the metaphyseal-diaphyseal region of the long bones, and computed tomography scan findings of "coated aorta" or "hairy kidneys". ECD in childhood with osteolytic lesion is extremely rare. We describe an unusual case with an expansile lytic bone lesion at presentation in a case of acute lymphoblastic leukemia.展开更多
BACKGROUND Osseous hemangiomas,especially those located in the manubrium,are rare benign tumors.In a review of the literature,only three case reports of sternal hemangioma were found.A precise diagnosis is difficult b...BACKGROUND Osseous hemangiomas,especially those located in the manubrium,are rare benign tumors.In a review of the literature,only three case reports of sternal hemangioma were found.A precise diagnosis is difficult because of their nonspecific findings on computed tomography(CT)/magnetic resonance imaging(MRI).CASE SUMMARY An 88-year-old woman was suffering from a progressively enlarging mass in the manubrium.Chest CT images showed an osteolytic and expansile lesion with cortical destruction.Vascular malformation was suspected after CT-guided biopsy.On the dynamic MRI scans,the mass showed a bright signal on the T2-weighted image,peripheral nodular enhancement on the early-phase images and progressive centripetal fill-in on the delayed-phase images.Cavernous hemangioma was suspected preoperatively based on the MRI features and finally confirmed by histopathologic analysis.CONCLUSION This uncommon case demonstrates the possible characteristic features of manubrium cavernous hemangioma on dynamic MRI scans;knowledge about these features may prevent patients from developing catastrophic complications,such as rupture or internal hemorrhage,caused by biopsy or surgery.展开更多
Objectives: To report an epidemiology study and prognosis for metastatic bone tumor. Methodology: It was a descriptive, transversal study on records of patients hospitalized in Rheumatology and Oncology-Radiotherapy d...Objectives: To report an epidemiology study and prognosis for metastatic bone tumor. Methodology: It was a descriptive, transversal study on records of patients hospitalized in Rheumatology and Oncology-Radiotherapy departments of the University Teaching Hospital of Brazzaville, Congo from 1 January 2005 to 31 July 2011 (7 years and 6 months). The diagnosis of bone metastasis was made because of the existence of bone pain, or pathological fracture, or bone swelling and a bone-condensing or mixed or osteolytic radiological image. The anatomo-pathological evidence was made after biopsy of the bone lesion or primary cancer. 3687 patients were hospitalized for active cancer, among them 81 had documented bone metastasis. Results: There were 60 men (74.1%) and 21 women (25.9%) with a sex ratio of 2.85. The average age was 53 years, ranging from 3 to 80 years. 75% of patients were more or equal to 50 years old at the discovery of the bone metastasis. Bone pain was the main mode of discovery (67.9% of cases). However, in 6.2% of cases, it was discovered incidentally. The metastasis was bone condensing in 50.7% of cases, osteolytic in 40.7% and mixed in 8.6%. They were unifocal in 25.9% and multifocal in 74.1% of cases. The Primary cancer most frequently found was that of the prostate in 55.6% of cases, breast in 20.7% and rhabdomyosarcoma in 4.9%. In 6.2% of cases, the primary site of cancer was unknown. The average survival was 25 months. Conclusion: The clinical and radiological presentation remains classic. Cancer of the prostate and breast are the main neoplasia responsible for bone metastasis in our series. The discovery of metastasis remains a major evolutionary step of cancer.展开更多
Metal wear particles generated by the movement of joint prostheses inevitably lead to aseptic osteolytic damage and ultimately prosthesis loosening,which are aggravated by various types of regulated cell death of bone...Metal wear particles generated by the movement of joint prostheses inevitably lead to aseptic osteolytic damage and ultimately prosthesis loosening,which are aggravated by various types of regulated cell death of bone.Nevertheless,the exact cellular nature and regulatory network underlying osteoferroptosis are poorly understood.Here,we report that titanium particles(TP)induced severe peri-implant osteolysis and ferroptotic changes with concomitant transcriptional repression of a key anti-ferroptosis factor,GPX4,in a mouse model of calvarial osteolysis.GPX4 repression was accompanied by an increase in DNA methyltransferases(DNMTs)1/3a/3b and hypermethylation of the Gpx4 promoter,which were partly mediated by the transcriptional regulator/co-repressor KLF5 and NCoR.Conversely,treatment with SGI-1027,a DNMT-specific inhibitor,resulted in marked reversal of Gpx4 promoter hypermethylation and GPX4 repression,as well as improvement in ferroptotic osteolysis to a similar extent as with a ferroptosis inhibitor,liproxstatin-1.This suggests that epigenetic GPX4 repression and ferroptosis caused by the increase of DNMT1/3a/3b have a causal influence on TP-induced osteolysis.In cultured primary osteoblasts and osteoclasts,GPX4 repression and ferroptotic changes were observed primarily in osteoblasts that were alleviated by SGI-1027 in a GPX4 inactivation-sensitive manner.Furthermore,we developed a mouse strain with Gpx4 haplodeficiency in osteoblasts(Gpx4^(0b+/-))thatexhibited worsened ferroptotic osteolysis in control and TP-treated calvaria and largely abolished the anti-ferroptosis and osteoprotective effects of SGl-1027.Taken together,our results demonstrate that DNMT1/3a/3b elevation,resulting GPX4 repression,and osteoblastic ferroptosis form a critical epigenetic pathway that significantly contributes to TP-induced osteolysis,and that targeting DNMT aberration and the associated osteoferroptosis could be a potential strategy to prevent or slow down prosthesis-related osteolytic complications.展开更多
Background:Multiple myeloma(MM)is the second most common hematological malignancy.An overwhelming majority of patients with MM progress to serious osteolytic bone disease.Aminoacyl-tRNA synthetase-interacting multifun...Background:Multiple myeloma(MM)is the second most common hematological malignancy.An overwhelming majority of patients with MM progress to serious osteolytic bone disease.Aminoacyl-tRNA synthetase-interacting multifunctional protein 1(AIMP1)participates in several steps during cancer development and osteoclast differentiation.This study aimed to explore its role in MM.Methods:The gene expression profiling cohorts of MM were applied to determine the expression of AIMP1 and its association with MM patient prognosis.Enzyme-linked immunosorbent assay,immunohistochemistry,and Western blotting were used to detect AIMP1 expression.Protein chip analysis,RNA-sequencing,and chromatin immunoprecipitation and next-generation sequencing were employed to screen the interacting proteins and key downstream targets of AIMP1.The impact of AIMP1 on cellular proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay in vitro and a xenograft model in vivo.Bone lesions were evaluated using tartrate-resistant acid phosphatase staining in vitro.A NOD/SCID-TIBIA mouse model was used to evaluate the effect of siAIMP1-loaded exosomes on bone lesion formation in vivo.Results:AIMP1 expression was increased in MM patients and strongly associated with unfavorable outcomes.Increased AIMP1 expression promoted MM cell proliferation in vitro and in vivo via activation of the mitogen-activated protein kinase(MAPK)signaling pathway.Protein chip assays and subsequent experiments revealed that AIMP1 interacted with acidic leucine-rich nuclear phosphoprotein 32 family member A(ANP32A)to regulate histone H3 acetylation.In addition,AIMP1 increased histone H3 acetylation enrichment function of GRB2-associated and regulator of MAPK protein 2(GAREM2)to increase the phosphorylation of extracellular-regulated kinase 1/2(p-ERK1/2).Furthermore,AIMP1 promoted osteoclast differentiation by activating nuclear factor of activated T cells c1(NFATc1)in vitro.In contrast,exosome-coated small interfering RNA of AIMP1 effectively suppressed MM progression and osteoclast differentiation in vitro and in vivo.Conclusions:Our data demonstrate that AIMP1 is a novel regulator of histone H3 acetylation interacting with ANP32A in MM,which accelerates MM malignancy via activation of the MAPK signaling pathway.展开更多
文摘Prostate cancer is one of the most common cancers among males worldwide and a common cause of cancer related mortality in males. Bone metastasis from prostate cancer is common in advanced stage disease leading to major complications including severe bone pain and fractures. Here, we present a case of 79-year-old male newly diagnosed metastatic prostate cancer, with metastasis to the lungs, liver and lymph nodes, and a solitary osteolytic bone metastasis seen in bone scan. It is well known that osseous metastasis from prostate cancer is primarily sclerotic, although lytic bone metastasis is rare, but it can also be seen as in our case.
基金We are grateful for the funding support for this work from the Leo and Anne Albert Charitable Foundation and the Phi Beta Psi Sorority.We deeply appreciate the invaluable contributions of Dr.Nissi Varki,Director,and Laarni Gapuz,Manager,Moores Cancer Center Histology Core.
文摘Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients.Thus,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments.The microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were determined.Methods:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2/gc/male mice.Results:Bone lesions formed only in femurs of mice injected with PCSD1 cells.Bone volume(BV)was significantly decreased at the proximal and distal ends of the femurs(p<0.01)whereas BV(p<0.05)and bone shaft diameter(p<0.01)were significantly increased along the femur shaft.Conclusion:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur shaft.Therefore,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion.Our approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments.
文摘Background: Elderly patients with primary intracranial osteolytic and externally growing atypical meningiomas are rare and easy to be misdiagnosed. Recently, a patient with an atypical meningioma was treated in our department and analyzed the case by reviewing the historical literature.Case presentation: We describe a 63-year-old female with primary intracranial osteolytic atypical meningioma at our neurosurgery department, and retrospectively reviewed previous literatures about its diagnosis, surgical treatment,pathological results, and clinical outcome. Simpson grade I resection was accomplished through a pterional approach.First-stage skull reconstruction was performed, and the patient underwent an uneventful recovery.Conclusions: The final diagnosis of the primary osteolytic atypical meningioma is dependent on a pathological examination. First-stage skull reconstruction could avoid a secondary lesion and improve the patient's quality of life.
文摘Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecu- lar components and mechanisms that are responsible for those interactions.
基金Supported by Grants from the Spanish Ministry of Economíay Competitividad-Instituto de Salud CarlosⅢ,No.PI12/02591European Funds for Regional Development+3 种基金the Spanish Health Thematic Networks of Cooperative Research in Cancer,No.RTICC RD12/0036/0058Cellular Therapy,No.TerCelRD12/0019/0001,group 8the Network of Centers for Regenera-tive Medicine and Cellular Therapy from Castilla y Leónthe Spanish Society of Hematology and Hemotherapy(to Garcia-Gomez A)
文摘Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.
文摘A 56-year-old male visited our hospital for evaluation of an occipital mass.Contrast computed tomography showed hypervascular enhancement with osteolytic change in the skull and a huge enhanced mass in the liver.Magnetic resonance imaging showed bone metastasis in the thoracic vertebrae.Assays for hepatitis B surface antigen and hepatitis B core antibody were positive and his liver condition was Child-Pugh grade A.Our diagnosis was hepatocellular carcinoma(HCC) with skull and vertebrae metastases on chronic hepatitis B.He was treated with radiation therapy for bone metastases and transcatheter arterial chemoembolization for HCC.But he developed acute respiratory failure because of aspiration pneumonia,congestion and oedema with haemorrhage of the lungs and died.Dissection showed HCC with multiple bone metastases.The liver tumor was categorized as well-differentiated HCC,Edmondson classification Ⅰ,trabecular type and pseudoglandular type.In the liver mild infiltration of lymphocytes was seen in Glisson's capsules which were signif icantly enlarged with well preserved limiting plates.Piecemeal necrosis was not obvious.No fibrosis was noted.An 8 cm × 7 cm × 3 cm metastatic lesion had formed in the left occipitotemporal part of the cranial bone.The lesion was osteolytic and showed invasion into the dura mater.Neither the subdural cavity nor the brain showed involvement from the metastatic tumor.However,skull metastasis from HCC is very rare and it affects the patient's prognosis and the quality of life.Therefore,it is very important to make an early diagnosis and carry out proper management of skull metastasis from HCC.
文摘Erdheim-Chester disease(ECD) is an uncommon, nonfamilial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic features include bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal parts of the long bones, or bilateral symmetrically abnormal intense 99 mTechnetium labelling of the metaphyseal-diaphyseal region of the long bones, and computed tomography scan findings of "coated aorta" or "hairy kidneys". ECD in childhood with osteolytic lesion is extremely rare. We describe an unusual case with an expansile lytic bone lesion at presentation in a case of acute lymphoblastic leukemia.
文摘BACKGROUND Osseous hemangiomas,especially those located in the manubrium,are rare benign tumors.In a review of the literature,only three case reports of sternal hemangioma were found.A precise diagnosis is difficult because of their nonspecific findings on computed tomography(CT)/magnetic resonance imaging(MRI).CASE SUMMARY An 88-year-old woman was suffering from a progressively enlarging mass in the manubrium.Chest CT images showed an osteolytic and expansile lesion with cortical destruction.Vascular malformation was suspected after CT-guided biopsy.On the dynamic MRI scans,the mass showed a bright signal on the T2-weighted image,peripheral nodular enhancement on the early-phase images and progressive centripetal fill-in on the delayed-phase images.Cavernous hemangioma was suspected preoperatively based on the MRI features and finally confirmed by histopathologic analysis.CONCLUSION This uncommon case demonstrates the possible characteristic features of manubrium cavernous hemangioma on dynamic MRI scans;knowledge about these features may prevent patients from developing catastrophic complications,such as rupture or internal hemorrhage,caused by biopsy or surgery.
文摘Objectives: To report an epidemiology study and prognosis for metastatic bone tumor. Methodology: It was a descriptive, transversal study on records of patients hospitalized in Rheumatology and Oncology-Radiotherapy departments of the University Teaching Hospital of Brazzaville, Congo from 1 January 2005 to 31 July 2011 (7 years and 6 months). The diagnosis of bone metastasis was made because of the existence of bone pain, or pathological fracture, or bone swelling and a bone-condensing or mixed or osteolytic radiological image. The anatomo-pathological evidence was made after biopsy of the bone lesion or primary cancer. 3687 patients were hospitalized for active cancer, among them 81 had documented bone metastasis. Results: There were 60 men (74.1%) and 21 women (25.9%) with a sex ratio of 2.85. The average age was 53 years, ranging from 3 to 80 years. 75% of patients were more or equal to 50 years old at the discovery of the bone metastasis. Bone pain was the main mode of discovery (67.9% of cases). However, in 6.2% of cases, it was discovered incidentally. The metastasis was bone condensing in 50.7% of cases, osteolytic in 40.7% and mixed in 8.6%. They were unifocal in 25.9% and multifocal in 74.1% of cases. The Primary cancer most frequently found was that of the prostate in 55.6% of cases, breast in 20.7% and rhabdomyosarcoma in 4.9%. In 6.2% of cases, the primary site of cancer was unknown. The average survival was 25 months. Conclusion: The clinical and radiological presentation remains classic. Cancer of the prostate and breast are the main neoplasia responsible for bone metastasis in our series. The discovery of metastasis remains a major evolutionary step of cancer.
基金supported by the National Major Research Plan of National Natural and Science Foundation of China(NSFC)(92368201)National Key Research and Development Project(2021YFA1201404)+4 种基金Major Project of NSFC(81991514)NSFC General Program(81970577)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Province Medical Innovation Center of Orthopedic Surgery(CXZX-202214)Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities(14380493 and 14380494)。
文摘Metal wear particles generated by the movement of joint prostheses inevitably lead to aseptic osteolytic damage and ultimately prosthesis loosening,which are aggravated by various types of regulated cell death of bone.Nevertheless,the exact cellular nature and regulatory network underlying osteoferroptosis are poorly understood.Here,we report that titanium particles(TP)induced severe peri-implant osteolysis and ferroptotic changes with concomitant transcriptional repression of a key anti-ferroptosis factor,GPX4,in a mouse model of calvarial osteolysis.GPX4 repression was accompanied by an increase in DNA methyltransferases(DNMTs)1/3a/3b and hypermethylation of the Gpx4 promoter,which were partly mediated by the transcriptional regulator/co-repressor KLF5 and NCoR.Conversely,treatment with SGI-1027,a DNMT-specific inhibitor,resulted in marked reversal of Gpx4 promoter hypermethylation and GPX4 repression,as well as improvement in ferroptotic osteolysis to a similar extent as with a ferroptosis inhibitor,liproxstatin-1.This suggests that epigenetic GPX4 repression and ferroptosis caused by the increase of DNMT1/3a/3b have a causal influence on TP-induced osteolysis.In cultured primary osteoblasts and osteoclasts,GPX4 repression and ferroptotic changes were observed primarily in osteoblasts that were alleviated by SGI-1027 in a GPX4 inactivation-sensitive manner.Furthermore,we developed a mouse strain with Gpx4 haplodeficiency in osteoblasts(Gpx4^(0b+/-))thatexhibited worsened ferroptotic osteolysis in control and TP-treated calvaria and largely abolished the anti-ferroptosis and osteoprotective effects of SGl-1027.Taken together,our results demonstrate that DNMT1/3a/3b elevation,resulting GPX4 repression,and osteoblastic ferroptosis form a critical epigenetic pathway that significantly contributes to TP-induced osteolysis,and that targeting DNMT aberration and the associated osteoferroptosis could be a potential strategy to prevent or slow down prosthesis-related osteolytic complications.
基金National Natural Science Foundation of China,Grant/Award Number:82173849Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20200097+1 种基金Priority Academic Program Development of Jiangsu Higher Education InstitutionsJiangsu Postgraduate Research and Practice Innovation Program,Grant/Award Numbers:KYCX21_1769,KYCX20_1451。
文摘Background:Multiple myeloma(MM)is the second most common hematological malignancy.An overwhelming majority of patients with MM progress to serious osteolytic bone disease.Aminoacyl-tRNA synthetase-interacting multifunctional protein 1(AIMP1)participates in several steps during cancer development and osteoclast differentiation.This study aimed to explore its role in MM.Methods:The gene expression profiling cohorts of MM were applied to determine the expression of AIMP1 and its association with MM patient prognosis.Enzyme-linked immunosorbent assay,immunohistochemistry,and Western blotting were used to detect AIMP1 expression.Protein chip analysis,RNA-sequencing,and chromatin immunoprecipitation and next-generation sequencing were employed to screen the interacting proteins and key downstream targets of AIMP1.The impact of AIMP1 on cellular proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay in vitro and a xenograft model in vivo.Bone lesions were evaluated using tartrate-resistant acid phosphatase staining in vitro.A NOD/SCID-TIBIA mouse model was used to evaluate the effect of siAIMP1-loaded exosomes on bone lesion formation in vivo.Results:AIMP1 expression was increased in MM patients and strongly associated with unfavorable outcomes.Increased AIMP1 expression promoted MM cell proliferation in vitro and in vivo via activation of the mitogen-activated protein kinase(MAPK)signaling pathway.Protein chip assays and subsequent experiments revealed that AIMP1 interacted with acidic leucine-rich nuclear phosphoprotein 32 family member A(ANP32A)to regulate histone H3 acetylation.In addition,AIMP1 increased histone H3 acetylation enrichment function of GRB2-associated and regulator of MAPK protein 2(GAREM2)to increase the phosphorylation of extracellular-regulated kinase 1/2(p-ERK1/2).Furthermore,AIMP1 promoted osteoclast differentiation by activating nuclear factor of activated T cells c1(NFATc1)in vitro.In contrast,exosome-coated small interfering RNA of AIMP1 effectively suppressed MM progression and osteoclast differentiation in vitro and in vivo.Conclusions:Our data demonstrate that AIMP1 is a novel regulator of histone H3 acetylation interacting with ANP32A in MM,which accelerates MM malignancy via activation of the MAPK signaling pathway.
