TY - JOUR. T1 - Severe osteolysis and soft tissue mass around total hip arthroplasty. T2 - Description of four cases and review of the literature with respect to clinico-radiographic and pathologic differential diagnosis. AU - Fabbri, N.. AU - Rustemi, E.. AU - Masetti, C.. AU - Kreshak, J.. AU - Gambarotti, M.. AU - Vanel, D.. AU - Toni, A.. AU - Mercuri, M.. PY - 2011. Y1 - 2011. N2 - Periprosthetic osteolysis is a well known phenomenon caused by wear particle-induced bone resorption, particularly common and extensively reported in total hip arthroplasty. Its typical radiographic feature is a radiolucent area adjacent to an implant, sometimes associated with a soft tissue mass. Osteolytic changes may be caused by numerous other pathologic processes, including infection, metabolic disease, and neoplasia. Four cases of massive periprosthetic bone destruction associated with a large soft tissue mass around a failed total hip replacement are presented. In three cases, a diagnosis of periprosthetic ...
A number of inflammatory cytokines may contribute to the periarticular bone loss of RA, but the most significant is TNF-α. Macrophages and T cells express TNF-α in the arthritic synovial tissue as a membrane-residing protein that does not promote osteoclast formation until it is cleaved to its soluble form (40). Like RANKL, TNF-α exerts its biological effects by clustering and trimerizing three monomeric receptors (41). In fact, TNF-α activates two known receptor complexes, namely TNF receptor type 1 (TNFR1) and type 2 (TNFR2), and each prompts different intracellular events. TNFR1, which is principally stimulated by soluble TNF-α, transmits proinflammatory signals and synergizes with RANK to promote osteoclastogenesis (42). Signals induced by TNFR2, which largely recognizes membrane-residing TNF-α, are pro-immunogenic and anti-inflammatory (43). Thus, TNFR1 is responsible for the crippling effects of RA, PsA, and other forms of focal osteolysis, such as that complicating orthopedic ...
There are many causes of inflammatory osteolysis, but regardless of etiology and cellular contexts, the osteoclast is the bone-degrading cell. Thus, the impact of inflammatory cytokines on osteoclast formation and function was among the most important discoveries advancing the treatment of focal osteolysis, leading to development of therapeutic agents that either directly block the bone-resorptive cell or do so indirectly via cytokine arrest. Despite these advances, a substantial number of patients with inflammatory arthritis remain resistant to current therapies, and even effective anti-inflammatory drugs frequently do not repair damaged bone. Thus, insights into events such as those impacted by inflammasomes, which signal through cytokine-dependent and -independent mechanisms, are needed to optimize treatment of inflammatory osteolysis.. ...
There are many causes of inflammatory osteolysis, but regardless of etiology and cellular contexts, the osteoclast is the bone-degrading cell. Thus, the impact of inflammatory cytokines on osteoclast formation and function was among the most important discoveries advancing the treatment of focal osteolysis, leading to development of therapeutic agents that either directly block the bone-resorptive cell or do so indirectly via cytokine arrest. Despite these advances, a substantial number of patients with inflammatory arthritis remain resistant to current therapies, and even effective anti-inflammatory drugs frequently do not repair damaged bone. Thus, insights into events such as those impacted by inflammasomes, which signal through cytokine-dependent and -independent mechanisms, are needed to optimize treatment of inflammatory osteolysis.. ...
In this study, we examined the potential role of a kernel-based Bayesian model in the prediction of osteolysis in the late period after cemented THA. We found that mean annual wear rate was the most predictive variable for osteolysis, followed by age at THA surgery. This model, based on Bayes theory, gave a correct classification rate for osteolysis of approximately 70%, using five-fold cross-validation to examine the accuracy of the model. When the data were divided into male and female subsets, the correct classification rate for female was 74% versus 66% for males.. The appropriate choice of the window width is crucial in constructing the classifier. There are various methods suggested in the literature to calculate the window width parameter [18], which can be easily incorporated to the proposed method in this work. One simple technique is to determine the window width based on the sample standard deviation or its alternative robust estimates [19]. This works well if the observation points ...
BACKGROUND: Wear particles, found at the bone-implant interface surrounding a loose prosthesis, are commonly phagocytosed by macrophages. Wear particles and wear particle-containing macrophages are also found in regional lymph nodes draining arthroplasty tissues. The means by which wear particles are transported from arthroplasty tissues to lymph nodes is uncertain, as the presence or absence of lymphatic vessels in periprosthetic tissues has not been established. METHODS: We determined immunophenotypic expression of LYVE-1 and podoplanin, two highly specific lymphatic endothelial cell markers, in the hip arthroplasty pseudocapsule surrounding the false joint and the bone-implant interface of the femoral and acetabular pseu-domembrane. RESULTS: LYVE-1+/podoplanin+ lymphatic vessels were not identified in the pseudomembrane but were found in the pseudocapsule. Normal bone did not contain lymphatic vessels. INTERPRETATION: Our findings suggest that the wear particles shed at the bone-implant interface are
Aims: The biological reaction to wear debris is critical to the osteolysis underlying aseptic loosening of joint prosthetic implants. In an attempt to reduce aseptic loosening, ceramics have been introduced. This study was designed to evaluate, compare and correlate the expression of Toll-like receptors (TLRs), their intracellular adaptors and proinflammatory cytokines in cultured macrophages challenged with titanium or zirconia particles, as well as particle-induced osteolysis in calvaria and hyperalgesia and edema in hind paw. Main methods: TLRs and their adaptors were evaluated at the mRNA level by RT-PCR, and cytokine expression was evaluated at the mRNA and protein levels. Osteolysis and hyperalgesia and edema were evaluated in vivo, in calvaria and hind paw, respectively. Key findings: Cultured macrophages challenged with zirconia or titanium particles expressed increased mRNA for TLRs 2, 3, 4 and 9, and their adaptors MyD88, TR1F and NF-kappa B and cytokines TNF-alpha, IL-1 beta and 1L-6, ...
Introduction Hip-revision surgery is frequently complicated by unexpected periacetabular osteolysis. Preoperative x-rays normally do not reveal sufficient information about the amount of osteolysis, but in the course of the operation, huge localized osteolytic lesions in the pelvic bone may appear. X-ray examinations often underestimate the extent of osteolysis, and CT-scans have not yet overcome the metal artifacts and high radiation doses to evolve into a useful tool in this matter. Wear-particles from polyethylene are suspected to play a role in the development of osteolysis. HA-coating of implants seems to reduce the risk by sealing off the bone-implant interface. DEXA-scanning has proven a sensitive tool in the assessment of bone mineral changes around femoral stems, and tibial plateaus. However, only few studies have focused on the bone mineral changes around acetabular components. The aim of the present studies was to utilize DEXA-scanning as a simple tool to determine periacetabular ...
Symptoms of lytic bone lesions vary since many different diseases can cause them. Typical symptoms include pain, pathologic bone fractures and high blood calcium, according to MedicineNet. Pathologic...
Abstract. Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. While the osteolytic cascade initiated by cytokine release from macrophages has been studied extensively, the involvement of T-lymphocytes in this context is controversial and has been addressed by only a few authors. In a former study we detected that the quantity of T-lymphocytes may be influenced by apoptosis in patients with aseptic loosening. In this study we intended to find out more details about the apoptosis-induced shifting of the T-cell number. We focused our interest on the CD4+ and CD8+ T-cells and their relative ratio. Caspase-3 cleaved was evaluated immunohistochemically to detect apoptotic T-cells in capsules and interface membranes from patients with aseptic hip implant loosening and a varying degree of caspase-3 cleaved expression in CD4+ and CD8+ T-lymphocytes was detected. Moreover, a relationship between the intensity of the apoptotic reactions and the radiological ...
Breast cancer is the second leading cause of cancer-related death in women in the United States. During the advanced stages of disease, many breast cancer patients suffer from bone metastasis. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. In vivo models that mimic the breast cancer-specific osteolytic bone microenvironment are limited. Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface. In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets. We identified a TB signature consisting of 934 genes that were
Osteolytic lesions often occur in people with myeloma or other types of cancer. The lesions can cause bones to become soft and prone to fracture.
Soft tissue biopsy from osteolytic lesions is a challenge for the interventionist. The Spirotome Bone is conceived for this intervention. The procedure is straigthforward and produces tissue specimens of high quality in sufficient amounts to allow quantitative molecular biology ...
In the current study, we have generated a faithful computational model of the BMU. It is important to note that the homeostatic behavior is not hardcoded but emerges from the interactions between the different primary cell types of the bone in response to TGF-β, RANKL, and BDFs. Furthermore, informed by experimental evidence, the introduction of a simulated TGF-β ligand and receptor expressing prostate cancer cell into the BMU resulted in a vicious cycle that yielded mixed osteogenic/osteolytic lesions over clinically relevant periods of time. Key findings arising from the computational model include: (i) the ability to assess temporal changes in cellular populations and dissect complex dynamics that are difficult to determine in vivo, (ii) the phasic osteolytic/osteogenic nature of the metastases, (iii) the application of clinically used therapies such as bisphosphonates and anti-RANKL therapies illustrate the usefulness of the model in predicting the efficacy of targeted inhibitors, and (iv) ...
Sophocleous A, Marino S, Logan JG et al. Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis. J Biol. Chem. 2015 Sep 4;290(36):22049-60. PMID: 26195631.. Tomar S, Zumbrun EE, Nagarkatti M, and Nagarkatti PS. Protective role of cannabinoid receptor 2 activation in galactosamine/lipopolysaccharide-induced acute liver failure through regulation of macrophage polarization and microRNAs. J Pharmacol Exp Ther. 2015 May;353(2):369-79. PMID: 25749929.. Zhang HY, Gao M, Liu QR et al. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proc Natl Acad Sci USA. 2014 Nov 18;111(46):E5007-15. PMID: 25368177.. ...
There was wide variation in the detectable levels of cytokines. No significant differences were found between patients with and without osteolysis in mean synovial fluid levels of IL-6 (p = 0.863), IL-18 (p = 0.324), M-CSF (p = 0.508), sRANKL (p = 0.884), OPG (p = 0.776) or mean serum levels of OPG (p = 0.993) or sRANKL (p = 0.565) (insufficient detection of IL-6, IL-18 or M-CSF in serum samples). A correlation was found between synovial fluid levels of IL-6 and OPG in patients without osteolysis (r2 = 0.618, p,0.001) but not with osteolysis (r2 = 0.0004).. ...
Project summary Breast cancer frequently metastasizes to be where it leads to osteolysis and poor clinical prognosis; however, the role of hydroxyapatite nanocrystals (HA, the mineral component of bone) in this process remains unclear due, in part, to the lack of appropriate culture models. The overall goal of these studies is to design a mineralized 3-D tumor model that captures the intrinsic 3-D cell-microenvironment interactions within bone- metastatic niches and nanostructural alterations of HA that may occur due to disease and aging. Specifically, we will develop porous poly (lactide-co-glycolide) (PLG) scaffolds that incorporate HA nanoparticles of defined physicochemical characteristics and assess the applicability and relevance of this 3-D tumor model to test the functional relationships between HA and osteolytic bone metastasis. This work will be accomplished in three specific aims: In Aim 1, we will develop the 3-D matrices by synthesizing monodispersed nanoparticles of HA with ...
Project summary Breast cancer frequently metastasizes to be where it leads to osteolysis and poor clinical prognosis; however, the role of hydroxyapatite nanocrystals (HA, the mineral component of bone) in this process remains unclear due, in part, to the lack of appropriate culture models. The overall goal of these studies is to design a mineralized 3-D tumor model that captures the intrinsic 3-D cell-microenvironment interactions within bone- metastatic niches and nanostructural alterations of HA that may occur due to disease and aging. Specifically, we will develop porous poly (lactide-co-glycolide) (PLG) scaffolds that incorporate HA nanoparticles of defined physicochemical characteristics and assess the applicability and relevance of this 3-D tumor model to test the functional relationships between HA and osteolytic bone metastasis. This work will be accomplished in three specific aims: In Aim 1, we will develop the 3-D matrices by synthesizing monodispersed nanoparticles of HA with ...
The syndrome of acute spontaneous absorption of bone is a rather rare and poorly understood condition. It is often referred to under such descriptive titles as "disappearing bone," "acute spontaneous absorption of bone," "phantom bone" and "idiopathic osteolysis of bone." In the cases reported to date, several common factors seem to occur repeatedly: The patient is usually a young adult in good general health; minor trauma, usually to the affected area, calls attention to the lesion; pain is not a striking symptom; there is no sex predilection. The course of the disease is variable. Cases have been reported where the ...
Osteolysis tends to remain clinically silent and presents a treatment challenge. In the past, the progression of implant wear was used to determine the timing of interventions. Recent reports of lesions associated with metal-on-metal implants and trunnion corrosion with femoral head sizes larger than 32 mm suggest that other mechanisms of wear debris production may be present; observation alone may not provide adequate monitoring. Advanced imaging modalities, such as MRI, should be used along with routine radiography to assess soft-tissue involvement and the size of osteolytic lesions. Intraoperative mechanical stress applied to the acetabular cup helps determine if revision or retention is selected when osteolysis is present. Options for the management of acetabular osteolysis include porous metal cups, oblong cups, antiprotrusio cages, impaction grafting, structural grafts, and, more recently, versatile porous metal cups. Porous metal cups can be used with or without augments or as cup-cage ...
Aseptic loosening (AL) because of osteolysis may be the primary reason behind joint prosthesis failure. the next factors were noticed: Interleukins 6 and 1 (IL16 and ), Tumor Necrosis Element (TNF), nuclear element kappa-light-chain-enhancer of triggered B cells (NFB), Nuclear element of triggered T-cells, cytoplasmic 1 (NFATC1), Cathepsin K (CATK) and Tartrate-resistant acidity phosphatase (Capture). Titanium (Ti) and Polyethylene (PE) had been the most researched contaminants, displaying that Ti up-regulated osteoclastogenesis and swelling related genes, while PE up-regulated osteoclastogenesis related genes mainly. in ZrO2 than Ti[54]0.05, 0.5, 1 mg/mL Ti alloy contaminants (? 0.52 m)SFs from OA pzProtein amounts (IRE1-, CHOP, RANKL, OPG, sRANKL) Gene expression ((at the best concentration)[45]0.1 mg/mL Ti particles (? 3.6 m)Mice BMMOCs number Bone resorption assay Gene expression ( cell viability, ALP, COLL I, OCN, mineralization, CMKBR7 membrane damage viability OBs, BMMs: (at 7 days), (at ...
www.sciencesignaling.org/cgi/content/full/9/413/ra12/DC1. Fig. S1. ABL family protein abundance is increased in breast cancer cells with enhanced bone metastatic activity, and ABL1/ABL2 depletion does not affect proliferation in vitro.. Fig. S2. ABL kinases promote breast cancer cell invasion.. Fig. S3. Depletion of ABL kinases does not inhibit metastasis of 4175 breast cancer cells, which show tropism to the lung.. Fig. S4. Treatment of breast cancer cells with imatinib but not GNF5 promotes ERK activation.. Fig. S5. CXCL12- and IGF-1-mediated survival pathways are independent of ABL kinases.. Fig. S6. Depletion of ABL kinases in SKBR3 breast cancer cells decreases tumor-induced osteoclast activation.. Fig. S7. IL-6 affects RANKL and OPG expression in osteoblasts.. Fig. S8. Quality control and global statistics of RNAseq analysis for transcriptome comparison of control versus ABL1/ABL2 knockdown breast cancer cells.. Fig. S9. ABL kinases increase TAZ protein abundance and STAT5 ...
Tumor-induced bone disease is common among patients with advanced solid cancers, especially those with breast, prostate, and lung malignancies. The tendency of these cancers to metastasize to bone and induce bone destruction is, in part, due to alterations in integrin expression and signaling. Substantial evidence from preclinical studies shows that increased expression of integrin αvβ3 in tumor cells promotes the metastatic and bone-invasive phenotype. Integrin αvβ3 mediates cell adhesion to several extracellular matrix proteins in the bone microenvironment which is necessary for tumor cell colonization as well as the transmission of mechanical signals for tumor progression. This review will discuss the αvβ3 integrin receptor in the context of tumor-induced bone disease. Specifically, the focus will be the role of αvβ3 in modulating cancer metastasis to bone and tumor cell response to the bone microenvironment, including downstream signaling pathways that contribute to tumor-induced osteolysis.
These authors provide a guide to reconstructive treatment for an 80-year-old patient who developed massive tibial and talar osteolysis after an ankle implant failed.
Recurring breast cancer can sometimes spread to your bones. A long-term study conducted by the by the Hacettepe University Institute of Oncology in Turkey on 141 women with breast cancer and bone metastasis found that the median survival rate was two years, according to ascopubs.org.
R.Coleman explains how the trial results can help plan treatment for women with metastatic BC, highlighting advantages of a less intensified approach
Bone destruction is a hallmark of myeloma and affects 80% of patients. Myeloma cells promote bone destruction by activating osteoclasts. In investigating the underlying mechanism, we found that C-reactive protein (CRP), a protein secreted in increased amounts by hepatocytes in response to myeloma-derived cytokines, activated myeloma cells to promote osteoclastogenesis and bone destruction in vivo. In mice bearing human bone grafts and injected with multiple myeloma cells, CRP bound to surface CD32 (also known as FcγRII) on myeloma cells, which activated a pathway mediated by the kinase p38 MAPK and the transcription factor Twist that enhanced the cells secretion of osteolytic cytokines. Furthermore, analysis of clinical samples from newly diagnosed myeloma patients revealed a positive correlation between the amount of serum CRP and the number of osteolytic bone lesions. These findings establish a mechanism by which myeloma cells are activated to promote bone destruction and suggest that CRP ...
Various compounds of BPs, striking for either oral or intravenous antibiotic, can have a beneficial effect on tumor-induced osteolysis, thereby preventing the. Your risk of osteoporosis (otitis thinning) can be affected by breast density treatment and other countries retin a while accutane lower your potassium levels. hormone therapy with a learn called an aromatase inhibitor (such as anastrozole, exemestane or letrozole); kies to your ovaries to stop them find; surgery to remove your. The U. Esc General estimates that by increasing of all Americans could have tried bones due to bone loss. These drugs, which include Arimidex® (anastrozole), Aromasin® retin a while accutane, and Femara® (letrozole), grand bone loss by reducing the amount of gamma in the body. I am currently on month 3 of my second course of Isotretinoin. My skin is still oily, and Im still getting acne break outs. Granted, they are less severe in size and number, but still happening nonetheless. I am just under lbs, and Im ...
Data & statistics on Bone Metastases Therapy: Bone metastases from hormone‐resistant prostate cancer., Kinetic analysis of 18F-fluoride PET images can differentiate osteoblastic and osteolytic lesions in breast cancer metastases. The authors concluded that fluoride flux and transport can be accurately and independently measured for bone metastases and normal vertebrae., Inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer,
Total hip arthroplasty (THA) has dramatically improved the treatment of an entire range of hip joint diseases. On the other hand, however, it has favored the development of a new disease - periprosthetic osteolysis with a consequent instability of THA. Aseptic instability is the major late complication of THA and the main reason of its malfunction. Molecular and cellular mechanisms of this complication have been thoroughly studied. The importance of prosthetic materials and design have been clearly demonstrated. However, existence of individual susceptibility to development of this complication that is determined neither by endoprothesis properties nor by demographic or morbidity characteristics of a patient has also been recognized. In the recent years, several smaller studies have tried to define the »genetic background of the individual susceptibility« towards the development of aseptic instability. All these studies followed the same logic - they searched for a link between the ...
Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbat
Dr. Rosol maintains an active, NIH-funded research laboratory that uses molecular, in vitro, and in vivo techniques to investigate the pathogenesis of human and animal cancers. Specifically, the laboratory develops mouse models of cancer to study the pathogenesis of bone metastasis, cancer-associated hypercalcemia, and human HTLV-1-induced T-cell lymphoma. The molecular regulation of parathyroid hormone-related protein is studied in vitro and in vivo using animal models of prostate, lung, and breast cancer, and lymphoma. Breast and prostate cancer both metastasize to bone in humans, but breast cancer typically induces osteolytic disease and prostate cancer typically induces osteoblastic metastases. The Rosol laboratory has developed mouse models of human cancer that mimic metastases in humans and are used to investigate the pathogenesis and treatment of metastasis. New laboratory expertise has been developed for in vivo imaging of cancer in mouse models using bioluminescence, high resolution ...
Objective: This retrospective study was aimed to evaluate the radiographic and clinical results of polyaxial locking compression osteosynthesis system..
2069 Multiple myeloma is a disease of malignant B-cells that have extended survival and a low proliferation rate which accumulate in the bone marrow causing osteolytic bone lesions. Treatment with current chemotherapeutic agents initially reduces tumour burden but the disease remains incurable, with the average patient survival time being three years. Therefore, there is an urgent need for novel therapies ideally based on an understanding of the biology of the disease. One area of interest is that of cyclin dependent kinases that regulate two main cellular processes essential for malignant cell survival; cell cycle progression and transcription. These kinases are good cellular targets for anti-neoplastic drugs. Seliciclib (CYC202, R-roscovitine) is a CDK inhibitor, currently in clinical trials, that principally targets CDK2, CDK7 and CDK9 and shows potent activity against multiple myeloma cells (MacCallum et al., 2005. Cancer Res. 65 pp5399). Selicliclib acts in part by inhibiting the kinases ...
HI CAN ANYONE TELL ME THE ICD-9 CODE FOR CLAVICLE OSTEOLYSIS? OSTEOLYSIS IS NOT IN THE CPT BOOK. ANY SUGGESTIONS WOULD BE GREATLY APPRECIATED. THANKS
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Abstract. Multiple myeloma (MM) patients develop devastating osteolytic bone disease causing non-healing bone fractures and pain. MM cells in the bone marrow m
It is true that in patients under 30 years a well-defined border means that we are dealing with a benign lesion, but in patients over 40 years metastases and multiple myeloma have to be included in the differential diagnosis. ...
It is true that in patients under 30 years a well-defined border means that we are dealing with a benign lesion, but in patients over 40 years metastases and multiple myeloma have to be included in the differential diagnosis. ...
It is true that in patients under 30 years a well-defined border means that we are dealing with a benign lesion, but in patients over 40 years metastases and multiple myeloma have to be included in the differential diagnosis. ...
Question: My dog is 11 and a half lab has been always healthy and her blood test back in September was just perfect. On November 5th, she started limping and when I took her to the vet, the xray showed that she has a lytic bone lesion in her right shoulder. Her lungs were clear. …
The major cause of knee prosthetic loosening is due to the development of inflammation in the knee joint which slowly begins to dissolve the knee bone around the prosthesis (a process called osteolysis) and the prosthesis eventually becomes loose. This 3D animation sequence visualizes the various causes of knee pros loosening along with associated radiographic comparisons. ...
Chest X-ray obtained at the time of admission. Bilateral osteomyelitis in the humerus presented as osteolysis and involucrum. Also, there is sequestration becau
Treatment of Myeloma Bone Disease James R. Berenson, MD Medical & Scientific Director Institute for Bone Cancer & Myeloma Research West Hollywood, CA Clinical Consequences of Myeloma Bone Disease Pathological
Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the
A useful mnemonic when you see tapered osteolysis of the distal clavicle is: SHIRT Pocket Mnemonic S: scleroderma H: hyperparathyroidism I: infection (osteomyelitis) R: rheumatoid arthritis T: trauma P: progeria
TY - JOUR. T1 - A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. AU - Noonan, Kimberly. AU - Marchionni, Luigi. AU - Anderson, Judy. AU - Pardoll, Drew. AU - Roodman, G. David. AU - Borrello, Ivan. PY - 2010/11/4. Y1 - 2010/11/4. N2 - Osteoclast (OC)-mediated lytic bone disease remains a cause of major morbidity in multiple myeloma. Here we demonstrate the critical role of interleukin-17-producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an interleukin-17 phenotype that enhances OC activation. In univariate analyses of factors mediating bone destruction, levels of cytokines that selectively induce and maintain the Th17 phenotype tightly correlated with the extent of bone disease in myeloma. In contrast, MILs activated under conditions that skew toward a Th1 phenotype ...
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In this study, we showed that TGF-β signaling in prostatic fibroblasts contributed to subsequent prostate cancer bone metastasis through paracrine interactions. Conditioned medium prepared from koPFs promoted the early development and growth of prostate cancer mixed bone lesions in the tibiae of mice. This effect was, in part, mediated by elevated expression of cytokines CXCL16 and CXCL1 present in the koPFCM, which stimulated prostate cancer cell adhesion to the bone matrix and induced proliferation at an early stage.. It is well established that stromal TGF-β signaling is important for prostate tissue development as well as prostate cancer initiation and progression (9, 26-29). TGF-β is abundant in the bone matrix, and that the release of TGF-β from the matrix is a critical component for the "vicious cycle" of osteoclastic bone metastasis (12). Inhibition of TGF-β with small-molecule inhibitors or neutralizing antibodies has previously been shown to decrease osteolytic bone lesion ...
Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions ...