Subjects -> MEDICAL SCIENCES (Total: 8810 journals)
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INTERNAL MEDICINE (180 journals)                     

Showing 1 - 180 of 180 Journals sorted alphabetically
Abdomen     Open Access  
ACP Hospitalist     Full-text available via subscription   (Followers: 9)
ACP Internist     Full-text available via subscription   (Followers: 10)
ACP Journal Club     Full-text available via subscription   (Followers: 11)
Acta Clinica Belgica     Hybrid Journal   (Followers: 1)
Acute and Critical Care     Open Access   (Followers: 11)
Acute Medicine     Full-text available via subscription   (Followers: 9)
Advances in Hepatology     Open Access   (Followers: 4)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
African Journal of Primary Health Care & Family Medicine     Open Access   (Followers: 6)
African Journal of Thoracic and Critical Care Medicine     Open Access  
American Family Physician     Full-text available via subscription   (Followers: 38)
American Journal of Hypertension     Hybrid Journal   (Followers: 31)
Anales de Medicina Interna     Open Access   (Followers: 1)
Anatomy & Physiology : Current Research     Open Access   (Followers: 9)
Angiology     Hybrid Journal   (Followers: 5)
Annals of Colorectal Research     Open Access   (Followers: 1)
Annals of Internal Medicine     Full-text available via subscription   (Followers: 392)
AORN Journal     Hybrid Journal   (Followers: 27)
Apollo Medicine     Open Access  
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archivos de Medicina Interna     Open Access   (Followers: 1)
Asia Oceania Journal of Nuclear Medicine & Biology     Open Access   (Followers: 4)
Asian Pacific Journal of Tropical Disease     Full-text available via subscription   (Followers: 3)
Australasian Physical & Engineering Sciences in Medicine     Hybrid Journal   (Followers: 1)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access   (Followers: 1)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 35)
BMJ Quality & Safety     Hybrid Journal   (Followers: 69)
Bone & Joint Journal     Hybrid Journal   (Followers: 138)
Brain Communications     Open Access   (Followers: 4)
Brain Science Advances     Open Access  
Canadian Journal of General Internal Medicine     Open Access   (Followers: 2)
Cardiovascular Medicine in General Practice     Full-text available via subscription   (Followers: 7)
Case Reports in Internal Medicine     Open Access   (Followers: 1)
Cell Death & Disease     Open Access   (Followers: 3)
Cellular and Molecular Gastroenterology and Hepatology     Open Access   (Followers: 3)
Cephalalgia     Hybrid Journal   (Followers: 8)
Cephalalgia Reports     Open Access   (Followers: 4)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinical Ethics     Hybrid Journal   (Followers: 13)
Clinical Liver Disease     Open Access   (Followers: 5)
Clinical Nutrition     Hybrid Journal   (Followers: 98)
Clinical Thyroidology     Full-text available via subscription   (Followers: 1)
CNE Pflegemanagement     Hybrid Journal  
Communication Law and Policy     Hybrid Journal   (Followers: 5)
Current Diabetes Reports     Hybrid Journal   (Followers: 30)
Current Hepatology Reports     Hybrid Journal  
Current Research: Integrative Medicine     Open Access  
CVIR Endovascular     Open Access   (Followers: 1)
Der Internist     Hybrid Journal   (Followers: 12)
Diabetes     Full-text available via subscription   (Followers: 603)
Diabetes Care     Full-text available via subscription   (Followers: 578)
Diabetes Internacional     Open Access  
Diabetes Spectrum     Full-text available via subscription   (Followers: 17)
Diagnosis     Hybrid Journal   (Followers: 1)
Egyptian Journal of Bronchology     Open Access  
Egyptian Journal of Internal Medicine     Open Access   (Followers: 1)
Egyptian Journal of Neurosurgery     Open Access  
Egyptian Liver Journal     Open Access   (Followers: 2)
Egyptian Spine Journal     Open Access  
EMC - Aparato Locomotor     Hybrid Journal  
Endovascular Neuroradiology / Ендоваскулярна нейрорентгенохірургія     Open Access   (Followers: 1)
eNeuro     Open Access   (Followers: 3)
Ergonomics     Hybrid Journal   (Followers: 24)
European Journal of Inflammation     Open Access   (Followers: 2)
European Journal of Internal Medicine     Full-text available via subscription   (Followers: 10)
European Journal of Translational Myology     Open Access  
European Radiology Experimental     Open Access   (Followers: 2)
Head and Neck Tumors     Open Access   (Followers: 1)
Health Sociology Review     Hybrid Journal   (Followers: 14)
HemaSphere     Open Access   (Followers: 2)
Hepatology Communications     Open Access  
Hepatoma Research     Open Access   (Followers: 3)
Human Physiology     Hybrid Journal   (Followers: 5)
ImmunoHorizons     Open Access  
Immunological Medicine     Open Access  
Infectious Diseases: Research and Treatment     Open Access   (Followers: 5)
Inflammation and Regeneration     Open Access   (Followers: 2)
Inflammatory Intestinal Diseases     Open Access  
Innere Medizin up2date     Hybrid Journal   (Followers: 1)
Internal and Emergency Medicine     Hybrid Journal   (Followers: 5)
Internal Medicine Journal     Hybrid Journal   (Followers: 9)
International Journal of Abdominal Wall and Hernia Surgery     Open Access   (Followers: 1)
International Journal of Anatomy and Research     Open Access   (Followers: 2)
International Journal of Angiology     Hybrid Journal  
International Journal of Artificial Organs     Hybrid Journal   (Followers: 3)
International Journal of Hyperthermia     Open Access  
International Journal of Internal Medicine     Open Access   (Followers: 3)
International Journal of Noncommunicable Diseases     Open Access  
International Journal of Psychiatry in Clinical Practice     Hybrid Journal   (Followers: 6)
Iranian Journal of Neurosurgery     Open Access   (Followers: 1)
Italian Journal of Anatomy and Embryology     Open Access   (Followers: 1)
JAC-Antimicrobial Resistance     Open Access   (Followers: 4)
JAMA Internal Medicine     Full-text available via subscription   (Followers: 364)
JCSM Clinical Reports     Open Access   (Followers: 3)
JHEP Reports     Open Access  
JIMD Reports     Open Access  
JMV - Journal de Médecine Vasculaire     Hybrid Journal   (Followers: 1)
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 41)
JOP. Journal of the Pancreas     Open Access   (Followers: 2)
Journal of Basic & Clinical Physiology & Pharmacology     Hybrid Journal   (Followers: 1)
Journal of Bone Oncology     Open Access   (Followers: 1)
Journal of Cancer & Allied Specialties     Open Access  
Journal of Clinical and Experimental Hepatology     Full-text available via subscription   (Followers: 3)
Journal of Clinical Movement Disorders     Open Access   (Followers: 3)
Journal of Community Hospital Internal Medicine Perspectives     Open Access  
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Developmental Origins of Health and Disease     Hybrid Journal   (Followers: 2)
Journal of Endoluminal Endourology     Open Access  
Journal of Gastroenterology and Hepatology Research     Open Access   (Followers: 4)
Journal of General Internal Medicine     Hybrid Journal   (Followers: 23)
Journal of Hypertension     Hybrid Journal   (Followers: 14)
Journal of Infectious Diseases     Hybrid Journal   (Followers: 48)
Journal of Interdisciplinary Medicine     Open Access  
Journal of Internal Medicine     Hybrid Journal   (Followers: 11)
Journal of Liver : Disease & Transplantation     Hybrid Journal   (Followers: 7)
Journal of Medical Internet Research     Open Access   (Followers: 24)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Pain and Symptom Management     Hybrid Journal   (Followers: 46)
Journal of Pancreatic Cancer     Open Access  
Journal of Renal and Hepatic Disorders     Open Access  
Journal of Solid Tumors     Open Access   (Followers: 1)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of the American Board of Family Medicine     Open Access   (Followers: 11)
Journal of the European Mosquito Control Association     Open Access  
Journal of Translational Internal Medicine     Open Access  
Jurnal Vektor Penyakit     Open Access  
La Revue de Medecine Interne     Full-text available via subscription   (Followers: 3)
Lege artis - Das Magazin zur ärztlichen Weiterbildung     Hybrid Journal   (Followers: 1)
Liver Cancer International     Open Access  
Liver Research     Open Access  
Molecular Diagnosis & Therapy     Hybrid Journal   (Followers: 3)
Molecular Therapy - Oncolytics     Open Access  
Multiple Sclerosis and Demyelinating Disorders     Open Access   (Followers: 7)
MYOPAIN. A journal of myofascial pain and fibromyalgia     Hybrid Journal   (Followers: 18)
Neuro-Oncology Advances     Open Access   (Followers: 1)
Neurobiology of Pain     Open Access   (Followers: 2)
Neurointervention     Open Access   (Followers: 6)
Neuromuscular Diseases     Open Access  
Nigerian Journal of Gastroenterology and Hepatology     Full-text available via subscription  
OA Alcohol     Open Access   (Followers: 5)
Oncological Coloproctology     Open Access  
Open Journal of Internal Medicine     Open Access  
Pleura and Peritoneum     Open Access  
Pneumo News     Full-text available via subscription  
Polish Archives of Internal Medicine     Full-text available via subscription   (Followers: 2)
Preventing Chronic Disease     Free   (Followers: 2)
Progress in Transplantation     Hybrid Journal   (Followers: 1)
Prostate International     Open Access   (Followers: 2)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Pulmonary Therapy     Open Access   (Followers: 2)
Quality of Life Research     Hybrid Journal   (Followers: 20)
Research and Practice in Thrombosis and Haemostasis     Open Access  
Revista Chilena de Fonoaudiología     Open Access   (Followers: 1)
Revista de la Sociedad Peruana de Medicina Interna     Open Access   (Followers: 4)
Revista del Instituto de Medicina Tropical     Open Access  
Revista Hispanoamericana de Hernia     Open Access   (Followers: 1)
Revista Médica Internacional sobre el Síndrome de Down     Full-text available via subscription   (Followers: 1)
Revista Virtual de la Sociedad Paraguaya de Medicina Interna     Open Access   (Followers: 1)
Romanian Journal of Diabetes Nutrition and Metabolic Diseases     Open Access   (Followers: 1)
Romanian Journal of Internal Medicine     Open Access  
Russian Journal of Child Neurology     Open Access   (Followers: 1)
Scandinavian Journal of Primary Health Care     Open Access   (Followers: 8)
Schlaf     Hybrid Journal  
Schmerzmedizin     Hybrid Journal  
Scientific Journal of the Foot & Ankle     Open Access   (Followers: 1)
SciMedicine Journal     Open Access   (Followers: 3)
SEMERGEN - Medicina de Familia     Full-text available via subscription   (Followers: 1)
The Journal of Critical Care Medicine     Open Access   (Followers: 9)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 8)
Therapeutic Advances in Musculoskeletal Disease     Hybrid Journal   (Followers: 6)
Thieme Case Report     Hybrid Journal   (Followers: 1)
Tijdschrift voor Urologie     Hybrid Journal  
Tissue Barriers     Hybrid Journal   (Followers: 1)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 3)
Transgender Health     Open Access   (Followers: 3)
Trends in Anaesthesia and Critical Care     Full-text available via subscription   (Followers: 23)
US Cardiology Review     Open Access  
Vascular and Endovascular Review     Open Access   (Followers: 1)
Ожирение и метаболизм     Open Access  


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Journal of Bone Oncology
Journal Prestige (SJR): 0.941
Citation Impact (citeScore): 3
Number of Followers: 1  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2212-1366 - ISSN (Online) 2212-1374
Published by Elsevier Homepage  [3303 journals]
  • mTOR inhibitor and bone-targeted drugs break the vicious cycle between
           clear-cell renal carcinoma and osteoclasts in an in vitro co-culture model

    • Abstract: Publication date: June 2019Source: Journal of Bone Oncology, Volume 16Author(s): Chiara Spadazzi, Federica Recine, Laura Mercatali, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Alberto Bongiovanni, Valentina Fausti, Toni Ibrahim The skeleton is one of the most common sites of metastatic spread from advanced clear-cell renal carcinoma (ccRCC). Most of the bone lesions observed in RCC patients are classified as osteolytic, causing severe pain and morbidity due to pathological bone destruction. Nowadays, it is well known that cancer induced bone loss in lytic metastasis is caused by the triggering of a vicious cycle between cancer and bone resident cells that leads to an imbalance between bone formation and degradation. Targeting the mammalian target of rapamycin (mTOR) is an efficient treatment option for metastatic renal carcinoma patients. Moreover, bone targeted therapy could benefit bone metastatic cancer patients caused by advanced RCC. However, more data is needed to support the hypothesis of the beneficial effect of a combined therapy. The aim of this work is to investigate the effect of targeting mTOR and the sequential combination with bone targeted therapy as a strategy to break the vicious cycle between ccRCC cells and osteoclasts. A previously optimized fully human co-culture model is used to mimic the crosstalk between Caki-2 cells (ccRCC) and osteoclasts. Cells are treated at fixed timing with everolimus, zoledronic acid and denosumab as single or sequential combined treatment. We show that Caki-2 cells can induce osteoclast cells differentiation from isolated human monocytes, as demonstrated by specific tartrate-resistant acid phosphatase (TRAP) staining and f-actin ring formation, in a statistically significant manner. Moreover, differentiated osteoclasts proved to be functionally active by pit formation assay. Caki-2 cells co-cultured with osteoclasts acquire a more aggressive phenotype based on gene expression analysis. Interestingly, the sequential combined treatment of everolimus and zoledronic acid is the most effective in the inhibition of both Caki-2 cells survival and osteoclastogenic potential, making it an effective strategy to inhibit the vicious cycle of bone metastasis. At preclinical level, this observation confirms the value of our co-culture model as a useful tool to mimic the bone microenvironment and to assess drug sensitivity in vitro. A better understanding of the molecular mechanisms involved in tumor-bone cells crosstalk will be investigated next.
  • Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on
           bone metastasis management

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Stella D'Oronzo, Robert Coleman, Janet Brown, Francesco Silvestris Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival.A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials.Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies.The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.
  • Advances in immune checkpoint inhibitors for bone sarcoma therapy

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Pichaya Thanindratarn, Dylan C. Dean, Scott D. Nelson, Francis J. Hornicek, Zhenfeng Duan Bone sarcomas are a collection of sporadic malignancies of mesenchymal origin. The most common subtypes include osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. Despite the use of aggressive treatment protocols consisting of extensive surgical resection, chemotherapy, and radiotherapy, outcomes have not significantly improved over the past few decades for osteosarcoma or Ewing sarcoma patients. In addition, chondrosarcoma and chordoma are resistant to both chemotherapy and radiation therapy. There is, therefore, an urgent need to elucidate which novel new therapies may affect bone sarcomas. Emerging checkpoint inhibitors have generated considerable attention for their clinical success in a variety of human cancers, which has led to works assessing their potential in bone sarcoma management. Here, we review the recent advances of anti-PD-1/PD-L1 and anti-CTLA-4 blockade as well as other promising new immune checkpoint targets for their use in bone sarcoma therapy.
  • Compliance and patient reported toxicity from oral adjuvant
           bisphosphonates in patients with early breast cancer. A cross sectional

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): C. Wilson, C. Martin, M.C. Winter BackgroundAdjuvant bisphosphonates (BPs) are recommended as part of routine early breast cancer treatment for many postmenopausal (PM) women within the past year. There is a paucity of ‘real world’ data on compliance and patient satisfaction with oral BPs in this population. The aim of our study was to investigate patient reported compliance and toxicity of these drugs in a retrospective cohort study.Patients and methods413 patient were identified as receiving adjuvant oral BPs as part of their breast cancer treatment in the past 12 months from five NHS hospitals. The validated Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q) was sent to all suitable patients (n = 389).Results295 (76%) of patients responded. Average age was median (range) 67 (35–89). The majority of patients had T1 (52%), N0 (61%) grade 2 (58%) ER positive (87%), HER2 negative (84%) breast cancer and were PM at diagnosis of breast cancer (93%). All patients had been prescribed at least 1 month of oral ibandronate 50 mg daily. Review of items rated on the 7-point scale (1 = very dissatisfied to 7 = very satisfied), the mean item scores ranged from 5.0 (lowest) for time required to take oral BPs, to 6.1 (highest) for how easy it is to remember to take the medication.
  • Prediction of survival after surgical management of femoral metastatic
           bone disease – A comparison of prognostic models

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Charles Meares, Alexander Badran, David Dewar BackgroundOperative fixation for femoral metastatic bone disease is based on the principles of reducing pain and restoring function. Recent literature has proposed a number of prognostic models for appendicular metastatic bone disease. The aim of this study was to compare the accuracy of proposed soring systems in the setting of femoral metastatic bone disease in order to provide surgeons with information to determine the most appropriate scoring system in this setting.MethodsA retrospective cohort analysis of patients who underwent surgical management of femoral metastatic bone disease at a single institution were included. A pre-operative predicted survival for all 114 patients was retrospectively calculated utilising the revised Katagiri model, PathFx model, SSG score, Janssen nomogram, OPTModel and SPRING 13 nomogram. Univariate and multivariate Cox regression proportional hazard models were constructed to assess the role of prognostic variables in the patient group. Area under the receiver characteristics and Brier scores were calculated for each prognostic model from comparison of predicted survival and actual survival of patients to quantify the accuracy of each model.ResultsFor the femoral metastatic bone disease patients treated with surgical fixation, multivariate analysis demonstrated a number of pre-operative factors associated with survival in femoral metastatic bone disease, consistent with established literature. The OPTIModel demonstrated the highest accuracy at predicting 12-month (Area Under the Curve [AUC] = 0.79) and 24-month (AUC = 0.77) survival after surgical management. PathFx model was the most accurate at predicting 3-month survival (AUC = 0.70) and 6-month (AUC = 0.70) survival. The PathFx model was successfully externally validated in the femoral patient dataset for all time periods.ConclusionsAmong six prognostic models assessed in the setting of femoral metastatic bone disease, the present study observed the most accurate model for 3-month, 6-month, 12-month and 24-month survival. The results of this study may be utilised by the treating surgical team to determine the most accurate model for the required time period and therefore improve decision-making in the care of patients with femoral metastatic bone disease.
  • A nomogram to predict prognosis in Ewing sarcoma of bone

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Qiang Zhou, Zong-yi Wu, Zhong-qin Lin ObjectiveThis study was designed to develop a nomogram for assessing the survival of patients with Ewing sarcoma (ES).MethodsData from patients diagnosed with ES between 2004 and 2013 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Based on patient registration, the primary cohort was divided into a training set (n = 479, data from 17 cancer registries) and a validation set (n = 137, data from 1 cancer registry). Then, the prognostic effects of variables were analyzed using Kaplan–Meier method and Cox proportional hazard model. Moreover, nomograms were established for estimating 3- and 5-year overall survival (OS) and cancer-special survival (CSS) based on Cox regression model. Last, nomogram was validated by training set and validation set.ResultsAccording to the multivariate analysis of training set, nomogram which combined age, race, stage, tumor site, tumor size and chemotherapy was identified. The internal bootstrap resampling approach suggested the nomogram had sufficient discriminatory power with the C-index of OS: 0.754 (95% CI, 0.705–0.802) and CSS: 0.759 (95% CI, 0.700–0.800). The calibration plots also demonstrated good consistence between the prediction and the observation.ConclusionOur nomogram is a reliable and powerful tool for distinguishing and predicting the survival of ES patients, thus helping to better select medical examinations and optimize treatment options in collaboration with medical oncologists and surgeons.
  • Local control and vertebral compression fractures following stereotactic
           body radiotherapy for spine metastases

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Yurday Ozdemir, Nese Torun, Ozan Cem Guler, Berna Akkus Yildirim, Ali A. Besen, Aylin Gunesli Yetisken, H. Cem Onal, Erkan Topkan PurposeWe aimed to retrospectively assess the incidence of vertebral compression fractures (VCF), examine clinicopathologic factors potentially associated with VCF, and evaluate treatment response in patients who received stereotactic body radiotherapy (SBRT) for spine metastases (spMets).Methods and MaterialsWe identified 78 patients with 125 spMets at baseline and subsequent assessments. Patients received SBRT doses of 16 or 18 Gy. Patients with pre-existing VCF and co-existing local progression were excluded. Spine instability neoplastic score (SINS) was used for spMets categorization. Response to SBRT and VCF were assessed according to the Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) and Genant scores, respectively. Kaplan–Meier analyses were used to assess local control of disease and vertebral compression fracture-free survival (FFS).ResultsWe treated 103 cases with single spMets and 11 cases involving double spMets with SBRT. Progressive disease was reported in 3.2% and 8.2% of the cases in the first and last PET/CT reports, respectively. The distribution of treatment response in the remaining patients was: complete response in 30.6% of patients, partial response in 47.1% of patients, and stable disease in 22.3% of patients in the first PET/CT; complete response in 62.3% of patients, partial response in 16.7% of patients, and stable disease in 21% of patients at the last monitoring. Local failures were observed in 15 (12%) of cases. Median SINS was 5 (range: 1−13); majority of patients in our cohort (70.4%) were categorized as stable according to SINS, five (4%) patients had Grade 3 VCF at a median time of 16 months after SBRT (range: 2−22 months), and 60% of VCF occurred after an interval of at least 12 months after SBRT. No bisphosphonate usage was significantly associated with VCF (r = −0.204; p = 0.022). Median FFS was 21 months. Univariate analyses indicated that female gender (p 6 months of bisphosphonates use (p = 0.002), and the lowest vertebral body collapse score (p = 0.023) were associated with higher FFS. Female gender (p = 0.007),>6 months of bisphosphonates usage (p = 0.018), and the lowest vertebral body collapse score (p = 0.044) retained independent significance.ConclusionsThis study demonstrated that spine SBRT with doses of 16–18 Gy promises good local control of disease with acceptable VCF rates. Lowest vertebral body collapse score, female gender, and>6 months of bisphosphonate use were significantly associated with longer FFS.
  • Exploration of the chondrosarcoma metabolome; the mTOR pathway as an
           important pro-survival pathway

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Ruben D. Addie, Yvonne de Jong, Gaia Alberti, Alwine B. Kruisselbrink, Ivo Que, Hans Baelde, Judith V.M.G. Bovée BackgroundChondrosarcomas are malignant cartilage-producing tumors showing mutations and changes in gene expression in metabolism related genes. In this study, we aimed to explore the metabolome and identify targetable metabolic vulnerabilities in chondrosarcoma.MethodsA custom-designed metabolic compound screen containing 39 compounds targeting different metabolic pathways was performed in chondrosarcoma cell lines JJ012, SW1353 and CH2879. Based on the anti-proliferative activity, six compounds were selected for validation using real-time metabolic profiling. Two selected compounds (rapamycin and sapanisertib) were further explored for their effect on viability, apoptosis and metabolic dependency, in normoxia and hypoxia. In vivo efficacy of sapanisertib was tested in a chondrosarcoma orthotopic xenograft mouse model.ResultsInhibitors of glutamine, glutathione, NAD synthesis and mTOR were effective in chondrosarcoma cells. Of the six compounds that were validated on the metabolic level, mTOR inhibitors rapamycin and sapanisertib showed the most consistent decrease in oxidative and glycolytic parameters. Chondrosarcoma cells were sensitive to mTORC1 inhibition using rapamycin. Inhibition of mTORC1 and mTORC2 using sapanisertib resulted in a dose-dependent decrease in viability in all chondrosarcoma cell lines. In addition, induction of apoptosis was observed in CH2879 after 24 h. Treatment of chondrosarcoma xenografts with sapanisertib slowed down tumor growth compared to control mice.ConclusionsmTOR inhibition leads to a reduction of oxidative and glycolytic metabolism and decreased proliferation in chondrosarcoma cell lines. Although further research is needed, these findings suggest that mTOR inhibition might be a potential therapeutic option for patients with chondrosarcoma.
  • Denosumab versus zoledronic acid in cases of surgically unsalvageable
           giant cell tumor of bone: A randomized clinical trial

    • Abstract: Publication date: April 2019Source: Journal of Bone Oncology, Volume 15Author(s): Shenglong Li, Peng Chen, Qiankun Yang BackgroundAlthough denosumab has been approved as an antiresorptive agent for giant cell tumor of bone, its efficacy has not been proven.ObjectivesTo compare the efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable giant cell tumor of bone.MethodsA total of 250 patients with surgically unsalvageable giant cell tumor of bone were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg per 4 weeks plus an additional 120 mg on days 8 and 15; n = 125) or intravenous zoledronic acid (ZA group; 4 mg per 4 weeks; n = 125) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals.ResultsDenosumab and zoledronic acid had similar tumor responses (p = 0.18) and clinical benefits (p = 0.476). Disease progression was observed in fewer patients in the DB group (1%) than ZA group (2%). Denosumab caused fatigue (p = 0.0004) and back pain (p 
  • Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical

    • Abstract: Publication date: Available online 19 March 2019Source: Journal of Bone OncologyAuthor(s): Alexandros Stamatopoulos, Theodosios Stamatopoulos, Zakareya Gamie, Eustathios Kenanidis, Ricardo Da Conceicao Ribeiro, Kenneth Samora Rankin, Craig Gerrand, Kenneth Dalgarno, Eleftherios Tsiridis Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cells selectively. Recently, Mesenchymal Stromal Cells (MSCs) have been the subject of significant research in orthopaedic clinical practice through their use in regenerative medicine. Further research has been directed at the use of MSCs for more personalized bone sarcoma treatments, taking advantage of their wide range of potential biological functions, which can be augmented by using tissue engineering approaches to promote healing of large defects. In this review, we explore the use of MSCs in bone sarcoma treatment, by analyzing MSCs and tumour cell interactions, transduction of MSCs to target sarcoma, and their clinical applications on humans concerning bone regeneration after bone sarcoma extraction.
  • Endoplasmic Reticulum Protein 29 (ERp29) as a Novel Prognostic Marker and
           Tumor Suppressor in Osteosarcoma

    • Abstract: Publication date: Available online 19 March 2019Source: Journal of Bone OncologyAuthor(s): Parunya Chaiyawat, Dumnoensun Pruksakorn, Prach Pipatwattana, Areerak Phanphaisarn, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Jongkolnee Settakorn Background: Diverse aberrancy in genetic background, protein profiling, and biological pathways have emerged as important factors hindering discovery of effective treatment of osteosarcoma. In a previous study, we used a proteomic approach to identify some osteosarcoma-related proteins by analysis of protein profiling in individual patients through primary cell culture. Endoplasmic reticulum protein 29 (ERp29) emerged as a protein of interest for further study since accumulating evidence suggests it has broad functions in tumorigenesis of different types of cancer. Importantly, until now no report on examination of the expression patterns of ERp29 in osteosarcoma has been published.Methods: In this study, an expression of ERp29 was examined in patient-derived osteosarcoma cells (7 cases) and normal bone graft-derived osteoblasts (7 cases) using western blotting. Expression profile of ERp29 in 94 osteosarcoma cases was investigated using immunohistochemically stained on formalin-fixed paraffin-embedded biopsied tissue. An association with clinicopathologic parameters and the patient survival was evaluated.Results: The results substantiate the outcome from the proteomic study in which ERp29 expression was significantly higher in primary osteosarcoma cells compared to osteoblastic cells. Immunohistochemical analysis found that expression of ERp29 was low in 79% of the cases (immunoreactive score (IRS)
  • Dovitinib dilactic acid reduces tumor growth and tumor-induced bone
           changes in an experimental breast cancer bone growth model

    • Abstract: Publication date: Available online 19 March 2019Source: Journal of Bone OncologyAuthor(s): Tiina E. Kähkönen, Johanna M. Tuomela, Tove J. Grönroos, Jussi M. Halleen, Kaisa K. Ivaska, Pirkko L. Härkönen Advanced breast cancer has a high incidence of bone metastases. In bone, breast cancer cells induce osteolytic or mixed bone lesions by inducing an imbalance in bone formation and resorption. Activated fibroblast growth factor receptors (FGFRs) are important in regulation of tumor growth and bone remodeling. In this study we used FGFR1 and FGFR2 gene amplifications containing human MFM223 breast cancer cells in an experimental xenograft model of breast cancer bone growth using intratibial inoculation technique. This model mimics bone metastases in breast cancer patients. The effects of an FGFR inhibitor, dovitinib dilactic acid (TKI258) on tumor growth and tumor-induced bone changes were evaluated. Cancer-induced bone lesions were smaller in dovitinib-treated mice as evaluated by X-ray imaging. Peripheral quantitative computed tomography imaging showed higher total and cortical bone mineral content and cortical bone mineral density in dovitinib-treated mice, suggesting better preserved bone mass. CatWalk gait analysis indicated that dovitinib-treated mice experienced less cancer-induced bone pain in the tumor-bearing leg. A trend towards decreased tumor growth and metabolic activity was observed in dovitinib-treated mice quantified by positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose at the endpoint. We conclude that dovitinib treatment decreased tumor burden, cancer-induced changes in bone, and bone pain. The results suggest that targeting FGFRs could be beneficial in breast cancer patients with bone metastases.
  • Bone tumours of the clavicle: histopathological, anatomical and
           epidermiological analysis of 113 cases

    • Abstract: Publication date: Available online 6 March 2019Source: Journal of Bone OncologyAuthor(s): Matthias H. Priemel, Norbert Stiel, Jozef Zustin, Andreas M. Luebke, Carsten Schlickewei, Alexander S. Spiro BackroundThis retrospective study aimed to determine the frequency of bone tumours of the clavicle and their histopathological, anatomical and epidermiological characteristics in a large case series.MethodsThe records of 327 lesions of the clavicle collected from 1976 to 2018 in our bone tumour registry and institute of pathology were reviewed. Following data were evaluated: age, gender, side, radiological assessment, tumour location within the clavicle, and histopathological findings.ResultsBone tumours were detected in 113 patients with a mean age of 40 years. The lateral third of the clavicle was most frequently involved. Analysis revealed 22 benign, 31 intermediate, and 60 malignant tumours. Eosinophilic granuloma was the most commonly found neoplasm, followed by bone metastases, Plasma cell myeloma, Ewing sarcoma, and Osteosarcoma. 53% of the tumours were malignant. Mean age was 51 years in the malignant tumour group and 28 years in patients with a benign/intermediate lesion (p < 0.001).ConclusionsBone tumours of the clavicle seem to have different histopathological and epidermiological characteristics than bone tumours at other sites. A high index of suspicion should be maintained when evaluating patients with clavicular lesions due to the high incidence of malignancy, especially in patients with increased age.
  • Long noncoding RNA UCA1 promotes osteosarcoma metastasis through
           CREB1-mediated epithelial-mesenchymal transition and activating
           PI3K/AKT/mTOR pathway

    • Abstract: Publication date: Available online 1 March 2019Source: Journal of Bone OncologyAuthor(s): Hangzhan Ma, Rujuan Su, Hongwei Feng, Yongliang Guo, Gengxun Su Increasing evidences have demonstrated that Long noncoding RNAs (lncRNAs) are key regulatory RNAs that participate in multiple biological processes. LncRNA urothelial carcinoma-associated 1 (UCA1) is a newly identified lncRNA and functions as a regulator of growth in several cancers. However, the biological function and molecular mechanism of UCA1 in the metastasis of osteosarcoma remain unclear. In this study, we firstly found UCA1 is upregulated in both osteosarcoma tissues and cell lines, and increased UCA1 is associated with higher tumor stage, larger tumor size and poorer prognosis. Then for the first time, we demonstrated that UCA1 promotes the invasion and metastasis of osteosarcoma both in vitro and in vivo. Further mechanistic investigation showed that UCA1 directly interactes with miR-582 and suppresses its expression. Moreover, UCA1 increases CREB1 expression by functioning as a ceRNA against miR-582, thus promoting the EMT process via CREB1-mediated PI3K/AKT/mTOR pathway and finally leading to osteosarcoma metastasis. These findings may extend the function of UCA1 in osteosarcoma progression and provide a promising therapeutic target for osteosarcoma treatment.
  • Bone transport using the Ilizarov method for osteosarcoma patients with
           tumor resection and neoadjuvant chemotherapy

    • Abstract: Publication date: Available online 12 February 2019Source: Journal of Bone OncologyAuthor(s): Wei Wang, Jing Yang, Yun Wang, Gang Han, Jin-Peng Jia, Meng Xu, Wen-Zhi Bi BackgroundStudies on the applications of bone transport using the Ilizarov method for osteosarcoma (OS) patients with surgical resection and neoadjuvant chemotherapy are rare.MethodsA retrospective analysis was conducted in 10 patients with limb OS receiving limb-salvage treatment by Ilizarov method from 2007 to 2012 in our hospital. The general information, treatment outcomes and follow-up data of the patients were collected.ResultsThe mean length of the transported fragment and the mean transport distance of the affected limb were both 14 cm. The mean time in the external fixator was 34.2±11.2 months (16-47 months) and the mean external fixation index (EFI) was 75 days/cm. The mean follow-up time was 68.6±26.6 months (37-103 months). Seven patients underwent additional operations to treat the postoperative complications, and the mean number of operation was 1.7 times. Only one patient underwent amputation due to tumor relapse and all patients survived without tumor. The limb-salvage rate was 90%. At the time of external fixator removal, the ASAMI-bone score was good in 66.7% of patients and the ASAMI-function score was fair in 66.7% of cases. The mean MSTS score was 18.6±3.2 (n=9). At 10 months after fixator removal, both the ASAMI-bone score and ASAMI-function score were both excellent in 80% and good in 20% cases, and the mean MSTS score was further improved to 27.2±1.11 (n=5).ConclusionBone transport using the Ilizarov method can achieve good therapeutic effectiveness in the limb-salvage treatment for OS patients with neoadjuvant chemotherapy as long as the complications can be timely recognized and well managed.
  • Allogenic γδ T cell and tumor cell fused vaccine for enhanced
           immunotherapeutic efficacy of osteosarcoma

    • Abstract: Publication date: Available online 26 December 2018Source: Journal of Bone OncologyAuthor(s): Yitian Wang, Jian Zhu, Wei Yu, Junjie Wang, Kaishun Xia, Chengzhen Liang, Huimin Tao Human γδ T cells have displayed the promising roles in cancer immunity through cytokine secretion and cytotoxic activity. Researches have implicated their principal characteristics as the antigen presentation cells. How to improve γδ T cells' immunotherapeutic effect as the cell vaccine is still a great challenge. Herein, we explore the human γδ T cell and tumor cell fused vaccine for enhanced immunotherapeutic efficacy of osteosarcoma. The fusion cell vaccine was prepared by chemical fusion between human γδ T cells and inactive osteosarcoma Saos-2 cells. The fusion process was confirmed by microcopy observation, and flow cytometry analysis further validated the antigen presenting functions of the fusion cells. Moreover, the immunotherapeutic potential of the fusion cells was then verified via cytotoxicity assay and cytokine release detection. Our study provided novel immunotherapeutic strategy for patients with osteosarcoma, which merits further practice in the near future.
  • Specific inhibition of PI3Kδ/γ enhances the efficacy of anti-PD1 against
           osteosarcoma cancer

    • Abstract: Publication date: Available online 7 November 2018Source: Journal of Bone OncologyAuthor(s): Xinge Shi, Xiqing Li, Hongqiang Wang, Zhenghong Yu, Yu Zhu, Yanzheng GaoABSTRACTImpressive responses have been observed in patients with cancer treated with checkpoint inhibitory anti-programmed cell death-1 (PD-1) or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies through disinhibiting the immune system. However, tumors possess complex immunosuppressive tumor microenvironment to present therapeutic obstacles and the response rates to immune checkpoint inhibition remain low. One significant barrier to the efficacy of anti-PD1 treatment is the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor. MDSCs dramatically increased in peripheral blood of patients with osteosarcoma and prohibited both T-cell activation and infiltration. Here we demonstrated functional inhibition of G-MDSCs with (S)-(-)-N-[2-(3-Hydroxy-1H-indol-3-yl)-methyl]-acetamide (SNA), a specific inhibitor of PI3Kδ/γ, could prime tumor microenvironment, resultantly enhancing the therapeutic efficacy of anti-PD1 treatment in a syngeneic osteosarcoma tumor model. Combining SNA with anti-PD1 dramatically slowed osteosarcoma tumor growth and prolonged survival time of tumor-bearing mice, at least in part mediated through CD8+ T cells. Our results demonstrated that addition of SNA to anti-PD1 significantly altered infiltration and function of innate immune cells, providing the rationale for combination therapy in patients with osteosarcoma through inhibiting the function of MDSCs with a selective PI3Kδ/γ inhibitor to enhance responses to immune checkpoint blockade.
  • The association between adherence with oral bisphosphonates and the risk
           of breast cancer in post-menopausal women

    • Abstract: Publication date: Available online 6 November 2018Source: Journal of Bone OncologyAuthor(s): Vanessa Rouach, Inbal Goldshtein, Assaf Buch, Raphael Catane, Gabriel Chodick, Naftali Stern, Varda Shalev, Daniel Cohen BackgroundSeveral observational studies have suggested a protective effect of oral bisphosphonates (BP) on the risk of breast cancer, but no such association has been seen in randomized control trials. The role of oral BP in breast cancer prevention remains unclear.AimTo investigate the association between different levels of BP exposure and breast cancer incidence in a cohort of osteoporotic post-menopausal women.Subjects and methodsThis historical prospective study was conducted using the computerized databases of Maccabi Healthcare Services (MHS) in Israel. Included in the study were osteopenic and osteoporotic women aged 55–75 years who started BP therapy between 1998 and 2012. The subjects were enrolled in MHS for at least 3 years before therapy initiation, and had a minimum follow-up of 5 years in MHS. Women with a previous cancer, and women treated with selective estrogen receptor modulators (SERMs) were excluded. BP exposure was expressed in quintiles of proportion of days covered (PDC) with BP during follow-up period and cancer incidence was ascertained by the Israel National Tumor Registry. Person-years of follow-up began on January 1st, 1998 and ended at the date of cancer diagnosis, death, or December 31st, 2012, whichever occurred first.ResultsA total of 11,717 patients (mean age = 66.87 ± 4.38) were eligible for the analysis. During a total of 130,252 person-years of follow-up, (mean 7.2 years) 173 incident cases of breast cancer were diagnosed. Compared to women with a PDC with BP of 20% or lower, the adjusted hazard ratio for breast cancer were HR = 0.81 (95%CI: 0.48–1.39), HR = 0.82 (95%CI: 0.50–1.33), HR = 0.72 (95%CI:0.45–1.15) and HR = 1.14 (95%CI:0.76–1.70) among women with 20–40%, 40–60%, 60%–80%, and 80% or higher, PDC, respectively.ConclusionIn this study, we did not find a significant association between oral BP therapy for osteoporosis and the risk of breast cancer in postmenopausal women. The discrepancy between our results and the reports of such an association in observational studies might originate from an indication bias.
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