Search

Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 % to circa 70 %. Different types of development of new antineoplastic agents are critical to achieve irreversible damage to cancer cells, while preserving the integrity of their healthy counterparts. In the present study, complexes with two and three Pd(II) centres linked by the biogenic polyamines: spermine (Pd 2 SpmCl 4 ) and spermidine (Pd 3 Spd 2 Cl 6 ) were tested against non-malignant (osteoblasts, HOb) and cancer (osteosarcoma, MG-63) human cell lines. Either alone or in combination according to the EURAMOS-1 protocol, they were used versus cisplatin as a drug reference. By evaluating the cytotoxic effects of both therapeutic approaches (single and drug combination) in HOb and MG-63 cell lines, the selective anti-tumoral potential is assessed. To understand the different treatments at a molecular level, Synchrotron Radiation Fourier Transform Infrared and Raman microspectroscopies were applied. Principal component analysis and hierarchical cluster analysis are applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug-to-cell impact. The main changes were observed for the B-DNA native conformation to either Z-DNA (higher in the presence of polynuclear complexes) or A-DNA (preferably after cisplatin exposure). Additionally, a higher effect upon variation in proteins content was detected in drug combination when compared to single drug administration proving the efficacy of the EURAMOS-1 protocol with the new drugs tested., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Osteosarcoma is the most common primary malignant bone tumor affecting the pediatric population with a high potential to metastasize. However, insights into the molecular features enabling its metastatic potential are limited. We mapped the active chromatin landscapes of osteosarcoma tumors by integrating histone H3 lysine-acetylated chromatin state (n = 13), chromatin accessibility profiles (n = 11), and gene expression (n = 13) to understand the differences in their active chromatin profiles and their impact on molecular mechanisms driving the malignant phenotypes. Primary osteosarcoma tumors from patients with metastasis (primary met) have a distinct active chromatin landscape compared with those without metastasis (localized). This difference shapes the transcriptional profile of osteosarcoma. We identified novel candidate genes, including PPP1R1B, PREX1, and IGF2BP1, that exhibit increased chromatin activity in primary met. Loss of PREX1 in primary met osteosarcoma cells significantly diminishes osteosarcoma proliferation, invasion, migration, and colony formation capacity. Differential chromatin activity in primary met is associated with genes regulating cytoskeleton organization, cellular adhesion, and extracellular matrix, suggesting their role in facilitating osteosarcoma metastasis. Chromatin profiling of tumors from metastatic lung lesions shows increased chromatin activity in genes involved in cell migration and Wnt pathway. These data demonstrate that metastatic potential is intrinsically present in primary met tumors, with cellular chromatin profiles further adapting for successful dissemination, migration, and colonization at the distal site. Implications: Our study demonstrates that metastatic potential is intrinsic to primary metastatic osteosarcoma tumors, with chromatin profiles further adapting for successful dissemination, migration, and colonization at the distal metastatic site., (©2024 American Association for Cancer Research.)

Chemoresistance is one of the major causes of poor prognosis in osteosarcoma. Alternative therapeutic strategies for osteosarcoma are limited, indicating that increasing sensitivity to currently used chemotherapies could be an effective approach to improve patient outcomes. Using a kinome-wide CRISPR screen, we identified PRKDC as a critical determinant of doxorubicin (DOX) sensitivity in osteosarcoma. The analysis of clinical samples demonstrated that PRKDC was hyperactivated in osteosarcoma, and functional experiments showed that the loss of PRKDC significantly increased sensitivity of osteosarcoma to DOX. Mechanistically, PRKDC recruited and bound GDE2 to enhance the stability of protein GNAS. The elevated GNAS protein levels subsequently activated AKT phosphorylation and conferred resistance to DOX. The PRKDC inhibitor AZD7648 and DOX synergized and strongly suppressed the growth of osteosarcoma in mouse xenograft models and human organoids. In conclusion, the PRKDC-GDE2-GNAS-AKT regulatory axis suppresses DOX sensitivity and comprises targetable candidates for improving the efficacy of chemotherapy in osteosarcoma. Significance: Targeting PRKDC suppresses AKT activation and increases sensitivity to doxorubicin in osteosarcoma, which provides a therapeutic strategy for overcoming chemoresistance., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background/aim: Benign and tumor-like lesions of the hindfoot and ankle are common, whereas malignant entities are rare. Accurate evaluation and timely management of these lesions can be challenging, making it crucial to understand their incidence and anatomic localization. This study retrospectively analyzed the distribution of benign and malignant bone and soft tissue tumors in the hindfoot and ankle., Patients and Methods: This study included patient data from a single center, such as age, sex, histologic diagnosis, and anatomic location over a 12.5 year period., Results: Of the 105 cases reviewed, 19 cases (18.1%) were osseous lesions and 86 cases (81.9%) were soft tissue lesions. The latter were divided into 77 benign and 9 malignant cases, resulting in an overall malignancy rate of 8.6%. The most common osseous lesion was the intraosseous ganglion (n=12). The majority of benign soft tissue lesions (75.3%) were located in the hindfoot, with TGCT, schwannoma, and ganglion cysts being the most common types. The nine malignant cases were distributed among seven entities and were evenly distributed among both regions and sexes. Malignant cases had a higher mean age (59.2 years) compared to benign cases (40.8 years; p=0.001)., Conclusion: Tumors, tumor-like lesions, and pseudotumors represent an important aspect of ankle pathology. The majority of focal masses and swellings are benign soft tissue or osseous lesions, but malignant entities can occur and may be mistaken for benign conditions. Preoperative imaging and histopathologic examination are essential, and preoperative presentation to a multidisciplinary tumor board is recommended in unclear cases., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

To investigate the potential of blue light photobiomodulation (PBM) in inducing ferroptosis, a novel form of regulated cell death, in OS cells, considering its known effectiveness in various cancer models. In this investigation, we exposed human OS cell lines, HOS and MG63, to different wavelengths (420, 460 and 480 nm) of blue light at varying irradiances, and examined cellular responses such as viability, apoptosis, levels of reactive oxygen species (ROS), and mitochondrial membrane potential (MMP). Transcriptome sequencing was employed to unravel the molecular mechanisms underlying blue light-induced effects, with validation via quantitative real-time PCR (qRT-PCR). Our findings revealed a wavelength- and time-dependent decrease in cell viability, accompanied by increased apoptosis and oxidative stress. Transcriptomic analysis identified differential expression of genes associated with ferroptosis, oxidative stress, and iron metabolism, further validated by qRT-PCR. These results implicated ferroptosis as a significant mechanism in the blue light-induced death of OS cells, potentially mediated by ROS generation and disruption of iron homeostasis. Also, An incomplete stress response was observed in MG63 cells induced by blue light exposure. Hence, blue light PBM holds promise as a therapeutic approach in OS clinical investigations; however, additional exploration of its underlying mechanisms remains imperative., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pharmacological vitamin C (VC) has gained attention for its pro-oxidant characteristics and selective ability to induce cancer cell death. However, defining its role in cancer has been challenging due to its complex redox properties. In this study, using a human osteosarcoma (OS) model, we show that the redox-active property of VC is critical for inducing non-apoptotic cancer cell death via intracellular reactive oxygen species (ROS)-iron-calcium crosstalk and mitochondrial dysfunction. In both 2D and 3D OS cell culture models, only the oxidizable form of VC demonstrated potent dose-dependent cytotoxicity, while non-oxidizable and oxidized VC derivatives had minimal effects. Live-cell imaging showed that only oxidizable VC caused a surge in cytotoxic ROS, dependent on iron rather than copper. Inhibitors of ferroptosis, a form of iron-dependent cell death, along with classical apoptosis inhibitors, were unable to completely counteract the cytotoxic effects induced by VC. Further pharmacological and genetic inhibition analyses showed that VC triggers calcium release through inositol 1,4,5-trisphosphate receptors (IP3Rs), leading to mitochondrial ROS production and eventual cell death. RNA sequencing revealed down-regulation of genes involved in the mitochondrial electron transport chain and oxidative phosphorylation upon pharmacological VC treatment. Consistently, high-dose VC reduced mitochondrial membrane potential, oxidative phosphorylation, and ATP levels, with ATP reconstitution rescuing VC-induced cytotoxicity. In vivo OS xenograft studies demonstrated reduced tumor growth with high-dose VC administration, concomitant with the altered expression of mitochondrial ATP synthase (MT-ATP). These findings emphasize VC's potential clinical utility in osteosarcoma treatment by inducing mitochondrial metabolic dysfunction through a vicious intracellular ROS-iron-calcium cycle., Competing Interests: Declaration of competing interest Authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Osteosarcoma (OS) has a high propensity for lung metastasis, which is the leading cause of OS-related death and treatment failure. Intercellular communication between OS cells and distant lung host cells is required for the successful lung metastasis of OS cells to the lung. Before OS cells infiltrate the lung, in situ OS cells secrete extracellular vesicles (EVs) that act as mediators of cell-to-cell communication. In recent years, EVs have been confirmed to act as bridges and key drivers between in situ tumors and metastatic lesions by regulating the formation of a pre-metastatic niche (PMN), defined as a microenvironment suitable for disseminated tumor cell engraftment and colonization, in distant target organs. This review summarizes the current knowledge about the underlying mechanisms of PMN formation induced by OS-derived EVs and the potential roles of EVs as targets or drug carriers in regulating PMN formation in the lung. We also provide an overview of their potential EV-based therapeutic strategies for hindering PMN formation in the context of OS lung metastasis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Metallocompounds are a class of anticancer compounds largely used in the treatment of several types of solid tumors, including bone cancer. Osteosarcoma (OS) is a primary malignant bone tumor that frequently affects children, adolescents and young adults. It is a very invasive type of tumor, so ∼40% of patients develop distant metastases, showing elevated mortality rates. In this review, we present an outline of the chemistry and antitumor properties of metal-based compounds in preclinical (in vitro and in vivo) and clinical OS models, focusing on the relationship between structure-activity, molecular targets and the study of the mechanism of action involved in metallocompound anticancer activity., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rationale: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up., Patients and Methods: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m 2 and CDDP 100 mg/m 2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives., Results: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months., Conclusion: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB., Methods: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups., Results: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001)., Conclusion: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background and Objectives: Curettage is the removal of a tumor from the bone while preserving the surrounding healthy cortical bone, and is associated with higher rates of local recurrence. To lower these rates, curettage should be combined with local adjuvants, although their use is associated with damage to nearby healthy bone., Objective: The purpose of this analysis is to determine the effect of local adjuvants on cortical porcine bone by using micro-computed tomography (micro-CT) along with histological and mechanical examination., Methods: Local adjuvants were applied to porcine specimens under defined conditions. To assess changes in bone mineral density (BMD), a micro-CT scan was used. The pixel gray values of the volume of interest (VOI) were evaluated per specimen and converted to BMD values. The Vickers hardness test was employed to assess bone hardness (HV). The depth of necrosis was measured histologically using hematoxylin and eosin-stained tissue sections., Results: A noticeable change in BMD was observed on the argon beam coagulation (ABC) sample. Comparable hardness values were measured on samples following electrocautery and ABC, and lowering of bone hardness was obtained in the case of liquid nitrogen. Extensive induced depth of necrosis was registered in the specimen treated with liquid nitrogen., Conclusion: This study determined the effect of local adjuvants on cortical bone by using micro-CT along with histological and mechanical examination. Phenolization and liquid nitrogen application caused a decrease in bone hardness. The bone density was affected in the range of single-digit percentage values. Liquid nitrogen induced extensive depth of necrosis with a wide variance of values., (© 2024. The Author(s).)

Background: Osteochondromas are benign osseous lesions often excised for pain, growth abnormalities, and aesthetic concerns. While characteristic clinical and radiographic features leave little diagnostic ambiguity in most cases of osteochondroma, pathologic analysis to confirm the diagnosis and screen for malignancy is routinely performed following surgical excision. The purpose of this study was to determine the clinical and economic value of routine pathologic analysis after osteochondroma excision in a pediatric population., Methods: A retrospective review of clinical records from 2 pediatric orthopaedic hospitals (St. Louis Children's Hospital and Shriner's Hospital for Children, St. Louis) identified 426 osteochondroma lesions surgically resected from 201 patients. Patients with solitary and multiple lesions were included. Clinical, radiographic, and surgical data were recorded for each resection surgery. Pathologic reports were evaluated. Costs incurred for routine pathologic assessment was also noted., Results: Totally, 132 patients were treated with surgical resection of a solitary osteochondroma lesion, while an additional 291 lesions were resected from 69 patients with multiple lesions. Average age at the time of surgical resection was 13.0 years (2.1 to 17.9). The most common anatomic locations of excised lesions included the distal femur (110, 25.8%), proximal tibia/fibula (95, 22.3%), and distal radius/ulna (58, 13.6%). All resected specimens were sent for pathologic analysis. The average size of the resected lesions was 19.9 mm 3 (0.02 to 385.0 mm 3 ). In all cases, the histologic diagnosis confirmed benign osteochondroma. The total charges of pathologic analysis including processing and interpretation fees was ∼$755.00 for each lesion assessed, for a total cohort charge of $321,630., Conclusion: We propose that in most cases of pediatric osteochondroma excision procedures, postoperative histologic analysis is not strictly indicated as it rarely, if ever, alters diagnosis or management. We suggest using a "gross only" analysis in these cases. However, we do believe that with preoperative diagnostic ambiguity, or if patients present with concerning features such as rapidly expansile lesions or cortical destruction, have axial skeleton or pelvic involvement, or enlarged cartilaginous caps, full histologic evaluation of the excised lesions will continue to be prudent., Level of Evidence: Level IV-case series., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations., (© 2024 Wiley‐VCH GmbH.)

Background: No previous reports have characterized national bone sarcoma profiles overall. We examined the nationwide statistics for bone sarcoma in Japan using data from the National Cancer Registry (NCR), a population-based cancer registry., Methods: We identified 3,755 patients with bone sarcomas entered in the NCR during 2016-2019 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient., Results: Bone sarcoma showed a slight male preponderance. The age distribution peaked at ages 10-20 and 60-80; approximately 44% of patients were aged over 60 years. Chordoma, chondrosarcoma, and malignant fibrous histiocytoma of bone peaked in the elderly, and Ewing's sarcoma peaked in children. Osteosarcoma had two peaks in Japan as well as in Western countries. The most frequent tumor locations were the limb (45%) and the pelvis (21%). Extent of disease was categorized as: "localized" (39%), "regional" (27%), and "distant" (11%). We found significant associations between overall survival and age, tumor location, facility type, hospital volume, histologic subtype, reason for diagnosis, and extent of disease. The latter had the poorest survival., Conclusions: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of bone sarcoma in Japan using the NCR. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences., Level of Evidence: Prognostic studies, Level III., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: To evaluate diagnostic yield and accuracy of image-guided core needle biopsy (ICNB) of suspected malignant osseous lesions in a large cohort of adults, evaluate what factors influence these measures, and offer technical recommendations to optimize yield., Methods: A retrospective analysis of 2321 ICNBs performed from 2010 to 2021 was completed. The diagnostic yield and accuracy of the biopsies as well as a series of patient, lesion-related, and technical factors were retrospectively analyzed. Multivariate statistical analysis was performed to evaluate what factors were associated with yield and accuracy. Different cutoff values of total core length and core number were then tested to determine threshold values in relation to increased diagnostic yield., Results: Diagnostic yield was 98.2% (2279/2321) and accuracy was 97.6% (120/123). Increased total core length (odds ratio [OR] = 2.34, 95% confidence interval [CI] (1.41-3.90), p = 0.001), core number (OR = 1.51, 95% CI (1.06-2.16), p = 0.02) and presence of primary malignancy (OR = 2.81, 95% CI (1.40-5.62), p = 0.004) were associated with improved yield. Lesion location in an extremity (OR = 0.27, 95% CI (0.11-0.68), p = 0.006) and using fluoroscopic imaging guidance (OR = 0.33, 95% CI (0.12-0.90), p = 0.03) were associated with lower yield. Cutoff thresholds in relation to increased diagnostic yield were found to be 20 mm total core length (marginal OR = 4.16, 95% CI = (2.09-9.03), p < 0.001), and three total cores obtained (marginal OR = 2.78, 95% CI (1.34-6.54), p = 0.005). None of the analyzed factors influenced diagnostic accuracy., Conclusions: ICNB has a high rate of diagnostic yield and accuracy. Several factors influence diagnostic yield; 20 mm core length and three total cores optimize yield., Clinical Relevance Statement: Image-guided core needle biopsy of suspected malignant osseous lesions is a safe procedure with a very high rate of diagnostic yield and accuracy. Obtaining 20 mm total core length and three total cores optimizes diagnostic yield., Key Points: • In a retrospective cohort study, image-guided core needle biopsy of suspected osseous malignant lesions in adults was found to have very high rates of diagnostic yield and accuracy. • Increased total core length and core number of biopsies were each associated with increased diagnostic yield, and these relationships reached thresholds at 20 mm total core length and three total cores obtained. • The presence of a known primary malignancy was also associated with increased yield while using fluoroscopic imaging guidance and lesion location in an extremity were associated with decreased yield., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Intra-osseous hemangiomas are uncommon tumors that can present diagnostic and treatment dilemmas. Bone hemangiomas with papillary and glomeruloid growth patterns are exceptionally rare. We present an example of an intra-osseous hemangioma of the rib displaying aggressive features on both radiology and histology. Morphologically, prominent papillary and glomeruloid architectural patterns were observed, in addition to features of cavernous and capillary hemangiomas. Extensive extra-osseous soft tissue involvement was seen. Awareness of the diverse histological features and locally aggressive behavior of bone hemangiomas is important in avoiding over-interpretation as a malignant lesion., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ewing sarcoma is a malignant round-cell tumor that primarily affects bones in children. It can also arise in extraosseous tissues, such as the lung, kidneys, and liver. The presentation symptoms of Ewing sarcoma may include cough, dyspnea, and chest pain., Case Presentation: This report details the history of a 15-year-old Syrian boy with a previous diagnosis of Hodgkin lymphoma who presented with chronic shoulder pain. Imaging studies revealed an 80 mm mass in the apex of the left lung, which was confirmed through histopathological examination to be Ewing sarcoma following a computed-tomography-guided biopsy. The patient received multiple cycles of chemotherapy and subsequently underwent surgical resection of the remaining mass., Conclusions: This case highlights the rare occurrence of Ewing sarcoma in the lung and the unusual clinical presentation of shoulder pain without other accompanying symptoms., (© 2024. The Author(s).)

Purpose: Osteosarcoma (OS) is a primary bone tumor with high malignancy and poor prognosis. Ferroptosis plays a crucial role in OS. This study aimed to evaluate the effects of Ankyrin 1 (ANK1) on OS and to investigate its specific mechanisms., Methods: Microarray datasets related to "osteosarcoma" were selected for this study. Relevant hub genes in OS were identified through bioinformatics analysis. Transfected U-2OS and MG-63 cells were used for in vitro experiments. The effects of ANK1 overexpression on cell viability, migration, and invasion were determined through CCK-8, wound healing, and transwell assays. An OS mouse model was established for the in vivo experiments. Hematoxylin-eosin staining and immunohistochemistry were conducted to observe the histological effects of ANK1 overexpression on mouse tumors. TUNEL staining was performed to evaluate apoptosis in mouse., Results: There were 159 common differentially expressed genes in the GSE16088 and GSE19276 datasets. The hub genes ANK1, AHSP, GYPB, GYPA, KEL, and ALAS2 were identified. Pan-cancer analysis verified that ANK1 was closely associated with cancer prognosis and immune infiltration. Furthermore, ANK1 overexpression inhibited the proliferation, migration, and invasion of OS cells and promoted ferroptosis, while ferroptosis inhibitor (fer-1) weakened these effects. Moreover, ANK1 overexpression suppressed tumor growth, promoted apoptosis, reduced the number of Ki67 positive cells, and elevated the number of caspase-3 positive cells in vivo., Conclusions: ANK1 is a prognosis biomarker of OS that can alleviate the progression of OS by promoting ferroptosis., (© 2024. The Author(s).)

Aims/Background Generally, pelvic osteosarcoma has a worse prognosis compared with limb osteosarcoma. This study aims to create and validate a new nomogram for predicting the prognosis of pelvic osteosarcoma. Methods Clinical data of 62 patients derived from the Surveillance, Epidemiology, and End Results (SEER) database and 31 Chinese patients diagnosed with pelvic osteosarcoma were gathered. Kaplan-Meier survival analysis was utilized to calculate the median survival time for all variables. Univariate and multivariate Cox regression models were employed to identify the prognostic factors of pelvic osteosarcoma. A nomogram was constructed using data gleaned from the SEER cohort and verified using the receiver operating characteristic (ROC) curve and calibration plot in the Chinese cohort. Results Kaplan-Meier analysis revealed that individuals of other races (Asians) (hazard ratio (HR) = 0.24, 95% confidence interval (CI): 0.1-0.57, p = 0.001), aged ≤51 years old (HR = 0.4, 95% CI: 0.22-0.73, p = 0.003), and with tumor size ≤160 mm (HR = 0.37, 95% CI: 0.2-0.71, p = 0.03) had better survival outcomes. Conversely, factors such as no primary surgery (HR = 3.6, 95% CI: 1.81-7.15, p < 0.001), lung metastasis (HR = 1.96, 95% CI: 1.17-3.28, p = 0.010), and radiotherapy (HR = 1.89, 95% CI: 1.10-3.25, p = 0.021) were associated with poorer survival. Multivariate Cox analysis indicated that lung metastasis (HR = 2.57, 95% CI: 1.29-5.13, p = 0.008), other races (Asians) (HR = 0.23, 95% CI: 0.07-0.75, p = 0.015), tumor size (HR = 0.28, 95% CI: 0.13-0.62, p = 0.001) and age (HR = 0.3, 95% CI: 0.16-0.59, p < 0.001) were independent prognostic factors for pelvic osteosarcoma. Univariate and multivariate Cox regression models identified three independent variables in the training cohort: age, lung metastasis, and tumor size. A predictive nomogram was developed based on the data from the SEER cohort and validated in the Chinese cohort. The areas under the curves (AUCs) that are used to predict 1-year, 2-year, and 3-year survival rates were 0.81 (95% CI: 0.68-0.94), 0.75 (95% CI: 0.63-0.86), and 0.80 (95% CI: 0.70-0.89) in the training cohort, and 0.67 (95% CI: 0.30-1.04), 0.66 (95% CI: 0.43-0.90) and 0.71 (95% CI: 0.50-0.93) in the validation cohort. Conclusion The predictive nomogram constructed in this study facilitates accurate and effective prediction of the overall survival of patients with pelvic osteosarcoma and helps enhance the clinical decision-making process.

Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

For many cancer patients tumor burden negatively impacts quality of life due to associated pain onset. Neuropathic pain is commonly associated with late cancer stages, and is resultant of tumor metastasis to bone, herein referred to as cancer-induced bone pain. Given the severe impact on quality of life and clinical treatment strategies focusing on symptom management, novel therapeutics are needed to alleviate cancer-induced bone pain and/or reduce cancer burden. In the current study we characterized a commercially available murine fibrosarcoma cell line, NCTC-2472 in vitro, which can be used to assess the capacity of novel compounds to impact cellular viability. We found that dimethyl sulfoxide, a known cytotoxic agent and common drug preparation compound, significantly decreased cell viability in a dose-related manner. We then characterized the in vivo tumor development and associated pain behavior characteristics following implantation of NCTC-2472 fibrosarcoma into male and female C3H/HeJ mice. The C3H/HeJ strain was utilized as these mice are syngeneic with NCTC-2472 fibrosarcoma and their use reduces potential implantation failure. We found that tumor development in mice resulted in the development of mechanical allodynia but not thermal hyperalgesia. Gabapentin, a clinically relevant analgesic, produced dose-related mechanical allodynia reversal. These studies provide further characterization of a cancer-induced bone pain model that can be used to examine novel compounds as anti-cancer and analgesic therapeutics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ortiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The survival rates for children and adolescents with osteosarcoma in low-income countries are poor. Insufficient data regarding the challenges of managing osteosarcoma in resource-limited settings has been published. We evaluated the treatment of osteosarcoma in children and adolescents with the aim of improving the health system and management outcomes., Methods: We sourced data on children under 18 years treated for osteosarcoma at the Uganda Cancer Institute between January 2016 and December 2020. Descriptive statistics and Kaplan-Meier survival analysis were used., Results: Seventy-four osteosarcoma cases were identified, with a median age of 13 years (IQR 9.8-15). Referrals were made after a median of 28 days (range 1-147). Before appropriate referral, more than a quarter (26%) had undergone invasive procedures that could compromise tumour integrity and outcome. Half (50%) of the patients had metastatic disease at diagnosis, primarily to the lungs (n = 43; 92%). Only 14 (33%) patients received neoadjuvant chemotherapy. Forty-three (58.1%) patients underwent limb amputation surgery, including 25 localized tumours and 18 patients with distant metastatic disease. No metastatectomies were performed. Adjuvant chemotherapy was delayed for longer than 21 days in 26 (61%) patients. No pathology reports described the status of resection margins or the degree of chemotherapy-induced necrosis. Twenty-six (35%) patients abandoned treatment, mainly due to pending radical surgery (n = 18/26; 69%). Only 18% (n = 13) were still alive; 46% (n = 34) had died; and 37% (n = 27) had an unknown status. The median overall survival was 1.1 years, and was significantly negatively affected by disease metastasis, timing of adjuvant therapy, and treatment abandonment., Conclusions: Osteosarcoma outcomes for children and adolescents at the Uganda Cancer Institute are extremely poor. The quality of care can be improved by addressing delayed referrals, high rates of prior manipulative therapy, metastatic disease, treatment abandonment, surgical challenges, and delayed resumption of adjuvant chemotherapy., (© 2024. The Author(s).)

While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease., (© 2024. The Author(s).)

Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients., (© 2024. The Author(s).)

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds whole genome sequencing and reverse-phase protein array profiling data, which can be correlated with drug testing results. In addition, four additional osteosarcoma models are described for use in the research community., (© 2024. The Author(s).)

Macrophage-to-osteoclast differentiation (osteoclastogenesis) plays an essential role in tumor osteolytic bone metastasis (BM), while its specific mechanisms remain largely uncertain in lung adenocarcinoma BM. In this study, we demonstrate that integrin-binding sialoprotein (IBSP), which is highly expressed in the cancer cells from bone metastatic and primary lesions of patients with lung adenocarcinoma, can facilitate BM and directly promote macrophage-to-osteoclast differentiation independent of RANKL/M-CSF. In vivo results further suggest that osteolytic BM in lung cancer specifically relies on IBSP-induced macrophage-to-osteoclast differentiation. Mechanistically, IBSP regulates the Rac family small GTPase 1 (Rac1)-NFAT signaling pathway and mediates the forward shift of macrophage-to-osteoclast differentiation, thereby leading to early osteolysis. Moreover, inhibition of Rac1 by EHT-1864 or azathioprine in mice models can remarkably alleviate IBSP-induced BM of lung cancer. Overall, our study suggests that tumor-secreted IBSP promotes BM by inducing macrophage-to-osteoclast differentiation, with potential as an early diagnostic maker for BM, and Rac1 can be the therapeutic target for IBSP-promoted BM in lung cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The drug efflux transporter P-glycoprotein, encoded by the ABCB1 gene, promotes acquired chemoresistance. We explored the presence and clinical relevance of circulating cell-free ABCB1 transcripts (cfABCB1 tx ) in ovarian cancer patients (173 longitudinal serum samples from 79 cancer patients) using digital droplet PCR. cfABCB1 tx  were readily detectable at primary diagnosis (median 354 mRNA copies/20 µl serum), paralleled FIGO-stage and predicted surgical outcome (p = 0.023, p=0.022, respectively). Increased cfABCB1 tx levels at primary diagnosis indicated poor PFS (HR = 2.329, 95%CI:1.374-3.947, p = 0.0017) and OS (HR = 2.074, 95%CI:1.194-3.601, p = 0.0096). cfABCB1 tx induction under platinum-based chemotherapy was an independent predictor for poor OS (HR = 2.597, 95%CI: 1.218-5.538, p = 0.013) and paralelled a micrometastatic phenotype, shaped by the presence of disseminated tumor cells in the bone marrow. A strong correlation was observed between cfABCB1 tx and circulating transcripts of the metastasis-inducer MACC1, which is the transcriptional activator of ABCB1. Combined assessment of cfABCB1 tx and circulating cell-free MACC1 transcripts (cfMACC1 tx ) resulted in an improved prognostic prediction, with  the cfABCB1 tx -high/cfMACC1 tx -high phenotype bearing the highest risk for relapse and death. Conclusively, we provide proof of principle, that ABCB1 transcripts are readily traceable in the liquid-biopsy of ovarian cancer patients, advancing a new dimension for systemic monitoring of ABCB1/P-glycoprotein expression dynamics., (© 2024. The Author(s).)

We present a presumptive case of metastatic carcinoma in an individual from the 11 th /12 th century CE from Vaduz, Principality of Liechtenstein. The skeleton exhibits extensive new bone formation in the axial skeleton and the proximal humerus and femur. Radiological examinations revealed further sclerotic lesions in the clavicles, the manubrium, the sternum, the femoral diaphysis, and possibly the frontal. The pelvic bones and the sacrum, as well as the spine, are the most heavily affected skeletal regions. The newly formed bone in some lesions has a "sun-burst" appearance. The sex and age at death of the individual, the distribution and the osteoblastic nature of the lesions suggest that prostate carcinoma is the most likely primary tumor.

This study analyzed the paleopathological conditions of a 30-year-old male unearthed at the site of Ya'amun in northern Jordan. The skeleton was dated back to Iron age. The paleopathological examinations were performed using macroscopic and radiological analyses. The results revealed multiple significant bone lesions, including periosteal osteosarcoma of the right femur, plagiocephaly, asymmetry of the sacrum, vertebral fractures, anemia, and osteoarthritis. This case represents the first example of neoplasm and plagiocephaly in the Iron Age of the region. Despite enduring severe health conditions, the individual managed to reach the third decade while facing the demands of strenuous daily activities that exemplified the harsh living and subsistence conditions characteristic of the Iron Age.

Background/objective: Omics technology has become a widely applied biological science that can be used to study the etiology, pathogenesis, and treatment of osteosarcoma(OS). Bibliometric analysis is still blank in this field.This study aimed to access the trends and hotspots of omics in OS research through the bibliometric analysis method., Methods: Relevant articles and reviews from 1999 to 2023 were retrieved from the Web of Science Core Collection. The data were processed with CiteSpace, and some graphs were generated with Graphpad, VOSviewer, Scimago Graphica, Bibliometrix and R Studio., Results: A total of 1581 papers were included. China (569, 36.0%) and the United States (523, 33.1%) took the dominant position in the number of published papers, and the links between countries most frequently occurred between North America and East Asia, and between Australia and Europe. Top institutions with the highest number of publications were almost located in the United States, with The University of Texas MD Anderson Cancer Center contributing the most (44, 2.78%). Among the researchers in this field, Cleton-Jansen AM was the author with the highest number of articles in the field (20, 1.27%). According to the keyword cluster analysis, most studies focused on the "comparative genomic hybridization" before 2012. The latest surge words "tumor microenvironment" and "immune infiltration" in the keyword heatmap indicate future research directions., Conclusion: Our study provided the current status of the omics research in OS on a global level and the hottest directions. The field of omics in OS was developing rapidly, and the main focuses of research were revealing the characteristics of tumor microenvironment of OS and how to activate the immune system to fight cancer cells. Research on the immune microenvironment and its relationship with genetic aberrations of OS will be a priority in the future., (© 2024. The Author(s).)

Background: Telangiectatic osteosarcoma is rare and it rarely affects flat bones, especially the bones of the pelvis. It is uncommon for telangiectatic osteosarcoma to be considered as a differential diagnosis when assessing a large intrabdominal mass., Case Report: We present our case of a 33-year-old African female who presented with a sizeable telangiectatic osteosarcoma of the left iliac bone. She reported a 3-year duration of a painless, slow-growing mass arising from the left flank. At examination, a large bony hard mass extending from the left ilium to the umbilicus was noted, almost mimicking an intra-abdominal pregnancy. All laboratory tests were within normal limits and an unconventional surgical approach was used for a one-stage excision of the tumor without complications. The definitive histopathological diagnosis postexcision was that of a telangiectatic osteosarcoma only on the second review of the histological specimen., Conclusions: Pelvic telangiectatic osteosarcoma is rare, and the ilium is the commonly affected pelvic bone. These tumors can be sizeable at presentation with intra-abdominal or pelvic extension with a high chance of misdiagnosis. Fortunately surrounding soft tissue involvement seems to be a rare and late finding when present., (© 2024. The Author(s).)

Inhibition of translation initiation using eIF4A inhibitors like (-)-didesmethylrocaglamide [(-)-DDR] and (-)-rocaglamide [(-)-Roc] is a potential cancer treatment strategy as they simultaneously diminish multiple oncogenic drivers. We showed that human and dog osteosarcoma cells expressed higher levels of eIF4A1/2 compared with mesenchymal stem cells. Genetic depletion of eIF4A1 and/or 2 slowed osteosarcoma cell growth. To advance preclinical development of eIF4A inhibitors, we demonstrated the importance of (-)-chirality in DDR for growth-inhibitory activity. Bromination of DDR at carbon-5 abolished growth-inhibitory activity, while acetylating DDR at carbon-1 was tolerated. Like (-)-DDR, (±)-DDR, and (-)-Roc, (±)-DDR-acetate increased γH2A.X levels and induced G 2 /M arrest and apoptosis. Consistent with translation inhibition, these rocaglates decreased the levels of several mitogenic kinases, the STAT3 transcription factor, and the stress-activated protein kinase p38. However, phosphorylated p38 was greatly enhanced in treated cells, suggesting activation of stress response pathways. RNA sequencing identified RHOB as a top upregulated gene in both (-)-DDR- and (-)-Roc-treated osteosarcoma cells, but the Rho inhibitor Rhosin did not enhance the growth-inhibitory activity of (-)-DDR or (-)-Roc. Nonetheless, these rocaglates potently suppressed tumor growth in a canine osteosarcoma patient-derived xenograft model. These results suggest that these eIF4A inhibitors can be leveraged to treat both human and dog osteosarcomas., (© 2024. The Author(s).)

Background: Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Despite more intensive chemotherapy regimens and improved local control therapy, there is still a considerable rate of recurrent/progressive disease., Methods: A retrospective study of 50 relapsed/progressive ES patients who were treated at the National Cancer Institute (NCI), Cairo University, during the period from 1st of January 2008 to the end of December 2018, to assess different prognostic variables and disease outcomes., Results: Out of fifty eligible cases, 32 patients (64%) had disease recurrence, and 18 (36%) developed disease progression on treatment. The median follow-up period was 7.4 months. The median overall survival (OS) was 7.5 months, and the cumulative OS was 64% at 6 months and 32.6% at 1 year. The cumulative event-free survival (EFS) was 41.3% at 6 months and 22.3% at 1 year. Patients with disease recurrence had better OS and EFS than patients with disease progression (p = 0.019). Patients who underwent local control at relapse/progression had a significantly better outcome than patients who received chemotherapy only (p < 0.001). Recurrence > 2 years from initial diagnosis was the only independent predictor of better survival outcome., Conclusions: Patients with relapsing/progressive ES portended a poor outcome, with disease progression on treatment faring worse than relapse. Better outcome was observed in patients who experienced recurrence > 2 years after diagnosis, patients with disease recurrence rather than disease progression on treatment, and patients who underwent local control along with intensive chemotherapy., (© 2024. The Author(s).)

Background: Osteosarcoma (OS) is a malignant bone tumor that commonly occurs in children and adolescents under the age of 20. Dysregulation of microRNAs (miRNAs) is an important factor in the occurrence and progression of OS. MicroRNA miR-744-5p is aberrantly expressed in various tumors. However, its roles and molecular targets in OS remain unclear., Methods: Differentially expressed miRNAs in OS were analyzed using the Gene Expression Omnibus dataset GSE65071, and the potential hub miRNA was identified through weighted gene co-expression network analysis. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-744-5p in OS cell lines. In vitro experiments, including CCK-8 assays, colony formation assays, flow cytometry apoptosis assays, and tube formation assays, were performed to explore the effects of miR-744-5p on OS cell biological behaviors. The downstream target genes of miR-744-5p were predicted through bioinformatics, and the binding sites were validated by a dual-luciferase reporter assay., Results: The lowly expressed miRNA, miR-744-5p, was identified as a hub miRNA involved in OS progression through bioinformatic analysis. Nuclear factor I X (NFIX) was confirmed as a direct target for miR-744-5p in OS. In vitro studies revealed that overexpression of miR-744-5p could restrain the growth of OS cells, whereas miR-744-5p inhibition showed the opposite effect. It was also observed that treatment with the conditioned medium from miR-744-5p-overexpressed OS cells led to poorer proliferation and angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, NFIX overexpression restored the suppression effects of miR-744-5p overexpression on OS cell growth and HUVECs angiogenesis., Conclusion: Our results indicated that miR-744-5p is a potential tumor-suppressive miRNA in OS progression by targeting NFIX to restrain the growth of OS cells and angiogenesis in HUVECs., (© 2024. The Author(s).)

It may be difficult to distinguish between enchondroma and low-grade malignant cartilage tumors (grade 1) radiologically. This study aimed to construct machine learning models using 3D computed tomography (CT)-based radiomics analysis to differentiate low-grade chondrosarcoma from enchondroma. A total of 30 patients with enchondroma and 26 with chondrosarcoma were included in this retrospective study. Tumor volume segmentation was manually performed by 2 musculoskeletal radiologists. In total, 107 radiomic features were obtained for each patient. The intraclass correlation coefficient was used to assess interobserver reliability and estimate the absolute agreement between the 2 radiologists. Algorithm-based information gain was used as a feature reduction method, and the 5 most important features were detected. For classification, 7 machine learning models were utilized. Classification was carried out using either all features or 5 features. There was good to excellent agreement between the 2 radiologists for the 107 features of each patient. Therefore, a dataset containing 107 features was used for machine learning classification. When assessed based on area under curve (AUC) values, classification using all features revealed that naive Bayes was the best model (AUC = 0.950), while classification using 5 features revealed that random forest was the best model for differentiating chondrosarcoma from enchondroma (AUC = 0.967). In conclusion, machine learning models using CT-based radiomics analysis can be used to differentiate between low-grade chondrosarcoma and enchondroma., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Osteosarcoma (OS) is a rare malignant tumor that has predominantly affected children and adolescents in the past 50 years. The genomes of OS tumors exhibit a high degree of complexity, which leads to the great challenge of target identification for anti-OS. To date, no efficient therapeutic target for the treatment of OS has been validated in clinical practice. In our previous drug hunting for the treatment of OS by phenotypic screening, we found that thiazolone derivate ( R )- 8i was an effective and selective inhibitor against OS in MNNG/HOS cells and in vivo. However, the mechanism of action and specific molecular targets of ( R )- 8i remain unclear. In this study, we design and synthesize the photo-cross-linking probes based on the lead compound ( R )- 8i and identify DDX5 as a potential target protein using an activity-based protein profiling strategy. Further experiments including Western blot, shRNA knockdown experiments, cell colony formation, wound healing assays, and cellular thermal shift assays support that ( R )- 8i binds to DDX5 and induces its degradation, which affect cell proliferation and migration through the PI3K-AKT-mTOR signaling pathway. The research shows that DDX5 is a potential therapeutic target for the treatment of OS.

Background: The efficiency of systemic immune-inflammation index (SII) in predicting prognosis of osteosarcoma (OSA) patients has been extensively analyzed, but no consistent findings are obtained. Therefore, this meta-analysis focused on identifying the precise prognostic value of SII for OSA., Methods: We comprehensively searched electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 24 February, 2024. Meanwhile, the efficiency of SII in predicting prognosis of OSA was evaluated by calculating pooled hazard ratios (HRs) as well as 95% confidence intervals (CIs). Additionally, the correlation of SII with the OSA clinicopathological characteristics was analyzed based on pooled odds ratios (ORs) and 95%CIs., Results: Six studies with 1015 cases were enrolled into this work. According to the combined data, the higher SII was markedly related to poor overall survival (OS) (HR=2.01, 95%CI=1.30-3.09, p=0.002) and Enneking stage III (OR=2.21, 95%CI=1.11-4.39, p=0.024) of patients with OSA. Nonetheless, SII was not significantly related to gender, age, pathological fracture, tumor size, tumor location, tumor differentiation, and metastasis in patients with OSA., Conclusions: In summary, the higher SII is markedly related to poor OS and advanced Enneking stage in OSA patients., Systematic Review Registration: https://inplasy.com/inplasy-2024-7-0107/, identifier INPLASY202470107., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Zhang and Jiang.)

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes., (©2024 The Authors; Published by the American Association for Cancer Research.)

EWSR1::FLI1-mediated dysregulation of cellular machinery opens up potential new avenues for Ewing sarcoma treatment. A recent study demonstrates that pharmacologic ATR kinase inhibition dramatically synergizes with low-dose cisplatin through EWSR1::FLI1-dependent rewiring of transcription, DNA repair, and translation machinery, which could maximize the therapeutic window of the combinatory therapy. See related article by Jess et al., p. 3533., (©2024 American Association for Cancer Research.)

Osteoporosis is the most common bone disorder, which is a highly dangerous condition that can promote bone metastases. As the current treatment for osteoporosis involves long-term medication therapy and a cure for bone metastasis is not known, ongoing efforts are required for drug development for osteoporosis. Animal experiments, traditionally used for drug development, raise ethical concerns and are expensive and time-consuming. Organ-on-a-chip technology is being developed as a tool to supplement such animal models. In this study, we developed a bone-on-a-chip by co-culturing osteoblasts, osteocytes, and osteoclasts in an extracellular matrix environment that can represent normal bone, osteopenia, and osteoporotic conditions. We then simulated bone metastases using breast cancer cells in three different bone conditions and observed that bone metastases were most active in osteoporotic conditions. Furthermore, it was revealed that the promotion of bone metastasis in osteoporotic conditions is due to increased vascular permeability. The bone-on-a-chip developed in this study can serve as a platform to complement animal models for drug development for osteoporosis and bone metastasis., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective: Sarcomas of the bone and soft tissues are detected after the onset of pain, detectable mass and related symptoms in the absence of a standardized screening examination. However, primary chest wall sarcomas can be incidentally detected upon chest X-ray or computed tomography. Previous studies of incidental primary chest wall sarcomas lack prognosis and disease-specific clinical data. This study aimed to investigate the prognoses of patients with incidental chest wall sarcomas and compare them with those of symptomatic patients., Methods: This study included 18 patients diagnosed with primary chest wall sarcoma between 2010 and 2023. Patient information such as age, sex, tumour diameter, tumour location, symptoms, treatment, time to treatment initiation, pathological diagnosis and outcome were retrospectively analysed., Results: Among the 18 patients, the sarcomas were incidentally detected in five by chest X-ray and computed tomography in three and two patients, respectively. The pathological diagnoses of the patients were Ewing sarcoma, Chondrosarcoma grade 1, grade 2, periosteal osteosarcoma and malignant peripheral nerve sheath tumour. The patients had no symptoms at the first visit to our hospital, and no lesions in other organs were detected at the time of the initial examination. At the final follow-up, the patients remained disease-free after radical treatment. The tumour sizes of the five patients were significantly smaller than those of patients with symptoms (P = 0.003)., Conclusions: The incidental detection of chest wall sarcomas and consequent early detection and treatment of tumours improves patient prognosis relative to that of symptomatically diagnosed patients., (© The Author(s) 2024. Published by Oxford University Press.)

Immune checkpoint therapy has limited efficacy for patients with bone-metastatic castration-resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC-induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32-gene M2-like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206-positive (CD206 + ) macrophages were enriched in bmCRPC bone biopsy specimens compared with primary tumors or lymph node metastases. In preclinical osteogenic prostate cancer (Pca) xenograft models, CD206 + macrophages were recruited to areas with tumor-induced bone. RNA sequencing (RNAseq) analysis showed higher expression of an M2-like gene signature, with activated canonical and noncanonical Wnt pathways, in tumor-associated macrophages isolated from osteogenic tumors (bone-TAMs) than in TAMs isolated from nonosteogenic tumors (ctrl-TAMs). Mechanistic studies showed that endothelial cells (ECs) that had undergone EC-to-osteoblast (EC-to-OSB) transition, the precursors of tumor-induced OSBs, produced paracrine factors, including Wnts, CXCL14, and lysyl oxidase, which induced M2 polarization and recruited M2-like TAMs to the bone-tumor microenvironment (bone-TME). Bone-TAMs suppressed CD8 + T cells' proliferation and cytolytic activity, and these effects were partially reversed by treating bone-TAMs with Wnt inhibitors. Genetic or pharmacological inhibition of Pca-induced EC-to-OSB transition reduced the levels of M2-like macrophages in osteogenic tumors. Our study demonstrates that Pca-induced EC-to-OSB transition drives immunosuppression in the bone-TME, suggesting that therapies that reduce Pca-induced bone formation may improve immunotherapeutic outcomes for bmCRPC., Competing Interests: Competing interests statement:The authors declare no competing interest.

ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25's biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients., (© 2024. The Author(s).)

Osteosarcoma (OS) is the most common primary malignant tumour of the bone with high mortality. Here, we comprehensively analysed the hypoxia signalling in OS and further constructed novel hypoxia-related gene signatures for OS prediction and prognosis. This study employed Gene Set Enrichment Analysis (GSEA), Weighted correlation network analysis (WGCNA) and Least absolute shrinkage and selection operator (LASSO) analyses to identify Stanniocalcin 2 (STC2) and Transmembrane Protein 45A (TMEM45A) as the diagnostic biomarkers, which further assessed by Receiver Operating Characteristic (ROC), decision curve analysis (DCA), and calibration curves in training and test dataset. Univariate and multivariate Cox regression analyses were used to construct the prognostic model. STC2 and metastasis were devised to forge the OS risk model. The nomogram, risk score, Kaplan Meier plot, ROC, DCA, and calibration curves results certified the excellent performance of the prognostic model. The expression level of STC2 and TMEM45A was validated in external datasets and cell lines. In immune cell infiltration analysis, cancer-associated fibroblasts (CAFs) were significantly higher in the low-risk group. And the immune infiltration of CAFs was negatively associated with the expression of STC2 (P < 0.05). Pan-cancer analysis revealed that the expression level of STC2 was significantly higher in Esophageal carcinoma (ESCA), Head and Neck squamous cell carcinoma (HNSC), Kidney renal clear cell carcinoma (KIRC), Lung squamous cell carcinoma (LUSC), and Stomach adenocarcinoma (STAD). Additionally, the higher expression of STC2 was associated with the poor outcome in those cancers. In summary, this study identified STC2 and TMEM45A as novel markers for the diagnosis and prognosis of osteosarcoma, and STC2 was shown to correlate with immune infiltration of CAFs negatively., (© 2024. The Author(s).)

Background: Myelolipoma is an uncommon benign tumor composed of mature adipose tissue and hematopoietic elements. These tumors generally affect the adrenal glands, with anomalous presentations being rare and with few cases described in the literature. Most myelolipomas are asymptomatic and discovered incidentally, either through imaging tests or at autopsies. However, depending on the location and size of the lesion, myelolipomas can cause symptoms of mass effect. This article aims to report a very rare presentation of a symptomatic primary myelolipoma affecting the ribs., Case Presentation: A 21-year-old white female patient presented with a complaint of burning chest pain over 3 months, with gradual worsening in intensity, accompanied by a progressively growing bulge in the right thoracic wall. The patient underwent thoracotomy of the fifth and sixth ribs with complete excision of the lesion with a safety margin. Thoracic wall reconstruction was performed using a polypropylene mesh. The patient had a good postoperative course and was discharged on postoperative day 3. Histopathological examination revealed a histological image consistent with myelolipoma., Conclusions: This report underscores the importance of considering a myelolipoma diagnosis for tumor masses in the ribs., (© 2024. The Author(s).)