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Effective prevention and treatment options for bone cancer-related pain (BCP) are lacking. In recent years, numerous studies have investigated the association between m6A epigenetic modifications and pain, revealing their significant role in pain initiation and maintenance. This study aimed to provide theoretical support for the treatment of BCP and to identify target drugs for future development. Specifically, we investigated the involvement of fat mass and obesity-related protein (FTO) in rat models of BCP by administering varying doses (1/5/10 mg/kg) of the FTO inhibitor meclofenamic acid (MA) and assessing changes in mechanical sensitivity through domain analysis, gait analysis, and open-field experiments. After successfully establishing the BCP model, we verified it by performing mechanical sensitivity assessments. We observed significantly increased expression levels of the demethylase FTO within the spinal dorsal horn accompanied by decreased m6A methylation levels in the model. Compared with untreated BCP rats, remarkably improved behavioral responses indicative of reduced pain were observed in the model rats after administration of 10 mg/kg MA, concomitant with decreased expression levels of FTO and increased m6A methylation levels. Compared with untreated BCP rats, the expression levels of p-ERK and pro-inflammatory cytokines were also significantly decreased after MA administration. Taken together, FTO can downregulate m6A methylation level and activate ERK/inflammatory cytokines signaling pathway to maintain BCP in rats. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a highly aggressive bone cancer primarily affecting children, adolescents, and young adults. The current gold standard for treatment of osteosarcoma patients consists of two to three rounds of chemotherapy, followed by extensive surgical intervention from total limb reconstruction to amputation, followed by additional rounds of chemotherapy. Although chemotherapy has advanced the treatment of osteosarcoma significantly, the overall 5-year survival rate in resistant forms of osteosarcoma is still below 20%. The interaction between cancer and the immune system has long been recognized as a critical aspect of tumour growth. Tumour cells within the tumour microenvironment (TME) suppress antitumour immunity, and immunosuppressive cells and cytokines provide the extrinsic factors of tumour drug resistance. Emerging research demonstrates an immunostimulatory role for the cGAS/STING pathway in osteosarcoma, typically considered an immunecold or immunosuppressed cancer type. cGAS/STING signalling appears to drive an innate immune response against tumours and potentiates the efficacy of other common therapies including chemo and radiotherapy. Nanotechnological delivery systems for improved therapy delivery for osteosarcoma have also been under investigation in recent years. This review provides an overview of cGAS/STING signalling, its divergent roles in the context of cancer, and collates current research which activates cGAS/STING as an adjuvant immunomodulatory target for the treatment of osteosarcoma. It will also discuss current nanotechnological delivery approaches that have been developed to stimulate cGAS/STING. Finally, it will highlight the future directions that we believe will be central to the development of this transformative field. [ABSTRACT FROM AUTHOR]

Objective: To find out the usefulness of bone scan in all stages of breast cancer. Study Design: Prospective Observation Study. Setting: Surgical Unit I & III Ghulam Muhammad Mahar Medical College Hospital, Sukkur. Period: October 2020 till September 2022. Methods: A total of 300 patients were selected who were newly diagnosed with breast cancer (Biopsy Proven). Data was collected for all these patients which included age, risk factors for breast cancer, findings on local examination, histopathology findings, stage of the cancer and result of the bone scan. Results: In our study, 78% patients were in 4th and 5th decade of life with mean age of 53.46±7.66 years. 'Age above 40' was the commonest risk factor for breast cancer followed by positive family history for breast cancer. Tumor size ranged from 2 to 13.2 cm with mean size of 6.06±1.92 cm. In our study, most common type of carcinoma was invasive ductal carcinoma (71.3%) followed by invasive lobar carcinoma (50%). Only 32 (10.67%) out of 300 patients had positive bone scan. Majority of the bone scan positive cases belonged to the Stage IIIB, IIIC and IV. Conclusion: It is concluded in our study that routine use of bone scan in cases of stage 1 and 2 breast cancer is not recommended; only stage 3A or advances cases should undergo bone scan. [ABSTRACT FROM AUTHOR]

Currently, the clinical treatment of bone cancer pain (BCP) is mainly related to its pathogenesis. The aim of the present study was to elucidate the potential role of N6‐methyladenosine (m6A) in BCP in the spinal cord dorsal root ganglia (DRG) of BCP rats and its specific regulatory mechanism in N‐methyl‐d‐aspartate receptor subunit 2B (NR2B). A rat model of BCP was constructed by tibial injection of Walker256 cells, and ALKBH5 and NR2B expression in the spinal cord DRG was detected. ALKBH5 was silenced or overexpressed in PC12 cells to verify the regulatory effect of ALKBH5 on NR2B. The specific mechanism underlying the interaction between ALKBH5 and NR2B was investigated using methylated RNA immunoprecipitation and dual‐luciferase reporter gene assays. The results showed increased expression of m6A, decreased expression of ALKBH5, and increased expression of NR2B in the DRG of the BCP rat model. Overexpression of ALKBH5 inhibited NR2B expression, whereas interference with ALKBH5 caused an increase in NR2B expression. In NR2B, interference with ALKBH5 caused an increase in m6A modification, which caused an increase in NR2B. Taken together, ALKBH5 affected the expression of NR2B by influencing the stability of the m6A modification site of central NR2B, revealing that ALKBH5 is a therapeutic target for BCP. [ABSTRACT FROM AUTHOR]

Endomucin (MUC14), encoded by EMCN gene, is an O‐glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory‐related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory‐related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin. [ABSTRACT FROM AUTHOR]

Treatment for breast cancer, including endocrine therapies, can contribute to bone loss and increase the risk of osteoporosis and fractures. Management of bone health in patients with cancer is often coordinated between oncologists, endocrinologists, and primary care physicians. In this article, we discuss the approach to screening for fracture risk among patients initiating treatments for breast cancer and recommendations for lifestyle modifications to optimize bone health. We will review 3 indications for pharmacologic bone-targeted therapies: prevention of cancer treatment-induced bone loss, adjuvant therapy to reduce recurrence, and management of bone metastases. [ABSTRACT FROM AUTHOR]

Gardner's syndrome has been recognized as a hereditary affliction that is autosomal in nature. This disorder is known to exhibit characteristics of familial adenomatous polyposis, of which it is also considered a variation. The features of this syndrome include the gradual development of osteomas and epidermoid cysts, including a characteristic feature that is the noted presence of intestinal polyps, which are generally multiple in number. Additionally, dental anomalies have been observed and recorded in a sizeable ratio of cases encompassing an increased frequency of multiple odontomas that are benign tumors linked to the development of a tooth and tooth agenesis/hypodontia that refers to developmental absence of one or more teeth. The other dental ascertainment includes abnormal morphology of the tooth/teeth as well as the presence of supernumerary teeth and impacted or unerupted teeth. This case report outlines the case of a 59-year-old male patient who had reported to the clinic, and was then diagnosed with Gardner's syndrome post a thorough examination. On radiographic examination, the manifestation of multiple osteomas in the frontal bone was revealed. The presence of a motley of diffused benign lesions of the bone in both the upper and lower jaw as well as the presence of an epidermoid cyst on the scalp was suggestive of an exemplar presentation of Gardner's syndrome. [ABSTRACT FROM AUTHOR]

Background: Denosumab is authorized to treat several diseases, including cancer and bone disorders. Nevertheless, its use in clinical practice has been affected by safety concerns. The work retrospectively investigated adverse events (AEs) of denosumab to better understand toxicities. Methods: The FAERS data base data from Q1 of 2010 to Q3 of 2023 was chosen. The definition of Medical Dictionary for Regulatory Activities (MedDRA) was dependent on preferred terms (PTs) and system organ class (SOCs). Following the removal of duplicate reports, a disproportionality analysis was conducted to identify safety signals through the calculation of reporting odds ratios (ROR). Results: During the reporting period, 130611 denosumab-related cases were identified; 670 pTs with a substantial disproportionality were retained. The connective and musculoskeletal tissue disorders, poisoning, injury, and procedural complications, as well as medical and surgical procedures, were among the important SOCs that satisfied the criteria. Reports at PT levels including off-label use, death, osteonecrosis of the jaw, arthralgia, and pain in extremities were determined. Severe consequences in terms of life-threatening injuries and death accounted for 841 and 19704 cases, respectively of the reported cases. Conclusion: These findings underscore the critical importance of pharmacovigilance and are consistent with established clinical observations. Notably, osteonecrosis of the jaw, arthralgia, pain in extremities, back pain, myalgia, and bone pain were identified as the most prevalent risk signals associated with denosumab. [ABSTRACT FROM AUTHOR]

Background: As the most common primary bone cancer, osteosarcoma (OS) still lacks satisfactory therapeutic outcomes. Therefore, it is crucial to further evaluate OS at different risk levels and identify new intervention targets. Many evidences suggest the important role of angiogenesis in OS, but further exploration is needed. Methods: We utilized public databases TARGET and GEO and employed bioinformatics algorithms such as LASSO, univariate and multivariate Cox regression analyses, and unsupervised consensus clustering to explore the role of angiogenesis-related genes (AGRGs) in OS. By calculating AGRG scores, we further analyzed OS molecular subtypes based on AGRGs. The correlation between AGRG scores and immune infiltration was subsequently examined. In vitro experiments, including WB, PCR, siRNA, migration, and invasion assays, were used to determine the value of the selected targets for OS. Results: Ultimately, we established an OS prognosis model based on five AGRGs (COL5A2, CXCL6, FSTL1, NRP1, and TNFRSF21) that can independently validate prognosis levels. In vitro experiments confirmed the aberrant expression of CXCL6 in OS and its potential role in migration and invasion. Conclusion: Our study reveals the impact of angiogenesis on OS from a novel perspective and provides potential intervention targets. [ABSTRACT FROM AUTHOR]

Gold nanostructures play a crucial role in medical applications, harnessing size and shape‐dependent properties. A prominent area of research is cancer treatment through the photothermal approach. Here, numerical simulation is explored to study the impact of gold nanostructure size, shape, and laser parameters on spatiotemporal temperature patterns during photothermal therapy (PTT). Spherical, rod, star, bipyramid, and cubic nanostructures in small, medium, and large sizes underwent 150 s of laser irradiation. COMSOL software, incorporating bioheat physics, precisely gauged thermal variations. The structural characteristics notably influence the temperature profiles, with medium‐sized rod, star, and bipyramid gold nanoparticles exhibiting superior thermal properties. Experimental validation of simulations focuses on the optimal nanostructure, synthesizing through the seed growth method. Transmission electron microscopy, UV‐visible spectroscopy, and X‐ray diffraction analysis confirm its proposed characteristics. Results demonstrate a robust correlation between experimental and simulation parameters, affirming precision. Findings showcase photothermal properties in line with theoretical predictions. The aim of this study is to determine the optimal gold nanostructure for bone cancer treatment using PTT, addressing the challenges presented by the dense and resilient nature of bone tissue and deep tumor locations. By utilizing multi‐physical modeling and simulations facilitated by COMSOL software, a novel method for pre‐clinical estimation is introduced. This research provides insights into each nanoparticle‐based PTT process prior to ex vivo and in vivo studies, offering a comprehensive understanding of the interplay between nanostructure characteristics and PTT outcomes. The approach contributes to advancing the field of cancer treatment by enhancing the predictability and effectiveness of nanoparticle‐mediated PTT. [ABSTRACT FROM AUTHOR]

Subperiosteal orbital hematoma secondary to sinusitis is rare. Thus far, 19 cases of this disease have been reported, of which none involved postoperative skin anesthesia in the region innervated by the supraorbital nerve. In this article, for the first time we report a case of subperiosteal orbital hematoma secondary to sinusitis with skin anesthesia in the area innervated by the supraorbital nerve after surgery. [ABSTRACT FROM AUTHOR]

Bone cancer pain (BCP) profoundly impacts patient's quality of life, demanding more effective pain management strategies. The aim of this systematic review was to investigate the role of inflammatory cytokines as potential molecular targets in BCP. A systematic search for animal rodent models of bone cancer pain studies was conducted in PubMed, Scopus, and Web of Science. Methodological quality and risk of bias were assessed using the SYRCLE RoB tool. Twenty-five articles met the inclusion criteria, comprising animal studies investigating molecular targets related to inflammatory cytokines in BCP. A low to moderate risk of bias was reported. Key findings in 23 manuscripts revealed upregulated classic pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-18, IL-33) and chemokines in the spinal cord, periaqueductal gray, and dorsal root ganglia. Interventions targeting these cytokines consistently mitigated pain behaviors. Additionally, it was demonstrated that glial cells, due to their involvement in the release of inflammatory cytokines, emerged as significant contributors to BCP. This systematic review underscores the significance of inflammatory cytokines as potential molecular targets for alleviating BCP. It emphasizes the promise of targeted interventions and advocates for further research to translate these findings into effective therapeutic strategies. Ultimately, this approach holds the potential to enhance the patient's quality of life. [ABSTRACT FROM AUTHOR]

Metastatic disease and myeloma present unique diagnostic challenges due to their multifocal nature. Accurate detection and staging are critical for determining appropriate treatment. Bone scintigraphy, skeletal radiographs and CT have long been the mainstay for the assessment of these diseases, but have limitations, including reduced sensitivity and radiation exposure. Whole-body MRI has emerged as a highly sensitive and radiation-free alternative imaging modality. Initially developed for skeletal screening, it has extended tumor screening to all organs, providing morphological and physiological information on tumor tissue. Along with PET/CT, whole-body MRI is now accepted for staging and response assessment in many malignancies. It is the first choice in an ever increasing number of cancers (such as myeloma, lobular breast cancer, advanced prostate cancer, myxoid liposarcoma, bone sarcoma, ...). It has also been validated as the method of choice for cancer screening in patients with a predisposition to cancer and for staging cancers observed during pregnancy. The current and future challenges for WB-MRI are its availability facing this number of indications, and its acceptance by patients, radiologists and health authorities. Guidelines have been developed to optimize image acquisition and reading, assessment of lesion response to treatment, and to adapt examination designs to specific cancers. The implementation of 3D acquisition, Dixon method, and deep learning-based image optimization further improve the diagnostic performance of the technique and reduce examination durations. Whole-body MRI screening is feasible in less than 30 min. This article reviews validated indications, recent developments, growing acceptance, and future perspectives of whole-body MRI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Current diagnostic tools are unable to distinguish low‐grade indolent prostate cancer (PrCa) from that with a propensity to become metastatic and/or lethal. Recent evidence suggests that reprogramming of the transcriptome may drive the metastatic phenotype, and that this reprogramming is controlled, at least in part, by epigenetic changes to the DNA of cancer cells, including methylation. These changes, referred to as 'epigenetic drivers,' have previously been associated with cancer cell survival. Methods: Here, using Illumina Methylation EPIC array data of paired primary PrCa and metastatic bone samples, we identified WNT5A as a putative epi‐driver of PrCa metastasis to the bone, which was further validated in vitro. Results: Significantly higher WNT5A methylation was observed in primary PrCa samples and 22Rv1 cells compared to metastatic bone samples and PC‐3 cells. This higher methylation was associated with significantly lower WNT5A gene expression. Conclusion: Given the limited effective therapies available for metastatic cancer sufferers, particularly those whose disease has metastasised to the bone, WNT5A presents as a potential putative target for therapy. [ABSTRACT FROM AUTHOR]

Metastatic prostate cancer (mPCa) is a widespread disease with high mortality. Unraveling molecular mechanisms of disease progression is of utmost importance. The microenvironment in visceral organs and the skeletal system is of particular interest as a harbinger of metastatic spread. Therefore, we performed a comprehensive transcriptomic analysis of prostate cancer lung metastases with a special focus on differentially expressed genes attributable to the microenvironment. Digital gene expression analysis using the NanoString nCounter analysis system was performed on formalin-fixed, paraffin-embedded (FFPE) tissue from prostate cancer (PCa) lung metastases (n = 24). Data were compared to gene expression data from primary PCa and PCa bone metastases. Bioinformatic analysis was performed using several publicly available tools. In comparison to prostate cancer bone metastases, 209 genes were significantly upregulated, and 100 genes were significantly downregulated in prostate cancer lung metastases. Among the up-regulated genes, the top 10 genes with the most significant P-value were HLA-DPB1, PTPRC, ITGB7, C3, CCL21, CCL5, ITGAM, SERPINA1, MFAP4, ARAP2 and among the down-regulated genes, the top 10 genes with the most significant P-value were FOXC2, TWIST1, CDK14, CHAD, IBSP, EPN3, VIT, HAPLN1, SLC44A4, TBX1. In PCa lung metastases genes associated with immunogenic responses were upregulated while genes associated with epithelial-mesenchymal transition were down-regulated. We also showed that CXCR3/CXCL10 axis plays a significant role in prostate cancer lung metastases in comparison to bone metastases. In this study, we comprehensively explored transcriptomic alterations in PCa lung metastases in comparison to primary PCa and PCa bone metastases. In PCa lung metastases genes associated with immunogenic responses are upregulated while genes associated with epithelial-mesenchymal transition are down-regulated. This points to a more immunogenic phenotype of PCa lung metastases thus potentially making patients more susceptible to immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5–78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96–96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77–105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression. [ABSTRACT FROM AUTHOR]

Aims: Bone cancer produces severe pain that is treated with opioids, but serious side effects limit opioid utilization. There is therefore a need to develop effective and safe non‐opioid alternatives. The lipid mediator, Resolvin D1 (RvD1), could be a prospective candidate for cancer pain treatment. To assess RvD1 and other potential candidates, appropriate animal models that recapitulate clinical features must be used. Although several preclinical models of cancer pain have been developed, the influence of sex on the development of cancer pain and the effectiveness of RvD1 have not been studied. Results: Using a mouse model of fibrosarcoma growth in and around the calcaneus bone, we demonstrated that the mechanical hyperalgesia in the tumor‐bearing hind paw develops independently of sex, except that it developed a little sooner in female mice. A single intravenous injection of RvD1 (0.001–10 μg/kg) decreased hyperalgesia in both sexes with similar potency (ED50 = 0.0015 μg/kg) and efficacy. Repeated daily administration of 10 μg/kg RvD1 prolonged the analgesic effect and completely abolished hyperalgesia. This was also independent of sex. Conclusion: In this preclinical mouse model of bone cancer pain, the development of pain and the analgesic effectiveness of RvD1 are not influenced by sex. [ABSTRACT FROM AUTHOR]

In Italy, 1400 children and 800 adolescents are diagnosed with cancer every year. About 80% of them can be cured but are at high risk of experiencing severe side effects, many of which respond to rehabilitation treatment. Due to the paucity of literature on this topic, the Italian Association of Pediatric Hematology and Oncology organized a Consensus Conference on the role of rehabilitation of motor impairments in children/adolescents affected by leukemia, central nervous system tumors, and bone cancer to state recommendations to improve clinical practice. This paper includes the consensus on the rehabilitation of children and adolescents with these cancers. [ABSTRACT FROM AUTHOR]

Mayo Clinic Florida will initially open with the capability to treat with a single horizontal port for carbon ion therapy. Carbon ion therapy is traditionally done using a multi fixed port treatment approach. In this study, for nine treatment sites, clinically approved treatment plan of Osaka Heavy Ion Therapy Center was compared to a treatment plan using only a horizontal port. The treatment sites evaluated in this study were prostate cancer, pancreatic cancer, cervical cancer, recurrent rectal cancer, liver cancer, head and neck cancer, bone cancer (sarcoma and chordoma), and lung cancer. As expected, the prostate plans are identical and are only included for completeness. The DVH results for the pancreas and cervical cancer were very similar. The results for recurrent rectal, head and neck, sarcoma, chordoma, and lung cancer indicate that a single horizontal port with couch roll and yaw will accommodate certain medial targets but will be challenging to treat for laterally located targets without creative mitigations. [ABSTRACT FROM AUTHOR]

Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B‐cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis‐HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin‐resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin‐resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Abstract Malignant bone tumors, including primary bone cancer and metastatic bone tumors, are a significant clinical challenge due to their high frequency of presentation, poor prognosis and lack of effective treatments and therapies. Bone tumors are often accompanied by skeletal complications such as bone destruction and cancer-induced bone pain. However, the mechanisms involved in bone cancer progression, bone metastasis and skeletal complications remain unclear. Lysophosphatidic acid (LPA), an intercellular lipid signaling molecule that exerts a wide range of biological effects mainly through specifically binding to LPA receptors (LPARs), has been found to be present at high levels in the ascites of bone tumor patients. Numerous studies have suggested that LPA plays a role in primary malignant bone tumors, bone metastasis, and skeletal complications. In this review, we summarize the role of LPA signaling in primary bone cancer, bone metastasis and skeletal complications. Modulating LPA signaling may represent a novel avenue for future therapeutic treatments for bone cancer, potentially improving patient prognosis and quality of life.

Bone cancer detection is an essential region of medical analysis but developments in medical imaging and artificial intelligence (AI) are vital. Using approaches, namely deep learning (DL) and machine learning (ML), radiologists and medical staff can examine X-ray, CT, and MRI scans to identify bone cancer and abnormalities. These technologies support earlier diagnosis, correct diagnosis, and treatment planning, enhancing patient solutions. The combination of AI-driven image analysis and the knowledge of medical practitioners improves the speed and precision of bone cancer detection, contributing to more effectual clinical activities. DL algorithms, particularly CNNs, are exposed to great performance in image classification tasks and are extremely utilized for medical image analysis. We offer a Hybrid Rice Optimization Algorithm with DL-Assisted Bone Cancer Detection (HROADL-BCD) technique on medical X-ray images. The major intention of the HROADL-BCD method is to examine the X-ray images for the recognition of bone cancer. In the presented HROADL-BCD method, a bilateral filtering (BF) process was performed to remove the noise. To derive feature vectors, the HROADL-BCD technique applied the EfficientNet model. The HROADL-BCD technique involved the HROA for hyperparameter tuning of the EfficientNet model. Last, the bone cancer detection and classification process were executed by the attention-based bidirectional long short-term memory (ABiLSTM) approach. A wide range of simulations could be applied for the simulation result analysis of the HROADL-BCD algorithm. The extensive outcome of the HROADL-BCD approach inferred the superior outcome of 97.62% outcome concerning various aspects.

Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Osteosarcoma is an aggressive bone cancer affecting both humans and dogs, often leading to pulmonary metastasis. Despite surgery and chemotherapy being the primary treatment modalities, survival rates remain low in both species, underscoring the urgent need for more efficacious therapeutic options. Accumulating evidence indicates numerous biological and clinical similarities between human and canine osteosarcoma, making it an ideal choice for comparative oncological research that should benefit both species. The EphA2 receptor has been implicated in controlling invasive responses across different human malignancies, and its expression is associated with poor prognosis. In this study, we utilized a comparative approach to match EphA2 functions in human and canine osteosarcoma models. Our objectives were to assess EphA2 levels and its pro-malignant action in osteosarcoma cells of both species. We found that EphA2 is overexpressed in most of both canine and human osteosarcoma cell lines, while its silencing significantly reduced cell viability, migration, and invasion. Moreover, EphA2 silencing enhanced the sensitivity of osteosarcoma cells to cisplatin, a drug commonly used for treating this cancer. Furthermore, inhibition of EphA2 expression led to a significant reduction in tumor development capability of canine osteosarcoma cells. Our data suggest that these EphA2 effects are likely mediated through various signaling mechanisms, including the SRC, AKT, and ERK–MAPK pathways. Collectively, our findings indicate that EphA2 promotes malignant behaviors in both human and canine osteosarcoma and that targeting EphA2, either alone or in combination with chemotherapy, could offer potential benefits to osteosarcoma patients. [ABSTRACT FROM AUTHOR]

The binding of peroxisome proliferator‐activated receptor γ (PPARγ) to the orphan nuclear receptor Nur77 facilitates the ubiquitination and degradation of Nur77, and leads to aberrant fatty acid uptake for breast cancer progression. Because of its crucial role in clinical prognosis, the interaction between Nur77 and PPARγ is an attractive target for anti‐breast‐cancer therapy. However, developing an inhibitor of the Nur77‐PPARγ interaction poses a technical challenge due to the absence of the crystal structure of PPARγ and its corresponding interactive model with Nur77. Here, ST‐CY14, a stapled peptide, is identified as a potent modulator of Nur77 with a KD value of 3.247 × 10−8 M by in silico analysis, rational design, and structural modification. ST‐CY14 effectively increases Nur77 protein levels by blocking the Nur77‐PPARγ interaction, thereby inhibiting lipid metabolism in breast tumor cells. Notably, ST‐CY14 significantly suppresses breast cancer growth and bone metastasis in mice. The findings demonstrate the feasibility of exploiting directly Nur77‐PPARγ interaction in breast cancer, and generate what to the best knowledge is the first direct inhibitor of the Nur77‐PPARγ interaction available for impeding fatty acid uptake and therapeutic development. [ABSTRACT FROM AUTHOR]

This study involved the preparation of the Saudi Arabian Cassia angustifolia Vahl methanolic extract and the production of polyvinylpyrrolidone (PVP) nanofibers that contained the Saudi Arabian C. angustifolia Vahl methanolic extract. The reason for using polyvinylpyrrolidone is its bioactivity and its physical and chemical properties. The structure and characterization of the newly synthesized nanofiber were confirmed using the Fourier-transform infrared (FTIR) spectrum, elemental analysis, scanning electron microscopy (SEM) image, N2 adsorption–desorption curve, hydrophilicity, compressive strength, and flexural strength. The biological activity, including anticancer properties against skin cancer cells and bone cancer cells and antibacterial activity against Gram-positive and Gram-negative strains, was assessed. The average diameter and the specific surface area of the synthesized polyvinylpyrrolidone nanofibers containing the Saudi Arabian Cassia angustifolia Vahl methanolic extract were 87 nm and 1,108 m² /g, respectively. High hydrophilicity compared to polyvinylpyrrolidone (contact angle of synthetic nanofibers was 21° and for polyvinylpyrrolidone was 52°), high compressive strength compared to polyvinylpyrrolidone (61.23 N/mm² and 34.52 N/mm², respectively), and high flexural strength compared to polyvinylpyrrolidone (16.1 N/mm2 and 11.4 N/mm², respectively) were other characteristics of the synthesized polyvinylpyrrolidone nanofibers containing the Saudi Arabian Cassia angustifolia Vahl methanolic extract. In the biological activities of the synthesized nanofiber, unique properties were observed. Regarding the anticancer activity, the IC50 values against skin cancer cells and bone cancer cells were observed to be 19.59 μg/mL and 29.57 μg/mL, respectively. For the antimicrobial activity, the MIC value between 4 and 128 mg/mL was observed. The biological activities of the synthesized polyvinylpyrrolidone nanofibers containing the Saudi Arabian Cassia angustifolia Vahl methanolic extract were higher than those of the Saudi Arabian Cassia angustifolia Vahl methanolic extract. The biological properties can be enhanced by various factors, including the high specific surface area of the synthesized nanofiber. [ABSTRACT FROM AUTHOR]

The early diagnosis of tumour is significant in biomedical research field to lower the severity level and restrict the process extension from cancer. Moreover, the detection of early sign of cancer is undertaken with extensive research efforts that dedicated to the disclosure and recognition of tumours. However, the limited data size as well as diverse appearance of images lowered the detection performance and failed to detect complex stage of tumour. So to solve these issues, a Weighted Adaptive Random Ensemble Support Vector-based Partial Reinforcement Search (WARES-PRS) algorithm is proposed that detected bone lesions accurately and also predicted the severity level stage efficiently. Further, the detection is performed with varied stages to diminish the presence of noise and undertaken effective classification. The performance is validated with CNUH dataset that enhanced image pre-processing tasks. Despite the proposed method uncover the mutual relationships between each pixel’s local texture and the overall image’s global context. The detection and classification efficiency is validated with various measures and the experimental results revealed that the detection accuracy is enhanced for the proposed approach by 98.5%. The outcomes of our study have exhibited a substantial contribution to assisting physicians in the detection of knee bone tumours. [ABSTRACT FROM AUTHOR]

Introduction. Internet searches reflect public awareness, which may be influenced by cancer epidemiology. The aim was to characterize the relationship between the occurrence of bone cancer and the number of Internet searches in Poland. A secondary goal was to assess the relationship between awareness campaigns and online searches. The last goal was to assess the incidence and mortality rate of bone sarcoma in Poland over 10 years. Material and methods. The epidemiology data of bone cancer in 2010-2020 were analyzed in relation to search volume index (SVI) in Google Trends for terms — ‘osteosarcoma’, ‘chondrosarcoma’, ‘Ewing sarcoma’, ‘bone cancer’, ‘bone tumor’. Results. On average, 317.6 (± 29.8) new cases of bone cancer were diagnosed annually, and 272.2 (± 43.3) patients died annually. Correlations between incidence rates and SVI for terms: osteosarcoma (r = 0.17; p = 0.035), chondrosarcoma (r = 0.36; p < 0.001) and Ewing sarcoma (r = 0.21; p = 0.008), and between mortality rate and SVI for terms: chondrosarcoma (r = 0.42; p < 0.001) and bone cancer (r = 0.20; p = 0.012) were noted. There was no increase in interest in the topic of bone cancer in July (Sarcoma Awareness Month) in Poland and worldwide. Conclusions. The incident and mortality rate of bone sarcomas is correlated with the number of online searches for individual phrases. Awareness campaigns do not significantly increase interest in the topic of bone sarcomas on the Internet. Epidemiological data on bone cancer in Poland are comparable to worldwide data. [ABSTRACT FROM AUTHOR]

Bone remodelling is a highly regulated process that maintains mineral homeostasis and preserves bone integrity. During this process, intricate communication among all bone cells is required. Indeed, adapt to changing functional situations in the bone, the resorption activity of osteoclasts is tightly balanced with the bone formation activity of osteoblasts. Recent studies have reported that RNA Binding Proteins (RBPs) are involved in bone cell activity regulation. RBPs are critical effectors of gene expression and essential regulators of cell fate decision, due to their ability to bind and regulate the activity of cellular RNAs. Thus, a better understanding of these regulation mechanisms at molecular and cellular levels could generate new knowledge on the pathophysiologic conditions of bone. In this Review, we provide an overview of the basic properties and functions of selected RBPs, focusing on their physiological and pathological roles in the bone. [ABSTRACT FROM AUTHOR]

The combination of therapeutic materials and biocompatible scaffolds to create multifunctional scaffolds with therapeutic and restorative functions has been investigated as a new therapeutic modality for bone cancers because the integration of multi-modal therapies into one platform can exhibit significant potential in overcoming the drawbacks of conventional therapy in bone cancers. In this study, we develop an IR780- and epigallocatechin gallate (EGCG)-loaded multifunctional polylactic acid (PLA) (E-PLMH780) composite scaffold for chemo-photothermal combination therapy without cytotoxicity. This bilayered E-PLMH780 scaffold is prepared using a layer of EGCG-loaded PLA monolith and a three-dimensionally printed PLA composite scaffold, followed by coating with IR780-loaded Mg-HA nanoparticles. The monolith layer in the composite scaffold exhibits a three-dimensional porous structure and a uniform morphology featuring small leaf-like units, whereas the three-dimensionally printed layer exhibits a uniform porous structure with a hierarchical architecture. The results of the chemo-photothermal combination therapy and cytotoxicity assays showed that the E-PLMH780 scaffold effectively inhibited bone cancer cell proliferation but did not cause cytotoxicity in normal osteoblastic cells. Therefore, chemo-photothermal combination therapy using IR780- and EGCG-loaded E-PLMH780 scaffolds can potentially provide a new generation of therapeutic modality for the improved treatment of bone cancers and repair of bone defects. Schematic diagram of the fabrication of IR780- and EGCG-loaded E-PLMH780 scaffolds and their therapeutic efficacy on cancer cells [ABSTRACT FROM AUTHOR]

Background: This study evaluates the repeatability and reproducibility of fat-fraction percentage (FF%) in whole-body magnetic resonance imaging (WB-MRI) of prostate cancer patients with bone metastatic hormone naive disease. Methods: Patients were selected from the database of a prospective phase-II trial. The treatment response was assessed using the METastasis Reporting and Data System for Prostate (MET-RADS-P). Two operators identified a Small Active Lesion (SAL, <10 mm) and a Large Active Lesion (LAL, ≥10 mm) per patient, performing manual segmentation of lesion volume and the largest cross-sectional area. Measurements were repeated by one operator after two weeks. Intra- and inter-reader agreements were assessed via Interclass Correlation Coefficient (ICC) on first-order radiomics features. Results: Intra-reader ICC showed high repeatability for both SAL and LAL in a single slice (SS) and volumetric (VS) measurements with values ranging from 0.897 to 0.971. Inter-reader ICC ranged from 0.641 to 0.883, indicating moderate to good reproducibility. Spearman's rho analysis confirmed a strong correlation between SS and VS measurements for SAL (0.817) and a moderate correlation for LAL (0.649). Both intra- and inter-rater agreement exceeded 0.75 for multiple first-order features across lesion sizes. Conclusion: This study suggests that FF% measurements are reproducible, particularly for larger lesions in both SS and VS assessments. [ABSTRACT FROM AUTHOR]

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis. [ABSTRACT FROM AUTHOR]

Malignant bone tumors, including primary bone cancer and metastatic bone tumors, are a significant clinical challenge due to their high frequency of presentation, poor prognosis and lack of effective treatments and therapies. Bone tumors are often accompanied by skeletal complications such as bone destruction and cancer-induced bone pain. However, the mechanisms involved in bone cancer progression, bone metastasis and skeletal complications remain unclear. Lysophosphatidic acid (LPA), an intercellular lipid signaling molecule that exerts a wide range of biological effects mainly through specifically binding to LPA receptors (LPARs), has been found to be present at high levels in the ascites of bone tumor patients. Numerous studies have suggested that LPA plays a role in primary malignant bone tumors, bone metastasis, and skeletal complications. In this review, we summarize the role of LPA signaling in primary bone cancer, bone metastasis and skeletal complications. Modulating LPA signaling may represent a novel avenue for future therapeutic treatments for bone cancer, potentially improving patient prognosis and quality of life. [ABSTRACT FROM AUTHOR]

Objective: While bone metastases (BMs) are present in a minority of thyroid cancer (TC) patients at the time of initial diagnosis, there has been growing concern regarding their impact on life expectancy and quality of life. The aim of this study was to identify prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in these patients and provide therapeutic recommendations based on the findings. Methods: In this retrospective cohort study, we included 82 patients diagnosed as TC with BM received treatment in our department from 2011.03 to 2023.03 (average follow-up duration was 3.02 years). The retrospective study was performed according to the inclusion and exclusion criteria. Kaplan-Meier analysis was used to estimate the OS and CSS, while the univariate and multivariate Cox proportional hazard models were employed to determine prognostic factors associated with OS and CSS. Also, 287 patients' data were collected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 to confirm the prognostic factors identified in the retrospective study. Results: The average survival time of the 82 patients was estimated to be 5.818 years (with a 95% confidence interval (CI) of 4.767 to 6.868 years). The cox regression analysis showed that older age (hazard ratio (HR) = 1.045, 95% CI: 1.001-1.092, P = 0.047), larger tumor size (>5cm, HR = 11.087, 95% CI: 3.728 - 32.976, P = 0.000), and the presence of extraosseous metastasis (HR = 3.247, 95% CI: 1.376 - 7.665, P = 0.007) were statistically significant factors associated with worse CSS. The results were furtherly confirmed in 287 SEER-sourced patients (age (HR = 1.020, 95% CI: 1.006 - 1.034, P = 0.006), tumor size (HR = 2.917, 95% CI: 2.044 - 4.161, P = 0.000), and extraosseous metastasis (HR = 3.726, 95% CI: 2.571 - 5.398, P = 0.000)). Conclusions: These results offer a population-based assessment of prognostic factors for patients with TC and BMs, revealing that age, primary tumor size (>5cm), and presence of extraosseous metastases are independent prognostic factors that correlate with worse survival. Accordingly, treatment for such patients ought to concentrate on systemic integrative therapy instead of surgical intervention. [ABSTRACT FROM AUTHOR]

Ewing sarcoma is the second most common bone cancer in children, and while patients who present with metastatic disease at the time of diagnosis have a dismal prognosis. Ewing sarcoma tumors are driven by the fusion gene EWS/Fli1, and while these tumors are genetically homogenous, the transcriptional heterogeneity can lead to a variety of cellular processes including metastasis. In this study, we demonstrate that in Ewing sarcoma cells, the canonical Wnt/β-Catenin signaling pathway is heterogeneously activated in vitro and in vivo, correlating with hypoxia and EWS/Fli1 activity. Ewing sarcoma cells predominantly express β-Catenin on the cell membrane bound to CDH11, which can respond to exogenous Wnt ligands leading to the immediate activation of Wnt/β-Catenin signaling within a tumor. Knockdown of CDH11 leads to delayed and decreased response to exogenous Wnt ligand stimulation, and ultimately decreased metastatic propensity. Our findings strongly indicate that CDH11 is a key component of regulating Wnt//β-Catenin signaling heterogeneity within Ewing sarcoma tumors, and is a promising molecular target to alter Wnt//β-Catenin signaling in Ewing sarcoma patients. [ABSTRACT FROM AUTHOR]

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9–43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93–11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01–0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13–11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68–15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases. [ABSTRACT FROM AUTHOR]

Targeted drug delivery has a positive impact on the concentration of anticancer drugs at the tumor site and can reduce harmful side effects. In this research, silk fibroin and sodium alginate were utilized to produce nanoparticles, which were then targeted using sodium alendronate (SF-SA-ALN NPs) to improve the effectiveness of chemotherapy on osteosarcoma. The resulting nanoparticles had a surface charge of -50.5 mV and an average size of 252 nm (with PDI = 0.157). Doxorubicin (DOX) was loaded onto the nanoparticles using ionic interaction with 96% drug loading efficiency. The nanoparticles showed higher drug release at pH 5.4 compared to pH 7.4. It was also investigated the effectiveness of in vitro bone targeting using hydroxyapatite (HA) as a bone model, and found that targeted nanoparticles accumulated in HA crystals. The toxicity of the drug-loaded nanoparticles on a human osteosarcoma cell line (MG-63) revealed that the drug-targeted nanoparticles were more toxic than free drug after 24 h. This may be due to the presence of alendronate on the SF-SA-ALN NPs, which allowed for internalization of the nanoparticles through endocytosis. Overall, these nanoparticles show promise as a potential drug delivery system for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi‐institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow‐up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty‐six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow‐up, resulting in an overall metastatic rate of 30%. Forty‐nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour‐specific survival (TSS) were not reached. One‐ and 2‐year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1‐ and 2‐year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P <.001) and TSS (P =.001) compared with non‐operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour‐related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain. [ABSTRACT FROM AUTHOR]

Purpose: Doxorubicin is a widely used chemotherapeutic drug that can be administered intravenously as both a bolus infusion and a continuous infusion. The latter is believed to lower the risk of cardiotoxicity, which is a critical long-term complication of doxorubicin treatment. The local tissue concentrations of doxorubicin will be reflected in both treatment efficacy and toxicity, but very limited information is available. The aim of this study was to measure the concentration of doxorubicin after continuous and bolus infusion in tissue compartments around a typical location of a bone tumour. Methods: Sixteen pigs (female, Danish Landrace, mean weight 77 kg) were randomized into two groups of eight. Both groups received an intravenous infusion of 150 mg doxorubicin; Group 1 received a bolus infusion (10–15 min) and Group 2 received a continuous infusion (6 h). Before infusion, microdialysis catheters were placed intravenously and in four bone tumour-relevant tissue compartments (cancellous bone, subcutaneous tissue, synovial fluid of the knee joint and muscle tissue). Sampling was done (n = 15) over 24 h, and venous blood samples were collected as a reference. Results: Area under the concentration–time curve (AUC0–24 h) for plasma (total concentration) was significantly different between the two groups, while peak drug concentration (Cmax) was significantly higher in two compartments (plasma and synovial fluid of the knee joint) in Group 1 compared to Group 2. Overall, the unbound tissue concentrations were extremely low with values below 0.20 µg/mL. Conclusion: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion. [ABSTRACT FROM AUTHOR]

To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance. Methods: Clinical data of 286 patients diagnosed with prostate cancer with bone metastasis, initially treated with endocrine therapy, and progressing to metastatic castration resistant prostate cancer (mCRPC) were collected. By comparing the differences in various factors between different groups with fast and slow occurrence of castration-resistant prostate cancer (CRPC). Kaplan-Meier survival analysis and COX multivariate risk proportional regression model were used to compare the differences in the time to progression to CRPC in different groups. The COX multivariate risk proportional regression model was used to evaluate the impact of candidate factors on the time to progression to CRPC and establish a predictive model. The accuracy of the model was then tested using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The median time for 286 mCRPC patients to progress to CRPC was 17 (9.5– 28.0) months. Multivariate analysis showed that the lowest value of PSA (PSA nadir), the time when PSA dropped to its lowest value (timePSA), and the number of BM, and LDH were independent risk factors for rapid progression to CRPC. Based on the four independent risk factors mentioned above, a prediction model was established, with the optimal prediction model being a random forest with area under curve (AUC) of 0.946[95% CI: 0.901– 0.991] and 0.927[95% CI: 0.864– 0.990] in the training and validation cohort, respectively. Conclusion: After endocrine therapy, the PSA nadir, timePSA, the number of BM, and LDH are the main risk factors for rapid progression to mCRPC in patients with prostate cancer bone metastases. Establishing a CRPC prediction model is helpful for early clinical intervention decision-making. [ABSTRACT FROM AUTHOR]

Bone cancer detection is an essential region of medical analysis but developments in medical imaging and artificial intelligence (AI) are vital. Using approaches, namely deep learning (DL) and machine learning (ML), radiologists and medical staff can examine X-ray, CT, and MRI scans to identify bone cancer and abnormalities. These technologies support earlier diagnosis, correct diagnosis, and treatment planning, enhancing patient solutions. The combination of AI-driven image analysis and the knowledge of medical practitioners improves the speed and precision of bone cancer detection, contributing to more effectual clinical activities. DL algorithms, particularly CNNs, are exposed to great performance in image classification tasks and are extremely utilized for medical image analysis. We offer a Hybrid Rice Optimization Algorithm with DL-Assisted Bone Cancer Detection (HROADLBCD) technique on medical X-ray images. The major intention of the HROADL-BCD method is to examine the X-ray images for the recognition of bone cancer. In the presented HROADL-BCD method, a bilateral filtering (BF) process was performed to remove the noise. To derive feature vectors, the HROADL-BCD technique applied the EfficientNet model. The HROADL-BCD technique involved the HROA for hyperparameter tuning of the EfficientNet model. Last, the bone cancer detection and classification process were executed by the attention-based bidirectional long short-term memory (ABiLSTM) approach. A wide range of simulations could be applied for the simulation result analysis of the HROADL-BCD algorithm. The extensive outcome of the HROADL-BCD approach inferred the superior outcome of 97.62% outcome concerning various aspects. [ABSTRACT FROM AUTHOR]

Background and Objectives: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients' ADL and QOL and examine the factors influencing changes in these parameters. Materials and Methods: We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2–8 weeks after the initial assessment. Patients' background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. Results: Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all p < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements (p = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, p = 0.049; OR: 8.42, p < 0.001), chemotherapy (OR: 0.43, p = 0.02; OR: 0.25, p = 0.007), and NRS average scores (OR: 0.38, p = 0.02; OR: 0.14, p < 0.001) were independent factors associated with ADL and QOL. Conclusions: Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a prevalent male malignancy that originates in the epithelial cells of the prostate. In terms of incidence and mortality of malignant tumors in men, PCa ranks second and fifth globally and first and third among men in Europe and the United States, respectively. These figures have gradually increased in recent years. The primary modalities used to diagnose PCa include prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and prostate puncture biopsy. Among these techniques, prostate puncture biopsy is considered the gold standard for the diagnosis of PCa; however, this method carries the potential for missed diagnoses. The preoperative evaluation of the patient in this study suggested advanced PCa. However, the initial prostate puncture biopsy was inconsistent with the preoperative diagnosis, and instead of waiting for a repeat puncture of the prostate primary, we performed a biopsy of the rib metastasis, which was later diagnosed as advanced PCa. [ABSTRACT FROM AUTHOR]

Despite growing evidence implicating the calcium-activated chloride channel anoctamin1 (ANO1) in cancer metastasis, its direct impact on the metastatic potential of prostate cancer and the possible significance of epigenetic alteration in this process are not fully understood. Here, we show that ANO1 is minimally expressed in LNCap and DU145 prostate cancer cell lines with low metastatic potential but overexpressed in high metastatic PC3 prostate cancer cell line. The treatment of LNCap and DU145 cells with DNMT inhibitor 5-aza-2′-deoxycytidine (5-Aza-CdR) potentiates ANO1 expression, suggesting that DNA methylation is one of the mechanisms controlling ANO1 expression. Consistent with this notion, hypermethylation was detected at the CpG island of ANO1 promoter region in LNCap and DU145 cells, and 5-Aza-CdR treatment resulted in a drastic demethylation at promoter CpG methylation sites. Upon 5-Aza-CdR treatment, metastatic indexes, such as cell motility, invasion, and metastasis-related gene expression, were significantly altered in LNCap and DU145 cells. These 5-Aza-CdR-induced metastatic hallmarks were, however, almost completely ablated by stable knockdown of ANO1. These in vitro discoveries were further supported by our in vivo observation that ANO1 expression in xenograft mouse models enhances the metastatic dissemination of prostate cancer cells into tibial bone and the development of osteolytic lesions. Collectively, our results help elucidate the critical role of ANO1 expression in prostate cancer bone metastases, which is epigenetically modulated by promoter CpG methylation. [ABSTRACT FROM AUTHOR]