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bone cancer

Molecular Analysis of PIK3CA in Metastatic Hormone Receptor-Positive Breast Cancer in Chile: Clinical and Pathological Insights.

Breast cancer is the most common cancer among women and a leading cause of cancer-related deaths. PIK3CA gene mutations, which are often present in advanced HR+ breast cancer, can be targeted by alpelisib. However, data on PIK3CA mutations in Chile are limited. Here, we aim to assess the mutational status of PIK3CA in metastatic breast cancer tissues from Chilean patients and describe their clinicopathological characteristics and survival outcomes. We analyzed 102 formalin-fixed, paraffin-embedded metastatic breast cancer samples from 96 patients diagnosed at three Chilean hospitals between 2007 and 2023. PIK3CA mutations were identified using targeted sequencing, and clinicopathological data were collected. We evaluated associations between mutational status, clinicopathological features, and survival. The median age at diagnosis was 56 years. The most common metastatic sites were liver (29.4%), bone (17.6%), and lung/pleura (16.7%). Most patients were HR+ HER2- (83.3%), with 57.3% showing HER2-low status. PIK3CA mutations were present in 40.6% of patients, mainly in exons 7, 9, and 20. No significant associations were found between PIK3CA mutations and clinicopathological characteristics or survival. Our study reveals a high frequency of PIK3CA mutations in HR+ metastatic breast cancer, consistent with global data. The majority of mutations are targetable with alpelisib. The proportion of HER2-low status patients suggests potential benefits from novel HER2-targeted therapies. These findings highlight the need for routine molecular diagnostics in Chile to improve personalized treatment and address economic and access challenges.

bone cancer

Monitoring and Treatment of Paroxysmal Nocturnal Hemoglobinuria in Patients with Aplastic Anemia in Asia: An Expert Consensus.

Paroxysmal nocturnal hemoglobinuria (PNH) clones can be identified in a significant proportion of patients with aplastic anemia (AA). Screening for PNH clones at the time of an AA diagnosis is recommended by national and international guidelines. In this report, an expert panel of physicians discusses current best practices and provides recommendations for managing PNH in patients with AA in the Asia-Pacific region. Plasma/serum lactate dehydrogenase (LDH) levels and reticulocyte count should be measured with every blood test. PNH clone size should be monitored regularly by flow cytometry, with on-demand testing in the event of a rise in LDH level ± reticulocyte count or development of symptoms such as thrombosis. Monitoring for PNH clones can guide the choice of initial AA treatment, although flow cytometry has resource implications which may present a challenge in some Asia-Pacific countries. The treatment of patients with both PNH and AA depends on which condition predominates; following PNH treatment guidelines if hemolysis is the main symptom and AA treatment guidelines if bone marrow failure is severe (regardless of whether hemolysis is mild or moderate). The expert panel's recommendations on the monitoring and treatment of PNH in patients with AA are practical for healthcare systems in the Asia-Pacific region.

bone cancer

The Link Between the Gut Microbiome and Bone Metastasis.

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.

bone cancer

Characterization and Experimental Use of Multiple Myeloma Bone Marrow Endothelial Cells and Progenitors.

Multiple myeloma (MM) is a plasma cell malignancy that resides within the bone marrow microenvironment, relying heavily on interactions with its cellular components. Among these, endothelial cells (ECs) play a pivotal role in MM progression and the development of therapeutic resistance. In this study, we analyzed publicly available single-cell RNA sequencing data to identify unique pathway activations distinguishing ECs from MM patients and healthy donors. We developed a novel protocol to isolate and culture endothelial progenitor cells (EPCs) and ECs directly from MM patient bone marrow, demonstrating their ability to promote myeloma cell proliferation. Validation studies confirmed that these MM-derived ECs exhibit angiogenic potential as well as the expression of characteristic endothelial lineage markers. These findings underscore the critical role of bone marrow ECs in the MM tumor microenvironment and highlight potential new therapeutic targets to disrupt MM progression.

bone cancer

The Interplay Between the

High-grade osteosarcoma (OS) is the most common primary bone tumor mainly affecting children and young adults. First-line treatment consists of neo-adjuvant chemotherapy with doxorubicin, cisplatin, and methotrexate and surgery. The mean long-term survival rate for localized disease at diagnosis is 65-70%, dropping down to 20% when metastases are present at diagnosis. Therefore, curing OS is a clinical challenge, particularly for patients that do not respond to standard treatments.

bone cancer

Novel Gene Biomarkers Specific to Human Mesenchymal Stem Cells Isolated from Bone Marrow.

In this paper, we present a comparative analysis of the transcriptomic profile of three different human cell types: hematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stem cells (MSCs) and fibroblasts (FIBs). The work aims to identify unique genes that are differentially expressed as specific markers of bone marrow-derived MSCs, and to achieve this undertakes a detailed analysis of three independent datasets that include quantification of the global gene expression profiles of three primary cell types: HSCs, MSCs and FIBs. A robust bioinformatics method, called

bone cancer

Psoriasis: The Versatility of Mesenchymal Stem Cell and Exosome Therapies.

Mesenchymal stem cells (MSCs) are multilineage differentiating stromal cells with extensive immunomodulatory and anti-inflammatory properties. MSC-based therapy is widely used in the treatment of various pathologies, including bone and cartilage diseases, cardiac ischemia, diabetes, and neurological disorders. Along with MSCs, it is promising to study the therapeutic properties of exosomes derived from MSCs (MSC-Exo). A number of studies report that the therapeutic properties of MSC-Exo are superior to those of MSCs. In particular, MSC-Exo are used for tissue regeneration in various diseases, such as healing of skin wounds, cancer, coronary heart disease, lung injury, liver fibrosis, and neurological, autoimmune, and inflammatory diseases. In this regard, it is not surprising that the scientific community is interested in studying the therapeutic properties of MSCs and MSC-Exo in the treatment of psoriasis. This review summarizes the recent advancements from preclinical and clinical studies of MSCs and MSC-Exo in the treatment of psoriasis, and it also discusses their mechanisms of therapeutic action involved in the treatment of this disease.

bone cancer

Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches.

Bone is the preferential site of metastasis for the most common tumors, including breast cancer. On the other hand, osteosarcoma is the primary bone cancer that most commonly occurs and causes bone cancer-related deaths in children. Several treatment strategies have been developed so far, with little or no efficacy for patient survival and with the development of side effects. Therefore, there is an urgent need to develop more effective therapies for bone primary tumors and bone metastatic disease. This almost necessarily requires the use of in vivo animal models that better mimic human pathology and at the same time follow the ethical principles for the humane use of animal testing. In this review we aim to illustrate the main and more suitable in vivo strategies employed to model bone metastases and osteosarcoma. We will also take a look at the recent technologies implemented for a partial replacement of animal testing.

bone cancer

Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML).

Despite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30-40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared to FLA-IDA. In this retrospective single-center analysis, we investigated the efficacy and safety of dose-reduced FLA-IDA with and without venetoclax to minimize the risk of infectious complications and excessive myelosuppression; Methods: Between 2011 and 2023, 89 R/R AML patients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m

bone cancer

Liposarcoma: A Journey into a Rare Tumor's Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies.

Sarcomas are a heterogeneous group of neoplasms that develop from bone and soft tissue. Approximately 80% of sarcomas affect soft tissue, with liposarcoma being one of the most common types, accounting for approximately 13-20% of all soft-tissue sarcomas. Per the World Health Organization, liposarcoma can be broadly classified into four different subtypes based on histologic examination: well-differentiated liposarcoma (WDLS)/atypical lipomatous tumors (ALT), dedifferentiated liposarcoma (DDLS), myxoid liposarcoma (MLS), and pleomorphic liposarcoma (PLS). WDLS/ALT is the most common liposarcoma subtype, accounting for approximately 31-33% of liposarcomas; DDLS accounts for 20%; MLS accounts for 19%; and PLS, the least common subtype, represents 7-8% of liposarcomas. Sarcoma diagnosis is challenging because of its rarity, intrinsic complexity, and diagnostic technological complexity. Sarcomas are misdiagnosed in approximately 30% of cases, leading to delays in diagnosis and access to appropriate therapy and clinical trials. Furthermore, treatment options are limited for those diagnosed with liposarcoma. This review discusses the epidemiology, pathology, and treatment options currently available for liposarcoma.

bone cancer

Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors.

The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse.

bone cancer

CD47 in Osteosarcoma: Correlation with Metastasis and Macrophage-Mediated Phagocytosis.

CD47 is expressed on cell surfaces and acts as a "don't eat me" signal by interacting with signal-regulatory protein-α on the macrophage surface. Some cancer cells express CD47 protein and can evade macrophage phagocytosis. Herein, we evaluated the feasibility of targeting CD47 for osteosarcoma by analyzing its expression patterns, clinicopathological correlations, and immunotherapeutic potential. We performed a retrospective analysis on 24 biopsy samples from patients with osteosarcoma to investigate correlations between CD47 protein positivity and clinicopathological characteristics. CD47 protein expression was detected in 20.8% of the biopsy samples. CD47 positivity correlated with metastasis at diagnosis. Patients with CD47-positive tumors were older than those with CD47-negative tumors. However, CD47 protein expression was not associated with sex, tumor size, or histologic response to preoperative chemotherapy. In vitro, CD47 antibody (B6H12) did not affect osteosarcoma cell viability or apoptosis. In a wound-healing assay, CD47 inhibited the migration of osteosarcoma cells. Differentiated macrophages exhibited higher phagocytic activity against osteosarcoma cells when pretreated with B6H12 compared with the isotype control. Our preliminary data suggest a possible interaction between CD47 protein and macrophage phagocytosis in osteosarcoma metastasis. A better understanding of the role of CD47 is necessary to develop an innovative immunotherapeutic approach against osteosarcoma.

bone cancer

Dysregulation of miRNAs in Soft Tissue Sarcomas.

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas-a diverse group of malignant tumors affecting soft tissues and bone sarcomas-miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.

bone cancer

Tellurium-Doped Bioactive Glass Induces Ferroptosis in Osteosarcoma Cells Regardless of FSP1.

Human osteosarcoma (OS) is a rare tumor predominantly affecting long bones and characterized by a poor prognosis. Currently, the first line of intervention consists of the surgical resection of primary tumors combined with radiotherapy and chemotherapy, with a profound impact on the patient's life. Since the surgical removal of OS frequently results in a large resection of bones, the use of biomaterials to sustain the stability of the remaining tissue and to stimulate bone regeneration is challenging. Moreover, residual neoplastic cells might be responsible for tumor recurrence. Here, we explored the potential of tellurium-ion-doped bioactive glass as a novel therapeutic intervention to both eradicate residual malignant cells and promote bone regeneration. Bioactive glass (BAG) has been extensively studied and employed in the field of regenerative medicine due to its osseointegration properties and ability to improve bone tissue regeneration. We found that the incorporation of tellurium (Te) in BAG selectively kills OS cells through ferroptosis while preserving the viability of hBMSCs and stimulating their osteodifferentiation. However, the mechanism of Te toxicity is still unclear: (i) Te-BAG generates lipid-ROS through LOXs activity but not iron overload; (ii) Te-dependent ferroptosis is mediated by GPX4 down-regulation; and (iii) the anti-ferroptotic activity of FSP1 is abrogated, whose expression confers the resistance of OS to the canonical induction of ferroptosis. Overall, our data show that Te-doped bioglass could represent an interesting biomaterial with both pro-ferroptotic activity towards residual cancer cells and pro-osteoregenerative activity.

bone cancer

Pediatric Bone Tumors: Location and Age Distribution of 420 Cases.

One of the most important diagnostic tools in bone tumors is X-rays. Preliminary and, in the case of some benign lesions, definitive diagnoses are formed using this basic tool. Part of the decision making in this stage is based on statistical probability using the patient's age, as well as the incidence and predilection sites of different entities. The information used today is based on older and fragmented data. To verify the underlying principles, we retrospectively evaluated all bone tumors in children and adolescents treated by our tertiary center in the last 20 years.

bone cancer

An Atypical Case of Pancreatic Cancer with Mesenchymal Differentiation in a Patient with Primary Lung Adenocarcinoma: Insights into Tumor Biology and Novel Therapeutic Pathways.

bone cancer

Bone Matrix-forming Tumors.

Bone matrix-forming tumors are a group of neoplasms that exhibit differentiation toward any stage of osteoblast development. Their clinicopathologic features can resemble one another, yet their clinical management may vary significantly. Therefore, appropriate treatment requires accurate diagnosis, which can be challenging, especially with limited biopsy specimens. Recently, the driver genetic alterations underlying these neoplasms have been discovered, and their protein products can be targeted for diagnosis and therapy. Herein, we summarize the recent advances in our understanding of bone matrix-forming tumors and emphasize the integration of molecular genetics into their conventional clinicopathologic evaluation.

bone cancer

Giant Cell-Rich Tumors of the Skeleton.

The accurate diagnosis of giant cell-rich tumors of bone is challenging, especially in limited tissue samples. This diverse group of neoplasms have similar and often ambiguous clinical presentations, radiologic features, and morphologic characteristics. During the last decade, the discovery of pathogenic recurrent genetic alterations has allowed the development of immunohistochemical surrogate markers and FISH assays that can help differentiate the entities of this broad group from one another. The correct diagnosis of these neoplasms is essential in the management of the affected patients.

bone cancer

The impact of qualitative [18F]FDG PET/CT in predicting clinical outcomes of post-surgical differentiated thyroid cancer patients with elevated thyroglobulin and negative radioiodine whole-body scan.

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bone cancer

IL-10RA governor the expression of IDO in the instruction of lymphocyte immunity.

Indoleamine 2,3-dioxygenase (IDO) impairs anti-pathogen and anti-tumour immunity. Mesenchymal stem cells (MSCs) modulate immunity via IDO but also suppress IFN-γ. While MSC IDO induction by IFN-γ is established, other drivers in this immunosuppressive setting remain unknown.

bone cancer

Long-Circulating and Targeted Liposomes Co-loading Cisplatin and Mifamurtide: Formulation and Delivery in Osteosarcoma Cells.

Osteosarcoma (OS) is one of the most common primary bone sarcoma with high malignant degree and poor prognosis, for which there is an urgent need to develop novel therapeutic approaches. Recent research has revealed that mifamurtide significantly improved the outcome of OS patients when combined with adjuvant chemotherapy drugs including cisplatin (DDP). The present study aimed to construct a drug delivery system co-loading DDP and mifamurtide. Long-circulating targeted liposomes co-loading DDP and mifamurtide were constructed with Soy lecithin (SPC), cholesterol (Chol) and 1,2-distearoylglycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)] (DSPE-PEG), modified with MMP14 targeting peptide BCY-B in the surface of liposomes. In addition to characterization, the cellular uptake, endocytosis pathway and inhibition on cell viability, migration, invasion and cell apoptosis of MG-63 cells were explored. The constructed liposomal delivery possessed the basic characteristics of liposomes and showed high affinity to MG-63 cells, resulting in high uptake efficiency in MG-63 cells. The endocytosis might be involved in multiple pathways including caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis, dependently on energy. The constructed long-circulating targeted liposomes co-loading DDP and mifamurtide significantly inhibited the cell viability, migration, invasion and cell apoptosis of MG-63 cells, improving the antitumor effect of DDP and mifamurtide in vitro. The constructed liposomal delivery system is suitable for co-loading DDP and mifamurtide to achieve active tumor targeting, supplying a new strategy for the treatment of OS.

bone cancer

Tissue-engineered patient-derived osteosarcoma models dissecting tumour-bone interactions.

Osteosarcoma is the most common malignant bone tumor, primarily affecting children and young adults. For these young patients, the current treatment options for osteosarcoma impose considerable constraints on daily life with significant morbidity and a low survival rate. Despite ongoing research efforts, the 5-year survival rate of first-diagnosed patients without metastases has not changed in the past four decades. The demand for novel treatments is currently still unmet, in particular for effective second-line therapy. Therefore, there is an urgent need for advanced preclinical models and drug-testing platforms that take into account the complex disease characteristics, the high heterogeneity of the tumour and the interactions with the bone microenvironment. In this review, we provide a comprehensive overview about state-of-the-art tissue-engineered and patient-specific models for osteosarcoma. These sophisticated platforms for advanced therapy trials aim to improve treatment outcomes for future patients by modelling the patient's disease state in a more accurate and complex way, thus improving the quality of preclinical research studies.

bone cancer

Interdisciplinary approach to prosthetic rehabilitation of a bilateral maxillectomy with a free fibula flap and zygomatic implants in a childhood cancer survivor: A clinical report.

Rehabilitation of a bilateral maxillectomy defect is highly challenging. Reconstruction with a free-fibula flap provides optimal coverage and allows prosthetic rehabilitation with dental implant-retained prostheses. Deficient height of the fibula bone, especially in the pediatric population or in young adults, may complicate the rehabilitation process. This report describes an interdisciplinary approach to the rehabilitation of a bilateral maxillectomy defect in a childhood cancer survivor using an innovative modification of an existing protocol. Patient acceptance and the quality-of-life outcome were high after secondary placement of bilateral zygomatic and conventional implants in the fibula flap, providing excellent anchorage for a bar-LOCATOR overdenture prosthesis.

bone cancer

Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma: Results From the Korean Renal Cancer Study Group Database.

In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.

bone cancer

A machine learning-based analysis of nationwide cancer comprehensive genomic profiling data across cancer types to identify features associated with recommendation of genome-matched therapy.

The low probability of identifying druggable mutations through comprehensive genomic profiling (CGP) and its financial and time costs hinder its widespread adoption. To enhance the effectiveness and efficiency of cancer precision medicine, it is critical to identify patient characteristics that are most likely to benefit from CGP.

bone cancer

Isolated plasmacytoma of the breast: A rare case report.

Solitary plasmacytoma of the breast is an extremely rare manifestation of plasma cell neoplasms, predominantly seen in the bone marrow and commonly associated with multiple myeloma. When it occurs as an isolated lesion in the breast, it presents unique diagnostic and therapeutic challenges due to its rarity and clinical similarity to other breast conditions.

bone cancer

Milk-Derived Extracellular Vesicles: A Novel Perspective on Comparative Therapeutics and Targeted Nanocarrier Application.

Milk-derived extracellular vesicles (mEVs) are emerging as promising therapeutic candidates due to their unique properties and versatile functions. These vesicles play a crucial role in immunomodulation by influencing macrophage differentiation and cytokine production, potentially aiding in the treatment of conditions such as bone loss, fibrosis, and cancer. mEVs also have the capacity to modulate gut microbiota composition, which may alleviate the symptoms of inflammatory bowel diseases and promote intestinal barrier integrity. Their potential as drug delivery vehicles is significant, enhancing the stability, solubility, and bioavailability of anticancer agents while supporting wound healing and reducing inflammation. Additionally, bovine mEVs exhibit anti-aging properties and protect skin cells from UV damage. As vaccine platforms, mEVs offer advantages including biocompatibility, antigen protection, and the ability to elicit robust immune responses through targeted delivery to specific immune cells. Despite these promising applications, challenges persist, including their complex roles in cancer, effective antigen loading, regulatory hurdles, and the need for standardized production methods. Achieving high targeting specificity and understanding the long-term effects of mEV-based therapies are essential for clinical translation. Ongoing research aims to optimize mEV production methods, enhance targeting capabilities, and conduct rigorous preclinical and clinical studies. By addressing these challenges, mEVs hold the potential to revolutionize vaccine development and targeted drug delivery, ultimately improving therapeutic outcomes across various medical fields.

bone cancer

Anti-Diabetic Effects of Oleuropein.

bone cancer

A Murine Model of Non-Wear-Particle-Induced Aseptic Loosening.

The current murine models of peri-implant osseointegration failure are associated with wear particles. However, the current clinical osseointegration failure is not associated with wear particles. Here, we develop a murine model of osseointegration failure not associated with wear particles and validate it by comparing the cellular composition of interfacial tissues with human samples collected during total joint arthroplasty revision for aseptic loosening.

bone cancer

Soft Tissue Reconstruction and Integration to Implant After Bone-Tumor Resection: A Current Concept Review.

With the advancements in chemotherapy for malignant bone tumors, the number of patients eligible for limb salvage surgery has increased. Surgeons face a subsequent challenge in limb-sparing resection due to the need for reconstructing soft tissue coverage. The aim of this review is to focus on the present state of the field in these areas, highlighting recent advancements.

bone cancer

Brain Metastasis in Pediatric Patients with Osteosarcoma.

Brain metastases in pediatric osteosarcoma are infrequent but associated with a dire prognosis.

bone cancer

Clinical Outcome Patterns of Use of Radium-223 in Patients with Metastatic Castration-Resistant Prostate Cancer.

bone cancer

Bone Mineral Density, C-Terminal Telopeptide of Type I Collagen, and Osteocalcin as Monitoring Parameters of Bone Remodeling in CML Patients Undergoing Imatinib Therapy: A Basic Science and Clinical Review.

Chronic myeloid leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a tyrosine kinase inhibitor (TKI), can be effectively used as therapy for CML. However, Imatinib can affect bone turnover thus having clinical implications on the bones of CML patients undergoing long-term Imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving Imatinib still need further study. A combination of imaging techniques such as bone mineral density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving Imatinib.

bone cancer

Preoperative Evaluation of Lingual Cortical Plate Thickness and the Anatomical Relationship of the Lingual Nerve to the Lingual Cortical Plate via 3T MRI Nerve-Bone fusion.

To evaluate the reliability of 3 T MRI nerve-bone fusion in assessing the lingual nerve (LN) and its anatomical relationship to the lingual cortical plate prior to the impacted mandibular third molar (IMTM) extraction.

bone cancer

Breast Cancer Subtype-Specific Organotropism is Dictated by FOXF2-Regulated Metastatic Dormancy and Recovery.

Breast cancer subtypes display different metastatic organotropism. Identification of the mechanisms underlying subtype-specific organotropism could help uncover potential approaches to prevent and treat metastasis. Herein, we found that FOXF2 promoted the seeding and proliferative recovery from dormancy of luminal breast cancer (LumBC) and basal-like breast cancer (BLBC) cells in the bone by activating the NF-κB and BMP signaling pathways. Conversely, FOXF2 suppressed the seeding and proliferative recovery of BLBC cells in the lung by repressing the TGF-β signaling pathway. FOXF2 directly upregulated RelA/p65 transcription and expression in LumBC and BLBC cells by binding to the RELA proximal promoter region, and RelA/p65 bound to the FOXF2 proximal promoter region to upregulate expression, forming a positive feedback loop. Targeting the NF-κB pathway efficiently prevented the metastasis of FOXF2-overexpressing breast cancer cells to the bone, while inhibiting TGF-β signaling blocked the metastasis of BLBC with low FOXF2 expression to the lung. These findings uncover critical mechanisms of breast cancer subtype-specific organotropism and provide insight into precision assessment and treatment strategies.

bone cancer

Solitary Fibrous Tumor of the Mandible.

A 41-year-old woman presented with a facial asymmetry in the mental region and a painful, well-circumscribed, tender mass in the right lower buccal vestibule, associated with extensive ill-defined bone rarefaction with subtle cortical bone resorption. Microscopically, a proliferation of bland spindle cells interspersed with collagen fibers and prominent staghorn-like blood vessels was observed. Immunohistochemical analysis revealed strong positivity for CD34, Bcl-2, CD99, and STAT-6, confirming the diagnosis of Solitary Fibrous Tumor (SFT). Conservative surgical enucleation was performed, and 4 years later, recurrence was observed with extensive bone involvement and moth-eaten margins resembling a malignant tumor. SFT is a distinctive spindle cell tumor of fibroblastic differentiation, characterized by prominent branching staghorn-like vessels and a specific NAB2::STAT6 gene fusion. We herein contribute with a central SFT of the mandible with recurrent behavior and radiographic appearance suggesting malignancy.

bone cancer

Letter to the Editor: EANM position paper on challenges and opportunities of full-ring 360° CZT bone imaging: it's time to let go of planar whole-body bone imaging.

No abstract found

bone cancer

Shifting the Landscape of Spine and Non-Spine Bone Metastases: A Review of Stereotactic Body Radiotherapy.

Both spine and nonspine bone metastases are frequent sites of spread from solid organ malignancies. As bone metastases frequently cause significant morbidity for patients, it is critical to offer a treatment that can achieve rapid and durable symptomatic relief and local control, without being associated with serious risks of toxicity. Conventional palliative radiation therapy has a key treatment component in the multidisciplinary management of these patients; however, over the past decade, it has evolved to routinely deliver high biologically effective doses with precision in the form of stereotactic body radiation therapy. This change in paradigm is a result of the shifting landscape in cancer care, such that short-term pain relief is no longer the sole therapeutic aim for selected patients, and durable symptom relief and local tumor control are the goals. This review discusses the randomized prospective evidence, ongoing trials, approach to surveillance imaging, and treatment delivery for stereotactic body radiation therapy, to both spine and nonspine bone metastases, with a specific section on sacral metastases.

bone cancer

VAV1 regulates cell growth in cutaneous T-cell lymphoma via the BAMBI/BMF signalling pathway.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of tumours originating from the cutaneous infiltration of clonal malignant T cells. VAV1 is a hematopoietic signal transducer and an oncogene in various cancers, however, the relevance of aberrant VAV1 expression in CTCL pathogenesis remains unclear. This study aimed to evaluate the expression pattern and underlying pathogenic mechanisms of VAV1 in CTCLs. The expression of VAV1 in CTCL tumour tissues and benign inflammatory dermatoses skin samples were examined by immunohistochemistry. CTCL cells were also transfected with lentiviral-based VAV1 gene knockdown vectors, and the effects of VAV1 knockdown on cell proliferation and apoptosis in CTCL cells was determined by MTS assay and flow cytometry. Transcriptomic sequencing was performed to detect the direct downstream targets of VAV1 silencing. RT-qPCR and western blot analysis were used to verify the transcriptomic analysis results. High expression of VAV1 was observed in CTCL tissues (n = 25) compared with benign inflammatory dermatoses (n = 23) using immunohistochemistry. VAV1 knockdown in two CTCL cell lines decreased cell proliferation and increased the percentage of apoptotic cells. Moreover, messenger RNA and protein expression of Bcl-2-modifying factor was increased, whereas that of bone morphogenetic proteins and activin membrane-bound inhibitor was downregulated in VAV1-silenced CTCL cells. VAV1 silencing induces apoptosis and inhibits cell growth, which is associated with upregulation of Bcl-2 modifying factor and downregulation of bone morphogenetic proteins and activin membrane-bound inhibitor. Therefore, VAV1 may be a potential tumour marker and therapeutic target for CTCLs.

bone cancer

Efficacy and safety analysis of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in the treatment of osteosarcoma: a systematic review and meta-analysis.

Osteosarcoma is a rare and aggressive bone cancer, with targeted therapy using VEGFR-TKIs (Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors) emerging as a promising treatment option.

bone cancer

Targeting RGMb interactions: Discovery and preclinical characterization of potent anti-RGMb antibodies blocking multiple ligand bindings.

Therapeutic efficacy with durable responses has been demonstrated with several antibody drugs that block key immune checkpoint receptors, including PD-1, PD-L1, and CTLA-4. Despite the success of these drugs, a substantial proportion of patients do not benefit. Targeting multiple inhibitory pathways simultaneously to augment anti-tumor immunity has proven to be a promising approach. The emergence of Repulsive Guidance Molecule b (RGMb), a ligand for PD-L2, as a novel co-inhibitory pathway in T cells, together with its regulation by the gut microbiome, encouraged the discovery and development of fully human anti-RGMb antibodies. Here, we describe phage display-derived monoclonal antibodies (mAbs) 2C11 and 5C10 that bind human RGMb with high affinities of 1.4 nM and 0.72 nM, respectively. Both mAbs 2C11 and 5C10 potently inhibited RGMb interaction with PD-L2. MAb 2C11 effectively inhibited RGMb interaction with bone morphogenetic proteins 2 and 4 (BMP2-4), while leaving RGMb interaction with Neogenin 1 (Neo1) unaffected. Conversely, mAb 5C10 disrupted RGMb interaction with Neo1 while maintaining RGMb binding to BMP2-4. These findings map the 2C11 epitope at the membrane-distal N-terminal region of RGMb, which coincides with both PD-L2- and BMP2-4-binding sites. The PD-L2 binding interface is likely positioned between RGMb's N-terminal BMP-binding and C-terminal Neo1-binding regions. The in vivo activity of mAb 2C11 in combination with anti-PD-1 or anti-PD-L1 was tested in MC38 and B16-OVA cancer models and demonstrated synergistic effects by significantly enhancing anti-tumor responses. These properties make mAb 2C11 a promising candidate for therapeutic use to overcome immune checkpoint inhibitor resistances, warranting further exploration in clinical settings.

bone cancer

Synergy Effects of HPV E6-E7 Encoding mRNA and Nucleic Acid Immunostimulators Improve Therapeutic Potential in TC-1 Graft Tumor.

Cervical cancer is the second most common cancer among women globally and the most prevalent cancer in developing countries, which was caused by human papillomavirus (HPV) infection. Messenger RNA (mRNA) vaccines have opened up new avenues for vaccine development and pandemic preparedness with potent scalability, which may possess the potential antitumor effects of an mRNA-HPV therapeutic vaccine containing nononcogenic E6 and E7 proteins. Here, we reported a lipid nanoparticle (LNP) plus nucleic acid immunostimulators (CPG 1018 and Poly I:C) mRNA vaccine platform. The LNP-CPG 1018 capsulated HPV E6-E7 mRNA significantly promoted the maturation of bone marrow-derived dendritic cells (BMDC) in vitro and were capable of efficiently migrating to lymph nodes (LN) in vivo. In TC-1 tumor-bearing mice, the subcutaneous immunization of LNP-CPG 1018 capsulated HPV E6-E7 mRNA elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In conclusion, the LNP-CPG 1018 system is a promising delivery platform for facilitating the development of HPV E6-E7 mRNA cancer vaccines.

bone cancer

Hsa_circ_0078767 Enhances Osteosarcoma Chemoresistance to Doxorubicin Through the Regulation of the miR-188-3p/GPX4 Axis.

Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS.

bone cancer

Bone Marrow Failure due to Aplastic Anemia, Associated With Serous Fat Atrophy, and Treated With Allogeneic, Haploidentical Stem Cell Transplantation: A Case Report.

We describe the case of a 27-year-old male, previously healthy though with a social history notable for recreational cocaine use, who developed bone marrow failure due to aplastic anemia (AA) with associated serous fat atrophy (SFA). After the SFA was corrected with nutritional supplementation, the patient underwent successful allogeneic, haploidentical stem cell transplantation with a regimen designed to treat AA. To our knowledge, this is the first case of hematopoietic stem cell transplantation (HSCT) performed following correction of SFA. Herein we propose our novel hypothesis that SFA, once resolved, is not a contraindication to stem cell transplantation, which we believe adds valuable insight toward an improved understanding of nutrition's role in HSCT. Additionally, the AA is thought to be toxin-induced and specifically levamisole-mediated after exposure to levamisole-adulterated cocaine. We highlight potential connections between levamisole, AA, and SFA and call for further efforts to understand these relationships-especially as the use of levamisole as a cocaine adulterant continues to rise across the globe.

bone cancer

The skeleton: an overlooked regulator of systemic glucose metabolism in cancer?

Recent discoveries demonstrated the skeleton's role as an endocrine organ regulating whole-body glucose homeostasis. Glucose metabolism is critical for rapid cell proliferation and tumour growth through increasing glucose uptake and fermentation of glucose to lactate despite being in an aerobic environment. This hypothesis paper discusses emerging evidence on how bones can regulate whole-body glucose homeostasis with potential to impact on tumour growth and proliferation. Moreover, it proposes a clinical link between bone glucose metabolism and prognosis of cancer based on recent clinical trial data. Targeting metabolic pathways related with classic glucose metabolism and also bone metabolism, novel methods of cancer therapy and treatment could be developed. This paper objective is to highlight the need for future research on this altered metabolism with potential to change future management of cancer patients.

bone cancer

Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report.

A 60-year-old woman with bilateral lower extremity oedema for several days was admitted to the hospital on 21 November 2023. Previously, after receiving rectal cancer resection in February 2023, she had been receiving drug chemotherapy, during which she had normal urinalysis and renal function. However, 10 days before admission, after the drug regimen was adjusted to tislelizumab + fruquintinib, she developed bilateral lower extremity oedema with foamy urine; this was later extended to facial oedema. After a histologic examination of renal biopsy, it was judged as drug-induced glomerular microangiopathy (GMA) with focal segmental glomerulosclerosis-like lesions accompanied by immune complex-mediated glomerulonephritis. The condition was controlled by stopping the anti-tumour drug, lowering glucose with linagliptin, and providing renal protection with Nephritis Rehabilitation Tablets, and the patient recovered well at the follow-up visit after 6 months. This case may be GMA induced by tislelizumab or fruquintinib and was examined in this study.

bone cancer

GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment.

Bone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC.

bone cancer

VprBP regulates osteoclast differentiation via an epigenetic mechanism involving histone H2A phosphorylation.

Bone remodeling is a continuous and balanced process which relies on the dynamic equilibrium between osteoclastic bone resorption and osteoblastic bone formation. During osteoclast differentiation, pro-osteoclastogenic and anti-osteoclastogenic genes are selectively targeted by positive and negative transcription regulators, respectively. VprBP, also known as DCAF1, is a recently identified kinase and plays an important role in driving epigenetic gene silencing and oncogenic transformation. However, nothing is currently known about a possible involvement of VprBP in signaling pathways that regulate other cellular processes.

bone cancer

Liu-Shen-Wan inhibits PI3K/Akt and TRPV1 signaling alleviating bone cancer pain in rats.

Patients with advanced-stage cancers often suffer from severe pain caused by bone metastasis and destruction, for which effective treatment options are limited. Liu-Shen-Wan (LSW) is a widely recognized herbal formula utilized for pain relief. This study aims to elucidate the effects of LSW on bone cancer pain (BCP). In this study, the pharmacology of LSW on BCP was screened by network pharmacology. A BCP model was conducted using Walker 256 cells. Paw withdrawal threshold and paw withdrawal latency were employed as measures to assess the pain threshold in rats. The pathways and cell types of LSW against BCP were explored. Next, the impact of LSW on Walker 256 cells was evaluated, and UPLC-MS was utilized to identify the active ingredients of LSW. Furthermore, the effects of the key active ingredient, Bufalin, on the BCP rats were evaluated. There were 275 shared targets between LSW and BCP, which were enriched in neural tissue ligand-receptor interaction pathway. LSW increased pain threshold and decreased inflammatory cytokines levels in BCP rats by inhibiting PI3K/Akt and transient receptor potential vanilloid 1 (TRPV1) signaling through astrocytes and microglia. LY294002 further alleviated BCP in rats, while the effects were reversed after treatment with insulin-like growth factor 1 (IGF-1). Both LSW and its active ingredient Bufalin were shown to inhibit the viability and migration of Walker 256 cells and induce apoptosis. Bufalin appears to be the key active ingredient of LSW and exerts its pain-relieving effects by suppressing PI3K/Akt and TRPV1 signaling in BCP.

bone cancer

A multifactorial risk scoring system for the prediction of early relapse in CMML patients with allo-HSCT: a nationwide representative multicenter study.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy and the only curable therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, allo-HSCT is not appropriate for all CMML patients, and relapse is the leading cause of treatment failure. This project conducted a nationwide multicenter real-world study to develop a novel prediction scoring system for early relapse. A total of 238 CMML patients from twenty-seven medical centers treated with allo-HSCT, and 307 adult patients with CMML who underwent allo-HSCT in a publicly available research dataset from the Center for International Blood and Marrow Transplantation Registry (CIBMTR) database were included. Independent prognostic factors for the early relapse of CMML posttransplantation were identified according to competing risk regression methods. Four prognostic factors were identified: bone marrow blasts >10% (hazard ratio [HR], 4.262; P = 0.014), age >60 years (HR, 6.221; P = 0.007), hemoglobin level <100 g/L (HR, 3.695; P = 0.004), and non TET2 gene mutation (HR, 3.425; P = 0.017). A risk-grading scoring system was developed based on the regression coefficients and patients were stratified into low-risk (0-1 point), intermediate-risk (1.5-2 points) and high-risk ( > 2 points) groups. The validated internal c-statistic was 0.767 (95% confidence interval [CI], 0.674-0.860), and the external c-statistic was 0.769 (95% CI, 0.703-0.836). In the derivation cohort, the cumulative incidence rates of early relapse in the low-risk, intermediate-risk, and high-risk groups were 1.35% (95% CI: 1-4%), 10.40% (95% CI: 4-16%), and 29.54% (95% CI: 16-39%) (P < 0.001), respectively. This scoring system can be utilized to early identification of patients at a high risk of relapse and contributing to the implementation of urgent medical support.

bone cancer

A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia.

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases. We identified a bone marrow progenitor (BMP)-like leukemia subpopulation associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL and revealed that NOTCH1 mutations additively drive T-ALL blasts away from the BMP-like state. Through in silico and in vitro drug screenings, we identified a therapeutic vulnerability of BMP-like blasts to apoptosis-inducing agents including venetoclax. Collectively, our study establishes multiomic signatures for rapid risk stratification and targeted treatment of high-risk T-ALL.

bone cancer

Bone marrow progenitor-like cells against leukemia cure.

No abstract found

bone cancer

Efficacy and safety of the combination of decitabine and CHAG priming regimen in the relapsed or refractory acute myeloid leukemia.

Efficacy and safety analysis of the combination of decitabine priming followed by CHAG chemotherapy in treatment of relapsed/refractory(r/r) acute myeloid leukemia (AML). Between January 2013 and June 2020, 62 r/r AML patients in our center receiving therapy including combination of decitabine and CHAG pre-excitation regimen were enrolled. Primary objectives were overall response (ORR: complete remission + partial remission), adverse events, overall survival (OS) and relapse-free survival (RFS). There were 46 patients (74.2%) with complete remission (CR), 5 patients (8.06%) with partial remission (PR), ORR was 82.2%. Main adverse events were bone marrow suppression, fever and infection, and no chemotherapy-related deaths occurred. The median RFS time was 4.3 months (0.3 ~ 65 months), and median OS time was 7.75 months (1 ~ 66.3 months). Decitabine priming followed by CHAG regimen is effective and tolerated in patients with r/r AML, and can be used as a salvage treatment for patients with r/r AML.

bone cancer

scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes.

A population of CD133

bone cancer

Using additive manufacturing for craniocervical reconstruction in traditionally challenging cases.

Retrospective case series. The aim of this study was to evaluate the clinical outcomes and effectiveness of using 3D printed implants in upper cervical spine and occipitocervical junction surgery. C2 primary tumor patients who required axial en bloc resection and other patients who required partial bone decompression using customized 3D printed implants or fixation devices for surgery were included. Evaluate the stability and surgical outcomes of 3D printed implants through perioperative and follow-up period. Five tumor patients underwent reconstruction using customized 3D printed artificial vertebral bodies, while another five patients with atlantoaxial joint dislocation underwent reduction and decompression using customized 3D printed internal fixation devices. The postoperative imaging results showed that the 3D printed structures had good immediate stability and had no signs of displacement or subsidence. Follow up showed that all five cases of vertebral body reconstruction had achieved fusion. Only one patient died one month after surgery due to infection and respiratory difficulties. Other patients showed excellent improvement in neurological function in follow up. The use of 3D printed implants in surgery involving the occipitocervical area is a feasible and reliable alternative choice. It is a valuable attempt for complex atlantoaxial dislocation that cannot be treated with conventional instruments. 3D printed implants can improve the safety and accuracy of surgery, provide good immediate stability, have a low incidence of subsidence, fewer related complications during the follow-up period.

bone cancer

Wnt/β-catenin Promotes Cementum Apposition in Periodontal Regeneration.

Regeneration of periodontal tissue, particularly the cementum-periodontal ligament (PDL)-bone complex, has long been challenging because the differentiation kinetics of cells and the molecular pathways contributing to the regeneration process are largely unknown. We aimed to evaluate the cell behavior and molecular pathways that contribute to periodontal tissue regeneration in vivo. We analyzed the process of periodontal tissue regeneration through subrenal capsule transplantation of immediately extracted molars in mice. We showed that the regenerated periodontal tissue in the subrenal capsule was morphologically comparable to the intact periodontal tissue, with increased cellular cementum thickness in the apical region. Cell tracing analysis revealed that the cells comprising the regenerated periodontal tissue were derived from transplanted teeth and were indispensable for periodontal tissue regeneration, whereas recipient mouse-derived cells partly contributed to angiogenesis. Bioinformatics analysis based on the gene expression profile in the transplanted teeth indicated that Wnt/β-catenin signaling is involved in periodontal tissue regeneration, which was further confirmed through β-catenin immunohistochemistry. Moreover, the constitutive activation of β-catenin in the cells of transplanted teeth was found to promote accelerated cellular cementum apposition, while the conditional knockout of β-catenin in the cells of transplanted teeth suppressed cellular cementum apposition. Notably, the manipulation of Wnt/β-catenin signaling did not interfere with the bone-PDL-cementum complex, while endogenous osteoclast activity was affected in bone. Our results demonstrated the essential roles of endogenous PDL cells in periodontal tissue regeneration and that Wnt/β-catenin signaling is involved in this process, particularly cellular cementum apposition. Hence, controlling this pathway could promote cementum regeneration, which is a critical process for the regeneration of the cementum-PDL-bone complex. This study provides novel insights into cell behavior and signaling pathways that will advance practical periodontal tissue regeneration.

bone cancer

Upper limb salvage with massive intercalary allograft for humeral chondrosarcoma.

chondrosarcoma is a high-grade malignant tumor composed of mesenchymal cells with cartilage differentiation. It most frequently appears in the bones of the pelvis, the femur, and the humerus. The main management method is oncological resection with wide margins and function-preserving reconstruction. The prognosis depends on the histologic grade and location of the tumor.

bone cancer

Silent surface osteosarcoma treated following the hemi-capanna technique. A case report.

surface sarcomas are a rare entity that need correct diagnosis to differentiate parosteal (cPOS), periosteal and the high grade surface osteosarcomas (HGSO). HGSO has malignant behavior similarities with osteosarcomas and wide resection is the key to a successful treatment.1 The Capanna and Hemi-Capanna reconstruction techniques have being developed in order to avoid amputation after an oncological resection, allowing structural support from an allograft and biological advantages from a vascularised autograft.

bone cancer

Replacement Therapy in Adults with GHD: How to Treat and Monitor.

The replacement therapy of growth hormone (GH) in adults suffering from GH deficiency (GHD) still presents several challenges and uncertainties for the clinical endocrinologist. The decision to initiate treatment for GHD in adults necessitates a careful and personalized evaluation of potential benefits and risks. Although improvements in body composition, bone health, cardiovascular risk factors, and quality of life have been observed, evidence supporting a reduction in cardiovascular events and mortality is still inadequate, and treatment expenses remain high. To optimize treatment outcomes while minimizing side effects, it is recommended to initiate GH replacement therapy with low doses, aiming for a proper clinical response and insulin-like growth factor-I levels within the age-appropriate reference range. Despite being generally safe, certain aspects of GH replacement therapy require continuous long-term monitoring, including the potential risks of glucose intolerance, recurrence of pituitary/hypothalamic tumors, and cancer.

bone cancer

Endoscopic Transsphenoidal Surgery in Growth-Hormone Pituitary Adenomas (GH PitNETs): Current Indications, Limitations, and the Importance of a Multidisciplinary Approach.

Acromegaly and gigantism are rare diseases, usually caused by a growth hormone-secreting pituitary adenoma, recently renamed GH-secreting pituitary neuroendocrine tumor (GH-PitNET). The transsphenoidal approach is the mainstay of treatment, although a non-negligible number of patients require a multimodal approach with neo-adjuvant or adjuvant medical and radiation therapy. Understanding the clinical complexity of acromegaly and gigantism is essential to improve treatment safety and success. A multidisciplinary skilled team is required to provide adequate pre-operative evaluation and management of the comorbidities associated with GH-PitNETs. Specific intraoperative surgical and anesthesiologic challenges (i.e., mucosal and bone hypertrophy, reduced intracarotid distance, and tumor invasiveness) to ensure maximal and safe resection. The same is for postoperative management to provide precise tumor histological characterization to be used in association with clinical-radiological and biochemical data to tailor patient management in terms of acromegaly control and treatment/prevention of comorbidities. This paper critically revises the indications and limitations of endoscopic transsphenoidal surgery for GH-PitNETs, discusses the frequently complex preoperative evaluation of patients with acromegaly, and analyzes the challenging aspects of the disease, underling the importance of a multidisciplinary framework, which should include a dedicated team of surgeons (neuro- and ENT-), endocrinologists, radiologists, pathologists, and anesthesiologists.

bone cancer

Growth Hormone Deficiency in the Transitional Age.

Transition is the time encompassing the achievement of full height and complete somatic development, representing a period of physical, psychological, and social changes. Considering the beginning of social adaptation, the research of independence, and the desire to manage health conditions, the acceptance of chronic care should be poor. Patients affected by growth hormone deficiency (GHD), characterized by heterogeneity in diagnosis, high comorbidity burden, need for daily injections, and lack of biological markers during follow-up, could have a high drop-out rate. Replacement treatment is meaningful because, even if GHD is not life-threatening, it could represent a risk for long-term metabolic, cardiovascular, bone, and psychosocial complications with, eventually, a reduction in quality of life. Moreover, the diagnosis is not always straightforward, since the studies on stimulation tests are limited, or molecules are lacking, cutoffs are often not validated in transition patients, and follow-up requires attention in specific cases (i.e., cancer survivors). The present review aims to describe the features of GHD during transition, focusing on etiologies, pitfalls in diagnosis, GH replacement therapy, and follow-up issues.

bone cancer

NF-κB c-Rel is a critical regulator of TLR7-induced inflammation in psoriasis.

Nuclear factor kappa B (NF-κB) c-Rel is a psoriasis susceptibility locus, however mechanisms underlying c-Rel transactivation during disease are poorly understood. Inflammation in psoriasis can be triggered following Toll-like Receptor 7 (TLR7) signalling in dendritic cells (DCs), and c-Rel is a critical regulator of DC function. Here, we studied the mechanism of TLR7-induced c-Rel-mediated inflammation in DCs.

bone cancer

Metabolic stress in space: ROS-induced mutations in mice hint at a new path to cancer.

Long-duration spaceflight beyond Earth's magnetosphere poses serious health risks, including muscle atrophy, bone loss, liver and kidney damage, and the Spaceflight-Associated Neuro-ocular Syndrome (SANS). RNA-seq of mice aboard the International Space Station (ISS) for 37 days revealed extraordinary hypermutation in tissue-specific genes, with guanine base conversion predominating, potentially contributing to spaceflight-associated health risks. Our results suggest that the genome-wide accelerated mutation that we measured, seemingly independent of radiation dose, was induced by oxidative damage from higher atmospheric carbon dioxide (CO

bone cancer

Myelofibrosis symptom assessment form total symptom score version 4.0: measurement properties from the MOMENTUM phase 3 study.

The Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) comprises 7 common MF symptom items (fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, bone pain) and is the first patient-reported outcome (PRO) instrument designed to assess MF symptom burden. Given that information on the psychometric properties of this instrument has been limited, we sought to evaluate its measurement properties and validate its use in the phase 3 MOMENTUM trial.

bone cancer

Role of Chemokines and Cytokines in Prostate Cancer Skeletal Metastasis.

Once prostate cancer (PCa) bone metastases develop, the prognosis dramatically declines. The precise mechanisms regulating bone metastasis remain elusive. This review will explore recent findings related to cytokines and chemokines in the process of bone metastases.

bone cancer

CT radiation dose reduction with tin filter for localisation/characterisation level image quality in PET-CT: a phantom study.

The tin filter has allowed radiation dose reduction in some standalone diagnostic computed tomography (CT) applications. Yet, 'low-dose' CT scans are commonly used in positron emission tomography (PET)-CT for lesion localisation/characterisation (L/C), with higher noise tolerated. Thus, dose reductions permissible with the tin filter at this image quality level may differ. The aim was to determine the level of CT dose reduction permitted with the tin filter in PET-CT, for comparable image quality to the clinical reference standard (CRS) L/C CT images acquired with standard filtration.

bone cancer

[Giant Ossifiant Fibrome Of The Mandibule In The Adolescent At The National Center D'odonto-Stomatologie Of Bamako].

Fibroma ossificans are usually well-defined tumours, but are rarely encapsulated. The choice of radical or conservative treatment is a challenge for the maxillofacial surgeon. The aim of this case report was to describe the particularities of the management of a case of ossifying fibroma of the mandible.

bone cancer

Multi-Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia.

Hyperleukocytic acute myeloid leukemia (HL-AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies.

bone cancer

The Impact of Preoperative Facial Nerve Weakness and Facial Nerve Outcomes in the Management of Patients With Parotid Metastases of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinomas (cSCC) metastasizing to the parotid gland can cause facial nerve (FN) dysfunction secondary to direct invasion, perineural spread, or surgical ablation. This study aims to characterize the prevalence of preoperative FN involvement in metastatic cSCC to the parotid and identify risk factors resulting in FN sacrifice.

bone cancer

Proteoglycans in Mechanobiology of Tissues and Organs: Normal Functions and Mechanopathology.

Proteoglycans (PGs) are a diverse class of glycoconjugates that serve critical functions in normal mechanobiology and mechanopathology. Both the protein cores and attached glycosaminoglycan (GAG) chains function in mechanically-sensitive processes, and loss of either can contribute to development of pathological conditions. PGs function as key components of the extracellular matrix (ECM) where they can serve as mechanosensors in mechanosensitive tissues including bone, cartilage, tendon, blood vessels and soft organs. The mechanical properties of these tissues depend on the presence and function of PGs, which play important roles in tissue elasticity, osmolarity and pressure sensing, and response to physical activity. Tissue responses depend on cell surface mechanoreceptors that include integrins, CD44, voltage sensitive ion channels, transient receptor potential (TRP) and piezo channels. PGs contribute to cell and molecular interplay in wound healing, fibrosis, and cancer, where they transduce the mechanical properties of the ECM and influence the progression of various context-specific conditions and diseases. The PGs that are most important in mechanobiology vary depending on the tissue and its functions and functional needs. Perlecan, for example, is important in the mechanobiology of basement membranes, cardiac and skeletal muscle, while aggrecan plays a primary role in the mechanical properties of cartilage and joints. A variety of techniques have been used to study the mechanobiology of PGs, including atomic force microscopy, mouse knockout models, and

bone cancer

A novel adjunctive diagnostic method for bone cancer: Osteosarcoma cell segmentation based on Twin Swin Transformer with multi-scale feature fusion.

Osteosarcoma, the most common primary bone tumor originating from osteoblasts, poses a significant challenge in medical practice, particularly among adolescents. Conventional diagnostic methods heavily rely on manual analysis of magnetic resonance imaging (MRI) scans, which often fall short in providing accurate and timely diagnosis. This underscores the critical need for advancements in medical imaging technologies to improve the detection and characterization of osteosarcoma.

bone cancer

AI based diagnostics product design for osteosarcoma cells microscopy imaging of bone cancer patients using CA-MobileNet V3.

The incidence of osteosarcoma (OS) is low, but primary malignant bone tumors rank third among the causes of death in cancer patients under the age of 20. Currently, analysis of cellular structure and tumor morphology through microscopic images remains one of the main diagnostic methods for osteosarcoma. However, this completely manual approach is tedious, time-consuming, and difficult to diagnose accurately due to the similarities in certain characteristics of malignant and benign tumors.

bone cancer

Transmembrane prostatic acid phosphatase: a therapeutic target in advanced prostate cancer.

Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic disease respond initially to androgen deprivation therapy (ADT), but almost inevitably progress to castration resistant prostate cancer (CRPC). Identification of markers and drivers of mCRPC that (a) represent a progenitor-type cancer cell population (b) persist in castration resistant disease (c) are actionable targets expressed on the cell surface, and (d) are induced by hypoxia, is required to facilitate the development of novel targeted therapies. We identified prostatic acid phosphatase (PAP), particularly the transmembrane form (TMPAP), as one such potential target. PAP is both a phosphatase and a 5'ectonucleotidase that generates adenosine. We herein demonstrate that PAP is expressed early on during fetal development and persists in castration-resistant disease. The VCaP and VCaP-enzalutamide-resistant PCa cell lines express secretory (sPAP) and TMPAP. Androgens downregulate while hypoxia upregulates PAP expression. In vivo, PAP persists in hypoxic areas of castration-resistant tumors. Knockdown of PAP decreases VCaP migration and colony formation. Finally, treatment of VCaP tumor-bearing mice with inhibitors of adenosine receptors reduces tumor growth. This data demonstrates that TMPAP is a novel therapeutic target in advanced prostate cancer.

bone cancer

Intraosseous hibernoma in a patient with vaginal cancer: Case report with radiologic and pathologic correlation.

•Intraosseous hibernomas are rare benign soft tissue tumors most often diagnosed incidentally.•Intraosseous hibernoma imaging characteristics can mimic bone metastases, including sclerosis, PET-avidity, and heterogenous enhancement.•Bone metastases seconadary to primary gynecologic cancers are rare, but present in 1 - 16% of cases.•Appropriate recognition of this rare benign finding dramatically change staging and management.

bone cancer

Clinical Characteristics and Treatment Outcomes of Thyroid Cancer at a Tertiary Care Hospital in Najran Region, Saudi Arabia: A Single-Centre Retrospective Study.

Background The global incidence of thyroid cancer has increased significantly over the past decades. This study aims to review the clinical characteristics and treatment outcomes of thyroid cancer at the Tertiary Care Hospital in the Najran region of Saudi Arabia. Material and methods We conducted a retrospective study of 279 patients diagnosed with thyroid cancer at our hospital from March 2014 to December 2021. Clinicopathologic parameters were obtained from the patient's medical records and examined using univariate and multivariate Cox regression to identify independent predictive markers. Result The mean age was 42.8 ±14.5 years, and most cases were female (n= 203, 72.8%). Most cases (n=170, 60.9%) underwent total thyroidectomy. Additionally, lymph node dissection was performed in 28 (10.0%) cases. Localized disease, distant, and regional metastasis were observed in 214 (76.7%), 34 (12.2%), and 31 (11.1%), respectively. The neck lymph nodes and lungs were the most common metastasis regions in 19 (6.8%) and 11 (3.9%) cases, respectively. Papillary thyroid cancer and follicular thyroid cancers accounted for the majority of cases in 236 (84.6%) and 33 (11.8%), respectively. Adjuvant therapy, including radioactive iodine ablation, was reported in 51 (18.3%) and external beam radiotherapy in four (1.4%). Independent prognostic factors of overall mortality of thyroid carcinoma were older age (Hazard ratio (HR):1.05, 95% confidence interval (CI): 1.01-1.09, p=0.008), Diabetic mellitus (HR: 4.30, 95% CI: 1.11-16.62, p=0.035), pathologic subtype of follicular carcinoma (HR: 4.48, 95% CI: 1.07-18.73, p=0.040) or non-papillary thyroid carcinoma subtypes (HR: 12.56, 95% CI: 2.44-64.74, p=0.002), metastasis presentation (HR: 11.70, 95% CI: 3.30-41.46, p<0.001), pulmonary metastasis (HR: 27.92, 95% CI: 6.96-111.98, p<0.001), bone and liver metastasis (HR: 15.20, 95% CI: 1.70-135.98, p=0.015), tumor size >4 cm (HR:121.21, 95% CI: 15.33-958.34, p<0.001), and extrathyroidal extension (HR: 6.15, 95% CI: 1.59-23.77, p=0.009). Conclusion This study demonstrates that advanced age, the presence of diabetes, non-papillary thyroid carcinoma subtypes, metastatic disease, tumor size greater than 4 cm, and extrathyroidal extension are independently associated with a poorer prognosis in patients with thyroid carcinoma. To offer the finest modern care, a multidisciplinary approach should be employed when developing a tailored treatment strategy, considering relevant recommendations and stratification systems.

bone cancer

Analysis of the effectiveness and efficiency of the    Indonesian metastatic bone disease of unknown origin algorithm (INA-MBD): time to diagnosis and cost to diagnosis : Quasi-experimental study.

Patients with Metastatic Bone Disease (MBD) often present with complaints of pain and multiple osteolytic lesions findings. Remarkably, 30% of these cases exhibit an undetected primary lesion. Hence, categorizing them as MBD of unknown origin. The diagnostic processes of patients with MBD of unknown origin typically takes up to four months, rendering it as a catastrophic disease with the second-highest financial burden. Given its urgency, it is necessary to develop a evidence-based consensus for managing cases of MBD with an unknown origin.

bone cancer

Expert Consensus on the Diagnosis and Treatment of FGFR Gene-Altered Solid Tumors.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

bone cancer

The role of neutrophils in osteosarcoma: insights from laboratory to clinic.

Osteosarcoma, a highly aggressive malignant bone tumor, is significantly influenced by the intricate interactions within its tumor microenvironment (TME), particularly involving neutrophils. This review delineates the multifaceted roles of neutrophils, including tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs), in osteosarcoma's pathogenesis. TANs exhibit both pro- and anti-tumor phenotypes, modulating tumor growth and immune evasion, while NETs facilitate tumor cell adhesion, migration, and immunosuppression. Clinically, neutrophil-related markers such as the neutrophil-to-lymphocyte ratio (NLR) predict patient outcomes, highlighting the potential for neutrophil-targeted therapies. Unraveling these complex interactions is crucial for developing novel treatment strategies that harness the TME to improve osteosarcoma management.

bone cancer

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Bone biopsy is the gold standard for diagnosing bone metastases. However, there is no clinical consensus regarding the optimal imaging test for determining the puncture site.

bone cancer

Clinico-epidemiological and treatment factors impact on survival in Egyptian patients with head and neck sarcoma: a retrospective case-series analysis.

Head and neck sarcomas are very rare accounting for about 1% of head and neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group compared to other sarcomas, due to anatomical constraints that make complete surgical removal difficult and increased local relapse rate. Surgery remains the main intervention although the data suggest the role of chemotherapy and irradiation as treatment options.

bone cancer

Comparison of survival, function and complication between intercalary frozen autograft versus massive allograft reconstruction after malignant bone tumors resection.

This study aims to compare the clinical outcomes of intercalary frozen autograft and allograft reconstruction for primary malignant bone tumors.

bone cancer

High-Resolution Sequencing Identifies a Novel HLA Allele: HLA-B*35:20:03.

The novel HLA-B*35:20:03 allele differs from B*35:20:01 by a change of C→A in exon 4.

bone cancer

Inula viscosa (L). Aiton leaves extract ameliorate arthritis by antioxidative and anti-inflammatory effects in formaldehyde-induced arthritis in mice.

Inula viscosa (L.) Aiton is a traditional medicinal plant widely distributed and used in Mediterranean countries, its leaves are prepared by maceration to treat, rheumatic pain, inflammatory diseases, diabetes, anemia and cancer.

bone cancer

CHEMOTHERAPY, IMMUNOTHERAPY, AND TARGETED THERAPY FOR OSTEOSARCOMA: RECENT ADVANCEMENTS.

Recent advancements in the treatment of osteosarcoma, a rare and aggressive form of bone cancer, have seen significant progress with chemotherapy, immunotherapy, and targeted therapy. Chemotherapy, the conventional approach, has witnessed refined drug regimens and novel agents tailored to enhance efficacy while minimizing adverse effects. This evolution aims to strike a balance between eradicating cancer cells and preserving patients' overall well-being. Immunotherapy has emerged as a promising avenue, leveraging the body's immune system to recognize and combat cancer cells. Innovative immunotherapeutic strategies, including immune checkpoint inhibitors, adoptive T cell therapy, and chimeric antigen receptor (CAR)-T cell therapy, exhibit the potential to enhance immune responses against osteosarcoma. Moreover, targeted therapy, designed to disrupt specific molecular pathways crucial for cancer growth, has gained traction in the treatment of osteosarcoma. Precision medicine approaches, such as identifying biomarkers and employing targeted agents, aim to tailor therapies to individual patients, maximizing effectiveness while minimizing collateral damage to healthy tissues. This article analyzes the current state of these three treatment modalities while comparing the efficacies of current chemotherapy, immunotherapy and targeted therapy agents.

bone cancer

iPSCs-derived iMSCs prevent osteoporotic bone loss and affect bone metabolites in ovariectomized mice.

Osteoporosis is a metabolic bone disease that seriously jeopardizes the health of middle-aged and elderly people. Mesenchymal stem cell-based transplantation for osteoporosis is a promising new therapeutic strategy. Induced mesenchymal stem cells (iMSCs) are a new option for stem cell transplantation therapy. Acquired mouse skin fibroblasts were transduced and reprogrammed into induced pluripotent cells and further induced to differentiate into iMSCs. The iMSCs were tested for pluripotency markers, trilineage differentiation ability, cell surface molecular marker tests, and gene expression patterns. The iMSCs were injected into the tail vein of mice by tail vein injection, and the distribution of cells in various organs was observed. The effect of iMSCs on the bone mass of mice was detected after injection into the mouse osteoporosis model. The effects of iMSCs infusion on metabolites in femoral tissue and peripheral blood plasma were detected based on LC-MS untargeted metabolomics. iMSCs have similar morphology, immunophenotype, in vitro differentiation potential, and gene expression patterns as mesenchymal stem cells. The iMSCs were heavily distributed in the lungs after infusion and gradually decreased over time. The iMSCs in the femoral bone marrow cavity gradually increased with time. iMSCs infusion significantly avoided bone loss due to oophorectomy. The results of untargeted metabolomics suggest that amino acid and lipid metabolic pathways are key factors involved in iMSCs bone protection and prevention of osteoporosis formation. iMSCs obtained by reprogramming-induced differentiation had cellular properties similar to those of bone marrow mesenchymal stem cells. The iMSCs could promote the remodelling of bone structure in ovariectomy-induced osteoporotic mice and affect the changes of several key metabolites in bone and peripheral blood. Some of these metabolites can serve as potential biomarkers and therapeutic targets for iMSCs intervention in osteoporosis. Investigating the effects of iMSCs on osteoporosis and the influence of metabolic pathways will provide new ideas and methods for the clinical treatment of osteoporosis.

bone cancer

A germline PDGFRB splice site variant associated with infantile myofibromatosis and resistance to imatinib.

Infantile myofibromatosis is characterized by the development of myofibroblastic tumors in young children. In most cases, the disease is caused by somatic gain-of-function variants in platelet-derived growth factor receptor beta (PDGFRB). Here, we report a novel germline intronic PDGFRB variant, c.2905-8G>A, in six unrelated infants with multifocal myofibromatosis and their relatives.

bone cancer

EEG features and synek scale indicate severity of neurotoxicity in adult patients treated with CD19 CAR T-cell therapy.

Patients who develop chimeric antigen receptor (CAR) T-cell-related immune effector cell-associated neurotoxicity syndrome (ICANS) frequently undergo evaluation with electroencephalography (EEG). We hypothesize that EEG features and Synek scale score, a measure of degree of EEG abnormality, are associated with ICANS severity. Here, we performed a retrospective review of 125 adult patients at Memorial Sloan Kettering Cancer Center (MSKCC) who received CAR-T cell therapy from 2010 to 2019, including 53 patients with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 72 patients with large B-cell lymphoma (LBCL) treated with the commercial CAR T products axicabtagene ciloleucel or tisagenlecleucel. We collected video EEG monitoring (27 with B-ALL and 20 with LBCL) and recorded daily EEG features, Synek scores, and ICANS grade for 47 eligible patients. Synek scale and ICANS grade were positively correlated (correlation coefficient 0.47, 95% CI: 0.31-0.60). This was further corroborated in the univariable model associating high Synek scale (3 or 4) with high ICANS grade (OR = 15.2; 95%CI:7.8-29.7, p < 0.0001). EEG features such as discontinuity, absence of posterior dominant rhythm, and presence of generalized sharp waves were statistically significantly associated with higher ICANS grade in univariable models. In the multivariable model, discontinuity (OR = 4.2 (95%CI:1.3-13.8, p = 0.02) and absence of posterior dominant rhythm (OR = 10.5 (95%CI:4.6-23.9, p < 0.0001) were statistically associated with higher ICANS grade. Overall, EEG discontinuity and absence of posterior dominant rhythm were independently associated with higher severity of neurotoxicity. Further, our data suggest that Synek Scale, may be a severity marker for neurotoxicity.

bone cancer

High CD44 expression and enhanced E-selectin binding identified as biomarkers of chemoresistant leukemic cells in human T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy characterized by increased proliferation and incomplete maturation of T-cell progenitors, for which relapse is often of poor prognosis. To improve patient outcomes, it is critical to understand the chemoresistance mechanisms arising from cell plasticity induced by the bone marrow (BM) microenvironment. Single-cell RNA sequencing of human T-ALL cells from adipocyte-rich and adipocyte-poor BM revealed a distinct leukemic cell population defined by quiescence and high CD44 expression (Ki67

bone cancer

In-situ collagen mineralization modulates metastatic properties of breast cancer cells.

Bone metastasis is the leading cause of morbidity and mortality in advanced-stage breast cancer patients. While most studies focus on the cellular and genetic factors associated with breast cancer metastasis, the role of the extracellular matrix (ECM) of bone in breast cancer metastasis remains elusive. In this study, we recapitulated the bone microenvironment using in-situ mineralized collagen type-I hydrogels and utilized them to understand breast cancer metastasis. Our results indicated successful mineralization of collagen type-I based hydrogels in the presence of serum proteins, which increased as a function of time. There was no difference in the adhesion of breast cancer cells seeded on collagen and mineralized collagen surfaces. However, there was a marked reduction in cell proliferation, down-regulation of various metastatic markers, and decreased migratory phenotype with a concomitant increase in cleaved caspase-3 on mineralized collagen compared to collagen hydrogels. In conclusion, our results suggest an inverse relationship between bone mineralization and the metastatic propensity of breast cancer cells. We further speculate the role of other factors in the skeletal ecosystem for mediating preferential homing of breast cancer cells to the bone microenvironment.

bone cancer

Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.

bone cancer

The Role of PSMA-Radioligand and Magnetic Resonance Imaging in Patients with Prostate Cancer Biochemical Recurrence.

A significant proportion of men with prostate cancer will experience biochemical recurrence (BCR), which is characterized by an elevation in prostate-specific antigen (PSA) levels after receiving treatment with curative intent. Imaging plays an important role in the management of patients with BCR. It can help identify sites of recurrence to determine the most appropriate management strategies, ranging from salvage treatment for local recurrences to systemic treatments for those with advanced, distant disease. PET/CT with prostate-specific membrane antigen (PSMA)-radioligands is the most sensitive method for the detection of prostate cancer recurrence, with significantly higher cancer detection rates compared to conventional imaging techniques such as bone scan and computed tomography, even at lower PSA levels. Nevertheless, interpretation of PSMA PET/CT images can be challenging, particularly for the evaluation of local recurrence due to urinary activity that can mimic or mask the presence of cancer. Furthermore, some prostate cancers may not express PSMA and have false negative results. Multiparametric prostate MRI is an excellent method for the evaluation of local recurrence and can overcome some of the limitations of PSMA PET/CT. In this review, we discuss the role of imaging in managing patients with prostate cancer BCR and describe the potential benefits of MRI in the PSMA-radioligand imaging era, emphasizing the assessment of local recurrence.

bone cancer

Osteogenic sarcomas in two fish species giant sea catfish (Arius thalassinus), and Delagoa threadfin bream (Nemipterus bipunctatu) caught from Saudi Arabia, the Arabian Gulf.

During routine veterinary inspection of fish from fishing boats, fish auction yards, and fish landing stations, as well as the large fish market for detection of fish diseases, abnormalities and/or overgrowth in body surfaces and evaluation of hygienic conditions and fish quality at El-Jubail Province, Saudi Arabia., external neoplastic overgrowths were observed in two fish species, giant sea catfish (Arius thalassinus) and Delagoa threadfin bream (Nemipterus bipunctatu). In both fishes, the neoplasms appeared as bony masses, and it was hard in its consistency. In the giant sea catfish (Arius thalassinus), the tumor appeared as three multifocal hard swellings at different locations (in the head region, at the dorsal fin, and near the caudal fin). The tumor mass in the head region of this fish was observed at the base of the right angle of the lower jaw, and it was hard, bony, nodular to round, and of 0.7 cm in diameter. The second one was observed at the dorsal fin and appeared as a small oval to rod hard mass of 0.5 cm in diameter, while the third mass appeared as a large and irregular wart-shaped bony swelling, about 3 cm in diameter, that extended laterally on the left aspect of the caudal peduncle near the caudal fin. In radiographic examination, the neoplasm appeared small, round to large, irregular, dense bony overgrowth with variable sizes. In histopathological examination, evidences of fibro-osteosarcoma associated with prominent multiple rounded eosinophilic apoptotic bodies in the neoplastic bony trabeculae were observed. On the other side, the Delagoa threadfin bream (Nemipterus bipunctatus) showed only one yellowish to reddish, pedunculated, irregular, and very hard swelling at the base of the median site of the dorsal fin, and it was firmly connected to the spine of the dorsal fin; it was about 1 cm high with a wide base of 0.5 cm. In histopathological examination, the bony neoplastic masses in this fish appeared with massive edematous fibrous connective tissue and newly formed blood capillaries; abnormal mitosis, hemorrhages, and hemosiderin pigment deposition in the central and peripheral parts of the neoplasm were observed. New bone formation was confirmed using histochemical staining. Our results indicated that these two species are vulnerable to fibro-osteosarcoma. Further environmental investigations as well as immunohistochemical and molecular studies are required to indicate the potential impact of the environmental pollution on the incidence of the neoplasms in this locality and to correlate the cellular evidence of the neoplasms to a specific fish species.

bone cancer

Improved quality of life of a patient with refractory aggressive Natural Killer/ T-cell lymphoma (NKTCL) on adjunct Ayurvedic treatment protocol: A case report of ten-years follow-up.

In an Indian female patient diagnosed as an aggressive refractory Natural Killer/T-cell Lymphoma treated with radiotherapy followed by chemotherapy, long term overall survival (OS) of 10 years was achieved. She refused Bone Marrow Transplant (BMT) after relapse and opted 2nd line chemotherapy. After completion of conventional treatment, she started Oral Ayurvedic Medicines (OAM) which possess immunomodulatory, anti-inflammatory, and to a certain extent anti-cancer activity. This female patient was diagnosed with Stage IIE NK/T-cell Lymphoma and treated with radiotherapy from May to July 2011 followed by 6 cycles of R - CHOP Protocol from August to November 2011. Within 3 months after completion of conventional treatment, the patient presented with a recurrence of palatal ulcer and the appearance of tender subcutaneous nodules on both legs. She visited Cancer Hospital for a further line of treatment. Her histopathological report of soft palate ulcer showed suspicion of Non-Hodgkin's Lymphoma (NHL) and a subcutaneous nodule over her right leg revealed cutaneous involvement by NHL. Oncologist advised Bone Marrow Transplant (BMT) after taking into consideration an early relapse and aggressiveness of the disease. However, the patient refused BMT and opted 6 cycles of SMILE protocol chemotherapy taken from October 2012 to January 2013. The patient is under OAM of our centre consisting of a well-planned and personalized 6 sets of herbo-mineral metallic Ayurvedic medicines to minimize the side effects of chemotherapy as well as to boost immunity to prevent further recurrence of the disease. Her quality of life is improved significantly without any disease recurrence to date. In this case of Refractory Natural Killer/T-cell Lymphoma having poor prognosis, 10 years OS after starting Ayurvedic treatment is reported. It has been achieved by personalized adjunct Ayurvedic treatment consisting combination of oral herbo-mineral metallic medicines.

bone cancer

Atypical femur fracture following romosozumab and bisphosphonate treatment.

Romosozumab, a monoclonal antibody against sclerostin, is a newly licensed dual-acting osteoporosis treatment for patients at very high risk of fracture. Sclerostin inhibition leads to stimulation of bone formation and simultaneous inhibition of bone resorption. Only three cases of atypical femur fractures were reported out of 5,621 patients who received romosozumab in the pivotal randomised controlled trials FRAME and ARCH; however, most enrolled clinical trial patients were osteoporosis treatment-naïve or had a prolonged washout period. We report a case of an atypical femur fracture that occurred after the completion of romosozumab treatment which was followed by one dose of 5 mg intravenous zoledronic acid. The patient had previously received a 2-year course of subcutaneous teriparatide and subsequent three consecutive yearly intravenous zoledronic acid infusions, followed by a 2-year treatment break. This case highlights the risks of prolonged suppression of bone resorption, which includes romosozumab due to its dual action and the need for further research on how to minimise such deleterious medication effects. Patients who are switched from prolonged antiresorptive treatment to romosozumab, should be risk-assessed and counselled for the risk of atypical femur fracture.

bone cancer

Acute Leukemias of Ambiguous Lineage With MDS-Associated Mutations Show Similar Prognosis Compared to Acute Myeloid Leukemia With MDS-Associated Mutations: A Study From the Bone Marrow Pathology Group.

No abstract found

bone cancer

Exploring Smad5: a review to pave the way for a deeper understanding of the pathobiology of common respiratory diseases.

Smad5 (small mothers against decapentaplegic 5) protein is a receptor-regulated member of the Smad family proteins, mainly participating in the bone morphogenetic protein (BMP) signaling pathway in its phosphorylated form. This article will provide a detailed review of Smad5, focusing on its gene characteristics, protein structure, and subcellular localization properties. We will also explore the related signaling pathways and the mechanisms of Smad5 in respiratory diseases, including chronic obstructive pulmonary disease (COPD), bronchial asthma, pulmonary arterial hypertension(PAH), lung cancer, and idiopathic pulmonary fibrosis (IPF). Additionally, the review will cover aspects such as proliferation, differentiation, apoptosis, anti-fibrosis, and mitochondrial function metabolism. In addition, the review will cover aspects of proliferation, differentiation, apoptosis, anti-fibrosis and functional mitochondrial metabolism related to the above topics. Numerous studies suggest that Smad5 may play a unique and important role in the pathogenesis of respiratory system diseases. However, in previous research, Smad5 was mainly used to broadly determine the activation of the BMP signaling pathway, and its own function has not been given much attention. It is worth noting that Smad5 has distinct nuclear-cytoplasmic distribution characteristics different from Smad1 and Smad8. It can undergo significant nuclear-cytoplasmic shuttling when intracellular pH (pHi) changes, playing important roles in both the classical BMP signaling pathway and non-BMP signaling pathways. Given that Smad5 can move intracellularly in response to changes in physicochemical properties, its cellular localization may play a crucial role in the development of respiratory diseases. This article will explore the possibility that its distribution characteristics may be an important factor that is easily overlooked and not adequately considered in disease research.

bone cancer

Polyploid cancer cells reveal signatures of chemotherapy resistance.

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and are associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and the expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.

bone cancer

Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes.

The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses reveal lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveils hyperactive CD8

bone cancer

The role of Cabazitaxel in Patients With Castration-Resistant and Osseous Metastases Prostate Cancer. A Hellenic Cooperative Oncology Group Phase II Study: Cabazitaxel in mCRPC patients with osseous metastases.

Cabazitaxel is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC) patients previously exposed to docetaxel and novel hormonal treatments. Understanding the molecular biology of mCRPC disease and taking into account the several approved treatment options, biomarkers are needed to guide decision making including cabazitaxel treatment.

bone cancer

Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.

BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective.