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The exploration of B cell maturation antigen expression in plasma cell dyscrasias beyond multiple myeloma.

BACKGROUND: B cell maturation antigen (BCMA) targeted immunotherapies have demonstrated remarkable clinical efficacy in multiple myeloma (MM). Here, we evaluated the BCMA expression in MM and other plasma cell dyscrasias (PCDs), hoping to provide a potential treatment strategy for the relapsed/refractory PCDs besides MM. METHODS: From January 2018 to August 2021, 377 patients with PCDs were enrolled in this study, including 334 MM, 21 systemic light chain amyloidosis (AL), 5 POEMS syndrome, 14 monoclonal gammopathy of undetermined significance (MGUS), and three monoclonal gammopathy of renal

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… Maes K Nemeth E Roodman GD Huston A Esteve F Freytes C Callander N Katodritou E Tussing-Humphreys L Rivera S In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2 Blood 2010 116 18 3635 3644 10.1182/blood-2010-03-274571 20679527 PMC2981483 35. …

Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis.

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expre

Denosumab induction and Zoledronic acid maintenance therapy for recurrent unresectable giant cell tumour of the distal tibia: A case report with sustained tumour control after drug withdrawal.

A 31-year-old woman was diagnosed with a recurrent and rapidly growing giant cell tumour of distal tibia with skin ulceration after intralesional curettage. The patient started on Denosumab 120 mg subcutaneously, once per month with additional loading doses on Days 8 and 15 attempting to avoid below-knee amputation. Twelve doses of Denosumab were administered in 9 months, resulting in resolution of pain, reduction of tumour size and calcification. Hence, the local surgical treatment was delayed and bisphosphonate maintenance therapy was initiated as skin healing was incomplete. The patient was

The Multiple Roles of Microrna-223 in Regulating Bone Metabolism.

Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this rev

Patients with type 1 Gaucher disease in South Florida, USA: demographics, genotypes, disease severity and treatment outcomes.

BackgroundGaucher disease, an autosomal recessive condition due to deficiency of lysosomal glucocerebrosidase, is a multisystemic disease, with variable age of onset, severity and progression. It is classified into subtypes delineated by the absence (type 1) or presence (type 2 and 3) of primary nervous system involvement. The ethnically diverse, largely immigrant population in South Florida has a spectrum of Gaucher disease phenotypes, creating a challenge for optimization of disease management and an opportunity to explore treatment patterns.MethodsNinety-three records from patients with Gau

The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging.

Non‑small cell lung cancer (NSCLC) metastasis commonly occurs in bone, which often results in pathological fractures. Sustained phosphoinositide‑3‑kinase (PI3K) signalling promotes the growth of PI3K‑dependent NSCLC and elevates osteoclastogenic potential. The present study investigated the effects of a PI3K inhibitor on NSCLC growth in bone and osteoclast formation, and aimed to determine whether it could control symptoms associated with bone metastasis. A bone metastasis xenograft model was established by implanting NCI‑H460‑luc2 lung cancer cells, which contain a phosphatidylinositol‑​4,5‑b

Epigenetic Regulation of Autophagy in Bone Metabolism.

The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's i

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… TET proteins engage with Runx2 via their catalytic domain, influencing cytosine methylation patterns around the Runx2 binding region. 35 Disruptions in the promoter methylation of key bone-related genes, such as bone morphogenetic protein 2 (BMP2), may lead to irregularities in bone formation. 29 Post-Translational …

Breast cancer metastasis to the bone: mechanisms of bone loss.

Breast cancer frequently metastasizes to the skeleton, interrupting the normal bone remodeling process and causing bone degradation. Osteolytic lesions are the end result of osteoclast activity; however, osteoclast differentiation and activation are mediated by osteoblast production of RANKL (receptor activator for NFκB ligand) and several osteoclastogenic cytokines. Osteoblasts themselves are negatively affected by cancer cells as evidenced by an increase in apoptosis and a decrease in proteins required for new bone formation. Thus, bone loss is due to both increased activation of osteoclasts

A novel application perspective of the clinical-used drug verapamil on osteoporosis via targeting Txnip.

BACKGROUND: RANKL and SCLEROSTIN antibodies have provided a strong effective choice for treating osteoporosis in the past years, which suggested novel molecular target identification and therapeutic strategies development are important for the treatment of osteoporosis. The therapeutic effect of verapamil, a drug previously used for cardiovascular diseases, on diabetes was due to the inhibition of TXNIP expression, which has also been reported as a target in mice osteoporosis. Whether verapamil-inhibited TXNIP expression is related to osteoporosis and how it works on the molecular level is wor

The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis.

Current methods for testing bone density lack the capability to detect patients with early bone loss, and existing osteoporosis therapies have limitations in their efficacy and safety. Therefore, the development of more precise and convenient diagnostic technologies and novel treatments is of paramount importance. Extracellular vesicle (EV)-mediated non-coding RNA (ncRNA) interaction networks enable both the detection of early bone loss and targeted therapy for enhanced treatment outcomes. In this review, we highlight the utility of EVs for carrying various ncRNAs (e.g., miRNAs, lncRNAs, and c

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… morphogenetic protein 2 c-Fos | FBJ murine osteosarcoma viral oncogene homolog c-Myc | MYC proto-oncogene CAR2 | Carbonic anhydrase 2 ceRNA | Competing endogenous RNA cGAS-STING | Cyclic GMP-AMP synthase/stimulator of interferon genes CGM | Children-derived gut microbiota circRNAs | Circular RNAs CMVs … At high expression levels, piR-36741 could competitively bind to METTL3 to inhibit its binding to bone morphogenetic protein 2 (BMP2) mRNA and reduce m6A modification, thus promoting the expression of BMP2, a positive regulator of osteoblast differentiation [ 94 ] ( Fig. 4 ). …

Роль микроглии в множественном склерозе: последствия для лечения ингибиторами тиросина Брютона.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, затрагивающее центральную нервную систему (CNS), характеризующееся воспалением и нейродегенерацией. Патофизиология MS, особенно его прогрессивные формы, включает различные клеточные компоненты, включая микроглию, являющиеся основными постоянными иммунными клетками CNS. В настоящем обзоре рассматривается роль микроглии в нейроинфламмации, ремонте тканей и нейронном гомеостазе, а также их участие в MS и изучаются потенциальные терапевтические стратегии, ориентированные на микроглиальную функцию.МЕТОДЫ: Поиск литературы, проведенн

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review.

PurposeBone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis.MethodsA comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analys

The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis.

Although it has long been recognized that inflammation, a consequence of immune-driven processes, significantly impacts bone turnover, the degree of centralization of skeletal and immune functions has begun to be dissected only recently. It is now recognized that formation of osteoclasts, the bone resorbing cells of the body, is centered on the key osteoclastogenic cytokine, receptor activator of NF- κ B ligand (RANKL). Although numerous inflammatory cytokines are now recognized to promote osteoclast formation and skeletal degradation, with just a few exceptions, RANKL is now considered to be

Not so Fast: Co-Requirements for Sonic Hedgehog Induced Brain Tumorigenesis.

The Sonic hedgehog (Shh) pathway plays an integral role in cellular proliferation during normal brain development and also drives growth in a variety of cancers including brain cancer. Clinical trials of Shh pathway inhibitors for brain tumors have yielded disappointing results, indicating a more nuanced role for Shh signaling. We postulate that Shh signaling does not work alone but requires co-activation of other signaling pathways for tumorigenesis and stem cell maintenance. This review will focus on the interplay between the Shh pathway and these pathways to promote tumor growth in brain tu

Sclerostin Alters Tumor Cell Characteristics of Oral Squamous Cell Carcinoma and May Be a Key Player in Local Bone Invasion.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin tr

Calculated haemorheological profile and laboratory parameters in new diagnosed multiple myeloma patients: retrospective analysis according to survival.

BackgroundMultiple myeloma is a malignant haematological neoplasm characterised by clonal proliferation of plasma cells, with a complex clinical picture, and a significant impact on patient survival, in which the prognosis evaluation of patients is of great importance.ObjectivesIn this single-centre retrospective analysis, performed in a group of newly diagnosed multiple myeloma patients, we examined several clinical and laboratory parameters in order to evaluate their trend according to survival of patients.DesignWe collected data from 190 newly diagnosed multiple myeloma evaluated at the Hem

The research progress on radionuclides in osteoporosis diagnosis and drug efficacy monitoring.

Osteoporosis is a common metabolic bone disease that seriously affects the quality of life and health of patients. Traditional diagnostic methods, such as dual energy X-ray absorptiometry (DXA), have limitations in early detection and dynamic monitoring, making it difficult to meet clinical needs. This paper focuses on the potential of radionuclide imaging techniques, such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), in the early diagnosis of osteoporosis. The paper further elaborates on the importance of radionuclides in evaluating the therapeu

Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia.

Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-β, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoi

Could Local Application of Hypoxia Inducible Factor 1-α Enhancer Deferoxamine Be Promising for Preventing of Medication-Related Osteonecrosis of the Jaw?

This experimental study investigates the prophylactic effect of deferoxamine (DFO) on medication-related osteonecrosis of the jaw (MRONJ). Thirty-six female Sprague Dawley rats received zoledronic acid (ZA) for eight weeks to create an osteonecrosis model. DFO was locally applied into the extraction sockets with gelatin sponge (GS) carriers to prevent MRONJ. The specimens were histopathologically and histomorphometrically evaluated. Hypoxia-inducible factor 1-alpha (HIF-1α) protein levels in the extraction sockets were quantified. New bone formation rate differed significantly between groups (

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… Manzano-Monero et al. (2018) reported that low-dose BP is effective by increasing levels of molecules such as TGF-β1 and VEGF, which affect cell growth, and decreasing levels of molecules such as bone morphogenetic protein 2 (BMP2) and receptor activator of nuclear factor kappa-Β ligand (RANKL), which …

Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury.

The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg-Gly-Asp-alginate (RGD-Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin-12 (IL-12) (RGD-Al

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… With the addition of Gel/Laponite@IL‐12 and the extension of co‐culture time, the expression of bone morphogenetic protein 2 ( BMP2 ), alkaline phosphatase (AKP), runt‐related transcription factor 2 (RUNX2), osteocalcin (OCN) and collagen type I alpha 1 ( COLA1 ) was significantly up‐regulated (Figure …