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Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update.

Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the

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… Interference with the interaction of myeloma cells and the microenvironment Monoclonal antibodies (mAbs) Elotuzumab (anti-CS1/anti-SLAM7) Daratumumab (anti-CD38) SAR650984 = isatuximab (anti-CD38) MOR202 (anti-CD38) Denosumab (anti-RANKL) Siltuximab (anti-IL6) IPH2101 (anti-KIR2DL1/2/3) | Direct induction …

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for

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… Prednisolone | CYP17 inhibitor | NCT02043678 (Phase III; active) | Prostate cancer [ 339 ] [ 223 Ra]Ra-dichloride + Enzalutamide | AR inhibitor | NCT02199197 (Phase II; completed) NCT03305224 (Phase II; ongoing) | Prostate cancer, [ 340 ], bone metastatic prostate cancer [ 341 ] [ 223 Ra]Ra-dichloride + Denosumab …

Critical considerations in the administration of antineoplastic therapy for patients with malignant solid tumors undergoing hemodialysis.

Patients with chronic kidney disease exhibit a higher risk of developing malignancies, and among those with end-stage renal disease (ESRD) on dialysis, approximately 7% are diagnosed with new-onset tumors within five years. Patients with ESRD who are receiving antineoplastic treatment exhibit a significantly higher incidence and greater severity of adverse effects associated with antineoplastic agents compared to individuals with normal renal function. This complexity involves multiple factors, including the therapy options and dose adjustment of antineoplastic agents, drug-related toxicities,

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… potential contribution of chemotherapy-associated bone disorders—including endocrine therapy and estrogen deprivation—to the pathogenesis and progression of renal osteodystrophy in patients with ESRD Well-designed clinical studies are needed to evaluate the safety and efficacy of targeted agents such as denosumab …

Time-dependent clearance can confound exposure-response analysis of therapeutic antibodies: A comprehensive review of the current literature.

Exposure-response (ER) analysis is used to optimize dose and dose regimens during clinical development. Characterization of relationships between drug exposure and efficacy or safety outcomes can be utilized to make dose adjustments that improve patient response. Therapeutic antibodies typically show predictable pharmacokinetics (PK) but can exhibit clearance that decreases over time due to treatment. Moreover, time-dependent changes in clearance are frequently associated with drug response, with larger decreases in clearance and increased exposure seen in patients who respond to treatment. Th

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… Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Clin Pharmacokinet. 2012;51:247‐260. 31. Porporato PE. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis. 2016;5:e200. 32. Tisdale MJ. …

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of

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… Currently, the only FDA approved therapies for bone metastasis are two anti-resorptive agents the bisphosphonate (zoledronate and ibandronate) and the anti-RANKL monoclonal antibody (denosumab), and a bone-targeted radioisotope (radium 223). …

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen s

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… Current management of MBD such as bisphosphonates (BPs) and denosumab reduce further bone destruction by OCs. Thus, they are therapeutic effects are limited due to the inability to actively stimulate bone formation. …

Oral Presentations

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Е-постеры.

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is

Oral Presentations

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Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

BACKGROUND: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the complement C3a activates osteoclasts to participate in the pathogenesis of MBD; however, its mechanism of action is diverse and complex. Studies have shown that the Sirtuin (Sirt) family of proteins (i.e., Sirt1-7) are expressed in human bone and cartilage, and participate in bone metabolic balance. METHODS AND RESULTS: We measured the levels of complement C3a, Sirt1, osteoclast-related genes, and bone disease-related biological indicators using enzyme-linked imm

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… Micro-CT and pathological analysis results confirmed that Sirt1 activators exert a therapeutic effect on bone disease; however, the only two currently approved drugs for treating MBD are bisphosphonates and denosumab—a monoclonal antibody that inhibits RANKL [ 49 ]. …

[Immunotherapy - The New Era of Oncology].

In the field of immunotherapy, essential progress was achieved over the past years partially demonstrating long lasting therapeutic responses in different tumor entities. A better understanding of the interactions between the tumor and the immune system as well as the integration of immunotherapeutic approaches into clinical routine were the foundations for this development. The different approaches intervene on multiple levels of the immune response and directly or indirectly mount the patient's own immune defense against tumor cells. Immunotherapeutic approaches are represented by cytokine t

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… leukemia (CLL), Non Hodgkin lymphoma (NHL), solid tumors IgG1 on PDGF receptor-α (platelet-derived growth factor receptor α) | Olaratumab | Sarcoma IL6 receptor | Tocilizumab | Cytokine storm after CART cell therapy IL6 | Siltuximab | Multiple myeloma RANK ligand (receptor activator of NF-κB ligands) | Denosumab …

Экстракорпоральные стратегии свободного освещения и гемоглозы в эпоху эффективной антимиеломной терапии.

Повреждение реналов затрагивает до половины пациентов с недавно поставленным диагнозом множественной миеломы, и примерно 2-4% из них требуют диализа при презентации, чаще всего из-за нефропатии легкой цепи. У этих пациентов восстановление почек связано со скоростью и величиной сокращения свободных световых цепей (SFLC) в наблюдательных группах - ассоциации, которая в основном отражает гематологическую реакцию на химиотерапию; постепенное преимущество удаления циркулирующих SFLC с помощью экстракорпоральных средств остается неопределенным, и эта повествование построена вокруг этого вопроса в ны

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… cornerstones of management include carefully monitored hydration, often targeting approximately 3 L/day in patients without oliguria, congestion, or cardiac contraindications; correction of hypercalcemia with bisphosphonates or, when bisphosphonates are unsuitable because of severe kidney impairment, denosumab …

Analysis of medical malpractice liability disputes related to novel antineoplastic drugs and research on risk prevention and control strategies.

OBJECTIVE: To investigate the general characteristics of litigation cases of medical malpractice liability disputes (MMLDs) related to novel antineoplastic drugs (NADs), the drugs involved, as well as the common types of medical errors related to NADs and their damages in the process of diagnosis and treatment, with the aims of improving the level of rational medication use in the clinical application of NADs and actively prevent medical disputes. METHODS: The China Judgments Online was searched for the cause of action using the key word "MMLDs" along with the name of 77 kinds of NADs. A tota

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… 2 Proteasome inhibitors | Bortezomib * ; Ixazomib | 2 Monoclonal antibodies (mAbs) [ 24 ] | | 10 Human/murine, chimeric anti-CD20 | Rituximab * | 1 BiTEs CD19/CD3 | Blinatumomab | 1 CD38 | Daratumumab | 1 EGFR | Cetuximab; Nimotuzumab * | 2 HER2 | Pertuzumab; Inetetamab; Trastuzumab * | 3 RANKL | Denosumab …

Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.

Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme

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… progression and spread of cancer to the bones: chemotherapy combined with pain killer medications (like anti-inflammatory drugs or opioids), corticosteroids, external radiation, radiopharmaceuticals to reduce tumor size and pain, bisphosphonates, making bones stronger (ex: zoledronate), and anti-RANKL (denosumab …

Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.

Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies-autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients' quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellula

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… Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis Arthritis Care Res. 2010 62 537 544 10.1002/acr.20172 20391509 39. Tournis S. Samdanis V. Psarelis S. Liakou C. Antoniou J. Georgoulas T. Dontas I. Papaioannou N. Gazi S. Lyritis G.P. …

Combinatorial targeting of cancer bone metastasis using mRNA engineered stem cells.

BACKGROUND: Bone metastases are common and devastating to cancer patients. Existing treatments do not specifically target the disease sites and are therefore ineffective and systemically toxic. Here we present a new strategy to treat bone metastasis by targeting both the cancer cells ("the seed"), and their surrounding niche ("the soil"), using stem cells engineered to home to the bone metastatic niche and to maximise local delivery of multiple therapeutic factors. METHODS: We used mesenchymal stem cells engineered using mRNA to simultaneously express P-selectin glycoprotein ligand-1 (PSGL-1)

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… Standard of care drugs targeting bone resorption, including bisphosphonates and Denosumab (antibody targeting the receptor activator of NF-κB ligand, RANKL), which act by inhibiting osteoclastogenesis through different mechanisms, are controversial in their anti-tumour mechanisms [ 6 , 7 ]. …

Bone sialoprotein: a multifunctional regulator of bone remodelling and tumour progression.

Bone sialoprotein (BSP) is a major non-collagenous protein of the bone extracellular matrix and an important regulator of bone formation and resorption. BSP is produced by bone cells and chondrocytes and present in the bone matrix, cells, dentin and cartilage. However, its aberrant expression in primary tumour tissues and the sera of cancer patients with metastases implicates BSP in tumour biology and progression. The Arg-Gly-Asp (RGD) motif of BSP may be crucial not only for the attachment of metastasising cells to the bone surface but also for tumour growth, survival and activity. This revie

Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients' quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducin

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases.

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, an

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… Risk Factors Associated with Onset of Medication-Related Osteonecrosis of the Jaw in Patients Treated with Denosumab Clin. Oral Investig. 2022 26 2839 2852 10.1007/s00784-021-04261-4 PMC8898220 34812959 9. Suresh E. Pazianas M. Abrahamsen B. …