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Epidemiology, genetics and treatment of multiple myeloma and precursor diseases.

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5-year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapi

Decoding Waldenström Macroglobulinemia Through Genomics, Epigenomics and Cellular Interactions

Waldenström macroglobulinemia is a rare lymphoplasmacytic malignancy characterized by bone marrow infiltration and monoclonal immunoglobulin M production. Despite its indolent clinical course, the disease exhibits considerable biological complexity driven by recurrent genetic alterations, dysregulated signaling pathways, and a supportive bone marrow microenvironment. The identification of MYD88 and CXCR4 mutations has significantly advanced understanding of disease pathogenesis, clonal evolution, and treatment response. Additional insights from cytogenetic, epigenetic, and microRNA studies hav

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compar

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… In more detail, different JAK2-induced pathophysiologic mechanisms contribute to the typically high thrombotic risk of MPNs: (i) blood viscosity related to hyper-cellularity and (ii) alterations in (a) plasmatic coagulation (b) vessel walls, (c) cell adhesion and function [ 4 ]. …

Nanomedicine Meets Immunotherapy: Advancing Adoptive Cell Therapy with Nanoparticles in the Treatment of Cancer with Sustainability Perspectives.

Immunotherapy has achieved remarkable clinical success in certain cancers, particularly through adoptive cell therapy (ACT), where T cell engineering with chimeric antigen receptor (CAR) has driven major clinical breakthroughs in the treatment of hematologic malignancies. However, efficacy against solid tumors remains limited due to multiple barriers, including the scarcity of tumor-specific antigens, antigen heterogeneity, immunosuppressive tumor microenvironment, and physical obstruction of T cell infiltration by dense extracellular matrix. Nanoparticle (NP)-based approaches can overcome the

Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.

Cardio-oncology is an emerging field that seeks to enhance quality of life and longevity of cancer survivors. It is pertinent for clinicians to understand the cellular mechanisms of prescribed therapies, as this contributes to robust understanding of complex treatments and off-target effects, improved communication with patients, and guides long term care with the goal to minimise or prevent cardiovascular complications. Our aim is to review the cellular mechanisms of cardiotoxicity involved in commonly used anti-cancer treatments and identify gaps in literature and strategies to mitigate card

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… In addition, myocardial ischaemia can result from erythrocyte membrane changes that lead to increased blood viscosity and decreased oxygen carrying capacity ( 126 ). …

KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP).

The 2026 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Anemia in Chronic Kidney Disease represents a substantial update, coming more than a decade since the previous KDIGO guideline on the topic. This time lapse was necessary in order to accumulate new scientific evidence that was meaningful for an updated guideline. The new guideline now includes updated recommendations and practice points for anaemia management, incorporating recent evidence on intravenous iron therapies and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This European R

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… On the other hand, these agents may induce erythrocytosis, which may be associated with a higher thrombotic risk due to an increase in blood viscosity [ 139 ]. …

From Innate Immunity to Cancer Therapy: Antimicrobial Peptides as Emerging Anticancer Agents.

The potential for the use of antimicrobial peptides (AMPs) as anticancer agents has garnered much interest because of their selective cytotoxicity to tumor cells and ability to evade multidrug resistance mechanisms. AMPs are shorter cationic amphiphilic molecules, part of our innate immune system, with direct membrane-disruptive activity and immunomodulatory effects. Anticancer peptides (ACPs) can be derived from natural biophysical sources or synthetically engineered, taking advantage of the unique biophysical properties of cancer cell membranes to exert their anti-tumor activities rapidly an

The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease.

Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapies are needed. During the last five years, the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, 54 drugs have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the four drugs (Hydroxyurea, L-Glutamine, Crizanlizumab tmca and Voxelotor) that have been approved by the United States Food and Drug Administration (FDA) based on suc

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… Consequently, higher hematocrit is associated with increased blood viscosity that promotes vaso-occlusion and the precipitation of a new VOC. …

Orthogonal targeting of osteoclasts and myeloma cells for radionuclide stimulated dynamic therapy induces multidimensional cell death pathways.

Rationale: Multiple myeloma (MM) is a multifocal malignancy of bone marrow plasma cells, characterized by vicious cycles of remission and relapse that eventually culminate in death. The disease remains mostly incurable largely due to the complex interactions between the bone microenvironment (BME) and MM cells (MMC). In the "vicious cycle" of bone disease, abnormal activation of osteoclasts (OCs) by MMC causes severe osteolysis, promotes immune evasion, and stimulates the growth of MMC. Disrupting these cancer-stroma interactions would enhance treatment response. Methods: To disrupt this cycle

Current Overview of Treatment for Metastatic Bone Disease.

The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient's prognosis, quality of life, postoperative function, and risk of pos

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review.

Haematological malignancies induce important alterations of the immune system, which account for the high frequency of autoimmune complications observed in patients. Cutaneous immune-mediated diseases associated with haematological malignancies encompass a heterogeneous group of dermatoses, including, among others, neutrophilic and eosinophilic dermatoses, autoantibody-mediated skin diseases, vasculitis and granulomatous dermatoses. Some of these diseases, such as paraneoplastic pemphigus, are associated with an increased risk of death; others, such as eosinophilic dermatoses of haematological

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… Of note, HMs augment blood viscosity, which can impair the clearance of normally produced immune complexes, and lead to their accumulation on small blood vessels [ 178 , 184 , 194 – 196 ]. …

Complication from Desensitization

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Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results.

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have f

Emergency Care

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A technical note on emerging combination approach involved in the onconanotherapeutics.

Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made

Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients.

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlappi

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… Several mechanisms underlie EPO-induced hypertension, including increased blood viscosity, and, potentially, a skewed balance between vasoconstrictor and vasodilator prostaglandins with vascular resistance to the vasodilator effects of NO. 183 Indeed, in rats treated with EPO, elevated vascular intracellular …

Plasma Cell Myeloma: Биохимический анализ диагноза, лечения и умного нанокарьера - терапевтического развития.

Плазменная миелома (ПХМ) классифицируется как рак крови и характеризуется аномальным распространением плазменных клеток в костном мозге и чрезмерным производством моноколональных иммуноглобулинов, что приводит к постоянному повреждению жизненно важных органов. Несмотря на то, что стратегии лечения улучшились благодаря разработке протеазонных ингибиторов (ИП), иммуноводных препаратов (ИМИД) и моноклонных антител (mAbs), ПХМ остается неизлечимым заболеванием из-за молекулярной неоднородности и развития сопротивляемости лекарствам. В этом обзоре мы обсуждаем биохимические и молекулярные основы, л

8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland.

The 8th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4th EAC. The new agenda format for 2012 included three parallel tracks on: (1) naked antibodies; (2) antibody drug conjugates (ADCs); and (3) bispecific antibodies and alternative scaffolds. The meeting started and closed with three plenary lectures to give common background and to share the final panel discussion and conclusions. The two day event included case studies and networking for nearly 250 delegates who learned of the latest adva

Co-Encapsulation of Multiple Antineoplastic Agents in Liposomes by Exploring Microfluidics.

The inherent complexity of cancer proliferation and malignancy cannot be addressed by the conventional approach of relying on high doses of a single powerful anticancer agent, which is associated with poor efficacy, higher toxicity, and the development of drug resistance. Multiple drug therapy (MDT) rationally designed to target tumor heterogeneity, block alternative survival pathways, modulate the tumor microenvironment, and reduce toxicities would be a viable solution against cancer. Liposomes are the most suitable carrier for anticancer MDT due to their ability to encapsulate both hydrophil