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Supportive Care and Symptom Management for Patients With Immunoglobulin Light Chain (AL) Amyloidosis.

Immunoglobulin light chain (AL) amyloidosis is a disorder of clonal plasma cells characterized by deposition of amyloid fibrils in a variety of tissues, leading to end-organ injury. Renal or cardiac involvement is most common, though any organ outside the central nervous system can develop amyloid deposition, and symptomatic presentations may consequently vary. The variability and subtlety of initial clinical presentations may contribute to delayed diagnoses, and organ involvement is often quite advanced and symptomatic by the time a diagnosis is established. Additionally, while organ function

Left Ventricular Hypertrophy: Etiology-Based Therapeutic Options.

Determining the etiologies of left ventricular hypertrophy (LVH) can be challenging due to the similarities of the different manifestations in clinical presentation and morphological features. Depending on the underlying cause, not only left ventricular mass but also left ventricular cavity size, or both, may increase. Patients with LVH remain asymptomatic for a few years, but disease progression will lead to the development of systolic or diastolic dysfunction and end-stage heart failure. As hypertrophied cardiac muscle disrupts normal conduction, LVH predisposes to arrhythmias. Distinguishin

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… In cardiac amyloidosis, amyloid is deposited in the extracellular space of the myocardium, resulting in thickening and stiffening of ventricular walls, with resultant heart failure and conductive dysfunction [ 128 – 130 ]. … Transthyretin Amyloidosis and Treatment Transthyretin amyloidosis is a condition in which transthyretin, a physiological protein primarily synthesized by the liver, misfolds into insoluble B-pleated sheets and deposits as amyloid in the extracellular space of the myocardium. …

Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies.

Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to as

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia.

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-2

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… Tumor-derived EVs, carrying specific miRNAs and proteins, can induce a metabolic remodeling of white adipocytes, leading to increased lipolysis and, therefore, to a higher availability of free FA and glucose in the extracellular space. …

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

Harnessing the Therapeutic Potential of Mesenchymal Stem Cells in Cancer Treatment.

Cancer, as a complicated disease, is considered to be one of the major leading causes of death globally. Although various cancer therapeutic strategies have been established, however, some issues confine the efficacies of the treatments. In recent decades researchers for finding efficient therapeutic solutions have extensively focused on the abilities of stem cells in cancer inhibition. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can the most widely extracted from various sources such as the bone marrow (BM), placenta, umbilical cord (UC), menses blood, Wharton's jelly (WJ

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… These EVs are actively released by all types of cells into the extracellular space and plentifully found in different body biofluids such as saliva, synovial fluid, amniotic fluid, ejaculate, cerebral spinal fluid, milk, and even urine. 118 - 121 These spherical, bilayered particles are rich in proteins …

Involvement of the Opioid Peptide Family in Cancer Progression.

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidenc

From Nanoparticles to Cancer Nanomedicine: Old Problems with New Solutions.

Anticancer nanomedicines have been studied over 30 years, but fewer than 10 formulations have been approved for clinical therapy today. Despite abundant options of anticancer drugs, it remains challenging to have agents specifically target cancer cells while reducing collateral toxicity to healthy tissue. Nanocompartments that can be selective toward points deeply within malignant tissues are a promising concept, but the heterogeneity of tumor tissue, inefficiency of cargo loading and releasing, and low uniformity of manufacture required from preclinical to commercialization are major obstacle

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article c

Аккумулирование опустошающих липидов в Arf1-Ablanted Neurorons способствует нейродегенерации с помощью mtDNA и активации воспаляющих путей в Микроглии.

В нейронах и глиальных клетках были обнаружены липидные метаболические расстройства у пациентов с нейродегенеративной (ND) и животных. Однако патологическая связь между липидными капельками и НУ остается слабой. Недавняя работа высветила полезность модели мыши Arf1-knockout с учетом особенностей нейронов и соответствующих клеток для разъяснения связи между расстройствами липидного метаболизма и амиотропическим боковым склерозом (ALS) и множественным склерозом (MS). В этом исследовании было установлено, что недостача арф1 вызвала первичный синтез избытка жирной кислоты через ось АКТ-mTORC1-SREB

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… However, when mitochondrial damage induces excessive elevation of ROS and defects in neuron‐glial lipid transfer, it can lead to the accumulation of oxidized lipids in neurons and extracellular spaces, thereby inducing neurodegeneration. [ 12 , 13 , 14 , 15 ] Our recent study …

Metabolic features of myeloma cells in the context of bone microenvironment: Implication for the pathophysiology and clinic of myeloma bone disease.

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) into the bone marrow (BM). The complex interaction between the BM microenvironment and MM PCs can lead to severe impairment of bone remodeling. Indeed, the BM microenvironment exerts a critical role in the survival of malignant PCs. Growing evidence indicates that MM cells have several metabolic features including enhanced glycolysis and an increase in lactate production through the upregulation of glucose transporters and enzymes. More recently, it has been reported that MM ce

Developing high-concentration monoclonal antibody formulations for subcutaneous administration to improve patient treatment.

The transition of immunotherapy administration from intravenous infusion to subcutaneous (SC) administration of monoclonal antibody formulations for oncology patients has garnered significant interest. SC administration offers multiple benefits, including potential for at-home administration, enhanced patient compliance, reduced hospital congestion, lowered health care costs, and improved sustainability by reducing drug wastage and minimizing environmental impact. However, for many biologics, the shift to SC administration requires the development of high-concentration monoclonal antibody prod

MSC-derived extracellular vesicles: Precision miRNA delivery for overcoming cancer therapy resistance.

Cancer remains a prominent worldwide health concern, presenting existing therapies with frequent difficulties, including major toxicity, limited effectiveness, and treatment resistance emergence. These issues highlight the necessity for novel and enhanced remedies. Exosomes, tiny extracellular vesicles that facilitate intercellular communication, have attracted interest for their potential medicinal applications. Carrying a variety of molecules, including microRNAs, small interfering RNAs, long non-coding RNAs, proteins, lipids, and DNA, these vesicles are positioned as promising cancer treatm

Сравнительный анализ нервно-воспалительных путей болезни Альцгеймера, болезни Паркинсона и множественного склероза: понимание сходства и различий.

Растет интерес к нейродегенеративным болезням, усугубляющим значительное социально-экономическое бремя, вызванное старением общества. Несмотря на то, что каждая болезнь имеет различные этиологии, нейроинфламмация, как считается, играет решающую роль в болезни Альцгеймера (AD), болезни Паркинсона (PD) и множественном склерозе (MS). Помимо патогенной функции воспаления мозга, растет число свидетельств того, что иммунная реакция необходима для нейрорегенерации. Этот обзор сравнивает и контрастирует с нейроинфламационными путями, которые характерны для различных нейродегенеративных заболеваний. В

Bone, a Secondary Growth Site of Breast and Prostate Carcinomas: Role of Osteocytes.

Bone is the primarily preferred site for breast and prostate cancer to metastasize. Bone metastases are responsible for most deaths related to breast and prostate cancer. The bone's particular microenvironment makes it conducive for the growth of cancer cells. Studies on bone metastasis have focused on the interaction between cancer cells and the bone microenvironment. Osteocytes, the most common cell type of bone tissue, have received little attention in bone metastasis, although they are master signal sensors, integrators, and skeleton transducers. They play an important role in regulating b

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… The extracellular space within the canaliculi is accessible to peripheral blood vessels. Osteocytes are immersed in a canalicular fluid that supplies them with nutrients, oxygen, and information from systemic circulation. …

Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.

Recently, increasing interest has been in utilizing mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially exosomes, as nanocarriers for miRNA delivery in cancer treatment. Due to such characteristics, nanocarriers are specific: biocompatible, low immunogenicity, and capable of spontaneous tumor accumulation. MSC-EVs were loaded with therapeutic miRNAs and minimized their susceptibility to degradation by protecting the miRNA from accessibility to degrading enzymes and providing targeted delivery of the miRNAs to the tumor cells to modulate oncogenic pathways. In vitro and i

Different types of amyloid concomitantly present in the same patients.

Different types of amyloid concomitantly present in the same patient is believed to be improbable. We reported four cases of patients with plasma cell disorders who were found to have biopsy proven concomitant different types of amyloid fibrils deposition. We characterized amyloid fibrils using immunogold electron microscopy. There is lack of experience in the treatment of these frail and elderly patients, who are on the threshold between necessity of chemotherapy for AL amyloidosis and necessity to avoid harmful treatment related toxicity. All patients with a systemic amyloid syndrome require

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… Introduction Amyloidosis covers a group of systemic disorders characterized by the deposition of misfolded protein within the extracellular space, with subsequent deposition in tissues and organ damage. …

Exploiting Literature-derived Knowledge and Semantics to Identify Potential Prostate Cancer Drugs.

In this study, we report on the performance of an automated approach to discovery of potential prostate cancer drugs from the biomedical literature. We used the semantic relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations using SemRep, to extract potential relationships using knowledge of cancer drugs pathways. Two cancer drugs pathway schemas were constructed using these relationships extracted from SemMedDB. Through both pathway schemas, we found drugs already used for prostate cancer therapy and drugs not currently listed as the prostate cancer

Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease.

Prognostic, diagnostic or predictive biomarkers are urgently needed for assessment of chronic graft-versus-host disease (cGvHD), a major risk for patients undergoing allogeneic hematopoietic stem cell transplantation. The main goal of this review generated within the COST Action EUROGRAFT "Integrated European Network on Chronic Graft Versus Host Disease" was to identify potential novel biomarkers for cGvHD besides the widely accepted molecular and cellular biomarkers. Thus, the focus was on cellular biomarkers, alloantibodies, glycomics, endothelial derived particles, extracellular vesicles, m

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… They are released by most, if not all cell types into the extracellular space and can be sub-classified based on their originating cell and their biogenesis. EVs contain a subset of proteins, lipids and nucleic acids, including microRNA, that are derived from the parent cell ( 92 ). …