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Radiation-Induced Oral Mucositis.

Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

The Impact and Molecular Mechanisms of Exercise in Cancer Therapy.

Cancer is a major global health issue, and exercise has become a key supportive treatment. It contributes to reducing cancer risk, enhancing prognosis, and aiding recovery, especially for survivors. However, the exact mechanisms, such as how exercise reduces cancer risk or enhances treatment, are still unclear. Current research often focuses on specific cancer types, ignoring the diverse needs of patients. This limits the development of personalized exercise plans. Additionally, there is insufficient comparison of exercise types-like aerobic, resistance, and high-intensity interval training-re

Update on current pancreatic treatments: from molecular pathways to treatment.

Pancreatic cancer is still diagnosed at a late stage although we have novel diagnostic tools. Pancreatic cancer chemotherapy treatment resistance is observed and therefore novel treatments are in need. Anti-cancer stem cell therapy, combination of chemotherapy and/or radiotherapy with immunotherapy, proteins/enzymes and gene therapy are currently under evaluation. Targeted treatment with tyrosine kinase inhibitors is also administered and novel inhibitors are also under evaluation. In the current review we present recent data from our search within the year 2018.

Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts.

Progression of multiple myeloma (MM) is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles takes place. This cross-talk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. In this paper, we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine model. We found that 5TGM1 sEVs, or 'exosomes', not only enhanced osteoclast activity, they also blo

Нейродегенеративные биомаркеры при множественном склерозе: на стыке между исследованиями и клинической практикой.

Множественный склероз (MS) — хроническое аутоиммунное расстройство, характеризующееся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (CNS). Хотя подстрекательские компоненты MS были тщательно изучены, прогрессивный нейродегенеративный аспект по-прежнему является одним из важнейших факторов, способствующих долгосрочной инвалидности. Поэтому выявление и проверка биомаркеров, связанных с нейродегенеративными процессами, имеют важнейшее значение для улучшения диагностики, прогнозирования и мониторинга лечения. В рамках этого обзора изучаются цереброспинные жидкости (

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… Certain ceramides and sphingolipids have been found at different levels in MS patients versus controls, implicating these molecules as potential biomarkers of neurodegeneration [ 38 ]. … Progression Monitoring Exploratory Mey et al. 2023 [ 35 ]; Sandi et al. 2021 [ 34 ] Lipid Biomarkers (Ceramides, Cholesterol, Oxysterols, Phospholipids) Blood, CSF Changes in lipid composition associated with myelin integrity and neurodegeneration. …

The Complexities of Diagnosis with Co-Existing Gaucher Disease and Hemato-Oncology-A Case Report and Review of the Literature.

Hematological abnormalities are the most common early symptoms of Gaucher disease (GD), with an increased risk of hematopoietic system malignancies reported in patients with GD. GD may be associated with monoclonal and polyclonal gammopathies; however, the mechanism of association of GD with multiple myeloma (MM) remains uncertain. Enzyme replacement therapy (ERT) has been shown to improve patients' cytopenia and it seems to facilitate anti-myeloma therapy in patients with co-occurring GD and MM. Although it is necessary to demonstrate the deficiency of enzymatic activity, as well as using gen

Ganglioside therapy in cancer molecular insights and therapeutic opportunities.

Gangliosides, a class of glycosphingolipids located on the plasma membrane of nearly all cells, play a crucial role in cell signaling and lipid raft dynamics. Their expression is notably high during embryonic development, markedly reduced in most adult tissues, but significantly elevated in various tumor tissues. This distinct expression pattern highlights gangliosides as promising therapeutic targets due to their roles in tumor progression, metastasis, and therapeutic resistance. Targeted ganglioside therapies, particularly monoclonal antibodies against GD2, have already demonstrated clinical

Insulin Resistance at the Crossroads of Metabolic Inflammation, Cardiovascular Disease, Organ Failure and Cancer.

Insulin resistance (IR) describes impaired hormone signaling that triggers compensatory homeostatic responses resulting in hyperinsulinemia, increased accumulation of fatty substrates, lipotoxicity, oxidative stress, inflammation, cell death and fibrosis in target tissues. These processes ultimately lead to organ dysfunction and predispose certain individuals to various types of cancer. In this context, we will review the molecular pathogenesis and clinical significance of IR, its role in 'metaflammation', and the damage caused by IR in the pancreas, cardiovascular system, liver, and kidneys.

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… These particles, along with elevated free fatty acids and ceramides, activate TLR4 and NLRP3 inflammasomes in macrophages, leading to foam-cell formation and unstable plaques [ 116 ]. … Elevated glucose boosts mitochondrial ROS, while free fatty acid influx generates toxic diacylglycerols and ceramides that activate PKCε, JNK, and endoplasmic reticulum (ER) stress pathways [ 129 , 130 ]. …

Profile of eliglustat tartrate in the management of Gaucher disease.

Gaucher disease (GD) is a lysosomal storage disorder caused by the deficient activity of acid beta glucosidase, with consequent accumulation of glucosylceramide in the spleen, liver, bone marrow, and various organs and tissues. Currently, the gold standard for GD treatment is enzyme replacement therapy (ERT). The efficacy of ERT in improving or stabilizing the visceral and hematological symptoms of GD is well-proven. However, since ERT has to be administered by frequent intravenous infusions, this therapeutic approach has an important impact on the patient's quality of life. Eliglustat tartrat

Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

The Endocannabinoid System as a Pharmacological Target for New Cancer Therapies.

Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons. Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and ep

Высокий уровень распространенности GALC Gene Options на взрослых с нейродегенеративными условиями.

ОКРУЖАЮЩАЯ СРЕДА И ЦЕЛЬ: Дефицит галактоцереброзидаза (ГАЛК) вызывает болезнь Краббе, тяжёлое лизосомальное нейродегенеративное состояние. Появляющиеся данные указывают на то, что гетерозиговые варианты GALC могут способствовать множеству склерозов, расстройству гиперактивности, отсутствию внимания, и синуклейнопатии. Мы намерены изучить потенциальную связь между гетероциговидными вариантами GALC и нейродегенеративными расстройствами, расширяя существующую литературу. МЕТОДЫ: Мы провели обследование 110 взрослых с симптомами, которые разделяются лизосомными расстройствами хранения (ЛСД) и расп

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

Raman Spectroscopic Stratification of Multiple Myeloma Patients Based on Exosome Profiling.

Multiple myeloma (MM) is a hematological malignancy characterized by abnormal plasma cell proliferation within the bone marrow which leads to progressive bone marrow failure, skeletal osteolytic lesions, and renal insufficiency, thus severely affecting the quality of life. MM is always preceded by monoclonal gammopathy of uncertain significance (MGUS), which progresses to asymptomatic-MM (aMM) or symptomatic-MM (sMM) at a rate of 1% per year. Despite impressive progress in the therapy of the disease, MM remains incurable. Based on these premises, the identification of biomarkers of MGUS progre

α2-3-sialylated Гликосфинголипиды при нейроинфламмации, иммунитете и запрограммированной смерти клеток: механистические доказательства и регулирование в зависимости от контекста: всеобъемлющий обзор.

α2-3-sialylated glycosphingolids (α2)3-GSLs) являются основными составляющими нейронных мембран и липидных плотов, где они формируют сепарацию рецепторов, комплекс сигналов и связь с клетками. Однако их биологическое воздействие варьируется в зависимости от молекулярного подтипа, типа клеток, стадии заболевания, концентрации и местной микроокружающей среды. В настоящем обзоре обобщены данные о перепончатых изменениях в α2-3-GSL профили и их связи с нейроинфламмацией, иммунной реакцией, протеостазом и запрограммированной клеточной смертностью через болезнь Паркинсона, болезнь Альцгеймера, болез

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nerv

Гипоксия в множестве склерозов.

Низкая доступность кислорода (гипоксии) является заметной, но плохо понимаемой особенностью множественного склероза (МС). Неизвестно, вызывает ли гипоксия патологию и симптомы MS или она является следствием других патологических явлений, таких, как воспаление и сосудистая дисфункция. Здесь мы резюмируем имеющуюся литературу о взаимосвязи между гипоксией и как патологическими, так и симптомными характеристиками MS. Острая экологическая гипоксия (т.е. высота) может вызвать или облегчить события, связанные с MS, возможно, путем усиления гипоксии тканей в центральной нервной системе. Соответственн

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… In this study, increased levels of ceramides (a class of sphingolipids, some types of which are associated with mitochondrial damage [ 126 , 127 ]) were found in MS cerebrospinal fluid and proposed to be the main factors leading to the observed mitochondrial alterations [ 125 ]. … Ceramides and sphingolipid metabolism are known to be highly sensitive to hypoxic stress and high levels of long-chain ceramides can induce mitochondrial dysfunction [ 128 ]. …

Tumour-Derived Extracellular Vesicles (EVs): A Dangerous "Message in A Bottle" for Bone.

Several studies have shown the importance of Extracellular Vesicles (EVs) in the intercellular communication between tumour and resident cells. Through EVs, tumour cells can trigger cell-signalling molecules and shuttle exogenous information to target cells, thus promoting spread of the disease. In fact, many processes are fuelled by EVs, such as tumour invasion and dormancy, drug-resistance, immune-surveillance escape, extravasation, extracellular matrix remodelling and metastasis. A key element is certainly the molecular profile of the shed cargo. Understanding the biochemical basis of EVs w