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Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play a vital role in the pathogenesis of multiple myeloma (MM), especially for tumor invasion and osteolytic osteopathy. By breaking down extracellular matrix (ECM) components and releasing the proteins composing the ECM and growth factors, as well as their receptors, MMPs affect tissue integrity and promote cancer cell invasion and metastasis. A vital pathophysiological characteristic of MM is the progress of osteolytic lesions, which are brought on by interactions between myeloma cells and the bone marrow mic

From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights.

Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte colony-stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone h

A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological sig

Novel agents for advanced pancreatic cancer.

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer.

A Narrative Review on the Antitumoral Effects of Selected Mediterranean Plant Products from Southern Italy.

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural comp

INSIGHT MM: a large, global, prospective, non-interventional, real-world study of patients with multiple myeloma.

With the introduction of new drugs with different mechanisms of action, multiple myeloma (MM) patients' outcomes have improved. However, the efficacy seen in clinical trials is often not seen in real-world settings and data on the effectiveness of MM therapies are needed. INSIGHT MM is a prospective, global, non-interventional, observational study that is enrolling approximately 4200 patients with newly diagnosed or relapsed/refractory MM, making it the largest study of its kind to date. The study aims to describe contemporary, real-world patterns of patient characteristics, clinical disease p

CAR-T cells targeting CD19 for the treatment of ANCA vasculitis.

Autoimmune anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) and glomerulonephritis is characterized by the presence of autoantibodies (so-called ANCA), which, by binding to the body's own antigens, lead to damaged blood vessels (vasculitis) and subsequently to organ damage, particularly of the kidneys. The primary endogenous antigens are the enzymes proteinase 3 (PR3) and myeloperoxidase (MPO) expressed by neutrophil granulocytes and monocytes. In addition to the autoantibodies, both T-cellular response to those autoantigens and monocyte/macrophage-mediated process

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has bee

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.

2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

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… Cytogenetic evaluation with array comparative genomic hybridization(CGH) analysis showed duplication of Xq25 and Xq28 consistent with MDS. Discussion: MDS is caused by duplications involving the MECP2 gene locus of the X chromosome at Xq28. …

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

Passive Monoclonal and Polyclonal Antibody Therapies

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Lifestyle Factors and Cancer: A Narrative Review.

Lifestyle factors and their impact on cancer prevention, prognosis, and survivorship are increasingly recognized in the medical literature. Lifestyle factors are primarily defined here as diet and physical activity. We conducted a narrative review of the primary published data, including randomized controlled trials and prospective studies, on the impact of primary lifestyle factors on oncogenesis and clinical outcomes in the preventative and survivorship setting. First, we discuss the oncogenic mechanisms behind primary lifestyle factors (diet, physical activity and, within these 2, obesity).

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research-practice gaps, challenges, and insights.

To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune-based therapeutic modalities of anticancer

The Role of t(11;14) in Tailoring Treatment Decisions in Multiple Myeloma.

Multiple myeloma (MM) represents a hematological neoplasia with an uncontrolled proliferation of malignant plasma cells and complex cytogenetic abnormalities. t(11;14) has emerged as a crucial genetic aberration and is one of the most common primary translocations in MM. Patients harboring t(11;14) represent a distinctive subgroup with a clinical profile that differs from t(11;14)-negative MM risk categories. One of the key features linked with t(11;14) is the BCL2 dependency, indicating vulnerability to BCL2 inhibition. BCL2 inhibitors, such as venetoclax, demonstrated impressive efficacy alo

Oral Communication abstracts

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Novel Therapeutic Approaches in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, characterized by the clonal proliferation of immature lymphoid precursors. The distinction between B-cell ALL (B-ALL) and T-cell ALL (T-ALL) is fundamental, as each subtype exhibits distinct cytomorphological, genetic, and clinical features influencing prognosis and therapeutic strategies. Conventional multi-phase chemotherapy has significantly improved survival rates, yet its efficacy is limited by severe short- and long-term toxicities, highlighting the need for more selective therapeutic approaches. Advances in mole

High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.

Vitamin C, also known as ascorbic acid, has sparked controversy since it first emerged as a potential anti-cancer agent. However, an increasing number of preclinical studies have demonstrated that high-dose vitamin C exhibits selective anti-tumor effects, including "pro-oxidative cytotoxicity", "anti-cancer epigenetic regulation", and "immune modulation". Consequently, vitamin C has reemerged as a promising anti-cancer therapy in the form of high-dose administration. Advancements in pharmacokinetic research have facilitated the development of clinical trials. Early clinical studies across vari

Экстраклектные везикли для клинической диагностики: от массовых измерений до одновидового анализа.

Экстраклектные везикулы (ЭМ) играют ключевую роль в межклеточном общении, сигнальных путях и патогенезе заболеваний, перевозя биомолекулы, такие, как ДНК, РНК, белки и липиды, полученные из клеток их происхождения, и они продемонстрировали значительный потенциал в области клинического применения. Их клиническое значение подчеркивает необходимость применения чувствительных методов для полной реализации их диагностического потенциала. В рамках этого всеобъемлющего обзора мы изучаем гетерогенность ЭМ, связанную с биогенезом, структурой, содержанием, происхождением, типом выборки и функциональными