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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

No patient left behind: The promise of immune priming with epigenetic agents.

Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as

Marizomib in the therapy of brain tumors-how far did we go and where do we stand?

Out of several types of tumors of the central nervous system (CNS), glioblastoma (GBM) represents one of the most frequent and malignant forms of brain neoplasms. To date, GBM holds very limited therapeutic options leaving patients with poor prognosis of survival. As such, novel treatment approaches are constantly quested. One of these strategies is based on the utilization of proteasome inhibitors (PIs). However, although several PIs have been approved as therapy for patients with hematological malignancies, these treatment benefits cannot not be easily extrapolated to brain tumors. This is m

Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

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… The activated STAT dimers dissociate from the receptor, rapidly translocate to the nucleus, specifically bind to DNA sequences in the promoter regions of target genes, recruit auxiliary transcription factors and RNA polymerase II, and initiate the transcriptional expression of target genes [ 66 ]. …

Advanced Diagnostic Techniques

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Эпигенетика и метаболическая метаболическая дисфункция при многоразовом склерозе: обзор подходов к травяным лекарствам и текущих клинических испытаний.

Множественный склероз (MS) — сложная аутоиммунная болезнь, характеризующаяся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (КНС). Хотя точные причины остаются неясными, недавние исследования подчеркивают важную роль эпигенетических изменений и митохондриальной дисфункции в начале и развитии болезни. Эпигенетические изменения, такие, как метилация ДНК, модификация гистона и регулирование микроРНК, влияют на генное выражение, не изменяя последовательности ДНК, что приводит к иммунной дисрегуляции и воспалению. Аналогичным образом, митохондриальная дисфункция, отме

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 1 : National Harbor, MD, USA. 6-10 November 2019.

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Hallmarks of Cancer Affected by the MIF Cytokine Family.

New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family of cytokines, comprising MIF and DDT (also known as MIF2), are overexpressed in almost all cancer types, and their high expressions are related to a worse prognosis for the patients. MIF is involved in 9 of the 10 hallmarks of cancer, and its inhibition by antibodies, nanobodies, or small synthe

JunB is a key regulator of multiple myeloma bone marrow angiogenesis.

Bone marrow (BM) angiogenesis significantly influences disease progression in multiple myeloma (MM) patients and correlates with adverse prognosis. The present study shows a statistically significant correlation of the AP-1 family member JunB with VEGF, VEGFB, and IGF1 expression levels in MM. In contrast to the angiogenic master regulator Hif-1α, JunB protein levels were independent of hypoxia. Results in tumor-cell models that allow the induction of JunB knockdown or JunB activation, respectively, corroborated the functional role of JunB in the production and secretion of these angiogenic fa

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The

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… The microRNAs are usually transcribed by RNA polymerase II, and sometimes by RNA polymerase III, into long primary precursor transcripts referred to as pri-miRNAs. miRNA are encoded by one arm of a stem loop structure embedded in introns or, less frequently, exons of protein-coding or noncoding transcripts …

Marine Natural Products with Activities against Prostate Cancer: Recent Discoveries.

Prostate cancer is the most common cancer in men, with over 52,000 new cases diagnosed every year. Diagnostics and early treatment are potentially hindered by variations in screening protocols, still largely reliant on serum levels of acid phosphatase and prostate-specific antigen, with tumour diagnosis and grading relying on histopathological examination. Current treatment interventions vary in terms of efficacy, cost and severity of side effects, and relapse can be aggressive and resistant to the current standard of care. For these reasons, the scientific community is looking for new chemoth

CD123 as a Therapeutic Target in the Treatment of Hematological Malignancies.

The interleukin-3 receptor alpha chain (IL-3R), more commonly referred to as CD123, is widely overexpressed in various hematological malignancies, including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, Hodgkin lymphoma and particularly, blastic plasmacytoid dendritic neoplasm (BPDCN). Importantly, CD123 is expressed at both the level of leukemic stem cells (LSCs) and more differentiated leukemic blasts, which makes CD123 an attractive therapeutic target. Various agents have been developed as drugs able to target CD123 on malignant leukemic cells and o

Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis.

Classic tumor therapy, consisting of cytotoxic agents and/or targeted therapy, has not overcome therapeutic limitations like poor risk genetic parameters, genetic heterogeneity at different metastatic sites or the problem of undruggable targets. Here we summarize data and trials principally following a completely different treatment concept tackling systems biologic processes: the principle of communicative reprogramming of tumor tissues, i.e., anakoinosis (ancient greek for communication), aims at establishing novel communicative behavior of tumor tissue, the hosting organ and organism via re

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values.

Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific database

Late Breaking Orals.

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Molecular Evaluation of Low-grade Low-stage Endometrial Cancer With and Without Recurrence.

Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences. Four cases of LGLS EC with recurrence and 8 cases without recurrence were evaluated via whole-exome sequencing. Three of the 4 recurrent tumors were evaluated via Oncomine Com

NF-κB in biology and targeted therapy: new insights and translational implications.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other importa

Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.

Immune evasion represents a significant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. Moreover, it explores the dynamic role of the tumor microenvironment (TME)

ISEV2018 абстрактная книга

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Specific epigenetic regulators serve as potential therapeutic targets in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), a disorder observed mostly in older human beings, is characterised by chronic and progressive lung scarring leading to an irreversible decline in lung function. This health condition has a dismal prognosis and the currently available drugs only delay but fail to reverse the progression of lung damage. Consequently, it becomes imperative to discover improved therapeutic compounds and their cellular targets to cure IPF. In this regard, a number of recent studies have targeted the epigenetic regulation by histone deacetylases (HDACs) to develop and categorise