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Maintenance therapy in acute myeloid leukemia: advances and controversies.

The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effe

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… A comparison of limited consolidation chemotherapy therapy or not, and demethylation maintenance or not in older patients with AML and high risk MDS: long term results of the UK NCRI AML16 trial. Haematologica. 2015;100(Suppl 1):194.25361944 20. Huls G, Chitu DA, Havelange V, et al. …

The Landscape of lncRNAs in Multiple Myeloma: Implications in the "Hallmarks of Cancer", Clinical Perspectives and Therapeutic Opportunities.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as "hallmarks of cancer" that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncR

The functional role of long noncoding RNA in resistance to anticancer treatment.

Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, e

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… After treating epithelial OC cell lines with curcumin and 5-AZA-dC, demethylation of MEG3 weakened the ability of extracellular vesicles (EVs) to enhance cisplatin resistance through binding with miR-214. 97 In GC patients with cisplatin resistance, the expression of ANRIL was significantly upregulated …

The Biogenesis and Functions of piRNAs in Human Diseases.

Piwi-interacting RNAs (piRNAs) are a novel type of small noncoding RNAs, which are 26-30 nt in length and bind to Piwi proteins. These short RNAs were originally discovered in germline cells and are considered as key regulators for germline maintenance. A growing body of evidence has now extended our views into piRNA biological significance showing that they can also regulate gene expression in somatic cells through transposon silencing, epigenetic programming, DNA rearrangements, mRNA turnover, and translational control. Mounting studies have revealed that the dysregulation of piRNAs may caus

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… Uni-strand clusters harbor the transcription-associated histone 3 lysine 4 demethylation (H3K4me2) mark at promoters. …

Genes, Gene Loci и их влияние на иммунную систему развития множественных склерозов: систематический обзор.

Множественный склероз (MS) — это состояние, характеризующееся повреждением центральной нервной системы (CNS), которое вызывает у пациентов когнитивные и физические трудности. Хотя болезнь имеет сложную этиологию, которая включает генетические и экологические факторы, мало что известно о роли генов и генологов в ее развитии. Цели: Данное исследование было направлено на изучение воздействия генов и ген-лочи на иммунную систему в ходе разработки MS. Мы стремились определить основные гены и генные лочи, которые играют роль в патогенезе MS, и последствия для будущей разработки подходов к клиническо

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… Secondary-Progressive MS (SPMS) | TNFRSF1A, HLA alleles | These genes can induce demethylation and chronic inflammation, which often causes patients to transition from RRMS to SPMS. 4.7. …

Lysine Methyltransferase Inhibitors Impair H4K20me2 and 53BP1 Foci in Response to DNA Damage in Sarcomas, a Synthetic Lethality Strategy.

BackgroundChromatin is dynamically remodeled to adapt to all DNA-related processes, including DNA damage responses (DDR). This adaptation requires DNA and histone epigenetic modifications, which are mediated by several types of enzymes; among them are lysine methyltransferases (KMTs).MethodsKMT inhibitors, chaetocin and tazemetostat (TZM), were used to study their role in the DDR induced by ionizing radiation or doxorubicin in two human sarcoma cells lines. The effect of these KMT inhibitors was tested by the analysis of chromatin epigenetic modifications, H4K16ac and H4K20me2. DDR was monitor

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… FIGURE 8 The assembly of 53BP1 foci is not affected by JMJD2i treatment, which inhibits lysine demethylation, after inducing DSBs with IR in U2OS cells. (A) γH2AX and 53BP1 foci formation in response to JMJD2 inhibitor and/or IR. …

Hepatocellular carcinoma: Understanding molecular mechanisms for defining potential clinical modalities.

Liver cancer is the sixth most commonly occurring cancer and costs millions of lives per year. The diagnosis of hepatocellular carcinoma (HCC) has relied on scanning techniques and serum-based markers such as α-fetoprotein. These measures have limitations due to their detection limits and asymptomatic conditions during the early stages, resulting in late-stage cancer diagnosis where targeted chemotherapy or systemic treatment with sorafenib is offered. However, the aid of conventional therapy for patients in the advanced stage of HCC has limited outcomes. Thus, it is essential to seek a new tr

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… hepatocellular carcinoma J Hepatol 2015 63 1164 1172 26095183 10.1016/j.jhep.2015.06.009 76 Lin Q Wu Z Yue X Yu X Wang Z Song X Xu L He Y Ge Y Tan S Wang T Song H Yuan D Gong Y Gao L Liang X Ma C ZHX2 restricts hepatocellular carcinoma by suppressing stem cell-like traits through KDM2A-mediated H3K36 demethylation …

MicroRNAs-Based Nano-Strategies as New Therapeutic Approach in Multiple Myeloma to Overcome Disease Progression and Drug Resistance.

MicroRNAs (miRNAs, or miRs) are single-strand short non-coding RNAs with a pivotal role in the regulation of physiological- or disease-associated cellular processes. They bind to target miRs modulating gene expression at post-transcriptional levels. Here, we present an overview of miRs deregulation in the pathogenesis of multiple myeloma (MM), and discuss the potential use of miRs/nanocarriers association in clinic. Since miRs can act as oncogenes or tumor suppressors, strategies based on their inhibition and/or replacement represent the new opportunities in cancer therapy. The miRs delivery s

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

Targeted Therapies in Adult B-Cell Malignancies.

B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted or common surface markers, activation of cellular pathways that regulate cell cycle, metabolism, proteasome activity, and protein synthesis. All molecules involved in these different cellular mechanisms are potent therapeutic targets. Nowadays, due to the progress of the biology, more and more targeted drugs are identified, a situation that is c

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

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… In the methylation module, the equilibrium between enhancer of zeste homolog 2 (EZH2)-mediated H3K27 trimethylation and lysine demethylase (KDM)-mediated demethylation interacts with the A20–NF-κB regulatory axis, thereby modulating inflammatory transcription. … The opposing demethylation process is facilitated by lysine demethylase 6A (KDM6A, also known as UTX) and KDM6B (also known as JMJD3), which are capable of removing trimethylation at lysine 27 on histone H3 (H3K27me3), thereby alleviating repression at relevant gene loci and promoting the expression …

Каннабиноиды в раке: Молекулярные механизмы смерти клеток и возможности перевода.

Каннабиноиды представляют собой терпенофенолические соединения, полученные из Cannabis sativa L., которые осуществляют широкий спектр биологической и фармакологической деятельности. Растущие данные свидетельствуют об их потенциале как модуляторов развития рака, особенно посредством подавления роста клеток опухоли, ангиогенеза и метастаза в различных моделях опухоли. В настоящем обзоре содержится всеобъемлющий обзор молекулярных механизмов, с помощью которых природные и синтетические каннабиноиды вызывают регулируемую смерть раковых клеток. Текущие данные свидетельствуют о том, что каннабиноиды

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… Mechanistically, these effects were mediated through the formation of a PPARγ-ten-eleven translocation 1 complex, which induced the demethylation and subsequent upregulation of leucine-rich repeat and sterile alpha motif-containing 1 , a tumor suppressor gene. …

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

The journey of boswellic acids from synthesis to pharmacological activities.

There has been a lot of interest in using naturally occurring substances to treat a wide variety of chronic disorders in recent years. From the gum resin of Boswellia serrata and Boswellia carteri, the pentacyclic triterpene molecules known as boswellic acid (BA) are extracted. We aimed to provide a detailed overview of the origins, chemistry, synthetic derivatives, pharmacokinetic, and biological activity of numerous Boswellia species and their derivatives. The literature searched for reports of B. serrata and isolated BAs having anti-cancer, anti-microbial, anti-inflammatory, anti-arthritic,

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… Fig. 4 Continue synthetic derivatives of BAs Fig. 4 Continue synthetic derivatives of BAs Pyrolyzed products of BAs Pyrolysis of the resin obtained from Boswellia sacra leads to aromatization of ring A caused by dehydration of the C-3 hydroxyl group of BAs, followed by dehydrogenation and demethylation … AKBA treatment resulted in a modest genome-wide demethylation, which then allowed simultaneous reactivation of the relevant tumor suppressor genes, including suppressor of mothers against decapentaplegic (Smad)14 and Smad3 (Shen et al. 2012 ) (Fig. 7 ). …

Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.

Thymoquinone (TQ), the active compound in Nigella sativa (black seed), has shown promising effects against cancer in many laboratory studies. In this review, we explore how TQ works on different aspects of cancer, from stopping cancer cell growth and spread, to triggering cancer cell death, reducing inflammation, and helping the immune system fight back. We also highlight how TQ may overcome one of the biggest problems in cancer treatment-chemoresistance. When used together with common treatments like chemotherapy, radiation, or immunotherapy, TQ has been shown to improve their effects and red

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… Additionally, TQ-induced demethylation has shown therapeutic promise against chemoresistance. For example, in doxorubicin-resistant breast cancer cells (MCF-7/DOX), aberrant DNA methylation patterns contribute to suppressed expression of tumor suppressors such as PTEN, BRCA1, and RB1. …

Exploring microRNA targeting as a promising approach for solid tumor treatment.

The discovery of microRNAs (miRNAs) and their pivotal role in gene regulation has opened up new avenues for innovative cancer treatments. Recent years have witnessed extensive research into the intricate mechanisms of miRNAs and their impact on solid tumors. These small non-coding RNA molecules are central to gene regulation and are frequently dysregulated in various cancers, particularly solid tumors. Dysregulation of specific miRNAs can initiate, progress, and metastasize tumors, making them appealing targets in cancer therapy. This article explores recent studies on identifying specific miR

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… Retracted: Demethylation of miR-195 suppresses prostate cancer cell proliferation, migration and invasion . FEBS Open bio . ( 2020 ) 10 : 525–34 . doi: 10.1002/2211-5463.12799 , PMID: 31977154 PMC7137791 73 Liu J Li Y Zou Y Zhang J An J Guo J . …

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment.

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body's inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby b

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… Meclofenamic Acid Restores Gefinitib Sensitivity by Downregulating Breast Cancer Resistance Protein and Multidrug Resistance Protein 7 via FTO/m6A-Demethylation/c-Myc in Non-Small Cell Lung Cancer. Front. Oncol. 2022;12:870636. doi: 10.3389/fonc.2022.870636. 132. …

Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the

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… Further, the Ube2b modulates the DNMT3a (DNA methyltransferase 3 alpha) ubiquitination degradation and CaMKK1 (calcium/calmodulin-dependent protein kinase) gene promoter demethylation increasing CaMKK1 level. …

The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing.

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the 'guardian of the genome' and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni syndrome (LFS), the inherited cance

Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms: minimal residual disease and cure?

The first clinical trials of the safety and efficacy of interferon-alpha2 (IFN-alpha2) were performed about 30 years ago. Since then, several single-arm studies have convincingly demonstrated that IFN-alpha2 is a highly potent anti-cancer agent in several cancer types but unfortunately not being explored sufficiently due to a high toxicity profile when using non-pegylated IFN-alpha2 or high dosages or due to competitive drugs, that for clinicians at first glance might look more attractive. Within the hematological malignancies, IFN-alpha2 has only recently been revived in patients with the Phi