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Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma.

Myeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotes DKK1 expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activate DKK1 transcription. In addition, high levels of DKK1 were associated with the presence of foca

Emerging Mechanisms and Treatment Progress on Liver Metastasis of Colorectal Cancer.

Colorectal cancer is currently the third largest malignant tumor in the world, with high new cases and high mortality. Metastasis is one of the most common causes of death of colorectal cancer, of which liver metastasis is the most fatal. Since the beginning of the Human Genome Project in 2001, people have gradually recognized the 3 billion base pairs that make up the human genome, of which only about 1.5% of the nucleic acid sequences are used for protein coding, including proto-oncogenes and tumor suppressor genes. A large number of differences in the expression of proto-oncogenes and tumor

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… SNCG can inhibit the effect of BubR1 by binding to BubR1-microtubulin E (CENP-E) complex, which makes cells escape the control of mitotic checkpoints and form aneuploidy of chromosomes, thus increasing genetic instability and inducing tumorigenesis. 51 (3) CpG island demethylation of SNCG can activate … Cigarette smoke induces demethylation of prometastatic oncogene synuclein-gamma in lung cancer cells by downregulation of DNMT3B . Oncogene . 2007 ; 26 ( 40 ): 5900 – 5910 . doi: 10.1038/sj.onc.1210400 17369845 53. Jiang Y , Liu YE , Lu A , et al. …

Research Progress of NK Cells in Glioblastoma Treatment.

NK cells are a type of antitumor immune cell with promising clinical application, following T cells. The activity of NK cells is primarily regulated by their surface receptors and immune microenvironment. In gliomas, the tumor microenvironment exerts a strong immunosuppressive effect, which significantly reduces the clinical efficacy of NK cell immunotherapy. Therefore, this review aims to discuss the latest research on the role of NK cells in glioma immunotherapy, focusing on aspects such as NK cell development, function, and localization. It summarizes information on the compounds, monoclona

Economic Burden of Intravenous Decitabine Administration in Patients Affected by Acute Myeloid Leukemia Ineligible for Induction Chemotherapy and Impact of Oral Formulation Introduction: A Micro-Costing Study in Italy.

PurposeIntravenous (IV) decitabine is a therapeutic option for patients with newly diagnosed acute myeloid leukemia (AML) ineligible for induction chemotherapy. Recently, the oral formulation of decitabine-cedazuridine demonstrated comparable efficacy and safety to IV decitabine, and pharmacokinetic equivalence. This study estimates the direct non-drug healthcare costs of IV decitabine administration in Italy, including central venous catheter (CVC) and infection management, and assesses the economic impact of oral decitabine introduction.MethodsA micro-costing analysis from the Italian Nation

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… The results demonstrated equivalent systemic decitabine exposures between the two formulations, with demethylation rates showing a minimal difference of ≤1.1%. 28–30 Furthermore, the median overall survival, clinical response, and safety profile observed with oral decitabine were consistent with those …

Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy.

Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular

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… A study found that lncRNA ThymoD could promote demethylation of the CTCF (DNA‐binding protein CCCTC‐binding factor) binding site in T cell chromatin, activating cohesin‐dependent looping that repositions the Bcl11b (Bcl11 transcription factor b) enhancer from the nuclear lamina to the interior. …

Лейкемия в период беременности: диагностика и терапевтический подход (обзор).

Цель настоящего исследования заключается в оценке эпидемиологических, диагностических и терапевтических данных о гематологических заболеваниях в период беременности. Лейкемия в период беременности встречается редко, а литературные данные не являются обширными. Факторы риска, эпидемиология и патогенез этих заболеваний не разработаны в полной мере. Кроме того, имеется подробный доклад о осложнениях в период беременности и об общем (на три месяца) лечении этих заболеваний, в частности о стратегии их лечения. В настоящем исследовании описывается возможность обеспечения в будущем беременности у жен

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… methyltransferase 3 alpha, which is involved in establishing and maintaining DNA methylation patterns, playing a crucial role in gene expression regulation and cellular differentiation, ii) Tet methylcytosine dioxygenase 2 (TET2), which encodes the TET2 protein, which is involved in the process of DNA demethylation …

Antidepressant Drug Sertraline against Human Cancer Cells.

The use of FDA-approved drugs for new indications represents a faster and more economical way to find novel therapeutic agents for cancer therapy, compared to the development of new drugs. Repurposing drugs is advantageous in a pharmacological context since these drugs already have extensive data related to their pharmacokinetics, facilitating their approval process for different diseases. Several studies have reported the promising anticancer effects of sertraline, both alone and combined, in different types of cancer cell lines. Here, we performed a literature review on the anticancer potent

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… The main metabolism of sertraline occurs in the liver ( Figure 2 ) and most studies have focused their attention on the demethylation of sertraline to desmethylsertraline, a reaction mediated by multiple cytochrome P450 (CYP) enzymes [ 28 ]. …

Pain Management in Patients with Multiple Myeloma: An Update.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblasti

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… Regarding opioids, CYP3A4 is involved in the metabolism of oxycodone (N-demethylation to inactive noroxycodone) [ 59 ] and fentanyl. Fentanyl may inhibit the activity of CYP3A4, resulting in increased bioavailability and toxicity of chemotherapeutic agents, e.g., paclitaxel [ 60 ]. …

Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy and mode of action.

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be

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… The 4 -demethylation and the introduction of a β-glycosidic moiety in position 7 of podophyllotoxin convert it into a potent irreversible inhibitor of DNA topoisomerase II. …

Are We Ready For "Triplet" Therapy in Higher-Risk MDS?

Higher-risk Myelodysplastic Syndromes/Neoplasms (MDS) represent an ongoing therapeutic challenge, with few effective therapies, many of which may have limited use in this older patient population often with considerations around comorbidities. Outside of transplant, azacitidine and decitabine remain the only disease-modifying therapies, and are palliative in nature. Recent interest has grown in extending combination chemotherapies used to treat acute myeloid leukemia (AML) to patients with MDS, including novel combination chemotherapy "doublets" and "triplets." In this review, we discuss consi

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… Aggressive Myelodysplastic Syndrome | Biological: Navitoclax|Drug: Venetoclax|Drug: Decitabine|Procedure: Bone Marrow Biopsy|Procedure: Biospecimen Collection|Other: Laboratory Biomarker Analysis|Other: Quality-of-Life Assessment NCT05426798 | Clinical Study of TQB2618 Injection in Combination With Demethylation …

Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations.

Curcumin has been extensively investigated as an anticancer agent, yet its clinical application remains constrained by low bioavailability, incomplete mechanistic understanding, and limited therapeutic optimization. In light of growing resistance to conventional chemotherapies and the demand for safer, multi-targeted agents, this review revisits curcumin with a contemporary lens. We critically evaluate the literature published since 2020, focusing on newly elucidated molecular mechanisms by which curcumin regulates tumor progression, including modulation of oncogenic signaling pathways (Wnt/β-

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… miR-483-3p mRNA expression | [ 144 ] PC-4, DU145 (in vitro) | 10 μM | m6A-modified circ0030568-FMR1 signaling pathway | Inhibits cell proliferation and migration Reduces FMR1 protein expression Induces apoptosis | [ 145 ] LNCaP, C4-2, PC3, DU145, C42R (in vitro and in vivo) | 4, 8, 12 μM | JARID1D demethylation …

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

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… Apoptosis | [ 110 ] | Clinical | AML patients | ATRA A + APO + Idarubicin | ↑ Relapse-free & failure-free survival | [ 111 ] | Clinical | APL patients | ATRA A + ATO | ↑ Complete remission, Event-free survival rates, Overall survival rates | [ 112 ] | In vitro | K562 cells | DAC + ATRA A | ↑RAR-β, p16 demethylation …

CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges.

Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-rela

A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies.

The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by

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… Moreover, the gut microbiota plays a crucial role in reductive metabolism, facilitating various biochemical reactions such as acetylation, deacylation, decarboxylation, dehydroxylation, demethylation and dehalogenation. …

The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through the regulation of protein degradation and function. By influencing the expression of immune checkpoint-associated proteins, the UPS modulates T cell-mediated anti-tumor immune responses and can potentially facilitate the immune escape of tumor cells. Additionally, the UPS contributes to the remodeling of the tumor immunosuppressive microenvironment (TIME) by regulating B cells, dendritic cells (DCs), macrophages, and Treg cells. Targeting the UP

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… Induction of CD4(+)CD25(+)FOXP3(+) regulatory T cells by mesenchymal stem cells is associated with modulation of ubiquitination factors and TSDR demethylation . Stem Cell Res Ther . ( 2018 ) 9 : 273 . doi: 10.1186/s13287-018-0991-1 30359308 PMC6203284 58 Li X Yang S Zhang H Liu X Gao Y Chen Y . …

Emerging disease-modifying therapies for sickle cell disease.

Sickle cell disease afflicts millions of people worldwide and approximately 100,000 Americans. Complications are myriad and arise as a result of complex pathological pathways 'downstream' to a point mutation in DNA, and include red blood cell membrane damage, inflammation, chronic hemolytic anemia with episodic vaso-occlusion, ischemia and pain, and ultimately risk of cumulative organ damage with reduced lifespan of affected individuals. The National Heart, Lung, and Blood Institute's 2014 evidence-based guideline for sickle cell disease management states that additional research is needed bef

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… Lysine-specific demethylase-1 (LSD1) is another enzyme and epigenetic target that modifies histones through demethylation in the process of γ-globin gene silencing at the γ-promoter DRED complex, which also contains the demethylase DNMT1. …

Properties of Approved Antitumour Chinese Herbal Medicines: Integrating Evidence and Tradition.

The properties and meridian affinities of Chinese herbal medicine are closely associated with their therapeutic efficacy. This review focuses on approved antitumour Chinese medicines listed in the Pharmacopoeia of the People's Republic of China (2020 Edition, Volume I), highlighting their key components. Statistical methods were used to analyse the properties, flavours and channel tropisms of antitumour traditional Chinese medicine (TCM), including both proprietary formulations and commercially available individual herbs. Distinctive patterns were identified by comparing herb profiles with con

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… Its antitumour effects are primarily mediated by promoting DNA demethylation of the tumour suppressor gene PTEN , thereby inhibiting PI3K/Akt signalling, regulating B-cell lymphoma-2 (Bcl-2) expression, activating mitochondrial apoptosis and inducing cell-cycle arrest to suppress tumour cell proliferation …

Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.

Glutamine is the most abundant amino acid in human serum, and it can provide carbon and nitrogen for biosynthesis, which is crucial for proliferating cells. Moreover, it is widely known that glutamine metabolism is reprogrammed in cancer cells. Many cancer cells undergo metabolic reprogramming targeting glutamine, increasing its uptake to meet their rapid proliferation demands. An increasing amount of study is being done on the particular glutamine metabolic pathways in cancer cells.Further investigation into the function of glutamine in immune cells is warranted given the critical role these

Успехи в сочетании CAR-T-терапии с небольшими молекуловыми реагентами для гематологовых магнатов.

Терапия против антигенного рецептора Т-клеток (CAR-T) стала краеугольным камнем лечения гематологовых магнестов. Однако, будучи монотерапией, она по-прежнему сталкивается с серьезными проблемами, такими, как сопротивление терапии, рецидив заболеваний и минимальное остаточное заболевание (МСД) после возвращения. Небольшие молекулные соединения, такие, как ингибиторы тирозиновой киназы Брютона (БТК), гипометилирующие вещества и иммуномодуляторные препараты, могут повысить эффективность антипухоза клеток CAR-T с помощью различных механизмов, повышая их стойкость и способность к разжижению. Комбин

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… For instance, DNA methyltransferase inhibitors (DNMTis), such as decitabine (DAC), could restore tumor-associated antigen expression via promoter demethylation-mediated epigenetic reprogramming, thus enhancing CD19 CAR-T cell recognition and cytolytic activity ( 32 ); Changju Qu et al ( 33 ). investigated …

A Review of Approaches to Potentiate the Activity of Temozolomide against Glioblastoma to Overcome Resistance.

A glioblastoma (GBM) is one of the most aggressive, infiltrative, and treatment-resistant malignancies of the central nervous system (CNS). The current standard of care for GBMs include maximally safe tumor resection, followed by concurrent adjuvant radiation treatment and chemotherapy with the DNA alkylating agent temozolomide (TMZ), which was approved by the FDA in 2005 based on a marginal increase (~2 months) in overall survival (OS) levels. This treatment approach, while initially successful in containing and treating GBM, almost invariably fails to prevent tumor recurrence. In addition to

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… MGMT promoter demethylation is the key mechanism that regulates MGMT gene expression and predicts TMZ response in GBM patients. …