Результаты поиска

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total anti

TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.

Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to

Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and system

Arsenic trioxide and triptolide synergistically induce apoptosis in the SKM‑1 human myelodysplastic syndrome cell line.

Although certain combination therapies comprising arsenic trioxide (As2O3) with other agents exist for the treatment of several types of human cancer, few As2O3 combination therapies are clinically effective for myelodysplastic syndromes (MDS). Triptolide (TL) may be an effective therapeutic agent for the treatment of MDS. However, to date, there is no combination therapy for MDS with As2O3 and TL. Therefore, the aim of the present study was to investigate this combination therapy on the apoptosis of MDS SKM‑1 cells. The MDS SKM‑1 cells were treated with As2O3, TL or the two in combination at

Control of viral infections by epigenetic-targeted therapy.

Epigenetics is defined as the science that studies the modifications of gene expression that are not owed to mutations or changes in the genetic sequence. Recently, strong evidences are pinpointing toward a solid interplay between such epigenetic alterations and the outcome of human cytomegalovirus (HCMV) infection. Guided by the previous possibly promising experimental trials of human immunodeficiency virus (HIV) epigenetic reprogramming, the latter is paving the road toward two major approaches to control viral gene expression or latency. Reactivating HCMV from the latent phase ("shock and k

С-терминальный связывающий белок 2 - новый дезинфицирующий опухоль, направленный на MYC-IRF4 ось в множестве миеломы.

Клетки с множественной миеломой (MM) подвержены зависимости от MYC, а их непосредственные цели по трансактивации IRF4 направлены на распространение и выживание. MYC и IRF4 по-прежнему считаются "ненаркоманными", поскольку большинство мелких ингибиторов молекулярного происхождения страдают от низкой производительности, неоптимальных фармакокинетических свойств и нежелательных нецелевых эффектов. Косвенное подавление MYC/IRF4 проявляется в качестве терапевтической уязвимости MM. Здесь мы обнаружили неоцененную опухоль, впечатляющую роль связующего белка С-терминала 2 (CTBP2) в MM путем сильного

Митохондриальная передача метаболических перепрограмм и лекарственная устойчивость в метастазе костей: механизмы и терапевтические стратегии.

Кость это one из наиболее распространенных участков удаленного метастаза в твердых опухолях, в частности рак груди, рак простаты и рак легких. Метатические повреждения костей часто свидетельствуют о стойком сопротивлении многосистемной терапии, включая химиотерапию, целевую терапию, эндокринную терапию и ингибиторы иммунных контрольно-пропускных пунктов (ИПК). Накопляющиеся данные свидетельствуют о том, что метаболическая перепрограммирование в пределах костной микроокружающей среды способствует этому сопротивлению, однако механизмы в верхнем течении по-прежнему недостаточно понятны. В качеств

Совпадение в полном тексте источника
… Accompanying accumulation of acetyl-CoA and α-KG drives histone acetylation and DNA demethylation through metabolism–epigenetics crosstalk, establishing a “metabolic memory” mechanism that sustains long-term therapy resistance. … Expansion of the acetyl-coenzyme A (acetyl-CoA) pool promotes increased histone H3 lysine 27 acetylation (H3K27ac) marks, activating metabolic gene cluster expression ( 147 ). α-KG mediates DNA demethylation through ten-eleven translocation (TET) enzymes, relieving the silencing of metabolism-related …

The next new target in leukemia: The embryonic stem cell gene SALL4.

The embryonic stem (ES) cell gene SALL4 has recently been identified as a new target for cancer therapy, including leukemia. SALL4 is expressed in ES cells and during embryonic development, but is absent in most adult tissues. It is, however, aberrantly expressed in various solid tumors and hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Aberrant expression of SALL4 is frequently associated with a more aggressive cancer phenotype, which includes high-risk MDS and its progression to AML. SALL4 contributes to leukemogenesis through multiple path

Совпадение в полном тексте источника
… In breast cancer cells, STAT3 has been shown to be an upstream transcriptional activator of SALL4. 44 The mechanism underlying aberrant SALL4 expression in leukemia is not known although recent studies have suggested DNA demethylation as one possibility. 25 In a study using B-ALL cell lines and primary …

Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?

Synthetic lethality strategies are likely to be integrated in effective and specific cancer treatments. These strategies combine different specific targets, either in similar or cooperating pathways. Chromatin remodeling underlies, directly or indirectly, all processes of tumor biology. In this context, the combined targeting of proteins associated with different aspects of chromatin remodeling can be exploited to find new alternative targets or to improve treatment for specific individual tumors or patients. There are two major types of proteins, epigenetic modifiers of histones and nuclear o

Роль антиоксидантов в множестве миеломы: диагностика, прогнозирование и терапевтическое применение: обзор сюжета.

Множественная миэлома (ММ) — злокачественная клетка B-клеток с моноклональными плазменными клетками, производящими нефункциональные иммуноглобулины. Она по-прежнему неизлечима из-за de novo или приобретенного сопротивления злокачественных клеток стандартным химиотерапиям. Таким образом, понимание механизма терапевтического сопротивления имеет важнейшее значение для разработки более эффективных мер вмешательства и определения новых целей лечения. MM - это разнородная болезнь, характеризующаяся сложными генетическими изменениями, которые имеют решающее значение для прогнозирования стратификации.

Совпадение в полном тексте источника
… DNA demethylation favors the expression of tumor suppressor genes and improve chemo-sensitivity. 95 Ten-eleven translocation (TET) dioxygenases initiate DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). …

Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy.

Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b

Совпадение в полном тексте источника
… Particularly, active DNA demethylation is carried out by the TET enzymes, which are frequently mutated in haematological malignancies. … In the treatment of cancer, high-dose VitC has been shown to induce DNA demethylation by restoring and regulating TET aberrant levels [ 3 ]. …

Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.

A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associate

Perturbing Enhancer Activity in Cancer Therapy.

Tight regulation of gene transcription is essential for normal development, tissue homeostasis, and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation.

Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve ove

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

The Impact and Safety of GLP-1 Agents and Breast Cancer.

IntroductionObesity and breast cancer rates are increasing globally, with obesity prevalence more than doubling since 1990. By 2022, 44% of women were overweight, and 18% were obese. Breast cancer remains the most common malignancy among women, with 2.2 million new cases in 2020. A significant proportion of breast cancer patients are overweight or obese at diagnosis, which is associated with higher recurrence and mortality rates. Recently, GLP-1 receptor agonists (GLP-1 RAs) have emerged as remarkably effective weight loss drugs. Understanding the relationship between obesity, breast cancer, a

High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanc

Kabuki Syndrome-Clinical Review with Molecular Aspects.

Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most c