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Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for over 90% of all cases. Patients with advanced-stage HCC are referred to systemic treatment. Although some advances in HCC therapy have been made in recent years, the prognosis for patients remains poor due to drug resistance, tumor relapse, and metastasis, implying that overall survival remains a challenge. Many studies have shown that tumor-initiating stem cells, also known as cancer stem cells (CSCs), play essential roles in tumorigenesis, metastasis, and treatment resistance in HCC and that future cancer

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… Wang et al. [ 157 ] investigated arsenic trioxide against liver CSCs and reported that the induction of DNA demethylation after arsenic trioxide treatment activated microRNA-148a, leading to the inhibition of the NF-κB pathway and CSC properties in the multidrug-resistant HCC cell line MDR Bel-7402 and … Li et al. [ 158 ] reported that arsenic trioxide elevated miR-491 expression via DNA demethylation, causing reduced SMAD3 expression and suppressing CSC-like features in HCC MHCC97H cells in vitro and in a mouse xenograft model. …

Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enha

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… Instead, it is mainly done by detecting mutations in regulatory genes that perform histone methylation and demethylation, which are reviewed in depth elsewhere [ 117 ]. … Relapsed or refractory follicular lymphoma (FL) IDH1 inhibitor: Inhibition leads to the production of oncometabolite 2-hydroxyglutarate (2-HG) instead of α-KG in the citric acid cycle; 2-HG inhibits histone demethylases and TET (ten-eleven translocation) enzymes involved in DNA demethylation, affecting …

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

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… Hydralazine induces demethylation in prostate cancer cells, re-expressing suppressed genes [ 97 , 98 ]. A Phase II trial is currently underway to evaluate minoxidil, a direct vasodilator antihypertensive medication, as a single treatment for ovarian cancer. … trials ( NCT03633747 ) Phase II trials ( NCT02596867 ) | [ 81 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 95 , 96 ] Direct Vasodilator | Minoxidil | | Ovarian cancer | Caspase-3 | ATP-sensitive potassium channels | Phase II trials ( NCT05272462 ) | [ 99 , 100 , 101 ] Hydralazine | | Prostate cancer | Induces demethylation …

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An

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… Disulfiram serves as a DNA methyltransferase (DNMT1) inhibitor that restores tumor suppressor genes and DNA demethylation in PCa cells. Mainly, it reduces 5-methyl cytosine (5meC) content and methylation in APC and RARB gene promoters [ 252 ]. …

Arsenic Sulfide Induces Apoptosis in Myelodysplastic Neoplasm Cells Through the Suppression of ABI2.

BackgroundMyelodysplastic neoplasms (MDS) are a category of myeloid malignancies that can progress to acute myeloid leukemia (AML). Arsenic sulfide (As₂S₂) has demonstrated efficacy in the treatment of MDS. However, further investigation is required to elucidate its specific therapeutic targets.ObjectiveTo examine the influence of ABI2 on MDS and clarify the regulatory role of As₂S₂ on ABI2 within the therapeutic framework of MDS.MethodsTo explore ABI2's role in the expression and prognosis of patients with hematological malignancies, RNA interference was used to reduce ABI2 expression in SKM-

5-Hydroxymethylcytosine Profiles of cfDNA in Urine as Diagnostic, Differential Diagnosis and Prognostic Markers for Multiple Myeloma.

BackgroundAn effective urine-based method for the diagnosis, differential diagnosis and prognosis of multiple myeloma (MM) has not yet been developed. Urine cell-free DNA (cfDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive "liquid biopsy" for diagnosis and monitoring of cancer.MethodsWe first identified MM-specific hydroxymethylcytosine signatures by comparing 64 MM patients, 23 amyloidosis (AM) patients and 59 healthy cohort. Then, we applied a machine learning algorithm to develop diagnostic and differential diagnosis model. Finally, the prognosis of

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… sensitively detect molecular residual disease in bladder cancer patients and accurately predict survival, and is far superior to plasma circulating tumor DNA (ctDNA). 5‐hydroxymethylcytosine (5hmC) is a stable epigenetic marker, which is a relatively stable product in the process of 5‐methylcytosine (5mC) demethylation …

A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia.

BACKGROUND: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK-228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL. METHODS: We conducted a single-arm multi-center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI-9775). RESULTS: Sixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), w

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

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… epigenetic changes encountered in CRC (and many other cancers), defined as chemical alterations to DNA or chromatin that do not affect the primary DNA sequence: those that directly modify DNA (DNA hypo- or hypermethylation) and those that modify DNA-binding proteins (histone modifications—methylation or demethylation …

Azoximer Bromide: Mystery, Serendipity, and Promise.

Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual's resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term p

MiRNA-29a as a tumor suppressor mediates PRIMA-1Met-induced anti-myeloma activity by targeting c-Myc.

The proto-oncogene c-Myc plays substantial role in multiple myeloma (MM) pathogenesis and is considered a potential drug target. Here we provide evidence of a novel mechanism for PRIMA-1Met, a small molecule with anti-tumor activity in phase I/II clinical trial, showing that PRIMA-1Met induces apoptosis in MM cells by suppressing c-Myc and upregulating miRNA-29a. Our study further demonstrates that miRNA-29a functions as a tumor suppressor which targets c-Myc. The baseline expression of miR-29a was significantly lower in MM cell lines and MM patient samples compared to normal hematopoietic cel

MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy.

In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regu

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… Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells. Br. J. Cancer. 2014;110:1645–1654. doi: 10.1038/bjc.2014.48. 34. Lin Y., Lin L., Jin Y., Zhang Y., Wang D., Tan Y., Zheng C. …

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

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… resistance | Saikosaponin D inhibits ADRB2 signaling and reverses drug resistance | [ 153 ] CCA | T3-HIF-1α-Glut1 axis | Enhanced glycolysis and HIF-1α stabilization | Gemcitabine resistance | Block upstream hormone signaling or downstream metabolic nodes | [ 153 ] T-ALL | ALKBH5-USP1-Aurora B | m6A demethylation-mediated …

Reciprocal regulation between m6 A modifications and non-coding RNAs: emerging roles in cancer therapeutic resistance.

In recent years, the interplay between N6-methyladenosine (m6A) modifications and non-coding RNAs (ncRNAs) has emerged as a pivotal research area, owing to their crucial involvement in the pathophysiological mechanisms underlying various diseases. A significant hurdle in cancer therapy is therapeutic resistance, which frequently contributes to adverse patient outcomes. Recent investigations have underscored the vital role that interactions between m6A modifications and ncRNAs play in mediating cancer therapeutic resistance via the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin, HIPPO, and NF-κB pathways.

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… Notably, exosome-derived piR-17560 from senescent neutrophils enhances FTO-mediated m6 A demethylation in breast cancer. The upregulation of FTO subsequently increases the stability of ZEBI transcripts, conferring chemoresistance to tumor cells [ 144 ]. … Senescent neutrophils-derived exosomal piRNA-17560 promotes chemoresistance and EMT of breast cancer via FTO-mediated m6A demethylation. Cell Death Dis. 2022;13(10):905. 145. Chen S, Wen JT, Zhang S, Wang JL, Yuan J, Bao HJ, et al. …

Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells.

Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents

Okay, so I need to translate this medical text into Russian. Let me first read through the original sentence carefully. The sentence is: "N-Azacytidine Inhibits Myeloma Cell Growth While Preserving Multiple Myeloma Patient Derived-Bone Marrow Mesenchymal Stromal Cells Differentiation." Hmm, the key here is to translate it accurately using proper clinical and anatomical terms. Let me break it down. First, "N-Azacytidine" is a drug name. In Russian, drug names are often transliterated or use the original name with some adaptation. I think in Russian medical literature, they might use the international nonproprietary name, which is "N-азацидидин" or maybe "N-азацидид"? Wait, no, let me check. Wait, the international nonproprietary name for N-Azacytidine is "азацидидин" (azacitidine) in Russian. Wait, but the chemical name is N-Azacytidine, which is a nucleoside analog. In Russian, the term for azacitidine is "азацидидин" (azacitidine). Wait, but the original says "N-Azacytidine", so maybe it's "N-азацидидин" but I think in Russian medical terms, they might just use "азацидидин" without the

Множественная миелома (ММ) — неизлечимая гематологическая порча, вызванная аномальным распространением неизлечимо дифференцированных плазменных клеток в костном мозге. Текущие исследования показывают, что N-azacytidine как эпигенетическое лекарство и нуклеозный метаболический ингибитор могут быть эффективными при лечении MM. Вместе с тем данные о мезенхимальных стромальных клетках костного мозга (МСЦВ) в качестве критической клеточной популяции в процессах гематопоизи и реконструирования костей ограничены.МЕТОДЫ: Воздействие N-azacytidine на клеточную линию миэломы AMO-1, мезенхимальные строма

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… De Sousa P.A. 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation PLoS ONE 2014 9 e90846 10.1371/journal.pone.0090846 24603866 PMC3946260 77. Bae Y.J. Kwon Y.R. Kim H.J. Lee S. Kim Y.J. …

Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!

Oncolytic viral therapy is a promising treatment for cancer, where 'cold' tumour cells can become 'hot' to the host immune system. However, with few FDA approved therapies, development of new strategies for more cancer types has been slow and relatively unsuccessful in recent years, Combination therapy has been successful for other types of cancer treatment, therefore, may be a viable alternative to improve the efficacy of oncolytic viral therapy which may reduce some of the adverse events of currently used monotherapies, oncolytic virus therapy and chemotherapy being mutually complimentary wi

The Role of Radiosensitizing Drugs in Osteosarcoma Treatment: Mechanisms and Clinical Perspectives.

Osteosarcoma is a highly malignant bone tumor that is resistant to radiotherapy and is associated with poor treatment outcomes and prognoses. Understanding the mechanisms of radioresistance and finding strategies to enhance the radiosensitivity is crucial for improving clinical efficacy. The aim of this review was to address the approaches for enhancing the efficacy of radiotherapy in osteosarcoma, thereby improving patient outcomes. Specifically, we have focused on the mechanisms of radiosensitization and the relationship between drugs that enhance radiosensitivity and cancer. These mechanism

SETD2 and EZH2: Two epigenetic drivers of prostate cancer.

Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Con

Role of growth differentiation factor 15 in cancer cachexia (Review).

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality

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… Growth differentiation factor-15: A p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells. Sci Rep. 2015;5:12870. doi: 10.1038/srep12870. 44. Joo M, Kim D, Lee MW, Lee HJ, Kim JM. …

A systematic review of ongoing clinical trials in optic pathway gliomas.

INTRODUCTION: Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order t

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… Demethylation and epigenetic modification with 5-azacytidine reduces IDH1 mutant glioma growth in combination with temozolomide. Neuro-Oncology. 2019;21:189–200. doi: 10.1093/neuonc/noy146. 63. Chiocca EA, Yu JS, Lukas RV, et al. …