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Aptamer Therapeutics in Cancer: Current and Future.

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesize

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resi

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… LncRNAs are a class of non-coding RNA molecules with a length of more than 200 nucleotides that are transcribed from different regions of the genome by RNA polymerase II. …

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achi

Circulating biosignatures in multiple myeloma and their role in multidrug resistance.

A major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance. This occurs when a tumour fails to reduce in size after treatment or when there is clinical relapse after an initial positive response to treatment. A unique and serious type of resistance is multidrug resistance (MDR). MDR causes the simultaneous cross resistance to unrelated drugs used in chemotherapy. MDR can be acquired through genetic alterations following drug exposure, or as discovered by us, through alternative pathways mediated by the transfer of functional MDR proteins and nucleic

Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients' quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducin

Identification of CKS2 and RRM2 as potential markers of vitiligo using bioinformatics analysis.

Previous studies have attempted to elucidate the molecular mechanism of vitiligo; however, its pathogenesis remains unclear. This study aimed to explore biomarkers related to vitiligo through bioinformatic analysis. The microarray datasets GSE53146 and GSE65127 were downloaded from the Gene Expression Omnibus database. Firstly, differentially expressed genes (DEGs) in GSE53146 were screened, and then an enrichment analysis was performed. Secondly, the protein-protein interaction (PPI) network of DEGs was constructed using the STRING database, and the key genes were screened using the MCODE plu

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… The downregulated DEGs were also associated with RNA polymerase II transcription factor activity, sequence-specific DNA binding, transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, and enhancer sequence-specific DNA binding in MF (Fig. 3 B). …

Conference Proceedings - 6th International Conference on Molecular Diagnostics and Biomarker Discovery (MDBD 2022): Building Resilience in Biomedical Research : Penang, Malaysia. 11-13 October 2022.

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Identification of potential biomarkers and therapeutic targets for osteoarthritis associated with arginine and proline metabolism based on transcriptome sequencing and bioinformatics.

Background and objectivesOsteoarthritis (OA) is a chronic degenerative joint disease. Approximately 300 million people worldwide suffer from OA, which shows a high incidence in middle-aged and elderly populations, with a prevalence of 50% among individuals aged over 60 years. Its core clinical symptoms consist of joint pain, swelling, and dysfunction. Studies have shown that arginine and proline metabolism play an important role in the pathogenesis and progression of OA, but the specific mechanism is still unclear. This study aimed to identify biomarkers and drug therapeutic targets for OA ass

Cystatin M/E Ameliorates Multiple Myeloma-Induced Hyper Osteolytic Bone Resorption.

Multiple myeloma (MM) is a malignancy of terminally differentiated B-cells that is localized primarily in the bone marrow (BM) but also can be present in peripheral blood and tissue/organs [...].

Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model.

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

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

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… SETD2 catalyzes histone methylation and interacts with RNA polymerase II to mediate transcriptional elongation. We noted that the development of several tumors is associated with mutations in SETD2; for instance, gastric, kidney, and lung cancers 6 . … Repression of pervasive antisense transcription is the primary role of fission yeast RNA polymerase II CTD serine 2 phosphorylation. Nucleic Acids Res. 2024;52(13):7572–7589. doi: 10.1093/nar/gkae436. 16. Kearns S, Mason FM, Rathmell WK, Park IY, Walker C, Verhey KJ. et al. …

RNF25 serves as a novel diagnostic and prognostic biomarker in multiple myeloma: a multi-cohort integrative analysis.

BackgroundUbiquitination-related genes (UbRGs) play critical roles in tumor biology. However, their functions in multiple myeloma (MM) remain insufficiently explored.MethodsTranscriptomic data from public databases were integrated to identify UbRGs in MM through WGCNA, differential expression, and protein-protein interaction (PPI) analyses. Functional roles were examined by GO, KEGG, and GSEA, while immune infiltration and drug sensitivity were evaluated using CIBERSORT, ESTIMATE, and OncoPredict. UbRG expression was validated in clinical samples and cell lines by qRT-PCR and western blot, and

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… In addition, RNF20–RNF40–mediated histone ubiquitination facilitates the recruitment of transcription factors and RNA polymerase II while reshaping chromatin structure, thereby playing a key role in transcriptional regulation [ 30 ]. … Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell. 2006;125(4):703–17. 10.1016/j.cell.2006.04.029. 31. Dang F, Nie L, Wei W. Ubiquitin signaling in cell cycle control and tumorigenesis. …

Молекулярная основа для человеческой митохондриальной модификации tRNA m3C с помощью альтернативной разбрызгивания METTL8.

METTL8 недавно был определен как катализатор метилпереносазы 3-methylcytidine Биогенез на месте 32 (м3С32) митохондриальных tRNA. METTL8 также потенциально участвует в мRNA метилации и R-loop Biogenesis. Как METTL8 играет многообразную роль в разных камерах, и митохондриальное образование митохондриала tRNA m3C остается неясным. Здесь мы обнаружили, что альтернативное скрещивание mRNA вызвало несколько изоформ METTL8. One (изоформ)METTL8-Iso1) был направлен на митохондрию через N-терминальную предпоследнюю последовательность, в то время как другой one (В тыс.METTL8-Iso4) в основном локализован

Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: in vitro and in vivo anti-tumor activity.

Multiple myeloma (MM) cells induce relevant angiogenic effects within the human bone marrow milieu (huBMM) by the aberrant expression of angiogenic factors. Hypoxia triggers angiogenic events within the huBMM and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is over-expressed by MM cells. Since synthetic miR-199a-5p mimics negatively regulates HIF-1α, we here investigated a miRNA-based therapeutic strategy against hypoxic MM cells. We indeed found that enforced expression of miR-199a-5p led to down-modulated expression of HIF-1α as well as of other pro-angiogenic factors such a

p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells.

The Wnt inhibitor Dickkopf-1 (DKK-1) has been associated with the occurrence of bone metastases in osteotropic prostate cancer by inhibiting osteoblastogenesis. P38 mitogen-activated protein kinase (MAPK) activity is also dysregulated in advanced prostate cancer. However, the impact of p38 MAPK signaling on DKK-1 remains unknown. Inhibition of p38 MAPK signaling in osteolytic PC3 cells by small molecule inhibitors (doramapimod, LY2228820 and SB202190) suppressed DKK-1 expression, whereas activation of p38 MAPK by anisomycin increased DKK-1. Further dissection by targeting individual p38 MAPK i

Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant.

Posttransplant vaccination targeting residual disease is an immunotherapeutic strategy to improve antigen-specific immune responses and prolong disease-free survival after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We conducted a phase 1 vaccine trial to determine the safety, toxicity, and immunogenicity of autologous Langerhans-type dendritic cells (LCs) electroporated with CT7, MAGE-A3, and Wilms tumor 1 (WT1) messenger RNA (mRNA), after ASCT for MM. Ten patients received a priming immunization plus 2 boosters at 12, 30, and 90 days, respectively, after ASCT. Vacc

Antileukemia Activity of Human Natural Killer Cell-Derived Nanomagic Bullets against Acute Myeloid Leukemia (AML).

Background: Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro. Materials and Methods: The MACS method was performed for the separation o

CeRNA Expression Profiling Identifies KIT-Related circRNA-miRNA-mRNA Networks in Gastrointestinal Stromal Tumour.

Gastrointestinal stromal tumours (GISTs) are the most common human sarcomas and are typically located in the stomach or small intestine. Although circular RNAs (circRNAs) reportedly play vital roles in tumour oncogenesis and progression, the molecular basis of the aggressive tumour biology of these circRNAs in GISTs remains unclear. In this study, we applied SBC ceRNA microarrays to screen for tumour-specific circRNA profiles in GISTs and identified that a total of 5,770 circRNAs and 1,815 mRNAs were differentially expressed in GISTs. Three significantly differential circRNAs (circ_0069765, ci