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Revealing the pharmacological effects of Remodelin against osteosarcoma based on network pharmacology, acRIP-seq and experimental validation.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. Remodelin, an inhibitor of the N (4)-Acetylcytidine (ac4C) acetylation modifying enzyme N-acetyltransferase 10 (NAT10), has been shown to have therapeutic effects on cancer in several studies, and our previous studies have confirmed the inhibitory effect of Remodelin on OS cells, however, the mechanism of action has not yet been elucidated. We used network pharmacological analysis to quantify the therapeutic targets of Remodelin against OS. acRIP-seq and RNA-seq were performed to investigate the inhibitory activity of Remode

Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this system is controlled by clock genes, which function to harmoniously express molecular levels that facilitate the orderly coordination of various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation and immunity. The root cause of tumorigenesis is that the body loses its normal regulation of cell growth at the genetic level. Long-term disruptions in circadian rhythms caused by factors such as shift work, jet lag, and unstable s

Research progress of novel anti-tumor drug formulations.

Cancers have become the second leading cause of death worldwide, following cardiovascular diseases.Traditional anti- cancer strategies, including radiotherapy chemotherapy, surgery, and targeted therapies, have been widely used but are often reassessed due to their significant side effects and relatively low cure rate. Recently, the development of novel formulations for anti-tumor drugs has gained considerable attention, marking a pivotal step forward in cancer treatment advancements. These innovative formulations aim to enhance the therapeutic efficacy of anti-tumor drugs by employing advance

Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma.

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given th

Асептический менингит, вызванный моноклональными антителами, используемыми для лечения рака: систематический обзор.

Фон и цель Monoclonal антитела (MAbs) революционизировали лечение рака, но связаны с целым спектром неблагоприятных явлений, включая неврологические осложнения. Понимание механизма и управления осложнениями имеет решающее значение для оптимизации ухода за пациентами. Цель настоящего систематического обзора заключалась в выявлении сообщений о случаях использования МБО для лечения рака, которые привели к появлению асептического менингита (АМ). 2024 (обновлено в мае) 2025). Для оценки качества тематических исследований использовался контрольный перечень критических оценок Института Джоанны Бриггс

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connec

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia.

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional land

Exosomes, MDSCs and Tregs: A new frontier for GVHD prevention and treatment.

The development of graft versus host disease (GVHD) represents a long-standing complication of allogeneic hematopoietic cell transplantation (allo-HCT). Different approaches have been used to control the development of GVHD with most relying on variations of chemotherapy drugs to eliminate allo-reactive T cells. While these approaches have proven effective, it is generally accepted that safer, and less toxic GVHD prophylaxis drugs are required to reduce the health burden placed on allo-HCT recipients. In this review, we will summarize the emerging concepts revolving around three biologic-based

WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.

The Wilms' Tumor 1 (WT1) gene has attracted significant attention in oncological research owing to its involvement in the pathogenesis of a variety of malignancies. Initially identified in association with Wilms' tumor, a pediatric renal carcinoma, WT1 is now recognized for its broader implications in the etiology of multiple cancers, including leukemia, ovarian cancer, and lung cancer. This review offers a comprehensive analysis of the historical development of WT1 research, explores its mechanisms in cancer progression, and assesses its potential as a therapeutic target, with an emphasis on

Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15).

BackgroundStudies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival.MethodA 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3,

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

Recent advances in understanding multiple myeloma.

There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach st

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer

The Osteoclast in Bone Metastasis: Player and Target.

Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenome

Совпадение в полном тексте источника
… IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J. Immunol. 2002;169:3353–3362. doi: 10.4049/jimmunol.169.6.3353. 55. …

CD70 as a target in cancer immunotherapy: advances, challenges, and future directions.

Cancer immunotherapy represents a paradigm shift in oncology by leveraging the immune system to target tumors. The therapeutic efficacy of these approaches depends critically on identifying molecular targets that enhance treatment responses while limiting toxicity. CD70, a TNF family member, has emerged as a promising target due to its overexpression in hematologic malignancies and solid tumors contrasted with restricted expression in healthy tissues. This differential expression profile implies that CD70-directed therapies could achieve tumor-specific cytotoxicity with reduced off-target effe

Cellular immunotherapy for hematological malignancy: recent progress and future perspectives.

Advancements in the field of cellular immunotherapy have accelerated in recent years and have changed the treatment landscape for a variety of hematologic malignancies. Cellular immunotherapy strategies exploit the patient's immune system to kill cancer cells. The successful use of CD19 chimeric antigen receptor (CAR) T-cells in treating B-cell malignancies is the paradigm of this revolution, and numerous ongoing studies are investigating and extending this approach to other malignancies. However, resistance to CAR-T-cell therapy and non-durable efficacy have prevented CAR-T-cells from becomin

Enhancing CAR T cells function: role of immunomodulators in cancer immunotherapy.

CAR T-cell therapy is a promising immunotherapy, providing successful results for cancer patients who are unresponsive to standard and traditional therapeutic approaches. However, there are limiting factors which create a hurdle in the therapy performing its role optimally. CAR T cells get exhausted, produce active antitumor responses, and might even produce toxic reactions. Specifically, in the case of solid tumors, chimeric antigen receptor T (CAR-T) cells fail to produce the desired outcomes. Then, the need to use supplementary agents such as immune system modifying immunomodulatory agents

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A m

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy.

Since the approval of rituximab in 1997, monoclonal antibodies (mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target speci

Killing me softly--future challenges in apoptosis research.

The induction of apoptosis, a highly regulated and clearly defined mode of cell dying, is a vital tenet of modern cancer therapy. In this review we focus on three aspects of apoptosis research which we believe are the most crucial and most exciting areas currently investigated and that will need to be better understood in order to enhance the efficacy of therapeutic measures. First, we discuss which target to select for cancer therapy and argue that not the cancer cell as such, but its interaction with the microenvironment is a more promising and genetically stable site of attack. Second, the