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Marine Natural Products as Potent Anticancer Agents (2020-2024): Structural Diversity, SARs and Target Prediction.

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer a

Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.

Despite advances in the clinical management of childhood acute myeloid leukemia (AML) during the last decades, outcome remains fatal in approximately one third of patients. Primary chemoresistance, relapse and acute and long-term toxicities to conventional myelosuppressive therapies still constitute significant challenges and emphasize the unmet need for effective targeted therapies. Years of scientific efforts have translated into extensive insights on the heterogeneous spectrum of genetics and oncogenic signaling pathways of AML and identified a subset of patients characterized by upregulati

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… Clinical trials in AML have analysed vitamin C levels ( NCT03526666 ) as well as the effect of oral vitamin C supplementation in improving the response to DNA methyltransferase inhibitors via increasing DNA demethylation (NCT0287727). 4.7. …

Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.

Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer resistance in myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated from IκBα-inhibited complex in response to TNF-induced canonical NFκB signal, mediates the pro-survival NFκB function in cancerous cells. Myeloma cells add

Identification of iron metabolism-related predictive markers of endometriosis and endometriosis-relevant ovarian cancer.

Endometriosis is associated with ovarian cancers, mainly endometrioid and clear-cell carcinomas. Iron metabolism has been shown to play a role in endometriosis. Therefore, it is vital to explore the relationship between iron metabolism and ovarian cancer and to identify novel markers for diagnostics and therapeutics. The endometriosis dataset GSE51981 and the ovarian cancer dataset GSE26712 were obtained from the gene expression omnibus database, and differentially expressed genes were identified. Iron metabolism genes were obtained from molecular signatures database, and hub genes from the 3

The functional role of long noncoding RNA in resistance to anticancer treatment.

Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, e

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

Протеин тиросин фосфатаза-рецептор типа каппа (ПТПРК) вернулся к рассмотрению: развивающееся понимание структуры, функций и патологии.

Protein Tyrosine Phosphataze Type Cappa (PTPRK) — мембранная тиросина фосфатаза, кодируемая часто удаляемой областью хромосомы 6q, которая играет ключевую роль в регулировании сигнала, сцепления и иммунной реакции клеток. Структурно PTPRK включает внеклеточную область, связанную с сцеплением клеток, область трансмембрана и две внутриклеточные каталитические области, ответственные за фосфатазу. В частности, PTPRK подвергается протеолитическому декольте с помощью Furin и ADAM10, в результате чего образуется внеклеточная подгруппа E и подгруппа P. Дальнейшая обработка с помощью β-Secretasa выпуск

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the parti

MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM.

ObjectiveTo investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway.MethodsThe expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic,

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. …

Starvation-induced long non-coding RNAs are significant for prognosis evaluation of bladder cancer.

BackgroundStarving intratumoral microenvironment prominently alters genic profiles including long non-coding RNAs (lncRNAs), which further regulate bladder cancer (BCa) malignant biological properties, such as invasion and migration.MethodsTranscriptome RNA-sequencing data of 414 BCa tumor tissues and 19 normal tissues were obtained from TCGA database and paired samples of 132 BCa patients. A chain of in vitro validations such as qPCR, migration and invasion assays were performed to reveal the clinical relevance of AC011472.4 and AL157895.1.ResultsA total of 11 lncRNAs were identified as starv

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

The Landscape of lncRNAs in Multiple Myeloma: Implications in the "Hallmarks of Cancer", Clinical Perspectives and Therapeutic Opportunities.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as "hallmarks of cancer" that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncR

Using ncRNAs as Tools in Cancer Diagnosis and Treatment-The Way towards Personalized Medicine to Improve Patients' Health.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular

Иммунофенотифицирование крови пациентов с множественным склерозом в диагнозе указывает на классическую подгруппу моноцитов, связанную с эволюцией болезней.

ВВЕДЕНИЕ: Торговля миелоидными клетками с периферии в центральную нервную систему является ключевым фактором в многократном склерозе (МС) посредством представления антигенов, секреции цитокинов и процессов ремонта. МЕТОДЫ: Комбинация массовой цитометрии на кровяных клетках от 60 пациентов, проходящих диагностику, и 29 здоровых методов контроля, а также секвенирование с одной клеткой РНК на спаренных образцах крови и цереброспинной жидкости (CSF), взятых из 5 пациентов с миэлоидными клетками. Результаты: Исследование отсека Myeloid показало обогащение специфической классической популяции моноци

CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1's molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotrans

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

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

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 ]. …