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Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas.

T-cell lymphomas are a heterogeneous group of cancers with different pathogenesis and poor prognosis. Histone deacetylases (HDACs) are epigenetic modifiers that modulate many key biological processes. In recent years, HDACs have been fully investigated for their roles and potential as drug targets in T-cell lymphomas. In this review, we have deciphered the modes of action of HDACs, HDAC inhibitors as single agents, and HDACs guided combination therapies in T-cell lymphomas. The overview of HDACs on the stage of T-cell lymphomas, and HDACs guided therapies both as single agents and combination

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival

Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis,

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

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… In the G1 phase, ROS promote G1/S transition via CDK2 oxidation/phosphorylation while inhibiting cyclin D–CDK4/6 through disulfide bond formation, reducing proliferation. … In the G1 phase, ROS promote G1/S transition via CDK2 oxidation/phosphorylation while inhibiting cyclin D–CDK4/6 through disulfide bond formation, reducing proliferation. …

Prevention of venous thromboembolism in ambulatory patients with cancer.

Patients with cancer are at high risk of venous thromboembolic events, and this risk can be further increased in patients with certain cancer types and by cancer treatments. Guidelines on the prevention of cancer-associated thrombosis (CAT) recommend thromboprophylaxis for hospitalised patients; however, this is not routinely recommended for ambulatory patients receiving chemotherapy and is limited to specified high-risk patients. Identification of the ambulatory patients at risk of CAT who would most benefit from anticoagulant therapy is therefore critical to reduce the incidence of this comp

Selinexor, a selective inhibitor of nuclear export, shows anti-proliferative and anti-migratory effects on male germ cells in vitro.

BackgroundSelinexor (SLX), a selective inhibitor of nuclear export (SINE), has been shown to interfere with nuclear export mechanisms and to exert antitumor effects in a variety of cancer cell types. It is known to regulate multiple fundamental cellular processes, including the DNA damage response, cell proliferation, and stress signaling pathways. Nevertheless, its potential effects on reproductive cells remain inadequately characterized. The present study was aimed to investigate the cytotoxic, apoptotic, anti-proliferative and anti-migratory effects of SLX on GC1 (spermatogonia) and GC2 (sp

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… Furthermore, a significant increase in the G0/G1 phase and a significant decrease in the S phase of the cell cycle were detected after treatment. It is stated that SLX suppresses DNA synthesis by stopping the cell cycle in the G0/G1 phase in AML cells and thus inhibits cell proliferation [ 47 ]. …

Anticancer Potential of Whey Proteins-A Systematic Review of Bioactivity and Functional Mechanisms.

Cancer remains a primary global health concern, with treatment-related side effects and malnutrition posing significant challenges to patient care and recovery. In recent years, there has been growing interest in the therapeutic potential of functional food components, especially whey proteins (WPs), due to their notable antioxidant, immunomodulatory, and anticancer properties. This systematic review explores the effects of WPs across various cancer types and assesses their value as supportive nutritional agents. A thorough literature search was conducted in PubMed, Scopus, and Web of Science

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… Preclinical research has demonstrated that WP can reduce oxidative stress in the tumor microenvironment, induce apoptosis (via caspase-3/7 activation), and arrest the cell cycle in the G0/G1 phase [ 7 ]. …

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estim

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… An extract containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell lines showed antiproliferative effects on LNCaP (IC50 ≅ 6 μg/mL) via a G0/G1 phase arrest, which was accompanied by the downregulation of CDK4, CDK2, Cyclin D1, and Cyclin D3, and the upregulation … Furthermore, they induced a Go/G1-phase arrest on PC-3 cells and an S-phase arrest on MeWo cells with an accumulation of cells in the Sub-G1 phase. …

Proceedings of Reanimation 2023, the French Intensive Care Society International Congress.

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Biomarker Jeopardy.

In the popular Biomarker Jeopardy session, Sandra E. Kurtin, PhD, ANP-C, AOCN®, Alyssa Henglefelt, PharmD, BCOP, and Haleigh Mistry, MS, PA-C, paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and discussed guidelines for biomarker testing.

Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury.

The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg-Gly-Asp-alginate (RGD-Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin-12 (IL-12) (RGD-Al

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… Conversely, IR‐con treatment led to greater G0/G1 phase arrest (Figure 4F,G ). Consistent with cell cycle analysis, the Gel/Laponite@IL‐12‐treated BM‐MSCs expressed more EdU‐positive cells compared to the IR‐Con group (Figure 4H ). … As shown in Figure 6H,I , PI3K/AKT inhibitor treatment led to a G0/G1 phase arrest and interference with cell cycle progression, indicating that LY294002 effectively suppressed the proliferation induced by Gel/Laponite@IL‐12. …

CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells.

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27

Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.

The tumor suppressor p53, often referred to as the “guardian of the genome,” is mutated in more than half of human cancers. These mutations have a significant impact on cancer biology and response to therapy. p53 mutations involve a range of changes that interfere with DNA binding, eliminate tumor suppressor functions, and, in many cases, confer dominant-negative or gain-of-function characteristics that actively promote oncogenesis. These mutations are closely linked to poor clinical outcomes and resistance to standard treatments. This review examines the impact of p53 mutations on cancer ther

The "Road" to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review.

Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR d

Regulating the regulators: long non-coding RNAs as autophagic controllers in chronic disease management.

The increasing prevalence of chronic diseases and their associated morbidities demands a deeper understanding of underlying mechanism and causative factors, with the hope of developing novel therapeutic strategies. Autophagy, a conserved biological process, involves the degradation of damaged organelles or protein aggregates to maintain cellular homeostasis. Disruption of this crucial process leads to increased genomic instability, accumulation of reactive oxygen species (ROS), decreased mitochondrial functions, and suppression of ubiquitination, leading to overall decline in quality of intrac

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer.

Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one suc

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… Further, GS treatment blocked IκBα phosphorylation induced by deoxycholic acid and decreased CDX2, COX-2, and prostaglandin E2 (PGE2) expressions in EAC cells, and also caused increased sub-G1 phase apoptosis in BE and EAC cells [ 115 ]. … For instance, treatment with GS significantly reduced the proliferation, induced G0/G1 phase arrest and apoptosis in HepG2 cells via regulating the expression of Bax, Bcl-2, TGF-β1, TNF-α, and VEGF [ 125 ]. Further, GS was also found to inhibit TGF-β-induced EMT in HCC cells [ 106 ]. …

Долгосрочная стабильность и производительность генных движителей на основе Cas9/Guide RNA в анофелиновых комарах.

Разрабатываются стратегии изменения численности населения с целью борьбы с распространением анофелиных комаров паразитов, вызывающих человеческую малярию. Эти подходы направлены на сокращение заболеваемости и заболеваемости за счет распространения доминирующих генов антипаратионного эффекта среди переносчиков инфекции. Для того чтобы штаммы могли оказывать эпидемиологическое воздействие, они должны в течение продолжительного периода времени сохранять свойства привода и подавления паразитов. Three Gene-drive штаммы, AcTP13 и AcTP43 в Anopheles coluszii и AgTP13 в Anopheles gambiae, с автономным

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the b