Histologic Transformation in Cancer: The Path for Clinical Translation.

Unlabelled: Lineage plasticity, a critical hallmark of cancer progression, enables tumor cells to evade inhibition of primary oncogenic pathways through histologic transformation. This adaptive process, driven by stemness-associated features and epigenetic reprogramming, poses significant challenges in treatment. Using non-small cell lung cancer and prostate cancer as models, we examine the utility of tissue and liquid biopsies in detecting histologic transformations and tailoring treatments to specific subtypes, which has profound clinical implications, potentially improving outcomes in patients with advanced, therapy-resistant disease.

Molecular Landscape and Therapeutic Strategies of Lung Cancer Lineage Plasticity.

Histologic transformation from lung adenocarcinoma (LUAD) to SCLC or lung squamous cell carcinoma (LUSC) represents distinct but converging processes of cellular plasticity. Cellular plasticity, the ability to switch phenotypes between distinct developmental lineages, is critical in embryogenesis, tissue repair, and homeostasis. Tumor cells exploit these mechanisms to adapt to external pressures, such as therapeutic interventions, resulting in phenotypic transitions that drive therapeutic resistance and poor prognosis.

Targeting Cellular Energetics via Ferroptosis Mediated Cell Death in Resistant Colorectal Cancer Stem Cells.

Ferroptosis, a newly discovered non-apoptotic form of cell death triggered by iron-dependent toxic membrane lipid peroxidation, establishes a link between redox biology, metabolism, and human health. By inducing ferroptosis, it is possible to selectively eliminate cancer cells and cancer stem cells (CSCs) that are resistant to traditional therapies. Recent research has shown that inducing ferroptosis can effectively kill colorectal cancer stem cells (CRC CSCs) that are resistant to other forms of cell death and treatment modalities, positioning it as a potentially innovative strategy for developing treatments for colorectal cancer.

SCD1 Inhibition Blocks the AKT-NRF2-SLC7A11 Pathway to Induce Lipid Metabolism Remodeling and Ferroptosis Priming in Lung Adenocarcinoma.

Unlabelled: Concurrent inactivating mutations in STK11 and KEAP1 drive primary resistance to therapies, leading to worse outcomes in KRAS-mutated lung adenocarcinoma (KRASmut LUAD), and are associated with metabolic alterations. Elucidation of the underlying biology of this aggressive LUAD subset is needed to develop effective treatments to improve patient outcomes. Our transcriptomic analysis of 5,498 "real-world" KRASmut LUADs demonstrated that STK11/KEAP1 co-mutation led to upregulation of fatty acid and redox signaling pathways and considerable enrichment of the metabolic genes SCD1 and SLC7A11.

Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies.

Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings.

Effective Targeting of Colorectal Cancer Stem Cells by Inducing Differentiation Mediated by Low-Dose Vitamin C via β-Catenin Retention in the Cell Membrane.

Cancer stem cells (CSCs) are implicated as the underlying cause of tumor recurrence due to their refractoriness to conventional therapies. Targeting CSCs through novel approaches can hinder their survival and proliferation, potentially reducing the challenges associated with tumor relapse. Our previous study demonstrated that colorectal cancer stem cells (CR-CSCs) showed sensitivity to Vitamin C (Vit C), displaying a dose-responsive effect where low doses (2-10 µM) promoted cell proliferation while high doses induced cell death.

Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer.

Lurbinectedin is an approved second-line treatment for small-cell lung cancer (SCLC). SCLC clinical trials combining lurbinectedin with PD-L1 blockade are currently ongoing. However, the immunomodulatory effects of lurbinectedin remain largely unknown.

Arachidonic acid modulates the cellular energetics of human pluripotent stem cells and protects the embryoid bodies from embryotoxicity effects in vitro.

Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos.

Stearoyl coenzyme A desaturase-1: multitasker in cancer, metabolism, and ferroptosis.

Cancer progression is a highly balanced process and is maintained by a sequence of finely tuned metabolic pathways. Stearoyl coenzyme A desaturase-1 (SCD1), the fatty enzyme that converts saturated fatty acids into monounsaturated fatty acids, is a critical modulator of the fatty acid metabolic pathway. SCD1 expression is associated with poor prognosis in several cancer types.

Significance of Oct-4 transcription factor as a pivotal therapeutic target for CD44 /24 mammary tumor initiating cells: Aiming at the root of the recurrence.

Breast cancer (BC) remains one of the deadliest and frequently diagnosed metastatic cancers worldwide. Cancer stem cells (CSCs) are the cell population within the tumor niche, having an epithelial to mesenchymal (EMT) transition phenotype, high self-renewal, vigorous metastatic capacity, drug resistance, and tumor relapse. Identification of targets for induction of apoptosis is essential to provide novel therapeutic approaches in BC.

Assessment of Threshold Dose of Thoron Inhalation and Its Biological Effects by Mimicking the Radiation Doses in Monazite Placer Deposits Corresponding to the Normal, Medium and Very High Natural Background Radiation Areas.

The dose contributed from thoron (Rn) and its progeny has been neglected in the dose assessment because of its short half-life (t = 55.6 s) and generally low concentrations. Recently, concentrations of Rn gas and its progeny were found to be pronounced in the traditional residential dwellings in China, on beaches of India and in other countries.

Thorium promotes lung, liver and kidney damage in BALB/c mouse via alterations in antioxidant systems.

Thorium (Th), long lived (14.05 billion years) most stable thorium isotope, is thrice naturally abundant than uranium. Th occurs as rocky deposits and black monazite sands on the earth's crust geographically distributed in coastal South India and other places globally.

Mitochondria-targeted half-sandwich iridium(iii)-Cp*-arylimidazophenanthroline complexes as antiproliferative and bioimaging agents against triple negative breast cancer cells MDA-MB-468.

To reduce the side effects of marketed cancer drugs against triple negative breast cancer cells we have reported mitochondria targeting half-sandwich iridium(iii)-Cp*-arylimidazophenanthroline complexes for MDA-MB-468 cell therapy and diagnosis. Out of five Ir(iii) complexes (IrL1-IrL5), [iridium(iii)-Cp*-2-(naphthalen-1-yl)-1-imidazo[4,5-][1,10]phenanthroline]PF (IrL1) has exhibited the best cytoselectivity against MDA-MB-468 cells compared to normal HaCaT cells along with excellent binding efficacy with DNA as well as serum albumin. The subcellular localization study of the complex revealed the localization of the compound in cytoplasm thereby pointing to a possible mitochondrial localization and consequent mitochondrial dysfunction MMP alteration and ROS generation.

2,2'-Bipyrimidine-based luminescent Ru(ii)/Ir(iii)-arene monometallic and homo- and hetero-bimetallic complexes for therapy against MDA-MB-468 and caco-2 cells.

To unearth suitable complexes that are capable of inhibiting the growth of MDA-MB-468 and Caco-2 cells, 2,2'-bipyrimidine-based luminescent Ru(ii)/Ir(iii)-arene monometallic and homo- and hetero-bimetallic complexes were synthesized. The complex [(η-p-cymene)(η-Cp*)RuIrCl(K-N,N-bipyrimidine)](PF) [LRuIr] exhibited the best potency in both cells along with good GSH stability and strong binding efficacy with the biomolecules. The apoptotic event occurred in MDA-MB-468 cancer cells via cell cycle arrest.

Mitochondria specific highly cytoselective iridium(iii)-Cp* dipyridophenazine (dppz) complexes as cancer cell imaging agents.

Cancer is the most incurable pernicious disease to date after cardiovascular disease with an immeasurable rate of mortality. However, effective cancer medication and therapy are still castles in the sky to researchers. Therefore, in search of an appropriate strategy to annihilate cancer, we have designed a set of Ir(iii)-Cp* dipyridophenazine complexes as luminescent anticancer agents combining the cancer inhibiting potency of the planar dipyridophenazine (dppz) moiety through DNA interaction and mitochondrial dysfunction with the wonderful photoluminescence ability and target specificity of iridium metal.

DNA targeting half sandwich Ru(II)--cymene-N^N complexes as cancer cell imaging and terminating agents: influence of regioisomers in cytotoxicity.

For diagnosing and annihilating cancer in the human body, herein, we have adopted a one pot convenient synthetic protocol to synthesize a library of half sandwich Ru(ii)-p-cymene-N^N complexes under continuous sonication and isolated their regioisomers by preparative thin layer chromatography followed by justification of stability using DFT. The present work has resulted in a library of ruthenium arene complexes and their isolated regioisomers following environmentally benign green processes and their screening of anticancer activity in terms of cytotoxicity and selectivity against cancer cell lines where [(η6-p-cymene)RuCl{2-(5,6-dichloro-1H-benzo[d]imidazole-2-yl)quinolone}] (11j) has been elicited to be significantly more potent as well as selective in Caco-2 and HeLa cell lines than the normal HEK-293 cell line compared to cisplatin and it has even shown marked cytotoxicity against the more aggressive HT-29 colorectal cancer cell line being capable of producing oxidative stress or arresting the cell cycle. Moreover, these types of Ru(ii)-arene complexes exhibited excellent binding efficacy with DNA and the compounds [(η6-p-cymene)RuCl{5-chloro-2-(6-(4-chlorophenyl)pyridin-2-yl)benzo[d]thiazole}]PF6 (8l4), [(η6-p-cymene)Ru-2-(6-(benzofuran-2-yl)pyridin-2-yl)-5-chlorobenzo[d]thiazole (8l9) and [(η6-p-cymene)RuCl{2-(6-nitro-1H-benzo[d]imidazol-2-yl)quinolone}]Cl (11f') and might be applied for cancer theranostic treatment due to their good fluorescence properties and remarkable potency.

Mitochondria-Targeting Click-Derived Pyridinyltriazolylmethylquinoxaline-Based Y-Shaped Binuclear Luminescent Ruthenium(II) and Iridium(III) Complexes as Cancer Theranostic Agents.

Due to several negative issues, market available drugs have been gradually losing their importance in the treatment of cancer. With a view to discover suitable drugs capable of diagnosing as well as inhibiting the growth of cancer cells, we have aspired to develop a group of theranostic metal complexes which will be (i) target specific, (ii) cytoselective, thus rendering the normal cell unaffected, (iii) water-soluble, (iv) cancer cell permeable, and (v) luminescent, being beneficial for healing the cancer eternally. Therefore, to reach our goal, we have prepared novel Ru(II)- and Ir(III)-based bimetallic and hetero bimetallic scaffolds using click-derived pyridinyltriazolylmethylquinoxaline ligands followed by metal coordination.

Differential sensitivities of triple-negative breast cancer stem cell towards various doses of vitamin C: An insight into the internal antioxidant systems.

Cancer stem cells (CSCs) are quiescent and self-renewing, having low levels of reactive oxygen species (ROS), and are responsible for cancer recurrence after chemotherapy and radiotherapy. However, the interplay between the ROS production and scavenging from the oxidative stress has never been studied in breast CSCs. In this present study, we have investigated the cellular energetics of two triple-negative breast cancer stem cells (MDA-MB-231 and MDA-MB-468) treated with two pharmacological doses of vitamin C (10 and 20 mM) that generated ROS.

Inhibition of PfMYST Histone Acetyltransferase Activity Blocks Plasmodium falciparum Growth and Survival.

One of the major barriers in the prevention and control of malaria programs worldwide is the growing emergence of multidrug resistance in parasites, and this necessitates continued efforts to discover and develop effective drug molecules targeting novel proteins essential for parasite survival. In recent years, epigenetic regulators have evolved as an attractive drug target option owing to their crucial role in survival and development of at different stages of its life cycle. PfMYST, a histone acetyltransferase protein, is known to regulate key cellular processes, such as cell cycle progression, DNA damage repair, and antigenic variation, that facilitate parasite growth, adaptation, and survival inside its host.

Lung damage by thoron progenies versus possible damage redemption by lung stem cells: a perspective.

Purpose: Natural radiation is the major source of human exposure to ionizing radiation. About 52% of the total dose received from the high natural background radiations (HNBR) areas are due to inhalation dose from radon (Rn)/thoron (Rn) and their progenies. Hence, we reviewed the biological effects of Rn/Rn and their progenies on lung tissue, and the possible role of lung stem cells in salvaging the damage caused by Rn/Rn and their progenies.

Sodium fluoride induced skeletal muscle changes: Degradation of proteins and signaling mechanism.

Fluoride is a well-known compound for its usefulness in healing dental caries. Similarly, fluoride is also known for its toxicity to various tissues in animals and humans. It causes skeletal fluorosis leading to osteoporosis of the bones.

Plasmodium falciparum RUVBL3 protein: a novel DNA modifying enzyme and an interacting partner of essential HAT protein MYST.

RUVBLs constitute a conserved group of ATPase proteins that play significant role in a variety of cellular processes including transcriptional regulation, cell cycle and DNA damage repair. Three RUVBL homologues, namely, PfRUVBL1, PfRUVBL2 and PfRUVBL3 have been identified in P. falciparum, unlike its eukaryotic counterparts, which have two RUVBL proteins (RUVBL1 & RUVBL2).