Assessment of cell cycle progression and mitotic slippage by videomicroscopy.

Senescence is a state of irreversible cell cycle arrest accompanied by the acquisition of the senescence-associated secretory phenotype (SASP), which is activated in response to a variety of damaging stimuli, including genotoxic therapy. Accumulating evidence indicates that mitotic stress also promotes entry into senescence. This occurs via a mechanism involving defective mitoses and mitotic arrest, followed by abortion of cell division and slippage in the G phase.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B.

Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape.

Catastrophic DNA replication in unscheduled tetraploid cells.

Unscheduled tetraploidy is a metastable state that rapidly evolves into aneuploidy. Recent findings reported by Gemble et al. demonstrate that freshly formed tetraploid cells fail to accumulate the required amounts of DNA replication factors during the first G phase after whole-genome duplication (WGD), culminating in genetic instability in the subsequent S phase and extensive karyotypic alterations.

The Targeting of MRE11 or RAD51 Sensitizes Colorectal Cancer Stem Cells to CHK1 Inhibition.

Cancer stem cells (CSCs) drive not only tumor initiation and expansion, but also therapeutic resistance and tumor relapse. Therefore, CSC eradication is required for effective cancer therapy. In preclinical models, CSCs demonstrated high capability to tolerate even extensive genotoxic stress, including replication stress, because they are endowed with a very robust DNA damage response (DDR).

Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51.

Cancer stem cells (CSCs) are tumor subpopulations driving disease development, progression, relapse and therapy resistance, and their targeting ensures tumor eradication. CSCs display heterogeneous replication stress (RS), but the functionality/relevance of the RS response (RSR) centered on the ATR-CHK1 axis is debated. Here, we show that the RSR is efficient in primary CSCs from colorectal cancer (CRC-SCs), and describe unique roles for PARP1 and MRE11/RAD51.

EFFECT OF BUILDUP FACTORS ON INDOOR GAMMA DOSE RATE.

The effect of buildup factors on absorbed dose rate in air and the effective dose from gamma rays of primordial radionuclides in building materials, was investigated in the article. Specific absorbed dose rates were calculated for the standard concrete room, as well as, for rooms where brick and covering building materials were used. For all room models the Harima (G-P) buildup factors were applied, while for the standard room the Berger's and Taylor's buildup factors were used, too.

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Cytofluorometric assessment of dendritic cell-mediated uptake of cancer cell apoptotic bodies.

Dendritic cells (DCs) are specialized antigen presenting cells (APCs) able to intake and crosspresent antigens (Ags) on major histocompatibility complex (MHC) class I and II molecules to T cells thus initiating primary and memory immune responses. DC-mediated Ag uptake and crosspresentation represent crucial steps toward cancer recognition and eventually elimination. Cytofluorometry is a standardized procedure to study phagocytosis.

Assessment of IFN-γ and granzyme-B production by in "sitro" technology.

Tumor neantigens (TNAs) and tumor-associated antigens (TAAs) are crucial triggers of anticancer immune responses. Through major histocompatibility complex, such antigens activate T cells, which, by releasing interferon gamma (IFN-γ) and granzyme B (GRZB), act as crucial effectors against tumor onset and progression. However, in response to immune pressure, cancer cells use different strategies to favor the establishment of an immunosuppressive tumor microenvironment (TME).

Macrophages and Metabolism in the Tumor Microenvironment.

Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can account for up to 50% of some solid neoplasms. Most often, TAMs support disease progression and resistance to therapy by providing malignant cells with trophic and nutritional support. However, TAMs can mediate antineoplastic effects, especially in response to pharmacological agents that boost their phagocytic and oxidative functions.

Stress responses in stromal cells and tumor homeostasis.

In most (if not all) solid tumors, malignant cells are outnumbered by their non-malignant counterparts, including immune, endothelial and stromal cells. However, while the mechanisms whereby cancer cells adapt to microenvironmental perturbations have been studied in great detail, relatively little is known on stress responses in non-malignant compartments of the tumor microenvironment. Here, we discuss the mechanisms whereby cancer-associated fibroblasts and other cellular components of the tumor stroma react to stress in the context of an intimate crosstalk with malignant, endothelial and immune cells, and how such crosstalk influences disease progression and response to treatment.

RADIOACTIVITY OF SOIL IN THE REGION OF THE TOWN OF NIŠ, SERBIA.

The concentration of radionuclides in samples of soil collected in the region of the town of Niš, was measured and presented in this paper. The naturally occurring radionuclides, 226Ra, 232Th and 40K, were found in all samples. In many of them, 137Cs was also measured, while the other artificial radionuclides were not detected.

Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy.

Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies.

Replication stress response in cancer stem cells as a target for chemotherapy.

Cancer stem cells (CSCs) are subpopulations of multipotent stem cells (SCs) responsible for the initiation, long-term clonal maintenance, growth and spreading of most human neoplasms. Reportedly, CSCs share a very robust DNA damage response (DDR) with embryonic and adult SCs, which allows them to survive endogenous and exogenous genotoxins. A range of experimental evidence indicates that CSCs have high but heterogeneous levels of replication stress (RS), arising from, and being boosted by, endogenous causes, such as specific genetic backgrounds (e.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes.

Type-I-interferons in infection and cancer: Unanticipated dynamics with therapeutic implications.

If there is a great new hope in the treatment of cancer, the immune system is it. Innate and adaptive immunity either promote or attenuate tumorigenesis and so can have opposing effects on the therapeutic outcome. Originally described as potent antivirals, Type-I interferons (IFNs) were quickly recognized as central coordinators of tumor-immune system interactions.

Caspase 2 in mitotic catastrophe: The terminator of aneuploid and tetraploid cells.

Mitotic catastrophe is an oncosuppressive mechanism that targets cells experiencing defective mitoses via the activation of specific cell cycle checkpoints, regulated cell death pathways and/or cell senescence. This prevents the accumulation of karyotypic aberrations, which otherwise may drive oncogenesis and tumor progression. Here, we summarize experimental evidence confirming the role of caspase 2 (CASP2) as the main executor of mitotic catastrophe, and we discuss the signals that activate CASP2 in the presence of mitotic aberrations.

Deciphering the loop of epithelial-mesenchymal transition, inflammatory cytokines and cancer immunoediting.

Tumorigenesis and tumor progression relies on the dialectics between tumor cells, the extracellular matrix and its remodelling enzymes, neighbouring cells and soluble cues. The host immune response is crucial in eliminating or promoting tumor growth and the reciprocal coevolution of tumor and immune cells, during disease progression and in response to therapy, shapes tumor fate by activating innate and adaptive mechanisms. The phenotypic plasticity is a common feature of epithelial and immune cells and epithelial-mesenchymal transition (EMT) is a dynamic process, governed by microenvironmental stimuli, critical in tumor cell shaping, increased tumor cell heterogeneity and stemness.

DNA Damage in Stem Cells.

Both embryonic and adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism. Inducible pluripotent stem cells also display a robust DNA damage response, but the stability of their genome is often conditioned by the mutational history of the cell population of origin, which constitutes an obstacle to clinical applications. Cancer stem cells are particularly tolerant to DNA damage and fail to undergo senescence or regulated cell death upon accumulation of genetic lesions.

ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.

The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels.