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Asian Pacific Journal of Cancer... 2000
PubMed: 12716297
DOI: No ID Found -
Chinese Medical Journal Nov 2007Previous studies have shown that oncosis in malignant tumors might be related to cellular energy supply. The aim of this study was to detect oncosis in human esophageal...
BACKGROUND
Previous studies have shown that oncosis in malignant tumors might be related to cellular energy supply. The aim of this study was to detect oncosis in human esophageal squamous cell carcinoma (ESCC), and to investigate its relationship with apoptosis and microvessel density (MVD).
METHODS
ESCC specimens were obtained from 30 patients with ESCC after surgery. Transmission electron microscopy, TUNEL, and immunohistochemistry were used to detect oncosis, apoptosis, and MVD. The relation of oncosis to apoptosis and MVD was analyzed by ANOVA, t test, and q test using SPSS 10.0.
RESULTS
Transmission electron microscopy revealed both oncosis and apoptosis in the ECSS tissues. About 10% of the TUNEL-positive cells, which were considered apoptotic cells, showed the characteristics of oncosis. In the areas, where oncotic cells accumulated, apoptotic cells were rare; contrarily, where apoptotic cells gathered, oncotic cells were sparse. Compared with the tissues with a high MVD, the number of oncotic cells was increased and that of apoptotic cells was decreased in the tissues with a low MVD.
CONCLUSIONS
Cellular oncosis can be detected in human ESCC tissues. The distribution of oncotic cells presents a close relationship with cellular apoptosis and MVD. Oncosis might be induced by poor blood supply.
Topics: Aged; Apoptosis; Carcinoma, Squamous Cell; Cell Death; Esophageal Neoplasms; Female; Humans; In Situ Nick-End Labeling; Male; Middle Aged
PubMed: 18067785
DOI: No ID Found -
Oncogene Nov 2017The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed...
The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype. We also report that pharmacological activation of TRPV4 with GSK1016790A reduced viability of two basal breast cancer cell lines with pronounced endogenous overexpression of TRPV4, MDA-MB-468 and HCC1569. Pharmacological activation of TRPV4 produced pronounced cell death through two mechanisms: apoptosis and oncosis in MDA-MB-468 cells. Apoptosis was associated with PARP-1 cleavage and oncosis was associated with a rapid decline in intracellular ATP levels, which was a consequence of, rather than the cause of, the intracellular ion increase. TRPV4 activation also resulted in reduced tumour growth in vivo. These studies define a novel therapeutic strategy for breast cancers that overexpress specific calcium permeable plasmalemmal ion channels with available selective pharmacological activators.
Topics: Animals; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; Leucine; Mice, Inbred BALB C; Mice, Nude; Necrosis; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides; TRPV Cation Channels; Xenograft Model Antitumor Assays
PubMed: 28759041
DOI: 10.1038/onc.2017.234 -
Journal of Clinical Laboratory Analysis Jun 2022As an important non-apoptotic cell death method, oncosis has been reported to be closely associated with tumors in recent years. However, few research reported the...
BACKGROUND
As an important non-apoptotic cell death method, oncosis has been reported to be closely associated with tumors in recent years. However, few research reported the relationship between oncosis and lung cancer.
METHODS
In this study, we established an oncosis-based algorithm comprised of cluster grouping and a risk assessment model to predict the survival outcomes and related tumor immunity of patients with lung adenocarcinomas (LUAD). We selected 11 oncosis-related lncRNAs associated with the prognosis (CARD8-AS1, LINC00941, LINC01137, LINC01116, AC010980.2, LINC00324, AL365203.2, AL606489.1, AC004687.1, HLA-DQB1-AS1, and AL590226.1) to divide the LUAD patients into different clusters and different risk groups. Compared with patients in clsuter1, patients in cluster2 had a survival advantage and had a relatively more active tumor immunity. Subsequently, we constructed a risk assessment model to distinguish between patients into different risk groups, in which low-risk patients tend to have a better prognosis. GO enrichment analysis revealed that the risk assessment model was closely related to immune activities. In addition, low-risk patients tended to have a higher content of immune cells and stromal cells in tumor microenvironment, higher expression of PD-1, CTLA-4, HAVCR2, and were more sensitive to immune checkpoint inhibitors (ICIs), including PD-1/CTLA-4 inhibitors. The risk score had a significantly positive correlation with tumor mutation burden (TMB). The survival curve of the novel oncosis-based algorithm suggested that low-risk patients in cluster2 have the most obvious survival advantage.
CONCLUSION
The novel oncosis-based algorithm investigated the prognosis and the related tumor immunity of patients with LUAD, which could provide theoretical support for customized individual treatment for LUAD patients.
Topics: Adenocarcinoma; Algorithms; CARD Signaling Adaptor Proteins; Humans; Lung; Lung Neoplasms; Neoplasm Proteins; Prognosis; Programmed Cell Death 1 Receptor; RNA, Long Noncoding; Risk Assessment; Tumor Microenvironment
PubMed: 35476781
DOI: 10.1002/jcla.24461 -
Medical Science Monitor Basic Research Feb 2019BACKGROUND Although originally described as a survival mechanism, it is unknown whether and to what extent autophagy is implicated in the terminal stages of heart...
BACKGROUND Although originally described as a survival mechanism, it is unknown whether and to what extent autophagy is implicated in the terminal stages of heart failure. Here, we studied magnitude and evolution of autophagy in patients with intractable heart failure. MATERIAL AND METHODS Myocardial samples were obtained from 22 patients with ischemic cardiomyopathy and idiopathic dilated cardiomyopathy who were undergoing cardiac transplantation. Hearts from 11 patients who died from non-cardiac causes were used as control samples. Autophagy was evaluated by immunostaining with a monoclonal microtubule associated protein light chain 3 (LC3)-II antibody, while the relationship of autophagy with apoptosis and oncosis was assessed by double staining with TUNEL (terminal deoxynucleotidyl transferase - mediated deoxyuridine triphosphate nick end labeling) assay and complement 9 (C9) immunological staining, respectively. In addition, several necroptotic markers, including RIP1 and RIP3 (receptor interacting protein kinase 1 and 3), anti-C3 (cleaved-caspase-3), and anti-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) were assessed by immunohistochemistry. RESULTS Anti-LC3-II staining was detected in 8.7±1.6% of the heart failure patient heart samples and in 1.2±0.3% of control patient heart samples. Vacuole formation started at one nuclear pole, before becoming bipolar and involving the cytosol. Subsequently, the autophagic process extended also to the nuclei, which underwent a progressive vacuolization and disintegration, assuming a peculiar "strawberry like appearance". Myocytes with extensive vacuole formation exhibited nuclear degeneration, which was associated with TUNEL, C3, C9, RIP1, and RIP3 positive staining. Conversely, myocytes with less extensive vacuole formation showed RIP1 and NF-κB positive staining, though not positivity for other cell death markers. CONCLUSIONS Autophagy was extensively detected in end-stage heart failure and its progression, resulted in secondary cell death, with occurrence of oncosis and necroptosis exceeding that of apoptosis. Conversely, activation of the RIP1/NF-κB pathway was associated with cell survival.
Topics: Apoptosis; Autophagy; Caspase 3; Heart Failure; Humans; Male; Middle Aged; Myocytes, Cardiac; NF-kappa B; Necrosis; Nuclear Pore Complex Proteins; RNA-Binding Proteins; Signal Transduction
PubMed: 30713336
DOI: 10.12659/MSMBR.913436 -
Biomedicine & Pharmacotherapy =... Jun 2018Gliomas, the most common primary malignant brain tumor, exhibit high metabolic activity. The targeting of metabolism alterations, particularly in mitochondria, is...
Gliomas, the most common primary malignant brain tumor, exhibit high metabolic activity. The targeting of metabolism alterations, particularly in mitochondria, is emerging as an efficient approach for curing cancers. Here, we showed that berberine, a natural compound that is used as an antibacterial agent, could reduce cellular viability and induce oncosis-like death, characterized by cell swelling, cytoplasmic vacuoles and plasma membrane blebbing, in gliomas, and that these effects were correlated with intracellular adenosine triphosphate (ATP) depletion. We also found that berberine induced autophagy as a protective effect and decreased the oxygen consumption rate (OCR), which could inhibit mitochondrial aerobic respiration by repressing phosphorylated extracellular regulated protein kinases (p-ERK1/2). Furthermore, the down-regulation of mitochondrial p-ERK1/2 by berberine inhibited aerobic respiration and led to glycolysis, an inefficient energy production pathway. In addition, berberine reduced tumor growth and inhibited Ki-67 and p-ERK1/2 expression in vivo. The results demonstrate that berberine, which represses aerobic oxidation in mitochondria and decreases their energy production efficiency, decreases metabolic activity by reducing ERK1/2 activity.
Topics: Adenosine Triphosphate; Aerobiosis; Animals; Apoptosis; Autophagy; Berberine; Brain Neoplasms; Cell Growth Processes; Cell Line, Tumor; Cell Respiration; Cell Survival; Glioma; MAP Kinase Signaling System; Male; Membrane Potential, Mitochondrial; Mice, Nude; Mitochondria; Rats, Wistar; Vacuoles; Xenograft Model Antitumor Assays
PubMed: 29604589
DOI: 10.1016/j.biopha.2018.03.132 -
Canadian Journal of Ophthalmology.... Oct 1995
Review
Topics: Apoptosis; Cell Death; Eye; Eye Diseases; Humans; Necrosis
PubMed: 8574975
DOI: No ID Found -
Molecules (Basel, Switzerland) Nov 2022The potentially therapeutic effects of the naturally abundant plant flavonoid quercetin have been extensively studied. An extensive body of literature suggests that... (Review)
Review
The potentially therapeutic effects of the naturally abundant plant flavonoid quercetin have been extensively studied. An extensive body of literature suggests that quercetin's powerful antioxidant effects may relate to its ability to treat disease. Glutamate excitotoxicity occurs when a neuron is overstimulated by the neurotransmitter glutamate and causes dysregulation of intracellular calcium concentrations. Quercetin has been shown to be preventative against many forms of neuronal cell death resulting from glutamate excitotoxicity, such as oncosis, intrinsic apoptosis, mitochondrial permeability transition, ferroptosis, phagoptosis, lysosomal cell death, parthanatos, and death by reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation. The clinical importance for the attenuation of glutamate excitotoxicity arises from the need to deter the continuous formation of tissue infarction caused by various neurological diseases, such as ischemic stroke, seizures, neurodegenerative diseases, and trauma. This review aims to summarize what is known concerning glutamate physiology and glutamate excitotoxic pathophysiology and provide further insight into quercetin's potential to hinder neuronal death caused by cell death pathways activated by glutamate excitotoxicity. Quercetin's bioavailability may limit its use clinically, however. Thus, future research into ways to increase its bioavailability are warranted.
Topics: Humans; Glutamic Acid; Quercetin; Antioxidants; Reactive Oxygen Species; Neurodegenerative Diseases
PubMed: 36364448
DOI: 10.3390/molecules27217620 -
Advanced Healthcare Materials Feb 2024Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non-apoptosis-inducing agents that circumvent...
Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non-apoptosis-inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt-Cu1-4) are reported. Although they are isomers, they exhibit significantly different organelle distributions and cell death mechanisms. AFt-Cu1 and AFt-Cu3 accumulate in the cytoplasm and induce autophagy, whereas AFt-Cu2 and AFt-Cu4 can quickly enter the nucleus and trigger oncosis. Excitedly, AFt-Cu2 and AFt-Cu4 show a strong tumor growth inhibition effect in mice models bearing multidrug-resistant colon xenograft via intravenous injection. To the best of the authors' knowledge, this is the first example of metal-based nucleus-targeted oncosis inducers overcoming multidrug resistance in vivo.
Topics: Humans; Mice; Animals; Copper; Apoferritins; Drug Resistance, Multiple; Cell Line, Tumor; Nanoparticles; Colonic Neoplasms; Drug Resistance, Neoplasm; Antineoplastic Agents
PubMed: 38073257
DOI: 10.1002/adhm.202302564 -
Reviews of Physiology, Biochemistry and... 2019Oncotic cell death or oncosis represents a major mechanism of cell death in ischaemic stroke, occurring in many central nervous system (CNS) cell types including... (Review)
Review
Oncotic cell death or oncosis represents a major mechanism of cell death in ischaemic stroke, occurring in many central nervous system (CNS) cell types including neurons, glia and vascular endothelial cells. In stroke, energy depletion causes ionic pump failure and disrupts ionic homeostasis. Imbalance between the influx of Na and Cl ions and the efflux of K ions through various channel proteins and transporters creates a transmembrane osmotic gradient, with ensuing movement of water into the cells, resulting in cell swelling and oncosis. Oncosis is a key mediator of cerebral oedema in ischaemic stroke, contributing directly through cytotoxic oedema, and indirectly through vasogenic oedema by causing vascular endothelial cell death and disruption of the blood-brain barrier (BBB). Hence, inhibition of uncontrolled ionic flux represents a novel and powerful strategy in achieving neuroprotection in stroke. In this review, we provide an overview of oncotic cell death in the pathology of stroke. Importantly, we summarised the therapeutically significant pathways of water, Na, Cl and K movement across cell membranes in the CNS and their respective roles in the pathobiology of stroke.
Topics: Blood-Brain Barrier; Brain Edema; Cell Death; Edema; Humans; Stroke
PubMed: 30515590
DOI: 10.1007/112_2018_13