scholarly journals Apoptosis in malignant diseases

2005 ◽  
Vol 13 (1) ◽  
pp. 19-22 ◽  
Author(s):  
Goran Brajuskovic
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Regression ◽  
Current Knowledge ◽  
Biological Significance ◽  
Multistage Carcinogenesis ◽  
Pathological Conditions ◽  
Wide Range ◽  
Homeostatic Function ◽  
Apoptotic Genes

Apoptosis is a special type of cell death essentially different from necrosis in nature and biological significance. It is an active process of genetically regulated cell auto destruction and in most cases has a homeostatic function. Apoptotic cells may be characterized by specific morphological and biochemical changes. A great number of genes are known today, whose protein products take part in regulation of the apoptotic process. Apoptosis or programmed cell death has been implicated in a wide range of pathological conditions. Studies of the correlation of programmed cell death with proliferation and the multistage carcinogenesis process are in the focus of modern research. Mutations and deletions of apoptotic genes play important roles in carcinogenesis, tumor growth, and tumor regression. This article reviews the current knowledge on mutations of apoptosis genes involved in pathogenesis of human cancers. Finally, we have recently summarized achievements in cancer therapy with a focus on the apoptotic genes.

scholarly journals Programmed cell death proteins and chronic leukemia

2011 ◽  
Vol 63 (3) ◽  
pp. 527-535
Author(s):  
G. Brajuskovic ◽  
Milica Strnad ◽  
Snezana Cerovic ◽  
Stanka Romac
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Chronic Leukemia ◽  
Morphological Aspects ◽  
Pathological Conditions ◽  
Wide Range ◽  
Induction Of Apoptosis ◽  
Apoptotic Genes

Apoptosis or programmed cell death is a genetically regulated process of cellular suicide. Apoptosis has been implicated in a wide range of pathological conditions, and mutations in apoptotic genes play important roles in the process of malignant transformation. Chronic leukemia represents a neoplastic disorder caused primarily by defective programmed cell death, as opposed to increased cell proliferation. This paper presents the main results of our ten-year research on the apoptosis of leukemia cells. The research included the morphological aspects of the process, the effect of antineoplastic agents on the induction of apoptosis in leukemia cells and expression analysis of the proteins involved in programmed cell death. Special attention was paid to the expression and interaction of the Bcl-2 family of proteins in leukemia cells. The ultimate aim of the study of apoptosis of leukemic cells is the discovery of new biological agents that might be used in the treatment of chronic leukemia.

scholarly journals The Molecular Links between Cell Death and Inflammasome

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1057 ◽  
Author(s):  
Kwang-Ho Lee ◽  
Tae-Bong Kang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Death Receptor ◽  
Signaling Molecules ◽  
Inflammasome Activation ◽  
Cell Death Pathways ◽  
Wide Range ◽  
Activation Pathways

Programmed cell death pathways and inflammasome activation pathways can be genetically and functionally separated. Inflammasomes are specialized protein complexes that process pro-inflammatory cytokines, interleukin-1β (IL-1β), and IL-18 to bioactive forms for protection from a wide range of pathogens, as well as environmental and host-derived danger molecules. Programmed cell death has been extensively studied, and its role in the development, homeostasis, and control of infection and danger is widely appreciated. Apoptosis and the recently recognized necroptosis are the best-characterized forms of programmed death, and the interplay between them through death receptor signaling is also being studied. Moreover, growing evidence suggests that many of the signaling molecules known to regulate programmed cell death can also modulate inflammasome activation in a cell-intrinsic manner. Therefore, in this review, we will discuss the current knowledge concerning the role of the signaling molecules originally associated with programmed cell death in the activation of inflammasome and IL-1β processing.

scholarly journals Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qingfei Chu ◽  
Xinyu Gu ◽  
Qiuxian Zheng ◽  
Jing Wang ◽  
Haihong Zhu
Keyword(s):  
Cell Death ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Cellular Energetics ◽  
Liver Cell Death

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

Binary cell death decision regulated by unequal partitioning of Numb at mitosis

Development ◽  
2002 ◽  
Vol 129 (20) ◽  
pp. 4677-4684 ◽  
Author(s):  
Virginie Orgogozo ◽  
François Schweisguth ◽  
Yohanns Bellaïche
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Daughter Cell ◽  
Asymmetric Cell Divisions ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Specific Manner ◽  
Asymmetric Divisions ◽  
Apoptotic Genes ◽  
Necessary And Sufficient

An important issue in Metazoan development is to understand the mechanisms that lead to stereotyped patterns of programmed cell death. In particular, cells programmed to die may arise from asymmetric cell divisions. The mechanisms underlying such binary cell death decisions are unknown. We describe here a Drosophila sensory organ lineage that generates a single multidentritic neuron in the embryo. This lineage involves two asymmetric divisions. Following each division, one of the two daughter cells expresses the pro-apoptotic genes reaper and grim and subsequently dies. The protein Numb appears to be specifically inherited by the daughter cell that does not die. Numb is necessary and sufficient to prevent apoptosis in this lineage. Conversely, activated Notch is sufficient to trigger death in this lineage. These results show that binary cell death decision can be regulated by the unequal segregation of Numb at mitosis. Our study also indicates that regulation of programmed cell death modulates the final pattern of sensory organs in a segment-specific manner.

scholarly journals The Evolving Landscape of Biomarkers for Anti-PD-1 or Anti-PD-L1 Therapy

2019 ◽  
Vol 8 (10) ◽  
pp. 1534 ◽  
Author(s):  
Antje Tunger ◽  
Ulrich Sommer ◽  
Rebekka Wehner ◽  
Anne Sophie Kubasch ◽  
Marc-Oliver Grimm ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Regression ◽  
Treatment Resistance ◽  
Immune Monitoring ◽  
Small Cell Lung ◽  
Tumor Patients ◽  
Programmed Cell Death 1 ◽  
Promising Treatment ◽  
Cell Death Protein

The administration of antibodies blocking the immune checkpoint molecules programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) has evolved as a very promising treatment option for cancer patients. PD-1/PD-L1 inhibition has significantly enhanced expansion, cytokine secretion, and cytotoxic activity of CD4+ and CD8+ T lymphocytes, resulting in enhanced antitumor responses. Anti-PD-1 or anti-PD-L1 therapy has induced tumor regression and improved clinical outcome in patients with different tumor entities, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. These findings led to the approval of various anti-PD-1 or anti-PD-L1 antibodies for the treatment of tumor patients. However, the majority of patients have failed to respond to this treatment modality. Comprehensive immune monitoring of clinical trials led to the identification of potential biomarkers distinguishing between responders and non-responders, the discovery of modes of treatment resistance, and the design of improved immunotherapeutic strategies. In this review article, we summarize the evolving landscape of biomarkers for anti-PD-1 or anti-PD-L1 therapy.

Mitochondrial quality control in aging and lifespan control of the fungal aging model Podospora anserina

2011 ◽  
Vol 39 (5) ◽  
pp. 1488-1492 ◽  
Author(s):  
Heinz D. Osiewacz
Keyword(s):  
Quality Control ◽  
Cell Death ◽  
Life Cycle ◽  
Programmed Cell Death ◽  
Podospora Anserina ◽  
Molecular Pathways ◽  
Mitochondrial Quality Control ◽  
Wide Range ◽  
Fundamental Process ◽  
Hierarchical Manner

Aging of biological systems is a fundamental process controlled by a complex network of molecular pathways. In the filamentous fungus Podospora anserina, a model in which organismal aging can conveniently be analysed, mitochondria play a central role. A wide range of relevant pathways were identified that contribute to the maintenance of a population of functional mitochondria. These pathways act in a hierarchical manner, but all the pathways are limited in capacity. At the end of the life cycle, when the various surveillance pathways are overwhelmed and damage has passed certain thresholds, programmed cell death brings the life of individual P. anserina to an end.

scholarly journals Comparative evaluation of the effectiveness of methods for certification of transplanted cell lines

2021 ◽  
Author(s):  
E.V. Markova ◽  
V.T. Nochevny ◽  
B.L. Manin ◽  
I.N. Matveeva
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Lines ◽  
Traditional Method ◽  
Biological Properties ◽  
International Standards ◽  
Growth Potential ◽  
Wide Range

The article presents the results of certification of two trofovariants of MDVK cell lines with the help of traditional method and flow cytometry. Research object was the test cultures MDBK-E and MDBK-B, which passed 30 and 43 passages, respectively, after cryopreservation. The traditional method of attestation of transplanted cell lines, widely used in practice, is rather laborious and requires significant expenditures of labor, money and time. The flow cytometry method is based on a wide range of cytochemical and fluorescent methods for the analysis of sizes, granularity, phases of the cell cycle, structural components (DNA, RNA, protein), cell apoptosis and a number of other indicators. It was experimentally established that the sublines of MDBK-E and MDBK-B cells differed in cultural, cytomorphological and karyological parameters, as well as in contamination by foreign agents and sensitivity to parainfluenza-3 viruses and infectious rhinotracheitis in cattle. Analysis of histograms of cell distribution depending on the DNA content showed that the studied lines MDBK-E and MDBK-B did not exceed the standard indicator in terms of apoptosis and were at the level of 3,9 and 6,8%, respectively. Cells of the MDBK-E line did not contain viral and mycoplasma contamination, were characterized by a pronounced growth potential, retained the original cell morphology and were the most promising substrate for the production of antigens of parainfluenza-3, infectious rhinotracheitis in cattle. Analysis of granularity distribution results testified to the violation of the division processes and the appearance in the population of the subline MDBK-B of abnormal cells, as well as inadequate conditions for maintaining the test culture. It has been established that the flow cytometry method is objective and quite promising in the selection of culture models that meet the requirements of domestic and international standards. The revealed correlation between the magnitude of apoptosis, cultural properties and parameters of the cell cycle makes it possible to assess the biological properties of the producer culture as one of the leading factors in the change in programmed cell death. Changes the index of programmed cell death underlies a number of important pathological conditions and degenerative processes.

scholarly journals Failure of Immunotherapy—The Molecular and Immunological Origin of Immunotherapy Resistance in Lung Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 9030
Author(s):  
Justyna Błach ◽  
Kamila Wojas-Krawczyk ◽  
Marcin Nicoś ◽  
Paweł Krawczyk
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Resistance ◽  
Immune Checkpoints ◽  
Cytotoxic T Cell ◽  
Number Of Patients ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) have a huge impact on clinical treatment results in non-small cell lung cancer (NSCLC). Blocking antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death protein ligand 1 (PD-L1) or CTLA-4 (cytotoxic T cell antigen 4) have been developed and approved for the treatment of NSCLC patients. However, a large number of patients develop resistance to this type of treatment. Primary and secondary immunotherapy resistance are distinguished. No solid biomarkers are available that are appropriate to predict the unique sensitivity to immunotherapy. Knowledge of predictive markers involved in treatment resistance is fundamental for planning of new treatment combinations. Scientists focused research on the use of immunotherapy as an essential treatment in combination with other therapy strategies, which could increase cancer immunogenicity by generating tumor cells death and new antigen release as well as by targeting other immune checkpoints and tumor microenvironment. In the present review, we summarize the current knowledge of molecular bases underlying immunotherapy resistance and discuss the capabilities and the reason of different therapeutic combinations.

scholarly journals Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Zhang ◽  
Xin-xing Wan ◽  
Xi-min Hu ◽  
Wen-juan Zhao ◽  
Xiao-xia Ban ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Programmed Cell Death ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Effects ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Wide Range

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.

Programmed cell death of keratinocytes culminates in apoptotic secretion of a humectant upon secretagogue action of acetylcholine

2001 ◽  
Vol 114 (6) ◽  
pp. 1189-1204 ◽  
Author(s):  
V.T. Nguyen ◽  
A. Ndoye ◽  
L.L. Hall ◽  
S. Zia ◽  
J. Arredondo ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Biological Significance ◽  
Granular Cell ◽  
Secretory Product ◽  
Intercellular Spaces ◽  
Dry Cell Weight ◽  
M1 Muscarinic ◽  
Dry Cell ◽  
Holocrine Secretion

The programmed cell death of the stratified squamous epithelial cells comprising human epidermis culminates in abrupt transition of viable granular keratinocytes (KC) into dead corneocytes sloughed by the skin. The granular cell-corneocyte transition is associated with a loss in volume and dry cell weight but the mechanism for and biological significance of this form of keratinocyte apoptosis remain obscure. We show that terminally differentiated KC extrude into the intercellular spaces of living epidermis the cytoplasmic buds containing randomly congregated components of the cytosol as well as filaggrin, a precursor of the natural moisturizing factor. The discharge of secretory product is reminiscent of holocrine secretion, suggesting the term ‘apoptotic secretion’ for this novel, essential step in the process of cornification. The secretory product may become a part of the glycocalyx (a.k.a. ‘intercellular cement substance’ of epidermis) and serve as a humectant that counterbalances the osmotic pressure imposed by the natural moisturizing factor located in the stratum corneum comprised by corneocytes. The apoptotic secretion commences upon secretagouge action of acetylcholine which is synthesized and released by KC. A combination of a cholinergic nicotinic agonist and a muscarinic antagonist which increases intracellular calcium levels is required to trigger the apoptotic secretion. Analysis of the relative amounts of cholinergic enzymes and receptors expressed by KC capable of secretion and the pharmacological profiles of secretion regulation revealed an upward concentration gradient of free acetylcholine in epidermis which may provide for its unopposed secretagogue action via the m1 muscarinic and the (α)7, and (α)9 nicotinic receptor types expressed by KC at the latest stage of their development in the epidermis.

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