scholarly journals Regulated Cell Death in Urinary Malignancies

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhenyu Nie ◽  
Mei Chen ◽  
Yuanhui Gao ◽  
Denggao Huang ◽  
Hui Cao ◽  
...  
Keyword(s):  
Cell Death ◽  
Malignant Tumors ◽  
Signal Molecules ◽  
Urinary System ◽  
Research Attention ◽  
Regulated Cell Death ◽  
Tnf Α ◽  
Caspase Family ◽  
Prostate Cancers ◽  
Factor Α

Urinary malignancies refer to a series of malignant tumors that occur in the urinary system and mainly include kidney, bladder, and prostate cancers. Although local or systemic radiotherapy and chemotherapy, immunotherapy, castration therapy and other methods have been applied to treat these diseases, their high recurrence and metastasis rate remain problems for patients. With in-depth research on the pathogenesis of urinary malignant tumors, this work suggests that regulatory cell death (RCD) plays an important role in their occurrence and development. These RCD pathways are stimulated by various internal and external environmental factors and can induce cell death or permit cell survival under the control of various signal molecules, thereby affecting tumor progression or therapeutic efficacy. Among the previously reported RCD methods, necroptosis, pyroptosis, ferroptosis, and neutrophil extracellular traps (NETs) have attracted research attention. These modes transmit death signals through signal molecules, such as cysteine-aspartic proteases (caspase) family and tumor necrosis factor-α (TNF-α) that have a wide and profound influence on tumor proliferation or death and even change the sensitivity of tumor cells to therapy. This review discussed the effects of necroptosis, pyroptosis, ferroptosis, and NETs on kidney, bladder and prostate cancer and summarized the latest research and achievements in these fields. Future directions and possibility of improving the denouement of urinary system tumors treatment by targeting RCD therapy were also explored.

scholarly journals Tuberculosis in patient with psoriasis receiving biologic therapy – case report

2020 ◽  
Author(s):  
Beata Wańczyk-Dręczewska ◽  
Agnieszka O wczarczyk-Saczonek ◽  
Waldemar Placek
Keyword(s):  
Biological Treatment ◽  
Biological Therapy ◽  
Malignant Tumors ◽  
Inhibitor Therapy ◽  
Interleukin 17 ◽  
Dermatology Clinic ◽  
Increased Risk ◽  
Tnf Α ◽  
Adalimumab Therapy ◽  
Factor Α

Introduction: The introduction of biological therapy has revolutionized the treatment of psoriasis. Due to its immunosuppressive effect, the following side effects might occur: injection-site reactions, exacerbation of autoimmune diseases, increased risk of malignant tumors and infections, including tuberculosis (TB). Aim: The aim of this report is to present a case of a patient who developed TB during tumornecrosis factor α (TNF-α) inhibitor therapy. Case study: A 52-year-old man was admitted to the Dermatology Clinic for re-qualification for biological treatment with adalimumab. The patient was treated with cyclosporin A and lefludomide combined with methotrexate with no effect and the adalimumab therapy was initiated with complete remission of psoriatic lesions. The patient was suspended in the drug program because of TB. TNF-α inhibitor therapy was resumed after antimycobacterial treatment, during which lymphadenopathy was observed and serous TB was confirmed. Three months after the treatment, the patient was rehospitalized because of suspicion of TB relapse. It was decided to requalify the patient for biological therapy after completion of antimycobacterial treatment. Due to the high risk of TB recurrence, switch to the interleukin-17 inhibitor was decided. Results and discussion: The proper qualification and thorough testing before biological treatment ensures patients’ safety and satisfactory therapeutic effect. It should be remembered that during longterm therapy with TNF antagonists, both reactivation of latent TB as well as new infection are serious problems. Therefore, regular tests should be performed, especially in countries with high prevalence of this disease. Conclusions: In patients who develop TB, particularly recurrent, switching to a drug with a different mechanism should be considered.

Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-α

2002 ◽  
Vol 282 (2) ◽  
pp. G257-G266 ◽  
Author(s):  
Hailing Liu ◽  
Brett E. Jones ◽  
Cynthia Bradham ◽  
Mark J. Czaja
Keyword(s):  
Cell Death ◽  
Oxidant Stress ◽  
Nuclear Factor Κb ◽  
Dominant Negative ◽  
Tnf Α ◽  
Cyp2e1 Expression ◽  
Factor Α ◽  
Jnk Activation ◽  
Cytochrome P 450 ◽  
Necrosis Factor

The mechanisms underlying hepatocyte sensitization to tumor necrosis factor-α (TNF-α)-mediated cell death remain unclear. Increases in hepatocellular oxidant stress such as those that occur with hepatic overexpression of cytochrome P-450 2E1 (CYP2E1) may promote TNF-α death. TNF-α treatment of hepatocyte cell lines with differential CYP2E1 expression demonstrated that overexpression of CYP2E1 converted the hepatocyte TNF-α response from proliferation to apoptotic and necrotic cell death. Death occurred despite the presence of increased levels of nuclear factor-κB transcriptional activity and was associated with increased lipid peroxidation and GSH depletion. CYP2E1-overexpressing hepatocytes had increased basal and TNF-α-induced levels of c-Jun NH2-terminal kinase (JNK) activity, as well as prolonged JNK activation after TNF-α stimulation. Sensitization to TNF-α-induced cell death by CYP2E1 overexpression was inhibited by antioxidants or adenoviral expression of a dominant-negative c-Jun. Increased CYP2E1 expression sensitized hepatocytes to TNF-α toxicity mediated by c-Jun and overwhelming oxidative stress. The chronic increase in intracellular oxidant stress created by CYP2E1 overexpression may serve as a mechanism by which hepatocytes are sensitized to TNF-α toxicity in liver disease.

scholarly journals Yersinia enterocolitica Impairs Activation of Transcription Factor NF-κB: Involvement in the Induction of Programmed Cell Death and in the Suppression of the Macrophage Tumor Necrosis Factor α Production

1998 ◽  
Vol 187 (7) ◽  
pp. 1069-1079 ◽  
Author(s):  
Klaus Ruckdeschel ◽  
Suzanne Harb ◽  
Andreas Roggenkamp ◽  
Mathias Hornef ◽  
Robert Zumbihl ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Tumor Necrosis Factor ◽  
Programmed Cell Death ◽  
Proteasome Inhibitor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

In this study, we investigated the activity of transcription factor NF-κB in macrophages infected with Yersinia enterocolitica. Although triggering initially a weak NF-κB signal, Y. enterocolitica inhibited NF-κB activation in murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y. enterocolitica prevented prolonged degradation of the inhibitory proteins IκB-α and IκB-β observed by treatment with lipopolysaccharide (LPS) or nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica mutants revealed a striking correlation between the abilities of these strains to inhibit NF-κB and to suppress the tumor necrosis factor α (TNF-α) production as well as to trigger macrophage apoptosis. When NF-κB activation was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF-α secretion. Y. enterocolitica also impaired the activity of NF-κB in epithelial HeLa cells. Although neither Y. enterocolitica nor TNF-α could induce HeLa cell apoptosis alone, TNF-α provoked apoptosis when activation of NF-κB was inhibited by Yersinia infection or by the proteasome inhibitor MG-132. Together, these data demonstrate that Y. enterocolitica suppresses cellular activation of NF-κB, which inhibits TNF-α release and triggers apoptosis in macrophages. Our results also suggest that Yersinia infection confers susceptibility to programmed cell death to other cell types, provided that the appropriate death signal is delivered.

Tumor necrosis factor-α and ceramide induce cell death through different mechanisms in rat mesangial cells

1999 ◽  
Vol 276 (3) ◽  
pp. F390-F397 ◽  
Author(s):  
Yan-Lin Guo ◽  
Baobin Kang ◽  
Li-Jun Yang ◽  
John R. Williamson
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mesangial Cells ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

It has been proposed that ceramide acts as a cellular messenger to mediate tumor necrosis factor-α (TNF-α)-induced apoptosis. Based on this hypothesis, it was postulated that resistance of some cells to TNF-α cytotoxicity was due to an insufficient production of ceramide on stimulation by TNF-α. The present study was initiated to investigate whether this was the case in mesangial cells, which normally are insensitive to TNF-α-induced apoptosis. Our results indicate that although C2ceramide was toxic to mesangial cells, the cell death it induced differed both morphologically and biochemically from that induced by TNF-α in the presence of cycloheximide (CHX). The most apparent effect of C2ceramide was to cause cells to swell, followed by disruption of the cell membrane. It is evident that C2ceramide caused cell death by necrosis, whereas TNF-α in the presence of CHX killed the cells by apoptosis. C2ceramide did not mimic the effects of TNF-α on the activation of c-Jun NH2-terminal protein kinase and nuclear factor-κB transcription factor. Although mitogen-activated protein kinase [extracellular signal-related kinase (ERK)] was activated by both C2ceramide and TNF-α, such activation appeared to be mediated by different mechanisms as judged from the kinetics of ERK activation. Furthermore, the cleavage of cytosolic phospholipase A2during cell death induced by C2ceramide and by TNF-α in the presence of CHX showed distinctive patterns. The present study provides evidence that apoptosis and necrosis use distinctive signaling machinery to cause cell death.

Contribution of caveolin-1α and Akt to TNF-α-induced cell death

2004 ◽  
Vol 287 (1) ◽  
pp. L201-L209 ◽  
Author(s):  
Koh Ono ◽  
Yoshitaka Iwanaga ◽  
Madoka Hirayama ◽  
Teruhisa Kawamura ◽  
Naoya Sowa ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepg2 Cells ◽  
Survival Rates ◽  
Random Mutagenesis ◽  
Pi3k Inhibitor ◽  
L929 Cells ◽  
Empty Vector ◽  
Tnf Α ◽  
Pi3k Activation ◽  
Factor Α

We used retrovirus insertion-mediated random mutagenesis to generate tumor necrosis factor-α (TNF-α)-resistant lines from L929 cells. Using this approach, we discovered that caveolin-1α is required for TNF-α-induced cell death in L929 cells. The need for caveolin-1α in TNF-α-induced cell death was confirmed by the restoration of sensitivity to TNF-α after ectopic reconstitution of caveolin-1α/β expression. This caveolin-1α-mutated line was also resistant to H2O2and staurosporine, but not to lonidamine. HepG2 cells are known to lack endogenous caveolins. HepG2 cells stably transfected with caveolin-1α/β were found to be much more sensitive to TNF-α than either parental cells transfected with caveolin-1β or parental cells transfected with an empty vector. In contrast to its extensively documented antiapoptotic effect, the elevated activity of Akt appears to be important in sensitizing caveolin-1-expressing cells to TNF-α, since pretreatment of cells with the phosphatidylinositide 3-kinase (PI3K) inhibitor LY-294002 or wortmannin completely blocked PI3K activation and markedly improved the survival of TNF-α-treated L929 cells. The survival rates of caveolin-1α-normal and caveolin-1α-deficient L929 cells were comparable after treatment with PI3K inhibitor and TNF-α. Similar results were obtained with HepG2 cells that stably expressed caveolin-1α/β or -β and parental cells transfected with an empty vector. In summary, our results indicate that caveolin-1α preferentially sensitizes L929 cells to TNF-α through the activation of a PI3K/Akt signaling pathway.

Type I interferons in combination with bacterial stimuli induce apoptosis of monocyte-derived dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 736-742 ◽  
Author(s):  
Manfred Lehner ◽  
Thomas Felzmann ◽  
Katharina Clodi ◽  
Wolfgang Holter
Keyword(s):  
Cell Death ◽  
Lipoteichoic Acid ◽  
Type I Interferons ◽  
Interleukin 4 ◽  
Type I ◽  
Cell Recovery ◽  
Activation Induced Cell Death ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Factor Α

Abstract Both type I interferons (IFNs) as well as lipopolysaccharide (LPS) individually compromise selected monocytic or dendritic cell (DC) functions. This study investigates the influence of these agents on the differentiation and the regulation of cell death of monocyte-derived DCs generated in the presence of granulocyte-macrophage colony-stimulating factor plus interleukin-4 (IL-4). It is reported that excessive apoptosis occurred rapidly in monocyte-derived DC cultures, if IFN-α or IFN-β was added in combination with LPS or lipoteichoic acid (LTA). The small fraction of cells surviving in such cultures displayed a mature DC phenotype with expression of CD83, CD80, and CD86. IL-10 was found in the supernatants of monocyte-derived DC cultures, if supplemented with LPS or IFN-α plus LPS but not in control cultures. When monocyte-derived DCs were generated in the presence of IFN-α without LPS, these cells displayed an immature DC phenotype with a reduction of cell recovery but no overt apoptosis. However, the addition of LPS, LTA, LPS plus IFN-γ, or tumor necrosis factor α (TNF-α) plus prostaglandin E2 to such cells again resulted in the rapid induction of apoptosis in the majority of cells, together with a reduced production of IL-12 p70 and TNF-α. Together, these data indicate an exquisite sensitivity of monocyte-derived DCs to activation-induced cell death if generated in the presence of IFN-α, indicating the existence of an important mechanism of immunosuppression caused by IFN-α–inducing agents, such as viral or bacterial stimuli.

scholarly journals The Molecular Analysis of rs11614913 Polymorphism from miRNA196a Gene and Its Relationship with TNF-α Gene Expression in Cervical Cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ahmad Hamta ◽  
Fatemeh Hajihassani
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Malignant Tumors ◽  
Control Group ◽  
Tissue Samples ◽  
Altered Expression ◽  
Tnf Α ◽  
Cancer Sample ◽  
Rs11614913 Polymorphism ◽  
Factor Α

Background: Cervical cancer (CC) is one of the most common malignant tumors in women, which has been diagnosed as fourth cancer in females worldwide. In addition to human papillomavirus (HPV), genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor α (TNF-α) gene, are involved in this cancer. Objectives: This study aimed to investigate the rs11614913 polymorphism from the miRNA196a gene and its association with the expression of the TNF-α gene in cervical cancer for early diagnosis and treatment. Methods: In this study, 52 samples of pre-cancerous and cancerous lesions, and 50 tissue samples were collected from healthy subjects in an Iranian population. DNA was extracted from the samples, and rs11614913 polymorphism of the miRNA196a gene was investigated by PCR. RNA was extracted from the samples, and the expression of the miRNA196a and TNF-α genes were evaluated. Finally, for data analysis, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used. Results: The frequency of CC, TC, and TT genotypes from rs11614913 polymorphism of miRNA196a gene was 0.58, 0.34, and 0.08, respectively, but in the healthy group it was 0.36, 0.46, and 0.18, respectively. The results also showed that the expression of miRNA196a and TNF-α genes in the patient group was higher than the control group. Conclusions: Based on the results of this study, a significant correlation was found between CC genotype and rs11614913 polymorphism of miRNA196a gene and TNF-α gene expression in the cervical cancer sample. Therefore, investigating these factors in patients with cervical cancer may be helpful.

Tumor necrosis factor α induces a caspase-independent death pathway in human neutrophils

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1987-1995 ◽  
Author(s):  
Nikolai A. Maianski ◽  
Dirk Roos ◽  
Taco W. Kuijpers
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Human Neutrophils ◽  
Dna Laddering ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) is a cytokine with multiple roles in the immune system, including the induction and potentiation of cellular functions in neutrophils (PMNs). TNF-α also induces apoptotic signals leading to the activation of several caspases, which are involved in different steps of the process of cell death. Inhibition of caspases usually increases cell survival. Here, we found that inhibition of caspases by the general caspase inhibitor zVAD-fmk did not prevent TNF-α–induced PMN death. After 6 hours of incubation, TNF-α alone caused PMN death with characteristic apoptotic features (typical morphologic changes, DNA laddering, external phosphatidyl serine [PS] exposure in the plasma membrane, Bax clustering and translocation to the mitochondria, and degradation of mitochondria), which coincided with activation of caspase-8 and caspase-3. However, in the presence of TNF-α, PMNs died even when caspases were completely inhibited. This type of cell death lacked nuclear features of apoptosis (ie, no DNA laddering but aberrant hyperlobulated nuclei without typical chromatin condensation) and demonstrated no Bax redistribution, but it did show mitochondria clustering and plasma membrane PS exposure. In contrast, Fas-triggered PMN apoptosis was completely blocked by zVAD-fmk. Experiments with scavengers of reactive oxygen species (ROS) and with inhibitors of mitochondrial respiration, with PMN-derived cytoplasts (which lack mitochondria) and with PMNs from patients with chronic granulomatous disease (which have impaired nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) indicated that TNF-α/zVAD-fmk–induced cell death depends on mitochondria-derived ROS. Thus, TNF-α can induce a “classical,” caspase-dependent and a “nonclassical” caspase-independent cell death.

scholarly journals Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis

2018 ◽  
Vol 49 (6) ◽  
pp. 2427-2442 ◽  
Author(s):  
Siming Li ◽  
Xiaohong Yang ◽  
Zhencheng Feng ◽  
Pengzhen Wang ◽  
Weicong Zhu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Oxygen Species ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Background/Aims: Both physiologic remodeling and pathologic regeneration of cartilage tissue rely upon chondrocyte functions and are benefited from factors that promote viability and inhibit apoptosis of the cell, and associated mechanisms. High level of reactive oxygen species (ROS) and proinflammatory cytokines activate apoptosis signaling and initiate cell death, which can be attenuated by antioxidants. This study examined the effect of catalase (CAT) on ROS and tumor necrosis factor-α (TNF-α)-induced apoptosis in human C28/I2 chondrocytes cultured in monolayer. Methods: Chondrocytes were treated with diluted CAT in the presence or absence of TNF-α and compared to untreated cells. Levels of hydrogen peroxide (H2O2) and mitochondrial membrane potential (Δψm) were measured using fluorescent labeling, cell apoptosis was assayed by flow cytometry using Annexin V/propidium iodide (PI) staining, gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and the proteins were investigated by Western blotting. Results: CAT effectively reduced the intracellular ROS caused by the monolayer culture system, enhanced the Δψm depending on the presence of TNF-α and promoted morphological features at sub-cellular level. CAT also attenuated the TNF-α-upregulated expression of factors/mediators of extrinsic cell death cascade and apoptotic caspases, ultimately resulted in promoted cellular viability. Conclusion: The anti-apoptotic effect of CAT on chondrocytes via scavenging ROS and suppressing TNF-α-induced cell apoptosis by TNF/TNF receptor (TNFR) mediated death signaling pathway and potentiate CAT as a complementary agent beneficial to cartilage remodeling and regeneration in vivo, and cell-based therapies of cartilage repair demanding viable cells expanded ex vivo.

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