scholarly journals A Proteomics Screen Implicates HSP83 and a Small Kinetoplastid Calpain-related Protein in Drug Resistance inLeishmania donovaniClinical Field Isolates by Modulating Drug-induced Programmed Cell Death

2006 ◽  
Vol 6 (1) ◽  
pp. 88-101 ◽  
Author(s):  
Baptiste Vergnes ◽  
Benjamin Gourbal ◽  
Isabelle Girard ◽  
Shyam Sundar ◽  
Jolyne Drummelsmith ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Related Protein ◽  
Drug Induced ◽  
Field Isolates

Dual function of programmed cell death 10 (PDCD10) in drug resistance

2018 ◽  
Vol 101 ◽  
pp. 129-136 ◽  
Author(s):  
Cagri Urfali-Mamatoglu ◽  
Hasan Hüseyin Kazan ◽  
Ufuk Gündüz
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Dual Function

scholarly journals The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3247
Author(s):  
Lingxiao Ye ◽  
Zhengxin Zhu ◽  
Xiaochuan Chen ◽  
Haoran Zhang ◽  
Jiaqi Huang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Progression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Escape ◽  
Tumor Treatment

Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

Autoregulation of Shh expression and Shh induction of cell death suggest a mechanism for modulating polarising activity during chick limb development

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4811-4823 ◽  
Author(s):  
J.J. Sanz-Ezquerro ◽  
C. Tickle
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Sonic Hedgehog ◽  
Limb Development ◽  
Retroviral Vector ◽  
Cellular Mechanism ◽  
Limb Bud ◽  
Drug Induced ◽  
Signalling Molecule ◽  
Vertebrate Limb

The polarising region expresses the signalling molecule sonic hedgehog (Shh), and is an embryonic signalling centre essential for outgrowth and patterning of the vertebrate limb. Previous work has suggested that there is a buffering mechanism that regulates polarising activity. Little is known about how the number of Shh-expressing cells is controlled but, paradoxically, the polarising region appears to overlap with the posterior necrotic zone, a region of programmed cell death. We have investigated how Shh expression and cell death respond when levels of polarising activity are altered, and show an autoregulatory effect of Shh on Shh expression and that Shh affects cell death in the posterior necrotic zone. When we increased Shh signalling, by grafting polarising region cells or applying Shh protein beads, this led to a reduction in the endogenous Shh domain and an increase in posterior cell death. In contrast, cells in other necrotic regions of the limb bud, including the interdigital areas, were rescued from death by Shh protein. Application of Shh protein to late limb buds also caused alterations in digit morphogenesis. When we reduced the number of Shh-expressing cells in the polarising region by surgery or drug-induced killing, this led to an expansion of the Shh domain and a decrease in the number of dead cells. Furthermore, direct prevention of cell death using a retroviral vector expressing Bcl2 led to an increase in Shh expression. Finally, we provide evidence that the fate of some of the Shh-expressing cells in the polarising region is to undergo apoptosis and contribute to the posterior necrotic zone during normal limb development. Taken together, these results show that there is a buffering system that regulates the number of Shh-expressing cells and thus polarising activity during limb development. They also suggest that cell death induced by Shh could be the cellular mechanism involved. Such an autoregulatory process based on cell death could represent a general way for regulating patterning signals in embryos.

Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance.

1998 ◽  
Vol 16 (11) ◽  
pp. 3674-3690 ◽  
Author(s):  
D M Bradshaw ◽  
R J Arceci
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Multidrug Resistance ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Efflux Pump ◽  
Active Form ◽  
Cytotoxic Agents ◽  
Transport Systems ◽  
Drug Efflux

For cytotoxic agents to have an effect on tumor cells, drugs must first be transported into the cell, potentially be metabolized to an active form, and interact appropriately with target molecules. A final common pathway of cytotoxic agents is usually the initiation of programmed cell death, or apoptosis. Tumor cells overcome the effects of cytotoxic agents at one or more of these levels. The classic multidrug-resistance (MDR) phenotype, as mediated by the drug efflux pump, P-glycoprotein, is one of the most extensively studied mechanisms of drug resistance. Additional drug transporters, such as the multidrug resistance-associated proteins (MRPs), have also been identified and can convey drug-resistance phenotypes. Important questions remain as to how and whether such transport systems can be specifically measured and effectively targeted to improve therapeutic outcomes. Furthermore, alterations in drug targets, drug metabolism, repair of DNA damage caused by drugs, and the inability to initiate programmed cell death can all contribute to drug resistance and must be ultimately considered in the explanation of tumor-cell resistance to therapy. Continued exploration of the pharmacologic methods to circumvent drug resistance, as well as strategies that involve targeted therapy and immunomodulation, should increase the specificity and efficacy of treatments for patients with cancer.

scholarly journals Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum

2011 ◽  
Vol 2 (10) ◽  
pp. e216-e216 ◽  
Author(s):  
J-H Ch'Ng ◽  
K Liew ◽  
A S-P Goh ◽  
E Sidhartha ◽  
K S-W Tan
Keyword(s):  
Cell Death ◽  
Plasmodium Falciparum ◽  
Programmed Cell Death ◽  
Digestive Vacuole ◽  
Drug Induced

scholarly journals Structural tuning of organoruthenium compounds allows oxidative switch to control ER stress pathways and bypass multidrug resistance

2016 ◽  
Vol 7 (7) ◽  
pp. 4117-4124 ◽  
Author(s):  
Mun Juinn Chow ◽  
Cynthia Licona ◽  
Giorgia Pastorin ◽  
Georg Mellitzer ◽  
Wee Han Ang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Multidrug Resistance ◽  
Programmed Cell Death ◽  
Er Stress ◽  
Resistance Mechanisms ◽  
Differential Activation ◽  
Arene Ligand

Varying the arene ligand on organoruthenium compounds induced the differential activation of ER stress pathways, leading to non-apoptotic programmed cell death and bypassing drug resistance mechanisms.

scholarly journals Investigating Programmed Cell Death and Tumor Invasion in a Three-Dimensional (3D) Microfluidic Model of Glioblastoma

2020 ◽  
Vol 21 (9) ◽  
pp. 3162
Author(s):  
Ehsan Samiei ◽  
Amir Seyfoori ◽  
Brian Toyota ◽  
Saeid Ghavami ◽  
Mohsen Akbari
Keyword(s):  
Cell Death ◽  
Survival Rate ◽  
Programmed Cell Death ◽  
Tumor Invasion ◽  
3D Model ◽  
Apoptotic Cell ◽  
Simultaneous Detection ◽  
Three Dimensional ◽  
Drug Induced ◽  
Induced Apoptosis

Glioblastoma multiforme (GBM) is a rapidly progressive and deadly form of brain tumor with a median survival rate of ~15 months. GBMs are hard to treat and significantly affect the patient’s physical and cognitive abilities and quality of life. Temozolomide (TMZ)—an alkylating agent that causes DNA damage—is the only chemotherapy choice for the treatment of GBM. However, TMZ also induces autophagy and causes tumor cell resistance and thus fails to improve the survival rate among patients. Here, we studied the drug-induced programmed cell death and invasion inhibition capacity of TMZ and a mevalonate cascade inhibitor, simvastatin (Simva), in a three-dimensional (3D) microfluidic model of GBM. We elucidate the role of autophagy in apoptotic cell death by comparing apoptosis in autophagy knockdown cells (Atg7 KD) against their scrambled counterparts. Our results show that the cells were significantly less sensitive to drugs in the 3D model as compared to monolayer culture systems. An immunofluorescence analysis confirmed that apoptosis is the mechanism of cell death in TMZ- and Simva-treated glioma cells. However, the induction of apoptosis in the 3D model is significantly lower than in monolayer cultures. We have also shown that autophagy inhibition (Atg7 KD) did not change TMZ and Simva-induced apoptosis in the 3D microfluidic model. Overall, for the first time in this study we have established the simultaneous detection of drug induced apoptosis and autophagy in a 3D microfluidic model of GBM. Our study presents a potential ex vivo platform for developing novel therapeutic strategies tailored toward disrupting key molecular pathways involved in programmed cell death and tumor invasion in glioblastoma.

scholarly journals Dissecting the Transcriptomes of Multiple Metronidazole-Resistant and Sensitive Trichomonas vaginalis Strains Identified Distinct Genes and Pathways Associated with Drug Resistance and Cell Death

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1817
Author(s):  
Po-Jung Huang ◽  
Ching-Yun Huang ◽  
Yu-Xuan Li ◽  
Yi-Chung Liu ◽  
Lichieh-Julie Chu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Trichomonas Vaginalis ◽  
Regulatory Networks ◽  
Efflux Pump ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Multidrug Efflux Pump ◽  
Drug Induced ◽  
Transmitted Infection

Trichomonas vaginalis is the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. Metronidazole (MTZ) is the mainstay of anti-trichomonal chemotherapy; however, drug resistance has become an increasingly worrying issue. Additionally, the molecular events of MTZ-induced cell death in T. vaginalis remain elusive. To gain insight into the differential expression of genes related to MTZ resistance and cell death, we conducted RNA-sequencing of three paired MTZ-resistant (MTZ-R) and MTZ-sensitive (MTZ-S) T. vaginalis strains treated with or without MTZ. Comparative transcriptomes analysis identified that several putative drug-resistant genes were exclusively upregulated in different MTZ-R strains, such as ATP-binding cassette (ABC) transporters and multidrug resistance pumps. Additionally, several shared upregulated genes among all the MTZ-R transcriptomes were not previously identified in T. vaginalis, such as 5′-nucleotidase surE and Na+-driven multidrug efflux pump, which are a potential stress response protein and a multidrug and toxic compound extrusion (MATE)-like protein, respectively. Functional enrichment analysis revealed that purine and pyrimidine metabolisms were suppressed in MTZ-S parasites upon drug treatment, whereas the endoplasmic reticulum-associated degradation (ERAD) pathway, proteasome, and ubiquitin-mediated proteolysis were strikingly activated, highlighting the novel pathways responsible for drug-induced stress. Our work presents the most detailed analysis of the transcriptional changes and the regulatory networks associated with MTZ resistance and MTZ-induced signaling, providing insights into MTZ resistance and cell death mechanisms in trichomonads.

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