scholarly journals Membrane expression and significance of TRAIL death receptors DR4 and DR5 in Pancreatic cancer

2020 ◽  
Vol 7 (3) ◽  
pp. 54-61
Author(s):  
Dipesh Kumar Yadav ◽  
Ze Sheng Wang ◽  
Yong Fei Hua ◽  
Cai De Lu
Keyword(s):  
Pancreatic Cancer ◽  
Expression Profiles ◽  
Tumor Staging ◽  
Death Receptor ◽  
Receptor Expression ◽  
Stage I ◽  
Membrane Expression ◽  
The Difference ◽  
Well Differentiated ◽  
Trail Death Receptor

Introduction: Tumor necrosis factor related-apoptosis-inducing ligand (TRAIL) is a powerful and selective activator of apoptosis in many cancer cells. We aim to investigate the expression and significance of TRAIL death receptor DR4 and DR5 in pancreatic cancer (PC) tissues. Method: Twenty-eight histologically verified samples of PC tissue were collected between 2018 and 2019. TRAIL death receptor expression profiles were determined by immunohistochemistry. Result: Death receptor DR4 and DR5 were expressed in the PC tissue and the adjacent non-cancerous pancreatic tissues, the expression of DR4 and DR5 in the PC tissue was significantly higher than that of the adjacent non-cancerous pancreatic tissues (p<0.05). Additionally, in both the tissue group, the expression of DR4 was significantly stronger than the DR5 (p<0.05). To assess the relationship between DR4 and DR5 expression, differentiation, and tumor staging of PC, the result reveals that the expression of DR4 and DR5 was significantly higher in stage I tumors than the stage II, III, IV tumors (p<0.05). In contrast, the expression of DR4 and DR5 was decreased with a decrease in the degree of differentiation of tumors. However, the difference was not statistically significant. Conclusion: The membrane expression of TRAIL death receptor DR4 and DR5 is greater in PC than in the adjacent non-cancerous pancreatic tissues. Furthermore, increased membrane expression of TRAIL death receptor DR4 and DR5 in stage I PC and well-differentiated PC may predict the prognosis and feasibility of using TRAIL gene therapy as a treatment option for early PC.

scholarly journals Cohort study of the overall survival of patients with pancreatic cancer in a hospital of specialties of Quito-Ecuador in the period 2007–2017

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Survival Time ◽  
Univariate Analysis ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Icd 10 ◽  
The Difference ◽  
Clinical Records

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.

scholarly journals A highly expressed mRNA signature for predicting survival in patients with stage I/II non-small-cell lung cancer after operation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nan Ma ◽  
Lu Si ◽  
Meiling Yang ◽  
Meihua Li ◽  
Zhiyi He
Keyword(s):  
High Risk ◽  
Roc Curve ◽  
Expression Profiles ◽  
Low Risk ◽  
Stage I ◽  
Risk Scores ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Nsclc Patients ◽  
Rna Signature

AbstractThere is an urgent need to identify novel biomarkers that predict the prognosis of patients with NSCLC. In this study,we aim to find out mRNA signature closely related to the prognosis of NSCLC by new algorithm of bioinformatics. Identification of highly expressed mRNA in stage I/II patients with NSCLC was performed with the “Limma” package of R software. Survival analysis of patients with different mRNA expression levels was subsequently calculated by Cox regression analysis, and a multi-RNA signature was obtained by using the training set. Kaplan–Meier estimator, log-rank test and receiver operating characteristic (ROC) curves were used to analyse the predictive ability of the multi-RNA signature. RT-PCR used to verify the expression of the multi-RNA signature, and Westernblot used to verify the expression of proteins related to the multi-RNA signature. We identified fifteen survival-related mRNAs in the training set and classified the patients as high risk or low risk. NSCLC patients with low risk scores had longer disease-free survival than patients with high risk scores. The fifteen-mRNA signature was an independent prognostic factor, as shown by the ROC curve. ROC curve also showed that the combined model of the fifteen-mRNA signature and tumour stage had higher precision than stage alone. The expression of fifteen mRNAs and related proteins were higher in stage II NSCLC than in stage I NSCLC. Multi-gene expression profiles provide a moderate prognostic tool for NSCLC patients with stage I/II disease.

Dexamethasone induces pancreatic β-cell apoptosis through upregulation of TRAIL death receptor

2021 ◽  
Author(s):  
Kanchana Suksri ◽  
Namoiy Semprasert ◽  
Mutita Junking ◽  
Suchanoot Kutpruek ◽  
Thawornchai Limjindaporn ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Death Receptor ◽  
Caspase 8 ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Apoptotic Protein ◽  
Induced Apoptosis ◽  
Trail Death Receptor

Long-term medication with dexamethasone (a synthetic glucocorticoid (GC) drug) results in hyperglycemia, or steroid-induced diabetes. Although recent studies revealed dexamethasone directly induces pancreatic β-cell apoptosis, its molecular mechanisms remain unclear. In our initial analysis of mRNA transcripts, we discovered the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway may be involved in dexamethasone-induced pancreatic β-cell apoptosis. In the present study, a mechanism of dexamethasone-induced pancreatic β-cell apoptosis through the TRAIL pathway was investigated in cultured cells and isolated mouse islets. INS-1 cells were cultured with and without dexamethasone in the presence or absence of a glucocorticoid receptor (GR) inhibitor, RU486. We found that dexamethasone induced pancreatic β-cell apoptosis in association with the upregulation of TRAIL mRNA and protein expression. Moreover, dexamethasone upregulated the TRAIL death receptor (DR5) protein but suppressed the decoy receptor (DcR1) protein. Similar findings were observed in mouse isolated islets: dexamethasone increased TRAIL and DR5 compared to that of control mice. Furthermore, dexamethasone stimulated pro-apoptotic signaling including superoxide production, caspase-8, -9, and -3 activities, NF-B, and Bax, but repressed the anti-apoptotic protein, Bcl-2. All these effects were inhibited by the GR-inhibitor, RU486. Furthermore, knock down DR5 decreased dexamethasone-induced caspase 3 activity. Caspase-8 and caspase-9 inhibitors protected pancreatic β-cells from dexamethasone-induced apoptosis. Taken together, dexamethasone induced pancreatic β-cell apoptosis by binding to the GR and inducing DR5 and TRAIL pathway.

PSIV-6 Differential gene expression of fibro/adipogenic progenitors between Wagyu and Brahman cattle: A possible contribution to their different meat quality

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 301-301
Author(s):  
Chaoyang Li ◽  
Qianglin Liu ◽  
Matt Welborn ◽  
Leshan Wang ◽  
Yuxia Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Meat Quality ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cattle Breed ◽  
Intramuscular Fat ◽  
Brahman Cattle ◽  
Differential Gene ◽  
The Difference

Abstract The amount of intramuscular fat directly influences the meat quality. However, significant differences in the ability to accumulate intramuscular fat are present among different beef cattle breeds. While Wagyu, a cattle breed that originated from Japan, is renowned for abundant intramuscular fat, Brahman cattle generally have very little intramuscular fat accumulation and produce tougher meat. We identified that bovine intramuscular fat is derived from a group of bipotent progenitor cells named fibro/adipogenic progenitors (FAPs) which also give rise to fibroblasts. Thus, the variation in intramuscular fat development between Wagyu and Brahman is likely attributed to the difference in FAPs between these two breeds. In order to understand the gene expression difference between FAPs of the two breeds, single-cell RNA-seq was performed using total single-nucleated cells isolated from the longissimus muscle of young purebred Wagyu, purebred Brahman, and Wagyu-Brahman cross cattle. FAPs constitute the largest single-nucleated cell population in both Wagyu and Brahman skeletal muscle. Multiple subpopulations of FAPs with different gene expression profiles were identified, suggesting that FAP is a heterogeneous population. A unique FAP cluster expressing lower levels of fibrillar collagen and extracellular remodeling enzyme genes but higher levels of select proadipogenic genes was identified exclusively in Wagyu skeletal muscle, which likely contributes to the robust intramuscular adipogenic efficiency of Wagyu FAPs. In conclusion, the difference in the cellular composition and gene expression of FAPs between Wagyu and Brahman cattle likely contribute to their distinct meat quality.

scholarly journals Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression

2018 ◽  
Vol 19 (10) ◽  
pp. 3187 ◽  
Author(s):  
Eun Lim ◽  
Yu Yoon ◽  
Jeonghoon Heo ◽  
Tae Lee ◽  
Young-Ho Kim
Keyword(s):  
Lung Cancer ◽  
Protein Stability ◽  
Cancer Cells ◽  
Death Receptor ◽  
Proteolytic Processing ◽  
Receptor Expression ◽  
Host Cells ◽  
Lung Cancer Cells ◽  
Regulation Of Transcription ◽  
Induced Apoptosis

Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.

Expression profiles for 14-3-3 zeta and CCL20 in pancreatic cancer and chronic pancreatitis

2014 ◽  
Vol 210 (6) ◽  
pp. 335-341 ◽  
Author(s):  
Christoph Klemm ◽  
Henrik Dommisch ◽  
Friederike Göke ◽  
Matthias Kreppel ◽  
Søren Jepsen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Expression Profiles

scholarly journals Expression Profiling of Nuclear Receptors in the NCI60 Cancer Cell Panel Reveals Receptor-Drug and Receptor-Gene Interactions

2010 ◽  
Vol 24 (6) ◽  
pp. 1287-1296 ◽  
Author(s):  
Susan Holbeck ◽  
Jianjun Chang ◽  
Anne M. Best ◽  
Angie L. Bookout ◽  
David J. Mangelsdorf ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cell Lines ◽  
Nuclear Receptors ◽  
Cancer Cell ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Cancer Drug ◽  
Mrna Levels

Abstract We profiled the expression of the 48 human nuclear receptors (NRs) by quantitative RT-PCR in 51 human cancer cell lines of the NCI60 collection derived from nine different tissues. NR mRNA expression accurately classified melanoma, colon, and renal cancers, whereas lung, breast, prostate, central nervous system, and leukemia cell lines exhibited heterogeneous receptor expression. Importantly, receptor mRNA levels faithfully predicted the growth-inhibitory qualities of receptor ligands in nonendocrine tumors. Correlation analysis using NR expression profiles and drug response information across the cell line panel uncovered a number of new potential receptor-drug interactions, suggesting that in these cases, individual receptor levels may predict response to chemotherapeutic interventions. Similarly, by cross-comparing receptor levels within our expression dataset and relating these profiles to existing microarray gene expression data, we defined interactions among receptors and between receptors and other genes that can now be mechanistically queried. This work supports the strategy of using NR expression profiling to classify various types of cancer, define NR-drug interactions and receptor-gene networks, predict cancer-drug sensitivity, and identify druggable targets that may be pharmacologically manipulated for potential therapeutic intervention.

The mechanism of work-hardening and slip-band formation

1957 ◽  
Vol 242 (1229) ◽  
pp. 147-159 ◽  
Keyword(s):  
Single Crystals ◽  
Slip Band ◽  
Work Hardening ◽  
Stage I ◽  
Polycrystalline Materials ◽  
Temperature Dependent ◽  
Band Formation ◽  
Slip Bands ◽  
Three Stages ◽  
The Difference

A summary is given of some present ideas on the mechanism of work-hardening of single crystals and polycrystalline materials. In particular, the difference is stressed between the three stages of hardening: stage I, or easy glide; stage II, the region of rapid hardening accompanied by short slip lines; and stage III, the region of slow or parabolic hardening which is temperature-dependent and in which long slip bands are formed.

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