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The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
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Humans , Prognosis , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics , Biological Assay , Cell CycleABSTRACT
Objective To investigate the expression of PRR11 in bladder cancer tissues and its effect on proliferation and apoptosis of bladder cancer cell line T24. Methods The expression of PRR11 was detected using immunohistochemistry method in 57 specimens of bladder urothelial carcinoma and adjacent tissues. The correlations of PRR11 expression with the clinicopathological characteristics of patients with bladder urothelial carcinoma were analyzed. The mRNA and protein expression levels of PRR11 in human immortalized bladder epithelial cell lines SV-HUC-1 and human bladder cancer cell lines HTB-9, T24, J82 and UM-UC-3 were measured by qRT-PCR and Western blot. The gene expression of PRR11 in T24 cells was silenced by lentivirus shRNA. The mRNA expression level of PRR11 was detected by qRT-PCR. CCK-8 was used to detect cell proliferative activity. Cell clonality was detected by plate cloning assays. The rate of apoptosis was evaluated using flow cytometry. The protein expression levels of PRR11, Caspase-3, Bcl-2 and Bax were assessed by Western blot. Results PRR11 was highly expressed in bladder urothelial carcinoma, and its expression level was correlated with the pathological grade and T stage of the tumor. The mRNA and protein expression levels of PRR11 in HTB-9, T24, J82 and UM-UC-3 cells were higher than those in SV-HUC-1 cells (P < 0.05), especially in T24 cells. PRR11 gene silence reduced the expression levels of PRR11 mRNA and protein, as well as the cell proliferation activity and cell clonality, elevated the apoptosis rate, up-regulated the protein expression levels of Cleaved caspase-3 and Bax, and down-regulated the protein expression level of Bcl-2. Conclusion The expression of PRR11 is upregulated in bladder urothelial carcinoma tissues and bladder cancer cell lines. Interfering with PRR11 expression can inhibit the proliferation and promote the apoptosis of bladder cancer T24 cells.
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Renal ischemia-reperfusion injury (IRI) commonly occurs in renal transplantation, which is an important pathophysiological process that causes acute renal failure and severely affects clinical prognosis of the recipients. Inflammatory response plays a critical role in the pathogenesis and pathological process of IRI. Activated NOD-like receptor protein 3(NLRP3) inflammasome can mediate the maturation and release of various pro-inflammatory cytokines, thereby regulating the inflammatory response and relevant cell functions. In this article, the mechanism underlying NLRP3 inflammasome and its related inflammatory signaling pathway in renal IRI were reviewed, aiming to provide novel ideas for clinical prevention and treatment of renal IRI.
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@# Objective: To investigate the expressionof proline-rich protein 11 (PRR11) in esophageal carcinoma (EC) tissues and to study it’s effect on the proliferation and metastasis of human EC TE-2 cells in vitro. Methods: Eighty patients were pathologically diagnosed with EC the Department of Thoracic Surgery of the Second Affiliated Hospital of Zhengzhou University from October 2016 to October 2018, and their surgically resected cancer tissues and corresponding para-cancerous tissues were collected for this study. qPCR was used to detect the expression of PRR11 mRNAin tissues or cells. Log-rank Test was used to analyzethe relationship between the expression of PRR11 in EC tissues and general data, histological type, lymphatic metastasis, depth of invasion and TNM stageof the EC patients. Kaplan-Meierplot was used to analyze the association between PRR11 mRNA and patients’prognosis. TE-2 cells were transfected with lentivirus shRNA to construct cell line with PRR11 knockout and corresponding control cell lines, as shPRR11#1, shPRR11#2 and control group. qPCR and WB assays were used to verify the mRNA and protein expressions of PRR11 in cell lines respectively. MTT was used to examine the proliferation of transfected cells, and Transwell experiments were used to detect cell invasion and migration. Results: The expression of PRR11 mRNA in EC was higher than that in para-cancer tissues (P<0.05). There was significant correlation between PRR11 over-expression and histological type, lymphatic metastasis, depth of invasion and TNM stage(all P <0.05), and high PRR11 expression was significantly related with the poor prognosis of EC patients (P<0.05). The mRNA and protein expressions of PRR11 in cells of shPRR11#1 and shPRR11#2 groups were significantly lower than those in control group (all P <0.05). MTT assay showed that the proliferation of cells in shPRR11#1 and shPRR11#2 groups was significantly lower than that in the control group (P<0.05 or P<0.01). The results of Transwell invasion and migration assays showed that the average number of cells with in each field of viewin shPRR11#1 and shPRR11#2 groups was significantly lower than that in the control group (P<0.01). Conclusion: PRR11 is over-expressed in EC tissues and PRR11 over-expression is closely related to the occurrence, progression and prognosis of esophageal cancer. In vitro experiments have also demonstrated that knockdown of PRR11 can inhibit the proliferation, invasion and migration of EC. PRR11 can be used as a potential molecule marker and drug targets for EC. ··
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OBJECTIVE:To mine the ADR signals of dasatinib and imatinib,and to provide reference for safe use of two drugs in clinic. METHODS:ROR and PRR method of disproportionality measures were used to mine the data in the reports about dasatinib and imatinib of 17 quarters from FDA ADE Reporting System during the fourth quarter of 2012-the fourth quarter of 2016. ADR description terms in reports were standardized with international medical terms dictionary. ADR with signal detected by both methods were screened again. RESULTS & CONCLUSIONS:Totally 505 ADR signals for dasatinib and 929 ADR signals for imatinib had been found by ROR and PRR. After re-screening,there were 351 ADR signals for dasatinib and 649 ADR signals for imatinib,including 153 ADR signals for both dasatinib and imatinib. ADR signals for both dasatinib and imatinib obtained in this study were in agreement with known safety information. ADR mainly occurred in gastrointestinal tract,blood and lymphatics,kidney and urinary system,cardiovascular and musculoskeletal tissue,etc. However,incomplete information in the instructions was also found,such as possible urinary system-related ADR signals caused by dasatinib were detected in this study is not mentioned in drug instruction;imatinib could cause ADR signals of left atrium and right atrium dilation,which were not included in their instructions. Common ADRs,such as headaches,metioned in drug instructions of imatinib,did not appear in the top 50 signal intensities in this study. In addition,the ADR of the two drugs also varied,such as 7 ADR signals as periorbital edema and ocular edoma of forimatinib were much stronger than dasatinib;5 ADR signals of dasatinib,such as pericardial effusion and pleural effusion were much stronger than imatinib,indicating clinical drug selection should be based on individual situation of patients.
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Objective To explore the expression of PRR11(Proline-rich protein 11) in human osteosarcoma and investigate the effect of PRR11 on the proliferation of human osteosarcoma cells.Methods Immunohistochemical staining was applied to detect the PRR11 expression in 75 cases of osteosarcoma and corresponding normal tissues.Western blotting was used to examine PRR11 protein expression levels in osteosarcoma cell lines.We used siRNA to knock down the expression of PRR11 and tested the effects of PRR11 down-regulation on the proliferation in SaOS2 cells.Results PRR11 was overexpressed in osteosarcoma specimens compared to their paired normal tissues,the over expression rate of PRR11 in osteosarcoma and corresponding paracancerous tissues were 76％(57/75) and 9.33％(7/75) with statistical difference(P<0.05).The high expression of PRR11 was correlated with tumor pathological grade and lymphatic metastasis(P<0.05).PRR11 was expressed in 4 osteosarcoma cell lines which were SaOS2,143B,U2OS and MG63 respectively,the expression was highest in SaOS2 cells.Silencing PRR11 inhibited cell growth as compared with control cells(P<0.05).Conclusion PRR11 is overexpression in human osteosarcoma and promotes its progression by enhancing proliferation.The increased expression of PRR11 in osteosarcoma is a new target for treatment and early diagnosis of human osteosarcoma patients.
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Background and purpose: Recent studies have shown that, the new gene PRR11 had abnormal expression in lung cancer, stomach cancer, speculated that it might be correlated with tumor progression. This study aimed to detect the expression of PRR11 protein in human pancreatic carcinoma, and to analyze the relationship between PRR11 protein level and the clinical pathological parameters of pancreatic carcinoma. Methods: Immunohistochemistry (SP) method was used to detect the expression of PRR11 protein in 32 cases of human pancreatic cancer tissues, 20 cases of paracancerous tissues and 6 cases of normal pancreatic tissue. Chi Square test was used to analyze the relationship between the expression levels of PRR11 protein and the clinical pathological parameters (age, gender, the size of tumor, the location of tumor, differentiation, lymph node metastasis and TNM stage). Results:The positive expression rates of PRR11 protein in pancreatic cancers, paracancerous tissues and normal pancreatic tissues were 78.1%(25/32), 5.0%(1/20) and 0.0%(0/6), respectively. The expression level of PRR11 in pancreatic cancer tissues was significantly higher than those in paracan-cerous tissues or normal tissues. The positive expression rate of PRR11 protein in pancreatic carcinoma was significantly associated with cell differentiation degree and TNM stage (P0.05). Survival analysis demonstrated that the survival rate in the patients with PRR11 protein positive expression was significantly lower than the patients with negative expression (P<0.05). Conclusion:PRR11 protein can be a possible prognostic indicator of pancreatic cancer.
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The new practical use example of the JADER datasets from Japanese Adverse Drug Event Report database opened by Independent Administrative Agency Pharmaceuticals and Medical Devices Agency in April, 2012 and afterwards will be reported. The purpose of this study is to examine the evaluating method of medicine concomitant use risk by the frequency at which two or more medicines were reported simultaneously, being assumed the possibility of the influence of drug interactions to be the concomitant use risk in an adverse drug event onset. In order to estimate the potential degree of the safety risk at the time of the concomitant use, the methodology was estimated by the following procedures. 1) For considering that two suspicion medicine targeted is one medicine, the statistical signal index which means those of medicines with use in the case where they both are indicated in one report, the index of the concomitant use, is computed. 2) The statistical signal index about two target suspicion medicines is computed individually. 3) The case where the ratio of the index of the concomitant use to the index obtained individually exceeds 2 also in any of two suspicion medicines is judged as there being the concomitant use risk. The Proportional Reporting Ratio (PRR) and the Reporting Odds Ratio (ROR) were used as a statistical signal index. In order to check the validity of this method, Stevens-Jonson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) which are known for the adverse events of critical drug rash reported in JADER were taken up, and the causality of medical supplies limited to the medicine with which they were reported as a suspicion medicine. As for the combination of the suspicion medicine which fulfills the conditions of the concomitant use risk, 10 kinds of candidates out of 159 combinations for SJS and 22 kinds of candidates out of 111 combinations for TEN were detected, respectively. Although this approach for the concomitant use risk was considered to be an effective means in showing the above results, some issues about the ratio of the index of the concomitant use and criteria in the report numbers of the medicine to be chosen, the effective calculation method for combinations in more than 3 medicines, etc. will be required for the further examination.
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NKR and TLR are most important receptor superfamilies in innate immunity and act as first line of host defense against infection. Those receptors exert peculiar recognition mechanisms to sense danger signals and distinguish infectious nonself from noninfectious self. More importantly, they coordinate and regulate each other and therefore play major roles in initiation of innate immunity and also help to direct adaptive immune responses. The importance of recognition and interaction of those receptors are highlighted. The precise mechanisms can be harnessed to aid the rational design of therapy against infection, inflammation, cancer or autoimmune diseases.
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How the hosts recognize and clear invading viruses is one of the key issues in molecular immunology. Previous studies uncovered that many early antiviral proteins, such as Type Ⅰ interferons and PKR, are strongly induced upon virus infection. These proteins not only limit virus replication and spread or cause infected cells to undergo apoptosis, but also induce consequently expression of cytokines and chemokines to initiate acquired immunity. However, the immediate-early signaling events among host and virus interaction were largely unknown. In the past few years, there are great breakthroughs in this rapidly evolving field. TLR3 and RIG-I/MDA5 signaling pathways were shown to play a crucial regulatory role in antiviral processes. These pathways are essential for the vertebrate immune system to recognize and clear RNA virus with different strategies, which are integral parts of innate immune response and directly affect later-stage acquired immunity. The recent know-how on TLR3 and RIG-I/MDA5 signal transduction pathways and their roles in antiviral immunity were summarized.