ABSTRACT
PURPOSE: The long noncoding RNA LINC00261 was reported to be involved in carcinogenesis and has been validated as a tumor suppressor in pancreatic cancer (PC); however, how LINC00261 is regulated has not been fully examined. Here, we attempted to investigate the upstream and downstream targets of LINC00261 in PC. METHODS: LINC00261 expression in PC tissues was examined by the Gene Expression Omnibus (GEO) datasets and the Gene Expression Profiling Interactive Analysis (GEPIA) database. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were performed to detect the expression level of LINC00261 in PC cells. The location of LINC00261 in PC cells was identified by RNA fluorescence in situ hybridization (RNA-FISH). Cell Counting Kit-8 (CCK-8), cell apoptosis assay, transwell invasion and migration assays testified the critical role of LINC00261 in PC. The luciferase reporter assay was applied to confirm the binding of LINC00261 to its upstream transcription factor KLF13. The changes in LINC00261 related target protein levels were analyzed by Western blotting assay. RESULTS: LINC00261 was significantly lower in PC tissues and was mainly concentrated in the nucleus. Overexpression of LINC00261 inhibited the invasion and migration of PC cells. Mechanistically, transcription factor KLF13 was confirmed to inhibit the epithelial-mesenchymal transition (EMT) process of PC cells by promoting the transcription of LINC00261 and suppressing the expression of metastasis-associated proteins, such as matrix metalloproteinase MMP2 and vimentin, thus inhibiting the metastasis of PC. CONCLUSION: LINC00261 regulates PC cell metastasis through the "KLF13-LINC00261-mTOR-P70S6K1-S6" signaling pathway, which provides a significant set of potential PC therapeutic targets.
Subject(s)
Kruppel-Like Transcription Factors , MicroRNAs , Pancreatic Neoplasms , RNA, Long Noncoding , Cell Cycle Proteins , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition , Humans , In Situ Hybridization, Fluorescence , Kruppel-Like Transcription Factors/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Repressor Proteins , Signal Transduction , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Up-Regulation , Pancreatic NeoplasmsABSTRACT
We conducted this case-control study to assess the role of the VEGF -2578C/A, +1612G/A, +936C/T and -634G/C gene polymorphisms in the development of renal cell carcinoma (RCC). A hospital-based case-control study was conducted in a 360 consecutive primary RCC patients and 360 age and gender-matched controls during January 2010 and January 2014. The polymerase chain reaction-restriction fragment length polymorphism was used for VEGF -2578C/A, +1612G/A, +936C/T and -634G/C genotyping. Multivariate conditional logistic regression analyses showed that subjects carrying the AA and the CA+AA genotypes of VEGF -2578C/A had significant association with increased risk of RCC compared to those having the CC genotype, and the ORs (95%CI) were 1.77 (1.10-2.85) and 1.37 (1.01-1.86), respectively. Using the conditional logistic regression model, CA+AA genotype of VEGF -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals with hypertension, and the ORs (95%CI) were 1.93 (1.08-3.45) and 2.57 (1.06-6.57), respectively. In conclusion, our results showed that AA genotype of VEGF -2578C/A genetic variants is associated with increased risk of RCC.
Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Vascular Endothelial Growth Factor A/genetics , Adult , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , RiskABSTRACT
The aim of this study was to evaluate the immune memory response 13-18 years after an hepatitis B virus (HBV) vaccine by performing a specific in vitro stimulation experiment. Thirty healthy volunteers who had been inoculated 13-18 years ago with the HBV vaccine were collected from the physical examination center. Peripheral blood mononuclear cells were stimulated with 50 ng/mL recombinant HBsAg. An ELISA kit was used for the detection of antibodies that were produced by these cells in vitro. It was found that even 13-18 years after inoculation with the HBV vaccine, an anamnestic antibody response still existed, and was not correlated with the serum antibody levels (r = -0.177, P = 0.377). In conclusion, our data showed that the individuals after inoculation, including those with anti-HBs <10 IU/L as well as those individuals in whom the antibody was not detected, retained immune memory, which may be the main role of memory B cells.
Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/immunology , Immunologic Memory/immunology , B-Lymphocytes/immunology , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B Vaccines/administration & dosage , HumansABSTRACT
Male circumcision is the most frequently performed procedure by urologists. Safety and efficacy of the circumcision procedure requires continual improvement. In the present study, we investigated the safety and efficacy of a new male circumcision technique involving the use of a circular stapler. In total, 879 consecutive adult male patients were randomly divided into 2 groups: 441 underwent stapler circumcision, and 438 underwent conventional circumcision. The operative time, pain score, blood loss volume, healing time, treatment costs, and postoperative complications were compared between the two groups. The operative time and blood loss volume were significantly lower in the stapler group than in the conventional group (6.8 ± 3.1 vs 24.2 ± 3.2 min and 1.8 ± 1.8 vs 9.4 ± 1.5 mL, respectively; P<0.01 for both). The intraoperative and postoperative pain scores were significantly lower in the stapler group than in the conventional group (0.8 ± 0.5 vs 2.4 ± 0.8 and 4.0 ±0.9 vs 5.8 ± 1.0, respectively; P<0.01 for both). Additionally, the stapler group had significantly fewer complications than the conventional group (2.7% vs 7.8%, respectively; P<0.01). However, the treatment costs in the stapler group were much higher than those in the conventional group (US$356.60 ± 8.20 vs US$126.50 ± 7.00, respectively; P<0.01). Most patients (388/441, 88.0%) who underwent stapler circumcision required removal of residual staple nails. Overall, the present study has shown that stapler circumcision is a time-efficient and safe male circumcision technique, although it requires further improvement.
Subject(s)
Adolescent , Adult , Aged , Humans , Male , Middle Aged , Young Adult , Circumcision, Male/instrumentation , Circumcision, Male/methods , Surgical Staplers , Circumcision, Male/adverse effects , Equipment Design , Follow-Up Studies , Medical Illustration , Operative Time , Patient Satisfaction , Postoperative Complications , Prospective Studies , Statistics, Nonparametric , Treatment Outcome , Wound HealingABSTRACT
Male circumcision is the most frequently performed procedure by urologists. Safety and efficacy of the circumcision procedure requires continual improvement. In the present study, we investigated the safety and efficacy of a new male circumcision technique involving the use of a circular stapler. In total, 879 consecutive adult male patients were randomly divided into 2 groups: 441 underwent stapler circumcision, and 438 underwent conventional circumcision. The operative time, pain score, blood loss volume, healing time, treatment costs, and postoperative complications were compared between the two groups. The operative time and blood loss volume were significantly lower in the stapler group than in the conventional group (6.8 ± 3.1 vs 24.2 ± 3.2 min and 1.8 ± 1.8 vs 9.4 ± 1.5 mL, respectively; P<0.01 for both). The intraoperative and postoperative pain scores were significantly lower in the stapler group than in the conventional group (0.8 ± 0.5 vs 2.4 ± 0.8 and 4.0 ±0.9 vs 5.8 ± 1.0, respectively; P<0.01 for both). Additionally, the stapler group had significantly fewer complications than the conventional group (2.7% vs 7.8%, respectively; P<0.01). However, the treatment costs in the stapler group were much higher than those in the conventional group (US$356.60 ± 8.20 vs US$126.50 ± 7.00, respectively; P<0.01). Most patients (388/441, 88.0%) who underwent stapler circumcision required removal of residual staple nails. Overall, the present study has shown that stapler circumcision is a time-efficient and safe male circumcision technique, although it requires further improvement.
Subject(s)
Circumcision, Male/instrumentation , Circumcision, Male/methods , Surgical Staplers , Adolescent , Adult , Aged , Circumcision, Male/adverse effects , Equipment Design , Follow-Up Studies , Humans , Male , Medical Illustration , Middle Aged , Operative Time , Patient Satisfaction , Postoperative Complications , Prospective Studies , Statistics, Nonparametric , Treatment Outcome , Wound Healing , Young AdultABSTRACT
The human breast cancer-associated gene (BCA3) was first discovered in breast and prostate cancer cells lines. In vivo studies have shown that BCA3 is mainly expressed in breast tumor cells and not in normal breast and prostate tissues. To date, 3 splice variants of BCA3 have been reported: a double-absent variant lacking exon 3 and exon 5 (BCA3-1), an exon 3-absent variant (BCA3-2), and full-length BCA3. In this study, we investigated whether a novel BCA3 splice variant exists that lacks only the exon 5-encoding sequence. BCA3 variant splices were subcloned and sequenced using reverse transcription-polymerase chain reaction. The preliminary biological functions of the splices were identified using confocal microscopy and a luciferase assay. The absence of exon 3 and exon 5 influenced the subcellular localization of BCA3 and nuclear factor kappa B (NF-kB)-dependent gene expression. Exon 3 and exon 5 of BCA3 may function together to provide a nuclear localization signal or transport sequence to enter the nucleus, and exon 3 may contain specific sequence(s) or domain(s) that influence the NF-κB signal cascade. The discovery of novel BCA3 splicing indicates a new cancer research area, which may increase the understanding of cancer generation and development.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Nuclear Proteins/metabolism , RNA Splicing , Adaptor Proteins, Signal Transducing/genetics , Cell Line , Cloning, Molecular , Cyclic AMP-Dependent Protein Kinases/metabolism , Exons , Humans , NF-kappa B/metabolism , Nuclear Proteins/genetics , PhosphorylationABSTRACT
Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues that form the pancreas. To investigate whether the tribbles homolog 1 (Drosophila) gene (TRIB1) is associated with pancreatic cancer in the Chinese Han population, we conducted this case-control study and genotyped 3 single nucleotide polymorphisms (rs2980879, rs2980874, and rs2235108) of the TRIB1 gene in 182 patients and 359 normal controls of Chinese Han origin and analyzed their association. The results showed that the rs2980879 polymorphism was associated with pancreatic cancer [allele: P = 0.023434, genotype: P = 0.03005; odds ratio (OR) and 95% confidence interval (CI) = 0.727788 (0.552664-0.958404)], whereas the rs2980874 polymorphism had no association with pancreatic cancer [allele: P = 0.749885, genotype: P = 0.699533; OR and 95%CI = 1.041981 (0.809196-1.341734)], and the rs2235108 polymorphism was not associated with the disease [allele: P = 0.629475, genotype: P = 0.547534, OR and 95%CI = 1.128290 (0.690829-1.842770)]. Haplotype analyses and linkage disequilibrium tests were also conducted, and the results showed that these 3 loci are not in the same block. In conclusion, our study indicated that the TRIB1 gene is associated with pancreatic cancer. More studies with larger samples are needed in order to support this finding.
Subject(s)
Genetic Association Studies , Intracellular Signaling Peptides and Proteins/genetics , Pancreatic Neoplasms/genetics , Polymorphism, Single Nucleotide , Protein Serine-Threonine Kinases/antagonists & inhibitors , Aged , Alleles , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Linkage Disequilibrium , Male , Middle Aged , Odds Ratio , Protein Serine-Threonine Kinases/geneticsABSTRACT
Here, 248 endophytic bacterial strains were isolated to assess the distribution and population diversity of endophytic bacteria in ginger plants. A total of 10.4 x 10(4) to 20.2 x 10(4) CFU/g fresh weight endophytic bacteria of different growth stages were isolated. Maximum bacterium numbers were obtained at the seedling stage. A total of 107 functional strains were screened, including 17 antibacterial strains and 90 indole acetic acid-producing strains. Based on 16S rDNA sequence restriction fragment length polymorphism and 16S rDNA sequences, these 107 strains were mapped and grouped into 16 genera. Bacillus and Pseudomonas were the dominant genera; however, the bacteria belonged to a tremendous range of genera, with the highest species richness being observed at the seedling stage. Sixteen strains exhibited antimicrobial activity against Pythium myriotylum Drechsler, while 7 strains exhibited antimicrobial activity against Phyllosticta zingiberi Hori. Bacillus was the dominant antibacterial strain. Pseudomonas fluorescens, B. megaterium, and Enterobacter ludwigii produced remarkably high levels of IAA. Only a few endophytic bacterial strains were inhibited in fresh ginger juice. Most of these strains were present during seedling stage, including Roseateles depolymerans, Chryseobacterium taiwanense, E. ludwigii, Agrobacterium larrymoorei, P. fluorescens, and Bacillus amyloliquefaciens. This study indicates that the community of endophytic bacteria in ginger changes with the synthesis of antibacterial substances.
Subject(s)
Bacteria/genetics , DNA, Bacterial/genetics , Endophytes/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , Antibiosis , Antimicrobial Cationic Peptides/biosynthesis , Antimicrobial Cationic Peptides/isolation & purification , Antimicrobial Cationic Peptides/pharmacology , Bacteria/classification , Bacteria/isolation & purification , Colony Count, Microbial , Endophytes/classification , Endophytes/isolation & purification , Fungi/drug effects , Fungi/growth & development , Fungi/pathogenicity , Zingiber officinale/microbiology , Microbial Consortia , Pythium/drug effects , Pythium/growth & development , Pythium/pathogenicity , Seedlings/microbiologyABSTRACT
We aimed to assess parameters reflecting left ventricular function by dual-source computed tomography (DSCT) with echocardiography (ECG) as control. Fifty-eight patients with coronary heart disease (CHD) were recruited from January to June 2011; 29 CHD patients had type II diabetes. All patients were assessed by cardiac DSCT and ECG examination. DSCT and ECG correlated well for ejection fraction (EF) (r = 0.70), end-systolic volume (ESV) (r = 0.87), stroke volume (SV) (r = 0.83), and end-diastolic volume (EDV) (r = 0.90). The mean ESV and EDV values measured by the two methods in CHD patients with type II diabetes were higher than those in non-diabetic patients, whereas the mean EF was lower. DSCT is an accurate and practical method for assessing left ventricular function.
Subject(s)
Coronary Disease/diagnostic imaging , Heart Ventricles/diagnostic imaging , Tomography, X-Ray Computed , Ventricular Function, Left , Adult , Aged , Aged, 80 and over , Coronary Disease/complications , Coronary Disease/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnostic imaging , Diabetes Mellitus, Type 2/pathology , Echocardiography , Female , Heart Ventricles/pathology , Humans , Male , Middle AgedABSTRACT
Type 1 diabetes is a chronic progressive autoimmune disease characterized by mononuclear cell infiltration, with subsequent destruction of insulin-producing ß-cells. Studies have identified strong associations between type 1 diabetes and several chromosome regions, including 12q24. Association between type 1 diabetes and 12q24 arises from SNP rs3184504; rs3184504 is a nonsynonymous SNP in exon 3 of SH2B3 (also known as LNK). Nonobese diabetic (NOD) mice recapitulate many aspects of the pathogenesis of type 1 diabetes in humans and are therefore frequently used in studies addressing the cellular and molecular mechanisms of this disease. It is of interest to know whether there is a similar mutation of SH2B3 in NOD mice. We found that the SH2B3 mutation is absent in NOD mice. To our knowledge, this is the first report of the sequence and the protein levels of SH2B3 in NOD mice.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Intracellular Signaling Peptides and Proteins/genetics , Mutation , Adaptor Proteins, Signal Transducing , Animals , Base Sequence , DNA Primers , Female , Membrane Proteins , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , Obesity , Polymorphism, Single NucleotideABSTRACT
Transitional cell carcinoma (TCC) of the urothelium is often multifocal and subsequent tumors may occur anywhere in the urinary tract after the treatment of a primary carcinoma. Patients initially presenting a bladder cancer are at significant risk of developing metachronous tumors in the upper urinary tract (UUT). We evaluated the prognostic factors of primary invasive bladder cancer that may predict a metachronous UUT TCC after radical cystectomy. The records of 476 patients who underwent radical cystectomy for primary invasive bladder TCC from 1989 to 2001 were reviewed retrospectively. The prognostic factors of UUT TCC were determined by multivariate analysis using the COX proportional hazards regression model. Kaplan-Meier analysis was also used to assess the variable incidence of UUT TCC according to different risk factors. Twenty-two patients (4.6%). developed metachronous UUT TCC. Multiplicity, prostatic urethral involvement by the bladder cancer and the associated carcinoma in situ (CIS) were significant and independent factors affecting the occurrence of metachronous UUT TCC (P = 0.0425, 0.0082, and 0.0006, respectively). These results were supported, to some extent, by analysis of the UUT TCC disease-free rate by the Kaplan-Meier method, whereby patients with prostatic urethral involvement or with associated CIS demonstrated a significantly lower metachronous UUT TCC disease-free rate than patients without prostatic urethral involvement or without associated CIS (log-rank test, P = 0.0116 and 0.0075, respectively). Multiple tumors, prostatic urethral involvement and associated CIS were risk factors for metachronous UUT TCC, a conclusion that may be useful for designing follow-up strategies for primary invasive bladder cancer after radical cystectomy.
Subject(s)
Carcinoma, Transitional Cell/pathology , Neoplasms, Second Primary/pathology , Urinary Bladder Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/surgery , Cystectomy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Urinary Bladder Neoplasms/surgeryABSTRACT
Transitional cell carcinoma (TCC) of the urothelium is often multifocal and subsequent tumors may occur anywhere in the urinary tract after the treatment of a primary carcinoma. Patients initially presenting a bladder cancer are at significant risk of developing metachronous tumors in the upper urinary tract (UUT). We evaluated the prognostic factors of primary invasive bladder cancer that may predict a metachronous UUT TCC after radical cystectomy. The records of 476 patients who underwent radical cystectomy for primary invasive bladder TCC from 1989 to 2001 were reviewed retrospectively. The prognostic factors of UUT TCC were determined by multivariate analysis using the COX proportional hazards regression model. Kaplan-Meier analysis was also used to assess the variable incidence of UUT TCC according to different risk factors. Twenty-two patients (4.6 percent). developed metachronous UUT TCC. Multiplicity, prostatic urethral involvement by the bladder cancer and the associated carcinoma in situ (CIS) were significant and independent factors affecting the occurrence of metachronous UUT TCC (P = 0.0425, 0.0082, and 0.0006, respectively). These results were supported, to some extent, by analysis of the UUT TCC disease-free rate by the Kaplan-Meier method, whereby patients with prostatic urethral involvement or with associated CIS demonstrated a significantly lower metachronous UUT TCC disease-free rate than patients without prostatic urethral involvement or without associated CIS (log-rank test, P = 0.0116 and 0.0075, respectively). Multiple tumors, prostatic urethral involvement and associated CIS were risk factors for metachronous UUT TCC, a conclusion that may be useful for designing follow-up strategies for primary invasive bladder cancer after radical cystectomy.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Transitional Cell/pathology , Neoplasms, Second Primary/pathology , Urinary Bladder Neoplasms/pathology , Cystectomy , Carcinoma, Transitional Cell/surgery , Follow-Up Studies , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Urinary Bladder Neoplasms/surgeryABSTRACT
INTRODUCTION: Anecdotal observations about prehospital emergency medical care in major natural and human-made disasters, such as earthquakes, have suggested that some injured victims survive the initial impact, but eventually die because of a delay in the application of life-saving medical therapy. METHODS: A multidisciplinary, retrospective structured interview methodology to investigate injury risk factors, and causes and circumstances of prehospital death after major disasters was developed. In this study, a team of United States researchers and Costa Rican health officials conducted a survey of lay survivors and health care professionals who participated in the emergency medical response to the earthquake in Costa Rica on 22 April 1991. RESULTS: Fifty-four deaths occurred prior to hospitalization (crude death rate = 0.4/1,000 population). Seventeen percent of these deaths (9/54) were of casualties who survived the initial impact but died at the scene or during transport. Twenty-two percent (2/9) were judged preventable if earlier emergency medical care had been available. Most injuries and deaths occurred in victims who were inside wooden buildings (p < .01) as opposed to other building types or were pinned by rubble from building collapse. Autopsies performed on a sample of victims showed crush injury to be the predominant cause of death. CONCLUSIONS: A substantial proportion of earthquake mortality in Costa Rica was protracted. Crush injury was the principal mechanism of injury and cause of death. The rapid institution of enhanced prehospital emergency medical services may be associated with a significant life-saving potential in these events.
Subject(s)
Disaster Planning/organization & administration , Disasters , Emergency Medical Services/organization & administration , Wounds and Injuries/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cause of Death , Child , Child, Preschool , Costa Rica/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Survival Analysis , Time Factors , Wounds and Injuries/etiology , Wounds and Injuries/therapyABSTRACT
INTRODUCTION: The 1991 earthquake in the Limón area of Costa Rica presented the opportunity to examine the effectiveness of a decade of disaster preparedness. HYPOTHESIS: Costa Rica's concentrated work in disaster preparedness would result in significantly better management of the disaster response than was evident in earlier disasters in Guatemala and Nicaragua, where disaster preparedness largely was absent. METHODS: Structured interviews with disaster responders in and outside of government, and with victims and victims' neighbors. Clinical and epidemiologic data were collected through provider agencies and the coroner's office. RESULTS: Medical aspects of the disaster response were effective and well-managed through a network of clinic-based radio communications. Nonmedical aspects showed confusion resulting from: 1) poor government understanding of the roles and responsibilities of the central disaster coordinating agency; and 2) poor extension of disaster preparedness activities to the rural area that was affected by the earthquake. CONCLUSION: To be effective, disaster preparedness activities need to include all levels of government and rural, as well as urban, populations.