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1.
Clin Trials ; : 1740774520931039, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522027

RESUMO

For utilizing electronic health records to help design and conduct clinical trials, an essential first step is to select eligible patients from electronic health records, that is, electronic health record phenotyping. We present two novel statistical methods that can be used in the context of electronic health record phenotyping. One mitigates the requirement for gold-standard control patients in developing phenotyping algorithms, and the other effectively corrects for bias in downstream analysis introduced by study samples contaminated by ineligible subjects.

2.
Urol Oncol ; 38(7): 641.e19-641.e29, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32389428

RESUMO

BACKGROUND: Accurate preoperative prediction of inguinal lymph node metastasis (LNM) aids in clinical decision making, especially for patients with penile cancer with clinically negative lymph nodes. We aim to develop a nomogram to predict the preoperative risk of LNM by incorporating clinicopathologic features and tumor biomarkers. METHODS: Eighty-four patients with penile cancer with clinically negative lymph nodes were enrolled. The programmed death ligand 1 (PD-L1) expression profile was detected by immunohistochemistry. The neutrophil-to-lymphocyte ratio (NLR) was calculated based on parameters of a routine blood examination. Multivariate logistic regression analysis was utilized to construct predictive nomograms for LNM based on data of 64 patients. The nomogram performance was assessed for calibration, discrimination, and clinical use. RESULTS: Tumor grade, lymphovascular invasion, PD-L1, and NLR were independent predictors of LNM. Then, 4 prediction models were constructed. Clinical model included tumor grade and lymphovascular invasion. NLR model was built by adding the NLR to clinical model. PD-L1 model was built by adding the PD-L1 to clinical model. Finally, a combined model was built by adding both PD-L1 and NLR to clinical model. Combined model showed the best performance compared with other models. It showed good discrimination with a C-index of 0.89, and good calibration. In addition, decision curve analysis suggested that model 4 was clinically useful. CONCLUSIONS: We developed a nomogram that incorporated tumor grade, lymphovascular invasion, PD-L1, and NLR that could be conveniently used to predict the preoperative individualized risk of inguinal LNM in patients with penile cancer.

3.
Mol Cell Biochem ; 470(1-2): 145-155, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32440841

RESUMO

Randall's plaque (RP) serves as a nidus on which idiopathic calcium oxalate stones form. Renal interstitial mineralization may be the cause underlying RP, and recent studies demonstrated the similarities between the interstitial mineralization and ectopic calcification. The present study aimed to investigate whether human renal interstitial fibroblasts (hRIFs) could form calcification under osteogenic conditions, and whether long non-coding RNA H19 participated in regulating osteogenic differentiation of hRIFs through Wnt-ß-catenin pathway. HRIFs were isolated and induced for osteogenic differentiation under osteogenic conditions. Runx2, OCN, alkaline phosphatase (ALP) activity, and the mineralized nodule formation were used to assess the osteogenic phenotype. Molecule expressions were determined by qRT-PCR, immunofluorescence staining, and western blot. The mineralized nodules were assessed by Alizarin red staining. Compared to the normal renal papillary tissue, Runx2, OCN, and H19 were significantly upregulated in RP. After hRIFs were induced with osteogenic medium, osteogenic markers (Runx2, OCN and ALP), ß-catenin and H19 were significantly upregulated, and the mineralized nodules are formed. Additionally, overexpression of H19 promoted the osteogenic phenotype of hRIFs and increased the expression of ß-catenin, whereas knock-down of H19 or XAV939 (inhibitor of Wnt-ß-catenin signaling pathway) significantly repressed the osteogenic phenotype of hRIFs and decreased the ß-catenin. Moreover, XAV939 was shown to abolish the osteogenic differentiation of hRIFs promoted by H19. The study demonstrated that ectopic calcification partly participated in the formation of RP, and H19 promoted osteogenic differentiation of hRIFs by activating Wnt-ß-catenin pathway, which shed new light on the molecular mechanism of the RP formation.

4.
Kidney Int ; 97(5): 1032-1041, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32247630

RESUMO

The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, to define the spectrum of phenotypes associated with APOL1 high-risk variants in 1,837 African American participants of Penn Medicine Biobank and 4,742 African American participants of Vanderbilt BioVU. In the Penn Medicine Biobank, outpatient creatinine measurement-based estimated glomerular filtration rate and multivariable regression models were used to evaluate the association between high-risk APOL1 status and renal outcomes. In meta-analysis of both cohorts, the strongest phenome-wide association study associations were for the high-risk APOL1 variants and diagnoses codes were highly significant for "kidney dialysis" (odds ratio 3.75) and "end stage kidney disease" (odds ratio 3.42). A number of phenotypes were associated with APOL1 high-risk genotypes in an analysis adjusted only for demographic variables. However, no associations were detected with non-renal phenotypes after controlling for chronic/end stage kidney disease status. Using calculated estimated glomerular filtration rate -based phenotype analysis in the Penn Medicine Biobank, APOL1 high-risk status was associated with prevalent chronic/end stage kidney disease /kidney transplant (odds ratio 2.27, 95% confidence interval 1.67-3.08). In high-risk participants, the estimated glomerular filtration rate was 15.4 mL/min/1.73m2; significantly lower than in low-risk participants. Thus, although APOL1 high-risk variants are associated with a range of phenotypes, the risks for other associated phenotypes appear much lower and in our dataset are driven by a primary effect on renal disease.

5.
Biometrics ; 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246839

RESUMO

Clinically relevant information from electronic health records (EHRs) permits derivation of a rich collection of phenotypes. Unlike traditionally designed studies where scientific hypotheses are specified a priori before data collection, the true phenotype status of any given individual in EHR-based studies is not directly available. Structured and unstructured data elements need to be queried through preconstructed rules to identify case and control groups. A sufficient number of controls can usually be identified with high accuracy by making the selection criteria stringent. But more relaxed criteria are often necessary for more thorough identification of cases to ensure achievable statistical power. The resulting pool of candidate cases consists of genuine cases contaminated with noncase patients who do not satisfy the control definition. The presence of patients who are neither true cases nor controls among the identified cases is a unique challenge in EHR-based case-control studies. Ignoring case contamination would lead to biased estimation of odds ratio association parameters. We propose an estimating equation approach to bias correction, study its large sample property, and evaluate its performance through extensive simulation studies and an application to a pilot study of aortic stenosis in the Penn medicine EHR. Our method holds the promise of facilitating more efficient EHR studies by accommodating enlarged albeit contaminated case pools.

6.
EMBO Rep ; 21(4): e48467, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32052578

RESUMO

The androgen receptor (AR) has been linked to bladder cancer (BCa) progression, but if this involves circular RNAs (circRNAs) remains unclear. Here, we find that AR alters the levels of circRNA-FNTA (circFNTA) to increase BCa cell invasion and chemo-resistance. Mechanistically, AR represses the RNA editing gene ADAR2 via direct binding to its 5' promoter region to increase circFNTA levels, which then sponges the microRNA miR-370-3p to increase the expression of its host gene FNTA. This AR-mediated ADAR2/circFNTA/miR-370-3p/FNTA pathway then activates KRAS signaling to alter BCa cell invasion and chemo-sensitivity to cisplatin. A clinical BCa sample survey shows that circFNTA expression is elevated in BCa tissues, and results from a BCa mouse model indicate that depletion of circFNTA leads to the suppression of BCa metastases and increased cisplatin chemo-sensitivity. Together, based on our results using multiple BCa cell lines and an in vivo mouse model we suggest that targeting this newly identified AR/ADAR2/circFNTA/miR-370-3p/FNTA/KRAS axis may lead to the development of therapies to suppress BCa metastasis and to increase its chemo-sensitivity.

7.
Gynecol Oncol ; 156(2): 363-376, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31918993

RESUMO

OBJECTIVES: Current risk-reducing salpingo-oophorectomy (RRSO) guidelines for individuals with BRCA1/2 mutations do not account for risk variability due to BRCA1/2 cluster region mutations that are associated with varying risks for the development of breast and ovarian cancer. We assessed whether current recommendations are appropriate for individual patients considering mutation-specific risks. METHODS: Using a hypothetical cohort of patients with BRCA1/2 mutations, we constructed Markov models allowing for the estimation of mean life expectancy based upon BRCA1/2 mutation, the presence of a cluster region mutation (Ovarian Cancer Cluster Region (OCCR), Breast Cancer Cluster Region (BCCR), or non-BCCR/OCCR), age at time of BRCA1/2 diagnosis (20-65), and age at time of RRSO (21-80). RESULTS: For all BRCA1/2 mutation types, the optimal strategy was to undergo RRSO as early as possible. For BRCA1/2 carriers who delayed RRSO or who were identified with a mutation later in life, the OCCR mutation tended to be associated with lower life expectancy estimates than the BCCR and non-BCCR/OCCR mutations. Minimal delays in RRSO (i.e., neighboring 5-year intervals) were associated with minor losses in life expectancy. Variables associated with greatest impact on life expectancy included ovarian cancer risk after RRSO, breast cancer mortality rate, non-cancer mortality associated with RRSO, and breast cancer stage distribution. CONCLUSIONS: BRCA1/2 cluster regions may provide more precise estimates of life expectancy in counselling and shared decision-making. The most appropriate timing for RRSO is a complex decision and must be individualized for each patient.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Modelos Estatísticos , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Tomada de Decisões , Feminino , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Predisposição Genética para Doença , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Família Multigênica , Neoplasias Ovarianas/diagnóstico , Salpingo-Ooforectomia , Adulto Jovem
8.
Stat Methods Med Res ; 29(2): 466-480, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30945605

RESUMO

In epidemiology cohort studies, exposure data are collected in sub-studies based on a primary outcome (PO) of interest, as with the extreme-value sampling design (EVSD), to investigate their correlation. Secondary outcomes (SOs) data are also readily available, enabling researchers to assess the correlations between the exposure and the SOs. However, when the EVSD is used, the data for SOs are not representative samples of a general population; thus, many commonly used statistical methods, such as the generalized linear model (GLM), are not valid. A prospective likelihood method has been developed to associate SOs with single-nucleotide polymorphisms under an extreme phenotype sequencing design. In this paper, we describe the application of the prospective likelihood method (STEVSD) to exposure-SO association analysis under an EVSD. We undertook extensive simulations to assess the performance of the STEVSD method in associating binary and continuous exposures with SOs, comparing it to the simple GLM method that ignores the EVSD. To demonstrate the cost-benefit of the STEVSD method, we also mimicked the design of two new retrospective studies, as would be done in actual practice, based on the PO of interest, which was the same as the SO in the EVSD study. We then analyzed these data by using the GLM method and compared its power to that of the STEVSD method. We demonstrated the usefulness of the STEVSD method by applying it to a benign ethnic neutropenia dataset. Our results indicate that the STEVSD method can control type I error well, whereas the GLM method cannot do so owing to its ignorance of EVSD, and that the STEVSD method is cost-effective because it has statistical power similar to that of two new retrospective studies that require collecting new exposure data for selected individuals.

9.
Biometrics ; 76(1): 210-223, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31449330

RESUMO

In biomedical cohort studies for assessing the association between an outcome variable and a set of covariates, usually, some covariates can only be measured on a subgroup of study subjects. An important design question is-which subjects to select into the subgroup to increase statistical efficiency. When the outcome is binary, one may adopt a case-control sampling design or a balanced case-control design where cases and controls are further matched on a small number of complete discrete covariates. While the latter achieves success in estimating odds ratio (OR) parameters for the matching covariates, similar two-phase design options have not been explored for the remaining covariates, especially the incompletely collected ones. This is of great importance in studies where the covariates of interest cannot be completely collected. To this end, assuming that an external model is available to relate the outcome and complete covariates, we propose a novel sampling scheme that oversamples cases and controls with worse goodness-of-fit based on the external model and further matches them on complete covariates similarly to the balanced design. We develop a pseudolikelihood method for estimating OR parameters. Through simulation studies and explorations in a real-cohort study, we find that our design generally leads to reduced asymptotic variances of the OR estimates and the reduction for the matching covariates is comparable to that of the balanced design.

10.
Oncogene ; 39(3): 574-586, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31506605

RESUMO

While androgens may function via nuclear androgen receptor (nAR) to increase bladder cancer (BCa) progression, the impact of androgens on muscle invasive BCa, which contains nearly 80% nAR-negative cells, remains unclear. To dissect the androgens potential impacts on these nAR-negative muscle invasive BCa, we first found that the androgens, dihydrotestosterone (DHT) might function via a novel membrane AR (mAR-SLC39A9) to increase nAR-negative BCa cell migration and invasion. Mechanism dissection revealed that DHT/mAR-SLC39A9 might function by altering Gαi protein-mediated MAPK/MMP9 intracellular signaling to increase nAR-negative BCa cell migration and invasion. Preclinical studies using multiple in vitro nAR-negative BCa cell lines and an in vivo mouse model all demonstrated that targeting this newly identified DHT/mAR-SLC39A9/Gαi/MAPK/MMP9 signaling with small molecules mAR-SLC39A9-shRNA or Gαi-shRNA, and not the classic antiandrogens including enzalutamide, bicalutamide, or hydroxyflutamide, could suppress nAR-negative BCa cell invasion. Results from human clinical samples surveys also indicated the positive correlation of this newly identified DHT/mAR signaling with BCa progression and prognosis. Together, these results suggest that androgens may not only function via the classic nAR to increase the nAR-positive BCa cell invasion, they may also function via this newly identified mAR-SLC39A9 to increase the nAR-negative/mAR-positive BCa cell invasion.

11.
J Am Med Inform Assoc ; 27(1): 119-126, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722396

RESUMO

OBJECTIVE: Phenotyping patients using electronic health record (EHR) data conventionally requires labeled cases and controls. Assigning labels requires manual medical chart review and therefore is labor intensive. For some phenotypes, identifying gold-standard controls is prohibitive. We developed an accurate EHR phenotyping approach that does not require labeled controls. MATERIALS AND METHODS: Our framework relies on a random subset of cases, which can be specified using an anchor variable that has excellent positive predictive value and sensitivity independent of predictors. We proposed a maximum likelihood approach that efficiently leverages data from the specified cases and unlabeled patients to develop logistic regression phenotyping models, and compare model performance with existing algorithms. RESULTS: Our method outperformed the existing algorithms on predictive accuracy in Monte Carlo simulation studies, application to identify hypertension patients with hypokalemia requiring oral supplementation using a simulated anchor, and application to identify primary aldosteronism patients using real-world cases and anchor variables. Our method additionally generated consistent estimates of 2 important parameters, phenotype prevalence and the proportion of true cases that are labeled. DISCUSSION: Upon identification of an anchor variable that is scalable and transferable to different practices, our approach should facilitate development of scalable, transferable, and practice-specific phenotyping models. CONCLUSIONS: Our proposed approach enables accurate semiautomated EHR phenotyping with minimal manual labeling and therefore should greatly facilitate EHR clinical decision support and research.

13.
Sensors (Basel) ; 19(24)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31817517

RESUMO

A portable capacitive sensor was designed to assess frying oil degradation by measuring the changes in electrical capacitance. An interdigital electrode (IDE) was designed to be implemented as the testing probe (as IDEs are resistive to parasitic capacitance), together with an adjacent capacitive chip Pcap01 and a further microprocessor STM32, which were used as the data-processing elements. Experimental results demonstrated that viscosity could be a useful frying oil quality indicator, and also proved a preliminary correlation between IDE capacitance and oils' total polar materials. This implies that IDE capacitance could be a suitable metric for conveniently assessing frying oil degradation. The designed capacitance sensor is light in weight, cost effective, and has excellent potential for simple, inexpensive, on-the-spot testing of the current quality of frying oil.

14.
Int J Surg ; 72: 85-90, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31689555

RESUMO

BACKGROUND: Staghorn calculi remain a treatment challenge for urologists. The aim of the study was to compare the treatment outcomes of suctioning minimally invasive percutaneous nephrolithotomy (MPCNL) and traditional MPCNL for renal staghorn stones. MATERIALS AND METHODS: Between April 2018 and June 2019, we included patients suffering from renal staghorn stones who were treated with modified MPCNL with a suctioning system. The outcomes of these patients were compared with those of a cohort of patients undergoing traditional MPCNL (between January 2017 and March 2018) using a 1:1 scenario matched-pair analysis. Cases were matched sequentially according to stone burden, stone branches, and stone hardness as well as age and sex. RESULTS: A total of 512 patients were included in this study (256 patients in each group). The baseline characteristics were equally distributed between the two groups. The suctioning MPCNL group achieved a significantly higher stone-free rate (SFR) (78.5% vs 69.1%; P = 0.016) after a single procedure and had a significantly shorter operative time (106.2 ±â€¯18.4 vs. 132.1 ±â€¯22.2 min; P < 0.001) than the traditional MPCNL group. The traditional MPCNL group experienced a significantly higher rate of overall complications than the suctioning MPCNL group (27.3% vs. 16.8%; P = 0.004). Regarding individual complications, a significantly higher rate of fever (13.7% vs. 7.4%; P = 0.021) and urosepsis requiring only additional antibiotics (8.2% vs. 3.5%; P = 0.024) was observed in the traditional MPCNL group than in the suctioning MPCNL group; there was a trend that the suctioning MPCNL group conferred a decreased risk of urosepsis shock (1.2% vs. 2.3%), but this trend failed to achieve statistical significance (P = 0.313). There was no significant difference between the two groups regarding the incidence of severe hemorrhage, the mean number of tracts used during a single procedure and the postoperative hospital stay. CONCLUSIONS: The use of suctioning MPCNL for staghorn calculi had advantages over the use of traditional MPCNL in terms of a higher SFR after a single procedure and fewer postoperative infectious complications. Further well-designed studies are needed to confirm the results.


Assuntos
Nefrolitotomia Percutânea/métodos , Cálculos Coraliformes/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/instrumentação , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Choque Séptico/etiologia , Sucção/instrumentação , Sucção/métodos , Resultado do Tratamento , Infecções Urinárias/etiologia
15.
J Cardiovasc Electrophysiol ; 30(12): 2759-2766, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31599040

RESUMO

BACKGROUND: Lifestyle and risk factor management may improve outcomes in patients with atrial fibrillation (AF). We aim to evaluate the prevalence of modifiable risk factors and how these factors impact clinical outcomes in patients with AF. METHODS AND RESULTS: Data on 17 898 AF cohort patients with AF enrolled between 2011 and 2016 was analyzed. A healthy lifestyle was defined as not smoking, not drinking, a healthy body mass index (BMI), untreated total cholesterol less than 200 mg/dL, untreated blood pressure (BP) less than 120/80 mm Hg, and untreated fasting plasma glucose (FPG) less than 100 mg/dL. The association between risk factors and risk of the composite endpoint of all-cause mortality and nonfatal ischemic stroke were assessed using Cox proportional hazards regression model. Only 4.0% of patients achieved a healthy lifestyle. In multivariate analysis, current smoking, a low BMI, not well-controlled FPG were independently and significantly associated with higher risk of all-cause mortality and nonfatal ischemic stroke, with corresponding hazard ratio (HR) estimates 1.22 (95% confidence interval [CI], 1.00-1.47), HR = 1.72 (95% CI, 1.34-2.20), and HR = 1.25 (95% CI, 1.06-1.46), respectively. High BP was also associated with higher risk with the outcomes (HR = 1.15, 95% CI, 1.00-1.34). Compared with patients with no risk factor, those who failed to maintained or achieved optimal risk factor control had a progressively higher risk of death and nonfatal ischemic stroke (HR for 1 risk factor = 1.44; 95% CI, 1.07-1.92; and more than 2 risk factors = 1.75; 95% CI, 0.99-3.09). CONCLUSIONS: Maintenance of well-controlled risk factors may substantially lower the risk of death and ischemic stroke in patients with AF.

16.
Acta Biochim Biophys Sin (Shanghai) ; 51(11): 1148-1157, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31650173

RESUMO

Cisplatin (CDDP)-based chemotherapy is a standard strategy for the clinical treatment of patients with bladder cancer (BC). However, the anti-tumor efficacy of cisplatin is affected by multiple chemoresistance with complex molecular mechanisms. Recent evidence highlights the crucial regulatory roles of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of cancers and development of drug resistance. However, the roles and underlying molecular mechanisms of MALAT1 in cisplatin resistance of the BC cells remain largely unclear. In this study, we firstly demonstrated that MALAT1 expression was up-regulated in the BC tissues compared to the normal adjacent tissues and elevated in the cancer cells compared to the epithelial immortalized cells. Secondly, we found that suppression of MALAT1 enhanced the chemotherapeutic drug sensitivity and inhibited the cisplatin resistance of the BC cells. Thirdly, we showed that MALAT1 affected the cisplatin resistance of the BC cells via regulating the miR-101-3p/VEGF-C pathway. In summary, this study demonstrates that MALAT1, miR-101-3p and VEGF-C form a regulatory axis to affect the chemo-resistance of BC cells to CDDP, and provides novel potential targets for treatment of BC.


Assuntos
Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/fisiologia , RNA Longo não Codificante/fisiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Neoplasias da Bexiga Urinária/patologia , Fator C de Crescimento do Endotélio Vascular/metabolismo
17.
Micromachines (Basel) ; 10(10)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581655

RESUMO

Micro/nano-manipulation is the fabrication of particular constructs on devices at the micro/nano-scale. Precise manipulation of microparticles is one of the key technological difficulties in manufacturing micro/nano-scale components. Based on scanning electron microscopy and nanomanipulator, this paper adopts a direct push method to operate randomly distributed microparticles into ordered structures. A two-probe interaction strategy is proposed to enable microparticle movements in all directions efficiently and avoid scratching the substrate surface. To overcome the uncertainties in micromanipulation, a virtual nano-hand strategy was also implemented: long-range advance of each microparticle is realized by multiple single-step pushes, whose trajectory is theoretically analyzed. The pushes are well programmed to imitate effects of a more powerful and determined hand. Experimental results show that the theoretical single-step motion trajectory is in line with actual operation, and the proposed strategy can ensure precise operation of the microparticles in all directions and improve reliability and effectiveness of operation.

18.
Biochem Biophys Res Commun ; 519(2): 246-252, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495492

RESUMO

BACKGROUND: Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). METHODS: ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients' clinicopathological features. RESULTS: ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. CONCLUSION: Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients' clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

19.
Oncogene ; 38(50): 7491-7503, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31435021

RESUMO

BP180, also termed collagen XVII, is a hemidesmosomal transmembrane glycoprotein expressed in basal keratinocytes, and functions as a cell-matrix adhesion molecule in the dermal-epidermal junction of the skin. Its function, other than cell-matrix adhesion, remains unclear. We generated a mouse strain with BP180 dysfunction (termed ∆NC16A), which develops spontaneous skin inflammation accompanied by an influx of myeloid derived suppressor cells (MDSCs). We used the B16 mouse melanoma model to demonstrate that BP180 dysfunction in either skin or basal keratinocytes promotes MDSC influx into skin and tumor progression. MDSC depletion reduced tumor progression in ∆NC16A mice, demonstrating a critical role for BP180 dysfunction-driven MDSCs in melanoma progression. This study provides the first direct evidence that BP180, a cell-cell matrix adhesion molecule, possesses antitumor function through modulating infiltration of MDSCs. Basal keratinocytes actively participate in skin microenvironment changes caused by BP180 dysfunction. ∆NC16A mice could be a new animal model to study the melanoma microenvironment.


Assuntos
Autoantígenos/genética , Melanoma Experimental/genética , Melanoma/genética , Células Supressoras Mieloides/metabolismo , Colágenos não Fibrilares/genética , Animais , Adesão Celular/genética , Modelos Animais de Doenças , Progressão da Doença , Humanos , Queratinócitos/patologia , Melanoma/patologia , Melanoma Experimental/patologia , Camundongos , Células Supressoras Mieloides/patologia , Pele/metabolismo , Pele/patologia , Microambiente Tumoral/genética
20.
Cancer Manag Res ; 11: 6425-6441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31372046

RESUMO

Purpose: Inguinal lymph node metastasis (LNM) is one of the most significant prognostic factors for patients with penile cancer. This study aimed to identify potential predictors of inguinal LNM. Patients and methods: A comprehensive search of the PubMed, Embase, and Cochrane Library databases for studies that reported predictors of inguinal LNM in penile cancer was performed. Finally, we selected 42 eligible studies with 4,802 patients. Accumulative analyses of odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were performed. All analyses were performed by using Review Manager software version 5.3. Results: Among the 4,802 patients, 1,706 (36%) were diagnosed with inguinal LNM. Predictors of LNM included two categories: tumor-associated biomarkers and invasive clinicopathologic characteristics. Biomarker-specific predictors: the program death ligand 1 (PD-L1) overexpression (OR=2.55, p=0.002), higher neutrophil-to-lymphocyte ratio (NLR) (OR=4.22, p=0.010), higher C-reactive protein (CRP) (OR=4.78, p<0.001), squamous cell carcinoma antigen (SCC-Ag) overexpression (OR=8.52, p<0.001), P53 protein overexpression (OR=3.57, p<0.001). Clinicopathological predictors: positive clinical lymph node (cN+) (OR=5.86, p<0.001), high-risk histopathological subtype (OR=14.63, p<0.001) and intermediate-risk subtype (OR=3.37, p<0.001), vertical growth pattern (OR=1.97, p=0.020), higher stage (AJCC: OR=3.66, p<0.001; UICC: OR=2.43, p<0.001), higher tumor grade (OR=3.37, p<0.001), tumor size (>3 cm) (OR=2.00, p=0.002), LVI (OR=3.37, p<0.001), invasion depth (>5 mm) (OR=2.58, p=0.002), nerve invasion (OR=2.84, p<0.001), corpora cavernosum invasion (OR=2.22, p<0.001), corpus spongiosum invasion (OR=1.73, p=0.002) and urethra invasion (OR=1.81, p=0.030). Conclusion: Current meta-analysis conclusively identified valuable predictors of inguinal LNM for patients with penile cancer. However, high-quality studies are warranted to further validate our conclusions. The intrinsic link between these predictors needs to be further investigated to create an accurate mathematical prediction model for LNM.

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