scholarly journals MTHFD2 Expression Association with Bladder Cancer and Screening of its Potential Inhibitor

2021 ◽  
Author(s):  
Maleeha Asif ◽  
Muhammad Ilyas ◽  
Muhammad Zafar ◽  
Muhammad Affan Elahi ◽  
Nazish Bostan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Binding Free Energy ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Tumor Stage ◽  
Low Grade ◽  
Library Screening ◽  
Quantitative Expression ◽  
Stage Progression ◽  
The Impact

Abstract BackgroundBladder cancer is the most common urological malignancy. Genes of folate mediated 1 carbon metabolism are found to be highly up regulated in tumor cells and promotes tumor cell proliferation. Rationale and aim of the studyThe aim of the current study was to determine the expression of MTHFD2 gene and the impact of intronic SNP rs1667627 on MTHFD2 expression Furthermore, determination of potential ligand based inhibitors against MTHFD2. Methods & ResultsSemi-quantitative expression analysis and sanger sequencing were used for this purpose. Moreover, structure based virtual ligand library screening in order to find plausible inhibitors.MTHFD2 expression was significantly increased with tumor stage progression both in low and high-grade bladder cancer. However, the relative fold change difference in low grade bladder cancer in correlation with the tumor stage progression was more dramatic. Contrary to the TCGA dataset analysis, increased MTHFD2 expression was observed in papillary bladder cancer tumor. G to A transition in the intronic variant rs1667627 SNP was determined in tumor tissues as compared to control. Virtual ligand based library screening against the three dimensional MTHFD2 protein lead to identification of a plausible inhibitor MCULE-8027924848 that displayed lower binding free energy as compared to already documented LY345899. ConclusionMTHFD2 might be used as low-grade bladder cancer biomarker since its expression level changes drastically with tumor progression. Further, experimental studies are required to establish the potential mode of inhibition of MCULE-8027924848 ligand.

scholarly journals PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer

BMC Urology ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Takashi Kawahara ◽  
Yukari Ishiguro ◽  
Shinji Ohtake ◽  
Ikuma Kato ◽  
Yusuke Ito ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Stage Progression

Investigation on Mechanical Properties of Fibreglass Reinforced Flexible Pipes Under Torsion

2018 ◽  
Author(s):  
Pan Fang ◽  
Yuxin Xu ◽  
Shuai Yuan ◽  
Yong Bai ◽  
Peng Cheng
Keyword(s):  
Mechanical Behavior ◽  
Torsion Angle ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Load Condition ◽  
Element Model ◽  
Flexible Pipe ◽  
Torsional Load ◽  
Flexible Pipes ◽  
The Impact

Fibreglass reinforced flexible pipe (FRFP) is regarded as a great alternative to many bonded flexible pipes in the field of oil or gas transportation in shallow water. This paper describes an analysis of the mechanical behavior of FRFP under torsion. The mechanical behavior of FRFP subjected to pure torsion was investigated by experimental, analytical and numerical methods. Firstly, this paper presents experimental studies of three 10-layer FRFP subjected to torsional load. Torque-torsion angle relations were recorded during this test. Then, a theoretical model based on three-dimensional (3D) anisotropic elasticity theory was proposed to study the mechanical behavior of FRFP. In addition, a finite element model (FEM) including reinforced layers and PE layers was used to simulate the torsional load condition in ABAQUS. Torque-torsion angle relations obtained from these three methods agree well with each other, which illustrates the accuracy and reliability of the analytical model and FEM. The impact of fibreglass winding angle, thickness of reinforced layers and radius-thickness ratio were also studied. Conclusions obtained from this research may be of great practicality to manufacturing engineers.

Numerical study of asymmetric and axisymmetric thermal jet with entropy generation concept

2021 ◽  
Vol 15 (1) ◽  
pp. 7628-7636
Author(s):  
D. Belakhal ◽  
Kouider Rahmani ◽  
Amel Elkaroui Elkaroui ◽  
Syrine Ben Haj Ayech ◽  
Nejla Mahjoub Saïd ◽  
...  
Keyword(s):  
Entropy Generation ◽  
Numerical Study ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Variable Density ◽  
Current Investigation ◽  
Numerical Resolution ◽  
Different Temperatures ◽  
Density Ratios ◽  
The Impact

In the current investigation, numerical study of a thermal jet of asymmetric (rectangular and elliptical) and axisymmetric (circular) geometry was investigated with variable density to verify the impact of the ratio of density and geometry on the generation of entropy. The central jet was brought to different temperatures (194, 293 and 2110 K) to obtain density ratios (0.66, 1 and 7.2) identical to a mixture jet ((Air-CO2), (Air-Air) and (Air-He)), respectively. Solving the three-dimensional numerical resolution of the Navier Stocks for turbulent flow permanent enclosed on the turbulence model K-εstandard was made. The results acquired are compared with that carried out in previous experimental studies, where it was concluded that, the axisymmetric (circular) geometry increases the entropy generation.

Salvage radiotherapy (SR) in patients (pts) with prostate cancer (PC) and rising prostate specific antigen (PSA) after radical prostatectomy (RP): Results from a single-center study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14556-14556
Author(s):  
T. Wiegel ◽  
G. Lohm ◽  
S. Hoecht ◽  
D. Bottke ◽  
K. Neumann ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Three Dimensional ◽  
Area Under The Curve ◽  
Surgical Margin ◽  
Conformal Radiotherapy ◽  
Roc Curves ◽  
Tumor Stage ◽  
Published Data ◽  
Therapeutic Success ◽  
The Impact

14556 Background: In pts with PC and biochemical relapse after RP SR is well established. However, the significance of pre-radiotherapeutic variables for guidance of treatment decisions is less clear. We analyzed prognostic factors in a large cohort of pts treated with SR after RP. Methods: 163 pts with PC and persisting PSA-levels (n = 60) or PSA-elevation following undetectable PSA-levels (n = 103) after RP received three-dimensional conformal radiotherapy (RT). None received androgen depriving therapy between prostatectomy and start of RT. We evaluated the impact of age, stage, surgical margin status (SMS), Gleason score and PSA-kinetics by survival and regression analysis. Biochemical progression (BP) was defined as PSA-increases at 3 consecutive time points after the post RT nadir. To detect thresholds for significant prognostic variables, we calculated receiver operating characteristic (ROC) curves. Results: Medians for pre-RT variables were: 11.97 ng/ml for pre-prostatectomy PSA (Pre-OP PSA), 5.4 months for PSA doubling time (PSADT) and 0.339 ng/ml for pre-radiotherapy PSA (Pre-RT PSA). Probability for a projected 4-year PFS was 50% (median follow-up: 33.5 months). Logistic regression revealed a significant impact on the probability of BP for Pre-OP PSA (p = 0.036), PSADT (p = 0.024) and tumor-stage (p = 0.043), whereas Pre-RT PSA and SMS had a significant impact on achievement of undetectable post-RT PSA (p = 0.009 and p = 0.028 respectively). Analysis of ROC-curves for Pre-OP PSA, Pre-RT PSA, PSADT revealed an area under the curve not exceeding 0.704 for any of these parameters. Conclusions: By analyzing ROC-curves we could not detect clear thresholds for PSA kinetic variables. In accordance with recently published data we found similar independent significant variables predicting a therapeutic success. However, we observed a lower median Pre-RT PSA and a higher probability of PFS in our patient cohort. This suggests, that early radiotherapeutic intervention improves PFS. No significant financial relationships to disclose.

Blue-light cystoscopy’s effects on management of bladder cancer when compared to traditional white-light cystoscopy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 378-378 ◽  
Author(s):  
Andrew Mount ◽  
Stephen Bentley Williams ◽  
Colin P. N. Dinney ◽  
H. Barton Grossman ◽  
Curtis Alvin Pettaway ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Blue Light ◽  
White Light ◽  
False Negative ◽  
Low Grade ◽  
High Grade ◽  
Real World Setting ◽  
White Light Cystoscopy ◽  
The Impact ◽  
Subsequent Patient

378 Background: Fluorescence cystoscopy (also known as blue-light cystoscopy (BL)) is an adjunct to white light cystoscopy (WL) and aids in visualization of tumors that may be missed with WL as well as allow more complete resection of tumors. Herein we present the impact of BL on subsequent patient management in a real world setting. Methods: A total of 116 consecutive patients who underwent simultaneous BL and WL from January 2013 through December 2014 were included in the study. Pathology and operative reports were reviewed to determine the grade and stage of the tumors and whether they were viewed under BL or WL. Results: Of the 116 patients, a total of 161 biopsies and/or transurethral resected specimens were analyzed. Of these, 46 (28.6%) lesions were seen only with BL, none were seen only with white light, 109 (67.7%) were seen with both, and 7 (4.4%) were identified via random biopsies. Of the 46 lesions seen only on BL, 17 (37%) were positive for cancer, while, of the 109 lesions seen with WL and BL, 84 (77%) were positive. Of the 17 (37%) true positive tumors seen only on BL, the stage and grades were; 5 (29.4%) low-grade Ta, 2 (11.8%) high-grade Ta, 1 (5.9%) high-grade T1, and 9 (52.9%) CIS. There were no instances of a tumor being found on WL that was not also visualized with BL. In this patient cohort, the false positive rates were 23% and 63% for WL and BL, respectively. The false negative rates were 0.9% and 2.1% for WL and BL, respectively. For the 46 (28.6%) lesions that were visible by BL, WL cystoscopy was not able to visualize 10 (21.7%) tumors visualized by BL. In addition, there was one patient who had multiple lesions sent for pathology by BL and WL, and the lesions identified by BL were of higher stage than the lesions visualized by WL. Conclusions: BL identified additional tumors that would have been missed with WL. Moreover, in patients who had tumors visualized only with BL, 11 (26.8%) were high-grade, including one (2.4%) patient with T1 tumor and 8 (19.5%) with CIS. Thus, BL identified a number of high-risk tumors, which had a significant impact on the subsequent management of patients with bladder cancer.

Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.

1995 ◽  
Vol 13 (6) ◽  
pp. 1384-1390 ◽  
Author(s):  
A S Sarkis ◽  
D F Bajorin ◽  
V E Reuter ◽  
H W Herr ◽  
G Netto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Value ◽  
Performance Status ◽  
Tumor Stage ◽  
Invasive Bladder Cancer ◽  
Relative Risk Ratio ◽  
P53 Overexpression ◽  
Term Survival ◽  
Palpable Mass ◽  
The Impact

PURPOSE This study sought to examine the prognostic role of p53 nuclear overexpression in muscle-invasive bladder cancer because of its correlation with progression of superficial bladder cancer. PATIENTS AND METHODS Ninety of 111 patients treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with a median follow-up duration of 5.8 years were evaluated. p53 nuclear overexpression was determined by immunohistochemistry on deparaffinized tissue sections. Patients were stratified into two groups according to the percent of tumor cells with positive nuclear reactivity. Overexpression was defined as tumors with > or = 20% cells with positive nuclear reactivity and nonoverexpression as tumors with less than 20% reactivity. RESULTS Nuclear overexpression was observed in 47 patients and nonoverexpression in 43 patients. Patients whose tumors had p53 overexpression had a significantly higher proportion of cancer deaths. A multivariate analysis that evaluated the pretreatment variables p53 nuclear overexpression, age, sex, palpable mass, prechemotherapy tumor stage, performance status, ureteral obstruction, tumor size, multifocality, and grade showed that p53 overexpression had independent significance for survival (P = .001; relative risk ratio, 3.1). The impact of p53 overexpression on survival was predominantly in T2 and T3a tumors. Long-term survival was evident in seven of 17 patients (41%) with p53 overexpression versus 20 of 26 (77%) in whom p53 was not overexpressed (P = .007). CONCLUSION p53 nuclear overexpression has independent prognostic value for survival in patients with invasive bladder cancer treated with neoadjuvant chemotherapy.

scholarly journals The Dependence between Urinary Levels of Angiogenesis Factors, 8-Iso-prostaglandin F2α, ɣ-Synuclein, and Interleukin-13 in Patients with Bladder Cancer: A Pilot Study

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Beata Szymańska ◽  
Ewa Sawicka ◽  
Michał Matuszewski ◽  
Janusz Dembowski ◽  
Agnieszka Piwowar
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Prostaglandin F2α ◽  
Invasive Bladder Cancer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Interleukin 13 ◽  
Urinary Levels ◽  
The Impact

During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth and metastasis. Additionally, the participation of oxidative stress and chronic inflammation in BC pathogenesis is indicated. The aim of the study was to evaluate the urinary levels of parameters of angiogenesis, stimulating angiogenin (ANG) and inhibiting angiostatin (ANGST), 8-iso-prostaglandin F2α (8-iso-PGF2α) as a marker of oxidative stress, ɣ-synuclein (SNCG) as a cancer progression parameter, and interleukin-13 (IL-13) as an anti-inflammatory immunomodulator. The levels of ANG, ANGST, 8-iso-PGF2α, SNCG, and IL-13 in the urine of BC patients and healthy controls were measured by the enzyme-linked immunosorbent assay. These parameters were examined in the whole group of BC patients and in subgroups depending on the clinical stage: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC); histopathologic malignancy: low grade (LG) and high grade (HG) and in primary and recurrent BC. Significantly, higher urinary parameters were found in BC patients in comparison to controls. Levels of all parameters increased with the development of cancer, with the exception of 8-iso-prostaglandin F2α, in which the level was higher in the early stages of the disease, but these differences were not statistically significant. Some correlations have been demonstrated between parameters in BC patients. Based on the receiver operating characteristic curves, ANG and ANGST had the best diagnostic value for BC. The obtained results indicate the important role of the examined parameters of angiogenesis, oxidative stress, and inflammation in the pathogenesis and development of BC. It is reasonable to continue research in order to thoroughly assess the impact of various associated processes on the course of BC. It is also important to carry out similar tests in patients with other urological diseases.

Grade and Stage at Presentation Do Not Predict Mortality in Patients With Bladder Cancer Who Survive Their Disease

2009 ◽  
Vol 27 (15) ◽  
pp. 2443-2449 ◽  
Author(s):  
Edward M. Messing ◽  
Ralph Madeb ◽  
Changyong Feng ◽  
Laura Stephenson ◽  
Kennedy W. Gilchrist ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cause Of Death ◽  
Tumor Stage ◽  
Low Grade ◽  
Tumor Registry ◽  
Hazard Ratios ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Threat To Life

Purpose Our goal was to determine whether presenting grade and stage of bladder cancer (BC), which directly affect disease-specific survival, also influence time to and cause of non-BC deaths. Methods Histology slides of all men who lived in Wisconsin age ≥ 50 years diagnosed with BC in 1988 were reviewed centrally, and time and cause of death as reported to the state's tumor registry were recorded. Competing risks analyses based on grade, tumor stage, and age at diagnosis were generated to correlate time and causes of death (BC or non-BC) with tumor histology and age at presentation. Results Grade-stage categories were assigned to 509 patients with BC as follows: LGN = low grade (grade 1 or 2), nonmuscle invading (stage Ta or T1); HGN = high grade (grade 3 or carcinoma in situ), nonmucle invading (stage Ta, T1, or TIS); and INV = any grade, muscle invasive (≥ stage T2). Three hundred nine patients (60.7%) were LGN, 80 (15.7%) were HGN, and 120 (23.6%) were INV. Grade-stage category predicted overall (P = .0001) and BC-specific (P < .0001) mortality but not non-BC mortality (P = .72), with hazard ratios of 1.095 (95% CI, 0.783 to 1.531) for HGN versus LGN, 1.137 (95% CI, 0.799 to 1.617) for INV versus LGN, and 1.038 (95% CI, 0.670 to 1.607) for INV versus HGN. Age had a highly significant effect on overall and non-BC deaths (P < .0001) but only marginally predicted BC deaths (P = .054). Time to non-BC death did not differ significantly between grade-stage category (P = .12) or cause of death (P = .81). Conclusion Grade-stage category at diagnosis predicts overall and BC mortality but not mortality from other causes. Thus, particularly for INV disease, because BC represents the major threat to life, aggressive therapies that have been shown to be effective are justified.

Studies of translocation catalysis

1991 ◽  
Vol 11 (6) ◽  
pp. 477-538 ◽  
Author(s):  
Peter J. F. Henderson
Keyword(s):  
Experimental Studies ◽  
Three Dimensional ◽  
Transport Processes ◽  
Symbiotic Relationship ◽  
Chemiosmotic Theory ◽  
Fundamental Theory ◽  
Experimental Knowledge ◽  
History Of ◽  
Experimental Approaches ◽  
The Impact

There is a symbiotic relationship between the evolution of fundamental theory and the winning of experimentally-based knowledge. The impact of the General Chemiosmotic Theory on our understanding of the nature of membrane transport processes is described and discussed. The history of experimental studies on transport catalysed by ionophore antibiotics and the membrane proteins of mitochondria and bacteria are used to illustrate the evolution of knowledge and theory. Recent experimental approaches to understanding the lactose-H+ symport protein of Escherichia coli and other sugar porters are described to show that the lack of experimental knowledge of the three-dimensional structures of the proteins currently limits the development of theories about their molecular mechanism of translocation catalysis.

scholarly journals Coupled SPH–FEM Modeling of Tsunami-Borne Large Debris Flow and Impact on Coastal Structures

2021 ◽  
Vol 9 (10) ◽  
pp. 1068
Author(s):  
Anis Hasanpour ◽  
Denis Istrati ◽  
Ian Buckle
Keyword(s):  
Turbulent Flows ◽  
Large Scale ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Fem Modeling ◽  
Vertical Column ◽  
Initial Water ◽  
Modeling Approach ◽  
Non Linear ◽  
The Impact

Field surveys in recent tsunami events document the catastrophic effects of large waterborne debris on coastal infrastructure. Despite the availability of experimental studies, numerical studies investigating these effects are very limited due to the need to simulate different domains (fluid, solid), complex turbulent flows and multi-physics interactions. This study presents a coupled SPH–FEM modeling approach that simulates the fluid with particles, and the flume, the debris and the structure with mesh-based finite elements. The interaction between the fluid and solid bodies is captured via node-to-solid contacts, while the interaction of the debris with the flume and the structure is defined via a two-way segment-based contact. The modeling approach is validated using available large-scale experiments in the literature, in which a restrained shipping container is transported by a tsunami bore inland until it impacts a vertical column. Comparison of the experimental data with the two-dimensional numerical simulations reveals that the SPH–FEM models can predict (i) the non-linear transformation of the tsunami wave as it propagates towards the coast, (ii) the debris–fluid interaction and (iii) the impact on a coastal structure, with reasonable accuracy. Following the validation of the models, a limited investigation was conducted, which demonstrated the generation of significant debris pitching that led to a non-normal impact on the column with a reduced contact area and impact force. While the exact level of debris pitching is highly dependent on the tsunami characteristics and the initial water depth, it could potentially result in a non-linear force–velocity trend that has not been considered to date, highlighting the need for further investigation preferably with three-dimensional models.

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