Displaying publications 21 - 40 of 64 in total

Abstract:
Sort:
  1. Dareng EO, Tyrer JP, Barnes DR, Jones MR, Yang X, Aben KKH, et al.
    Eur J Hum Genet, 2022 Jan 14.
    PMID: 35027648 DOI: 10.1038/s41431-021-00987-7
    Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
  2. Dareng EO, Tyrer JP, Barnes DR, Jones MR, Yang X, Aben KKH, et al.
    Eur J Hum Genet, 2022 May;30(5):630-631.
    PMID: 35314806 DOI: 10.1038/s41431-022-01085-y
  3. Wang H, Chen M, Sang X, You X, Wang Y, Paterson IC, et al.
    Eur J Med Chem, 2020 Apr 01;191:112154.
    PMID: 32092587 DOI: 10.1016/j.ejmech.2020.112154
    Transforming growth factor-β (TGF-β) is a member of a superfamily of pleiotropic proteins that regulate multiple cellular processes such as growth, development and differentiation. Following binding to type I and II TGF-β serine/threonine kinase receptors, TGF-β activates downstream signaling cascades involving both SMAD-dependent and -independent pathways. Aberrant TGF-β signaling is associated with a variety of diseases, such as fibrosis, cardiovascular disease and cancer. Hence, the TGF-β signaling pathway is recognized as a potential drug target. Various organic molecules have been designed and developed as TGF-β signaling pathway inhibitors and they function by either down-regulating the expression of TGF-β or by inhibiting the kinase activities of the TGF-β receptors. In this review, we discuss the current status of research regarding organic molecules as TGF-β inhibitors, focusing on the biological functions and the binding poses of compounds that are in the market or in the clinical or pre-clinical phases of development.
  4. Wu H, Sun Y, Wong WL, Cui J, Li J, You X, et al.
    Eur J Med Chem, 2020 Mar 01;189:112042.
    PMID: 31958737 DOI: 10.1016/j.ejmech.2020.112042
    Transforming growth factor-β (TGF-β) plays an important role in regulating epithelial to mesenchymal transition (EMT) and the TGF-β signaling pathway is a potential target for therapeutic intervention in the development of many diseases, such as fibrosis and cancer. Most currently available inhibitors of TGF-β signaling function as TGF-β receptor I (TβR-I) kinase inhibitors, however, such kinase inhibitors often lack specificity. In the present study, we targeted the extracellular protein binding domain of the TGF-β receptor II (TβR-II) to interfere with the protein-protein interactions (PPIs) between TGF-β and its receptors. One compound, CJJ300, inhibited TGF-β signaling by disrupting the formation of the TGF-β-TβR-I-TβR-II signaling complex. Treatment of A549 cells with CJJ300 resulted in the inhibition of downstream signaling events such as the phosphorylation of key factors along the TGF-β pathway and the induction of EMT markers. Concomitant with these effects, CJJ300 significantly inhibited cell migration. The present study describes for the first time a designed molecule that can regulate TGF-β-induced signaling and EMT by interfering with the PPIs required for the formation of the TGF-β signaling complex. Therefore, CJJ300 can be an important lead compound with which to study TGF-β signaling and to design more potent TGF-β signaling antagonists.
  5. Li Y, Ouyang Y, Wu H, Wang P, Huang Y, Li X, et al.
    Eur J Med Chem, 2022 Jan 15;228:113979.
    PMID: 34802838 DOI: 10.1016/j.ejmech.2021.113979
    The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.
  6. Shi T, Huang Q, Liu K, Du S, Fan Y, Yang L, et al.
    Eur Urol, 2020 10;78(4):592-602.
    PMID: 32305170 DOI: 10.1016/j.eururo.2020.03.020
    BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described.

    OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT.

    DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019.

    SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals.

    MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed.

    RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed.

    CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation.

    PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

  7. Yang X, Wang S, King TL, Kerr CJ, Blanchet C, Svergun D, et al.
    Faraday Discuss, 2016 Jul 18.
    PMID: 27430046
    We have developed a new class of lanthanide nano-clusters that self-assemble using flexible Schiff base ligands. Cd-Ln and Ni-Ln clusters, [Ln8Cd24(L(1))12(OAc)39Cl7(OH)2] (Ln = Nd, Eu), [Eu8Cd24(L(1))12(OAc)44], [Ln8Cd24(L(2))12(OAc)44] (Ln = Nd, Yb, Sm) and [Nd2Ni4(L(3))2(acac)6(NO3)2(OH)2], were constructed using different types of flexible Schiff base ligands. These molecular nano-clusters exhibit anisotropic architectures that differ considerably depending upon the presence of Cd (nano-drum) or Ni (square-like nano-cluster). Structural characterization of the self-assembled particles has been undertaken using crystallography, transmission electron microscopy and small-angle X-ray scattering. Comparison of the metric dimensions of the nano-drums shows a consistency of size using these techniques, suggesting that these molecules may share similar structural features in both solid and solution states. Photophysical properties were studied by excitation of the ligand-centered absorption bands in the solid state and in solution, and using confocal microscopy of microspheres loaded with the compounds. The emissive properties of these compounds vary depending upon the combination of lanthanide and Cd or Ni present in these clusters. The results provide new insights into the construction of novel high-nuclearity nano-clusters and offer a promising foundation for the development of new functional nanomaterials.
  8. Li R, Cao C, Zheng Z, Yang X, Tan CP, Xu Y, et al.
    Food Funct, 2021 Mar 15;12(5):2020-2031.
    PMID: 33565560 DOI: 10.1039/d0fo02511a
    The consumption of saturated lipids in combination with a sedentary lifestyle increases the risk of obesity and metabolic syndrome. However, the distribution of endogenous fatty acids (FA) after the consumption of saturated lipids and the connection between FA distribution and lipid metabolism-related genes relative expression have not been fully elucidated to date. In this study, we characterized FA profiles in the liver and visceral fats of Sprague Dawley (SD) rats fed with a high-palm-oil diet. The investigation showed that the levels of C16:0 and C18:1 (n-9) increased significantly (P < 0.05) in the liver of the high-palm-oil group (POG), while C16:1 (n-7) and C18:2 (n-6) accumulated markedly (P < 0.05) in the visceral fats of the control group (CN). A correlation analysis indicated a negative correlation between C16:0 and C16:1 (n-7) in the epididymal fat of POG. Our study also demonstrated that the intake of saturated lipids caused changes in lipid metabolism-related gene expression, especially stearoyl-CoA desaturase (SCD), which was upregulated at the third week but was inhibited in the subsequent weeks in the POG liver and perirenal fat. The SCD had a notable positive correlation with C16:1 (n-7) in the POG liver and perirenal fat but a significant negative correlation with C16:0 in the POG epididymal fat. In conclusion, the results of this study indicate that a high-C16:0 diet may result in adaptive SCD expression, and these findings may help to elucidate the effects of dietary fat on lipid metabolism.
  9. Gao D, Chen H, Li H, Yang X, Guo X, Zhang Y, et al.
    Front Nutr, 2023;10:1149137.
    PMID: 37025610 DOI: 10.3389/fnut.2023.1149137
    INTRODUCTION: Arctium lappa L. root has high nutritional and medicinal values and has been identified as a healthy food raw material by the Ministry of Health of the People's Republic of China.

    METHODS: In the present study, an aqueous two-phase system (ATPS) of polyethylene glycol (PEG)-(NH4)2SO4 was used to extract Arctium lappa L. polysaccharides (ALPs) from the Arctium lappa L. roots, the optimal extraction conditions of crude ALPs were optimized by using the single-factor experiment and response surface methodology. The structure and composition of ALPs were determined by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and high-performance liquid chromatography (HPLC). At the same time, the antioxidant activity of ALPs was investigated by in vitro antioxidant experiment.

    RESULTS: The optimized extraction parameters for extraction ALPs were as follows: the PEG relative molecular weight of 6,000, a quality fraction of PEG 25%, a quality fraction of (NH4)2SO4 18%, and an extraction temperature of 80°C. Under these conditions, the extraction rate of ALPs could reach 28.83%. FTIR, SEM and HPLC results showed that ALPs were typical acidic heteropolysaccharides and had uneven particle size distribution, an irregular shape, and a rough surface. The ALPs were chiefly composed of glucose, rhamnose, arabinose, and galactose with a molar ratio of 70.19:10.95:11.16:6.90. In addition, the ALPs had intense antioxidant activity in vitro with IC50 values in the ·OH radical (1.732 mg/ml), DPPH radical (0.29 mg/ml), and superoxide anion (0.15 mg/ml) scavenging abilities.

    DISCUSSION: The results showed that ATPS was an efficient method to extract polysaccharides and could be used for the extraction of other polysaccharides. These results indicated that ALPs had great prospects as a functional food and could be exploited in multiple fields.

  10. Wang X, Wang Y, Yang X, Mohd Nasiruddin NJB, Dong D, Samsudin SB, et al.
    Front Physiol, 2023;14:1212927.
    PMID: 37621760 DOI: 10.3389/fphys.2023.1212927
    Introduction: The efficacy of low-intensity blood flow restriction (LI-BFR) training programs in bone metabolism remains unclear compared to low-intensity (LI) training and high-intensity (HI) training. The aim of this review was to quantitatively identify the effects of LI-BFR training on changes in bone formation markers (i.e., bone-specific alkaline phosphatase, BALP), bone resorption (i.e., C-terminal telopeptide of type I collagen, CTX) and bone mineral density (BMD) compared with conventional resistance training programmes. Additionally, the effectiveness of walking with and without BFR was assessed. Methods: PubMed, Scopus, SPORTDiscus, Web of Science and Google Scholar databases were searched for articles based on eligibility criteria. Review Manager Version 5.4 was used for Meta-analysis. Physiotherapy Evidence Database (PEDro) was applied to assess the methodological quality of studies. Results: 12 articles were included in the meta-analysis, with a total of 378 participants. Meta-results showed that compared with LI training, LI-BFR training induced greater increments in BALP (young adults: MD = 6.70, p < 0.001; old adults: MD = 3.94, p = 0.002), slight increments in BMD (young adults: MD = 0.05, p < 0.00001; old adults: MD = 0.01, p < 0.00001), and greater decrements in CTX (young adults: MD = -0.19, p = 0.15; old adults: MD = -0.07, p = 0.003). Compared with HI training, LI-BFR training produced smaller increments in BALP (young adults: MD = -6.87, p = 0.24; old adults: MD = -0.6, p = 0.58), similar increments in BMD (MD = -0.01, p = 0.76) and similar decrements in CTX (young adults: MD = 0, p = 0.96; old adults: MD = -0.08, p = 0.13). Although there were only two studies on walking training intervention, walking training with BFR had a better effect on bone metabolism than training without BFR. Discussion: In conclusion, LI-BFR training induces greater improvements in bone health than LI training, but is less effective than HI training. Therefore, LI-BFR training may be an effective and efficient way to improve bone health for untrained individuals, older adults, or those undergoing musculoskeletal rehabilitation. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42023411837].
  11. Barnes DR, Rookus MA, McGuffog L, Leslie G, Mooij TM, Dennis J, et al.
    Genet Med, 2020 10;22(10):1653-1666.
    PMID: 32665703 DOI: 10.1038/s41436-020-0862-x
    PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.

    METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.

    RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar.

    CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

  12. Wang X, Yang X, Juzaily Bin Mohd Nasiruddin N, Wei S, Dong D, Bin Samsudin S
    Health Educ Behav, 2024 Feb 02.
    PMID: 38305027 DOI: 10.1177/10901981231216735
    Although physical activity (PA) has a profound impact on health, many college and university students are still physically inactive. There is some evidence to suggest that social support (SS) could impact the PA levels of students, but the internal relationship and specific effects are not very clear. The purpose of this review was to determine the strength of the relationship between SS and PA and examine whether any potential associations differed in terms of age, gender, and region among college and university students. Studies were identified using the following electronic databases: PubMed, SPORTDiscus, Web of Science, and Sociological Abstracts. Moderator analyses investigating the effects of students' age, gender, and region (nation) were performed. This review included 19 articles. The results showed total SS was significantly associated with PA (r = 0.30, 95% confidence interval [CI]: [0.22, 0.37], p < .001). With respect to different types of support, friend support was more strongly associated with PA than family support. Gender factors had a significant moderating effect on the correlation between SS and PA (QM = 17.433, p < .001). Separate analyses examining the moderating effects of gender (percentage of females) found that the association between SS and PA was stronger with the increase in female percentage. In conclusion, SS is an important factor associated with PA levels and should foster SS within intervention programs according to types of SS and gender differences to increase PA levels among college and university students.
  13. Shahzad MF, Xu S, Lim WM, Yang X, Khan QR
    Heliyon, 2024 Apr 30;10(8):e29523.
    PMID: 38665566 DOI: 10.1016/j.heliyon.2024.e29523
    The advancement of artificial intelligence (AI) and the ubiquity of social media have become transformative agents in contemporary educational ecosystems. The spotlight of this inquiry focuses on the nexus between AI and social media usage in relation to academic performance and mental well-being, and the role of smart learning in facilitating these relationships. Using partial least squares-structural equation modeling (PLS-SEM) on a sample of 401 Chinese university students. The study results reveal that both AI and social media have a positive impact on academic performance and mental well-being among university students. Furthermore, smart learning serves as a positive mediating variable, amplifying the beneficial effects of AI and social media on both academic performance and mental well-being. These revelations contribute to the discourse on technology-enhanced education, showing that embracing AI and social media can have a positive impact on student performance and well-being.
  14. Yuan Y, Ji X, Yang X, Wang C, Samsudin S, Omar Dev RD
    Int J Environ Res Public Health, 2022 Sep 12;19(18).
    PMID: 36141724 DOI: 10.3390/ijerph191811451
    The effect of persistence of physical exercise on the psychological and emotional aspects of primary school students is studied to improve the comprehensive quality of current Chinese primary school students and explore the effect of physical exercise on students' emotions under the science, technology, engineering, art, mathematics (STEAM) education concept. First, students in a primary school in Nanchang are taken as the survey participants. Second, by formulating a physical exercise scale and a psychological and emotional scale, the current situation of physical exercise of primary school students is investigated by means of mathematical statistics. Finally, the current situation of physical exercise and the overall situation of positive psychological emotions of primary school students are analyzed, and the effect of physical exercise on the positive psychological emotions of primary school students is studied. The data show that there are significant differences in the amount of exercise and its three dimensions of intensity, time, and frequency, as well as the scores of positive emotions in the gender dimension, with the boys scoring higher than the girls. In terms of grades, students in grades 1, 2, and 6 are higher than students in grades 3, 4, and 5 on the level of a small amount of exercise, while students in grades 3, 4, and 5 are higher than the other three grades in terms of a moderate amount of exercise. Moreover, in the aspect of positive psychological emotions, the lower-grade students are obviously higher than the upper-grade students, and the second- and third-grade students present marginal significance, p = 0.058. The correlation and regression between physical exercise and positive psychological emotions are calculated and analyzed, and it is found that there is a significant positive correlation between physical exercise indicators and positive psychological emotions, with a correlation coefficient of 0.297. Physical exercise explains 8.8% of positive emotions. This research also makes relevant recommendations for students and schools and has played a role in strengthening the physical exercise and mental health of primary and secondary school students. Greater attention to the physical exercise of primary school students is recommended.
  15. Mei T, Li Y, Li X, Yang X, Li L, Yan X, et al.
    Int J Sports Med, 2023 Dec 20.
    PMID: 38122824 DOI: 10.1055/a-2234-0159
    This study develops a comprehensive genotype-phenotype model for predicting the effects of resistance training on leg press performance. A cohort of physically inactive adults (N=193) underwent 12 weeks of resistance training, and measurements of maximum isokinetic leg press peak force, muscle mass, and thickness were taken before and after the intervention. Whole-genome genotyping was performed, and genome-wide association analysis identified 85 novel SNPs significantly associated with changes in leg press strength after training. A prediction model was constructed using stepwise linear regression, incorporating 7 lead SNPs that explained 40.4% of the training effect variance. The polygenic score showed a significant positive correlation with changes in leg press strength. By integrating genomic markers and phenotypic indicators, the comprehensive prediction model explained 75.4% of the variance in the training effect. Additionally, five SNPs were found to potentially impact muscle contraction, metabolism, growth, and development through their association with REACTOME pathways. Individual responses to resistance training varied, with changes in leg press strength ranging from -55.83% to 151.20%. The study highlights the importance of genetic factors in predicting training outcomes and provides insights into the potential biological functions underlying resistance training effects. The comprehensive model offers valuable guidance for personalized fitness programs based on individual genetic profiles and phenotypic characteristics.
  16. Xu YJ, Jiang F, Song J, Yang X, Shu N, Yuan L, et al.
    J Agric Food Chem, 2020 Aug 19;68(33):8847-8854.
    PMID: 32806128 DOI: 10.1021/acs.jafc.0c03539
    The thermal pretreatment of oilseed prior to oil extraction could increase the oil yield and improve the oil quality. Phenolic compounds are important antioxidants in rapeseed oil. In this study, we investigated the impact of thermal pretreatment method on the rapeseed oil based on phenolic compound levels. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis showed that the phenolic compound contents in the microwave-pretreated oil were higher than those in the oven- and infrared-treated oils. Sinapic acid (SA) and canolol (CA), which are the top two phenolic compounds in rapeseed oil, exerted well 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with IC50 values of 8.45 and 8.80 μmol/L. The cell experiment uncovered that SA and CA have significant biological activities related to rapeseed oil quality, including increase of antioxidant enzymes superoxide dismutase (SOD), alleviation of reactive oxygen species (ROS), and cytotoxicity of HepG2 cells after the intake of excessive oleic acid. Further investigation indicated that SA and CA reduced cell apoptosis rate through Bax-Bcl-2-caspase-3 and p53-Bax-Bcl-2-caspase-3, respectively. Taken together, our findings suggest that microwave pretreatment is the best method to improve the content of phenolic compounds in rapeseed oil compared with oven and infrared pretreatments.
  17. Liu X, Yang X, Shao J, Hong Y, Gopinath SCB, Chen Y, et al.
    J Anal Methods Chem, 2020;2020:6528572.
    PMID: 32309010 DOI: 10.1155/2020/6528572
    Cervical, ovarian, and endometrial cancers are common in the female reproductive system. Cervical cancer starts from the cervix, while ovarian cancer develops when abnormal cells grow in the ovary. Endometrial or uterine cancer starts from the lining of the womb in the endometrium. Approximately 12,000 women are affected every year by cervical cancer in the United States. Squamous cell carcinoma antigen (SCC-Ag) is a well-established biomarker in serum for diagnosing gynecological cancers, and its levels were observed to be elevated in cervical, ovarian, and endometrial cancer patients. Moreover, SCC-Ag was used to identify the tumor size and progression stages. Various biosensing systems have been proposed to identify SCC-Ag; herein, enhanced interdigitated electrode sensing is presented with the use of gold nanoparticles (GNPs) to conjugate an antigen/antibody. It was proved that the limit of detection is 62.5 fM in the case of antibody-GNP, which is 2-fold higher than that by SCC-Ag-GNP. Furthermore, the antibody-GNP-modified surface displays greater current increases with concomitant dose-dependent SCC-Ag levels. High analytical performance was shown by the discrimination against α-fetoprotein and CYFRA 21-1 at 1 pM. An enhanced sensing system is established for gynecological tumors, representing an advance from the earlier detection methods.
  18. Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, et al.
    J Clin Oncol, 2020 03 01;38(7):674-685.
    PMID: 31841383 DOI: 10.1200/JCO.19.01907
    PURPOSE: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized.

    METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.

    RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.

    CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links