Publications by authors named "Anna Li"

223 Publications

Gender Gap in Neurology Research Authorship (1946-2020).

Front Neurol 2021 23;12:715428. Epub 2021 Aug 23.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, United States.

Gender disparity in the field of neurology impedes scientific advancements and innovations. In 2018, 45.0% of neurology and neurological subspecialty residents were women. Despite a notable rise in the proportion of women neurologists over the past decades, inequalities regarding publication proportions between men and women persist in the field. This cohort study examines authorship trends in articles published in 155 international neurology journals, identified as those listed in the annual Journal Citation Reports' "Clinical Neurology" section. Authors' names, authorship positions and countries of affiliation were extracted from PubMed for indexed articles published from 1946 to 2020. Gender-API (a validated and highly accurate application program interface) assigned binary genders to authors. Author gender proportions were compared across subspecialties, authorship position and years. In 303,385 unique articles, 1,663,036 total authors were identified of which 34.1% were women. Neuroradiology demonstrated the lowest proportion of women authors (21.3%), while neurogenetics displayed the highest (44.5%). In articles with multiple authors, both men and women last authors were more likely to publish with a male first author, though this was significantly more pronounced for men last authors (1.86 vs. 1.08; < 0.001). From 2002 to 2020, women remained in the minority of last (24.6%), first (36.2%), and middle author positions (35.8%). The authorship gender distribution in neurological journals neither reflects the gender proportion of neurologists in the field overall nor in any subspecialty examined. We also find a tendency for senior and junior authors of the same gender to publish together which perpetuates authorship inequity. Further work is needed to identify underlying causes so that interventions might be developed to improve authorship diversity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.715428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419229PMC
August 2021

Trans-cricoid thyroid injection of local anaesthesia: a serious complication.

BMJ Case Rep 2021 Aug 17;14(8). Epub 2021 Aug 17.

Respiratory Medicine, Flinders Medical Centre, Bedford Park, South Australia, Australia.

Transcricothyroid membrane (CTM) injection of local anaesthesia is widely used during bronchoscopic procedures. It is an effective way of delivering topical anaesthesia, and has been shown to reduce patient discomfort, improve clinician satisfaction and reduce overall sedation requirements. Risks from this procedure are uncommon and usually minor. Localisation of the CTM is usually performed clinically by palpation of anatomical landmarks and can vary depending on clinician skillset and experience. Clinical identification may be less accurate compared with ultrasound guidance in identifying puncture site, however, ultrasound is not always readily available and seldom used for this purpose. This case describes a rare complication following attempted local anaesthetic infiltration into the cricothyroid space, after clinical identification of puncture site. An obstructive fluid-filled mass formed around the site of injection on the right vocal cord; resulting in airway compromise, abandonment of procedure and subsequent intubation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2021-244493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372785PMC
August 2021

[ω-3 Fatty acids intake level of vegetarians in Shanghai].

Wei Sheng Yan Jiu 2021 Jul;50(4):558-563

Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.

Objective: To assess the ω-3 fatty acids intake level of vegetarians in Shanghai, and compare with the sex and age matched omnivores.

Methods: The present observational study included 282 vegetarians aged 18 to 60 years old who had been vegetarian for at least one year and 282 sex and age matched omnivores recruited among Shanghai citizens. Daily food consumption was assessed through frequency and average intake of 149 kinds of food by food frequency questionnaire(FFQ) conducted by experienced dietitians. Dietary intake of ALA, EPA and DHA was calculated by R(Software). The differences of ω-3 fatty acids dietary intake between vegetarians and omnivores were analyzed with non-parametric test.

Results: The ALA intake of vegetarian group was(1669.00±1340.67)mg/d, which was significantly higher than that of omnivore group((1298.56±1041.96)mg/d). However, the EPA intake of vegetarian group((8.45±12.69)mg/d) was significantly less than the omnivore group((128.63±144.15)mg/d). The DHA intake of vegetarian group((28.75±35.38)mg/d) was also significantly less than the omnivore group((236.88±223.05)mg/d). Most of the dietary intake of EPA and DHA was supplied by seafood.

Conclusion: Vegetarians EPA and DHA intake was significantly lower than omnivores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.04.005DOI Listing
July 2021

Outcomes of a holistic admissions process in an Accelerated Baccalaureate Nursing Program.

J Prof Nurs 2021 Jul-Aug;37(4):714-720. Epub 2021 May 12.

Duke University School of Nursing, 307 Trent Drive, Durham, NC 27710, United States of America.

An accelerated bachelor of science in nursing program adopted holistic admissions practices to increase diversity in the student body. This quality improvement project aimed to compare three cohorts of students accepted before holistic admissions practices to three cohorts accepted after holistic admissions. The authors examined demographic data, on-time graduation rate, licensure exam passing rate, remediation status, and student perceptions expressed on exit surveys. After holistic admissions were implemented, student diversity increased and on-time graduation and licensure exam pass rates were maintained. The need for student remediation decreased after holistic admissions were implemented, and student perceptions of their classmates and the relevance of their schooling to their future professional career increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.profnurs.2021.05.006DOI Listing
July 2021

Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification.

Front Oncol 2021 8;11:632609. Epub 2021 Jun 8.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC).

Methods: In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients.

Results: Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased amplification than in patients with intestinal-type GC and was associated with increased expression in patients with diffuse-type GC.

Conclusions: Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, amplification was more common, and in those with diffuse-type GC, expression was more common. Targeted therapy may be beneficial for these patient subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.632609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217656PMC
June 2021

A prototype closed-loop brain-machine interface for the study and treatment of pain.

Nat Biomed Eng 2021 Jun 21. Epub 2021 Jun 21.

Department of Anesthesiology, Perioperative Care and Pain, New York University School of Medicine, New York, NY, USA.

Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain-machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top-down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41551-021-00736-7DOI Listing
June 2021

Hepatoma upregulated protein and Ki-67 expression in resectable hepatocellular carcinoma.

J Chin Med Assoc 2021 Jun;84(6):623-632

Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: Hepatoma upregulated protein (HURP) and Ki-67 have been identified as cancer-related genes involved in cell growth and proliferation. Previous experimental studies have suggested an essential role for HURP expression in liver carcinogenesis. However, data regarding HURP expression in hepatocellular carcinoma (HCC) and its correlation with patient outcomes are limited. In this study, we examined the clinicopathologic features associated with HURP expression in HCC, and compared them to the results of the Ki-67 study.

Methods: Eighty-seven resected HCC at tumor, node, metastasis (TNM) stages I (n = 28), II (n = 29), and III (n = 30) were evaluated. HURP and Ki-67 expression were assessed by immunohistochemistry. Multivariate analysis was used to examine the prognostic significance of HURP and Ki-67 expression.

Results: HURP expression in HCC tissue was observed in 59% of patients and associated with female sex, low white blood cell count, and low platelet count. Ki-67 expression was observed in 67% of patients and associated with younger age, higher serum α-fetoprotein (AFP) levels, and frequent microvascular invasion. Univariate analysis showed that factors related to overall survival were: age >55 years, AFP >20 ng/mL, indocyanine green retention rate at 15 minutes (ICG-15) >15%, tumor size >5 cm, multiple tumors, macrovascular invasion, microvascular invasion, Ki-67 expression, and serum vascular endothelial growth factor >170 pg/mL. HURP expression was not associated with postresection survival. Multivariate analysis indicated that macrovascular invasion, multiple tumors, ICG-15 >15%, and Ki-67 expression were independent factors for overall survival. Multiple tumors and Ki-67 expression were independent factors related to recurrence-free survival.

Conclusion: In our study, HURP expression in HCC tissue was not associated with post-resection survival. Ki-67 expression was an independent prognostic factor for survival. Our results suggest that the effect of HURP activity on growth, invasion, and postresection outcome of HCC in actual patients is less than previously demonstrated in experimental studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCMA.0000000000000540DOI Listing
June 2021

Burden of smoking in Asia-Pacific countries.

Tob Induc Dis 2021 15;19:28. Epub 2021 Apr 15.

Centre for Learning Enhancement and Research, The Chinese University of Hong Kong, Hong Kong.

Introduction: Smoking is a modifiable risk factor for many diseases. The public should recognize the impact of smoking on their health and their wealth. The current study aimed to evaluate the cost burden of smoking to target Asia-Pacific countries.

Methods: The current study estimated the annual spending and lifetime spending of smokers in the target Asia-Pacific countries (Hong Kong, Malaysia, Thailand, South Korea, Singapore, and Australia) on purchasing cigarettes, as well as predicted the revenue that could be generated if smokers spent the money on investment instead of buying cigarettes. Smokers' spending on cigarettes and the potential revenue generated from investment were estimated based on the selling prices of cigarettes, Standards & Poor's 500 Index, and life expectancies of smokers. Data were extracted from reports released by the World Health Organization or government authorities.

Results: The annual expenses (in US$) on purchasing one pack of cigarettes, in decreasing order, were: Australia ($5628.30), Singapore ($3777.75), Hong Kong ($2799.55), Malaysia ($1529.35), South Korea ($1467.30), and Thailand ($657.00). The lifetime spending on purchasing one pack of cigarettes each day were: Australia ($308993.67), Singapore ($207398.48), Hong Kong ($151735.61 for male and $166853.18 for female), South Korea ($80261.31), Malaysia ($72338.26), and Thailand ($31207.50).

Conclusions: The cost burden of smoking is high from a smoker's perspective. Smokers should recognize the high economic burden and quit smoking to enjoy better health and wealth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18332/tid/133633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049108PMC
April 2021

Predicting the risk of fetal macrosomia at pregnancy in Shandong province: a case-control study.

J Matern Fetal Neonatal Med 2021 Apr 18:1-7. Epub 2021 Apr 18.

Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Shandong University, Jinan, China.

Background And Aim: Macrosomia is used to describe an infant born with excessively high weight, and it brings lots of unexpected risks in clinical work. Macrosomia causes considerable challenges for both physicians and pregnant women. Our objectives were to identify factors in gravida to be associated with the risk of macrosomia, to guide clinical prevention and treatment.

Methods: The study assessed risk factors of macrosomia by comparison with normal birth weight neonates, and a case-control study was conducted at Shandong Provincial Maternity and Child Healthcare Hospital. We followed and selected the relevant indicators of gravida who gave birth to macrosomia or normal infants, and applied statistical analysis to identify clinical indicators related to macrosomia.

Results: Maternal blood glucose (OR 3.88 (1.07, 14.15)), history of abnormal conception (OR 18.44 (1.05, 322.89)), situation of menarche (OR 13.53 (1.28, 142.66)), and menstrual cycle of gravida (OR 13.24 (1.17, 150.24)) were significant influencing factors of macrosomia, but did not appear in the univariate analysis. Adding gestational age at delivery (OR 4.00 (1.45, 11.09)), triglyceride (OR 0.01 (<0.01, 0.40)), and MBI (OR 46.35 (2.08, >99.99)) of pregnant women, the area under the curve (AUC) curve was drawn for forecasting the risk of macrosomia, and the value of AUC was 0.9174. The triglyceride blood index of pregnant women was the only one that was inversely proportional to the probability of giving birth to macrosomic infants. The low-density lipoprotein (LDL) (OR 0.29 (0.12, 0.72)) and total cholesterol (OR 0.39 (0.20, 0.75)) were important factors in univariate analysis, and both of them were negative correlation factors of macrosomia. All influencing factors in multivariate analysis were selected for drawing a receiver operating characteristic (ROC) curve, and the value of the AUC was 0.9174.

Conclusions: This analysis could therefore accurately predict the risk of pregnant women who would deliver macrosomic infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2021.1910662DOI Listing
April 2021

Pulmonary carcinoid presenting in pregnancy with an unusual radiological feature.

BMJ Case Rep 2021 Apr 15;14(4). Epub 2021 Apr 15.

Radiology, Flinders Medical Centre, Bedford Park, South Australia, Australia.

Pulmonary carcinoid tumours are a rare form of malignancy that often present with clinical heterogeneity and are challenging to diagnose. Diagnosis during pregnancy is further complicated by delays in imaging and procedures to minimise harm to the fetus. This case describes a primigravid healthcare worker who was diagnosed with pulmonary carcinoid in her first trimester of pregnancy, with particular focus on the unique radiological findings of subpleural blebs as a feature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2020-241231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054049PMC
April 2021

Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19.

Part Fibre Toxicol 2021 03 11;18(1):11. Epub 2021 Mar 11.

Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Beitou Dist., Taipei, 112, Taiwan.

Background: Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.

Results: In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.

Conclusions: These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12989-021-00404-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948665PMC
March 2021

AMPAkines potentiate the corticostriatal pathway to reduce acute and chronic pain.

Mol Brain 2021 03 2;14(1):45. Epub 2021 Mar 2.

Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University School of Medicine, New York, NY, USA.

The corticostriatal circuit plays an important role in the regulation of reward- and aversion-types of behaviors. Specifically, the projection from the prelimbic cortex (PL) to the nucleus accumbens (NAc) has been shown to regulate sensory and affective aspects of pain in a number of rodent models. Previous studies have shown that enhancement of glutamate signaling through the NAc by AMPAkines, a class of agents that specifically potentiate the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, reduces acute and persistent pain. However, it is not known whether postsynaptic potentiation of the NAc with these agents can achieve the full anti-nociceptive effects of PL activation. Here we compared the impact of AMPAkine treatment in the NAc with optogenetic activation of the PL on pain behaviors in rats. We found that not only does AMPAkine treatment partially reconstitute the PL inhibition of sensory withdrawals, it fully occludes the effect of the PL on reducing the aversive component of pain. These results indicate that the NAc is likely one of the key targets for the PL, especially in the regulation of pain aversion. Furthermore, our results lend support for neuromodulation or pharmacological activation of the corticostriatal circuit as an important analgesic approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13041-021-00757-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923831PMC
March 2021

Bilateral temporomandibular joint dislocations post-bronchoscopy in a case of paclitaxel-induced pneumonitis.

BMJ Case Rep 2021 Feb 22;14(2). Epub 2021 Feb 22.

Respiratory, Flinders Medical Centre, Bedford Park, South Australia, Australia.

This case report presents the unusual complication of bilateral temporomandibular joint dislocation following bronchoscopy, highlighting the importance of recognising it as a differential diagnosis in patients having jaw symptoms. The delayed diagnosis in this case resulted in multiple unsuccessful reduction attempts under sedation, which added to the distress of the patient. Notably, the procedure yielded a rare diagnosis for the patient that intrinsically changed the management of her breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2020-240146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903068PMC
February 2021

Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain.

Prog Neurobiol 2021 Jun 2;201:102001. Epub 2021 Feb 2.

Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University Langone Health, New York, NY 10016, United States; Neuroscience Institute, New York University Langone Health, New York, NY 10016, United States; Department of Neuroscience and Physiology, New York University Langone Health, New York, NY 10016, United States. Electronic address:

Chronic pain affects one in four adults, and effective non-sedating and non-addictive treatments are urgently needed. Chronic pain causes maladaptive changes in the cerebral cortex, which can lead to impaired endogenous nociceptive processing. However, it is not yet clear if drugs that restore endogenous cortical regulation could provide an effective therapeutic strategy for chronic pain. Here, we studied the nociceptive response of neurons in the prelimbic region of the prefrontal cortex (PL-PFC) in freely behaving rats using a spared nerve injury (SNI) model of chronic pain, and the impact of AMPAkines, a class of drugs that increase central glutamate signaling, on such response. We found that neurons in the PL-PFC increase their firing rates in response to noxious stimulations; chronic neuropathic pain, however, suppressed this important cortical pain response. Meanwhile, CX546, a well-known AMPAkine, restored the anti-nociceptive response of PL-PFC neurons in the chronic pain condition. In addition, both systemic administration and direct delivery of CX546 into the PL-PFC inhibited symptoms of chronic pain, whereas optogenetic inactivation of the PFC neurons or administration of AMPA receptor antagonists in the PL-PFC blocked the anti-nociceptive effects of CX546. These results indicate that restoration of the endogenous anti-nociceptive functions in the PL-PFC by pharmacological agents such as AMPAkines constitutes a successful strategy to treat chronic neuropathic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pneurobio.2021.102001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126990PMC
June 2021

The effect of proton pump inhibitor uses on outcomes for cancer patients treated with immune checkpoint inhibitors: a meta-analysis.

Ann Transl Med 2020 Dec;8(24):1655

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Guangdong, Shenzhen, China.

Background: Proton pump inhibitors (PPIs) are commonly prescribed for preventing and treating gastrointestinal ulcers. In patients with advanced cancer, it is unclear whether concomitant use of immune checkpoint inhibitors (ICIs) and PPIs could result in poorer outcomes. This study investigates the impact of PPIs on the survival of cancer patients treated with ICIs.

Methods: PubMed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from January 1, 1970 to June 2, 2020 for studies reporting the prognoses of cancer patients receiving antitumor therapies including ICIs with or without PPIs. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Hazard ratios (HRs) with a 95% confidence interval (CI) were reported to express the effectiveness of ICIs in PPI users compared to non-PPI users, using a random effects model.

Results: Five studies were identified comprising 1,167 cancer patients. Concomitant use of PPIs with ICIs did not result in statistically significant changes in OS (HR 0.996; 95% CI: 0.486-1.447) and PFS (HR 0.858; 95% CI: 0.388-1.328). Statistical testing suggested heterogeneity among studies. Sensitivity analyses confirmed the stability of our results.

Conclusions: Concomitant ICI-PPI therapy does not appear to be significantly associated with OS or PFS, and further research on the effect of individual ICIs in different cancer patients is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-7498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812177PMC
December 2020

Gut Commensal Segmented Filamentous Bacteria Fine-Tune T Follicular Regulatory Cells to Modify the Severity of Systemic Autoimmune Arthritis.

J Immunol 2021 03 18;206(5):941-952. Epub 2021 Jan 18.

Department of Immunobiology, University of Arizona, Tucson, AZ 85719; and

Autoantibodies play a major pathogenic role in rheumatoid arthritis. T follicular helper (Tfh) cells promote germinal center B cell and Ab responses. Excessive Tfh cell responses lead to autoimmunity, and therefore, counterregulation is crucial. T follicular regulatory (Tfr) cells, mainly differentiated from T regulatory cells, can negatively regulate Tfh and germinal center B cells. Dysbiosis is involved in rheumatoid arthritis's pathogenesis. We previously demonstrated that the gut microbiota, segmented filamentous bacteria (SFB), promote autoimmune arthritis by inducing Tfh cells. However, little is known regarding whether gut microbiota influence systemic (nongut) Tfr cells, impacting gut-distal autoimmunity. In this study, using SFB in autoimmune arthritic K/BxN mice, we demonstrated that SFB-induced arthritis is linked to the reduction of Tfr cells' CTLA-4, the key regulatory molecule of Tfr cells. This SFB-mediated CTLA-4 reduction is associated with increased Tfr glycolytic activity, and glycolytic inhibition increases Tfr cells' CTLA-4 levels and reduces arthritis. The surface expression of CTLA-4 is tied to TCR signaling strength, and we discovered that SFB-reduced CTLA-4 is associated with a reduction of Nur77, an indicator of TCR signaling strength. Nur77 is known for repressing glycolytic activity. Using a loss-of-function study, we demonstrated that Nur77 haplodeficiency increases glycolysis and reduces CTLA-4 on Tfr cells, which is associated with increased arthritis and anti-glucose-6-phosphate isomerase titers. Tfr-specific deletion (KRN.Foxp3CreBcl-6) in autoimmune condition reveals that Tfr cells repress arthritis, Tfh cells, and autoantibody responses and that SFB can mitigate this repression. Overall, these findings demonstrated that gut microbiota distally impact systemic autoimmunity by fine-tuning Tfr cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2000663DOI Listing
March 2021

Pandemic aspect of dexamethasone: Molecular mechanisms and clinical application.

J Chin Med Assoc 2021 03;84(3):245-247

Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a corticosteroid applied in clinical medicine since 1957, especially in immune therapy fields. Herein, we present the characteristics of Dexamethasone, from molecular mechanisms such as genomic and nongenomic pathways by cellular signal regulations, to clinical applications in various phases of the disease. During COVID-19 pandemic, Dexamethasone given to patients who required oxygen or ventilation therapy showed improved life efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCMA.0000000000000485DOI Listing
March 2021

Genetic alterations in gastric cancer patients according to sex.

Aging (Albany NY) 2020 12 3;13(1):376-388. Epub 2020 Dec 3.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

To date, few reports have investigated the genetic alterations and clinicopathological features in gastric cancer (GC) according to sex. In total, 2673 GC patients receiving curative surgery were enrolled. Among the 2673 GC patients, 1979 (74.0%) patients were male. After propensity-score matching, 846 patients were enrolled for the analysis, including 423 males and 423 females. There was no significant difference in the clinicopathological features between the sexes. Regarding the initial recurrence pattern, the males were more likely to develop tumor recurrence and liver metastasis than the females, especially in stage III GC. Regarding the molecular analysis, the males had higher expression than the females, especially in stage III GC. In addition, the patients aged ≥ 65 years had higher expression than the patients younger than 65 years. The multivariate analysis demonstrated that sex was among the independent prognostic factors affecting overall survival (OS) and disease-free survival (DFS). Among the patients with liver metastases, expression was more common among the aged male patients. The males were associated with more tumor recurrence and higher expression than the females, especially in stage III GC. For GC patients with liver metastases, testing is recommended, especially among aged male patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835020PMC
December 2020

Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP).

Cancers (Basel) 2020 Nov 23;12(11). Epub 2020 Nov 23.

Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Background: The 5'-C-phosphate-G-3' island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors.

Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS.

Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of , , , and mutations but lower frequencies of , , and mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors.

Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700556PMC
November 2020

DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells.

Cancers (Basel) 2020 Nov 20;12(11). Epub 2020 Nov 20.

Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.

Background: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated.

Methods: The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells.

Results: Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown-induced cell migration and invasion of gastric cancer cells.

Conclusions: Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699785PMC
November 2020

Comparison of the Long-term Outcome Between Billroth-I and Roux-en-Y Reconstruction Following Distal Gastrectomy for Gastric Cancer.

J Gastrointest Surg 2021 08 17;25(8):1955-1961. Epub 2020 Nov 17.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan.

Background: Various reconstruction methods have been performed following distal gastrectomy; however, each reconstruction method has its own advantages and disadvantages. This study aims to compare the long-term outcomes between Billroth-I (B-I) and Roux-en-Y (RY) reconstruction after distal gastrectomy for gastric cancer.

Methods: A total of 459 patients who underwent distal gastrectomy (B-I: 166, RY: 293) were included. Postoperative endoscopic findings and biliary tract stone formation were compared between the two groups.

Results: At 1 year and 2 years postoperatively, gastric residue was more common in the RY group, gastritis was similar between groups, and bile reflux was more common in the B-I group. At 5 years postoperatively, gastric residue was similar between the groups, while gastritis and bile reflux were more common in the B-I group. Gastroesophageal reflux was more common in the B-I group at 1 year postoperatively, but gastroesophageal reflux became not significantly different between the groups at 2 and 5 years postoperatively. Gallstone formation was more common in the RY group and in patients aged ≥ 65 years.

Conclusion: During long-term follow-up, RY reconstruction was associated with lower incidence of bile reflux and gastritis, and higher incidence of gallstone formation than B-I reconstruction. The incidence of gastric residue was more common in the RY reconstruction group in the early postoperative period and became not significantly different between the two groups over time. For aged patients with RY reconstruction, cholecystectomy is recommended concurrently as gastrectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-020-04867-1DOI Listing
August 2021

Improved placental vascular repair in a rat preeclampsia model by implantation of endothelial progenitor cells treated with platelet microparticles.

Hypertens Pregnancy 2020 Nov 23;39(4):461-470. Epub 2020 Oct 23.

Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Maternal and Child Health Care Hospital , Jinan, China.

To detect the role of endothelial progenitor cells (EPCs) treated with platelet microparticles (PMPs) in preeclampsia. EPCs treated with/without PMPs were labeled and injected to PE rats. The differentiation of EPCs, the change of endothelial nitric oxide synthase (eNOS), blood pressure and proteinuria were measured. The blood pressure and proteinuria increased in each of PE groups, and were improved by EPCs which was strengthened by PMPs. Transplantation of EPCs increased placental angiogenesis. The trend of change of NO was the same as blood pressure. Transplantation of EPCs treated with PMPs improved blood pressure and proteinuria more effectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10641955.2020.1833914DOI Listing
November 2020

Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases.

Medicine (Baltimore) 2020 Oct;99(41):e22497

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital.

Rationale: Paragangliomas (PGLs) are rare neuroendocrine tumors that are strongly influenced by genetics, and succinate dehydrogenase-deficient PGLs appear to constitute one of the most important categories. Interestingly, somatic PGLs only possess genomic alterations involving the SDHB and SDHD subunits, and no SDHA alterations have been described. Here, we are presenting the clinical and genetic analyses of 2 cases with the first somatic SDHA variant identified in PGLs.

Patient Concerns: Here, we reported 2 family members with the diagnosis of PGL. Patient 1 is a 55-year-old woman with a functionally perigastric PGL that co-occurred with a gastric gastrointestinal stromal tumor (GIST), and patient 2 is a 43-year-old woman with a nonfunctionally pericardial PGL, who was the younger sister of the first patient.

Diagnoses: Imaging surveys of the 2 cases depicted the presence of a perigastric and a pericardial mass, respectively. A diagnosis of paragangliomas was established by immunohistochemistry (IHC).

Interventions: Both patients underwent single-stage resection of the lesion after preoperative oral α-adrenoceptor therapy for 2 weeks. We later performed comprehensive genomic profiling on the tumor samples, including PGL and GIST from patient 1 and PGL from patient 2, and searched for novel actionable mutations, including in all succinate dehydrogenase subunits, as the IHC results were negative for SDHB.

Outcomes: Both patients had an uneventful recovery after surgery and the sequencing showed a novel somatic variant in the SDHA gene on chromosome 5q11 (c.1945_1946delTT). Regular follow-up with biochemical testing and image studies showed no evidence of recurrence after a year for patient 1 and 6 years for patient 2.

Lessons: PGLs often lead to considerable diagnostic difficulty due to their multiple anatomical locations and variable symptoms, as presented by our cases. The comprehensive use of images and plasma/urine catecholamine measurement can aid the diagnosis of PGLs. In addition, our findings also demonstrate the usefulness and importance of genetic analysis of SDHA mutations in patients exhibiting SDHB IHC-negative PGL. Additional studies utilizing comprehensive genomic profiling are needed to identify the group of PGLs harboring this SDHA genomic alteration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000022497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544306PMC
October 2020

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis.

J Cell Mol Med 2020 11 6;24(22):13397-13407. Epub 2020 Oct 6.

Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province, Jinan, China.

Chorioamnionitis (CAM), as a common intrauterine infectious disease, is the leading cause of premature birth, stillbirth, neonatal infection and sepsis. The formyl peptide receptor 2 (FPR2) is a member of GPCRs widely distributed in a variety of tissues and is associated with many inflammatory diseases. With the discovery of FPR2 in human placenta, the possibility of exploring the function of FPR2 in obstetrics is evolving. The Resolvin D1 (RvD1) plays an important role in the resolution of inflammation by combining with FPR2. In this study, we evaluated the role of FPR2 and RvD1 in CAM, not only in the human placenta but also in mouse models. The expression of FPR2 increased in the placenta of CAM patients and the downstream PPARγ/NF-κB signalling changed accordingly. Moreover, Fpr2 mice were highly susceptible to LPS, displaying a worse CAM symptom, compared with WT mice. By establishing a model of trophoblast inflammation in vitro, it was confirmed that RvD1 rescued the effect of LPS on inflammation by combining with FPR2 and its downstream PPARγ/NF-κB pathway. Otherwise, RvD1 improved the preterm labour in a mouse model of CAM induced by LPS. Altogether, these findings show that RvD1 alleviated the inflammation of trophoblast in vivo and in vitro through FPR2/PPARγ/NF-κB pathway, suggesting RvD1/FPR2 might be a novel therapeutic strategy to alleviate CAM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.15963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701521PMC
November 2020

Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model.

Mol Brain 2020 09 23;13(1):129. Epub 2020 Sep 23.

Department of Anesthesiology, Perioperative Care and Pain, New York University School of Medicine, New York, NY, 10016, USA.

Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood at the network level. In this study, we recorded local field potentials from the ACC of freely moving rats. Animals were injected with complete Freund's adjuvant (CFA) to induce persistent inflammatory pain. Mechanical stimulations were administered to the hind paw before and after CFA administration. We found a significant increase in the high-gamma band (60-100 Hz) power in response to evoked pain after CFA treatment. Ketamine, however, reduced the high-gamma band power in response to evoked pain in CFA-treated rats. In addition, ketamine had a sustained effect on the high-gamma band power lasting up to five days after a single dose administration. These results demonstrate that ketamine has the potential to alter maladaptive neural responses in the ACC induced by chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13041-020-00670-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513294PMC
September 2020

The clinicopathological characteristics and genetic alterations between younger and older gastric cancer patients with curative surgery.

Aging (Albany NY) 2020 Aug 18;12(18):18137-18150. Epub 2020 Aug 18.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (<65 years) and older (≥65 years) patients. Genetic mutations were analyzed using mass spectrometric single nucleotide polymorphism genotyping technology, including 68 validated mutations within eight genes (, , , and the pathway) previously reported in relation to age. Younger patients were more likely to be female and have poor cell differentiation, diffuse-type tumors, less lymphovascular invasion, fewer liver metastases, and better 5-year overall survival (OS) (68.0% vs. 54.6%, <0.001) and disease-free survival (DFS) (65.4% vs. 53.0%, <0.001) rates than older patients. Regarding the genetic alterations, older patients had more microsatellite instability-high (MSI-H) tumors and more mutations than younger patients. Younger patients had significantly better OS and DFS rates than older patients for each pathological Tumor, Node, Metastasis (TNM) stage. Older patients had a significantly higher non-cancer related death rate than younger patients (36.2% vs. 12.3%, <0.001). Age was an independent prognostic factor in GC. In conclusion, age was associated with different clinicopathological features and genetic alterations in GC with curative surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585087PMC
August 2020

Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement.

Elife 2020 09 10;9. Epub 2020 Sep 10.

The Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to solely in a C3b-dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3-depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defense bridging pattern recognition and specific AP activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.60908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511233PMC
September 2020

The Clinicopathological Characteristics And Genetic Alterations of Signet-ring Cell Carcinoma in Gastric Cancer.

Cancers (Basel) 2020 Aug 17;12(8). Epub 2020 Aug 17.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have expression. For advanced GC without SRC, patients with liver metastasis tended to have expression, pathway mutations, mutations and MSI-H tumors. For advanced GC, expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have pathway mutations, mutations and expression; immunotherapy and targeted therapy may be beneficial for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12082318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463705PMC
August 2020

Evaluate the Differences in CT Features and Serum IgG4 Levels between Lymphoma and Immunoglobulin G4-Related Disease of the Orbit.

J Clin Med 2020 Jul 29;9(8). Epub 2020 Jul 29.

Department of Radiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)-characterized as tumors mimicking malignant orbital lymphoma (OL)-responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL.

Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios.

Results: Significantly related to IgG4-ROD (all < 0.05) were the presence of lesions with regular borders, presence of multiple lesions-involving both lacrimal glands on CT scans-higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674-1.000, = 0.005] vs. 0.766 [95% CI: 0.615-0.917, = 0.002]), higher sensitivity (0.889 [95% CI: 0.518-0.997] vs. 0.75 [95% CI: 0.509-0.913]), higher specificity (0.813 [95% CI: 0.544-0.960] vs. 0.778 [95% CI: 0.578-0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5).

Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9082425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463766PMC
July 2020

The Clinicopathological Features and Genetic Alterations in Epstein-Barr Virus-Associated Gastric Cancer Patients after Curative Surgery.

Cancers (Basel) 2020 Jun 10;12(6). Epub 2020 Jun 10.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Background: Epstein-Barr virus (EBV)-associated gastric cancer (GC) is one of four major gastric cancer types and is traditionally considered to be related to lymphoepithelioma-like GC. Few studies have investigated the clinical significance of EBV infection in intestinal/solid type, diffuse (poorly cohesive) type, and lymphoepithelioma-like GC.

Methods: A total of 460 GC patients receiving curative surgery were enrolled. The clinicopathological features, genetic alterations and prognoses were compared between patients with and without EBV infection.

Results: EBV-positive GC patients ( = 43) had more tumors located in the upper and middle stomach, more common in lymphoepithelioma-like carcinoma, more lymphoid stroma, fewer Helicobacter pylori infections, and higher programmed death-ligand 1 (PD-L1) expression than EBV-negative GC patients. For intestinal/solid type GC, EBV-positive tumors were more likely to be located in the upper and middle stomach, have more lymphoid stroma, fewer Helicobacter pylori infections, higher PD-L1 expression, and more liver metastases than EBV-negative tumors. For diffuse (poorly cohesive) type GC, EBV-positive tumors were more likely to be located in the upper stomach, and have more lymphoid stroma than EBV-negative tumors. For lymphoepithelioma-like GC, EBV-positive tumors had more PI3K/AKT pathway mutations than EBV-negative tumors.

Conclusions: Intestinal/solid type GC patients with EBV-positive tumors were associated with higher PD-L1 expression and more liver metastases, while lymphoepithelioma-like GC patients with EBV-positive tumors had more PI3K/AKT pathway mutations. Immunotherapy and targeted therapy may be beneficial for these groups of patients. Routine EBV survey is recommended in GC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12061517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352714PMC
June 2020
-->