Publications by authors named "Xin An"

129 Publications

Optimal first-line treatment for platinum-eligible metastatic urothelial carcinoma: Comparison of chemo-immunotherapy, immunotherapy, and chemotherapy- A systematic review and meta-analysis.

Clin Immunol 2022 Jan 11:108927. Epub 2022 Jan 11.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address:

Background: The role of first-line of immunotherapy in metastatic urothelial carcinoma (mUC) remains unclear. This meta-analysis aimed to explore an optimal first-line treatment strategy for mUC patients.

Methods: We carried out a meta-analysis between chemo-immunotherapy, immunotherapy, and chemotherapy in mUC based on randomized trials. The outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.

Results: Three trials involving 3238 patients were included. PD-1/PD-L1 inhibitor plus platinum-based chemotherapy was associated with the improvements of OS (HR, 0.85; 95% CI 0.75-0.99), PFS (HR, 0.80; 95% CI 0.71-0.90) and ORR (OR, 1.32; 95% CI 1.07-1.63) when compared with platinum-based chemotherapy, but not with better DCR (OR, 1.07; 95% CI 0.78-1.46). PD-1/PD-L1 inhibitor alone was associated with worse ORR (OR, 0.38; 95% CI 0.17-0.87) and DCR (OR, 0.20; 95% CI 0.16-0.25) when compared with platinum-based chemotherapy while it did not statistically reduce the risk of mortality (HR 0.97 for entire cohort; 0.90 for PD-L1 high cohort). In safety analyses, the incidence of adverse events (AEs) between regimens showed no difference, but the frequency of AEs of grade 3 or severity was higher in chemo-immunotherapy compared to chemotherapy.

Conclusions: Compared with platinum-based chemotherapy, chemo-immunotherapy is associated with significantly improved PFS, OS, and ORR in the first-line therapy for mUC at the expanse of increased toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clim.2022.108927DOI Listing
January 2022

Discovery of a widespread presence bunyavirus that may have symbiont-like relationships with different species of aphids.

Insect Sci 2021 Dec 7. Epub 2021 Dec 7.

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.

Aphids are important agricultural pests, vectors of many plant viruses and have sophisticated relationships with symbiotic microorganisms. Abundant asymptomatic RNA viruses have been reported in aphids due to the application of RNA-seq, but aphid-virus interactions remain unclear. Bunyavirales is the most abundant RNA virus order, which can infect mammals, arthropods and plants. However, many bunyaviruses have specific hosts, such as insects. Here, we discovered 18 viruses from 10 aphid species by RNA-seq. Importantly, a widespread presence bunyavirus, Aphid bunyavirus 1 (ABV-1), was determined to have a wide host range, infecting and replicating in all 10 tested aphid species. ABV-1 may be transmitted horizontally during feeding on plant leaves and vertically through reproduction. In a comparison of the physiological parameters of ABV-1 and ABV-1 strains of pea aphid, higher ABV-1 titers reduced the total nymphal duration and induced the reproduction. Moreover, viral titer significantly affected the lipid and protein contents in pea aphids. In summary, we proposed that ABV-1 may have stable symbiont-like relationships with aphids, and these observations may provide a new direction for studying bunyaviruses in aphids and establishing a model for virus-aphid interactions. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-7917.12989DOI Listing
December 2021

Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002).

Clin Cancer Res 2021 Nov 22. Epub 2021 Nov 22.

Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Purpose: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR) and HER2-positive (HER2) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy.

Patients And Methods: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses.

Results: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, = 196) or trastuzumab plus chemotherapy (CT group, = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group.

Conclusions: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HRHER2 MBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-21-3435DOI Listing
November 2021

Treatment Outcome of Different Chemotherapy in Patients With Relapsed or Metastatic Malignant Urachal Tumor.

Front Oncol 2021 15;11:739134. Epub 2021 Sep 15.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Malignant urachal tumor is a rare subtype of genitourinary cancer. Our aim was to explore the optimal chemotherapy regimens for relapsed or metastatic urachal carcinoma.

Materials And Methods: We retrospectively enrolled 24 adult patients with relapsed or metastatic urachal carcinoma from January 2014 to September 2020 at Sun Yat-sen University Cancer Center. We summarized the chemotherapy regimens and classified them as fluorouracil based, platinum based, and paclitaxel based. Nine patients received XELOX (capecitabine and oxaliplatin) regimens, seven patients received TX (paclitaxel and capecitabine) regimens, and eight of them received chemotherapy including GP (gemcitabine and cisplatin), TP (paclitaxel and cisplatin), TN (paclitaxel and nedaplatin), and tislelizumab.

Results: The disease control rate was 75%. Among all patients, one patient treated with XELOX achieved partial remission (PR), while 17 patients showed stable disease. The median progression-free survival (PFS) and overall survival (OS) in all treated patients was 7.43 and 29.7 months, respectively. The patients receiving first-line platinum-based chemotherapy presented better PFS than those without platinum (median PFS 8.23 . 3.80 months, = 0.032), but not significant for OS between two groups. There is no significant difference in PFS and OS for fluorouracil-based and paclitaxel-based groups as first-line regimen. Next-generation gene sequencing revealed TP53 mutation and low tumor mutational burden in five out of seven cases.

Conclusion: The platinum-based chemotherapy regimen is effective for relapsed or metastatic urachal carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.739134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479186PMC
September 2021

Representation of molecules for drug response prediction.

Brief Bioinform 2022 Jan;23(1)

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

The rapid development of machine learning and deep learning algorithms in the recent decade has spurred an outburst of their applications in many research fields. In the chemistry domain, machine learning has been widely used to aid in drug screening, drug toxicity prediction, quantitative structure-activity relationship prediction, anti-cancer synergy score prediction, etc. This review is dedicated to the application of machine learning in drug response prediction. Specifically, we focus on molecular representations, which is a crucial element to the success of drug response prediction and other chemistry-related prediction tasks. We introduce three types of commonly used molecular representation methods, together with their implementation and application examples. This review will serve as a brief introduction of the broad field of molecular representations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bib/bbab393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769696PMC
January 2022

Evolution of Non-Gaussian Hydrodynamic Fluctuations.

Phys Rev Lett 2021 Aug;127(7):072301

Department of Physics, University of Illinois, Chicago, Illinois 60607, USA.

In the context of the search for the QCD critical point using non-Gaussian fluctuations, we obtain the evolution equations for non-Gaussian cumulants to the leading order of the systematic expansion in the magnitude of thermal fluctuations. We develop a diagrammatic technique in which the leading order contributions are given by tree diagrams. We introduce a Wigner transform for multipoint correlators and derive the evolution equations for three- and four-point Wigner functions for the problem of nonlinear stochastic diffusion with multiplicative noise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevLett.127.072301DOI Listing
August 2021

Role of a Modified Urothelium Immune Prognostic Index in Patients With Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1-Based Therapy.

Front Mol Biosci 2021 12;8:621883. Epub 2021 Aug 12.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

The use of antibodies against programmed death receptor-1 (PD-1) and its ligand (PD-L1) has improved survival in metastatic urothelial carcinoma (mUC) patients. However, reliable and convenient biomarkers of early responses and outcomes are still lacking. We retrospectively screened mUC patients who received anti-PD-1/PD-L1-based therapy at our institute. A modified urothelium immune prognostic index (mUIPI) based on the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was developed to characterize the three groups as good, intermediate, and poor mUIPI. Major observations were progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). We identified 52 mUC patients with a median follow-up time of 29.8 months (95% CI, 26.3-53.2). Low NLR was with improved PFS and OS (hazard ratio [HR], 0.40, 95% CI, 0.18-0.92; HR, 0.27, 95% CI, 0.11-0.69, respectively). Normal LDH was associated with improved PFS but not OS (HR, 0.22, 95% CI, 0.10-0.52; HR, 0.86, 95% CI, 0.34-2.13, respectively). The median PFS for the poor, intermediate, and good mUIPI groups was 1.97 months (95% CI, 1.15 to NR), 3.48 months (95% CI, 1.58 to NR), and 14.52 months (95% CI, 5.75 to NR), respectively ( < 0.001). The median OS for the poor, intermediate, and good mUIPI was 12.82, 18.11, and 34.87 months, respectively ( = 0.28). A good mUIPI was associated with a higher DCR compared to intermediate and poor mUIPI (odds ratio [OR] 7.58, 95% CI, 1.73-43.69; OR, 6.49, 95% CI, 0.14-295.42, respectively). In the subgroup analysis, a good mUIPI was associated with improved PFS in the subgroups of male patients and patients with low urinary tract primary tumors, liver metastases, non-first-line treatment, and monotherapy. mUIPI predicts early responses in mUC patients who received anti-PD-1/PD-L1-based therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.621883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387676PMC
August 2021

Identification and Validation of Immune-Related Methylation Clusters for Predicting Immune Activity and Prognosis in Breast Cancer.

Front Immunol 2021 30;12:704557. Epub 2021 Jun 30.

Department of Breast Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

The role of DNA methylation of breast cancer-infiltrating immune cells has not been fully explored. We conducted a cohort-based retrospective study analyzing the genome-wide immune-related DNA methylation of 1057 breast cancer patients from the TCGA cohort and GSE72308 cohort. Based on patients' overall survival (OS), a prognostic risk score system using 18 immune-related methylation genes (IRMGs) was established and further validated in an independent cohort. Kaplan-Meier analysis showed a clear separation of OS between the low- and high-risk groups. Patients in the low-risk group had a higher immune score and stromal score compared with the high-risk group. Moreover, the characteristics based on 18-IRMGs signature were related to the tumor immune microenvironment and affected the abundance of tumor-infiltrating immune cells. Consistently, the 18-IRMGs signatures showed similar influences on immune modulation and survival in another external validation cohort (GSE72308). In conclusion, the proposed 18-IRMGs signature could be a potential marker for breast cancer prognostication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.704557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278823PMC
December 2021

A new way for punicalagin to alleviate insulin resistance: regulating gut microbiota and autophagy.

Food Nutr Res 2021 1;65. Epub 2021 Jul 1.

Department of Nutrition and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, China.

Background: Insulin resistance, defined as a diminished ability to respond to the stimulation of insulin, is the main line for a variety of metabolic-related diseases. Punicalagin (PU), a hydrolyzable tannin of pomegranate juice, exhibits multiple biological properties, including anti-oxidant, anti-cancer and anti-inflammatory activities.

Objective: This research study aimed at determining the protective effect of PU on insulin resistance and to uncover the underlying mechanism based on the gut microbiota, IKKβ/NF-κB pathway, and autophagy.

Design: An insulin resistance animal model was established using C57BL/6 mice fed with a high-fat diet (HFD) for 8 weeks. The model included two groups continuing a HFD for 12 weeks with or without administering via gavage with PU 20 mg/kg/day. Changes in fasting plasma glucose levels, fasting serum insulin levels, glucose and insulin tolerance, glycolipid metabolism, gut microbiota composition (16S rRNA gene sequencing), inflammatory responses, and autophagy in the liver were evaluated. Body weight gain, glycolipid metabolic disorder, liver injury, as well as systemic and hepatic insulin sensitivity, were significantly attenuated after supplementing with PU.

Results: This research study revealed that PU alleviated HFD-induced glucose and lipid disorders, liver injury and insulin resistance; decreased the ratio, decreased the abundance of and and increased ; and decreased serum and liver tumor necrosis factor-alpha and interleukin-1β levels, inhibited liver IKKβ and NF-κB phosphorylation; and increased liver autophagy-related proteins LC3-II, P62, and Beclin1, and increased the number of liver autophagosomes.

Conclusion: PU can improve HFD-induced insulin resistance, improved liver glucose and lipid metabolism disorder and liver injury, and the potential mechanism is that PU inhibited the IKKβ/NF-κB inflammatory pathway by regulating gut microbiota homeostasis and up-regulating liver autophagy activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.29219/fnr.v65.5689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254469PMC
July 2021

Unfractionated Heparin Improves the Intestinal Microcirculation in a Canine Septic Shock Model.

Mediators Inflamm 2021 23;2021:9985397. Epub 2021 Jun 23.

Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Alterations of microcirculation are associated with organ hypoperfusion and high mortality in septic shock. This study is aimed at investigating the effects of unfractionated heparin (UFH) on intestinal microcirculatory perfusion and systemic circulation in a septic shock model.

Methods: Twenty-four beagle dogs were randomly allocated into four groups: (a) sham group: healthy controls, (b) shock group: septic shock induced by , (c) basic therapy group: septic shock animals treated with antibiotics and 10 ml/kg/h saline, and (d) heparin group: septic shock animals treated with basic therapy plus UFH. Hemodynamic variables were measured within 24 h after administration. The intestinal microcirculation was simultaneously investigated with a sidestream dark-field imaging technique. Additionally, the function of vital organs was evaluated at 12 h postadministration (T12).

Results: induced a progressive septic shock in which the mean arterial pressure (MAP) decreased and lactate levels sharply increased, accompanied by deteriorated microvessel perfusion. While basic therapy partially improved the microvascular flow index and the perfused microvessel density in the jejunal villi, UFH significantly restored major microcirculation variables at T12. Physiological variables, including MAP, urine output, and lactate levels, were improved by UFH, whereas some hemodynamic indices were not affected by UFH. With respect to organ function, UFH increased the platelet count and decreased the creatinine level.

Conclusions: UFH improves microcirculatory perfusion of the small intestine independently of the changes in systemic hemodynamic variables in a canine model of septic shock, thereby improving coagulation and renal function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9985397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245220PMC
January 2022

A Novel Ferroptosis-Related Gene Signature Predicts Overall Survival of Breast Cancer Patients.

Biology (Basel) 2021 Feb 14;10(2). Epub 2021 Feb 14.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.

Breast cancer is the second leading cause of death in women, thus a reliable prognostic model for overall survival (OS) in breast cancer is needed to improve treatment and care. Ferroptosis is an iron-dependent cell death. It is already known that siramesine and lapatinib could induce ferroptosis in breast cancer cells, and some ferroptosis-related genes were closely related with the outcomes of treatments regarding breast cancer. The relationship between these genes and the prognosis of OS remains unclear. The data of gene expression and related clinical information was downloaded from public databases. Based on the TCGA-BRCA cohort, an 8-gene prediction model was established with the least absolute shrinkage and selection operator (LASSO) cox regression, and this model was validated in patients from the METABRIC cohort. Based on the median risk score obtained from the 8-gene model, patients were stratified into high- or low-risk groups. Cox regression analyses identified that the risk score was an independent predictor for OS. The findings from CIBERSORT and ssGSEA presented noticeable differences in enrichment scores for immune cells and pathways between the abovementioned two risk groups. To sum up, this prediction model has potential to be widely applied in future clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biology10020151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917807PMC
February 2021

Growing Living Composites with Ordered Microstructures and Exceptional Mechanical Properties.

Adv Mater 2021 Apr 19;33(13):e2006946. Epub 2021 Feb 19.

Sonny Astani Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA, 90089, USA.

Living creatures are continuous sources of inspiration for designing synthetic materials. However, living creatures are typically different from synthetic materials because the former consist of living cells to support their growth and regeneration. Although natural systems can grow materials with sophisticated microstructures, how to harness living cells to grow materials with predesigned microstructures in engineering systems remains largely elusive. Here, an attempt to exploit living bacteria and 3D-printed materials to grow bionic mineralized composites with ordered microstructures is reported. The bionic composites exhibit outstanding specific strength and fracture toughness, which are comparable to natural composites, and exceptional energy absorption capability superior to both natural and artificial counterparts. This report opens the door for 3D-architectured hybrid synthetic-living materials with living ordered microstructures and exceptional properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202006946DOI Listing
April 2021

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study.

Cancer Commun (Lond) 2021 02 2;41(2):171-182. Epub 2021 Feb 2.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

Background: The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.

Methods: This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective.

Results: Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients.

Conclusions: BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cac2.12135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896747PMC
February 2021

Photosynthesis-assisted remodeling of three-dimensional printed structures.

Proc Natl Acad Sci U S A 2021 01;118(3)

Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA 91125

The mechanical properties of engineering structures continuously weaken during service life because of material fatigue or degradation. By contrast, living organisms are able to strengthen their mechanical properties by regenerating parts of their structures. For example, plants strengthen their cell structures by transforming photosynthesis-produced glucose into stiff polysaccharides. In this work, we realize hybrid materials that use photosynthesis of embedded chloroplasts to remodel their microstructures. These materials can be used to three-dimensionally (3D)-print functional structures, which are endowed with matrix-strengthening and crack healing when exposed to white light. The mechanism relies on a 3D-printable polymer that allows for an additional cross-linking reaction with photosynthesis-produced glucose in the material bulk or on the interface. The remodeling behavior can be suspended by freezing chloroplasts, regulated by mechanical preloads, and reversed by environmental cues. This work opens the door for the design of hybrid synthetic-living materials, for applications such as smart composites, lightweight structures, and soft robotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2016524118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826334PMC
January 2021

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

JAMA 2021 01;325(1):50-58

Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed.

Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer.

Design, Setting, And Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy.

Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy.

Main Outcomes And Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events.

Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event.

Conclusions And Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2020.23370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729589PMC
January 2021

Current management of chemotherapy-induced neutropenia in adults: key points and new challenges: Committee of Neoplastic Supportive-Care (CONS), China Anti-Cancer Association Committee of Clinical Chemotherapy, China Anti-Cancer Association.

Cancer Biol Med 2020 11 15;17(4):896-909. Epub 2020 Dec 15.

Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China.

Chemotherapy-induced neutropenia (CIN) is a potentially fatal and common complication in myelosuppressive chemotherapy. The timing and grade of CIN may play prognostic and predictive roles in cancer therapy. CIN is associated with older age, poor functional and nutritional status, the presence of significant comorbidities, the type of cancer, previous chemotherapy cycles, the stage of the disease, specific chemotherapy regimens, and combined therapies. There are many key points and new challenges in the management of CIN in adults including: (1) Genetic risk factors to evaluate the patient's risk for CIN remain unclear. However, these risk factors urgently need to be identified. (2) Febrile neutropenia (FN) remains one of the most common reasons for oncological emergency. No consensus nomogram for FN risk assessment has been established. (3) Different assessment tools [e.g., Multinational Association for Supportive Care in Cancer (MASCC), the Clinical Index of Stable Febrile Neutropenia (CISNE) score model, and other tools] have been suggested to help stratify the risk of complications in patients with FN. However, current tools have limitations. The CISNE score model is useful to support decision-making, especially for patients with stable FN. (4) There are still some challenges, including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN. In view of the current reports, our group discusses the key points, new challenges, and management of CIN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721096PMC
November 2020

An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer.

Theranostics 2020 25;10(26):11938-11949. Epub 2020 Oct 25.

The Second Affiliated Hospital of Dalian Medical University; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.

Immune cells have essential auxiliary functions and influence clinical outcomes in cancer, with high immune infiltration being associated with improved clinical outcomes and better response to treatment in breast cancer (BC). However, studies to date have not fully considered the tumor-infiltrating immune cell (TIIC) landscape in tumors. This study investigated potential biomarkers based on TIICs to improve prognosis and treatment effect in BC. We enrolled 5112 patients for analysis and used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT), a new computational algorithm, to quantify 22 TIICs in primary BC. From the results of univariate Cox regression, 12 immune cells were determined to be significantly related to the overall survival (OS) of BC patients. Furthermore, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to construct an immune prognostic model based on six potential biomarkers. By dividing patients into low- and high-risk groups, a significant distinction in OS was found in the training cohort, with 20-year survival rates of 42.6% and 26.3%, respectively. Applying a similar protocol to validation and test cohorts, we found that OS was significantly shorter in the high-risk group than in the low-risk group, regardless of the molecular subtype of BC. Using the immune score model to predict the effect of BC patients to chemotherapy, the survival advantage for the low-risk group was evident among those who received chemotherapy, regardless of the chemotherapy regimen. In evaluating the predictive value of the nomogram, a decision curve showed better predictive accuracy than the standard tumor-node-metastasis (TNM) staging system. The immune cell infiltration-based immune score model can be effectively and efficiently used to predict the prognosis of BC patients as well as the effect of chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.49451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667685PMC
June 2021

Docetaxel exposure and hematological toxicity in Chinese patients with locally advanced/metastatic nasopharyngeal carcinoma.

Int J Clin Pharmacol Ther 2021 Mar;59(3):216-223

Objective: This study aimed to describe the area under the plasma concentration-time curve (AUC) and the relationship with hematological toxicity plus clinical responses of docetaxel in patients with nasopharyngeal carcinoma. Furthermore, a suitable docetaxel exposure level would be identified to guide clinical dosing.

Materials And Methods: 96 patients with locally advanced or metastatic nasopharyngeal carcinoma treated with docetaxel-based chemotherapy were enrolled. Docetaxel was measured by turbidimetric immunoassay. Associations between docetaxel exposure and hematologic toxicity, effect, and recurrence time were analyzed. Receiver operating characteristic curve analysis was performed to determine an optimal AUC value to predict the decrease in absolute neutrophil counts.

Results: Interpatient variability was large with regard to exposure (AUC) and clearance. The AUC values of 76 patients in course 1 varied more than 4 fold (3.17 ± 0.84 µg×h/mL, ranging from 1.4 to 6.0 µg×h/mL). Clearance was 42.8 L/h (ranging from 20.8 to 73.7 L/h) with ~ 3-fold interindividual variability. The incidence of grade 3/4 leukopenia, 3/4 neutropenia, and febrile neutropenia was 46.3, 85.2, and 13.5%, respectively, in course 1. Docetaxel exposure was the only significant predictor (p < 0.001) of severe toxicity, including grade 4 neutropenia and febrile neutropenia. A cutoff value of 2.85 µg×h/mL was selected as the target AUC. Higher AUC values were not observed to be associated with better drug effect.

Conclusion: The dose was calculated based on individual clearance and a target AUC of 2.85 µg×h/mL, helping to adjust the next cycle of doses and solve interpatient variability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5414/CP203668DOI Listing
March 2021

Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer.

Front Oncol 2020 7;10:568015. Epub 2020 Oct 7.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 () as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression of was significantly higher in tumor tissues, while high expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A () as a new downstream target of in bladder cancer cells. knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas overexpression reversed this inhibition effect. Overexpression of significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with specific inhibitor reversed this promotive effect. Mechanistically, specifically bound to the promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between and expression in bladder cancer tissues, and and expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the axis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.568015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576680PMC
October 2020

Cavin3 Suppresses Breast Cancer Metastasis Inhibiting AKT Pathway.

Front Pharmacol 2020 30;11:01228. Epub 2020 Sep 30.

Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Objective: Cavin3 is a putative tumor suppressor protein. However, its molecular action on tumor regulation is largely unknown. The aim of the current study is to explore the implication of cavin3 alteration, its clinical significance, and any potential molecular mechanisms in the regulation of breast cancer (BC).

Methods: TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) data bases, and 17 freshly paired BC and adjacent normal tissues were analyzed for mRNA levels of . Furthermore, cavin3 protein expression from 407 primary BC samples were assessed by immunohistochemistry (IHC) and measured by H-score. The clinical significance of cavin3 expression was explored by Kaplan-Meier analysis and the Cox regression method. biological assays were performed to elucidate the function and underlying mechanisms of cavin 3 in BC cell lines.

Results: mRNA was dramatically down-regulated in BC compared with the negative control. The median H-score of cavin3 protein by IHC was 50 (range 0-270). There were 232 (57%) and 175 (43%) cases scored as low (H-score≤50) and high (H-score >50) levels of cavin3, respectively. Low cavin3 was correlated with a higher T and N stage, and worse distant metastasis-free survival (DMFS) and overall survival (OS). Multivariate survival analysis revealed low cavin3 was an independent fact for worse DMFS. In BC cells, an overexpression of cavin3 could inhibit cell migration and invasion, and significantly decreased the level of p-Akt. Knockout of cavin3, meanwhile, promoted cell invasion ability and increased the level of p-AKT.

Conclusion: Cavin3 expression is significantly lower in BC and is correlated with distant metastasis and worse survival. Cavin3 functions as a metastasis suppressor inhibiting the AKT pathway, suggesting cavin3 as a potential prognostic biomarker and a target for BC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.01228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556234PMC
September 2020

Poly(U) binding splicing factor 60 promotes renal cell carcinoma growth by transcriptionally upregulating telomerase reverse transcriptase.

Int J Biol Sci 2020 25;16(15):3002-3017. Epub 2020 Sep 25.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Abnormal transcriptional upregulation of telomerase reverse transcriptase (TERT) plays a dominant role in telomerase activation in various cancers. TERT promoter mutations (TPMs) have been identified as a key mechanism in TERT upregulation. However, the mechanism of TERT upregulation in cancers with low frequency of TPMs are not fully elucidated so far. The expression of PUF60 and TERT was detected by real-time PCR, western blot and immunohistochemistry. TERT promoter binding proteins were identified by streptavidin-agarose pulldown assay and mass spectrum (MS) analysis. The role of PUF60/TERT in renal cancer was evaluated on cell growth and . In this study, we identify the regulation mechanism of TERT in renal cell carcinoma (RCC) cells which have rare TPMs but exert significant upregulation of TERT. We found that TERT was highly expressed in RCC tumor tissues, and elevated TERT expression was associated with poor prognosis for patients. We also detected the relatively rare TPM status in both RCC tumor tissues and RCC cell lines. Mechanistically, PUF60, a RNA binding protein, was identified as a novel TERT regulator which bound to the TERT and transcriptionally upregulated TERT expression in RCC cells. The and experiments also demonstrated that PUF60 could promote RCC cell growth through activation of TERT expression in a TPM status independent way. Furthermore, we showed that there was a strong correlation of the expression of PUF60 and TERT in RCC tumor tissues and RCC cell lines, and the patients with high expression of PUF60 and TERT had significantly shorter survival. Collectively, these results indicated that PUF60 transcriptionally upregulated TERT expression to promote RCC growth and progression in a TPM status independent way suggesting that the PUF60/TERT signaling pathway may serve as potential prognostic biomarkers and therapeutic targets for RCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.45115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545719PMC
September 2020

Adjuvant chemotherapy for small, lymph node-negative, triple-negative breast cancer: A single-center study and a meta-analysis of the published literature.

Cancer 2020 08;126 Suppl 16:3837-3846

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node-negative, triple-negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes.

Methods: The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat-Sen University Cancer Center. For the meta-analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population.

Results: Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence-free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/bN0M0) were included in the meta-analysis. The meta-analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease.

Conclusions: Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta-analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32878DOI Listing
August 2020

Punicalagin Protects Diabetic Nephropathy by Inhibiting Pyroptosis Based on TXNIP/NLRP3 Pathway.

Nutrients 2020 May 22;12(5). Epub 2020 May 22.

Xiangya School of Public Health, Central South University, Changsha 410128, China.

Diabetic nephropathy is a diabetic complication caused by chronic inflammation. As the primary polyphenol in pomegranate, punicalagin is believed to have significant anti-inflammatory properties. In this study, we established a mice model for diabetes induced by high-fat diet (HFD)/ streptozotocin (STZ) to verify the protective effect of punicalagin in vivo. The results show that the blood urea nitrogen (BUN), serum creatinine (CREA), and the urine albumin to creatinine ratio (UACR) were significantly decreased in diabetic mice after punicalagin intervention, and the symptoms of glomerular interstitial hyperplasia and glomerular hypertrophy were alleviated. Pyroptosis is an essential manner of programmed cell death in the inflammatory response; the expression of pyroptosis-related proteins such as interleukin-1 (IL-1β), cysteinyl aspartate-specific protease-1 (caspase-1), gasdermin D (GSDMD), and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) was decreased in our study, which proved that the administration of punicalagin for eight weeks can significantly inhibit pyroptosis in mice. In addition, punicalagin reduced high glucose-mediated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and alleviated mitochondria damage. Low expression of NOX4 inhibits the dissociation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP) and the suppression of NLRP3 inflammasome activation. To summarize, our study provided evidence that punicalagin can alleviate diabetic nephropathy, and the effect is associated with downregulating the expression of NOX4, inhibiting TXNIP/NLRP3 pathway-mediated pyroptosis, suggesting its therapeutic implications for complications of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12051516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284711PMC
May 2020

[A Standard Method for Performance Detection of Fluorescence Imaging System].

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Jan;44(1):60-64

Guangdong OptoMedic Technologies Inc. Foshan, 528200. ##Email#.

Fluorescence imaging now becomes an intraoperative navigation technique that gaining popularity in surgery and clinical research. However, at present, there is no mature and reliable method or other related guidance documents for the detection of fluorescence imaging performance. The performance analysis and quality supervision of products on the market could not be performed, which affects their clinical use and image quality. In this paper, a standard method of fluorescence imaging performance testing for fluorescence imaging system is proposed. Several kinds of fluorescence imaging performance parameters affecting fluorescence images are defined strictly. We also recommend scientific and feasible methods for their detections and analyses, which are verified by practical examples. This paper aims to provide a feasible reference standard for fluorescence performance evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3969/j.issn.1671-7104.2020.01.013DOI Listing
January 2020

Automated Breast Ultrasound: Interobserver Agreement, Diagnostic Value, and Associated Clinical Factors of Coronal-Plane Image Features.

Korean J Radiol 2020 05;21(5):550-560

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Objective: To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breast ultrasound (ABUS) coronal features in differentiating breast lesions.

Materials And Methods: This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years), including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon, hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. The interobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesion size, distance to the nipple or skin, palpability, and the histological grade were analyzed.

Results: Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for image type and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated with malignancies ( < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histological grade ( = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive of benign masses ( < 0.001), whereas discontinuous rims were predictive of malignancies ( < 0.001). A hyperechoic rim was more commonly detected in masses more distant from the nipple ( = 0.027), and a hypoechoic rim was more frequently found in large superficial masses ( < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies ( = 0.040).

Conclusion: The coronal plane of ABUS may provide useful diagnostic value for breast lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2019.0525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183827PMC
May 2020

Sharkskin-Inspired Magnetoactive Reconfigurable Acoustic Metamaterials.

Research (Wash D C) 2020 5;2020:4825185. Epub 2020 Feb 5.

Sonny Astani Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA 90089, USA.

Most of the existing acoustic metamaterials rely on architected structures with fixed configurations, and thus, their properties cannot be modulated once the structures are fabricated. Emerging active acoustic metamaterials highlight a promising opportunity to on-demand switch property states; however, they typically require tethered loads, such as mechanical compression or pneumatic actuation. Using untethered physical stimuli to actively switch property states of acoustic metamaterials remains largely unexplored. Here, inspired by the sharkskin denticles, we present a class of active acoustic metamaterials whose configurations can be on-demand switched via untethered magnetic fields, thus enabling active switching of acoustic transmission, wave guiding, logic operation, and reciprocity. The key mechanism relies on magnetically deformable Mie resonator pillar (MRP) arrays that can be tuned between vertical and bent states corresponding to the acoustic forbidding and conducting, respectively. The MRPs are made of a magnetoactive elastomer and feature wavy air channels to enable an artificial Mie resonance within a designed frequency regime. The Mie resonance induces an acoustic bandgap, which is closed when pillars are selectively bent by a sufficiently large magnetic field. These magnetoactive MRPs are further harnessed to design stimuli-controlled reconfigurable acoustic switches, logic gates, and diodes. Capable of creating the first generation of untethered-stimuli-induced active acoustic metadevices, the present paradigm may find broad engineering applications, ranging from noise control and audio modulation to sonic camouflage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.34133/2020/4825185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025040PMC
February 2020

ZIC2 is downregulated and represses tumor growth via the regulation of STAT3 in breast cancer.

Int J Cancer 2020 07 25;147(2):505-518. Epub 2020 Feb 25.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China.

Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32922DOI Listing
July 2020

[Research progress in molecular pharmacognosy of Pogostemon cablin].

Zhongguo Zhong Yao Za Zhi 2019 Nov;44(22):4781-4785

School of Pharmaceutial Sciences,Guangzhou University of Chinese Medicine Guangzhou 510006,China.

Molecular pharmacognosy( MP) is a new interdisciplinary science,which integrates the pharmacognosy and molecular biology,and focuses on the crude drugs' classification and identification,cultivation and protection,and production of active ingredients at the molecular level. Pogostemon cablin is one of the ten major southern medicines in China,MP research on this famous herb has developed on the basis of traditional research methods,and achieved certain results. This article summarized the MP research achievements of P. cablin in recent years,the prospect of this field is also discussed to provide references for the protection,development and utilization of P. cablin resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20190729.105DOI Listing
November 2019

Origin of two-band chorus in the radiation belt of Earth.

Nat Commun 2019 10 14;10(1):4672. Epub 2019 Oct 14.

Laboratory for Atmospheric and Space Physics, University of Colorado, Boulder, CO, USA.

Naturally occurring chorus emissions are a class of electromagnetic waves found in the space environments of the Earth and other magnetized planets. They play an essential role in accelerating high-energy electrons forming the hazardous radiation belt environment. Chorus typically occurs in two distinct frequency bands separated by a gap. The origin of this two-band structure remains a 50-year old question. Here we report, using NASA's Van Allen Probe measurements, that banded chorus waves are commonly accompanied by two separate anisotropic electron components. Using numerical simulations, we show that the initially excited single-band chorus waves alter the electron distribution immediately via Landau resonance, and suppress the electron anisotropy at medium energies. This naturally divides the electron anisotropy into a low and a high energy components which excite the upper-band and lower-band chorus waves, respectively. This mechanism may also apply to the generation of chorus waves in other magnetized planetary magnetospheres.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12561-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791895PMC
October 2019

Clinical genetic features and related survival implications in patients with surgically resected large-cell lung cancer.

Cancer Manag Res 2019 14;11:5489-5499. Epub 2019 Jun 14.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.

Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options. Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations // mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan-Meier method with log-rank test was used for analyzing patient survival. Major events, including , , and mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan-Meier analysis showed that patients with a mutation had ower 5-year overall survival than those with wild-type (25.4% vs 47.8%, =0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, =0.044). mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S200263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585161PMC
June 2019
-->