Publications by authors named "Xiangyi Kong"

148 Publications

Over-Expression of GUSB Leads to Primary Resistance of Anti-PD1 Therapy in Hepatocellular Carcinoma.

Front Immunol 2022 22;13:876048. Epub 2022 Jun 22.

Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.

Immunotherapy treatments, particularly immune checkpoint blockade, can result in benefits in clinical settings. But many pre-clinical and clinical studies have shown that resistance to anti-PD1 therapy frequently occurs, leading to tumor recurrence and treatment failure, including in patients with hepatocellular carcinoma (HCC). In this study, 10 patients with HCC were remedied with anti-PD1, and pre-treatment biopsy samples were sequenced for 289 nanostring panel RNA to compare responsive and non-responsive tumors to identify possible pretreatment biomarkers or targets of anti-PD1 therapeutic responses. Fortunately, the expression of β-Glucuronidase (GUSB) in the non-responding tumors was found to be remarkably higher than that in responding tumors. Results of the cell counting kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell, wound healing test, and flow cytometry showed that GUSB facilitated proliferation, invasion, as well as migration of human HCC cells and downregulated PD-L1 expression by promoting miR-513a-5p. Additionally, as a GUSB inhibitor, amoxapine can reduce the progression of human HCC cells, and was an effective treatment for HCC and improved the sensitivity of anti-PD1 therapy. In summary, this study reveals that increased GUSB downregulates PD-L1 expression by promoting miR-513a-5p, leading to primary resistance to anti-PD1 treatment in HCC, and amoxapine enhances the sensitivity of anti-PD1 therapy by inhibiting GUSB, providing a new strategy and method for improving the efficacy of anti-PD1 therapy and bringing new prospects for therapy of HCC.
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http://dx.doi.org/10.3389/fimmu.2022.876048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257027PMC
July 2022

Treadmill Training Reduces Cerebral Ischemia-Reperfusion Injury by Inhibiting Ferroptosis through Activation of SLC7A11/GPX4.

Oxid Med Cell Longev 2022 6;2022:8693664. Epub 2022 Jun 6.

Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, China.

The mechanism by which exercise training attenuates cerebral ischemia/reperfusion (I/R) injury, especially in the regulation of iron level in neuronal damage, has not been systematically studied. Here, we showed that treadmill training inhibited ferroptosis after I/R injury in rats. Modified neurologic severity score (mNSS) test showed that the motor function, reflex, and balance abilities in the I/R injury rats after treadmill intervention were significantly improved. Treadmill training decreased the level of lipid peroxides in the cerebral cortex of ischemic rats. We found that the protein levels of ferroptosis-related proteins including nuclear transcription factor E2-related factor 2 (Nrf2), cystine/glutamate reverse transporter (SLC7A11), and glutathione peroxidase 4 (GPx4) were decreased in rats after cerebral I/R injury, while treadmill training prevented the reduction of these proteins. Furthermore, we demonstrated that erastin- (a ferroptosis activator-) induced downregulation of SLC7A11 reversed the neuroprotective effect of treadmill training. This study provides the first evidence suggesting that treadmill training suppresses ferroptosis by activating the SLC7A11/GPx4 pathway, thereby protecting against cerebral I/R injury.
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http://dx.doi.org/10.1155/2022/8693664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192201PMC
June 2022

PD-L1 Protein Expression Is Associated With Good Clinical Outcomes and Nomogram for Prediction of Disease Free Survival and Overall Survival in Breast Cancer Patients Received Neoadjuvant Chemotherapy.

Front Immunol 2022 20;13:849468. Epub 2022 May 20.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: This study aims to investigate the potential prognostic significance of programmed death ligand-1 (PD-L1) protein expression in tumor cells of breast cancer patients received neoadjuvant chemotherapy (NACT).

Methods: Using semiquantitative immunohistochemistry, the PD-L1 protein expression in breast cancer tissues was analyzed. The correlations between PD-L1 protein expression and clinicopathologic characteristics were analyzed using Chi-square test or Fisher's exact test. The survival curve was stemmed from Kaplan-Meier assay, and the log-rank test was used to compare survival distributions against individual index levels. Univariate and multivariate Cox proportional hazards regression models were accessed to analyze the associations between PD-L1 protein expression and survival outcomes. A predictive nomogram model was constructed in accordance with the results of multivariate Cox model. Calibration analyses and decision curve analyses (DCA) were performed for the calibration of the nomogram model, and subsequently adopted to assess the accuracy and benefits of the nomogram model.

Results: A total of 104 breast cancer patients received NACT were enrolled into this study. According to semiquantitative scoring for IHC, patients were divided into: low PD-L1 group (61 cases) and high PD-L1 group (43 cases). Patients with high PD-L1 protein expression were associated with longer disease free survival (DFS) (mean: 48.21 months vs. 31.16 months; P=0.011) and overall survival (OS) (mean: 83.18 months vs. 63.31 months; P=0.019) than those with low PD-L1 protein expression. Univariate and multivariate analyses indicated that PD-L1, duration of neoadjuvant therapy, E-Cadherin, targeted therapy were the independent prognostic factors for patients' DFS and OS. Nomogram based on these independent prognostic factors was used to evaluate the DFS and OS time. The calibration plots shown PD-L1 based nomogram predictions were basically consistent with actual observations for assessments of 1-, 3-, and 5-year DFS and OS time. The DCA curves indicated the PD-L1 based nomogram had better predictive clinical applications regarding prognostic assessments of 3- and 5-year DFS and OS, respectively.

Conclusion: High PD-L1 protein expression was associated with significantly better prognoses and longer DFS and OS in breast cancer patients. Furthermore, PD-L1 protein expression was found to be a significant prognostic factor for patients who received NACT.
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http://dx.doi.org/10.3389/fimmu.2022.849468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163312PMC
May 2022

Downregulation of NF-κB by Shp-1 Alleviates Cerebral Venous Sinus Thrombosis-Induced Brain Edema Via Suppression of AQP4.

J Stroke Cerebrovasc Dis 2022 Aug 26;31(8):106570. Epub 2022 May 26.

Department of Neurosurgery, The Affiliated Hospital of Qingdao University, 16 Jiangsu Street, Qingdao 266000, China. Electronic address:

Aquaporin 4 (AQP4), a water channel protein, has been well studied in arterial stroke-induced brain edema. However, the role of AQP4 in cerebral venous sinus thrombosis (CVST) has not been reported. Here, we showed that AQP4 expression was increased in the brain of a rat CVST model, whereas inhibition of AQP4 decreased cerebral edema. Subsequent experiments showed that Shp-1 (Src homology 2-containing phosphatase-1) expression and NF-κB phosphorylation were upregulated after CVST. We found that Shp-1 inhibition resulted in enhancement of NF-κB activation and increased AQP4 expression accompanied by aggravated brain edema. We further showed that NF-κB inhibition led to decreased AQP4 expression and subsequent attenuation of brain edema but had no significant effect on Shp-1 expression. These results provide the first evidence suggesting that downregulation of NF-κB by Shp-1 alleviates CVST-induced brain edema through suppression of AQP4.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2022.106570DOI Listing
August 2022

Ischemic stroke and intestinal flora: an insight into brain-gut axis.

Eur J Med Res 2022 May 25;27(1):73. Epub 2022 May 25.

Department of Biological Science, Jining Medical University, Rizhao, Shandong, China.

Stroke is a type of cerebrovascular disease that significantly endangers human health and lowers quality of life. This understandably places a heavy burden on society and families. In recent years, intestinal flora has attracted increasing attention from scholars worldwide, and its association with ischemic stroke is becoming a hot topic of research amongst researchers in field of stroke. After suffering from a stroke, intestinal microbial dysbiosis leads to increased intestinal permeability and activation of the intestinal immune system, which in turn leads to ectopic intestinal bacteria and pro-inflammatory cells that enter brain tissue through the damaged blood-brain barrier. This exacerbates ischemia-reperfusion injury. Interestingly, after a stroke, some metabolites produced by the intestinal flora attenuate ischemia-reperfusion injury by suppressing the post-stroke inflammatory response and promotes the repair of neurological function. Here we elucidate the changes in gut flora after occurrence of a stroke and highlight the immunomodulatory processes of the post-stroke gut flora.
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http://dx.doi.org/10.1186/s40001-022-00691-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131669PMC
May 2022

Editorial: Toxicity Mechanism and Clinical Features of PD-1/PD-L1 Inhibitors in Treatment of Cancer, Volume I.

Front Pharmacol 2022 5;13:898368. Epub 2022 May 5.

School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.3389/fphar.2022.898368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118018PMC
May 2022

A Meta-analysis of 37 Studies on the Effectiveness of Microsurgical Techniques for Lymphedema.

Ann Vasc Surg 2022 May 16. Epub 2022 May 16.

Division of Lymphatic Surgery, Department of Vascular Surgery, Engineering Laboratory of Memory and Cognitive Impairment Disease Jilin Province, China‒Japan Union Hospital of Jilin University, Jilin University, Changchun, PR China.

Background: Microsurgery is a new technique for lymphedema treatment. Its advantages and disadvantages remain controversial. This study is sought to collect clinical data from patients who underwent lymphovenous bypass and vascularized lymph node transplantation to explore whether surgical procedures can effectively treat lymphedema.

Methods: We performed a meta-analysis of the effectiveness of lymphatic microsurgery. We searched the databases of literature for articles in Chinese and English. These articles were graded for quality. Report details and outcomes were recorded. Data extraction, systematic review, and meta-analysis were performed.

Results: Thirty-seven studies were included. Patients who underwent microsurgery had a significantly better chance of achieving an excellent result than patients who received conservative treatment (odds ratio = 7.07). The affected limb circumference was reduced by approximately, 44.68% after the microsurgery. After the microsurgery, 63% of the patients did not need physiotherapy, and 96% were free from painful skin infections. Lymphography showed that lymphatic transport capacity was enhanced. Moreover, 12% of the patients reported that edema reappeared in the long-term, 26% required reoperation for unsatisfactory results, and 32% experienced lymphatic leakage.

Conclusions: A vast majority of patients derive more benefit from lymphatic microsurgery than from conventional treatment. The advantages of lymphatic microsurgery outweigh the disadvantages for patients in the early and middle stages of chronic secondary lymphedema and patients in whom conventional treatment failed.
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http://dx.doi.org/10.1016/j.avsg.2022.04.038DOI Listing
May 2022

Salt-mediated, plasmonic field-field/field-lattice coupling-enhanced NIR-II photodynamic therapy using core-gap-shell gold nanopeanuts.

Nanoscale Horiz 2022 05 31;7(6):589-606. Epub 2022 May 31.

Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China.

Plasmonic field-field coupling-induced enhancement of the optical properties of dye molecules in the nanogaps among metal nanoparticle clusters and thin films has attracted significant attention especially in disease-related theranostic applications. However, it is very challenging to synthesize plasmonic core-gap-shell nanostructures with a well-controlled nanogap, uniform shape, and distances to maximize the plasmonic field-field coupling between the core and the shell. Herein, we synthesized [email protected]@AuAg nanopeanut-shaped core-gap-shell nanostructures (Au NPN) and tuned their optical absorption from near-infrared region-I (NIR-I) to near-infrared region-II (NIR-II) by filling their nanogap with a high dielectric NaCl aqueous solution, which led to a dramatic redshift in the plasmonic absorption band by 320 nm from 660 to 980 nm and a 12.6-fold increase (at 1064 nm) in the extinction coefficient in the NIR region (1000-1300 nm). Upon filling the nanogap with NaCl aqueous solution, the Au NPN6.5(NaCl) (, ∼6.5 nm nanogap)-mediated NIR-II photodynamic therapy effect was dramatically enhanced, resulting in a much longer average lifespan of >55 days for the mice bearing a murine colon tumor and treated with Au NPN6.5(NaCl) plus 1064 nm light irradiation compared to the mice treated with Au NPN6.5 + 1064 nm light irradiation (without nanogap filled with dielectric NaCl, 40 d) and the doxorubicin-treated group (23 d). This study demonstrates a simple but effective method to tune and maximize the plasmonic field-field coupling between the metal shell and metal core of core-gap-shell nanostructures, the plasmonic field-lattice interactions, and biomedical applications for the treatment of tumors. Overall, our work presents a new way to enhance/maximize the plasmonic field-field and field-lattice coupling, and thus the performance/sensitivities in nanogap-based bioimaging, sensing, and theranostic nanomaterials and devices.
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http://dx.doi.org/10.1039/d1nh00631bDOI Listing
May 2022

PD-1/PD-L1 Inhibitor-Associated Myocarditis: Epidemiology, Characteristics, Diagnosis, Treatment, and Potential Mechanism.

Front Pharmacol 2022 19;13:835510. Epub 2022 Apr 19.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Immune checkpoint inhibitors (ICIs) induce T-cell activation against cancer cells, and due to their anti-tumor function in multiple cancers, ICIs have been considered an important option for oncotherapy. PD-1/PD-L1 inhibitors are now widely used as ICIs for many types of cancers in clinical practices. Myocarditis induced by anti-PD-1/PD-L1 agents is uncommon but shows potentially fatal toxicity. In this review, we attempted to conclude the incidence, characteristics, diagnosis, and treatments, as well as illustrate the potential pathogenesis from the perspectives of T-lymphocyte infiltration, disturbance of regulatory T cells, cytokines, macrophage-mediated inflammatory response, and synergistic effect of PD-1/PD-L1 and CTLA4.
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http://dx.doi.org/10.3389/fphar.2022.835510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062035PMC
April 2022

Treatment of patients with cancer using PD‑1/PD‑L1 antibodies: Adverse effects and management strategies (Review).

Int J Oncol 2022 06 29;60(6). Epub 2022 Apr 29.

Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210001, P.R. China.

In 2020, there were an estimated 19.3 million new cancer cases and close to 10 million cancer deaths worldwide. Cancer remains one of the leading causes of death. In recent years, with the continuous improvement of our understanding of tumor immunotherapy, immunotherapeutics, such as immune checkpoint inhibitors, have gradually become a hot spot for tumor treatment. Amongst these, programmed cell death protein 1/programmed cell death protein ligand 1 (PD‑1/PD‑L1) related inhibitors, such as nivolumab and pembrolizumab, atezolizumab, avelumab and durvalumab have been shown to exhibit a high level of efficacy in several types of tumors. It has been confirmed that these inhibitors play an important role in the anti‑tumor process, significantly improving the survival rate of patients and delaying the progress of the underlying cancer. However, its method of therapeutic interference and potential for damaging the immune system has caused concern regarding its suitability. As these adverse effects are caused by an immune response to endogenous tissues, they are designated as immune‑related adverse events (irAEs). In this review, the typical irAEs reported in recent years and the management strategies adopted are highlighted, to serve as a reference in assessing the clinical response to these adverse reactions.
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http://dx.doi.org/10.3892/ijo.2022.5364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084612PMC
June 2022

The role of ER stress and ATP/AMPK in oxidative stress meditated hepatotoxicity induced by citrinin.

Ecotoxicol Environ Saf 2022 Jun 25;237:113531. Epub 2022 Apr 25.

Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Hunan Collaborative Innovation Center of Animal Production Safety, Changsha 410128, PR China. Electronic address:

Citrinin, a secondary metabolite, can pose serious risks to the environment and organisms, but its hepatotoxic mechanisms are still unclear. Histopathological and ultrastructural results showed that citrinin-induced liver injury in Kunming mice, and the mechanism of citrinin-induced hepatotoxicity was studied in L02 cells. Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Secondly, citrinin inhibits proliferation and promotes apoptosis of L02 cells via disruption of mitochondria membrane potential, increase Bax/Bcl-2 ration, activation of caspase-3, 9, and enhance lactate dehydrogenase (LDH) release. Then, citrinin inhibits superoxide dismutase (SOD) activity and increases the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting oxidative damage in L02 cells; upregulates the protein expression of binding immunoglobulin protein (Bip), C/EBP homologous protein (CHOP), PKR-like ER kinase (PERK) and activating transcription factor6 (ATF6), inducing ER stress in L02 cells; increases the phosphorylation of AMP-activated protein kinase (AMPK) and decreases the content of adenosine-triphosphate (ATP), activating AMPK pathway in L02 cells. Eventually, pretreatment with NAC, an ROS inhibitor, alleviates citrinin-induced cell cycle G2/M arrest and apoptosis by inhibiting ROS-mediated ER stress; pretreatment with 4-PBA, an ER stress inhibitor, reversed ER stress and p-AMPK; pretreatment with dorsomorphin, an AMPK inhibitor, decreases citrinin-induced cell cycle G2/M arrest and apoptosis. In summary, citrinin induces cell cycle arrest and apoptosis to aggravate liver injury by activating ROS-ER stress-AMPK signaling pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113531DOI Listing
June 2022

Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial.

J Immunother Cancer 2022 04;10(4)

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China

Objective: This study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy.

Methods: Initially, 20 patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery. Four to 8 weeks after surgery, patients received eight cycles of adjuvant therapy with camrelizumab in combination with apatinib. Major pathological reactions (MPR), complete pathological reactions (pCR), objective response rate (ORR), relapse-free survival (RFS), and adverse events (AE) were assessed. In addition, cancer tissue and plasma samples were collected before and after treatment, and genetic differences between responding and non-responding lesions were compared by tumor immune microenvironment (TIME) analysis, circulating tumor DNA (ctDNA) analysis and proteomics analysis.

Results: In 18 patients with HCC who completed neoadjuvant therapy, 3 (16.7%) and 6 (33.3%) patients with HCC reached ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST criteria, respectively. Of the 17 patients with HCC who received surgical resection, 3 (17.6%) patients with HCC reported MPR and 1 (5.9%) patient with HCC achieved pCR. The 1-year RFS rate of the enrolled patients was 53.85% (95% CI: 24.77% to 75.99%). Grade 3/4 AEs were reported in 3 (16.7%) of the 18 patients, with the most common AEs being rash (11.1%), hypertension (5.6%), drug-induced liver damage (5.6%), and neutropenia (5.6%) in the preoperative phase. The 289 NanoString panel RNA sequencing showed that TIME cell infiltration especially dendritic cells (DCs) infiltration was better in responding tumors than in non-responding tumors. Our results of ctDNA revealed a higher positive rate (100%) among patients with HCC with stage IIb-IIIa disease. When comparing patients with pCR/MPR and non-MPR, we observed more mutations in patients who achieved pCR/MPR at baseline (6 mutations vs 2.5 mutations, p=0.025). Patients who were ctDNA positive after adjuvant therapy presented a trend of shorter RFS than those who were ctDNA negative. Proteomic analysis suggested that abnormal glucose metabolism in patients with multifocal HCC might be related to different sensitivity of treatment in different lesions.

Conclusion: Perioperative camrelizumab plus apatinib displays a promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients' recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions.

Trial Registration Number: NCT04297202.
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http://dx.doi.org/10.1136/jitc-2022-004656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981365PMC
April 2022

PD-1/PD-L1 Inhibitors in Patients With Preexisting Autoimmune Diseases.

Front Pharmacol 2022 18;13:854967. Epub 2022 Mar 18.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Autoimmune diseases and malignant tumors are the two hotspots and difficulties that are currently being studied and concerned by the medical field. The use of PD-1/PD-L1 inhibitors improves the prognosis of advanced tumors, but excessive immune responses can also induce immune-related adverse events (irAEs). Due to this concern, many clinical trials exclude cancer patients with preexisting autoimmune disease (AID). This review outlines the possible mechanisms of irAE, discusses the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients with preexisting AID, and emphasizes the importance of early recognition, continuous monitoring, and multidisciplinary cooperation in the prevention and management of cancer patients with preexisting AID.
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http://dx.doi.org/10.3389/fphar.2022.854967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971753PMC
March 2022

Preoperative Breast Immune Prognostic Index as Prognostic Factor Predicts the Clinical Outcomes of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

Front Immunol 2022 7;13:831848. Epub 2022 Mar 7.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: This study aims at investigating the potential prognostic significance of the breast immune prognostic index (BIPI) in breast cancer patients who received neoadjuvant chemotherapy (NACT).

Methods: The optimal cutoff value was calculated through the receiver operating characteristic curve (ROC). The correlations between BIPI and clinicopathologic characteristics were determined by the chi-square test or Fisher's exact test. The Kaplan-Meier method was used to estimate the survival probability, and the log-rank test was used to analyze the differences in the survival probability among patients. The univariate and multivariate Cox proportional hazard regression model was used to screen the independent prognostic factors. A prognostic nomogram for disease-free survival (DFS) and overall survival (OS) was built on the basis of the multivariate analyses. Furthermore, the calibration curve and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.

Results: All enrolled patients were split into three subgroups based on the BIPI score. The mean DFS and OS of the BIPI score 0 group and BIPI score 1 group were significantly longer than those of the BIPI score 2 group (42.02 vs. 38.61 vs. 26.01 months, 77.61 vs. 71.83 vs. 53.15 months; p < 0.05). Univariate and multivariate analyses indicated that BIPI was an independent prognostic factor for patients' DFS and OS (DFS, hazard ratio (HR): 6.720, 95% confidence interval (CI): 1.629-27.717; OS, HR: 8.006, 95% CI: 1.638-39.119). A nomogram with a C-index of 0.873 (95% CI: 0.779-0.966) and 0.801 (95% CI: 0.702-0.901) had a favorable performance for predicting DFS and OS survival rates for clinical use by combining immune scores with other clinical features. The calibration curves at 1-, 3-, and 5-year survival suggested a good consistency between the predicted and actual DFS and OS probability. The DCA demonstrated that the constructed nomogram had better clinical predictive usefulness than only BIPI in predictive clinical applications of 5-year DFS and OS prognostic assessments.

Conclusions: The patients with low BIPI score have better prognoses and longer DFS and OS. Furthermore, the BIPI-based nomogram may serve as a convenient prognostic tool for breast cancer and help in clinical decision-making.
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http://dx.doi.org/10.3389/fimmu.2022.831848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8937039PMC
May 2022

The Systemic Inflammation Response Index as an Independent Predictor of Survival in Breast Cancer Patients: A Retrospective Study.

Front Mol Biosci 2022 28;9:856064. Epub 2022 Feb 28.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

There is a close relationship between inflammatory cells and tumors, but the pathways that connect the two remain unclear. This research explores the clinical and prognostic value of the systemic inflammation response index (SIRI) in breast cancer patients. The study included 477 breast cancer patients who underwent neoadjuvant chemotherapy and 308 breast cancer patients who did not in our center between January 1998 and December 2016. Optimal SIRI threshold values were determined using the receiver operating characteristic curve (ROC). Patients were then reclassified as SIRI ≥0.80 group (High SIRI group) and SIRI <0.80 group (Low SIRI group). The outcomes were analyzed by statistical methods. The univariate and multivariate analyses demonstrated that SIRI independently predicted survival in breast cancer. The disease-free survival (DFS) and overall survival (OS) in patients with low SIRI scores were significantly longer in contrast to those with high SIRI scores (41.50 vs. 37.63 months, and 64.57 vs. 58.42 months). Further subgroup analyses revealed that low SIRI score patients who also had either early breast cancer, advanced breast cancer, or different molecular subtypes also possessed longer mean survival time of DFS and OS in contrast to those with high SIRI levels (2 = 2.379, = 0.123, and 2 = 5.153, = 0.023; 2 = 11.080, = 0.0009 and 2 = 15.900, < 0.0001; 2 = 16.020, < 0.0001 and 2 = 22.050, < 0.0001, respectively). SIRI serves as an easily accessible, replicable, and minimally invasive prognostic tool in breast cancer patients. Lower SIRI scores were predictive of a longer DFS and OS after surgery in breast cancer patients. SIRI may serve as a marker to guide clinical management and prognostication of breast cancer.
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http://dx.doi.org/10.3389/fmolb.2022.856064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918696PMC
February 2022

The Systemic Immune-Inflammation Index is an Independent Predictor of Survival in Breast Cancer Patients.

Cancer Manag Res 2022 25;14:775-820. Epub 2022 Feb 25.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.

Purpose: The current investigation examines the potential clinical value and prognostic significance of a systemic immune-inflammation index (SII) in patients with breast cancer.

Patients And Methods: A total of 477 individuals underwent neoadjuvant chemotherapy, and 308 individuals did not at our center between January 1998 and December 2016 were selected. An optimized SII threshold was generated using a receiver operating characteristic curve (ROC). The relationship between various factors and breast cancer in predicting disease-free survival (DFS) and overall survival (OS) were analyzed.

Results: The SII < 560 group (Low SII group) and SII ≥ 560 group (High SII group) are divided according to the threshold value. SII was an independent predictor for breast cancer DFS and OS based on univariate and multivariate analyses. Low SII patients had higher mean DFS and OS in contrast to those in the high SII groups (46.65 vs 27.37 months and 69.92 vs 49.53 months). Those in the low SII cohort who also had early or advanced breast cancer, different molecular subtypes, and with or without lymph vessel invasion all had higher mean survival time of DFS and OS in contrast to those with raised SII values (P<0.05). The mean DFS and OS durations also varied based on different Miller and Payne grades (MPG) (P <0.005), and different response groups (P<0.05).

Conclusion: SII can be used as an easily accessible and minimally invasive potential prognostic factor in individuals with breast cancer and may also guide clinicians in treating and prognosticating patients with breast cancer.
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http://dx.doi.org/10.2147/CMAR.S346406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887616PMC
February 2022

Meloxicam Inhibits Hepatocellular Carcinoma Progression and Enhances the Sensitivity of Immunotherapy via the MicroRNA-200/PD-L1 Pathway.

J Oncol 2022 21;2022:4598573. Epub 2022 Feb 21.

Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China.

Background: Hepatocellular carcinoma (HCC) has become the sixth most common cancer and the third leading cause of cancer death in the world. Although the research achievements of tumor immunotherapy have made great progress, especially the combination of immune targeted therapy has achieved good curative effect in HCC, but only a few patients are suitable for it and benefit from it. Therefore, there is an urgent need to find new effective drugs to treat HCC or to enhance the sensitivity of immunotherapy.

Methods: Meloxicam, a COX2 inhibitor with strong anti-HCC potential, was screened from 800 small molecules approved by FDA. The effect of meloxicam on the proliferation, invasion, and migration of HCC cell lines was evaluated by cell phenotype analysis. The Human Protein Atlas database and the TISCH database were used to analyze COX2 data in single cells, and the TISIDB database was used to analyze the correlation of COX2 with immune function. The real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to evaluate the level of PD-L1 and CD155 in HCC cell lines treated with meloxicam and further explore its possible mechanism. In vivo experiments were applied to verify the effect of meloxicam combined with anti-PD1 therapy on HCC tumor growth in mice.

Results: Meloxicam can significantly inhibit the proliferation, invasion, and migration of HCC cells. The TISIDB database indicated that the COX2 was strongly associated with immunoinhibitors and immunostimulators. Meloxicam upregulated the level of PD-L1 in HCC cell lines and animal models. In terms of mechanism, meloxicam inhibited microRNA-200, thereby upregulating PD-L1. In vitro experiments showed that both meloxicam and anti-PD1 had inhibitory effects on the growth of HCC tumors. Compared with meloxicam and anti-PD1 alone, the combination therapy showed stronger antitumor properties. Immunohistochemical analysis confirmed that meloxicam enhanced the antitumor immune activity in the tumor microenvironment.

Conclusion: Our study showed meloxicam inhibited HCC progression and enhanced the sensitivity of immunotherapy via the microRNA-200/PD-L1 pathway.
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http://dx.doi.org/10.1155/2022/4598573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885196PMC
February 2022

Meloxicam Inhibits Hepatocellular Carcinoma Progression and Enhances the Sensitivity of Immunotherapy via the MicroRNA-200/PD-L1 Pathway.

J Oncol 2022 21;2022:4598573. Epub 2022 Feb 21.

Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China.

Background: Hepatocellular carcinoma (HCC) has become the sixth most common cancer and the third leading cause of cancer death in the world. Although the research achievements of tumor immunotherapy have made great progress, especially the combination of immune targeted therapy has achieved good curative effect in HCC, but only a few patients are suitable for it and benefit from it. Therefore, there is an urgent need to find new effective drugs to treat HCC or to enhance the sensitivity of immunotherapy.

Methods: Meloxicam, a COX2 inhibitor with strong anti-HCC potential, was screened from 800 small molecules approved by FDA. The effect of meloxicam on the proliferation, invasion, and migration of HCC cell lines was evaluated by cell phenotype analysis. The Human Protein Atlas database and the TISCH database were used to analyze COX2 data in single cells, and the TISIDB database was used to analyze the correlation of COX2 with immune function. The real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to evaluate the level of PD-L1 and CD155 in HCC cell lines treated with meloxicam and further explore its possible mechanism. In vivo experiments were applied to verify the effect of meloxicam combined with anti-PD1 therapy on HCC tumor growth in mice.

Results: Meloxicam can significantly inhibit the proliferation, invasion, and migration of HCC cells. The TISIDB database indicated that the COX2 was strongly associated with immunoinhibitors and immunostimulators. Meloxicam upregulated the level of PD-L1 in HCC cell lines and animal models. In terms of mechanism, meloxicam inhibited microRNA-200, thereby upregulating PD-L1. In vitro experiments showed that both meloxicam and anti-PD1 had inhibitory effects on the growth of HCC tumors. Compared with meloxicam and anti-PD1 alone, the combination therapy showed stronger antitumor properties. Immunohistochemical analysis confirmed that meloxicam enhanced the antitumor immune activity in the tumor microenvironment.

Conclusion: Our study showed meloxicam inhibited HCC progression and enhanced the sensitivity of immunotherapy via the microRNA-200/PD-L1 pathway.
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http://dx.doi.org/10.1155/2022/4598573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885196PMC
February 2022

Patient-Reported Outcomes and Complications Following Breast Reconstruction: A Comparison Between Biological Matrix-Assisted Direct-to-Implant and Latissimus Dorsi Flap.

Front Oncol 2022 27;12:766076. Epub 2022 Jan 27.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Implant-based breast reconstruction is increasingly becoming the most common method of postmastectomy breast reconstruction in use today. As the traditional autologous reconstruction technique, latissimus dorsi flap (LDF) is employed by surgeons for reconstruction after breast cancer surgery, including partial mastectomy, modified radical mastectomy, and others. The authors aim to compare patient-reported outcomes (PROs) and complications between the SIS matrix-assisted direct-to-implant (DTI) breast reconstruction and the autologous LDF breast reconstruction.

Methods: Patients undergoing the SIS matrix-assisted DTI reconstruction or mastectomy with LDF reconstruction or partial mastectomy with mini latissimus dorsi flap (MLDF) reconstruction were enrolled in a single institution from August 2010 to April 2019. Patients were included for analysis and divided into three groups: those who underwent LDF reconstruction, those who underwent MLDF reconstruction, and patients who underwent SIS matrix-assisted DTI breast reconstruction. PROs (using the BREAST-Q version 2.0 questionnaire) and complications were evaluated.

Results: A total of 135 patients met the inclusion criteria: 79 patients (58.5%) underwent SIS matrix-assisted DTI, 29 patients (21.5%) underwent LDF breast reconstruction, and 27 patients (20%) underwent MLDF breast reconstruction. PROs and complication rates between LDF reconstruction group and MLDF reconstruction group showed no statistically significant differences. Furthermore, BREAST-Q responses found that patients in the whole autologous LDF reconstruction group had better psychosocial well-being, showing a mean score of 84.31 ± 17.28 compared with SIS matrix-assisted DTI reconstruction, with a mean score of 73.52 ± 19.96 (p = 0.005), and expressed higher sexual well-being (69.65 ± 24.64 vs. 50.95 ± 26.47; p = 0.016). But there were no statistically significant differences between the two groups for postoperative complications.

Conclusion: This retrospective study showed no statistically significant differences between LDF breast reconstruction and MLDF breast reconstruction. However, patients in the whole autologous LDF reconstruction group yielded superior PROs than patients in the SIS matrix-assisted DTI reconstruction group in the psychosocial well-being and sexual well-being domains.
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http://dx.doi.org/10.3389/fonc.2022.766076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828647PMC
January 2022

Recent advances of transcriptomics and proteomics in triple-negative breast cancer prognosis assessment.

J Cell Mol Med 2022 03 11;26(5):1351-1362. Epub 2022 Feb 11.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Triple-negative breast cancer (TNBC), a heterogeneous tumour that lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), is often characterized by aggressiveness and tends to recur or metastasize. TNBC lacks therapeutic targets compared with other subtypes and is not sensitive to endocrine therapy or targeted therapy except chemotherapy. Therefore, identifying the prognostic characteristics and valid therapeutic targets of TNBC could facilitate early personalized treatment. Due to the rapid development of various technologies, researchers are increasingly focusing on integrating 'big data' and biological systems, which is referred to as 'omics', as a means of resolving it. Transcriptomics and proteomics analyses play an essential role in exploring prospective biomarkers and potential therapeutic targets for triple-negative breast cancers, which provides a powerful engine for TNBC's therapeutic discovery when combined with complementary information. Here, we review the recent progress of TNBC research in transcriptomics and proteomics to identify possible therapeutic goals and improve the survival of patients with triple-negative breast cancer. Also, researchers may benefit from this article to catalyse further analysis and investigation to decipher the global picture of TNBC cancer.
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http://dx.doi.org/10.1111/jcmm.17124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899180PMC
March 2022

Nutritional Risk Index Predicts Survival in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy.

Front Nutr 2021 13;8:786742. Epub 2022 Jan 13.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Nutritional risk index (NRI) is an index based on ideal body weight that aims to present body weight and serum albumin levels. It has been utilized to discriminate patients at risk of postoperative complications and predict the postoperative outcome of major surgeries. However, this index remains limited for breast cancer patients treated with neoadjuvant chemotherapy (NACT). The research explores the clinical and prognostic significance of NRI in breast cancer patients. This study included 785 breast cancer patients (477 cases received NACT and 308 cases did not) were enrolled in this retrospective study. The optimal NRI cutoff value was evaluated by receiver operating characteristic (ROC) curve, then reclassified as low NRI group (<112) and high NRI group (≥112). The results demonstrated that NRI independently predicted survival on disease-free survival (DFS) and overall survival (OS) by univariate and multivariate Cox regression survival analyses [ = 0.019, hazard ratio (HR): 1.521, 95% CI: 1.071-2.161 and = 0.004, HR: 1.415, 95% CI: 1.119-1.789; and = 0.026, HR:1.500, 95% CI: 1.051-2.143 and < 0.001, HR: 1.547, 95% CI: 1.221-1.959]. According to the optimal cutoff value of NRI, the high NRI value patients had longer mean DFS and OS time in contrast to those with low NRI value patients (63.47 vs. 40.50 months; 71.50 vs. 56.39 months). Furthermore, the results demonstrated that the high NRI score patients had significantly longer mean DFS and OS time than those with low NRI score patients in early-stage breast cancer (χ = 9.0510, = 0.0026 and χ = 9.2140, = 0.0024) and advanced breast cancer (χ = 6.2500, = 0.0124 and χ = 5.8880, = 0.0152). The mean DFS and OS values in patients with high NRI scores were significantly longer in contrast to those with low NRI scores in different molecular subtypes. The common toxicities after NACT were hematologic and gastrointestinal reactions, and the NRI had no statistically significant effects on toxicities, except in nausea (χ = 9.2413, = 0.0024), mouth ulcers (χ = 4.8133, = 0.0282), anemia (χ = 8.5441, = 0.0140), and leukopenia (χ = 11.0951, = 0.0039). NRI serves as a minimally invasive, easily accessible and convenient prognostic tool for evaluating breast cancer prognoses and treatment efficacy, and may help doctors in terms of selecting measures of greater efficiency or appropriateness to better treat breast cancer.
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http://dx.doi.org/10.3389/fnut.2021.786742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793025PMC
January 2022

Clinical outcomes and patient satisfaction with the use of biological and synthetic meshes in one-stage implant-based breast reconstruction.

Breast Cancer 2022 May 3;29(3):450-457. Epub 2022 Jan 3.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Background: Biological and synthetic meshes were used to cover the damaged muscle and augment the subpectoral pocket in breast reconstruction. However, few studies have directly compared the effects of biological and synthetic meshes. This study analyzed postoperative complications and assessed the patient-reported outcomes with the use of BioDesign® Surgisis and TiLOOP Bra/TiMesh® in one-stage implant-based breast reconstruction.

Methods: Patients undergoing one-stage implant-based breast reconstruction were enrolled in this study. Post-mastectomy breast reconstructions were facilitated with either Surgisis mesh or TiLOOP mesh. Complications were examined and patient-reported quality-of-life outcomes were evaluated using the BREAST-Q questionnaire (ver 2.0). The multivariate linear regression models were used for data analysis.

Results: Overall, 79 of 116 patients (68%) received breast reconstruction with Surgisis mesh and 37 (32%) with TiLOOP mesh. There was no difference in complication rates between the two groups postoperatively. But patient-reported satisfaction was higher with the use of Surgisis mesh than with TiLOOP mesh (P = 0.05).

Conclusions: This study reported no difference between the Surgisis group and the TiLOOP group in either complication rates or most patient-reported outcomes postoperatively. Yet the assessment of patient-reported satisfaction showed preference toward Surgisis mesh, a finding with a potential implication for mesh selection.
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http://dx.doi.org/10.1007/s12282-021-01324-yDOI Listing
May 2022

Metastasis to Breast from Extramammary Solid Tumors and Lymphomas: A 20-Year Population-Based Study.

Cancer Invest 2022 Apr 23;40(4):325-336. Epub 2021 Dec 23.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

To discuss the clinicopathological features and prognosis of metastases to the breast from extramammary solid tumors and lymphomas, we reviewed Cancer Hospital of Chinese Academy of Medical Sciences database from 01/01/2000 to 12/31/2020. Fifty-nine patients were identified. The most common primary sites for breast metastases were lymph node and pulmonary, followed by nasal cavity, ovary, skin, etc. All the patients were treated with chemotherapy, 18 were operated, 14 accepted radiotherapy. Metastasis to breast should be considered in any patient with tumor history presenting a breast lump. Pathological with immunohistochemical examination should be performed to identify the original site.
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http://dx.doi.org/10.1080/07357907.2021.2019264DOI Listing
April 2022

Targeting Immune Cells in the Tumor Microenvironment of HCC: New Opportunities and Challenges.

Front Cell Dev Biol 2021 12;9:775462. Epub 2021 Nov 12.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China.

Immune associated cells in the microenvironment have a significant impact on the development and progression of hepatocellular carcinoma (HCC) and have received more and more attention. Different types of immune-associated cells play different roles, including promoting/inhibiting HCC and several different types that are controversial. It is well known that immune escape of HCC has become a difficult problem in tumor therapy. Therefore, in recent years, a large number of studies have focused on the immune microenvironment of HCC, explored many mechanisms worth identifying tumor immunosuppression, and developed a variety of immunotherapy methods as targets, laying the foundation for the final victory in the fight against HCC. This paper reviews recent studies on the immune microenvironment of HCC that are more reliable and important, and provides a more comprehensive view of the investigation of the immune microenvironment of HCC and the development of more immunotherapeutic approaches based on the relevant summaries of different immune cells.
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http://dx.doi.org/10.3389/fcell.2021.775462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633569PMC
November 2021

Recent Advances in the Role of Discoidin Domain Receptor Tyrosine Kinase 1 and Discoidin Domain Receptor Tyrosine Kinase 2 in Breast and Ovarian Cancer.

Front Cell Dev Biol 2021 3;9:747314. Epub 2021 Nov 3.

Department of Breast Surgical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Discoidin domain receptor tyrosine kinases (DDRs) are a class of receptor tyrosine kinases (RTKs), and their dysregulation is associated with multiple diseases (including cancer, chronic inflammatory conditions, and fibrosis). The DDR family members (DDR1a-e and DDR2) are widely expressed, with predominant expression of DDR1 in epithelial cells and DDR2 in mesenchymal cells. Structurally, DDRs consist of three regions (an extracellular ligand binding domain, a transmembrane domain, and an intracellular region containing a kinase domain), with their kinase activity induced by receptor-specific ligand binding. Collagen binding to DDRs stimulates DDR phosphorylation activating kinase activity, signaling to MAPK, integrin, TGF-β, insulin receptor, and Notch signaling pathways. Abnormal DDR expression is detected in a range of solid tumors (including breast, ovarian, cervical liver, gastric, colorectal, lung, and brain). During tumorigenesis, abnormal activation of DDRs leads to invasion and metastasis, via dysregulation of cell adhesion, migration, proliferation, secretion of cytokines, and extracellular matrix remodeling. Differential expression or mutation of DDRs correlates with pathological classification, clinical characteristics, treatment response, and prognosis. Here, we discuss the discovery, structural characteristics, organizational distribution, and DDR-dependent signaling. Importantly, we highlight the key role of DDRs in the development and progression of breast and ovarian cancer.
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http://dx.doi.org/10.3389/fcell.2021.747314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595330PMC
November 2021

Primary Giant Cell Tumor of the Breast With Pulmonary Metastasis: A Case Report and Review of the Literature.

Front Oncol 2021 5;11:638237. Epub 2021 Nov 5.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Giant cell tumor of soft tissue (GCT-ST) is an extremely rare tumor that is similar in morphology and immunohistochemistry to giant cell tumor of the bone. Almost 80% of these tumors occur in the upper and lower extremities, and the breast is a very rare location. Here, we report a case of a 65-year-old female patient with a small mobile palpable lump in the left breast. Although the left breast tumor was considered malignant on preoperative imaging, no evidence of malignant tumor was found by ultrasound-guided core needle biopsy (CNB). Subsequently, the left breast tumor was confirmed as a malignant tumor by intraoperative rapid pathological examination. The initial treatment of the tumor was wide local excision and sentinel lymph node biopsy, and it was confirmed to be GCT-ST by histopathology and immunohistochemistry. Despite surgical treatment achieving clear surgical margins, the patient experienced lung metastases within a year of her initial treatment. Fortunately, the patient underwent surgical treatment of lung metastases, and at the last follow-up, the patient was still alive. This is the first case of a primary soft tissue tumor of the breast that has undergone surgical intervention after lung metastasis. This case report highlights the complexity of the clinical diagnosis and treatment of GCT-ST arising from the breast. Surgery may be another good treatment when the patient develops lung metastases.
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http://dx.doi.org/10.3389/fonc.2021.638237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602786PMC
November 2021

Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression.

J Neuroinflammation 2021 Oct 30;18(1):249. Epub 2021 Oct 30.

Institute of Neuroregeneration & Neurorehabilitation, Department of Pathophysiology, Qingdao University, Ningxia Road 308, Qingdao, 266071, China.

Background: Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis.

Methods: Here, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions.

Results: We found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions.

Conclusions: These data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.
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http://dx.doi.org/10.1186/s12974-021-02231-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557003PMC
October 2021

Review on Emotion Recognition Based on Electroencephalography.

Front Comput Neurosci 2021 1;15:758212. Epub 2021 Oct 1.

The Boiler and Pressure Vessel Safety Inspection Institute of Henan Province, Zhengzhou, China.

Emotions are closely related to human behavior, family, and society. Changes in emotions can cause differences in electroencephalography (EEG) signals, which show different emotional states and are not easy to disguise. EEG-based emotion recognition has been widely used in human-computer interaction, medical diagnosis, military, and other fields. In this paper, we describe the common steps of an emotion recognition algorithm based on EEG from data acquisition, preprocessing, feature extraction, feature selection to classifier. Then, we review the existing EEG-based emotional recognition methods, as well as assess their classification effect. This paper will help researchers quickly understand the basic theory of emotion recognition and provide references for the future development of EEG. Moreover, emotion is an important representation of safety psychology.
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http://dx.doi.org/10.3389/fncom.2021.758212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518715PMC
October 2021

Prolactin and endocrine therapy resistance in breast cancer: The next potential hope for breast cancer treatment.

J Cell Mol Med 2021 11 15;25(22):10327-10348. Epub 2021 Oct 15.

Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Breast cancer, a hormone-dependent tumour, generally includes four molecular subtypes (luminal A, luminal B, HER2 enriched and triple-negative) based on oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Multiple hormones in the body regulate the development of breast cancer. Endocrine therapy is one of the primary treatments for hormone-receptor-positive breast cancer, but endocrine resistance is the primary clinical cause of treatment failure. Prolactin (PRL) is a protein hormone secreted by the pituitary gland, mainly promoting mammary gland growth, stimulating and maintaining lactation. Previous studies suggest that high PRL levels can increase the risk of invasive breast cancer in women. The expression levels of PRL and PRLR in breast cancer cells and breast cancer tissues are elevated in most ER and ER tumours. PRL activates downstream signalling pathways and affects endocrine therapy resistance by combining with prolactin receptor (PRLR). In this review, we illustrated and summarized the correlations between endocrine therapy resistance in breast cancer and PRL, as well as the pathophysiological mechanisms and clinical practices. The study on PRL and its receptor would help explore reversing endocrine therapy-resistance for breast cancer.
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http://dx.doi.org/10.1111/jcmm.16946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581311PMC
November 2021

Research Progresses in Immunological Checkpoint Inhibitors for Breast Cancer Immunotherapy.

Front Oncol 2021 23;11:582664. Epub 2021 Sep 23.

Department of Breast Surgical Oncology, China National Cancer Center/Cancer Hospital, Chinese Academy of Medical and Peking Union Medical College, Beijing, China.

Tumor immune escape refers to the phenomenon in which tumor cells escape the recognition and attack of the body's immune system through various mechanisms so that they can survive and proliferate . The imbalance of immune checkpoint protein expression is the primary mechanism for breast cancer to achieve immune escape. Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) are critical immune checkpoints for breast cancer. Immune checkpoint inhibitors block the checkpoint and relieve its inhibition effect on immune cells, reactivate T-cells and destroy cancer cells and restore the body's ability to resist tumors. At present, immunological checkpoint inhibitors have made significant progress in breast cancer immunotherapy, and it is expected to become a new treatment for breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.582664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495193PMC
September 2021
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