Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in hu...Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in humans and other species have demonstrated its pivotal role in regulating the sodium ion balance and mediating sodium and water reabsorption in the kidney's proximal tubules.However,the impact of EGFR gene in how the Yarkand hare(Lepus yarkandensis)adapts to extreme environmental habitat remains unclear,The Yarkand hare is a desert-dwelling animal with multiple adaptations to cope with drought.Given the important physiological function of EGFR gene,we strived to understand its role in arid environment and explore the molecular mechanism of drought tolerance in the Yarkand hare.We first performed segmental cloning of the CDS of the Yarkand hare EGFR gene.Then,We constructed the phylogenetic tree of the Yarkand hare's EGFR gene and compared it with that of other species.The results showed that the Yarkand hare was most closely related to the Tolai hare(Lepus tolai).Through quantitative reverse transcription polymerase chain reaction(RT-qPCR),we discovered that EGFR expression in the kidneys of the Yarkand hare was higher than in the allopatric Tolai hare from non-arid areas.Therefore,we hypothesized that EGFR gene overexpression in the kidney of the Yarkand hare may play a crucial role in drought adaptability.Subsequently,we inserted CDS of EGFR gene into a pcDNA3.1-EGFP expression vector to construct recombinant plasmid,which was transfected into HeLa cells and overexpressed.RT-qPCR demonstrated a notable and statistically significant increase in EGFR mRNA expression and western blot proved stable expression of this protein in HeLa cells.Through cell experiments,EGFR gene overexpression markedly enhanced the survival of Hela cells subjected to NaCl,H_(2)O_(2),and heat stresses,increased superoxide dismutase activity,and decreased malondialdehyde content.In conclusion,these findings preliminarily suggest that EGFR might help the Yarkand hare adapt to extreme environmental conditions.EGFR manipulation in vivo could be a promising strategy to enhance the resilience of animals to extreme conditions.展开更多
BACKGROUND Interleukin-22(IL-22)belongs to the IL-10 cytokine family,recognized for its ability to modulate diverse immune responses.Previous studies have indicated that IL-22 promotes cancer advancement and metastasi...BACKGROUND Interleukin-22(IL-22)belongs to the IL-10 cytokine family,recognized for its ability to modulate diverse immune responses.Previous studies have indicated that IL-22 promotes cancer advancement and metastasis.However,the precise function of IL-22 in colorectal cancer(CRC)remains unclear.AIM To investigate the role of IL-22 in promoting stem cell-like characteristics and chemotherapy resistance in CRC cells,as well as to elucidate the mechanisms underlying these effects.METHODS HCT116 cells were treated with IL-22(50 ng/mL)and oxaliplatin(L-OHP,5μg/mL).A series of functional assays-including cell counting kit-8 assay,tumor sphere formation assay,and cell apoptosis assay-were conducted to assess the effects of IL-22 on cell viability and stem cell-like characteristics.The expression of stemness-related markers(SOX2,Oct4,NANOG,and Bmi-1)was examined using Western blot analysis.Additionally,the total and phosphorylated levels of epidermal growth factor receptor(EGFR),protein kinase B(AKT),and extracellular signal-regulated kinase(ERK)were evaluated by Western blot.An EGFR inhibitor,osimertinib(Osi),was used to assess the pathway's functional relevance.RESULTS IL-22 treatment promotes CRC cell proliferation,enhances sphere formation,and elevates the expression of stem cell markers,including SOX2,Oct4,NANOG,and Bmi-1.IL-22 treatment increases the phosphorylation of EGFR,AKT,and ERK.Additionally,IL-22 treatment mitigates the cytotoxic effects and the ability to induce apoptosis of L-OHP.Furthermore,IL-22 treatment activated the EGFR/ERK signaling pathway by increasing the phosphorylation of EGFR,AKT,and ERK.Importantly,the use of the EGFR inhibitor Osi significantly counteracted the chemoresistance induced by IL-22 in CRC cells.CONCLUSION IL-22 promotes tumor growth and induces chemotherapy resistance in CRC cells by activating the EGFR/ERK signaling pathway.These findings suggest that targeting IL-22 or its downstream signaling may offer novel therapeutic strategies in CRC.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of h...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.展开更多
BACKGROUND In patients with colorectal cancer(CRC),tumour metastasis is the leading cause of death.The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments.SPDL1 has b...BACKGROUND In patients with colorectal cancer(CRC),tumour metastasis is the leading cause of death.The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments.SPDL1 has been implicated in the deve-lopment of CRC,however,its mechanism of action remains unclear.AIM To investigate the role and mechanism of action by which SPDL1 inhibits the development and metastasis of CRC.METHODS In this study,we examined the relationship between SPDL1 expression and CRC prognosis using immunohistochemistry.Survival analyses were performed using Kaplan-Meier analysis and log-rank test.After knocking down SPDL1 in the HCT116 cancer cell line changes in cell viability,migration,invasion,and gene expression were examined using a cell counting kit 8 assay,Transwell assay,and Western blot.The effect of SPDL1 on the cell cycle was assessed using flow cy-tometry.RNA sequencing was used to analyse the effect of SPDL1 on gene expression of CRC cells.The mechanism of action of SPDL1 in CRC was further clarified using U0126,an inhibitor of the mitogen-activated protein kinase signaling pathway.RESULTS SPDL1 is expressed at low levels in tissues of patients with CRC,and this reduced expression is associated with poor prognosis.Functionally,low expression of SPDL1 in CRC promotes cell proliferation,migration,invasion,and affects the cell cycle.Mechanistically,SPDL1 affects the progression of CRC through its regulation of the process of epithelial-mesenchymal transition(EMT)and of the epidermal growth factor receptor(EGFR)/extracellular signal-regulated kinase(ERK)signaling pathways.CONCLUSION This study showed that the loss of SPDL1 may induce EMT and promote cell migration and invasion in CRC through the EGFR/ERK pathway.展开更多
The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its ...The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its implications for various kidney diseases.EGFR signaling is essential for kidney function and repair mechanisms,and its dysregulation significantly impacts both acute and chronic kidney conditions.The review discusses the normal distribution of EGFR in kidney tubular segments,the mechanism of its activation and inhibition,and the therapeutic potential of EGFR-targeting antagonists and ligands.Additionally,it explores the pathophysiological characteristics observed in rodent models of kidney diseases through pharmacological and genetic inhibition of EGFR,highlighting therapeutic challenges and limitations such as species differences,variability in disease models,and potential adverse effects.Overall,the findings underscore the multifaceted role of EGFR in kidney diseases,influencing inflammation,fibrosis,and tissue injury.This complex involvement suggests that targeting EGFR may be a beneficial therapeutic strategy for managing these conditions,potentially mitigating inflammation and fibrosis while promoting tissue repair.展开更多
BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is over...BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is overexpressed in a subset of pa-tients with colorectal cancer and has been established as a therapeutic target.CASE SUMMARY This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors(ICIs)in combination with pyrotinib.The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression.CONCLUSION ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer.Chemotherapy following disease progression could enhance efficacy synergistically.展开更多
BACKGROUND Yinchenhao decoction(YCHD)is a traditional Chinese medicine widely used to treat liver damage caused by obstructive jaundice(OJ).Although YCHD has demonstrated protective effects against liver damage,reduce...BACKGROUND Yinchenhao decoction(YCHD)is a traditional Chinese medicine widely used to treat liver damage caused by obstructive jaundice(OJ).Although YCHD has demonstrated protective effects against liver damage,reduced apoptosis,and mitigated oxidative stress in OJ,the precise molecular mechanisms involved remain poorly understood.AIM To investigate the beneficial effects of YCHD on OJ and elucidate the underlying mechanisms.METHODS The active constituents of YCHD were identified using liquid chromatography tandem mass spectrometry,and their potential targets for OJ treatment were predicted through network pharmacology.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.An OJ rat model was established by common bile duct ligation.Rats were divided into three groups:Sham surgery(S Group),model(O Group),and YCHD(Y Group).YCHD was administered to Group Y for one week.Bilirubin levels,liver function parameters,and bile acid concentrations in blood and urine were measured by enzyme-linked immunosorbent assay.The bile acid renal clearance rate(Clr)was calculated.Histopathological evaluation of liver and kidney tissues was performed using hematoxylin-eosin staining.Western blotting was utilized to assess the expression of key bile acid metabolism and transport proteins in both liver and kidney tissues.The expression of the constitutive androstane receptor(CAR)and its nuclear localization were evaluated by immunohistochemistry.Molecular docking studies identified the epidermal growth factor receptor(EGFR)as a potential target of YCHD's active components.An OJ cell model was created using human liver(L02)and renal tubular epithelial(HK-2)cells,which were treated with YCHD-containing serum.Western blotting and immunofluorescence assays were employed to evaluate CAR expression and its nuclear localization in relation to EGFR activation.RESULTS Network analysis identified the EGFR signaling pathway as a key mechanism through which YCHD exerts its effects on OJ.In vivo experiments showed that YCHD improved liver function,reduced OJ-induced pathology in liver and kidney tissues,and decreased serum bile acid content by enhancing bile acid Clr and urine output.YCHD also increased CAR expression and nuclear heterotopy,upregulating proteins involved in bile acid metabolism and transport,including CYP3A4,UGT1A1,MRP3,and MRP4 in the liver,and MRP2 and MRP4 in the kidneys.In vitro,YCHD increased CAR expression and nuclear heterotopy in L02 and HK-2 cells,an effect that was reversed by EGFR agonists.CONCLUSION YCHD enhances bile acid metabolism in the liver and promotes bile acid excretion in the kidneys,ameliorating liver damage caused by OJ.These effects are likely mediated by the upregulation of CAR and its nuclear translocation.展开更多
BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regim...BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase III clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.展开更多
BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC r...BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability.Reliable prognostic markers are critical to guide clinical management.AIM To investigate the prognostic factors,including human epidermal growth factor receptor 2(HER2)expression,associated with survival outcomes in patients with gastric SRCC.METHODS A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted,assessing demographic,clinical,and pathological data.HER2 expression was analyzed using immunohistochemistry,and survival outcomes,including overall survival and disease-free survival,were examined.RESULTS With a median follow-up of 43 months,the median patient age was 50 years,and males exhibited a higher mortality rate(P=0.0107).Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality(P=0.00149 and P=0.00163,respectively).Advanced tumornode-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes(P<0.001 and P=0.019).HER2 positivity correlated with higher mortality(P=0.00882)but was not significantly linked to recurrence(P=0.53).Surgical treatment significantly improved survival compared with non-surgical approaches(P=0.0226).CONCLUSION These findings highlight the aggressive nature of SRCC with advanced disease stage,elevated tumor markers,and lymphovascular invasion contributing to poor outcomes.HER2 expression,though infrequent,may indicate worse prognosis,reinforcing the role of surgical intervention in survival improvement.展开更多
BACKGROUND Epidermal growth factor receptor(EGFR)is a transmembrane protein that is differentially expressed in gestational diabetes mellitus(GDM).Endothelial dy-sfunction is a hallmark of GDM and plays a key role in ...BACKGROUND Epidermal growth factor receptor(EGFR)is a transmembrane protein that is differentially expressed in gestational diabetes mellitus(GDM).Endothelial dy-sfunction is a hallmark of GDM and plays a key role in its pathogenesis.EGFR is associated with endothelial dysfunction in the context of various diseases.How-ever,the exact mechanism by which EGFR causes endothelial dysfunction in GDM is unknown,particularly its regulation at the transcriptional and protein levels.METHODS Quantitative real-time polymerase chain reaction was used to detect the ex-pression of EGFR and H19.Western blotting was used to detect the expression of endothelial cell dysfunction markers.A cell counting kit 8 assay was used to assess cell viability,flow cytometry was used to assess apoptosis,scratch and Transwell assays were used to assess cell migration,and a tube formation assay was used to assess cell vascular formation.Hematoxylin-eosin staining was used to observe histopathological changes in the placentas of the mice.RESULTS In this study,EGFR was upregulated in clinical samples,GDM animal models and GDM cell models,and the knockdown of EGFR could mitigate the effect of streptozotocin(STZ)and high glucose(HG);promoted the proliferation,migration and vascularization of human umbilical vein endothelial cells(HUVECs);inhibited cell apoptosis and the expression of endothelial cell dysfunction markers(vascular cell adhesion molecule-1,tumor necrosis factor-α,vascular endothelial growth factor-A,and intercellular cell adhesion molecule-1);and alleviated the process of GDM in vivo.Mechanistically,EIF4A3 binding to long noncoding RNA H19 increased the stability of EGFR messenger RNA,thereby promoting HG-induced HUVECs dysfunction or STZ-induced endothelial cell dysfunction in GDM mice.In addition,ERRFI1 also regulated the expression of EGFR,and ERRFI1 inhibited EGFR activity by binding to EGFR,thereby inhibiting HG-induced HUVECs dysfunction.CONCLUSION Our study revealed that EGFR can accelerate the development of GDM by promoting endothelial cell dysfunction.展开更多
BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ...BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.展开更多
BACKGROUND Dry eye syndrome(DES)after diabetic cataract surgery can seriously affect the patient’s quality of life.Therefore,effective alleviation of symptoms in patients with this disease has important clinical sign...BACKGROUND Dry eye syndrome(DES)after diabetic cataract surgery can seriously affect the patient’s quality of life.Therefore,effective alleviation of symptoms in patients with this disease has important clinical significance.AIM To explore the clinical effect of recombinant human epidermal growth factor(rhEGF)plus sodium hyaluronate(SH)eye drops on DES after cataract surgery in patients with diabetes.METHODS We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital,Affiliated Hospital of Nankai University between April 2021 and April 2023.They were classified into an observation group(42 cases,rhEGF+SH eye drops)and a control group(40 cases,SH eye drops alone),depending on the different treatment schemes.The therapeutic efficacy,dry eye symptom score,tear film breakup time(TFBUT),basic tear secretion score[assessed using Schirmer I test(SIt)],corneal fluorescein staining(FL)score,tear inflammatory markers,adverse reactions during treat-ment,and treatment satisfaction were compared between the two groups.RESULTS Therapeutic efficacy was higher in the observation group compared with the control group.Both groups showed improved TFBUT and dry eye,as well as improved SIt and FL scores after treatment,with a more pronounced improvement in the observation group.Although no marked differences in adverse reactions were observed between the two groups,treatment satisfaction was higher in the observation group.CONCLUSION rhEGF+SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy,fewer adverse reactions,and high safety levels.Thus,this treatment should be promoted in clinical practice.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explo...Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.展开更多
BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically conside...BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.展开更多
Background:Toxic Epidermal Necrolysis(TEN)is a potentially fatal dermatological condition primarily triggered by adverse drug reactions.It is characterized by extensive epidermal necrosis and separation,affecting more...Background:Toxic Epidermal Necrolysis(TEN)is a potentially fatal dermatological condition primarily triggered by adverse drug reactions.It is characterized by extensive epidermal necrosis and separation,affecting more than 30%of the body surface area,and leading to severe complications such as sepsis and multi-organ failure.Common causative agents include antibiotics,anticonvulsants,and NSAIDs.The pathophysiology of TEN in-volves an immune-mediated response,where cytotoxic T lymphocytes(CTLs)and natural killer(NK)cells release cytotoxic proteins such as perforin,granzyme B,and granulysin,leading to widespread keratinocyte apoptosis.This immune response results in massive skin detachment and mucosal damage.Despite its rarity,TEN has a high mortality rate,necessitating early diagnosis and intervention.Case presentation:This paper provides a comprehensive review of TEN,discussing its history,pathophysiology,clinical features,and current understanding of treatment strategies.A case series of 11 patients who developed TEN after exposure to various drugs,including Lamotrigine,Phenytoin,Diclofenac,Ibuprofen,Aceclofenac,Amoxicillin,Sulfadoxine-Pyrimethamine,Amoxiclav,and Gabapentin,is presented.The cases highlight the importance of early drug discontinuation,supportive care,and adjunctive therapies such as intravenous immunoglobulin(IVIG)and corticosteroids.Prognostic factors,such as the extent of skin detachment and sys-temic complications,significantly influenced patient outcomes.All patients recovered with timely intervention and intensive care,except for a few who succumbed to the severity of the condition.Conclusion:This study underscores the need for early intervention,multidisciplinary care,and robust pharma-covigilance systems to reduce the incidence and severity of TEN.Increased awareness of risk factors and early recognition of symptoms associated with high-risk medications are crucial in improving patient outcomes and reducing mortality.展开更多
Continuous monitoring of biosignals is essential for advancing early disease detection,personalized treatment,and health management.Flexible electronics,capable of accurately monitoring biosignals in daily life,have g...Continuous monitoring of biosignals is essential for advancing early disease detection,personalized treatment,and health management.Flexible electronics,capable of accurately monitoring biosignals in daily life,have garnered considerable attention due to their softness,conformability,and biocompatibility.However,several challenges remain,including imperfect skin-device interfaces,limited breathability,and insufficient mechanoelectrical stability.On-skin epidermal electronics,distinguished by their excellent conformability,breathability,and mechanoelectrical robustness,offer a promising solution for high-fidelity,long-term health monitoring.These devices can seamlessly integrate with the human body,leading to transformative advancements in future personalized healthcare.This review provides a systematic examination of recent advancements in on-skin epidermal electronics,with particular emphasis on critical aspects including material science,structural design,desired properties,and practical applications.We explore various materials,considering their properties and the corresponding structural designs developed to construct high-performance epidermal electronics.We then discuss different approaches for achieving the desired device properties necessary for long-term health monitoring,including adhesiveness,breathability,and mechanoelectrical stability.Additionally,we summarize the diverse applications of these devices in monitoring biophysical and physiological signals.Finally,we address the challenges facing these devices and outline future prospects,offering insights into the ongoing development of on-skin epidermal electronics for long-term health monitoring.展开更多
BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive...BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.展开更多
BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses si...BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.展开更多
基金supported by the Central Guidance for Local Projects of Xinjiang(ZYYD2024ZY04)the National Natural Science Foundation of China(32260116).
文摘Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in humans and other species have demonstrated its pivotal role in regulating the sodium ion balance and mediating sodium and water reabsorption in the kidney's proximal tubules.However,the impact of EGFR gene in how the Yarkand hare(Lepus yarkandensis)adapts to extreme environmental habitat remains unclear,The Yarkand hare is a desert-dwelling animal with multiple adaptations to cope with drought.Given the important physiological function of EGFR gene,we strived to understand its role in arid environment and explore the molecular mechanism of drought tolerance in the Yarkand hare.We first performed segmental cloning of the CDS of the Yarkand hare EGFR gene.Then,We constructed the phylogenetic tree of the Yarkand hare's EGFR gene and compared it with that of other species.The results showed that the Yarkand hare was most closely related to the Tolai hare(Lepus tolai).Through quantitative reverse transcription polymerase chain reaction(RT-qPCR),we discovered that EGFR expression in the kidneys of the Yarkand hare was higher than in the allopatric Tolai hare from non-arid areas.Therefore,we hypothesized that EGFR gene overexpression in the kidney of the Yarkand hare may play a crucial role in drought adaptability.Subsequently,we inserted CDS of EGFR gene into a pcDNA3.1-EGFP expression vector to construct recombinant plasmid,which was transfected into HeLa cells and overexpressed.RT-qPCR demonstrated a notable and statistically significant increase in EGFR mRNA expression and western blot proved stable expression of this protein in HeLa cells.Through cell experiments,EGFR gene overexpression markedly enhanced the survival of Hela cells subjected to NaCl,H_(2)O_(2),and heat stresses,increased superoxide dismutase activity,and decreased malondialdehyde content.In conclusion,these findings preliminarily suggest that EGFR might help the Yarkand hare adapt to extreme environmental conditions.EGFR manipulation in vivo could be a promising strategy to enhance the resilience of animals to extreme conditions.
文摘BACKGROUND Interleukin-22(IL-22)belongs to the IL-10 cytokine family,recognized for its ability to modulate diverse immune responses.Previous studies have indicated that IL-22 promotes cancer advancement and metastasis.However,the precise function of IL-22 in colorectal cancer(CRC)remains unclear.AIM To investigate the role of IL-22 in promoting stem cell-like characteristics and chemotherapy resistance in CRC cells,as well as to elucidate the mechanisms underlying these effects.METHODS HCT116 cells were treated with IL-22(50 ng/mL)and oxaliplatin(L-OHP,5μg/mL).A series of functional assays-including cell counting kit-8 assay,tumor sphere formation assay,and cell apoptosis assay-were conducted to assess the effects of IL-22 on cell viability and stem cell-like characteristics.The expression of stemness-related markers(SOX2,Oct4,NANOG,and Bmi-1)was examined using Western blot analysis.Additionally,the total and phosphorylated levels of epidermal growth factor receptor(EGFR),protein kinase B(AKT),and extracellular signal-regulated kinase(ERK)were evaluated by Western blot.An EGFR inhibitor,osimertinib(Osi),was used to assess the pathway's functional relevance.RESULTS IL-22 treatment promotes CRC cell proliferation,enhances sphere formation,and elevates the expression of stem cell markers,including SOX2,Oct4,NANOG,and Bmi-1.IL-22 treatment increases the phosphorylation of EGFR,AKT,and ERK.Additionally,IL-22 treatment mitigates the cytotoxic effects and the ability to induce apoptosis of L-OHP.Furthermore,IL-22 treatment activated the EGFR/ERK signaling pathway by increasing the phosphorylation of EGFR,AKT,and ERK.Importantly,the use of the EGFR inhibitor Osi significantly counteracted the chemoresistance induced by IL-22 in CRC cells.CONCLUSION IL-22 promotes tumor growth and induces chemotherapy resistance in CRC cells by activating the EGFR/ERK signaling pathway.These findings suggest that targeting IL-22 or its downstream signaling may offer novel therapeutic strategies in CRC.
基金This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City(No.FZ202103).
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.
基金Supported by the Natural Science Foundation of Guangxi Province,No.2019GXNSFAA185030 and No.2023GXNSFBA026129the Scientific Research Project of the Second Affiliated Hospital of Guangxi Medical University,No.EFYKY2020013the Cultivation Science Foundation of the Second Affiliated Hospital of Guangxi Medical University,No.GJPY2023005 and No.GJPY2023009.
文摘BACKGROUND In patients with colorectal cancer(CRC),tumour metastasis is the leading cause of death.The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments.SPDL1 has been implicated in the deve-lopment of CRC,however,its mechanism of action remains unclear.AIM To investigate the role and mechanism of action by which SPDL1 inhibits the development and metastasis of CRC.METHODS In this study,we examined the relationship between SPDL1 expression and CRC prognosis using immunohistochemistry.Survival analyses were performed using Kaplan-Meier analysis and log-rank test.After knocking down SPDL1 in the HCT116 cancer cell line changes in cell viability,migration,invasion,and gene expression were examined using a cell counting kit 8 assay,Transwell assay,and Western blot.The effect of SPDL1 on the cell cycle was assessed using flow cy-tometry.RNA sequencing was used to analyse the effect of SPDL1 on gene expression of CRC cells.The mechanism of action of SPDL1 in CRC was further clarified using U0126,an inhibitor of the mitogen-activated protein kinase signaling pathway.RESULTS SPDL1 is expressed at low levels in tissues of patients with CRC,and this reduced expression is associated with poor prognosis.Functionally,low expression of SPDL1 in CRC promotes cell proliferation,migration,invasion,and affects the cell cycle.Mechanistically,SPDL1 affects the progression of CRC through its regulation of the process of epithelial-mesenchymal transition(EMT)and of the epidermal growth factor receptor(EGFR)/extracellular signal-regulated kinase(ERK)signaling pathways.CONCLUSION This study showed that the loss of SPDL1 may induce EMT and promote cell migration and invasion in CRC through the EGFR/ERK pathway.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)and funded by the Ministry of Education(2021R1I1A3056002,to Jinu Kim,RS-2023-00274853,to Daeun MOON).
文摘The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its implications for various kidney diseases.EGFR signaling is essential for kidney function and repair mechanisms,and its dysregulation significantly impacts both acute and chronic kidney conditions.The review discusses the normal distribution of EGFR in kidney tubular segments,the mechanism of its activation and inhibition,and the therapeutic potential of EGFR-targeting antagonists and ligands.Additionally,it explores the pathophysiological characteristics observed in rodent models of kidney diseases through pharmacological and genetic inhibition of EGFR,highlighting therapeutic challenges and limitations such as species differences,variability in disease models,and potential adverse effects.Overall,the findings underscore the multifaceted role of EGFR in kidney diseases,influencing inflammation,fibrosis,and tissue injury.This complex involvement suggests that targeting EGFR may be a beneficial therapeutic strategy for managing these conditions,potentially mitigating inflammation and fibrosis while promoting tissue repair.
基金Supported by the Jiangsu Provincial Health and Family Planning Commission Personnel Talent Project,No.R2017005.
文摘BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is overexpressed in a subset of pa-tients with colorectal cancer and has been established as a therapeutic target.CASE SUMMARY This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors(ICIs)in combination with pyrotinib.The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression.CONCLUSION ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer.Chemotherapy following disease progression could enhance efficacy synergistically.
基金Supported by Tianjin Municipal Education Commission Scientific Research Program,China,No.2022KJ271.
文摘BACKGROUND Yinchenhao decoction(YCHD)is a traditional Chinese medicine widely used to treat liver damage caused by obstructive jaundice(OJ).Although YCHD has demonstrated protective effects against liver damage,reduced apoptosis,and mitigated oxidative stress in OJ,the precise molecular mechanisms involved remain poorly understood.AIM To investigate the beneficial effects of YCHD on OJ and elucidate the underlying mechanisms.METHODS The active constituents of YCHD were identified using liquid chromatography tandem mass spectrometry,and their potential targets for OJ treatment were predicted through network pharmacology.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.An OJ rat model was established by common bile duct ligation.Rats were divided into three groups:Sham surgery(S Group),model(O Group),and YCHD(Y Group).YCHD was administered to Group Y for one week.Bilirubin levels,liver function parameters,and bile acid concentrations in blood and urine were measured by enzyme-linked immunosorbent assay.The bile acid renal clearance rate(Clr)was calculated.Histopathological evaluation of liver and kidney tissues was performed using hematoxylin-eosin staining.Western blotting was utilized to assess the expression of key bile acid metabolism and transport proteins in both liver and kidney tissues.The expression of the constitutive androstane receptor(CAR)and its nuclear localization were evaluated by immunohistochemistry.Molecular docking studies identified the epidermal growth factor receptor(EGFR)as a potential target of YCHD's active components.An OJ cell model was created using human liver(L02)and renal tubular epithelial(HK-2)cells,which were treated with YCHD-containing serum.Western blotting and immunofluorescence assays were employed to evaluate CAR expression and its nuclear localization in relation to EGFR activation.RESULTS Network analysis identified the EGFR signaling pathway as a key mechanism through which YCHD exerts its effects on OJ.In vivo experiments showed that YCHD improved liver function,reduced OJ-induced pathology in liver and kidney tissues,and decreased serum bile acid content by enhancing bile acid Clr and urine output.YCHD also increased CAR expression and nuclear heterotopy,upregulating proteins involved in bile acid metabolism and transport,including CYP3A4,UGT1A1,MRP3,and MRP4 in the liver,and MRP2 and MRP4 in the kidneys.In vitro,YCHD increased CAR expression and nuclear heterotopy in L02 and HK-2 cells,an effect that was reversed by EGFR agonists.CONCLUSION YCHD enhances bile acid metabolism in the liver and promotes bile acid excretion in the kidneys,ameliorating liver damage caused by OJ.These effects are likely mediated by the upregulation of CAR and its nuclear translocation.
基金Supported by CAMS Innovation Fund for Medical Sciences CIFMS,No.2023-I2M-3-012.
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase III clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.
文摘BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability.Reliable prognostic markers are critical to guide clinical management.AIM To investigate the prognostic factors,including human epidermal growth factor receptor 2(HER2)expression,associated with survival outcomes in patients with gastric SRCC.METHODS A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted,assessing demographic,clinical,and pathological data.HER2 expression was analyzed using immunohistochemistry,and survival outcomes,including overall survival and disease-free survival,were examined.RESULTS With a median follow-up of 43 months,the median patient age was 50 years,and males exhibited a higher mortality rate(P=0.0107).Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality(P=0.00149 and P=0.00163,respectively).Advanced tumornode-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes(P<0.001 and P=0.019).HER2 positivity correlated with higher mortality(P=0.00882)but was not significantly linked to recurrence(P=0.53).Surgical treatment significantly improved survival compared with non-surgical approaches(P=0.0226).CONCLUSION These findings highlight the aggressive nature of SRCC with advanced disease stage,elevated tumor markers,and lymphovascular invasion contributing to poor outcomes.HER2 expression,though infrequent,may indicate worse prognosis,reinforcing the role of surgical intervention in survival improvement.
基金Supported by the Youth Talent Program of Yunnan“Ten-thousand Talents Program”,No.YNWR-QNBJ-2018-169the Science Project of Yunnan Science and Technology Department,No.202201AY070001-068.
文摘BACKGROUND Epidermal growth factor receptor(EGFR)is a transmembrane protein that is differentially expressed in gestational diabetes mellitus(GDM).Endothelial dy-sfunction is a hallmark of GDM and plays a key role in its pathogenesis.EGFR is associated with endothelial dysfunction in the context of various diseases.How-ever,the exact mechanism by which EGFR causes endothelial dysfunction in GDM is unknown,particularly its regulation at the transcriptional and protein levels.METHODS Quantitative real-time polymerase chain reaction was used to detect the ex-pression of EGFR and H19.Western blotting was used to detect the expression of endothelial cell dysfunction markers.A cell counting kit 8 assay was used to assess cell viability,flow cytometry was used to assess apoptosis,scratch and Transwell assays were used to assess cell migration,and a tube formation assay was used to assess cell vascular formation.Hematoxylin-eosin staining was used to observe histopathological changes in the placentas of the mice.RESULTS In this study,EGFR was upregulated in clinical samples,GDM animal models and GDM cell models,and the knockdown of EGFR could mitigate the effect of streptozotocin(STZ)and high glucose(HG);promoted the proliferation,migration and vascularization of human umbilical vein endothelial cells(HUVECs);inhibited cell apoptosis and the expression of endothelial cell dysfunction markers(vascular cell adhesion molecule-1,tumor necrosis factor-α,vascular endothelial growth factor-A,and intercellular cell adhesion molecule-1);and alleviated the process of GDM in vivo.Mechanistically,EIF4A3 binding to long noncoding RNA H19 increased the stability of EGFR messenger RNA,thereby promoting HG-induced HUVECs dysfunction or STZ-induced endothelial cell dysfunction in GDM mice.In addition,ERRFI1 also regulated the expression of EGFR,and ERRFI1 inhibited EGFR activity by binding to EGFR,thereby inhibiting HG-induced HUVECs dysfunction.CONCLUSION Our study revealed that EGFR can accelerate the development of GDM by promoting endothelial cell dysfunction.
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
基金Supported by the National Natural Science Foundation of China,No.82100685the Scientific Research Fund of Xi’an Health Commission,No.2021yb08+1 种基金Scientific Research Fund of Xi’an Central Hospital,No.2022QN07Innovation Capability Support Plan of Xi’an Science and Technology Bureau,No.23YXYJ0097.
文摘BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.
基金Supported by Tianjin Health Research Project,No.TJWJ2023MS062。
文摘BACKGROUND Dry eye syndrome(DES)after diabetic cataract surgery can seriously affect the patient’s quality of life.Therefore,effective alleviation of symptoms in patients with this disease has important clinical significance.AIM To explore the clinical effect of recombinant human epidermal growth factor(rhEGF)plus sodium hyaluronate(SH)eye drops on DES after cataract surgery in patients with diabetes.METHODS We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital,Affiliated Hospital of Nankai University between April 2021 and April 2023.They were classified into an observation group(42 cases,rhEGF+SH eye drops)and a control group(40 cases,SH eye drops alone),depending on the different treatment schemes.The therapeutic efficacy,dry eye symptom score,tear film breakup time(TFBUT),basic tear secretion score[assessed using Schirmer I test(SIt)],corneal fluorescein staining(FL)score,tear inflammatory markers,adverse reactions during treat-ment,and treatment satisfaction were compared between the two groups.RESULTS Therapeutic efficacy was higher in the observation group compared with the control group.Both groups showed improved TFBUT and dry eye,as well as improved SIt and FL scores after treatment,with a more pronounced improvement in the observation group.Although no marked differences in adverse reactions were observed between the two groups,treatment satisfaction was higher in the observation group.CONCLUSION rhEGF+SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy,fewer adverse reactions,and high safety levels.Thus,this treatment should be promoted in clinical practice.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.
基金Supported by Wu Jieping Medical Foundation,No.320.6750.2022-20-25and Chongqing Health Commission,No.[2020]68.
文摘BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.
文摘Background:Toxic Epidermal Necrolysis(TEN)is a potentially fatal dermatological condition primarily triggered by adverse drug reactions.It is characterized by extensive epidermal necrosis and separation,affecting more than 30%of the body surface area,and leading to severe complications such as sepsis and multi-organ failure.Common causative agents include antibiotics,anticonvulsants,and NSAIDs.The pathophysiology of TEN in-volves an immune-mediated response,where cytotoxic T lymphocytes(CTLs)and natural killer(NK)cells release cytotoxic proteins such as perforin,granzyme B,and granulysin,leading to widespread keratinocyte apoptosis.This immune response results in massive skin detachment and mucosal damage.Despite its rarity,TEN has a high mortality rate,necessitating early diagnosis and intervention.Case presentation:This paper provides a comprehensive review of TEN,discussing its history,pathophysiology,clinical features,and current understanding of treatment strategies.A case series of 11 patients who developed TEN after exposure to various drugs,including Lamotrigine,Phenytoin,Diclofenac,Ibuprofen,Aceclofenac,Amoxicillin,Sulfadoxine-Pyrimethamine,Amoxiclav,and Gabapentin,is presented.The cases highlight the importance of early drug discontinuation,supportive care,and adjunctive therapies such as intravenous immunoglobulin(IVIG)and corticosteroids.Prognostic factors,such as the extent of skin detachment and sys-temic complications,significantly influenced patient outcomes.All patients recovered with timely intervention and intensive care,except for a few who succumbed to the severity of the condition.Conclusion:This study underscores the need for early intervention,multidisciplinary care,and robust pharma-covigilance systems to reduce the incidence and severity of TEN.Increased awareness of risk factors and early recognition of symptoms associated with high-risk medications are crucial in improving patient outcomes and reducing mortality.
基金supported by National Natural Science Foundation of China(Grant Nos.52025055,52375576,52350349)Key Research and Development Program of Shaanxi(Program No.2022GXLH-01-12)+2 种基金Joint Fund of Ministry of Education for Equipment Pre-research(No.8091B03012304)Aeronautical Science Foundation of China(No.2022004607001)the Fundamental Research Funds for the Central Universities(No.xtr072024031).
文摘Continuous monitoring of biosignals is essential for advancing early disease detection,personalized treatment,and health management.Flexible electronics,capable of accurately monitoring biosignals in daily life,have garnered considerable attention due to their softness,conformability,and biocompatibility.However,several challenges remain,including imperfect skin-device interfaces,limited breathability,and insufficient mechanoelectrical stability.On-skin epidermal electronics,distinguished by their excellent conformability,breathability,and mechanoelectrical robustness,offer a promising solution for high-fidelity,long-term health monitoring.These devices can seamlessly integrate with the human body,leading to transformative advancements in future personalized healthcare.This review provides a systematic examination of recent advancements in on-skin epidermal electronics,with particular emphasis on critical aspects including material science,structural design,desired properties,and practical applications.We explore various materials,considering their properties and the corresponding structural designs developed to construct high-performance epidermal electronics.We then discuss different approaches for achieving the desired device properties necessary for long-term health monitoring,including adhesiveness,breathability,and mechanoelectrical stability.Additionally,we summarize the diverse applications of these devices in monitoring biophysical and physiological signals.Finally,we address the challenges facing these devices and outline future prospects,offering insights into the ongoing development of on-skin epidermal electronics for long-term health monitoring.
基金Supported by China Scientific Research Fund for HER2 Target from China Anti-Cancer Association,No.CORP-239-M9.
文摘BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.
基金the Tianjin Municipal Education Commission Scientific Research Project,No.2018KJ055.
文摘BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.
