Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

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.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

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.

Efficacy of recombinant human epidermal growth factor plus sodium hyaluronate eye drops in diabetic dry eye post-cataract surgery

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.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

A Generic Strategy to Create Mechanically Interlocked Nanocomposite/Hydrogel Hybrid Electrodes for Epidermal Electronics

Stretchable electronics are crucial enablers for next-generation wearables intimately integrated into the human body.As the primary compliant conductors used in these devices,metallic nanostructure/elastomer composites often struggle to form conformal contact with the textured skin.Hybrid electrodes have been consequently developed based on conductive nanocomposite and soft hydrogels to establish seamless skin-device interfaces.However,chemical modifications are typically needed for reliable bonding,which can alter their original properties.To overcome this limitation,this study presents a facile fabrication approach for mechanically interlocked nanocomposite/hydrogel hybrid electrodes.In this physical process,soft microfoams are thermally laminated on silver nanowire nanocomposites as a porous interface,which forms an interpenetrating network with the hydrogel.The microfoam-enabled bonding strategy is generally compatible with various polymers.The resulting interlocked hybrids have a 28-fold improved interfacial toughness compared to directly stacked hybrids.These electrodes achieve firm attachment to the skin and low contact impedance using tissue-adhesive hydrogels.They have been successfully integrated into an epidermal sleeve to distinguish hand gestures by sensing mus-cle contractions.Interlocked nanocomposite/hydrogel hybrids reported here offer a promising platform to combine the benefits of both materials for epidermal devices and systems.

Gigantic occipital epidermal cyst in a 56-year-old female:A case report

BACKGROUND Gigantic epidermal cysts(GECs)are rare benign skin appendicular tumours also known as keratinocysts.GECs have a high incidence and their wall is made up of epidermis.Epidermal cysts can occur in any part of the skin;clinical manifestations include skin colour hemispherical swelling;cystic;mobile;0.5 cm to several centimetres in diameter;and slow growth.CASE SUMMARY Herein,we report a case involving a 56-year-old female with a GEC in the occipitalia.On July 25,2023,a patient with a GEC was admitted to the neurosurgery Department of the Second Affiliated Hospital of Xi'an Medical University.The phyma was shown to be a solid mass during the operation and was confirmed to be a GEC based on pathological examination.CONCLUSION Epidermal cysts are common cystic nodules on the surface of the body,the aetiology is unclear,the clinical manifestations can vary,and the misdiagnosis rate is high.However,giant epidermal cysts are rare.In most cases,however,the prognosis is satisfactory.This paper analyses and summarizes the population,location,clinical and pathological characteristics and pathogenesis of the disease to strengthen the understanding of this disease and improve the accuracy of clinical diagnosis.

Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis:A case report

BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.

Double plasma molecular adsorption system for Stevens–Johnson syndrome/toxic epidermal necrolysis:A case report

BACKGROUND Stevens–Johnson syndrome and toxic epidermal necrolysis(SJS/TEN)are very serious skin allergies,with an etiology related to infections and medication.Since the coronavirus disease 2019(COVID-19)pandemic,severe acute respiratory syndrome coronavirus-2 has also been considered to cause SJS/TEN.CASE SUMMARY We report the case of a woman in her thirties who took acetaminophen after contracting COVID-19.After 3 d of fever relief,she experienced high fever and presented with SJS/TEN symptoms,accompanied by intrahepatic cholestasis.Three days of corticosteroid treatment did not alleviate the skin damage;therefore,double plasma molecular adsorption system(DPMAS)therapy was initiated,with treatment intervals of 48 h.Her skin symptoms improved gradually and were resolved after seven DPMAS treatments.CONCLUSION DPMAS therapy is beneficial for abrogating SJS/TEN because plasma adsorption and perfusion techniques reduce the inflammatory mediators(e.g.,tumor necrosis factor-alpha and interleukin-10 and-12)speculated to be involved in the pathology of the skin conditions.

The Effect of a Novel Complex, Composed of Ceramide, Energizing Peptide and Camu Camu Extract, on Epidermal Barrier Function and Dermal Antiaging Properties in Ex Vivo Human Skin Small Live Cohort

The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary structures and components responsible for the skin’s barrier function are susceptible to environmental variables, dermatological conditions, and the aging process. The ensuing alterations to structure, composition, and organizational attributes of the epidermal barrier can impact its integrity and functionality. The aim of this study was to assess the effect of a novel complex composed of a ceramide, energizing peptide, and Camu Camu extract (SUPCERATTM complex) on specific markers of epidermal barrier integrity, as well as epidermal and dermal function. All the experiments were conducted on fresh human abdominal skin explants. Intradermal production of hyaluronic acid, epidermal claudin-1, and ceramide synthase 3 expressions, as well as epidermal lipids content were assessed using specific fluorescent stainings on ex vivo skin after the application of the complex or placebo. Additionally, dermal elastase and collagenase activities were assessed using in tubo enzymatic assays. Lastly, the effect of a cosmetic cream containing SUPCERATTM complex was assessed using subjective Global Aesthetic Improvement Scale (GAIS) in a small cohort of patients after 60 days of use. The application of the SUPCERATTM complex on ex vivo skin led to significant increase in dermal hyaluronic acid content and epidermal activity of claudin-1, ceramide synthase 3 and epidermal ceramide content. Furthermore, in tubo enzymatic assays demonstrated inhibition of both dermal elastase and collagenase activities. In addition, the patient-reported results indicated significant improvements in skin quality and appearance. .

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

Design of Novel Wound Dressing Composed of Collagen and Hyaluronic Acid Containing Epidermal Growth Factor

This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable state. The sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of Col. Both sides of sponge were treated with ultraviolet (UV) irradiation to introduce intermolecular cross links between collagen molecules. This sponge was named Sponge-Col. Another sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of HA containing EGF. This sponge was named Sponge-HA/EGF. The wound dressing was manufactured by laminating Sponge-Col on the top, Sponge-HA/EGF in the middle, and Sponge-Col on the bottom to create a sandwich structure. This method can prevent the reducing of EGF activity due to UV irradiation for intermolecular cross-linking. Second important issue is to enable gradual release of EGF from the wound dressing. The elution behavior of this wound dressing was investigated by measuring the weight change after immersion in water for a predetermined time. This wound dressing showed initially fast elution and subsequent very slow elution properties. The upper layer and lower layer Sponge-Col enabled gradual release of the middle layer Sponge-HA/EGF. This result suggests that EGF contained in the wound dressing is gradually released together with HA from the wound dressing. Third important issue is to provide moist wound-healing environment. The upper layer and lower layer Sponge-Col can provide the wound dressing with high water absorption and long-term water retention properties.

Comparative Observation on Nursing Effect of Nursing Intervention and Routine Nursing in Patients with Renal Calculi and Gastric Ulcer and the Impacts on Epidermal Growth Factor

Objective: To explore the comparative observation on nursing effect of nursing intervention and routine nursing in patients with renal calculi and gastric ulcer and the impacts on epidermal growth factor. Methods: A total of 72 patients with renal calculi and gastric ulcer were selected and treated in our hospital from January 2018 to December 2018. They were divided into the observation group and the control group, 36 for each. Comprehensive nursing intervention was implemented in the observation group, whereas routine nursing was implemented in the control group. The level of epidermal growth factor, nursing satisfaction, renal calculi recurrence rate, average hospital stay and postoperative blood loss were compared between the two groups after nursing. Results: There was no significant difference in the level of epidermal growth factor between the two groups before nursing (P > 0.05), while after nursing, the level in the observation group was higher compared with the control group, and the difference between the two groups was significant (P Conclusion: With regard to patients with renal calculi and gastric ulcer, comprehensive nursing intervention can improve nursing satisfaction and quality of patients’ lives, reduce calculi recurrence rate, and increase the level of epidermal growth factor, which has clinical application value.

Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.

Epidermal growth factor prevents gut atrophy and maintains intestinal integrity in rats with acute pancreatitis

INTRODUCTIONThere is abundant evidence that stressful insults suchas acute pancreatitis may significantly alter themetabolism of the gut mucosa and therefore itsbarrier integrity,resulting in an increase in mucosalpermeability and subsequent translocation of entericbacteria and their cndotoxins.The fact thatmost bacteria associated with acute pancreatic andperipancreatic infections are of enteric originimplies that the gut plays a major role in

A CT-based radiomics nomogram for prediction of human epidermal growth factor receptor 2 status in patients with gastric cancer

Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric cancer.Methods: This retrospective study included 134 patients with gastric cancer(HER2-negative: n=87;HER2-positive: n=47) from April 2013 to March 2018, who were then randomly divided into training(n=94) and validation(n=40) cohorts. Radiomics features were obtained from the CT images showing gastric cancer. Least absolute shrinkage and selection operator(LASSO) regression analysis was utilized for building the radiomics signature. A multivariable logistic regression method was applied to develop a prediction model incorporating the radiomics signature and independent clinicopathologic risk predictors, which were then visualized as a radiomics nomogram. The predictive performance of the nomogram was assessed in the training and validation cohorts.Results: The radiomics signature was significantly associated with HER2 status in both training(P<0.001) and validation(P=0.023) cohorts. The prediction model that incorporated the radiomics signature and carcinoembryonic antigen(CEA) level demonstrated good discriminative performance for HER2 status prediction,with an area under the curve(AUC) of 0.799 [95% confidence interval(95% CI): 0.704-0.894] in the training cohort and 0.771(95% CI: 0.607-0.934) in the validation cohort. The calibration curve of the radiomics nomogram also showed good calibration. Decision curve analysis showed that the radiomics nomogram was useful.Conclusions: We built and validated a radiomics nomogram with good performance for HER2 status prediction in gastric cancer. This radiomics nomogram could serve as a non-invasive tool to predict HER2 status and guide clinical treatment.

Role of human epidermal growth factor receptor 2 in gastric cancer:Biological and pharmacological aspects

Amplification of the human epidermal growth factor receptor 2(HER2)gene and overexpression of the HER2protein is found in 15%-20%of patients with gastric and gastroesophageal junction cancer.The degree of HER2 overexpression and amplification varies with the location of the carcinoma,with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach.Further,HER2 overexpression and amplification also seems to be related to the Lauren histological classification,with higher levels found in the intestinal phenotype compared to the diffuse and mixed types.The prognostic properties of HER2 overexpression and amplification are still under debate,but a large number of studies seem to indicate that HER2 is a negative prognostic factor.The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial,where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive5-FU/capecitabine and cisplatin,either alone or in combination with trastuzumab.A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy.Patients with a strong overexpression of the HER2 protein(IHC3+)specifically benefited from the treatment,with a median overall survival of 17.9 mo.As a consequence of the positive results of the ToGA trial,patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2.The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab,ado-trastuzumab emtansine,lapatinib,afatinib,and dacomitinib,which are currently undergoing phaseⅡandⅢclinical testing.Overall,this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in relation to HER2 target therapy.

Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome

AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's corre-lation analysis. SERT function was examined by tritiated serotonin(5-HT) uptake experiments. Rat intestinal epithelial cells(IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor(EGFR).RESULTS: EGF levels were significantly lower in th rats with visceral hypersensitivity as measured in plas ma(2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, < 0.01) and in colonic tissue(3.244 ± 0.135 ng/10 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P 0.01) compared with controls. Moreover, the EGF leve were positively correlated with SERT levels(r = 0.820 P < 0.01). EGF displayed dose- and time-dependen increased SERT gene expressions in IEC-6 cells. A EGFR kinase inhibitor inhibited the effect of EGF o SERT gene upregulation. SERT activity was enhance following treatment with EGF(592.908 ± 31.515 fmo min per milligram vs 316.789 ± 85.652 fmol/min pe milligram protein, P < 0.05) and blocked by the EGF kinase inhibitor in IEC-6 cells(590.274 ± 25.954 fmo min per milligram vs 367.834 ± 120.307 fmol/min pe milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.