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 composite...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.展开更多
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...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.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 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
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 target...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.展开更多
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 o...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.展开更多
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,se...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.展开更多
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 s...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 (SUPCERAT<sup>TM</sup> 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 SUPCERAT<sup>TM</sup> 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 SUPCERAT<sup>TM</sup> 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. .展开更多
Efficient and flexible interactions require precisely converting human intentions into computer-recognizable signals,which is critical to the breakthrough development of metaverse.Interactive electronics face common d...Efficient and flexible interactions require precisely converting human intentions into computer-recognizable signals,which is critical to the breakthrough development of metaverse.Interactive electronics face common dilemmas,which realize highprecision and stable touch detection but are rigid,bulky,and thick or achieve high flexibility to wear but lose precision.Here,we construct highly bending-insensitive,unpixelated,and waterproof epidermal interfaces(BUW epidermal interfaces)and demonstrate their interactive applications of conformal human–machine integration.The BUW epidermal interface based on the addressable electrical contact structure exhibits high-precision and stable touch detection,high flexibility,rapid response time,excellent stability,and versatile“cut-and-paste”character.Regardless of whether being flat or bent,the BUW epidermal interface can be conformally attached to the human skin for real-time,comfortable,and unrestrained interactions.This research provides promising insight into the functional composite and structural design strategies for developing epidermal electronics,which offers a new technology route and may further broaden human–machine interactions toward metaverse.展开更多
Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin com...Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin compliance,mechanical properties,environmental adaptation,and biocompatibility to avoid signal attenuation and motion artifacts is challenging,and accurate physiological feature extraction necessitates effective signal-processing algorithms.This review presents the latest advancements in smart electrodes for epidermal electrophysiological monitoring,focusing on materials,structures,and algorithms.First,smart materials incorporating self-adhesion,self-healing,and self-sensing functions offer promising solutions for long-term monitoring.Second,smart meso-structures,together with micro/nanostructures endowed the electrodes with self-adaption and multifunctionality.Third,intelligent algorithms give smart electrodes a“soul,”facilitating faster and more-accurate identification of required information via automatic processing of collected electrical signals.Finally,the existing challenges and future opportunities for developing smart electrodes are discussed.Recognized as a crucial direction for next-generation epidermal electrodes,intelligence holds the potential for extensive,effective,and transformative applications in the future.展开更多
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 inhibitor...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.展开更多
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 t...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.展开更多
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 st...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.展开更多
An epidermal nevus(EN)is a common disease of various types,including verrucous EN,nevus sebaceous,inflammatory linear verrucous EN,Becker nevus,smooth muscle hamartoma,and nevus comedonicus.EN syndrome is a serious an...An epidermal nevus(EN)is a common disease of various types,including verrucous EN,nevus sebaceous,inflammatory linear verrucous EN,Becker nevus,smooth muscle hamartoma,and nevus comedonicus.EN syndrome is a serious and difficult-to-treat syndrome that is complicated by two or more abnormal organs or systems.To date,the mechanism of an EN is still unclear,and the therapies remain unsatisfactory.The most frequently used treatments are surgery and laser therapy.Several drugs have also been tested.An EN requires more attention,and further research is needed to provide appropriate and effective treatments for each patient.展开更多
Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), s...Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), such as monoclonal antibodies against epidermal growth factor receptor(anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent(40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.展开更多
Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced ...Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.展开更多
Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects...Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.展开更多
BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute lifethreatening skin reactions.AZD9291 has been developed as a third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhib...BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute lifethreatening skin reactions.AZD9291 has been developed as a third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)with activity against T790M mutation.CASE SUMMARY Herein we report a 68-year-old woman who developed a large area of skin necrosis and was diagnosed with toxic epidermal necrolysis after AZD-9291 ingestion.To the best of our knowledge,this is the first case reported in patients with EGFR T790M mutation in non-small cell lung cancer(NSCLC).Cabozantinib combined with erlotinib had clinically meaningful effectiveness,with additional toxicity that was generally manageable.CONCLUSION Treatment with AZD-9261 is effective in regressing the growth of the NSCLC and can bring some hope to despairing patients.We hope that more research will be carried out on the association between severe rashes and EGFR-TKIs,and more safe and effective drugs can be developed.展开更多
Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been de...Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.展开更多
BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal g...BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.展开更多
基金We acknowledge the support from the National Key Research and Development Program of China(Grant No.2022YFA1405000)the Natural Science Foundation of Jiangsu Province,Major Project(Grant No.BK20212004)+1 种基金the National Natural Science Foundation of China(Grant No.62374083)the State Key Laboratory of Analytical Chemistry for Life Science(Grant No.5431ZZXM2205).
文摘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.
文摘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.
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.
基金Supported by the Science and Technology Innovation Development Project of Tai’an,No.2021NS160the Medical and Health Science and Technology Development Plan of Shandong Province,No.202102010647。
文摘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.
文摘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.
文摘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.
文摘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 (SUPCERAT<sup>TM</sup> 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 SUPCERAT<sup>TM</sup> 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 SUPCERAT<sup>TM</sup> 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. .
基金supported by National Natural Science Foundation of China(52202117,52232006,52072029,and 12102256)Collaborative Innovation Platform Project of Fu-Xia-Quan National Independent Innovation Demonstration Zone(3502ZCQXT2022005)+3 种基金Natural Science Foundation of Fujian Province of China(2022J01065)State Key Lab of Advanced Metals and Materials(2022-Z09)Fundamental Research Funds for the Central Universities(20720220075)the Ministry of Education,Singapore,under its MOE ARF Tier 2(MOE2019-T2-2-179).
文摘Efficient and flexible interactions require precisely converting human intentions into computer-recognizable signals,which is critical to the breakthrough development of metaverse.Interactive electronics face common dilemmas,which realize highprecision and stable touch detection but are rigid,bulky,and thick or achieve high flexibility to wear but lose precision.Here,we construct highly bending-insensitive,unpixelated,and waterproof epidermal interfaces(BUW epidermal interfaces)and demonstrate their interactive applications of conformal human–machine integration.The BUW epidermal interface based on the addressable electrical contact structure exhibits high-precision and stable touch detection,high flexibility,rapid response time,excellent stability,and versatile“cut-and-paste”character.Regardless of whether being flat or bent,the BUW epidermal interface can be conformally attached to the human skin for real-time,comfortable,and unrestrained interactions.This research provides promising insight into the functional composite and structural design strategies for developing epidermal electronics,which offers a new technology route and may further broaden human–machine interactions toward metaverse.
基金supported by Science and Technology Innovation 2030-Major Project(Grant No.2022ZD0208601)the National Natural Science Foundation of China(Grant Nos.62104056,62106041,and 62204204)+2 种基金the Shanghai Sailing Program(Grant No.21YF1451000)the Key Research and Development Program of Shaanxi(Grant No.2022GY-001)the Fundamental Research Funds for the Central Universities(Grant No.223202100019).
文摘Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin compliance,mechanical properties,environmental adaptation,and biocompatibility to avoid signal attenuation and motion artifacts is challenging,and accurate physiological feature extraction necessitates effective signal-processing algorithms.This review presents the latest advancements in smart electrodes for epidermal electrophysiological monitoring,focusing on materials,structures,and algorithms.First,smart materials incorporating self-adhesion,self-healing,and self-sensing functions offer promising solutions for long-term monitoring.Second,smart meso-structures,together with micro/nanostructures endowed the electrodes with self-adaption and multifunctionality.Third,intelligent algorithms give smart electrodes a“soul,”facilitating faster and more-accurate identification of required information via automatic processing of collected electrical signals.Finally,the existing challenges and future opportunities for developing smart electrodes are discussed.Recognized as a crucial direction for next-generation epidermal electrodes,intelligence holds the potential for extensive,effective,and transformative applications in the future.
基金Supported by the Elsa U.Pardee Foundation Grant,No.671432(to Sahu RP)NIH R21 Grant,No.ES033806(to Sahu RP).
文摘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.
文摘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.
文摘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.
文摘An epidermal nevus(EN)is a common disease of various types,including verrucous EN,nevus sebaceous,inflammatory linear verrucous EN,Becker nevus,smooth muscle hamartoma,and nevus comedonicus.EN syndrome is a serious and difficult-to-treat syndrome that is complicated by two or more abnormal organs or systems.To date,the mechanism of an EN is still unclear,and the therapies remain unsatisfactory.The most frequently used treatments are surgery and laser therapy.Several drugs have also been tested.An EN requires more attention,and further research is needed to provide appropriate and effective treatments for each patient.
文摘Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), such as monoclonal antibodies against epidermal growth factor receptor(anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent(40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.
文摘Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.
文摘Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.
基金National Natural Science Foundation of China,No.81974570.
文摘BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute lifethreatening skin reactions.AZD9291 has been developed as a third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)with activity against T790M mutation.CASE SUMMARY Herein we report a 68-year-old woman who developed a large area of skin necrosis and was diagnosed with toxic epidermal necrolysis after AZD-9291 ingestion.To the best of our knowledge,this is the first case reported in patients with EGFR T790M mutation in non-small cell lung cancer(NSCLC).Cabozantinib combined with erlotinib had clinically meaningful effectiveness,with additional toxicity that was generally manageable.CONCLUSION Treatment with AZD-9261 is effective in regressing the growth of the NSCLC and can bring some hope to despairing patients.We hope that more research will be carried out on the association between severe rashes and EGFR-TKIs,and more safe and effective drugs can be developed.
文摘Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.
基金Supported by National Natural Science Foundation of China,No. 81502556Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province,No. 2X2019-01-02
文摘BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.
