Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors.However,prognosis-related serum enzymes are rarely reported for nasopharyng...Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors.However,prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC).To clarify whether the level of serum enzymes is linked to the prognosis of NPC,we reviewed the pretreatment data of lactate dehydrogenase(LDH),alkaline phosphatase (ALP),and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center.Patients were grouped according to the upper limit of normal values of LDH,ALP,and GGT.The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes,and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes.Finally,a Cox proportional hazards model was used to identify the independent prognostic factors.We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival(P=0.009 and 0.035,respectively),and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival(P=0.037 and 0.039,respectively).In multivariate analysis,increased LDH level was identified as an independent prognostic factor for overall survival.Therefore,we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.展开更多
Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers fo...Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.展开更多
Epstein-Barr virus(EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma(NPC), strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in nor...Epstein-Barr virus(EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma(NPC), strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in normal nasopharyngeal epithelial tissues. In general, EBV does not show a strong tropism for infecting human epithelial cells, and EBV infection in oropharyngeal epithelial cells is believed to be lytic in nature. To establish life-long infection in humans, EBV has evolved efficient strategies to infect B cells and hijack their cellular machinery for latent infection. Lytic EBV infection in oropharyngeal epithelial cells, though an infrequent event, is believed to be a major source of infectious EBV particles for salivary transmission. The biological events associated with nasopharyngeal epithelial cells are only beginning to be understood with the advancement of EBV infection methods and the availability of nasopharyngeal epithelial cell models for EBV infection studies. EBV infection in human epithelial cells is a highly inefficient process compared to that in B cells, which express the complement receptor type 2(CR2) to mediate EBV infection. Although receptor(s) on the epithelial cell surface for EBV infection remain(s) to be identified, EBV infection in epithelial cells could be achieved via the interaction of glycoproteins on the viral envelope with surface integrins on epithelial cells, which might trigger membrane fusion to internalize EBV in cells. Normal nasopharyngeal epithelial cells are not permissive for latent EBV infection, and EBV infection in normal nasopharyngeal epithelial cells usually results in growth arrest. However, genetic alterations in premalignant nasopharyngeal epithelial cells, including p16 deletion and cyclin D1 overexpression, could override the growth inhibitory effect of EBV infection to support stable and latent EBV infection in nasopharyngeal epithelial cells. The EBV episome in NPC is clonal in nature, suggesting that NPC develops from a single EBV-infected nasopharyngeal epithelial cell, and the establishment of persistent and latent EBV infection in premalignant nasopharyngeal epithelium may represent an early and critical event for NPC development.展开更多
Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47Δ is a third-generation HSV vector. In this study, the therapeutic effects of G47Δ on human nasopharyngea...Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47Δ is a third-generation HSV vector. In this study, the therapeutic effects of G47Δ on human nasopharyngeal carcinoma (NPC) were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells (NPECs), and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmi1 were infected with G47Δ at different multiplicities of infection (MOIs). The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47Δ or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47Δ infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi-1. A moderate effect of G47Δ was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47Δ-treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47Δ would be applicable for treatment of NPC patients in the future.展开更多
Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,includin...Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.展开更多
The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer ...The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein-protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation. Previous studies have shown that flotillins are closely associated with tumor development, invasion, and metastasis. In this article, we review the functions of flotillins in relevant cell processes, their underlying mechanisms of action in a variety of tumors, and their potential applications to tumor molecular diagnosis and targeted therapy.展开更多
AIM To identify whether chitinase 3-like 1(CHI3 L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma(ESCC) and to analyze this protein's cellular source.METHODS An ELISA was c...AIM To identify whether chitinase 3-like 1(CHI3 L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma(ESCC) and to analyze this protein's cellular source.METHODS An ELISA was conducted to detect the concentration of CHI3 L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3 L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed,and fluorescent staining was utilized to explore the cellular origins of CHI3 L1. We stimulated monocyte-derived macrophages(MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3 L1 by q PCR and ELISA.RESULTS The level of serum CHI3 L1 was higher in older patients(≥ 60) than in patients under the age of 60(P = 0.001). The patients with higher levels of CHI3 L1 had a significantly shorter overall survival,whereas the traditional markers,carcinoembryonic antigen and squamous cell carcinoma antigen,were less effective(P > 0.05). A multivariate Cox analysis(P = 0.001) indicated that CHI3 L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3 L1. Interleukin-6(IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3 L1. The serum concentration of CHI3 L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil(NEU,P = 0.045),neutrophil/lymphocyte rate(NLR,P = 0.016),and C-reactive protein(CRP,P < 0.001).CONCLUSION Our study first established a connection between the pretreated CHI3 L1 and patients with ESCC,and the serum CHI3 L1 was primarily secreted by ESCC-surrounded macrophages.展开更多
The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from...The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from the patients in this region. In this study, we established a new NPC cell line, termed SUNE2, from a Cantonese patient with undifferentiated NPC. This cell line had extremely low concentrations of Epstein-Barr virus (EBV) DNA in long-term culture and expressed low levels of latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), BamH1-A right frame 1 (BARF1), EBV-encoded RNA-1 (EBER1), and EBV-encoded RNA-2 (EBER2) in early passages. SUNE2 cells also showed much stronger transforming ability than 5-8F cells in colony formation assays and anchorage- independent growth assays in soft agar, and they only need 2 weeks to form tumors in nude mice. In summary, the SUNE2 cell line is a new in vitro model that can be used for further research on the mechanisms underlying the occurrence and development of NPC.展开更多
There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and th...There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.展开更多
Epstein-Barr virus(EBV),the first human oncovirus discovered in 1964,has become a focal point in virology,immunology,and oncology because of its unique biological characteristics and significant role in human diseases...Epstein-Barr virus(EBV),the first human oncovirus discovered in 1964,has become a focal point in virology,immunology,and oncology because of its unique biological characteristics and significant role in human diseases.As we commemorate the 60th anniversary of EBV's discovery,it is an opportune moment to reflect on the major advancements in our understanding of this complex virus.In this review,we highlight key milestones in EBV research,including its virion structure and life cycle,interactions with the host immune system,association with EBV-associated diseases,and targeted intervention strategies.展开更多
Coronaviruses are enveloped RNA viruses distinguished by their crown-like surface spikes. These viruses cause various diseases in humans and animals, including respiratory, gastrointestinal, and neurological disorders...Coronaviruses are enveloped RNA viruses distinguished by their crown-like surface spikes. These viruses cause various diseases in humans and animals, including respiratory, gastrointestinal, and neurological disorders. The health risks posed by coronaviruses are substantial, as demonstrated by severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2. SARS-CoV triggered a global outbreak of SARS in 2003, and SARS-CoV-2 has been responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic since the end of 2019. Furthermore, four human coronaviruses (HCoVs), HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, have been implicated in 15% to 30% cases of the common cold.[1] Given their prevalence and potential to cause various diseases, understanding the mechanisms underlying the invasion into cells of the coronavirus is essential for public health. By binding to specific cell receptors, the spike protein of coronaviruses undergoes conformational changes that promote membrane fusion and entry of the virus into host cells. Although significant progress has been made in elucidating the mechanisms of coronavirus entry, the detailed molecular interactions between viral proteins and host receptors remain incompletely understood.展开更多
The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome.The consistently emerging SARS-CoV-2 variants ...The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome.The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion,transmissibility,and the clinical manifestation during infection,which differ each strain and endow them with distinguished features during populational spread.Several SARS-CoV-2 variants,identified as Variants of Concern(VOC)by the World Health Organization,challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines.Moreover,the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic.Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity,which would greatly facilitate drug and vaccine development and benefit the global public health policymaking.Hence in this review,we summarized the molecular characteristics,immune evasion,and impacts of the SARSCoV-2 variants and focused on the parallel comparison of different variants in mutational profile,transmissibility and tropism alteration,treatment effectiveness,and clinical manifestations,in order to provide a comprehensive landscape for SARS-CoV-2 variant research.展开更多
SARS-CoV-2 variants have evolved a variety of critical mutations,leading to antigenicity changes and immune escape.The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resis...SARS-CoV-2 variants have evolved a variety of critical mutations,leading to antigenicity changes and immune escape.The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines.展开更多
In a recent study published in Cell,Vietzen and colleagues discovered the novel role of natural killer(NK)cells and EBVspecific CD8+T cell response in controlling EBV-inducing autoimmune response and collectively defi...In a recent study published in Cell,Vietzen and colleagues discovered the novel role of natural killer(NK)cells and EBVspecific CD8+T cell response in controlling EBV-inducing autoimmune response and collectively defined virus and host genetics factors associated with a significantly raised risk of multiple sclerosis.展开更多
Host antiviral strategies have been studied for a long time,and the antibody response and T-cell response represent the classic host antiviral strategies.The entry of enveloped viruses into host cells is a complex pro...Host antiviral strategies have been studied for a long time,and the antibody response and T-cell response represent the classic host antiviral strategies.The entry of enveloped viruses into host cells is a complex process that could involve interactions ofmultiple viral glycoproteins and host-cell receptors.Blocking this process is the key to preventing infection.In general,antigenspecific neutralizing antibodies are thought to effectively bind to viral glycoproteins to block virus entry.However,there are other unknown host factors that inhibit or enhance the virus entry into the host cell.Recently,Yang et al.discovered that interferon-induced transmembrane protein-1(IFITM1)inhibited Epstein–Barr virus(EBV)infection in epithelial cells(ECs)by competing with viral glycoproteins to bind to Ephrin receptor A2(EphA2),thereby blocking this key entry receptor[1](Figure 1).Together with previous research,this finding hints at the importance of discovering broader host protective factors.ECs are known to be critical sites for EBV infection and replication.EphA2 has been reported as one of the most crucial EBV entry receptors on the EC surface,which binds to viral glycoprotein H/L(gH/gL)and glycoprotein B(gB)[2]to drive the internalization and fusion of EBV[3].However,ECs with low susceptibility to EBV can still express a high level of EphA2[4],raising questions about additional factors that influence host susceptibility.展开更多
Dear Editor,The continued evolution of the SARS-CoV-2 Omicron variant has contributed to the emergence of various novel sublineages that can evade the neutralizing activities of antibodies and vaccine sera,including B...Dear Editor,The continued evolution of the SARS-CoV-2 Omicron variant has contributed to the emergence of various novel sublineages that can evade the neutralizing activities of antibodies and vaccine sera,including BA.2,BA.5,and the recently reported BQ.1,BQ.1.1,BF.7,XBB.1.展开更多
Axis inhibition protein 1(AXIN1),a scaffold protein interacting with various critical molecules,plays a vital role in determining cell fate.However,its impact on the antiviral innate immune response remains largely un...Axis inhibition protein 1(AXIN1),a scaffold protein interacting with various critical molecules,plays a vital role in determining cell fate.However,its impact on the antiviral innate immune response remains largely unknown.Here,we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections.In the resting state,AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3(IRF3)by preventing p62-mediated autophagic degradation of IRF3.This is achieved by recruiting ubiquitin-specific peptidase 35(USP35),which removes lysine(K)48-linked ubiquitination at IRF3 K366.Upon virus infection,AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1(TBK1).This leads to increased phosphorylation of IRF3 and a boost in IFN-I production.Moreover,KYA1797K,a small molecule that binds to the AXIN1 RGS domain,enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses.Clinically,patients with HBV-associated hepatocellular carcinoma(HCC)who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates,as well as higher HBV levels in their blood.Overall,our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses,underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.展开更多
Most approved clinical vaccines for COVID-19 are administered intramuscularly[1].COVID-19 vaccines have played a crucial role in saving countless lives throughout the pandemic and continue to effectively mitigate hosp...Most approved clinical vaccines for COVID-19 are administered intramuscularly[1].COVID-19 vaccines have played a crucial role in saving countless lives throughout the pandemic and continue to effectively mitigate hospitalization risks for vulnerable individuals.However,it is important to note that updated iterations of these vaccines offer limited and short-lived protection against reinfection and transmission[2,3].To address these limitations,an emerging strategy involves the development of vaccines deliverable through the airways to elicit mucosal immunity[4,5].Recently,Ye et al.[6]developed a dry powder nanoparticlebased SARS-CoV-2 vaccine designed for airway administration.This vaccine,which was an optimal size,was delivered directly into the alveoli through inhalation.In animal models,pulmonary vaccine delivery can induce potent systemic and mucosal immune responses,effectively protecting against COVID-19.Notably,a significant reduction in host-to-host viral transmission has also been demonstrated in vaccinated hamster models,indicating the crucial role of the mucosal immune response in treating respiratory virus infections.展开更多
Human herpesviruses(HHV),including the alpha,beta,andgamma subfamilies,are enveloped viruses with broad prevalence,establishing life-time latent infections and inducing a variety of diseases[1].Among them,herpes simpl...Human herpesviruses(HHV),including the alpha,beta,andgamma subfamilies,are enveloped viruses with broad prevalence,establishing life-time latent infections and inducing a variety of diseases[1].Among them,herpes simplex virus(HSV),consists of two HSV-1 and HSV-2 variants,ubiquitouslyaffecting global populations[2].As an enveloped virus,HSV features a repertoire of glycoproteins such as glycoproteins D(gD),glycoproteins H(gH),glycoproteins L(gL),and glycoproteins B(gB),to orchestrate host cell recognition and infection[3,4].展开更多
As a major kind of cell surface adhesion molecules with signal transduction function,integrins play a major role in tumorigenesis and tumor progression.The role of integrins in tumor cells and the tumor microenvironme...As a major kind of cell surface adhesion molecules with signal transduction function,integrins play a major role in tumorigenesis and tumor progression.The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed.Among the integrin family,integrinαvβ3 is the most studied integrin in the past 20 years.Plenty of preclinical and clinical studies have been conducted,which showed clinical benefits of targeting integrinαvβ3 in tumor imaging and treatment.Currently,the focus of interest is gradually shifting from integrinαvβ3 toward other integrin subtypes.Integrinα6 is expressed in many malignant tumors,such as colorectal cancer,head and neck squamous cell carcinoma,breast cancer,pancreatic cancer,and liver cancer,and its expression is correlated with poor survival of the patients.Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrinα6 have excellent safety and efficacy in preclinical mouse models,encouraging clinical translation of this promising target.In this review,we briefly overview the physiological and pathological function of integrinα6 and highlight the recent advances in integrinα6-targeted imaging and therapeutics in tumors.展开更多
基金supported by grant from Hi-Tech Research and Development Program of China(No.2006AA02Z4B4)
文摘Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors.However,prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC).To clarify whether the level of serum enzymes is linked to the prognosis of NPC,we reviewed the pretreatment data of lactate dehydrogenase(LDH),alkaline phosphatase (ALP),and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center.Patients were grouped according to the upper limit of normal values of LDH,ALP,and GGT.The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes,and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes.Finally,a Cox proportional hazards model was used to identify the independent prognostic factors.We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival(P=0.009 and 0.035,respectively),and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival(P=0.037 and 0.039,respectively).In multivariate analysis,increased LDH level was identified as an independent prognostic factor for overall survival.Therefore,we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.
基金supported by grants from the Ministry of Science and Technology of China(2011CB504304 and 2012CB967003)the National Natural Science Foundation of China(81271902 and 81230045)
文摘Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.
基金support of the various funding sources from the Research Grant Council, Hong Kong: GRF (777809, 779810, 780911, 779312, 470708, 471709, 471610, 471211, 470312), CRF (CUHK8/CRF/11R), AoE NPC Grant (AoE/ M-06/08),and Theme-Based Research Scheme (T12-401/13-R)funding from the HMRF Grant, Hong Kong (12110942, 13120872 and 12110782)the CRCG Grant from the University of Hong Kong
文摘Epstein-Barr virus(EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma(NPC), strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in normal nasopharyngeal epithelial tissues. In general, EBV does not show a strong tropism for infecting human epithelial cells, and EBV infection in oropharyngeal epithelial cells is believed to be lytic in nature. To establish life-long infection in humans, EBV has evolved efficient strategies to infect B cells and hijack their cellular machinery for latent infection. Lytic EBV infection in oropharyngeal epithelial cells, though an infrequent event, is believed to be a major source of infectious EBV particles for salivary transmission. The biological events associated with nasopharyngeal epithelial cells are only beginning to be understood with the advancement of EBV infection methods and the availability of nasopharyngeal epithelial cell models for EBV infection studies. EBV infection in human epithelial cells is a highly inefficient process compared to that in B cells, which express the complement receptor type 2(CR2) to mediate EBV infection. Although receptor(s) on the epithelial cell surface for EBV infection remain(s) to be identified, EBV infection in epithelial cells could be achieved via the interaction of glycoproteins on the viral envelope with surface integrins on epithelial cells, which might trigger membrane fusion to internalize EBV in cells. Normal nasopharyngeal epithelial cells are not permissive for latent EBV infection, and EBV infection in normal nasopharyngeal epithelial cells usually results in growth arrest. However, genetic alterations in premalignant nasopharyngeal epithelial cells, including p16 deletion and cyclin D1 overexpression, could override the growth inhibitory effect of EBV infection to support stable and latent EBV infection in nasopharyngeal epithelial cells. The EBV episome in NPC is clonal in nature, suggesting that NPC develops from a single EBV-infected nasopharyngeal epithelial cell, and the establishment of persistent and latent EBV infection in premalignant nasopharyngeal epithelium may represent an early and critical event for NPC development.
基金supported by grants from the NationalScience Foundation of China (30672410)theGuangdong Natural Science Foundation (06104599)
文摘Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47Δ is a third-generation HSV vector. In this study, the therapeutic effects of G47Δ on human nasopharyngeal carcinoma (NPC) were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells (NPECs), and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmi1 were infected with G47Δ at different multiplicities of infection (MOIs). The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47Δ or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47Δ infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi-1. A moderate effect of G47Δ was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47Δ-treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47Δ would be applicable for treatment of NPC patients in the future.
文摘Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.
基金Project supported by the National Natural Science Foundation of China(Nos.81773179 and 81272972)the National Basic Research Program(973)of China(No.2010CB833605)+3 种基金the Hunan Provincial Science and Technology Department(Nos.2013FJ4010 and2014FJ6006)the Open-End Fund for the Valuable and Precision Instruments of Central South University(Nos.CSUZC201634 and CSUZC201638)the Natural Science Foundation of Hunan Province(No.2016JJ2172)the National College Students Innovation Projects(Nos.201610533264 and 201610533538),China
文摘The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein-protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation. Previous studies have shown that flotillins are closely associated with tumor development, invasion, and metastasis. In this article, we review the functions of flotillins in relevant cell processes, their underlying mechanisms of action in a variety of tumors, and their potential applications to tumor molecular diagnosis and targeted therapy.
文摘AIM To identify whether chitinase 3-like 1(CHI3 L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma(ESCC) and to analyze this protein's cellular source.METHODS An ELISA was conducted to detect the concentration of CHI3 L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3 L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed,and fluorescent staining was utilized to explore the cellular origins of CHI3 L1. We stimulated monocyte-derived macrophages(MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3 L1 by q PCR and ELISA.RESULTS The level of serum CHI3 L1 was higher in older patients(≥ 60) than in patients under the age of 60(P = 0.001). The patients with higher levels of CHI3 L1 had a significantly shorter overall survival,whereas the traditional markers,carcinoembryonic antigen and squamous cell carcinoma antigen,were less effective(P > 0.05). A multivariate Cox analysis(P = 0.001) indicated that CHI3 L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3 L1. Interleukin-6(IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3 L1. The serum concentration of CHI3 L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil(NEU,P = 0.045),neutrophil/lymphocyte rate(NLR,P = 0.016),and C-reactive protein(CRP,P < 0.001).CONCLUSION Our study first established a connection between the pretreated CHI3 L1 and patients with ESCC,and the serum CHI3 L1 was primarily secreted by ESCC-surrounded macrophages.
基金Jaap Middeldorp (Amsterdam Free University) for a kind gift of anti-EBNA1 (OTX-1)supported by grants from National Natural Science Foundation of China (No. 81025014, 91019015)
文摘The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from the patients in this region. In this study, we established a new NPC cell line, termed SUNE2, from a Cantonese patient with undifferentiated NPC. This cell line had extremely low concentrations of Epstein-Barr virus (EBV) DNA in long-term culture and expressed low levels of latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), BamH1-A right frame 1 (BARF1), EBV-encoded RNA-1 (EBER1), and EBV-encoded RNA-2 (EBER2) in early passages. SUNE2 cells also showed much stronger transforming ability than 5-8F cells in colony formation assays and anchorage- independent growth assays in soft agar, and they only need 2 weeks to form tumors in nude mice. In summary, the SUNE2 cell line is a new in vitro model that can be used for further research on the mechanisms underlying the occurrence and development of NPC.
基金supported by grants from the National Natural Science Foundation of China (81972531, 82373175, 82102775, and 82002466)the Major Scientific and Technological Projects of Guangdong Province (2019B020202002)the Young Talents Program of Sun Yat-sen University Cancer Center (YTP-SYSUCC-0067)
文摘There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.
基金supported by the National Key Research and Development Program of China(2022YFC3400900)the National Natural Science Foundation of China(82030046,82402614)+3 种基金the Postdoctoral Fellowship Program of CPSF(GZB20230886)the Chinese Postdoctoral Science Foundation(2023M743998,2024T171080)Fundamental Research Funds for the Central Universities(24qnpy278)Shenzhen Medical Research Fund(A2302028)。
文摘Epstein-Barr virus(EBV),the first human oncovirus discovered in 1964,has become a focal point in virology,immunology,and oncology because of its unique biological characteristics and significant role in human diseases.As we commemorate the 60th anniversary of EBV's discovery,it is an opportune moment to reflect on the major advancements in our understanding of this complex virus.In this review,we highlight key milestones in EBV research,including its virion structure and life cycle,interactions with the host immune system,association with EBV-associated diseases,and targeted intervention strategies.
基金supported by grants from the Key Technologies Research and Development Program(2022YFC3400900)Postdoctoral Fellowship Program of CPSF(GZB20230886)+3 种基金China Postdoctoral Science Foundation(2023M743998)National Natural Science Foundation of China(82030046)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2019BT02Y198)Guangdong Science and Technology Department(2020B1212030004).
文摘Coronaviruses are enveloped RNA viruses distinguished by their crown-like surface spikes. These viruses cause various diseases in humans and animals, including respiratory, gastrointestinal, and neurological disorders. The health risks posed by coronaviruses are substantial, as demonstrated by severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2. SARS-CoV triggered a global outbreak of SARS in 2003, and SARS-CoV-2 has been responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic since the end of 2019. Furthermore, four human coronaviruses (HCoVs), HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, have been implicated in 15% to 30% cases of the common cold.[1] Given their prevalence and potential to cause various diseases, understanding the mechanisms underlying the invasion into cells of the coronavirus is essential for public health. By binding to specific cell receptors, the spike protein of coronaviruses undergoes conformational changes that promote membrane fusion and entry of the virus into host cells. Although significant progress has been made in elucidating the mechanisms of coronavirus entry, the detailed molecular interactions between viral proteins and host receptors remain incompletely understood.
基金supported by the National Natural Science Foundation of China(82030046,81621004)Guangdong Science and Technology Department(2020B1212030004)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2019BT02Y198).
文摘The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome.The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion,transmissibility,and the clinical manifestation during infection,which differ each strain and endow them with distinguished features during populational spread.Several SARS-CoV-2 variants,identified as Variants of Concern(VOC)by the World Health Organization,challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines.Moreover,the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic.Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity,which would greatly facilitate drug and vaccine development and benefit the global public health policymaking.Hence in this review,we summarized the molecular characteristics,immune evasion,and impacts of the SARSCoV-2 variants and focused on the parallel comparison of different variants in mutational profile,transmissibility and tropism alteration,treatment effectiveness,and clinical manifestations,in order to provide a comprehensive landscape for SARS-CoV-2 variant research.
基金This work was supported by China’s National Key Research and Development Program(No.2016YFA0502100,No.2017YFA0505600)the National Natural Science Foundation of China(No.81801645,No.82030046).
文摘SARS-CoV-2 variants have evolved a variety of critical mutations,leading to antigenicity changes and immune escape.The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines.
基金supported by grants from the National Key Research and Development Program of China(2022YFC3400900)Postdoctoral Fellowship Program of CPSF(GZB20230886)+3 种基金Chinese Postdoctoral Science Foundation(2023M743998)Natural Science Foundation of China(82030046)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2019BT02Y198)Guangdong Science and Technology Department(2020B1212030004).
文摘In a recent study published in Cell,Vietzen and colleagues discovered the novel role of natural killer(NK)cells and EBVspecific CD8+T cell response in controlling EBV-inducing autoimmune response and collectively defined virus and host genetics factors associated with a significantly raised risk of multiple sclerosis.
基金supported by grants from the Key Technologies Research and Development Program(2022YFC3400900)Postdoctoral Fellowship Program of CPSF(GZB20230886)+3 种基金China Postdoctoral Science Foundation(2023M743998)NationalNatural Science Foundation of China(82030046)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2019BT02Y198)Guangdong Science and Technology Department(2020B1212030004).
文摘Host antiviral strategies have been studied for a long time,and the antibody response and T-cell response represent the classic host antiviral strategies.The entry of enveloped viruses into host cells is a complex process that could involve interactions ofmultiple viral glycoproteins and host-cell receptors.Blocking this process is the key to preventing infection.In general,antigenspecific neutralizing antibodies are thought to effectively bind to viral glycoproteins to block virus entry.However,there are other unknown host factors that inhibit or enhance the virus entry into the host cell.Recently,Yang et al.discovered that interferon-induced transmembrane protein-1(IFITM1)inhibited Epstein–Barr virus(EBV)infection in epithelial cells(ECs)by competing with viral glycoproteins to bind to Ephrin receptor A2(EphA2),thereby blocking this key entry receptor[1](Figure 1).Together with previous research,this finding hints at the importance of discovering broader host protective factors.ECs are known to be critical sites for EBV infection and replication.EphA2 has been reported as one of the most crucial EBV entry receptors on the EC surface,which binds to viral glycoprotein H/L(gH/gL)and glycoprotein B(gB)[2]to drive the internalization and fusion of EBV[3].However,ECs with low susceptibility to EBV can still express a high level of EphA2[4],raising questions about additional factors that influence host susceptibility.
基金supported by the National Natural Science Foundation of China (82030046)the support from National Supercomputer Center,Guangzhou with the Tianhe-2 super-computer。
文摘Dear Editor,The continued evolution of the SARS-CoV-2 Omicron variant has contributed to the emergence of various novel sublineages that can evade the neutralizing activities of antibodies and vaccine sera,including BA.2,BA.5,and the recently reported BQ.1,BQ.1.1,BF.7,XBB.1.
基金funded through allocations from the National Key Research and Development Program of China(Grant No.2022YFC3400900)the China National Natural Science Foundation(Grant No.82301985)the Fundamental Research Funds for the Central Universities at Sun Yat-sen University(Project No.23ptpy21).
文摘Axis inhibition protein 1(AXIN1),a scaffold protein interacting with various critical molecules,plays a vital role in determining cell fate.However,its impact on the antiviral innate immune response remains largely unknown.Here,we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections.In the resting state,AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3(IRF3)by preventing p62-mediated autophagic degradation of IRF3.This is achieved by recruiting ubiquitin-specific peptidase 35(USP35),which removes lysine(K)48-linked ubiquitination at IRF3 K366.Upon virus infection,AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1(TBK1).This leads to increased phosphorylation of IRF3 and a boost in IFN-I production.Moreover,KYA1797K,a small molecule that binds to the AXIN1 RGS domain,enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses.Clinically,patients with HBV-associated hepatocellular carcinoma(HCC)who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates,as well as higher HBV levels in their blood.Overall,our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses,underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.
基金supported by the Postdoctoral Fellowship Program of CPSF(GZB20230886)the Chinese Postdoctoral Science Foundation(2023M743998,2023M744021,2024T171080)+1 种基金the National Key Research and Development Program of China(2022YFC3400900)the National Natural Science Foundation of China(82030046).
文摘Most approved clinical vaccines for COVID-19 are administered intramuscularly[1].COVID-19 vaccines have played a crucial role in saving countless lives throughout the pandemic and continue to effectively mitigate hospitalization risks for vulnerable individuals.However,it is important to note that updated iterations of these vaccines offer limited and short-lived protection against reinfection and transmission[2,3].To address these limitations,an emerging strategy involves the development of vaccines deliverable through the airways to elicit mucosal immunity[4,5].Recently,Ye et al.[6]developed a dry powder nanoparticlebased SARS-CoV-2 vaccine designed for airway administration.This vaccine,which was an optimal size,was delivered directly into the alveoli through inhalation.In animal models,pulmonary vaccine delivery can induce potent systemic and mucosal immune responses,effectively protecting against COVID-19.Notably,a significant reduction in host-to-host viral transmission has also been demonstrated in vaccinated hamster models,indicating the crucial role of the mucosal immune response in treating respiratory virus infections.
基金supported by grants from the NationalKey Research and Development Program of China(2022YFC3400900)Chinese Postdoctoral Science Foundation(GZB20230886,2023M743998)+2 种基金Natural Science Foundationof China(82030046 to M.S.Z,82070329 and 32241028 toZ.L.)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2019BT02Y198)Guangdong Science and Technology Department(2020B1212030004).
文摘Human herpesviruses(HHV),including the alpha,beta,andgamma subfamilies,are enveloped viruses with broad prevalence,establishing life-time latent infections and inducing a variety of diseases[1].Among them,herpes simplex virus(HSV),consists of two HSV-1 and HSV-2 variants,ubiquitouslyaffecting global populations[2].As an enveloped virus,HSV features a repertoire of glycoproteins such as glycoproteins D(gD),glycoproteins H(gH),glycoproteins L(gL),and glycoproteins B(gB),to orchestrate host cell recognition and infection[3,4].
基金National Natural Science Foundation of China(81972531)。
文摘As a major kind of cell surface adhesion molecules with signal transduction function,integrins play a major role in tumorigenesis and tumor progression.The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed.Among the integrin family,integrinαvβ3 is the most studied integrin in the past 20 years.Plenty of preclinical and clinical studies have been conducted,which showed clinical benefits of targeting integrinαvβ3 in tumor imaging and treatment.Currently,the focus of interest is gradually shifting from integrinαvβ3 toward other integrin subtypes.Integrinα6 is expressed in many malignant tumors,such as colorectal cancer,head and neck squamous cell carcinoma,breast cancer,pancreatic cancer,and liver cancer,and its expression is correlated with poor survival of the patients.Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrinα6 have excellent safety and efficacy in preclinical mouse models,encouraging clinical translation of this promising target.In this review,we briefly overview the physiological and pathological function of integrinα6 and highlight the recent advances in integrinα6-targeted imaging and therapeutics in tumors.
