In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

Objective To observe the efficacy of hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib for treating Barcelona clinic liver cancer(BCLC)stage B or C hepatocellular carcinoma(HCC),and to explore the impact factors of patients'survival time.Methods Data of 104 patients with BCLC stage B or C HCC were retrospectively analyzed.The patients were divided into observation group(n=46,underwent HAIC combined with lenvatinib)and control group(n=58,underwent HAIC alone).The clinical efficacy and adverse reactions of treatments,as well as patients'overall survival(OS)and progression free survival(PFS)were recorded and compared between groups.Cox regressions were used to explore the impact factors of patients'survival time.Results Three months and 6 months after HAIC,the results of modified response evaluation criteria in solid tumors(mRECIST)in observation group were both better than those in control group(both P＜0.05),while no significant difference was found between groups one year after HAIC(P＞0.05).The overall survival rate in observation group was higher than that in control group(P＜0.05),while there was no significant difference of progression free survival rate between groups(P＞0.05).The incidence of rash in observation group was higher than that in control group(P＜0.05).Multiple Cox regression showed prolonged OS in HCC patients in observation group(hazard ratio[HR]=0.425,95%CI[0.255,0.791])compared with that in control group.Compared with pre-treatment Eastern Cooperative Oncology Group(ECOG)score 1,AFP≥400 μg/ml,the number of tumor foci≥3 and BCLC stage C,pre-treatment ECOG score 0,AFP＜400 μg/ml,the number of tumor foci≤2 and BCLC stage B were all independent protective factors of OS in HCC patients(all P＜0.05).Conclusion HAIC combined with lenvatinib was safe and effective for treating BCLC stage B or C HCC.Pre-treatment ECOG score,serum AFP level,the number of tumor foci and BCLC stage were all independent impact factors of OS.

Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.
Humans ; Carcinoma, Squamous Cell/pathology* ; DNA ; Down-Regulation ; Flap Endonucleases/metabolism* ; Head and Neck Neoplasms ; Interferon-gamma/metabolism* ; Mouth Neoplasms/pathology* ; Phenotype ; Squamous Cell Carcinoma of Head and Neck ; Tumor Microenvironment ; Janus Kinases/metabolism*

Objective Toinvestigatethemethod,safetyandefficacyoftranscatheterarterialchemoembolization(TACE)combined withargonheliumknifecryoablationintreatmentofadvancedprimaryhepaticcancer.Methods FiftyGfourpatientswithadvanced primaryhepaticcancerunderwentTACEfirstly,andfollowedbytheargonhelium knifecryoablationunderCT/ultrasoundguiding percutaneouspunctureafter1－2weeks.2－3cyclesofcryotherapywereperformedduringtheoperation.Afteroperation,enhanced CT/MRIwasperformedtofollowGup.Results Themediansurvivaltimewas17.6months.The6Gmonthsurvivalratewas100%,the 12Gmonthsurvivalratewas89.34%,thetumorprogressiontimewas9.3 months,andtheshortestsurvivalperiodwas8 months.Recent curativeeffectevaluationshowedCRin9patients,PRin34patients,SDin6patients,PDin5patients(RR＝79.62%,DCR＝90.74%). Conclusion TACEcombinedwithargonheliumknifecryoablationisasafeandeffectivetreatment,whichprovidesanewtreatment planforpatientswithprimaryhepaticcancer.

Objective To investigate the efficacy of transcatheter selective cystic arterial infusion chemotherapy embolization in the treatment of invasive bladder cancer with hemorrhage.Methods 81 cases of with invasive bladder cancer and hemorrhage treated by superselective intervention in hospital were selected,as well as postoperative complications and tumor volume changes were recorded in followG up.Results The success rate of intubation and embolization was 100%,the immediate hemostasis rate was 97.53%,and the preoperative bladder tumor volume (4.08±1.66)cm was significantly larger than that of the six months after surgery (3.45±1.33)cm.Conclusion Superselective cystic arterial perfusion embolization is a safe and effective treatment for patients with invasive bladder cancer complicated with hemorrhage.

Objective ToexploretheeffectofTIPS+GCVEcombinedwithPSEonhemodynamicsinpatientswithlivercirrhosis,portal hypertensionandsplenomegaly.Methods 56patientswereincludedfromJanuary2015toDecember2016 whounderwentTIPS+GCVEcombinedwithPSE.Patientswerefollowed-upon1month,3months,6monthsand1yearaftersurgery,andstatisticanalysis weredoneonportalveinhemodynamicindex:portalveintrunkdiameter(PVD),portalveinvelocity(PVV),portalvenousbloodflow (PVF),splenicveintrunkdiameter(SVD)andvelocityofbloodflowinsplenicvein(SVV).Results Thereweresignificantdifferencesinportal veinpressurebeforeandafterthebypassinall56patients.PVDandPVV weresignificantlydifferentbetween3and6 monthsafter surgeryandpre-surgery.PVF wassignificantlydifferentcomparing6 monthsand1yearaftersurgery withpre-surgery.SVDand SVV weresignificantlydifferentbetween3 months,6 monthsand1yearaftersurgeryandpre-surgery.Conclusion TIPS+GCVE combinedwithPSEcouldeffectivelyreduceportalveinpressure,improveportalveinandspleenveinbloodflow,increaseportalvenousblood flow,andimprovepatients’liverfunction.

Objective To investigate the clinical curative effect and significance of partial splenic artery embolization (PSE) for the treatment of patients with hypersplenism at high altitude region. Methods The clinical data of 66 patients with cirrhosis complicated by portal hypertension and hypersplenism, who lived in Xining City of Qinghai Province, the high altitude region in China, and were admitted to authors' hospital during the period from March 2015 to December 2016 to receive PSE, were retrospectively analyzed. White blood cell (WBC) count, red blood cell (RBC) count and platelet (PLT) count were calculated at one day before operation as well as at one, 7, 30 and 90 days after operation. Results The technical success rate of PSE was 100％. The mean WBC count determined at one, 7, 30 and 90 days after PSE was obviously different from that determined at one day before PSE, the differences were statistically significant (P＜0. 05). Conclusion For the treatment of patients with cirrhosis complicated by portal hypertension and hypersplenism, who live at high altitude region, PSE has reliable curative effect, therefore, this therapy is worth promoting in clinical practice. (J Intervent Radiol, 2018, 27: 271-273)

At present,the combined interventional therapy that is based on transcatheter arterial chemoembolization (TACE) technique can control the progression of primary hepatocellular carcinoma (PHC)in different degrees,at the same time the clinical objectives,such as relieving portal hypertension,eliminating portal vein occlusion,controlling refractory ascites and lowering upper gastrointestinal bleeding probability,can be reliably achieved.Thus,the quality of life of the patients can be effectively improved and the survival time will be reliably prolonged.This paper aims to make a comprehensive review about the medical articles concerning TACE combined with other interventional therapies for PHC complicated by portal vein tumor thrombus,which have been published both at home and abroad in recent years,in order to provide practical help for clinical diagnosis and treatment of PHC.

Objective To explore the abilities and personal qualities that medical undergraduates need for their future clinical work, and develop their competency model. Methods The self-made ques-tionnaire survey on medical undergraduates' competencies was conducted among the 1326 medical under-graduates in a medical university by using the cluster sampling method, and the 1099 effective question-naires were collected with effective rates of 82.88%. The exploratory factor analysis was used to analyze the internal structure of competency item and to build the competency model. The rating method was used to calculate the weight of each competency item. Results The overall Cronbach's alpha coefficient of the competency questionnaire was 0.965, and the coefficient of each dimension was above 0.832. The KMO statistic value was 0.970, and the probability associated with Bartlett test statistic was P=0.000, showing that the questionnaire has high reliability and validity. The competency model of medical undergraduates covers six aspects, namely, craftsmanship, personal qualities, professional learning, interpersonal communication, psychological adaptation and the pursuit of excellence, which contain 49 factors. The cumulative variance contribution rate was 54.729%. The weights of these six aspects in the model were 0.204 4, 0.202 1, 0.175 3, 0.158 8, 0.137 6 and 0.121 8 respectively. Conclusion The competency model of undergraduate medi-cal students has a certain scientific and practical value, which can provide new evaluation methods and ideas for medical education objectives, quality assurance, teaching evaluation, medical personnel selection and training.

Objective To investigate the frequency of c-kit mutation and prognosis in t (8;21) acute myeloid leukemia (AML) patients with trisomy 4. Methods A total of 145 de novo t(8;21) AML patients from February 2005 to January 2013 were analyzed retrospectively. Detection of exons 8 and 17 mutation of c-kit by PCR and cytogenetic analysis by R-banding technologies were performed on bone marrow samples of all patients at diagnosis. Clinical data were collected and analyzed statistically. Results Among 145 t (8;21) AML patients, 12 cases (8.3 %) were trisomy 4, 91.7 % (11/12) of them were identified with c-kit mutation, which was significantly higher than that without trisomy 4 [26.3 % (35/133), P< 0.01]. The follow-up data showed that the patients with trisomy 4 were correlated with the lower overall survival (OS) rate (15 % vs 56 %, P< 0.01) and disease-free survival (DFS) rate (0 vs 51 %, P< 0.01) when compared with patients without trisomy 4. Furthermore, the subgroup of patients with both trisomy 4 and c-kit mutation had a worse OS and DFS (P< 0.05). Conclusions Trisomy 4 is associated with high frequency of c-kit mutation and demonstrates poor prognosis in t(8;21) AML patients. Trisomy 4 or it combined with c-kit gene mutation is the main influencing factor on the survival of the patients with t(8;21) AML.