CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

2016 Chinese expert consensus and guidelines for the diagnosis and treatment of papillary thyroid microcarcinoma

The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,

An international survey of classification and treatment choices for group D retinoblastoma

AIM： To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS： An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS： The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children＇s Hospital of Los Angeles （CHLA） version, 33% used the Children＇s Oncology Group （COG） version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were： Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were： Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center （P〈0.0001）. CONCLUSION： Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.

Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: a study of 1,587 patients

Objective: The purposes of this study were to identify risk factors for cervical lymph node metastasis and to examine the association between BRAF^(V600E) status and clinical features in papillary thyroid microcarcinoma(PTMC).Methods: A total of 1,587 patients with PTMC, treated in Tianjin Medical University Cancer Institute and Hospital from January2011 to March 2013, underwent retrospective analysis. We reviewed and analyzed factors including clinical results, pathology records, ultrasound results, and BRAF^(V600E) status.Results: Multivariate logistic regression analyses demonstrated that gender(male) [odds ratio(OR) = 1.845, P = 0.000], age(< 45 years)(OR = 1.606, P = 0.000), tumor size(> 6 mm)(OR = 2.137, P = 0.000), bilateralism(OR = 2.011, P = 0.000) and extrathyroidal extension(OR = 1.555, P = 0.001) served as independent predictors of central lymph node metastasis(CLNM).Moreover, CLNM(OR = 29.354, P = 0.000) served as an independent predictor of lateral lymph node metastasis(LLNM). Among patients with a solitary primary tumor, those with tumor location in the lower third of the thyroid lobe or the isthmus were more likely to experience CLNM(P < 0.05). Univariate analyses indicated that CLNM, LLNM, extrathyroidal extension, and multifocality were not significantly associated with BRAF^(V600E) mutation.Conclusions: The present study suggested that prophylactic neck dissection of the central compartment should be considered in patients with PTMC, particularly in men with tumor size greater than 6 mm, age less than 45 years, extrathyroidal extension, and tumor bilaterality. Among patients with PTMC, BRAF^(V600E) mutation is not significantly associated with prognostic factors. For a better understanding of surgical management of PTMC and the risk factors, we recommend multicenter research and long-term follow-up.

2017 Chinese expert consensus on the clinical application ofserum marker for thyroid cancer

In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.

Re-operation for parotid gland cancer following non-standard surgical treatment

Objective:The purpose of this study was to analyze the clinical disadvantages of non-standard surgical treatment for parotid gland cancer and probe the re-operative indication following non-standard surgical treatment.Methods: Data of 58 cases suffered parotid gland cancer who received non-standard operation at other hospital and received re-operation in tumor hospital of Ganzhou from June 1998 to October 2010 were retrospectively reviewed.Results: In all cases,parotid gland cancer were residual in 46 cases,the facial nerve remaining rate was 81.0% (47/58),facial nerve branches injury rate was 3.5% (2/58),facial nerve partial resection rate was 8.6% (5/58) and total resection rate was 6.9% (4/58).The sensitivity of residual tumor was 83.3%,scanned by contrast-enhanced CT and the CT positive predictive value was 86.9%. Conclusion: Consideration of the higher residual tumor rate in patients who received non-standard operations,the re-operations were necessary.Contrast-enhanced CT positive predictive value was high for residual tumor and it was important for re-operation.

Efficacy and safety of anlotinib plus penpulimab as second-line treatment for small cell lung cancer:A multicenter,open-label,single-arm phase Ⅱ trial

Background:Currently,the need for new therapeutic strategies involving programmed cell death protein-1(PD-1)monoclonal antibodies in the second-line setting of small cell lung cancer(SCLC)is urgent.This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.Methods:This study included the patients from Cohort 4 of a single-arm,open-label,multicenter,phase II clinical trial.A safety run-in phase was performed under anlotinib(10/12 mg quaque die[QD],days 1–14)plus penpulimab(200 mg intravenously[IV],day 1)in a 21-day cycle,followed by the formal trial in which the patients received anlotinib(12 mg QD,days 1–14)plus penpulimab(200 mg IV,day 1)in a 21-day cycle.The primary endpoint of the safety run-in phase was safety.The primary endpoint of the formal trial phase was the objective response rate(ORR).Results:From April 28,2020,to November 24,2020,21 patients were enrolled from 11 hospitals,including 2 in the safety run-in phase and 19 in the formal trial phase.In the formal trial phase,the ORR was 42.1%(8/19;95%confidence interval[CI]:17.7–66.6%).The median progression-free survival was 4.8 months(95%CI:2.9–11.3 months),and the median overall survival was 13.0 months(95%CI:4.6–not applicable[NA]months).The incidence of grade 3 treatment-related adverse events(TRAEs)was 52.4%(11/21),and the incidence of treatment-related serious adverse events(AEs)was 28.6%(6/21).Two AE-related deaths occurred.The most common AEs were hypertension(57.1%,12/21),hypothyroidism(42.9%,9/21),and hypertriglyceridemia(38.1%,8/21).Conclusions:In patients with SCLC who progressed after first-line platinum-based chemotherapy,the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile,which warrants further investigation.

Active surveillance as a management strategy for papillary thyroid microcarcinoma

Active surveillance(AS)can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma(PTMC),with the absence of clinically apparent lymph nodes,extrathyroidal extensions,and distant metastasis.After reviewing the reports on AS of low risk PTMCs worldwide,we introduced AS,and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up schedules.Moreover,the requirement of cytological diagnosis,progression evaluation methods,necessity of thyrotropin suppression,and medical costs were issues that both clinicians and patients considered.The usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient risk.Clinicians may adopt measures like dynamic monitoring,risk stratification,and making personal follow-up schedules to minimize these potential risks.By appropriately selecting PTMC patients,AS can be an effective alternative treatment to immediate surgery.

Correlation between the expression of thrombospondin-1 and neovascularization in mucoepidermoid carcinoma

Background Researchers have recently demonstrated that thrombospondin-1 （TSP-1） has an important function in regulating neovascularization. Whether it inhibits or accelerates neovascularization, however, is still controversial. We found few reports about the correlation between TSP-1 and vascularization in mucoepidermoid carcinoma. In this research, the distribution and expression of TSP-1 in mucoepidermoid carcinoma were investigated. We also analyzed （1） the correlation between the expression of TSP-1 and microvessel density （MVD）, as an indicator of neovascularization activity, and （2） the effect of TSP-1 on neovascularization and tumor growth in the subcutaneous xenotransplanted model of mucoepidermoid carcinoma. Method （1） The sites and intensity of expression of TSP-1 and the MVD were analyzed in 45 cases of mucoepidermoid carcinoma after surgery by the method of streptavidin-peroxidase （SP） immunohistochemistry; and （2） recombinant human thrombospondin-1 （rhTSP-1） was injected twice a week for five consecutive weeks around the tumor in the subcutaneous xenotransplanted tumor model of mucoepidermoid carcinoma in nude mice. Each week, the tumor size was measured, in order to draw the growth curve of the xenotransplanted tumor model of mucoepidermoid carcinoma, and MVD was measured. Results （1） The positive expression of TSP-1 protein was 57.78% （26/45）. Most positive staining for TSP-1 was found in the cytoplasm of the cancer cells, while some staining occurred in the extracellular matrix. The mean MVD in 45 cases of m ucoepidermoid carcinoma was 58.17±19.77 per 100 visual fields. Tumors with a high expression of TSP-1 showed a low MVD value, and the TSP-1 immunocompetence and microvessel density showed a significant negative correlation （rs=-0.947, P 〈0.001）. （2） The xenotransplanted tumors with the injection doses of 1.25, 0.75 and 0.25 ug/ml respectively were 36.97%, 53.36% and 73.61% of the size of the control group （（451±92）, （651±113）, （898±86） and （1220±157） mm^3 respectively, F=-53.167, P 〈0.001）, and their weights were respectively 35.14%, 51.35% and 70.27% of the control group （（1.3±0.5）, （1.9±0.5）, （2.6±0.3）, and （3.7±0.7） g respectively, F=-62.669, P 〈0.001）. Their MVDs were 25.00%, 45.93%, and 72.20% respectively of the control group and concentration dependent （15.43±3.45, 28.35±4.24, 44.57±3.35 and 61.73±5.43 per 100 visual fields respectively, F=54.582, P 〈0.001）. Conclusions The TSP-1 has a higher expression in mucoepidermoid carcinoma and the expression has a significant negative correlation with neovascularization. The TSP-1 inhibits neovascularization and tumor growth, and it might be a new biological therapy for treatment of patients with mucoepidermoid carcinoma.

Safety and Current Status of the COVID-19 Vaccine among Patients with Breast cancer: A Cross-Sectional Study from China

In this study,we aimed to explore the safety and vaccination coverage data of Chinese patients with breast cancer receiving coronavirus disease 2019(COVID-19)vaccination.The patients were recruited from 41 hospitals across 20 Chinese provinces.The vaccination coverage was approximately 22.4%,and the frequency of total adverse events was 13.3%after the first dose and 9.9%after the second dose.The most frequent adverse reaction within 14 days of the first dose was local pain(5.7%).Unvaccinated patients were very likely to reject the vaccine rather than be hesitant in patients with old age(odds ratio[OR],1.238;95%confidence interval[CI],1.101-1.391),chronic disease history(OR,1.189;95%CI,1.057-1.337),and cancer relapse(OR,1.398;95%CI,1.233-1.585).Of the unvaccinated patients with breast cancer,54.1%opted to receive COVID-19 vaccines if more data were available.Considering the safety but low vaccination coverage for breast cancer,increased positive attitudes and acceptance toward COVID-19 vaccines are important.

Derived vascular endothelial cells induced by mucoepidermoid carcinoma cells:3-dimensional collagen matrix model

Mucoepidermoid carcinoma undergoes uniquely vigorous angiogenic and neovascularization processes,possibly due to proliferation of vascular endothelial cells(ECs) induced by mucoepidermoid carcinoma cells(MCCs) in their three-dimensional(3D) microenvironment.To date,no studies have dealt with tumor cells and vascular ECs from the same origin of mucoepidermoid carcinoma using the in vitro 3D microenvironment model.In this context,the current research aims to observe neovascularization with mucoepidermoid carcinoma microvascular ECs(MCMECs) conditioned by the microenvironment in the 3D collagen matrix model.We observed the growth of MCMECs purified by immunomagnetic beads and induced by MCCs,and characteristics of tubule-like structures(TLSs) formed by induced MCMECs or non-induced MCMECs.The assessment parameters involved the growth curve,the length,the outer and inner diameters,and the wall thickness of the TLSs,and the cell cycle.Results showed that MCCs induced formation of the TLSs in the 3D collagen matrix model.A statistically significant difference was noted regarding the count of TLSs between the control group and the induction group on the 4th day of culture(t=5.00,P=0.001).The outer and inner diameters(t1=5.549,P1=0.000;t2=10.663,P2=0.000) and lengths(t=18.035,P=0.000) of the TLSs in the induction group were statistically significant larger than those in the control group.The TLSs were formed at the earlier time in the induction group compared with the control group.It is concluded that MCCs promote growth and migration of MCMECs,and formation of the TLSs.The 3D collagen matrix model with MCMECs induced by MCCs in the current research may be a favorable choice for research on pro-angiogenic factors in progression of mucoepidermoid carcinoma.