Soft tissue sarcoma is highly heterogeneous, and clear cell sarcoma (CCS) is a rare, aggressive subtype prone to recurrence and lymph node or lung metastasis. This report describes a patient with upper-limb CCS who developed postoperative recurrence and pulmonary metastasis. After transient benefit from first-line doxorubicin plus ifosfamide chemotherapy, the disease progressed despite second-line PD-1 inhibitor combined with anlotinib. Treatment was subsequently switched to cadonilimab, a PD-1/CTLA-4 bispecific antibody, in combination therapy, resulting in a progression-free survival of more than 24 months. This outcome appears encouraging compared with previously reported CCS benchmarks; however, given the single-case nature and combined treatment strategy, the specific contribution of cadonilimab should be interpreted with caution.

Pleural mesothelioma (PM) usually manifests as local intrathoracic invasion, and small intestinal involvement is rare. A 37-year-old man with initially diagnosed stage IV diffuse PM and no definite history of asbestos exposure or other specific occupational or environmental exposure except for long-term smoking was reported. After first-line treatment with Pemetrexed, Carboplatin and Bevacizumab, the disease remained stable. However, acute abdomen occurred during maintenance therapy, and emergency surgery confirmed terminal ileal perforation. Postoperative pathology suggested PM-related ileal involvement/metastatic involvement, with a higher Ki-67 proliferation index than that of the primary lesion. Because only perforation repair rather than segmental bowel resection was performed, the available pathological material could not determine whether full-thickness bowel-wall involvement was present or the direction of tumor invasion. Imaging findings, intraoperative findings and pathological results did not support primary peritoneal mesothelioma or direct contiguous invasion of the ileum by the diaphragmatic lesion; however, microscopic peritoneal dissemination with secondary bowel-wall involvement could not be completely excluded. The aim of this report, together with literature review, is to summarize the diagnostic challenges, management strategies and clinical implications of PM-related small intestinal involvement.

BackgroundPrimary cardiac angiosarcoma is a rare and aggressive malignancy originating from the endothelial lining of cardiac blood vessels. The prognosis remains extremely poor. The study was to evaluate postoperative survival in patients with primary cardiac angiosarcoma after treated with adjuvant therapy.MethodsA systematic review of PubMed from January 1985 to December 2023 was performed to establish a synthetic cohort of patients undergoing surgery for primary cardiac angiosarcoma. Survival analysis was used to assess the relationship between postoperative adjuvant therapy and prognosis. Univariable and multivariable cox regression analyses were used to identify prognostic factors. We then established and validated a nomogram by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Moreover, we present a case of 49-year-old patient with primary cardiac angiosarcoma.ResultsIn the synthetic cohort, the patients with postoperative adjuvant therapy reached longer overall survival (OS) and progression-free survival (PFS) than those without postoperative adjuvant therapy (median OS: 14 VS 8 months, HR = 5.62, 95%CI: 1.66-19.08, P<0.001; median PFS: 12 VS 6 months, HR = 2.98, 95%CI: 1.03-8.66, P = 0.007; Log rank test). Radiotherapy (HR = 0.14, 95% CI: 0.04-0.54, P = 0.004) and chemotherapy (HR = 0.03, 95% CI: 0.00-0.27, P = 0.002) were significantly correlated with better OS. DCA and ROC curves confirmed the nomogram can predict postoperative 6-month survival in patients with primary cardiac angiosarcoma. OS was indistinguishable between patients with R0 or R1 resection (10 VS 10 months, HR = 0.99; 95%CI: 0.34-2.86; P = 0.986). However, compared to patients underwent R1 resection, patients undergoing R0 resection have longer but not statistically significant PFS (10 VS 7 months, HR = 2.16; 95%CI: 0.83-5.61; P = 0.090).ConclusionThe prognosis of patients with primary cardiac angiosarcoma remains extremely poor, even with surgical resection. Postoperative adjuvant therapy was associated with significantly better survival in a small cohort of patients with primary cardiac angiosarcoma. Further studies are warranted to guide future recommendations.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251139779.

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.

Background : Resistance to PD-1 inhibitors poses a major challenge in treating NSCLC. This study explores the epigenetic mechanisms of PD-1 inhibitor resistance, focusing on piRNA expression and related signaling pathways. Methods : High-throughput sequencing was performed on blood samples from three NSCLC patient pairs before and after PD-1 inhibitor resistance to identify differentially expressed piRNAs. The top five were selected for further study. Serum piRNA levels and clinical data from 50 NSCLC patients pre- and post-resistance were analyzed. Target genes of candidate piRNAs were predicted using TargetScan and miRanda, followed by GO and KEGG enrichment analyses. Gene expression was validated via qRT-PCR. Spearman correlation assessed relationships between piRNAs and clinical indicators. ROC curves evaluated predictive value. Results: Five piRNAs (Hsap_2765751, Hsap_249, Hsap_1847317, Hsap_681799, Hsap_857420) were differentially expressed, with Hsap_1847317 significantly upregulated post-resistance (p < 0.001). Target prediction revealed involvement of Hsap_1847317 in the Wnt pathway via AXIN2, NFATC1, PRICKLE4, and CTBP1, with AXIN2 significantly upregulated (p < 0.001). Neutrophil-to-lymphocyte ratio (NLR) also increased post-resistance (p < 0.001) and positively correlated with Hsap_1847317 (r = 0.395, p < 0.05). AUC values were 0.94 for Hsap_1847317 and 0.72 for NLR. Conclusion : Our study showed that Hsap_1847317 and NLR could serve as biomarker for NSCLC immune resistance. These findings contribute to a deeper understanding of the epigenetic regulation of immunotherapy resistance in NSCLC.

BACKGROUND:Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 that has shown significant survival benefits in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) that has progressed after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy. METHODS:In this phase 3 trial, we enrolled patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy. The patients were randomly assigned, in a 1:1 ratio, to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. The primary end point was progression-free survival as assessed by blinded independent review. Overall survival was a hierarchically tested key secondary end point. In the interim analysis of progression-free survival as assessed by blinded independent review, sac-TMT monotherapy met the prespecified criterion for significance (two-sided P<0.0001); we report here the prespecified final analysis of progression-free survival and the preplanned interim analysis of overall survival. RESULTS:Overall, 376 patients underwent randomization, with 188 assigned to each group. After a median follow-up of 18.9 months, the median progression-free survival was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group (hazard ratio for disease progression or death, 0.49; 95% confidence interval [CI], 0.39 to 0.62). Overall survival was significantly longer with sac-TMT than with chemotherapy (hazard ratio for death, 0.60; 95% CI, 0.44 to 0.82; two-sided P = 0.001); 18-month overall survival was 65.8% and 48.0%, respectively. Treatment-related adverse events of grade 3 or higher occurred in 58.0% of patients receiving sac-TMT and in 53.8% of those receiving chemotherapy, with the most common being a decreased neutrophil count (39.9% vs. 33.0%); treatment-related serious adverse events occurred in 9.0% and 17.6%, respectively. CONCLUSIONS:In patients with EGFR-mutated advanced or metastatic NSCLC that had progressed after previous EGFR-TKI therapy, progression-free survival and overall survival outcomes were significantly better with sac-TMT than with platinum-based chemotherapy. (Funded by Sichuan Kelun-Biotech Biopharmaceutical; OptiTROP-Lung04 ClinicalTrials.gov number, NCT05870319.).

Low-dose radiotherapy (LDRT) is a localized irradiation technique that utilizes a relatively low radiation dose, typically ranging from 1 to 5 Gy, which is significantly lower than the dose of 20–60 Gy administered in conventional radical radiotherapy. Chemoimmunotherapy (CIT) is a combined therapeutic approach that integrates chemotherapy and immunotherapy, aiming to improve antitumor efficacy through the synergistic interaction of both modalities. This retrospective study aimed to evaluate the survival outcomes of LDRT combined with CIT vs. CIT alone among small cell lung cancer (SCLC) patients with liver metastasis (LM). This retrospective analysis included 74 SCLC patients with LM from our hospital between September 1, 2019 and September 1, 2024. The 74 included patients were divided into two groups: the CIT group and the LDRT + CIT group. Kaplan-Meier analysis was used to estimate the progression-free survival (PFS) and overall survival (OS). Subgroup analyses based on the line of therapy and the number of metastatic organs were also performed via univariate Cox proportional hazards regression analysis. The results revealed that the median PFS of the LDRT + CIT group was longer than that of the CIT group (5.1 months vs. 4.0 months, p = 0.016), and the beneficial effects of LDRT + CIT on PFS were observed across multiple subgroups. Most subgroups did not exhibit improvements in OS. However, when the patients were stratified on the basis of line of therapy, the median OS (11.0 months vs. 6.0 months, p = 0.047) improved in the LDRT + CIT group receiving later-line treatment. Among SCLC patients with LM, LDRT + CIT may yield superior survival outcomes compared with CIT alone, particularly when LDRT is administered in later-line therapy and among specific subgroups. The findings of this study offer new treatment options for improving survival and quality of life in this challenging patient population.

Background and purpose: For patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients. However, the reference original research trastuzumab (Herceptin®) is more expensive. Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment. This clinical trial aimed to evaluate the efficacy, pharmacokinetics, safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer. Methods: This multi-center, randomised, double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China. This study complied with the research protocol, the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials. It was approved by the hospital's medical ethics committee. The clinical trial registration agency is the State Food and Drug Administration (clinical trial approval number: 2015L04224; clinical trial registration number: CTR20170516). Written informed consent was obtained from subjects before enrollment. Enrolled patients were randomly assigned to the AK-HER2 group and the control group, respectively receiving AK-HER2 or trastuzumab (initial loading dose 8 mg/kg, maintenance dose 6 mg/kg, every 3 weeks as a treatment cycle, total treatment time is 16 cycles) in combination with docetaxel (75 mg/m2, treatment duration is at least 9 cycles). The primary endpoint of this clinical trial was the objective response rate (ORR9) between the AK-HER2 group and the control group in the 9th cycle. Secondary efficacy endpoints included ORR16, disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS) and 1-year survival rate. In this study, 100 subjects (AK-HER2 group to control group=1:1) were randomly selected for blood sample collection after the 6th cycle of medication, The collection time points were 45 minutes after infusion (the end of administration), 4, 8, 24, 72, 120, 168, 336, and 504 hours after the end of administration. After collection, blood samples were analyzed by PK parameter set (PKPS). Other evaluation parameters included safety and immunogenicity assessment. Results: A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep. 2017 and Mar. 2021. In the AK-HER2 group (n=237), 129 subjects in the experimental group achieved complete response (CR) or partial response (PR), and the ORR9 was 54.4%. There were 134 subjects in the control group (n=241) who achieved CR or PR, and the ORR9 was 55.6%. The ORR9 ratio between the AK-HER2 group and the control group was 97.9% [90% confidence interval (CI): 85.4%-112.2%, P=0.784], which was not statistically significant. In all secondary efficacy endpoints, no statistically significant differences were observed between the two groups. We conducted a mean ratio analysis of pharmacokinetics (PK) parameters between the AK-HER2 group and the control group, and the results suggested that the pharmacokinetic characteristics of the two drugs are similar. The incidence of treatment emergent adverse event (TEAE) leading to drug reduction or suspension during trastuzumab treatment was 3.6% (10 cases) in the AK-HER2 group and 8.1% (22 cases) in the control group. There was statistically significant difference between the two groups (P=0.027). The incidence rate was significantly lower in the AK-HER2 group than in the control group, and there was no statistically significant difference among the other groups. The differences in the positive rates of anti-drug antibodies (ADA) and neutralizing antibodies (NAB) between groups were of no statistical significance (P=0.385 and P=0.752). Conclusion: In patients with HER2-positive metastatic breast cancer, AK-HER2 was comparable to the trastuzumab (Herceptin®) in terms of drug efficacy, pharmacokinetics, safety and immunogenicity.

Pulmonary adenocarcinoma with breast metastasis is rarely encountered in clinical practice. Therefore, precise clinical diagnosis of patients with this disease is crucial when selecting subsequent treatment modalities and for overall prognosis assessment. The present study reported on a case of lung cancer with breast metastasis harboring the EML4-ALK fusion. The patient was initially diagnosed with triple-negative breast cancer with lung metastasis, but comprehensive breast cancer treatment was ineffective. Reevaluation of the patient's condition via lung biopsy revealed primary lung adenocarcinoma. In addition, the results of genetic testing revealed the EML4-ALK fusion protein in both lung and breast tissues. After treatment with ALK inhibitors, the patient's symptoms improved rapidly. This case highlights the prolonged diagnostic journey from presentation with a breast mass to ultimately being diagnosed with lung cancer with breast metastasis, underscoring the critical need for heightened awareness among clinicians regarding the possibility of rare metastatic patterns. Timely identification of lung cancer with breast metastasis, facilitated by comprehensive genetic testing, not only refines treatment decisions but also emphasizes the importance of interdisciplinary collaboration in navigating complex clinical scenarios. Such insight contributes to the ongoing development of personalized cancer care that guides clinicians toward more effective and tailored therapeutic strategies for patients with similar diagnostic challenges.

The CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6), a member of the chemokine-like factor superfamily, binds to programmed death-ligand 1 (PD-L1) on the cell membrane, thereby impeding PD-L1’s lysosomal degradation and sustaining its expression. In recent years, extensive studies on PD-L1 have provided insights into its function as an immunepoint inhibitor involved in tumor cell immune evasion. The specific interaction between CMTM6 and PD-L1 suggests a potential role in tumor cell immune evasion and suppression, potentially offering a novel therapeutic target for cancer immunotherapy. Currently, the research on CMTM6 and PD-L1 in diverse tumors and diseases is limited, but their significant roles are indicated. This article provides an overview of the impact of CMTM6 on the immune microenvironment in different types of cancer (such as lung cancer, breast cancer, and liver cancer), and summarizes the effects of CMTM6 on the occurrence and development of various tumors.

Background Cadonilimab (AK104) is a bispecific IgG-single-chain Fv fragment (ScFv) antibody that binds to PD-1 and CTLA-4. Cadonilimab has shown encouraging anti-tumour activity and a favourable safety profile in several tumour types. In second-line treatment, there is no defined standard of care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Cadonilimab is expected to show substantial clinical efficacy. Objective To assess the antitumor activity and safety of cadonilimab monotherapy or combination with conventional therapy in ES-SCLC patients who failed first-line treatment. Methods In this multicenter, open-label, phase II study, ES-SCLC patients who had failed first-line treatment, also aged 18 years to 70 years with histologically or cytologically confirmed ES-SCLC, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–2 were eligible. Patients will receive cadonilimab 10 mg/kg every three weeks (Q3 W) among 24 months until progressive disease (PD) or adverse events (AE) discovery. The primary endpoint is progression-free survival (PFS). Trial registration NCT05901584.

Thymic carcinoma (TC) is an uncommon type of thymic epithelial tumors. Patients with relapsed or refractory TCs have a poor prognosis. Immune checkpoint inhibitor monotherapy can be applied as a second-line treatment for such cases. This study reported a TC patient who did not respond to conventional chemotherapy and radiotherapy but achieved prolonged partial remission lasting 17 months following the third-line treatment with anti-programmed cell death-1 inhibitor sintilimab. This patient did not experience any serious side effects associated with sintilimab treatment. The above results demonstrated that sintilimab could be a feasible therapeutic option for refractory TC patients.

Non-small cell lung cancer (NSCLC) is an aggressive and rapidly expanding lung cancer. Abnormal upregulation or knockdown of PDIA6 expression can predict poor prognosis in various cancers. This study aimed to investigate the biological function of PDIA6 in NSCLC. SOX2 and PDIA6 expression in NSCLC tissues and regulatory relationship between them were analyzed using bioinformatics. GSEA was performed on the enrichment pathway of PDIA6. qRT-PCR was utilized to examine expression of SOX2 and PDIA6 in NSCLC tissues and cells, and dual-luciferase reporter assay and ChIP experiments were performed to validate their regulatory relationship. CCK-8 experiment was conducted to assess cell viability, western blot was to examine levels of stem cell markers and proteins related to aerobic glycolysis pathway in cells. Cell sphere formation assay was used to evaluate efficiency of cell sphere formation. Reagent kits were used to measure glycolysis levels and glycolysis products. High expression of PDIA6 in NSCLC was linked to aerobic glycolysis. Knockdown of PDIA6 reduced cell viability, expression of stem cell surface markers, and cell sphere formation efficiency in NSCLC. Overexpression of PDIA6 could enhance cell viability and promote aerobic glycolysis, but the addition of 2-DG could reverse this result. Bioinformatics predicted the existence of upstream transcription factor SOX2 for PDIA6, and SOX2 was significantly upregulated in NSCLC, and they had a binding relationship. Further experiments revealed that PDIA6 overexpression restored repressive effect of knocking down SOX2 on aerobic glycolysis and cell stemness. This work revealed that the SOX2/PDIA6 axis mediated aerobic glycolysis to promote NSCLC cell stemness, providing new therapeutic strategies for NSCLC.

Radiotherapy is one of the most important methods in the treatment of malignant tumors. However, the decrease of radiosensitivity of tumor cells is the main reason affecting the efficacy of radiotherapy. Epithelial-mesenchymal transition (EMT) is a complex biological process that confers several characteristics necessary for the progression of malignant tumors, such as tumor initiation, aggressiveness, transmissibility, and tolerance to chemotherapy and radiotherapy. In addition, EMT can also be induced by radiation, which endows tumor cells with radiation resistance. Previous studies have shown that inhibition of EMT could enhance the radiosensitivity of tumor cells, but the overall understanding of the molecular mechanisms, key targets and pathways involved are still lacking. In this article, recent studies on the role of EMT in tumor radiation therapy were reviewed, focusing on the signaling pathway, EMT-induced transcription factors, aiming to deepen the understanding of the effect of EMT on the sensitivity of radiotherapy and provide ideas for improving the clinical therapeutic effect of radiotherapy.

Non-small cell lung cancer (NSCLC), as the main type of lung cancer, has a long history of high incidence and mortality. Despite the continuous updates to the American Joint Committee on Cancer (AJCC) staging system, which adapt to evolving treatment modalities and diagnostic advancements, it is evident that patients at the same stage exhibit varying prognoses. The heterogeneity of tumors underscores the need for molecular diagnostics to assume a pivotal role in tumor staging and patient stratification. In our investigation, we meticulously analyzed the data of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, incorporating clinical patients and scrutinizing pathological specimens. Through this comprehensive approach, we established a correlation between the expression of the Thymosin beta 4 X-linked (TMSB4X) gene and poorer disease-free survival (DFS) and overall survival (OS) post-surgery. Compared to the TMSB4X positive expression group, patients in the negative expression group had a better prognosis, with longer DFS (median disease-free survival (median DFS): 16.2 months vs. 11.3 months, P = 0.032) and OS (median overall survival (mOS): 29.8 months vs. 18.5 months, P = 0.033). Furthermore, our findings suggest that TMSB4X may facilitate immune evasion in non-small cell lung cancer cells by influencing the activation of infiltrating dendritic cells (DCs) in tumor infiltrating immune cells (TIICs) (R = 0.27, P = 4.8E+08). In summary, TMSB4X emerges as an unfavorable prognostic factor for NSCLC, potentially modulating the tumor immune microenvironment through its regulatory impact on dendritic cell function, thus facilitating tumor immune escape.

目的 探讨鼻咽癌放疗患者临床因素及口腔剂量体积参数与重度(≥3级)放射性口腔黏膜炎(ROM)发生的关系,分析发生重度ROM的预测因素,为预防重度ROM的发生提供理论依据.方法 回顾性收集本院头颈肿瘤科2020-01-01-2021-12-31收治的173例鼻咽癌患者临床资料,单因素和多因素logistic回归分析鼻咽癌患者临床因素和口腔剂量体积参数与重度ROM的关系.结果 重度ROM的发生率为50.9％(88/173).单因素分析结果显示,吸烟(x2=7.985,P=0.005)、原发肿瘤体积≥55.28 cm3(x2=8.787,P=0.003)、口腔剂量体积参数 V20(t=-5.307,P＜0.001)、V30(t＝-5.549,P＜0.001)、V40(t=-2.824,P=0.005)、V50(t＝-2.444,P=0.016)、V60(t=-2.440,P=0.016)、V70(t=-3.389,P=0.001)、平均剂量 Dmean(t=-2.911,P=0.004)和最大剂量 Dmax(t=-2.963,P=0.003)与重度 ROM的发生有统计学关联.多因素logistic回归分析结果显示,吸烟(RR=2.802,95％CI:1.167～6.729,P=0.021)、原发肿瘤体积 ≥55.28 cm3(RR=2.497,95％CI:1.305～4.777,P=0.006)和 口 腔黏膜受照体积 V30(RR=1.061,95％CI:1.010～1.115,P=0.018)是重度ROM发生的独立危险因素.受试者工作特征曲线分析明确口腔V30的临界值为80.55％,曲线下面积为0.766(95％CI:0.695～0.838).结论 吸烟、肿瘤体积大小和口腔V30是鼻咽癌放疗期间发生重度ROM的独立危险因素,可作为重度ROM发生的预测指标.

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Thyroidal control of the transition of myosin isoforms during flounder metamorphosis was examined by the administration of either only thiourea (TU), a potent inhibitor of thyroid hormone synthesis, or thyroxine (T4) together with TU into premetamorphic larvae. Immersion of premetamorphic larvae in 400 μM of TU inhibited the appearance of the adult-type DTNB (5,5′-dithio-bis-nitrobenzonic acid) light chain, LC2, whereas administration of T4 with TU induced a precocious appearance of LC2 and decreased the relative amount of the larval-type DTNB light chain, LC2*. TU was administered into juveniles just after completion of metamorphosis. The treatment did not affect the composition of the myosin light chains. These results suggest that thyroid hormone irreversibly turns on the switch for transition of the DTNB light chains from larval to adult type during metamorphosis of the flounder.

9031 Background: rh-Endostatin, an antiangiogenic agent, in combination with chemotherapy is recommended by the CSCO guideline as the first-line treatment for EGFR/ALK-negative, advanced or metastatic, non-squamous non–small-cell lung cancer (NSCLC). However, evidence supporting the application of rh-Endostatin plus PD-1 antibody in clinical settings has been limited. The ENPOWER study is an open-label, multicenter, phase II and cohort study to evaluate the efficacy and safety of three days of continuous intravenous infusion (CIV) of rh-Endostatin in combination with PD-1 antibody plus chemotherapy as the first-line regimen for EGFR/ALK-negative, advanced or metastatic, non-squamous NSCLC. Methods: ENPOWER was an open label, multicenter, phase II and cohort study. Patients with EGFR/ALK-negative, advanced or metastatic, non-squamous NSCLC were enrolled and assigned into the following two cohorts. Patients in Cohort 1 (PD-1 combination) received rh-Endostatin plus PD-1 antibody plus standard chemotherapy (Carboplatin or Cisplatin plus Pemetrexed) during the induction period up to 4 - 6 cycles and rh-Endostatin plus PD-1 antibody during the maintenance period until disease progression or intolerable adverse events. Those in cohort 2 different from in cohort 1 was not subject to PD-1 antibody. Results: 43 subjects were evaluable for efficacy analysis, with 15 in Cohort 1 (PD-1 combination) and 28 in Cohort 2. ORR and DCR was 53% and 93% in Cohort 1 (CR, 0; PR, 8; SD, 6; PD,1) and 39% and 86% in Cohort 2 (CR 0; PR 11; SD, 13; PD, 4), respectively. 50 subjects were included in safety analysis. The overall incidence of AEs of any grade was 89%. 92% of the patients in the cohort 1 and 85% in the cohort 2. The majority of AEs was grade 1 or 2. Adverse events of any grade that occurred in at least 10% of patients were neutropenia（76%），nausea/vomiting (61%), AST/ALT abnormal (33%), palpitate (28%), anemia (22%) and skin hypersensitivity (11%) in the cohort 1 and neutropenia（68%），nausea/vomiting (59%), AST/ALT abnormal (21%), palpitate (16%), anemia (40%) in the cohort 2, respectively. Adverse events of grade 3 or higher found in the cohort 1 were neutropenia (23%) and those were neutropenia (19%), AST/ALT abnormal (3%) and anemia (3%) in the cohort 2. Seemingly, Adverse events that occurred more frequently in the cohort 1 than in the cohort 2 were AST/ALT abnormal, palpitate and skin hypersensitivity. Conclusions: Three days of CIV rh-Endostatin in combination with PD-1 antibody plus chemotherapy for the first line treatment of EGFR/ALK negative, advanced or metastatic, non-squamous NSCLC could obtain the better improvement in the efficacy and result in the higher frequent in some of AEs. Clinical trial information: NCT: 04063449.

患者男,67岁.因"左肺鳞状细胞癌切除术,胸部放化疗后1年半余,胸骨后闷痛、乏力10d"入院.一年半余前无明显诱因出现间断咳嗽1个月,支气管镜细胞学提示左肺上叶支气管开口处鳞状细胞癌.颈胸腹增强CT:左肺上叶中央型肺癌伴左肺上叶不张,纵膈、左肺门多发淋巴结转移,双侧胸腔积液.全身骨ECT:未见骨转移征象.行左肺全切及淋巴结清扫术,术中见:病变位于上下叶支气管嵴之间,上下叶疑似受侵.