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Objective:To explore the correlation between SAM domain and HD domain-containing protein 1 (SAMHD1) and programmed death-ligand 1 (PD-L1) expression in lung adenocarcinoma.Methods:The expression of SAMHD1 in lung adenocarcinoma and its effect on prognosis were analyzed by online database GEPIA and Kaplan-Meier Plotter. The expression of SAMHD1 in lung adenocarcinoma cell lines was detected by quantitative real-time PCR (qPCR) and Western blotting. SAMHD1 gene was silenced in H1975, H1299 and LLC cells by small interfering RNA transfection and lentivirus infection, respectively. The mRNA and protein expression levels of PD-L1 in lung adenocarcinoma cells of control group, siSAMHD1-1 group and siSAMHD1-2 group were detected by qPCR and Western blotting. The membrane PD-L1 level was detected by flow cytometry. A mouse lung adenocarcinoma xenograft model was constructed. The PD-L1 levels in the tumor tissues of control group and shSAMHD1 group were detected by immunohistochemistry. Cell proliferation activities of the control, siSAMHD1-1 and siSAMHD1-2 groups were detected by CCK-8 assays.Results:The GEPIA database results showed that the mRNA expression of SAMHD1 in lung adenocarcinoma was lower than that in normal lung tissue (4.81±0.90 vs. 5.99±0.76, t=20.67, P<0.001) . The median overall survival time of patients with high SAMHD1 expression was significantly longer than that of patients with low SAMHD1 expression (109.0 months vs. 87.7 months, χ2=26.83, P=0.002) . The relative mRNA expression levels of SAMHD1 in A549, PC9, H1299 and H1975 cells were 1.00±0.02, 0.75±0.05, 3.49±0.19 and 7.25±0.38 ( F=589.00, P<0.001) , and the relative protein expression levels were 1.00±0.06, 0.34±0.07, 1.67±0.22 and 2.11±0.63 ( F=15.79, P=0.001) . In H1975 cells, the relative mRNA levels of PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 1.00±0.00, 1.54±0.26 and 2.89±0.13 ( F=102.30, P<0.001) , and the relative protein expression levels were 1.00±0.01, 1.50±0.10 and 1.52±0.33 ( F=6.65, P=0.030) . In H1299 cells, the relative mRNA levels of PD-L1 in the three groups were 1.00±0.08, 1.63±0.03 and 2.14±0.03 ( F=368.80, P<0.001) , and the relative protein levels of PD-L1 were 1.00±0.07, 1.88±0.35 and 2.05±0.38 ( F=10.66, P=0.011) . The expression level of PD-L1 in the siSAMHD1-1 and siSAMHD1-2 groups was higher than that in the control group (all P<0.05) . Flow cytometry results showed that in H1975 cells, the fluorescence intensity of membrane PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 246.83±27.59, 325.60±8.00 and 308.93±7.60 ( F=17.56, P=0.003) , and in H1299 cells, the fluorescence intensity of membrane PD-L1 in the three groups were 959.00±6.25, 1 084.33±7.64 and 1 085.33±21.22 ( F=86.74, P<0.001) . The fluorescence intensity of PD-L1 in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . In xenograft mouse model, the H-SCORE of PD-L1 in the shSAMHD1 group was higher than that in the control group (7.99±1.10 vs. 4.49±0.43, t=5.13, P=0.007) . The proliferative activities of H1975 cells in the control group, siSAMHD1-1 group and siSAMHD1-2 group at 72 h were 0.50±0.02, 0.75±0.05 and 0.73±0.06 ( F=25.01, P=0.001) . The proliferative activities of H1299 cells in the three groups at 72 h were 0.80±0.01, 1.00±0.04 and 0.93±0.07 ( F=13.90, P=0.006) . The cell proliferation activity in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . Conclusion:SAMHD1 silencing induces PD-L1 expression in lung adenocarcinoma.
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Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system. cGMP-AMP synthase (cGAS) is a key regulator of innate immune response to both exogenous and endogenous DNA. After recognizing the cytoplasmic DNA, cGAS produces the second messenger cyclic GMP-AMP (cGAMP), which subsequently combines with the adaptor STING (also known as MITA, MPYS and ERIS) to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines. Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors, which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy. In this article, current understanding of cGAS/STING signaling pathway in tumors was summarized, the pivotal role in tumor immunity and radiotherapy was highlighted, and the potential targeted or alternative therapy of this signaling pathway was reviewed.
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Objective:To investigate the effect and mechanism of Myosin X on the radiosensitivity of non-small cell lung cancer (NSCLC) cell line H1975 in vitro. Methods:Western blot was applied to detect the expression level of Myosin X expression. The H1975 cell line with stable knockout of Myosin X (KO group) and infected with control virus (NC group) were constucted by using CRISPR/Cas9 technique. The knockout efficiency was validated. The radiosensitivity of two cell lines was measured by colony formation assay and single-hit multi-target model. γ-H 2AX focus formation test and RNA sequencing (RNAseq) analysis were employed to identify the regulatory mechanism of the radiosensitivity of lung cancer cell lines mediated by Myosin X. Results:The expression level of Myosin X in the H1975 cells was significantly up-regulated than those in other NSCLC cell lines (all P<0.01). The lentiviral vector of Myosin X sgRNA-Lenti-CRISPR v2 was successfully constructed. After the puromycin screening, H1975 cell lines with complete knockout of Myosin X and control cell lines (NC group) were obtained. Colony formation assay demonstrated that compared with the NC group, the radiosensitivity in the KO group was significantly higher (The D 0 value was decreased from 1.28 Gy to 1.03 Gy, SF 2 decreased from 0.29 to 0.21, and the sensitization ratio was 1.24). The γ-H 2AX focus formation test showed that the number of damage focus formed at 1 h and 6 h after irradiation in the KO group was significantly larger than that in the NC group ( P<0.05. RNAseq analysis indicated that the expression level of ISLR in the KO group was significantly down-regulated than that IN the NC group ( P<0.05). Conclusion:Knockout of Myosin X can increase the radiosensitivity of H1975 cells probably by interfering the repair of DNA double-strand damage and down-regulating the expression level of ISLR.
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Background:Malnutrition is common in patients with cancer, whichadversely affectsthesurvival and quality of life ofcancer patients.However, there is no national data on the prevalence of malnutrition inChinese cancer patients. Thisstudy aims to evaluate the prevalenceof malnutrition and quality of life(QOL)ofChinese patients with localregional, recurrentor metastatic cancer,to address the prognostic value of nutritional status and QOLon the survival of cancer patients in China and to validate the patient-generated subjective global assessment (PG-SGA) questionnaire in Chinese cancer patients.Methods:Thisisanobservational,multi-centered,and hospital-based prospective cohort study.We aimed to recruit 50,000 cancer patients (age 18and above)overan 8-year period.Data collection will occur within 48hrafter patientsare admitted to hospital, 30-days after hospital admission, and the follow-up will be conducted1-8years after enrolment. The primary outcomeisoverall survival, and secondaryoutcomes arelength of hospital stay and hospital costs. Factors measured are demographic characteristics, tumor characteristics, anthropometry measurements,hematological measurement, body composition, PG-SGAscores,Karnofsky performance status scores,and QLQ C30 scores. This protocol wasapproved by local ethical committees of all the participant hospitals.Conclusions: This multi-centered, large-scale, long-time follow-up prospective study will help diagnose malnutrition in cancer patients in China, and identify the related risk factors associated with the negative outcomes. The anticipated results will highlight the need for a truly scientific appraisal of nutrition therapy, and help to improve outcomes among cancer patients in China.Trial Registration: The trial has been registered with the Chinese Clinical Trial Registry, ChiCTR1800020329. Registered on 19 December 2018
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Objective:To explore the appropriate radiotherapy time and method in the treatment of patients with brain metastases (BM) due to from non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation.Methods:Totally 69 EGFR-mutant NSCLC patients with BM treated in Zhongnan Hospital of Wuhan University from January 2014 to September 2018 were retrospectively reviewed. The patients were divided into two groups according to the time of brain radiotherapy, including the upfront radiotherapy group ( n=45) who received concurrent brain radiotherapy and EGFR-tyrosine kinase inhibitors(TKI)treatments and deferred radiotherapy group ( n=24) who received brain radiotherapy after intracranial progression during EGFR-TKI treatment. The upfront radiotherapy group was further divided into two groups, the group treated with WBRT concurrent with EGFR-TKI ( n=20) and the group treated with SRS concurrent with EGFR-TKI ( n=25). Overall survival (OS), progression-free survival (PFS) and intracranial progression-free survival (iPFS) time were evaluated. Results:The median OS of 69 patients was 31.2 months. For the upfront and deferred radiotherapy groups, the 1-, 2- year OS were 95%, 64% and 80%, 35%, the difference between the two groups was statistically significant. On subgroup analysis, the upfront WBRT, upfront SRS and deferred radiotherapy groups 1-, 2- year OS were 95%, 96%, 80% and 42%, 88%, 35%. Moreover, the upfront SRS group was associated with improved OS relative to the deferred radiotherapy group ( HR: 0.10, 95% CI: 0.23-0.46, P=0.003), but the upfront WBRT and deferred radiotherapy groups shared similar OS ( HR: 0.54, 95% CI: 0.21-1.32, P=0.180). There were no significant difference in iPFS and PFS between the upfront and deferred radiotherapy groups( P>0.05). Conclusions:Upfront brain radiotherapy prolonged the survival of BM patients metastasized from EGFR-mutant NSCLC. SRS concurrent with EGFR-TKI may be superior to WBRT concurrent with EGFR-TKI in the treatment of BM metastasized from EGFR-mutant NSCLC.
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Lung cancer is the leading cause of cancer death worldwide as well as in China. For many years, conventional oncologic treatments such as surgery, chemotherapy, and radiotherapy (RT) have dominated the field of non-small cell lung cancer (NSCLC). The recent introduction of immunotherapy in clinical practice, led to a paradigm shift in lung cancer as in many other solid tumors. Recent pre-clinical and clinical data have shown RT may also modify antitumor immune responses through induction of immunogenic cell death and reprogramming of the tumor microenvironment. This has led many to reexamine RT as a partner therapy to immuno-oncology treatments and investigate their potential synergy in an exponentially growing number of clinical trials. Clinical trials combining radiotherapy and immunotherapy are attracting major attention, experts were invited to discuss frontier and controversial academic topics: (1) Recent developments of clinical synergy between radiation and immune checkpoint inhibitors (ICIs) in the treatment of NSCLC; (2) Will immunotherapy and radiotherapy increase the toxicity risk for cancer patients; (3) How to cope the mixed responses/disassociated responses phenomenon in checkpoint inhibition therapy to NSCLC with local ablative therapy; (4) Combining radiotherapy and immunotherapy in the treatment of NSCLC brain metastases.
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Objective@#To investigate postoperative recurrent pattern of the thoracic esophageal squamous cell carcinoma (TESCC), aiming to provide a basis for the delineation of postoperative radiotherapy volume for TESCC.@*Methods@#Clinical data of 66 TESCC patients who recurred after the radical esophagectomy in Zhongnan Hospital of Wuhan University from 2011 to 2017 were retrospectively analyzed. According to the AJCC 8th edition-defined classification of esophageal carcinoma, regional lymph node stations 1 to 8M were defined as the upper-middle mediastinum region (UMMR), and stations 8Lo, 9 and 15 were defined as the inferior mediastinum region (IMR), stations 16 to 20 were regarded as the upper abdominal lymph node region (UAR).@*Results@#Among all 66 patients, 41 cases (62%) experienced loco-regional recurrence alone, 25 cases (38%) presented with distant metastasis alone. A total of 54 patients with 148 lymph node recurred after treatment. The highest risk region of lymph node recurrence was UMMR (118/148, 80%), after that, followed by UAR (24/148, 17%). With regard to 9 cases of UAR, 6 patients had lower TESCC, and 8 patients (89%) were graded as ≥ pathological stage Ⅲ.@*Conclusions@#The highest risk region of lymph node recurrence is UMMR in TESCC patients undergoing radical esophagectomy, which should be considered as the target volume in postoperative radiotherapy. For patients with lower TESCC ≥ pathological stage Ⅲ, UAR might be the target volume with cautions. Anastomosis and IMR are probably not the routine treatment volumes.
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Objective To evaluate the clinical application value of a novel immobilization system in total marrow irradiation ( TMI) with MVCT image. Methods From 2016 to 2017, a retrospective analysis of the setup errors of 22 patients receiving TMI in two groups ( twelve patients were immobilized with the novel immobilization system in group 1, ten patients were immobilized with the combinatorial immobilization devices in group 2) was performed in this study on Zhongnan Hospital of Wuhan University. Two-sample t-test was used to analyze the differences of setup errors and the consistency of setup between two groups. Results In group 1, the setup errors on left-right, superior-inferior, anterior-posterior and rotation directions were ( 1.06±0.79) , ( 1.34±0.66) , ( 2.45±1.48) mm and ( 0.63°±0.65°) for the head and neck position, ( 1.58±1.13) , ( 2.38±1.99) , ( 2.05± 1.68) mm and ( 0.31°± 0.32°) for the chest position, ( 1.67± 1.24) , ( 3.88±2.20) , ( 1.96± 1.32) mm and ( 0.48°± 0.53°) for the pelvis position, and ( 0.95± 0.73) , ( 1.99± 1.35) , ( 3.66±2.13) mm and ( 0.24°±0.31°) for the lower limb, respectively. In group 2, the setup errors were ( 2.59±2.58) , ( 3.28±1.85) , ( 3.71±2.43) mm and ( 1.15°±1.18°) for the head and neck position, ( 4.38±3.69) , ( 5.64±3.78) , ( 2.72± 1.91) mm and ( 1.55°± 0.86°) for the chest position, ( 4.14± 2.97) , ( 6.97±3.68) , ( 2.21±2.26) mm and ( 1.23°±0.74°) for the pelvis position, ( 2.28± 1.15) , ( 5.97± 3.00) , ( 3.44±1.93) mm and ( 1.09°±0.94°) for the lower limb, respectively. The setup errors significantly differed between two groups on the left-right, superior-inferior and rotation directions for all positions ( all P<0.05) . The setup consistency significantly differed between two groups on the left-right, superior-inferior and rotation directions for the chest and pelvis positions ( all P<0.05) . Conclusion The novel immobilization system can significantly improve the setup accuracy and setup consistency, and enhance the precision of treatment for patients.
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Objective To analyze the clinical efficacy and prognosis of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases.Methods Medical records of 104 patients with SBRT for pulmonary oligometastases in our hospital between 2012 and 2018 were retrospectively reviewed.SBRT was performed by intensity modulated radiation therapy (IMRT) technique before December 2015,and by helical tomotherapy (HT) technique in others.The local control (LC),progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.Cox-regression was used for univariate analyses and multivariate analyses.The radiotherapy-related adverse events were evaluated by NCICTCAE V4.0.Results The 1-,2-and 3-year LC rates were 86.6％,75.9％ and 72.3％,respectively.The 1-,2-and 3-year PFS rates were 40.9％,28.4％ and 22.1％,respectively.The 1-,2-and 3-year OS rates were 75.9％,53.2％ and 43.53％,respectively.The median OS time was 26.6 months.Multivariate analyses showed that the pathologic type of primary tumor,the volume of lung oligometastases and the carcino-embryonic antigen (CEA) level before SBRT were the independent prognostic factors of LC (x2 =28.66,P＜0.05).The way of tumor progression after SBRT was the independent prognostic factor of OS (x2=40.01,P＜0.05).Meanwhile,there were no significant differences in the LC and OS between HTSBRT and IMRT-SBRT.Radiation pneumonitis was the major adverse event of SBRT (n =25,24.04％).Less than 7％ patients experienced grade 2 and above radiation pneumonitis.Conclusions SBRT shows high local control rates and tolerable adverse events in the treatment of pulmonary oligometastases.There were no significant differences in the clinical efficacy and adverse events between HT-SBRT and IMRT-SBRT,which means they are all suitable for clinical application.
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Primary central nervous system lymphoma (PCNSL) is a type of extranodal non-Hodgkin lymphoma.Whole brain radiation therapy (WBRT) combined with high-dose methotrexate is the standard treatment.Although PCNSL patients are sensitive to radiation therapy,the duration of response is relatively short and it is likely to provoke delayed neurotoxicity,especially in the elderly patients.Reduced-dose WBRT and autologous stem cell transplantation (ASCT) can lower the risk of neutotoxicity,whereas the clinical efficacy remains to be validated.For the elderly patients with PCNSL,application of WBRT in the first-line treatment should be cautiously considered.
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Objective To investigate postoperative recurrent pattern of the thoracic esophageal squamous cell carcinoma (TESCC),aiming to provide a basis for the delineation of postoperative radiotherapy volume for TESCC.Methods Clinical data of 66 TESCC patients who recurred after the radical esophagectomy in Zhongnan Hospital of Wuhan University from 2011 to 2017 were retrospectively analyzed.According to the AJCC 8th edition-defined classification of esophageal carcinoma,regional lymph node stations Ⅰ to 8M were defined as the upper-middle mediastinum region (UMMR),and stations 8Lo,9 and 15 were defined as the inferior mediastinum region (IMR),stations 16 to 20 were regarded as the upper abdominal lymph node region (UAR).Results Among all 66 patients,41 cases (62％) experienced locoregional recurrence alone,25 cases (38％) presented with distant metastasis alone.A total of 54 patients with 148 lymph node recurred after treatment.The highest risk region of lymph node recurrence was UMMR (118/148,80％),after that,followed by UAR (24/148,17％).With regard to 9 cases of UAR,6 patients had lower TESCC,and 8 patients (89％) were graded as ≥ pathological stage Ⅲ.Conclusions The highest risk region of lymph node recurrence is UMMR in TESCC patients undergoing radical esophagectomy,which should be considered as the target volume in postoperative radiotherapy.For patients with lower TESCC ≥ pathological stage Ⅲ,UAR might be the target volume with cautions.Anastomosis and IMR are probably not the routine treatment volumes.
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Objective@#To investigate the expression of DNA damage repair factor PDZ binding kinase (PBK) and matrix metalloproteinase 9 (MMP-9) in cervical cancer and the effect on clinical outcomes of concurrent chemoradiotherapy.@*Methods@#A total of 65 cervical cancer pathological specimens were collected from January 2014 to July 2016. Immunohistochemistry was used to detect PBK and MMP-9 expression in the specimens.External irrsdeation was treated with intensity-modulated radiation therapy at a dose of 50 Gy/25 F. After 18 times of external irradiation, high-dose rate postoperative treatment was giver at a dose of 30-36 Gy/5-6 F which lasts 3-4 weeks. Weekly chemotherapy with Cisplatin(DDP) begins simultaneously at the beginning of external irradiation. DDP was administered intravenously at a dosage of 40 mg/m2 for 2 to 6 week. All patients were followed-up as routine. The relationship between clinical characteristics and prognosis of patients and the expression of PBK and MMP-9 were analyzed.@*Results@#PBK was expressed in 92.3% of tissues and MMP-9 was expressed in 69.2% of tissues. The expression of PBK was positively associated with overall survival (OS) and disease progression-free survival (PFS) of cervical cancer patients (χ2=4.324, 8.068, P<0.05). The expression of MMP-9 was related with PFS (χ2=5.134, P<0.05). Patients with PBK and MMP-9 expression suffered poor OS and PFS (χ2=5.382, 9.364, P<0.05).@*Conclusions@#PBK and MMP-9 could be a biomarker to predict the prognosis of cervical cancer.
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Objective The aims of this study were to investigate the correlation between the early stage of severe granulocy-topenia and the curative effect on clinical prognosis of chemotherapy in the first-line EP regimen of small cell lung cancer(SCLC). Methods A retrospective study analysis of 82 cases of first-line EP chemotherapy in patients with SCLC was collected clinical da-ta,according to the time of patients with severe neutropenia.Patients were divided into two groups i.e.early-onset group(the first two cycles appeared Ⅲ-Ⅳ neutrophil decline)and non-early-onset group(Ⅲ~Ⅳneutropenia did not appear or three cycles and lat-er).The main indicators for the observation were objective response rate(ORR),disease control rate(DCR),time to progression (TTP)and overall survival(OS).Kaplan-Meier method and Log-rank test were used to analyze univariate survival and Cox propor-tional hazards model to analyze multivariate survival.Results The effective rates of chemotherapy were 81.8% and 75.5%(P=0.499),and DCRs were 97.0% and 95.9% in early-onset and non-early-onset groups,respectively(P>0.05).The median survival time was 10.4 months and 6.9 months in early-onset and non-early-onset groups,respectively(P=0.001).The median OSs were 22.4 months and 16.0 months in early-onset and non-early-onset groups,respectively(P=0.023).Multivariate surviv-al analysis revealed that smoking index,number of chemotherapy cycles,chest radiotherapy and early-onset severe neutropenia were independent prognostic factors for SCLC(P<0.05).Conclusion Chemotherapy-related loss of early severe neutropenia correlates with the efficacy of chemotherapy in SCLC and is an independent predictor of prognosis in SCLC.
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Objective KV-CBCT was utilized to evaluate the setup errors in lung SBRT with R624-SCF immobilization equipment,quantitatively analyze the percentage of all types of errors in the cumulative errors and unravel the main sources of setup errors.Methods The CBCT data weekly and QA data monthly from 32 patients diagnosed with lung neoplasms were collected to quantitatively analyze the setup errors.The cumulative errors were calculated by statistical model.The proportion and source of each type of setup error was analyzed.Results All 32 patients received a total of 420 times of CBCT.The setup errors of immobilization equipment in the lateral,supine-inferior,anterior-posterior directions were (0.03±0.72) mm,(0.73± 1.16) mm and (0.21±0.95) mm,respectively.The errors of tumor motion in three directions were (0.71±2.61) mm,(-0.80±2.60) mm and (0.075± 1.77) mm,respectively.According to the calculation formula proposed by Vance Keeling,the proportion of the cumulative error was 54.55％,9.21％ for immobilization equipment,12.97％ for tumor motion,2.55％ for couch sagging,5.70％ for Gantry radiation isocenter,4.73％ for Collimator radiation isocenter,4.61％ for couch radiation isocenter and 5.70％ for Xray field isocenter,respectively.Conclusions The main factors of setup errors during SBRT treatment for lung cancer are setup random,tumor motion,immobilization equipment,couch sagging and machine isocenter.During radiotherapy,targeted control of tumor motion is of significance for minimizing the cumulative errors.
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Small cell lung cancer (SCLC) is typified by early recurrence and metastasis associated with many genetic changes.The drug ROVA-T composed of the DLL3 antibody Rovalpituzumab and the cytotoxic drug Tesirine achieves the tumor-killing effect by releasing the Tesirine when bound to DLL3.Nfib promotes the SCLC metastasis by altering the structure of the chromosome.The PRAP,EZH2 and Weel inhibitors inhibit the DNA damage repair to improve the antitumor activity of chemotherapeutic drugs.Combination of Ipilimumab and Nivolumab can activate the human immune system to exert antitumor effect.
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Objective To evaluate cytotoxic effects of cytokine-induced killer cells (CIK cells) transfected with the interleukin-2 (IL-2) gene on malignant melanoma cells.Methods Mouse spleen cells were extracted,lymphocyte cells were separated,and CIK cells were prepared from these lymphocyte cells.PEGF-N1 plasmids containing IL-2 gene (PEGF-NI-IL-2) were transfected into CIK cells.Fluorescence microscopy was used to observe transfection products,and reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to determine the IL-2 mRNA expression.Then,effector cells such as CIK cells and IL-2-transfected CIK cells were separately co-cultured with target cells (B16 melanoma cells) at effector-target ratios of 10∶ 1,20∶1 and 40∶1,then 4-hour lactate dehydrogenase release assay was performed to evaluate cytotoxic effects of the two kinds of CIK cells on B 16 cells.After effector cells were cocultured with target cells at the effector-target ratio of 40∶1 for 48 hours,enzyme-linked immunosorbent assay (ELISA) was conducted to detect levels of IL-2,interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of the two kinds of CIK cells.Finally,mouse models of melanoma were established,and a total of 28 melanoma-bearing mice were divided into 4 groups to be peritumorally injected with 0.2 ml sodium chloride physiological solution (control group),100 IU IL-2 solution (IL-2 group),CIK cell suspension at a cell density of 1 × 106 cells per milliliter (CIK group) and IL-2-transfected CIK cell suspension at a cell density of 1 × 106 cells per milliliter (IL-2-transfected CIK group) respectively.Tumor morphology,tumor inhibition rate and cell apoptosis rate were used to evaluate tumor growth in the above groups.If data were normally distributed,t-test was used for comparing means between two groups,and analysis of variance and least significant difference (LSD)-t test were used for comparing means among multiple groups.Results Fluorescence microscopy and RT-PCR both showed that IL-2 was successfully transfected into CIK cells.The cytotoxic effect of IL-2-transfected CIK cells on B16 cells was strongest at the effector-target ratio of 40:1.Levels of IL-2,IFN-γ and TNF-α were also significantly higher in the supernatant of IL-2-transfected CIK cells [(1107.26 ± 6.49) pg/ml,(50.01 ± 3.35) pg/ml,(39.86 ± 3.25) pg/ml] than those in that of CIK cells [(51.09 ± 3.85) pg/ml,(32.71 ± 2.43) pg/ml,(30.11 ± 3.08) pg/ml,t =442.60,14.93,6.89,all P ＜ 0.01].Animal experiments showed that the tumor volume obviously increased in the control group (P ＜ 0.05),but significantly decreased in the IL-2 group,CIK group and IL-2-transfected CIK group (all P ＜ 0.001) after intervention compared with those before intervention.Furthermore,the tumor volume in the IL-2-transfected CIK group was significantly less than that in the other three groups (all P ＜ 0.01),but no significant difference was observed between the IL-2 group and CIK group (P ＞ 0.05).In addition,the apoptosis rate was significantly higher in the IL-2 group,CIK group,and IL-2-transfeeted CIK group than that in the control group (all P ＜ 0.01).The apoptosis rate and tumor inhibition rate were significantly higher in the IL-2-transfected CIK group than those in the IL-2 group and CIK group (all P ＜ 0.01),but insignificantly different between the IL-2 group and CIK group (P ＞ 0.05).Conclusion IL-2-transfected CIK cells had stronger killing effects on malignant melanoma.
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Objective The objective of this study was to provide a way to assess the nutritional status of patients and to afford targeted nutritional supports during the radiotherapy on the basis of the laboratory parameters related to nutrition and chest muscle size in lung cancer patients at the different time.Methods The laboratory parameters were obtained in a cohort of 160 lung cancer patients who received thoracic radiotherapy in our department from March 2012 to November 2015.Fourteen patients who had complete chest CT scan images during radiotherapy were selected to evaluate chest muscles volume.The Chest muscles and its volume were delineated and calculated by CT scan images.Results The levels of(Hemoglobin)HGB,lymphocyte,total protein and albumin were decreased in different degrees during and after radiotherapy,which had the positive correlation with the number and doses of radiotherapy(P0.05).Conclusion Cancer patients were prone to suffer from malnutrition during radiotherapy.The intake of energy and protein was less than the requirements.We should always take the nutritional status of patients into account and provide targeted nutritional support to improve treatment tolerance and quality of life of patients during radiotherapy.
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Objective To analyze the incidence and risk factors of pelvic insufficiency fractures (PIF) in patients with cervical cancer who received pelvic intensity-modulated radiotherapy.Methods This study a retrospective review of all patients was performed with cervical cancer who received pelvic intensity-modulated radiotherapy at our institution from November 2013 to December 2015,and the incidence and risk factors of insufficiency fractures were analyzed.Results Among the 104 patients,16 (with a total of 31 lesions) were diagnosed with pelvic insufficiency fracture.The occurrence rate of pelvic insufficiency was 15.4％.Ten patients (62.5％) had multiple fractures and five patients (31％) complained of pain.All patients' pain was relieved by rest or analgesic drugs.Insufficiency fractures were detected at a median of 6.5 months (range 1-16) from radiotherapy completion.The distribution of PIFs was followed:sacral had 16 cases (51.6％),sacroiliac joint had 7 cases (22.6％),iliac had 6 cases (19.4％),femoral head had 1 case (3.2％) and pubis had 1 case (3.2％).Univariate analysis and multiple analysis showed that postmenopausal status and low body weight (≤55 kg) were thought to be risk factors for PIF(P ＜ 0.05).Subgroup analysis also confirmed that postmenopausal status was a risk factor for PIF (P ＜ 0.05) in postoperative cervical cancer patients after pelvic intensity-modulated radiation therapy.Conclusions Cervical cancer patients with menopausal status and low body weight (≤55 kg) are at some risk for the development of PIF after pelvic intensity-modulated radiotherapy.
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Objective To evaluate the clinical efficacy and prognostic factors of stereotactic body radiotherapy(SBRT)for pulmonary oligometastases,and to further explore the patients most suitable for SBRT. Methods From 2012 to 2105,51 patients with 76 oligometastatic lung tumors were treated with SBRT.In those patients,27 had primary lung tumors and the others had extrapulmonary tumors. Seven patients had squamous cell carcinoma,thirty-five had adenocarcinoma, and the rest had other types of cancer. The patients received radiotherapy at a dose of 50 Gy in five fractions or 60 Gy in three fractions. Survival analysis was made by the Kaplan-Meier method. A multivariate analysis was made by the Cox model. Results The 1-and 2-year local control rates were 86%(65/76)and 80%(61/76),respectively. The 1-and 2-year overall survival(OS)rates were 80%(41/51)and 55%(28/51),respectively. The median survival time was 30(2-57)months,while the median progression-free survival time was 8(1-32)months. Twenty-one patients had grade 1 radiation pneumonitis(RP),while one patient had grade 2 RP. The multivariate analysis revealed that no more than 2 oligometastatic lung tumors,progression-free interval(PFI), and a performance score(PS)no higher than 1 were independent factors for OS(all P<0.05). Conclusions SBRT is effective and safe for treating pulmonary oligometastases. The number of oligometastatic lung tumors,PFI,and PS are independent prognostic factors for OS. Suitable patients and the appropriate timing of treatment are key to the efficacy of SBRT.
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Myocardial fibrosis is a predominant pathological change of radiation-induced heart disease (RIHD) in late stage.It often occurs several or more than ten years after radiotherapy and can lead to myocardial remodeling, impaired cardiac function, and heart failure.At present there is no effective method to prevent or reverse the development of radiation-induced myocardial fibrosis.Many cells, cytokines, and other factors are involved in the development and progression of myocardial fibrosis in RIHD and some of them have been validated.But most investigators focused on the pathological changes and related mechanisms in early stage, and myocardial fibrosis was just regarded as an endpoint event.The definitive mechanisms of myocardial fibrosis in late stage remain unclear.This paper reveiws the studies about general mechanisms of myocardial fibrosis in RIHD and summarizes the roles of microcirculation dysfunction, mast cells, several cytokines, hypoxia, oxidative stress, and renin-angiotensin system, and points out the future research direction of the pathogenesis of myocardial fibrosis in RIHD.It provides new ideas for discovering the potential targets for clinical intervention of myocardial fibrosis in RIHD.