BACKGROUND Lung cancer is a clinical disease with multiple malignant tumors.Currently,it is difficult for patients to benefit from routine clinical nursing due to the lack of a pertinent and systematic approach.AIM To...BACKGROUND Lung cancer is a clinical disease with multiple malignant tumors.Currently,it is difficult for patients to benefit from routine clinical nursing due to the lack of a pertinent and systematic approach.AIM To investigate the effect of integrated nursing care on the negative emotions and satisfaction of lung cancer patients.METHODS From January 2018 to December 2019,92 patients with lung cancer were selected and divided into the study group and the control group;there were 46 patients in each group.The control group received routine nursing,and the study group received integrated medical care in addition to the care received by the control group.Negative emotions before and after the intervention,the self-management ability score after the intervention,family care burden after the intervention and nursing satisfaction after the intervention were measured in the two groups.RESULTS After the intervention,the self-rating anxiety scale and self-rating depression scale scores in the study group were lower than those in the control group(P<0.05);the scores for health knowledge,self-concept,self-responsibility and self-care skills in the study group were higher than those in the control group(P<0.05);the scores for individual burden and responsibility burden in the study group were lower than those before the intervention(P<0.05);and the nursing satisfaction in the study group(93.48%)was higher than that in the control group(78.26%,P<0.05).CONCLUSION An integrated nursing care approach for lung cancer patients can effectively relieve the patient’s negative feelings,improve their self-management ability,help to reduce the burden of family care and improve patient satisfaction with nursing activities.展开更多
To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry （FCM） and PI staining were...To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry （FCM） and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration （IC50） of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RToPCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was （19.7±1.04）% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group （p〈0.05）. The relative reversal rate of A2780/Taxol cells to paclitaxel was （57.18±2.01）%. As compared with the control group and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.展开更多
The androgen receptor （AR） plays an important role in the development and progression of prostate cancer （PCa）. Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads...The androgen receptor （AR） plays an important role in the development and progression of prostate cancer （PCa）. Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads to the hormonerefractory state. The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear. Several PCa cell lines were established to study the role of AR in PCa, but the results were often inconsistent or contrasting in different cell lines, or in the same cell line grown under different conditions. The cellular and molecular alteration of epithelial cells and their microenvironments are complicated, and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR. In this paper, we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa. We also discuss the advantages of widely used epithelium-stroma co-culture systems, xenograft mouse models, and genetically engineered PCa mouse models. The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.展开更多
Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent stu...Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.展开更多
Objective： To assess whether the polymorphism of ERCC1 Asn118Asn （C → T） had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen f...Objective： To assess whether the polymorphism of ERCC1 Asn118Asn （C → T） had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer. Methods： ERCC1 Asn 118Asn polymorphism was analyzed in 99 patients with stages Ⅲ and Ⅳ advanced colorectal cancer treated with oxaliplatin-based chemotherapy, For all of the patients, ERCC1 Asnl18Asn genotype was analyzed for associations with treatment response and time to disease progress （TTP）. Results： The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% （50/99）, C/T 41.41% （41/99）, T/T 8.08% （8/99）, respectively. Patients with C/C genotype showed higher response rate than those with C/T ＋ T/T （OR = 3.764, 95% CI： 1.310-10.813）. The median TTP of all patients was 7 months （95% CI： 5.569--8.431）. Patients with C/C genotype showed a median TTP of 10 months （95% CI： 8.924-11.076）, which was longer than 5 months （95% CI： 4.424-5.576） in patients with C/T ＋ T/T genotypes. Conclusion： Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based chemotherapy and time to disease progress in Chinese patients with advanced colorectal cancer. ERCC1 Asn 118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.展开更多
Objective:Esophageal cancer(EC)ranks eighth among cancers in cancer-related deaths globally,and~44%of new cases occur in China.We sought to describe the clinical characteristics and treatment landscape of EC in China ...Objective:Esophageal cancer(EC)ranks eighth among cancers in cancer-related deaths globally,and~44%of new cases occur in China.We sought to describe the clinical characteristics and treatment landscape of EC in China before the approval of immunotherapy in 2020.Methods:CHANNEL was a large,retrospective study using patient-level data from 14 hospitals/cancer centers across China,including adults initiating therapy for newly diagnosed EC(January to December 2018).Demographics,clinicopathologic characteristics,and treatment patterns over 6 months were descriptively summarized.Results:Of 3,493 patients,75.7%were men,the mean age was 64.1 years,and 75.0%had no family history of cancer.Most(92.8%)had squamous cell carcinoma,with a primary lesion in the middle esophagus(56.4%).Among patients with resectable EC,92.9%received initial surgery,and 7.1%received neoadjuvant therapy,primarily chemotherapy(85.5%platinum-taxane).Among patients with unresectable early or locally advanced EC,50.8%and 49.2%received palliative and radical therapy,respectively,as the initial treatment,primarily chemotherapy(66.5%platinum-taxane)and chemoradiotherapy(50.8%platinum-taxane),respectively.Adjuvant therapy was administered to 22.9%of patients undergoing initial surgery,and 2.4%receiving neoadjuvant therapy and surgery.Among patients with advanced EC,84.6%received systemic therapy as an initial treatment,primarily chemotherapy(61.5%platinum-taxane).Conclusions:Before the approval of immunotherapy in China,most patients with resectable early or locally advanced EC underwent radical surgery without preoperative treatment,whereas most patients with advanced EC received platinum-taxane chemotherapy.These findings highlight the need for novel EC treatments before immunotherapy was introduced,and provide a baseline for evaluating the benefits of immunotherapy,now that this treatment is widely used in this setting.展开更多
Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicente...Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.展开更多
Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expres...Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expressing PC-3（AR）9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3（AR）2 （stable clone that expresses AR under the control of the cytomegalovirus （CMV） promoter, established by Heisler et al.） after androgen treatment. Results： We found that dihydrotestosterone （DHT） from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3（AR）2 compared with its vector control, PC-3（plRES）. In contrast, PC-3（AR）9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion： These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer （AIPC） PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3（AR）9 prostate cancer cells.展开更多
Squamous cell carcinoma (SCC) is a significant cause of cancer morbidity and mortality worldwide, with an incidence of up to 166 cases per 100 000 population. It arises in the skin, upper aerodigestive tract, lung, an...Squamous cell carcinoma (SCC) is a significant cause of cancer morbidity and mortality worldwide, with an incidence of up to 166 cases per 100 000 population. It arises in the skin, upper aerodigestive tract, lung, and cervix and affects more than 200 000 Americans each year. We report here that a microarray experiment comparing 41 SCC and 13 normal tissue specimens showed that Id2, a gene that controls the cell cycle, was significantly up-regulated in SCC. Enforced expression of Id2 in vitro stimulated the proliferation of SCC cells and up-regulated the transcription of nuclear factor kappa B (NF-κB) and cyclin D1. Enhancement of the NF-κB activity with p65 significantly increased the cell proliferation and the transcription of cyclin D1, whereas inhibition of the NF-κB activity with I kappa B alpha mutant (IκBα M) and pyrroline dithiocarbamate (PDTC) abrogated cell proliferation and transcription of cyclin D1. Furthermore, a mutated NF-κB binding site in the cyclin D1 promoter fully abrogated the Id2-induced transcription of cyclin D1. Taken together, these data indicate that Id2 induces SCC tumor growth and proliferation through the NF-κB/cyclin D1 pathway.展开更多
Generation of induced pluripotent stem （iPS） cells from somatic cells has been achieved successfully by simultaneous viral transduction of defined reprogramming transcription factors （TFs）. However, the process re...Generation of induced pluripotent stem （iPS） cells from somatic cells has been achieved successfully by simultaneous viral transduction of defined reprogramming transcription factors （TFs）. However, the process requires multiple viral vectors for gene delivery. As a result, generated iPS cells harbor numerous viral integration sites in their genomes. This can increase the probability of gene mutagenesis and genomic instability, and present significant barriers to both research and clinical application studies of iPS cells. In this paper, we present a simple lentivirus reprogramming system in which defined factors are fused in-frame into a single open reading frame （ORF） via self-cleaving 2A sequences. A GFP marker is placed downstream of the transgene to enable tracking of transgene expression. We demonstrate that this polycistronic expression system efficiently generates iPS cells. The generated iPS cells have normal karyotypes and are similar to mouse embryonic stem cells in morphology and gene expression. Moreover, they can differentiate into cell types of the three embryonic germ layers in both in vitro and in vivo assays. Remarkably, most of these iPS cells only harbor a single copy of viral vector. This system provides a valuable tool for generation of iPS cells, and our data suggest that the balance of expression of transduced reprogramming TFs in each cell is essential for the reprogramming process. More importantly, when delivered by non-integrating gene-delivery systems, this re-engineered single ORF will facilitate efficient generation of human iPS cells free of genetic modifications.展开更多
The expression levels and changes of endogenous acid fibroblast growth factor （aFGF） in microwave burn wound tissues were detected in order to investigate how to get better therapeutic effects by using the exogenous...The expression levels and changes of endogenous acid fibroblast growth factor （aFGF） in microwave burn wound tissues were detected in order to investigate how to get better therapeutic effects by using the exogenous aFGF for repairing trauma. A burnt-wound animal model was established by NS-FⅡ multifunction spectrum therapeutics equipment, and reverse transcriptase-polymerase chain reaction （RT-PCR） and immunohistochemistry assay were applied to detect the expression levels of endogenous aFGF mRNA in microwave burn wound tissues. The expression level of endogenous aFGF mRNA was significantly increased in the burn wound tissues 12 h after burn, reached the peak at 48 h, and gradually deceased 96 h after burn. The expression of endogenous aFGF mRNA after tissue damage was reversible, and its intensity was in accordance with the repair process of tissue damage, suggesting endogenous aFGF may take part in the cell metabolism and proliferation, and then promote the repair of the burn wound.展开更多
Objective:The aim of this study was to observe the effect of the Prunella vulgaris L extract on the Jurkat human T lymphoma cell line.Methods:Jurkat cells were cultivated with different concentrations of the extract f...Objective:The aim of this study was to observe the effect of the Prunella vulgaris L extract on the Jurkat human T lymphoma cell line.Methods:Jurkat cells were cultivated with different concentrations of the extract from Prunella vulgaris L.The MTT assay and flow cytometry were employed to determine the cells' proliferation inhibition ratio and the apoptosis rates,respectively.Agarose gel electrophoresis was used to observe cellular DNA fragmentation,and western blotting was used to observe changes in Bcl-2 and Bax protein expression.Results:The Prunella vulgaris L extract remarkably inhibited the proliferation of Jurkat cells.This inhibition exhibited dose dependence,with an IC50 of 20.23 ± 0.31 μg/mL.Agarose gel electrophoresis showed that the apoptosis strap became wider and brighter,and flow cytometry showed that the apoptosis rate increased in a concentration-dependent manner.Western blotting showed that Bcl-2 protein was down-regulated and Bax protein was up-regulated during apoptosis.Conclusion:The extract from Prunella vulgaris L induced apoptosis of Jurkat cells by down-regulating Bcl-2 protein and up-regulating Bax protein.These actions inhibited the growth of Jurkat cells.展开更多
An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanom...An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.展开更多
Objective: This study evaluated the therapeutic effect of external beam radiotherapy (RT) combined with trans- catheter arterial chemoembolization (TACE) on the patients with unresectable hepatocellular carcinoma (HCC...Objective: This study evaluated the therapeutic effect of external beam radiotherapy (RT) combined with trans- catheter arterial chemoembolization (TACE) on the patients with unresectable hepatocellular carcinoma (HCC). Methods: From June 1994 to April 2002, 114 patients with unresectable HCC were nonrandomized prospectively stepped into our study. All patients received TACE as initial therapy, except 54 also received combination therapy with external beam therapy. Sur- vival failure patterns were analyzed and compared between the two groups. Results: Overall survival rates in the patients in the radiotherapy group were 65%, 47%, 38% at 1, 2, 3 years, respectively, improved over the non-radiotherapy group rates of 54%, 36.5%, 18% at 1, 2, 3 years, respectively. There was significant difference between two groups (P < 0.05). The survival rates correlated with tumor size, number of tumors, and portal vein embolus. Conclusion: TACE combined with RT is a more effective treatment than TACE alone in patients with unresectable HCC.展开更多
Objective:To observe the effects of Methyl Carboprost and Diclofenac Sodium on opening orifice of uterus and pain controlling in patients with uterine cervix cancer (UCC) when receiving intracavitary brachytherapy. Me...Objective:To observe the effects of Methyl Carboprost and Diclofenac Sodium on opening orifice of uterus and pain controlling in patients with uterine cervix cancer (UCC) when receiving intracavitary brachytherapy. Methods: Sixty patients with UCC of stage IIA-IIIB were divided into three groups randomly before receiving the intracavitary brachytherapy: the patients in group A received Methyl Carboprost in the hind fornix of the vagina, group B received Diclofenac Sodium in the anus, while group C was the control group. Results: The painlessness rates in groups A, B and C were 89.9%, 91.3% and 36.4%, respectively. The incidences of patients with relaxed uterus cervix in groups A, B and C were 91.7%, 85.9% and 48.9%, respectively. Conclusion: Methyl Carboprost and Diclofenac Sodium are useful in relaxing uterus cervix and pain controlling in patients with UCC when receiving intracavitary brachytherapy.展开更多
Background: In linear accelerators, the treatment field’s uniform intensity is achieved by including a flattening filter in the beam. However, to produce more conformal dose distributions, contemporary radiotherapy p...Background: In linear accelerators, the treatment field’s uniform intensity is achieved by including a flattening filter in the beam. However, to produce more conformal dose distributions, contemporary radiotherapy practice now frequently uses fluence and aperture modifying techniques, such as volumetric modulated arc therapy. In these circumstances, the flattening filter in the beam manufacturing process is no longer required. It is therefore necessary to compare the monitor units of 6 MV and flattening filter free plans and how it influences the gamma pass rates to determine which is best for treating cervical cancer with pelvic lymph node metastasis. Methods: VMAT plans for fifteen patients with cervical cancer with pathological pelvic lymph node metastasis were included in this study. Each patient had two VMAT plans using conventional 6 MV beam with flattening filter and one with flattening filter free beam (FFF). The VMAT plans were made using two arcs, and then recalculated to give the planned dose distribution to the detectors in a Delta4 phantom. The VMAT plans were irradiated on the Delta4 phantom using an Elekta linear accelerator (6 MV). Results: The mean monitor unit for the 6 MV plans was 506.3 MU and a standard deviation of 48.6 while that of the FFF plans had a mean MU of 701.5 with a standard deviation of 87.6. The total monitor units (MUs) for the FFF plans were significantly greater than the 6 MV plans (p = 6.1 × 10<sup>-5</sup>). Conclusion: Flattening filter free (FFF) plans require more numbers of monitor units in comparison to conventional 6 MV filtered beams for external radiation of cervical cancer with pelvic lymph nodes involvement.展开更多
The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B Gurdon and Shinya Ya-manaka “for the discovery that mature cells can be re-programmed to become pluripotent”. Professor John B Gordon ...The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B Gurdon and Shinya Ya-manaka “for the discovery that mature cells can be re-programmed to become pluripotent”. Professor John B Gordon who pioneered the feld of somatic cell nuclear transfer was the frst to show that a nucleus of a ma-ture cell can be transplanted into an enucleated egg and give rise to a living organism. His pioneering “clon-ing” technique paved the way for genome reprogram-ming and has led to subsequent cloning of differentani-mal species. Professor Shinya Yamanaka revolutionized the fled of stem cell production by showing that the introduction of four selected genes into cells transform them into induced pluripotent stem cells that resemble embryonic stem cells and serve as promising cells for future regenerative medicine.展开更多
The mesenchymal-epithelial transition factor(MET)proto-oncogene plays impor-tant roles during tumor development.Recently,evidence has revealed MET signaling may impact tumor immunogenicity and regulate the immune resp...The mesenchymal-epithelial transition factor(MET)proto-oncogene plays impor-tant roles during tumor development.Recently,evidence has revealed MET signaling may impact tumor immunogenicity and regulate the immune response.Here we conducted a comprehensive bioinformatic and clinical analysis to explore the characteristics of MET muta-tion and its association with the outcomes in pan-cancer immunotherapy.In 4149 patients with 12 tumor types treated with immune checkpoint inhibitors,MET mutation indicated favorable overall survival(hazard ratio Z 0.61;95%CI,0.50e0.74;P<0.001),progression-free survival(hazard ratio Z 0.74;95%CI,0.60e0.92;P Z 0.01),and objective response rate(40.3%vs.28.1%;P Z 0.003).Moreover,we developed a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy.Further multi-omics anal-ysis on both intrinsic and extrinsic immune landscapes revealed that MET mutation enhanced tumor immunogenicity,enriched infiltration of immune cells,and improved immune re-sponses.In summary,MET mutation improves cancer immunity and is an independent biomarker for favorable outcomes in pan-cancer immunotherapy.These results may influence clinical practices,guide treatment decision-making,and develop immunotherapy for person-alized care.展开更多
The authors regret to note that the affiliations in the above paper were incorrect.The correct author affiliations should be:Lijin Chen a,b,1,Yingying Li b,1,Hong Zhao c,1,Jinyuan Huangb,Huimeng Yan b,Xiaoyan Lin b,∗∗...The authors regret to note that the affiliations in the above paper were incorrect.The correct author affiliations should be:Lijin Chen a,b,1,Yingying Li b,1,Hong Zhao c,1,Jinyuan Huangb,Huimeng Yan b,Xiaoyan Lin b,∗∗,Bin Zhao a,∗a Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou,Fujian 362000,China.展开更多
Background:IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer(SCLC).While,over...Background:IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer(SCLC).While,overprice limited its broad use in clinical.The aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China.Methods:A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients.Utility values were obtained from published studies,and the costs were acquired from real world and literature.Additionally,sensitivity analyses based on a willingness-to-pay(WTP)threshold were performed to identify the uncertain parameters of Markov model.Results:Total costs of atezolizumab group were$48,129,while cost of chemotherapy alone was just$12,920 in placebo group.The quality-adjusted life-years(QALYs)in atezolizumab group was just 0.072 higher than that in placebo group(0.858 QALYs vs.0.786 QALYs).The cost-effectiveness ratio between atezolizumab combination with chemotherapy and chemotherapy alone was$489,013/QALY in China.The net benefit of placebo group was significantly higher than atezolizumab group.One-way sensitivity analyses highlighted that utilities of the progression-free survival(PFS)and progression disease state in placebo group were the most influential parameter.Conclusions:Atezolizumab combination therapy was not more cost-effective than chemotherapy alone at a WTP threshold of$25,929/QALY in China.展开更多
文摘BACKGROUND Lung cancer is a clinical disease with multiple malignant tumors.Currently,it is difficult for patients to benefit from routine clinical nursing due to the lack of a pertinent and systematic approach.AIM To investigate the effect of integrated nursing care on the negative emotions and satisfaction of lung cancer patients.METHODS From January 2018 to December 2019,92 patients with lung cancer were selected and divided into the study group and the control group;there were 46 patients in each group.The control group received routine nursing,and the study group received integrated medical care in addition to the care received by the control group.Negative emotions before and after the intervention,the self-management ability score after the intervention,family care burden after the intervention and nursing satisfaction after the intervention were measured in the two groups.RESULTS After the intervention,the self-rating anxiety scale and self-rating depression scale scores in the study group were lower than those in the control group(P<0.05);the scores for health knowledge,self-concept,self-responsibility and self-care skills in the study group were higher than those in the control group(P<0.05);the scores for individual burden and responsibility burden in the study group were lower than those before the intervention(P<0.05);and the nursing satisfaction in the study group(93.48%)was higher than that in the control group(78.26%,P<0.05).CONCLUSION An integrated nursing care approach for lung cancer patients can effectively relieve the patient’s negative feelings,improve their self-management ability,help to reduce the burden of family care and improve patient satisfaction with nursing activities.
基金a grant from R&D program of Heilongjiang Province (No. GB05C402-11).
文摘To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry （FCM） and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration （IC50） of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RToPCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was （19.7±1.04）% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group （p〈0.05）. The relative reversal rate of A2780/Taxol cells to paclitaxel was （57.18±2.01）%. As compared with the control group and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.
文摘The androgen receptor （AR） plays an important role in the development and progression of prostate cancer （PCa）. Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads to the hormonerefractory state. The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear. Several PCa cell lines were established to study the role of AR in PCa, but the results were often inconsistent or contrasting in different cell lines, or in the same cell line grown under different conditions. The cellular and molecular alteration of epithelial cells and their microenvironments are complicated, and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR. In this paper, we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa. We also discuss the advantages of widely used epithelium-stroma co-culture systems, xenograft mouse models, and genetically engineered PCa mouse models. The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.
基金Supported by a grant from the Qingdao 2020 Medical Scientific Research Guidance Plan(No.2020-WJZD036).
文摘Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.
文摘Objective： To assess whether the polymorphism of ERCC1 Asn118Asn （C → T） had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer. Methods： ERCC1 Asn 118Asn polymorphism was analyzed in 99 patients with stages Ⅲ and Ⅳ advanced colorectal cancer treated with oxaliplatin-based chemotherapy, For all of the patients, ERCC1 Asnl18Asn genotype was analyzed for associations with treatment response and time to disease progress （TTP）. Results： The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% （50/99）, C/T 41.41% （41/99）, T/T 8.08% （8/99）, respectively. Patients with C/C genotype showed higher response rate than those with C/T ＋ T/T （OR = 3.764, 95% CI： 1.310-10.813）. The median TTP of all patients was 7 months （95% CI： 5.569--8.431）. Patients with C/C genotype showed a median TTP of 10 months （95% CI： 8.924-11.076）, which was longer than 5 months （95% CI： 4.424-5.576） in patients with C/T ＋ T/T genotypes. Conclusion： Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based chemotherapy and time to disease progress in Chinese patients with advanced colorectal cancer. ERCC1 Asn 118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.
文摘Objective:Esophageal cancer(EC)ranks eighth among cancers in cancer-related deaths globally,and~44%of new cases occur in China.We sought to describe the clinical characteristics and treatment landscape of EC in China before the approval of immunotherapy in 2020.Methods:CHANNEL was a large,retrospective study using patient-level data from 14 hospitals/cancer centers across China,including adults initiating therapy for newly diagnosed EC(January to December 2018).Demographics,clinicopathologic characteristics,and treatment patterns over 6 months were descriptively summarized.Results:Of 3,493 patients,75.7%were men,the mean age was 64.1 years,and 75.0%had no family history of cancer.Most(92.8%)had squamous cell carcinoma,with a primary lesion in the middle esophagus(56.4%).Among patients with resectable EC,92.9%received initial surgery,and 7.1%received neoadjuvant therapy,primarily chemotherapy(85.5%platinum-taxane).Among patients with unresectable early or locally advanced EC,50.8%and 49.2%received palliative and radical therapy,respectively,as the initial treatment,primarily chemotherapy(66.5%platinum-taxane)and chemoradiotherapy(50.8%platinum-taxane),respectively.Adjuvant therapy was administered to 22.9%of patients undergoing initial surgery,and 2.4%receiving neoadjuvant therapy and surgery.Among patients with advanced EC,84.6%received systemic therapy as an initial treatment,primarily chemotherapy(61.5%platinum-taxane).Conclusions:Before the approval of immunotherapy in China,most patients with resectable early or locally advanced EC underwent radical surgery without preoperative treatment,whereas most patients with advanced EC received platinum-taxane chemotherapy.These findings highlight the need for novel EC treatments before immunotherapy was introduced,and provide a baseline for evaluating the benefits of immunotherapy,now that this treatment is widely used in this setting.
基金supported by the National Natural Science Foundation of China(Grant No.82272744)Natural Science Foundation of Guangdong Province(Grant No.2022A1515010814)Sun Yat-sen University Clinical Research 5010 Program(Grant No.2022008).
文摘Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.
文摘Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expressing PC-3（AR）9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3（AR）2 （stable clone that expresses AR under the control of the cytomegalovirus （CMV） promoter, established by Heisler et al.） after androgen treatment. Results： We found that dihydrotestosterone （DHT） from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3（AR）2 compared with its vector control, PC-3（plRES）. In contrast, PC-3（AR）9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion： These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer （AIPC） PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3（AR）9 prostate cancer cells.
文摘Squamous cell carcinoma (SCC) is a significant cause of cancer morbidity and mortality worldwide, with an incidence of up to 166 cases per 100 000 population. It arises in the skin, upper aerodigestive tract, lung, and cervix and affects more than 200 000 Americans each year. We report here that a microarray experiment comparing 41 SCC and 13 normal tissue specimens showed that Id2, a gene that controls the cell cycle, was significantly up-regulated in SCC. Enforced expression of Id2 in vitro stimulated the proliferation of SCC cells and up-regulated the transcription of nuclear factor kappa B (NF-κB) and cyclin D1. Enhancement of the NF-κB activity with p65 significantly increased the cell proliferation and the transcription of cyclin D1, whereas inhibition of the NF-κB activity with I kappa B alpha mutant (IκBα M) and pyrroline dithiocarbamate (PDTC) abrogated cell proliferation and transcription of cyclin D1. Furthermore, a mutated NF-κB binding site in the cyclin D1 promoter fully abrogated the Id2-induced transcription of cyclin D1. Taken together, these data indicate that Id2 induces SCC tumor growth and proliferation through the NF-κB/cyclin D1 pathway.
文摘Generation of induced pluripotent stem （iPS） cells from somatic cells has been achieved successfully by simultaneous viral transduction of defined reprogramming transcription factors （TFs）. However, the process requires multiple viral vectors for gene delivery. As a result, generated iPS cells harbor numerous viral integration sites in their genomes. This can increase the probability of gene mutagenesis and genomic instability, and present significant barriers to both research and clinical application studies of iPS cells. In this paper, we present a simple lentivirus reprogramming system in which defined factors are fused in-frame into a single open reading frame （ORF） via self-cleaving 2A sequences. A GFP marker is placed downstream of the transgene to enable tracking of transgene expression. We demonstrate that this polycistronic expression system efficiently generates iPS cells. The generated iPS cells have normal karyotypes and are similar to mouse embryonic stem cells in morphology and gene expression. Moreover, they can differentiate into cell types of the three embryonic germ layers in both in vitro and in vivo assays. Remarkably, most of these iPS cells only harbor a single copy of viral vector. This system provides a valuable tool for generation of iPS cells, and our data suggest that the balance of expression of transduced reprogramming TFs in each cell is essential for the reprogramming process. More importantly, when delivered by non-integrating gene-delivery systems, this re-engineered single ORF will facilitate efficient generation of human iPS cells free of genetic modifications.
基金This project was supported by a grant from Foundation of National 863 Program for Research and Development of Class I Novel Drug rh-aFGF (No 2002AA2Z3349)
文摘The expression levels and changes of endogenous acid fibroblast growth factor （aFGF） in microwave burn wound tissues were detected in order to investigate how to get better therapeutic effects by using the exogenous aFGF for repairing trauma. A burnt-wound animal model was established by NS-FⅡ multifunction spectrum therapeutics equipment, and reverse transcriptase-polymerase chain reaction （RT-PCR） and immunohistochemistry assay were applied to detect the expression levels of endogenous aFGF mRNA in microwave burn wound tissues. The expression level of endogenous aFGF mRNA was significantly increased in the burn wound tissues 12 h after burn, reached the peak at 48 h, and gradually deceased 96 h after burn. The expression of endogenous aFGF mRNA after tissue damage was reversible, and its intensity was in accordance with the repair process of tissue damage, suggesting endogenous aFGF may take part in the cell metabolism and proliferation, and then promote the repair of the burn wound.
文摘Objective:The aim of this study was to observe the effect of the Prunella vulgaris L extract on the Jurkat human T lymphoma cell line.Methods:Jurkat cells were cultivated with different concentrations of the extract from Prunella vulgaris L.The MTT assay and flow cytometry were employed to determine the cells' proliferation inhibition ratio and the apoptosis rates,respectively.Agarose gel electrophoresis was used to observe cellular DNA fragmentation,and western blotting was used to observe changes in Bcl-2 and Bax protein expression.Results:The Prunella vulgaris L extract remarkably inhibited the proliferation of Jurkat cells.This inhibition exhibited dose dependence,with an IC50 of 20.23 ± 0.31 μg/mL.Agarose gel electrophoresis showed that the apoptosis strap became wider and brighter,and flow cytometry showed that the apoptosis rate increased in a concentration-dependent manner.Western blotting showed that Bcl-2 protein was down-regulated and Bax protein was up-regulated during apoptosis.Conclusion:The extract from Prunella vulgaris L induced apoptosis of Jurkat cells by down-regulating Bcl-2 protein and up-regulating Bax protein.These actions inhibited the growth of Jurkat cells.
基金Supported by a grant from the Qingdao 2020 Medical Scientific Research Guidance Plan(No.2020-WJZD036)。
文摘An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.
文摘Objective: This study evaluated the therapeutic effect of external beam radiotherapy (RT) combined with trans- catheter arterial chemoembolization (TACE) on the patients with unresectable hepatocellular carcinoma (HCC). Methods: From June 1994 to April 2002, 114 patients with unresectable HCC were nonrandomized prospectively stepped into our study. All patients received TACE as initial therapy, except 54 also received combination therapy with external beam therapy. Sur- vival failure patterns were analyzed and compared between the two groups. Results: Overall survival rates in the patients in the radiotherapy group were 65%, 47%, 38% at 1, 2, 3 years, respectively, improved over the non-radiotherapy group rates of 54%, 36.5%, 18% at 1, 2, 3 years, respectively. There was significant difference between two groups (P < 0.05). The survival rates correlated with tumor size, number of tumors, and portal vein embolus. Conclusion: TACE combined with RT is a more effective treatment than TACE alone in patients with unresectable HCC.
文摘Objective:To observe the effects of Methyl Carboprost and Diclofenac Sodium on opening orifice of uterus and pain controlling in patients with uterine cervix cancer (UCC) when receiving intracavitary brachytherapy. Methods: Sixty patients with UCC of stage IIA-IIIB were divided into three groups randomly before receiving the intracavitary brachytherapy: the patients in group A received Methyl Carboprost in the hind fornix of the vagina, group B received Diclofenac Sodium in the anus, while group C was the control group. Results: The painlessness rates in groups A, B and C were 89.9%, 91.3% and 36.4%, respectively. The incidences of patients with relaxed uterus cervix in groups A, B and C were 91.7%, 85.9% and 48.9%, respectively. Conclusion: Methyl Carboprost and Diclofenac Sodium are useful in relaxing uterus cervix and pain controlling in patients with UCC when receiving intracavitary brachytherapy.
文摘Background: In linear accelerators, the treatment field’s uniform intensity is achieved by including a flattening filter in the beam. However, to produce more conformal dose distributions, contemporary radiotherapy practice now frequently uses fluence and aperture modifying techniques, such as volumetric modulated arc therapy. In these circumstances, the flattening filter in the beam manufacturing process is no longer required. It is therefore necessary to compare the monitor units of 6 MV and flattening filter free plans and how it influences the gamma pass rates to determine which is best for treating cervical cancer with pelvic lymph node metastasis. Methods: VMAT plans for fifteen patients with cervical cancer with pathological pelvic lymph node metastasis were included in this study. Each patient had two VMAT plans using conventional 6 MV beam with flattening filter and one with flattening filter free beam (FFF). The VMAT plans were made using two arcs, and then recalculated to give the planned dose distribution to the detectors in a Delta4 phantom. The VMAT plans were irradiated on the Delta4 phantom using an Elekta linear accelerator (6 MV). Results: The mean monitor unit for the 6 MV plans was 506.3 MU and a standard deviation of 48.6 while that of the FFF plans had a mean MU of 701.5 with a standard deviation of 87.6. The total monitor units (MUs) for the FFF plans were significantly greater than the 6 MV plans (p = 6.1 × 10<sup>-5</sup>). Conclusion: Flattening filter free (FFF) plans require more numbers of monitor units in comparison to conventional 6 MV filtered beams for external radiation of cervical cancer with pelvic lymph nodes involvement.
基金Supported by The United States-Israel Binational Science Foundationthe Israel Science Foundation administered by the Israel Academy of Science and Humanities,in partIsakov N holds the Joseph H Krupp Chair in Cancer Immunobiology
文摘The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B Gurdon and Shinya Ya-manaka “for the discovery that mature cells can be re-programmed to become pluripotent”. Professor John B Gordon who pioneered the feld of somatic cell nuclear transfer was the frst to show that a nucleus of a ma-ture cell can be transplanted into an enucleated egg and give rise to a living organism. His pioneering “clon-ing” technique paved the way for genome reprogram-ming and has led to subsequent cloning of differentani-mal species. Professor Shinya Yamanaka revolutionized the fled of stem cell production by showing that the introduction of four selected genes into cells transform them into induced pluripotent stem cells that resemble embryonic stem cells and serve as promising cells for future regenerative medicine.
基金supported by the National Natural Science Foundation of China(No.82373367).
文摘The mesenchymal-epithelial transition factor(MET)proto-oncogene plays impor-tant roles during tumor development.Recently,evidence has revealed MET signaling may impact tumor immunogenicity and regulate the immune response.Here we conducted a comprehensive bioinformatic and clinical analysis to explore the characteristics of MET muta-tion and its association with the outcomes in pan-cancer immunotherapy.In 4149 patients with 12 tumor types treated with immune checkpoint inhibitors,MET mutation indicated favorable overall survival(hazard ratio Z 0.61;95%CI,0.50e0.74;P<0.001),progression-free survival(hazard ratio Z 0.74;95%CI,0.60e0.92;P Z 0.01),and objective response rate(40.3%vs.28.1%;P Z 0.003).Moreover,we developed a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy.Further multi-omics anal-ysis on both intrinsic and extrinsic immune landscapes revealed that MET mutation enhanced tumor immunogenicity,enriched infiltration of immune cells,and improved immune re-sponses.In summary,MET mutation improves cancer immunity and is an independent biomarker for favorable outcomes in pan-cancer immunotherapy.These results may influence clinical practices,guide treatment decision-making,and develop immunotherapy for person-alized care.
文摘The authors regret to note that the affiliations in the above paper were incorrect.The correct author affiliations should be:Lijin Chen a,b,1,Yingying Li b,1,Hong Zhao c,1,Jinyuan Huangb,Huimeng Yan b,Xiaoyan Lin b,∗∗,Bin Zhao a,∗a Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou,Fujian 362000,China.
基金This work was supported by Research on Chronic Noncommunicable Diseases Prevention and Control of National Ministry of Science and Technology(2016YFC1303804)the National Natural Science Foundation of China(81802487)+2 种基金China Postdoctoral Foundation Project(2019M651217)Youth Development Foundation of the First Hospital of Jilin University(JDYY92018028)the National Natural Science Foundation of China(81500116).
文摘Background:IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer(SCLC).While,overprice limited its broad use in clinical.The aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China.Methods:A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients.Utility values were obtained from published studies,and the costs were acquired from real world and literature.Additionally,sensitivity analyses based on a willingness-to-pay(WTP)threshold were performed to identify the uncertain parameters of Markov model.Results:Total costs of atezolizumab group were$48,129,while cost of chemotherapy alone was just$12,920 in placebo group.The quality-adjusted life-years(QALYs)in atezolizumab group was just 0.072 higher than that in placebo group(0.858 QALYs vs.0.786 QALYs).The cost-effectiveness ratio between atezolizumab combination with chemotherapy and chemotherapy alone was$489,013/QALY in China.The net benefit of placebo group was significantly higher than atezolizumab group.One-way sensitivity analyses highlighted that utilities of the progression-free survival(PFS)and progression disease state in placebo group were the most influential parameter.Conclusions:Atezolizumab combination therapy was not more cost-effective than chemotherapy alone at a WTP threshold of$25,929/QALY in China.
