Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18....Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.展开更多
Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment o...Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.展开更多
In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor （GIST） in China, the members of Chinese Society of Clinical Oncology （CSCO） Expert Committee on GIST tho...In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor （GIST） in China, the members of Chinese Society of Clinical Oncology （CSCO） Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST （2017 edition） was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.展开更多
Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment ...Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment is important for improving treatment strategy.This study aimed to identify the critical targets for regulating the efficacy of RFA.Methods:The RFA treatment in hepatocellular carcinoma(HCC)tumor models in vivo,was analyzed by RNA sequencing technology.The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells.Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase(MELK).Results:It was found that RFA treatment upregulated MELK expression,and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response,including anti-tumoral macrophage polarization and increased CD8+T cell cytotoxicity in HCC.Mechanically,MELK binds to fatty acid-binding protein 5(FABP5),and affects its ubiquitination through the K48R pathway to increase its stability,thereby activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling axis to weaken the RFA-mediated antitumor effect.In addition,the synthesis of arginylglycylaspartic acid(RGD)-lipid nanoparticles(LNPs)targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.Conclusions:MELK is a therapeutic target by regulating RFA efficacy in HCC,and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.展开更多
AIM:To investigate the ultrasonographic features of ciliary body mesectodermal leiomyomas(CBL).METHODS:Ultrasonographic data of 18 eyes from 18 patients with histopathologically confirmed CBL were analyzed,covering th...AIM:To investigate the ultrasonographic features of ciliary body mesectodermal leiomyomas(CBL).METHODS:Ultrasonographic data of 18 eyes from 18 patients with histopathologically confirmed CBL were analyzed,covering the period from March 2018 to February 2024.The study included 5 male and 13 female patients,aged 14-64y,with a mean age of 40.11±13.54y.The following ultrasonographic features were evaluated:tumor base diameter,thickness,maximum base diameterto-thickness ratio,shape,internal echogenicity,margin echogenicity,internal echo homogeneity,secondary changes,color Doppler flow imaging(CDFI)findings,and contrast-enhanced ultrasound(CEUS)characteristics.RESULTS:Conventional ultrasound findings of the 18 CBL cases were as follows:1)Tumor size:base diameter of(13.48±4.74)×(11.57±4.00)mm^(2),thickness of 7.70±2.60 mm,and maximum base diameter-to-thickness ratio of 1.77±0.36.2)Shape:14 cases(77.8%)were hemispherical,and 4 cases(22.2%)were irregular.3)Internal echogenicity:the solid component of the tumor was hypoechoic in 16 cases(88.9%)and low-to-medium echogenic in 2 cases(11.1%).4)Margin echogenicity:relatively hyperechoic with a“ring-shaped”margin in 15 cases(83.3%)and isoechoic in 3 cases(16.7%;compared with internal echogenicity).5)Internal echo homogeneity:homogeneous in 11 cases(61.1%)and heterogeneous in 7 cases(38.9%),with 6 cases(33.3%)among the 7 heterogeneous cases exhibiting cystic anechoic areas.6)Secondary retinal detachment was observed in 4 cases(22.2%).CDFI revealed heterogeneous vascularity within the tumors,with blood flow signals ranging from minimal to marked.CEUS was performed in 14 patients:complete contrast agent perfusion was observed in 10 cases(71.4%),and partial perfusion was noted in 4 cases(28.6%).Additionally,8 cases(57.1%)showed a rapid wash-in and slow wash-out pattern,while 6 cases(42.9%)demonstrated a rapid wash-in and rapid wash-out pattern.CONCLUSION:CBL exhibit relatively typical ultrasonographic features,which can provide valuable evidence for the clinical diagnosis and differential diagnosis of intraocular tumors.展开更多
Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
The experimental data obtained from yaw-roll coupled wind tunnel tests are used for lateral-directional departure prediction,by linearizing the_b model to extract nominal dynamic derivatives at each coupling ratio.The...The experimental data obtained from yaw-roll coupled wind tunnel tests are used for lateral-directional departure prediction,by linearizing the_b model to extract nominal dynamic derivatives at each coupling ratio.The prediction results are compared with those of the existing engineering methods which are based on the conventional aerodynamic derivatives.The comparison shows that the yaw-roll coupling ratio has a great influence on the departure susceptibility.The departure resistance will loss in partial region of the coupling ratio when the angle of attack is higher than a critical value.According to the stable and unstable regions of coupling ratio,a two-segment stability augmentation system with two different feedback gain matrices is obtained by pole-placement method.The two-segment stability augmentation system is used in the simulations of straight and level flight,steady turn,spin recovery and Herbst maneuver.The simulation results are also compared with the applications of a fixed-gain stability augmentation system designed by the conventional aerodynamic derivatives.When the yaw-roll coupling effects are fully considered,the two-segment stability augmentation system is more effective for departure restraint and can provide a better flying quality with less control energy.展开更多
Experimental investigation of large amplitude yaw-roll coupled oscillations was conducted in a low-speed wind tunnel using an aircraft configuration model. A special test rig was designed and constructed to provide di...Experimental investigation of large amplitude yaw-roll coupled oscillations was conducted in a low-speed wind tunnel using an aircraft configuration model. A special test rig was designed and constructed to provide different coupled motions from low to high angles of attack.A parameter ‘‘coupling ratio" was introduced to indicate the extent of yaw-roll coupling. At each pitch angle, seven coupling ratios were designed to study the yaw-roll coupling effects on the lateraldirectional aerodynamic characteristics systematically. At high angles of attack, the damping characteristics of yawing and rolling moments drastically varied with coupling ratios. In the coupled motions with the rotation taking place about the wind axis, the lateral-directional aerodynamic moments exhibited unsteady characteristics and were different from the ‘‘quasi-steady" results of the rotary balance tests. The calculated results of the traditional aerodynamic derivative method were also compared with the experimental data. At low and very high angles of attack, the aerodynamic derivative method was applicative. However, within a wide range of angles of attack, the calculated results of aerodynamic derivative method were inconsistent with the experimental data, due to the drastic changes of damping characteristics of lateral-directional aerodynamic moments with yaw-roll coupling ratios.展开更多
Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From O...Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index （MI） in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles （SonoVue） to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 （CTCAE V4.03）. Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.Results： All the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease （SD）, and one patient had a partial response （PR） after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.Conclusions： Our preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.展开更多
Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, w...Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal展开更多
Background: The prognostic role of the V600 E mutation of v-raf murine sarcoma viral oncogene homolog B1(BRAF)in metastatic colorectal cancer(mCRC) is well established, but the therapeutic regimen targeting this disea...Background: The prognostic role of the V600 E mutation of v-raf murine sarcoma viral oncogene homolog B1(BRAF)in metastatic colorectal cancer(mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs.Methods: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute(Beijing, China) between July 2011 and July 2016. Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS), and BRAF mutational status was assayed using direct sequencing. The details of clinicopathologic characteristics of patients and their responses to FOLFOXIRI regimen or standard therapy were obtained by reviewing the medical records. The progression-free survival(PFS) and overall survival(OS)were assessed using Kaplan-Meier analysis and compared using the log-rank test.Results: Of 1694 patients studied, 75 had BRAF exon 15 mutations. Of these 75 patients, 71 had V600 E mutation, 1 had D594 G mutation, 2 had K601 E mutation, and 1 had a novel T599_V600 insAGA alteration. No patients had KRAS or NRAS mutations. Of 63 patients with BRAFV600 E-mutated mCRC and sufficient clinical data, 27(42.9%) had right-sided colon tumors, 19(30.2%) had left-sided colon tumors, and 17(26.9%) had rectal tumors; 26(41.3%) had peritoneal metastases, and 50(79.4%) had distant lymph node metastases.The patients with BRAF K601 E-and T599_V600 insAGA-mutated tumors had similar clinicopathologic features to those with BRAFV600 E-mutated tumors. Patients with the BRAFV600 E mutation benefited more from FOLFOXIRI regimen compared with patients who underwent standard therapy(overall response rate 83.3% vs. 14.0%; median PFS 6.4 months vs. 2.8 months, P = 0.220; median OS11.0 months vs. 6.9 months, P = 0.048).Conclusions: BRAFV600 E mutations were commonly identified in right-sided tumors and showed a high incidence of peritoneal and distant lymph nodes metastases.This subtype of mCRC was characterized by short OS and unique patterns of metastasis. Compared with standard treatment regimens, the FOLFOXIRI regimen had acceptable and manageable toxicities and favorable efficacy on patients with BRAF-mutated mCRC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment....BACKGROUND Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment.Although tremendous advances have been made in the investigation of HCC,the specific mechanisms of the progression of this disease are still only partially established.Hence,more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC.AIM To determine the role of developing brain homeobox 2(Dbx2)gene in promoting the development of HCC.METHODS Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot(WB)and immunohistochemistry.Gain and loss of Dbx2 function assays were performed in vitro and in vivo.Cell viability assays were used to investigate cell growth,flow cytometry was employed to assess cell cycle and apoptosis,and trans-well assays were conducted to evaluate cell migration,invasion,and metastasis.The expression of key molecules in the sonic hedgehog(Shh)signaling was determined by WB.RESULTS Compared to matched adjacent non-tumorous tissues,Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues.Dbx2 overexpression was correlated with large tumor size.Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase,attenuating apoptosis and promoted HCC proliferation,migration,and invasion in vitro and in vivo.Mechanistically,Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2,which was reversed in HCC cells with Dbx2 knockdown.CONCLUSION Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway.展开更多
Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from...Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients in maintenance group were treated with capecitabine 1000 mg/m2 po bid d1-14,q21d.Fifty-two patients in non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%) patients in maintenance group and 47/52(90.4%) in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6) and 9.0 months(95%CI:6.7-11.3) in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015) and 6.5 months(95%CI:4.4-8.5,P=0.007) in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.展开更多
基金supported by Beijing Natural Science Foundation (No. Z20J00105)the National Natural Science Foundation of China (No. 82272627)。
文摘Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.
基金the National Natural Science Foundation of China(No.32272575)National College Student Innovation and Entrepreneurship Training Program(No.202210459164)for financial support.
文摘Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.
文摘In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor （GIST） in China, the members of Chinese Society of Clinical Oncology （CSCO） Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST （2017 edition） was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.
基金supported by the National Natural Science Foundation of China(82072025,82072026,82102162,and 82303886)the“Leading Goose”Research and Development Program of Zhejiang Province(2023C03062)+1 种基金the National Natural Science Foundation of Zhejiang Province(LY22H160040 and LQ22H180010)the Key Research and Development Project of Lishui City(2022ZDYF12,2022ZDYF20,and 2022ZDYF20).
文摘Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment is important for improving treatment strategy.This study aimed to identify the critical targets for regulating the efficacy of RFA.Methods:The RFA treatment in hepatocellular carcinoma(HCC)tumor models in vivo,was analyzed by RNA sequencing technology.The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells.Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase(MELK).Results:It was found that RFA treatment upregulated MELK expression,and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response,including anti-tumoral macrophage polarization and increased CD8+T cell cytotoxicity in HCC.Mechanically,MELK binds to fatty acid-binding protein 5(FABP5),and affects its ubiquitination through the K48R pathway to increase its stability,thereby activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling axis to weaken the RFA-mediated antitumor effect.In addition,the synthesis of arginylglycylaspartic acid(RGD)-lipid nanoparticles(LNPs)targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.Conclusions:MELK is a therapeutic target by regulating RFA efficacy in HCC,and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.
基金Supported by National Key R&D Program of China(No.2018YFC0116000).
文摘AIM:To investigate the ultrasonographic features of ciliary body mesectodermal leiomyomas(CBL).METHODS:Ultrasonographic data of 18 eyes from 18 patients with histopathologically confirmed CBL were analyzed,covering the period from March 2018 to February 2024.The study included 5 male and 13 female patients,aged 14-64y,with a mean age of 40.11±13.54y.The following ultrasonographic features were evaluated:tumor base diameter,thickness,maximum base diameterto-thickness ratio,shape,internal echogenicity,margin echogenicity,internal echo homogeneity,secondary changes,color Doppler flow imaging(CDFI)findings,and contrast-enhanced ultrasound(CEUS)characteristics.RESULTS:Conventional ultrasound findings of the 18 CBL cases were as follows:1)Tumor size:base diameter of(13.48±4.74)×(11.57±4.00)mm^(2),thickness of 7.70±2.60 mm,and maximum base diameter-to-thickness ratio of 1.77±0.36.2)Shape:14 cases(77.8%)were hemispherical,and 4 cases(22.2%)were irregular.3)Internal echogenicity:the solid component of the tumor was hypoechoic in 16 cases(88.9%)and low-to-medium echogenic in 2 cases(11.1%).4)Margin echogenicity:relatively hyperechoic with a“ring-shaped”margin in 15 cases(83.3%)and isoechoic in 3 cases(16.7%;compared with internal echogenicity).5)Internal echo homogeneity:homogeneous in 11 cases(61.1%)and heterogeneous in 7 cases(38.9%),with 6 cases(33.3%)among the 7 heterogeneous cases exhibiting cystic anechoic areas.6)Secondary retinal detachment was observed in 4 cases(22.2%).CDFI revealed heterogeneous vascularity within the tumors,with blood flow signals ranging from minimal to marked.CEUS was performed in 14 patients:complete contrast agent perfusion was observed in 10 cases(71.4%),and partial perfusion was noted in 4 cases(28.6%).Additionally,8 cases(57.1%)showed a rapid wash-in and slow wash-out pattern,while 6 cases(42.9%)demonstrated a rapid wash-in and rapid wash-out pattern.CONCLUSION:CBL exhibit relatively typical ultrasonographic features,which can provide valuable evidence for the clinical diagnosis and differential diagnosis of intraocular tumors.
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
基金supported by the National Natural Science Foundation of China(No.11872209)
文摘The experimental data obtained from yaw-roll coupled wind tunnel tests are used for lateral-directional departure prediction,by linearizing the_b model to extract nominal dynamic derivatives at each coupling ratio.The prediction results are compared with those of the existing engineering methods which are based on the conventional aerodynamic derivatives.The comparison shows that the yaw-roll coupling ratio has a great influence on the departure susceptibility.The departure resistance will loss in partial region of the coupling ratio when the angle of attack is higher than a critical value.According to the stable and unstable regions of coupling ratio,a two-segment stability augmentation system with two different feedback gain matrices is obtained by pole-placement method.The two-segment stability augmentation system is used in the simulations of straight and level flight,steady turn,spin recovery and Herbst maneuver.The simulation results are also compared with the applications of a fixed-gain stability augmentation system designed by the conventional aerodynamic derivatives.When the yaw-roll coupling effects are fully considered,the two-segment stability augmentation system is more effective for departure restraint and can provide a better flying quality with less control energy.
基金supported by the National Natural Science Foundation of China (No. 11072111)
文摘Experimental investigation of large amplitude yaw-roll coupled oscillations was conducted in a low-speed wind tunnel using an aircraft configuration model. A special test rig was designed and constructed to provide different coupled motions from low to high angles of attack.A parameter ‘‘coupling ratio" was introduced to indicate the extent of yaw-roll coupling. At each pitch angle, seven coupling ratios were designed to study the yaw-roll coupling effects on the lateraldirectional aerodynamic characteristics systematically. At high angles of attack, the damping characteristics of yawing and rolling moments drastically varied with coupling ratios. In the coupled motions with the rotation taking place about the wind axis, the lateral-directional aerodynamic moments exhibited unsteady characteristics and were different from the ‘‘quasi-steady" results of the rotary balance tests. The calculated results of the traditional aerodynamic derivative method were also compared with the experimental data. At low and very high angles of attack, the aerodynamic derivative method was applicative. However, within a wide range of angles of attack, the calculated results of aerodynamic derivative method were inconsistent with the experimental data, due to the drastic changes of damping characteristics of lateral-directional aerodynamic moments with yaw-roll coupling ratios.
基金sponsored by National Key Research and Development Plan(No.2017YFC0107300 and No.2017YFC0107303)
文摘Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index （MI） in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles （SonoVue） to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 （CTCAE V4.03）. Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.Results： All the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease （SD）, and one patient had a partial response （PR） after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.Conclusions： Our preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.
文摘Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal
文摘Background: The prognostic role of the V600 E mutation of v-raf murine sarcoma viral oncogene homolog B1(BRAF)in metastatic colorectal cancer(mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs.Methods: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute(Beijing, China) between July 2011 and July 2016. Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS), and BRAF mutational status was assayed using direct sequencing. The details of clinicopathologic characteristics of patients and their responses to FOLFOXIRI regimen or standard therapy were obtained by reviewing the medical records. The progression-free survival(PFS) and overall survival(OS)were assessed using Kaplan-Meier analysis and compared using the log-rank test.Results: Of 1694 patients studied, 75 had BRAF exon 15 mutations. Of these 75 patients, 71 had V600 E mutation, 1 had D594 G mutation, 2 had K601 E mutation, and 1 had a novel T599_V600 insAGA alteration. No patients had KRAS or NRAS mutations. Of 63 patients with BRAFV600 E-mutated mCRC and sufficient clinical data, 27(42.9%) had right-sided colon tumors, 19(30.2%) had left-sided colon tumors, and 17(26.9%) had rectal tumors; 26(41.3%) had peritoneal metastases, and 50(79.4%) had distant lymph node metastases.The patients with BRAF K601 E-and T599_V600 insAGA-mutated tumors had similar clinicopathologic features to those with BRAFV600 E-mutated tumors. Patients with the BRAFV600 E mutation benefited more from FOLFOXIRI regimen compared with patients who underwent standard therapy(overall response rate 83.3% vs. 14.0%; median PFS 6.4 months vs. 2.8 months, P = 0.220; median OS11.0 months vs. 6.9 months, P = 0.048).Conclusions: BRAFV600 E mutations were commonly identified in right-sided tumors and showed a high incidence of peritoneal and distant lymph nodes metastases.This subtype of mCRC was characterized by short OS and unique patterns of metastasis. Compared with standard treatment regimens, the FOLFOXIRI regimen had acceptable and manageable toxicities and favorable efficacy on patients with BRAF-mutated mCRC.
基金Supported by the National Natural Science Foundation of China,No.81571781
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment.Although tremendous advances have been made in the investigation of HCC,the specific mechanisms of the progression of this disease are still only partially established.Hence,more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC.AIM To determine the role of developing brain homeobox 2(Dbx2)gene in promoting the development of HCC.METHODS Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot(WB)and immunohistochemistry.Gain and loss of Dbx2 function assays were performed in vitro and in vivo.Cell viability assays were used to investigate cell growth,flow cytometry was employed to assess cell cycle and apoptosis,and trans-well assays were conducted to evaluate cell migration,invasion,and metastasis.The expression of key molecules in the sonic hedgehog(Shh)signaling was determined by WB.RESULTS Compared to matched adjacent non-tumorous tissues,Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues.Dbx2 overexpression was correlated with large tumor size.Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase,attenuating apoptosis and promoted HCC proliferation,migration,and invasion in vitro and in vivo.Mechanistically,Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2,which was reversed in HCC cells with Dbx2 knockdown.CONCLUSION Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway.
文摘Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients in maintenance group were treated with capecitabine 1000 mg/m2 po bid d1-14,q21d.Fifty-two patients in non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%) patients in maintenance group and 47/52(90.4%) in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6) and 9.0 months(95%CI:6.7-11.3) in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015) and 6.5 months(95%CI:4.4-8.5,P=0.007) in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.
