Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective To investigate the diagnostic value of endoscopic ultrasonography(EUS)for esophageal submucosal tumor(SMT). Methods Clinical data of 388 patients with esophageal SMT, who underwent EUS and endoscopic treatment in Tianjin Medical University General Hospital were collected from May 2010 to September 2016. The golden standard for the origin of esophageal SMT was the diagnosis during endoscopic treatment, and the golden standard of pathological type was the combination of postoperative pathological and immunohistochemical findings. The diagnostic accuracy of EUS for esophageal SMT was evaluated. Results The conventional endoscopy revealed that 31.70%(123/388)and 43.81%(170/388)esophageal SMTs were located in the middle and lower segments of esophagus,respectively. The diagnostic consistency of EUS for the origin of lesion was 71.51%(251/351), while the diagnostic consistency of EUS for lesion originated from the muscularis mucosae, submucosa and muscularis propria layer was 92.90%(170/183), 34.38%(11/32), and 51.47%(70/136), respectively. The diagnostic consistency of EUS for the type of lesion was 81.00%(260/321), while the diagnostic consistency of leiomyoma, esophageal cyst, and lipoma were 88.42%(252/285), 14.81%(4/27), and 80.00%(4/5), respectively. Conclusion EUS can preliminarily diagnose the origin and pathological type of esophageal SMT,but there are limitations on the diagnosis of uncommon lesions,which need combination of pathological and immunohistochemical findings.

OBJECTIVE: To obtain the microcrystal agents of sorafenib and examine the in vivo anti-tumor efficiency of sorafenib-microcrystal on hepatocellular carcinoma cells. METHODS: The solubilizing solution or microcrystal of sorafenib was obtained. A highly aggressive HCC cell line, MHCC97-H, was used to form the subcutaneous or intra-hepatic tumor model in nude mice. Sorafenib-solution or microcrystal was injected into tumors. The clearance curve or anti-tumor efficiency of solubilizing solution or microcrystal was identified. Endogenous of EMT related indicators was identified by qPCR. RESULTS: Sorafenib slowly released in tumor tissues by sorafenib-microcrystal but not sorafenib-solution. Treatment of sorafenib-microcrystal inhibited the in vivo growth of MHCC97-H cells. CONCLUSION: The microcrystal agents of sorafenib is prepared. This work also establishes the in vivo anti-tumor efficiency of sorafenib-microcrystal on HCC cells.

Objective To investigate the characteristics,treatment and prognosis of the gastrointes-tinal iatrogenic perforation resulting from endoscopic operations.Methods The clinical data of the 107 pa-tients with gastrointestinal iatrogenic perforations caused by endoscopic operations from October 2003 to Octo-ber 2013 were retrospectively studied,and the characteristics,treatment and prognosis of these patients were analysed.Results The incidence of the gastrointestinal iatrogenic perforation resulting from endoscopic oper-ations was 0.041%(107 /263 549,among which 0.006% was diagnostic(13 /232 011),and 0.298% was therapeutic (94 /31 538).A total of 107 patients with gastrointestinal iatrogenic chose conservative medical management,endoscopic clipping or surgery according to different conditions after perforations.All patients had good prognosis.Conclusion Endoscopic therapeutic operations are more likely to lead to the occurrence of iatrogenic gastrointestinal perforations compared with diagnostic operations.And most patients could get good prognosis as long as the appropriate treatment is performed when the perforation occurs.

BACKGROUNDThree randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.

METHODSIn the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.

RESULTSOf 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.

CONCLUSIONSWe found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Bevacizumab ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; Bridged-Ring Compounds ; adverse effects ; therapeutic use ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; genetics ; metabolism ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

ObjectiveTo review the clinical characteristics of patients with gastric mucosa-associated lymphoid tissue(MALT) lymphoma and to investigate the effects of Helicobacter pylori (Hp) eradication therapy in these patients.MethodsClinical data of ninety-five patients with gastic MALT lymphoma were reviewed with respect to their clinical manifestations,endoscopic features,histopathological features and Hp infection.The follow-up data of patients treated by Hp eradication therapy were analyzed.The survival curve was calculated with Kaplan-Meier,while the predictive factors for resistance to Hp eradiation were then analyzed by using Cox proportional hazards model.ResultsThe clinical manifestations and endoscopic features of 85 patients with gastric MALT lymphoma were non-specific.Hp positive was found in 97.9％ (93/95) patients at presentation,and 36 patients were treated by Hp eradication with a median follow-up duration of ( 58.1 ± 29.9) months.Total remission was achieved in 94.4％ ( 34/36),including 24 complete remission 10 partial remission.Therapy failure occurred in 2 patients.3-year survival rate of patients treated by Hp eradication were 86.2％ (25/29). Cox multivariate analysis showed that age ( ≥60 years),multiple lesions and non-superficial lesions were independent predictors of resistance to Hp eradication therapy.ConclusionGastric MALT lymphoma is associated with Hp infection.Eradication of Hp can effectively induce remission in these patients.

OBJECTIVETo investigate the treatment and prognosis of the patients with oral mucosal melanoma (OMM).

METHODSThe clinicopathological and follow-up data of patients with OMM in Sun Yat-sen University Cancer Center from January 1976 to December 2005 were analyzed retrospectively.

RESULTSFifty-one cases were analyzed. The pathological lymph node metastasis rate was 61% (31/51) and the affected sites were confined to level I(b)-III (94%). The overall three year and five yearsurvival rates were 35% and 21% respectively. No significant difference of three year and five year survival rates were found between the group of incisional biopsy and the group of excisional biopsy. The prognosis was not affected by pigmentation. The survival rate of the patients receiving surgery combined with biotherapy or biochemotherapy was significantly higher than that of the patients treated by other modalities (P = 0.003).

CONCLUSIONSIn patients with OMM, lymph node metastasis was mostly confined to level I(b)-III. Incisional biopsy and pigmentation were not associated with an unfavorable prognosis. The prognosis of the patients with OMM was poor and the patients may get a better prognosis by receiving surgery combined with biotherapy or biochemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; BCG Vaccine ; therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma ; therapeutic use ; Interleukin-2 ; therapeutic use ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Melanoma ; drug therapy ; pathology ; surgery ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; Mouth Mucosa ; pathology ; surgery ; Mouth Neoplasms ; drug therapy ; pathology ; surgery ; Retrospective Studies ; S100 Proteins ; metabolism ; Survival Rate

ObjectiveTo study the relationship between C-erbB-2 and estrogen (ER) and progesterone (PR) receptors, and the relationship between C-erbB-2, ER, PR with histologic grade. MethodsTo detect ER, PR and C-erbB-2 states by using immunohistochemical analysis and fluorescence in situ hybridization for C-erbB-2 in 163 unselected invasive breast carcinomas. ResultsC-erbB-2, ER ,PR were expressed in 21.5％ ,64.4％ ,44.2％ of 163 cases respectivly . 5 pure mucinous carcinomas , 3 tubular carcinomas and 1 micropapillary carcinoma were ER + ( 100.0％ ) 、C-erbB-2 - ( 100.0％ ) and PR + (40.0％ ,66.7％, 100.0％ ). C-erbB-2 was positive in 22.3％ of grade Ⅱ and 27.0％ of grade Ⅲ invasive ductal carcinomas and negative in all grade Ⅰ invasive ductal carcinomas.ER and PR expression were decreased significantly in C-erbB-2 + tumors compared with C-erbB-2 - tumors( ER,25. 7％ vs 75.0％ ; PR,25.7％ vs 49.2％ ). Although ER or PR expression is decreased in C-erbB-2 + tumors, a substantial proportion of them still express ER or PR. ConclusionC-erbB-2 overexpression or amplifcation was limited to a minority of invasive breast carcinomas. Tumour grade was an independent predictor for ER expression. ER was expressed in small number of high-grade and in large number of grade Ⅰ invasive ductal carcinomas. C-erbB-2 overexpression or amplification essentially was limited to grades Ⅱ and Ⅲ ductal carcinomas and correlated inversely with ER or PR expression.

Objective To investigate the relationship between myocardial ischemia and slow coronary flow phenomenon with 99Tcm-methoxyisobutylisonitrile (MIBI) adenosine myocardial perfusion SPECT imaging. Methods Forty-four patients were divided to three groups according to the result of coronary angiography(CAG). There were GAG-positive(P-GAG) (n=12),slow coronary flow (CSF) (n =22),and normal coronary flow (NCF) (n = 10). Results of adenosine myocardial perfusion imaging were compared among these three groups. Semi-quantitative visual scoring method was used to evaluate the myocardial perfusion:0 = normal,1 = mild decrease,2 = moderate decrease,3 = severe decrease,4 = defect. Statistical analysis was performed using variance analysis,t-test and x2-test. Results No significance was observed at age ( t =0.27,0. 54 and 0. 59),sex (x2 = 0. 92),hypertension,hyperlipemia and diabetes (x2 = 1.23,all P ＞ 0.05 ) among the three groups. A significantly higher frames of the coronary thrombolysis in myocardial infarction (TIMI) flow was noted in CSF than in NCF groups (33.7 ±5.5 vs 17.6 ±3.9,t = 9. 58,P ＜0. 001 ). The positive adenosine myocardial perfusion imaging rate were significant among these three groups with 100% (12/12) in P-CAG group,77.3% (17/22) in CSF group,and 20% (2/10) in NCF group. When using semi-quantitative visual scoring method,significantly higher average ischemia segments were noted in CSF group than in NCF group ( 1.06 ± 0.77 and 0. 91 ± 0.80,t = - 2. 02,P ＜ 0. 05 ),but was less than that in P-CAG group (2.41 ±0.79,t =4. 54,P ＜0.001 ). The degree of ischemia of CSF group was higher than that in NCF group ( 8.01 ± 6.06,and 2.73 ± 2.60,t = - 2.07,P ＜ 0.05 ) and was less than that in P-CAG group (14. 07 ±12. 77 ,t=1.44,P＞0. 05). Conclusion Slow coronary flow phenomenon can be detected by adenosine myocardial perfusion image to offer the evidence of diagnosis and treatment for the chest pain patients with negative coronary angiography results.