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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 3605-3605
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 3605-3605
    Abstract: 3605 Background: Recombinant human adenovirus serotype 5 injection (H101), obtained through genetic engineering to delete the E1B domain and part of the E3 domain and then selectively replicated in tumor cells, has been approved in 2005 for the local treatment of nasopharyngeal carcinoma and head and neck cancers. This trial aimed to evaluate the safety and the preliminary treatment efficacy of H101 combined with standard treatments in patients with liver metastases from colorectal cancer. Methods: In this phase 1, dose-escalation trial (ChiCTR1900027922), 17-75 years old colorectal cancer patients with unresectable liver metastases that failed to first-line therapy were included at The Tenth People's Hospital Affiliated to Tongji University between 2018.9 and 2020.12. All patients received H101 combined with standard therapy (bevacizumab + mFOLFOX6/FOLFIRI). Ultrasound-guided injection of H101 into the liver metastases was performed for all patients, with one of the following doses: 5×10 11 vp/injection for the low, 1×10 12 vp/injection for the moderate, 2×10 12 vp/injection for the moderate-high, and 3×10 12 vp/injection for the high dose groups. Intravenous infusion of bevacizumab (5 mg/kg) and administration of standard-dose mFOLFOX6 or FOLFIRI within 48 h after the intratumor injection was performed. The primary endpoint of the trial was the maximum tolerated dose (MTD). The secondary endpoints included safety, tumor responses, and tumor marker CEA. The adverse events (AEs) were monitored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) and evaluated within 1 week after injection. Imaging examinations were performed for all patients to evaluate the tumor responses, according to the irRECIST. Results: Finally, 8 patients were included; the numbers of patients in the 4 groups were 1, 3, 3, and 1, respectively. MTD was not observed in this study. No grade 〉 4 AEs were observed. The major AE included fatigue (5/8), fever (4/8), shiver (3/8), abdominal pain (3/8), and night sweat (3/8). The tumor responses included partial response in one patient (moderate dose group), stable disease in 6 patients (1, 1, 3, and 1 in the low, moderate, moderate-high, and high dose groups, respectively), and progressive disease in 1 patient (moderate group). No dose-effect response was found. The tumor marker CEA was reduced in 6 of the 8 patients, including 1 (1/1), 3 (3/3), 2 (2/3), and 0 patients in the low, moderate, moderate-high, and high-dose groups, respectively. Conclusions: The safety of H101 combined with standard therapy for liver metastases from colorectal cancer is acceptable, which also shows certain preliminary efficacy. The phase 2 trial is now ongoing. Clinical trial information: ChiCTR1900027922. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3039-3039
    Abstract: 3039 Background: The limitations of chimeric antigen receptor T cells (CAR-T) in solid tumors are immunosuppressive tumor microenvironment and difficult infiltration to tumor. In order to reduce on-target off-tumor toxicities and circumvent the immune-suppressive tumor microenvironment(TME), we modified autologous CAR-T to be specific for mesothelin (MSLN) on cancer cells and secrete PD-1 antibodies (aPD1-MSLN-CAR T cells). Here, we report the safety and efficacy of aPD1-MSLN-CAR T cells in 10 patients with relapsed/refractory solid cancers in this single-arm, open-label, first-in-human phase I pilot study (ClinicalTrial.gov: NCT03615313). Methods: aPD1-MSLN-CAR T cells were prepared from peripheral blood mononuclear cells and engineered using PiggyBac Transposon System to target MSLN and secrete PD-1 antibodies. 10 patients with mesothelin positive relapsed/refractory solid cancers after failure to standard therapies were treated with aPD1-MSLN-CAR T cells for two or more cycles until disease progression or intolerable toxicity. The dose escalation of CAR T cells was designed to be 5×10 6 /kg, 5×10 7 /kg, and 1×10 8 /kg, respectively. Adverse events were evaluated according to CTCAE-V4.03 and clinical response was assessed by RECIST 1.1. CAR expression was analyzed using quantitative real-time polymerase chain reaction. PD-1 antibodies were detected by ELISA. Serum IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α were measured using flow cytometry. Results: The most common adverse events were mild fatigue and fever. Abdominal pain was also observed in 1 patient. Grade 1 and 2 cytokine release syndromes were observed without neurologic symptoms in 10 patients. After aPD1-MSLN-mRNA-CAR T cells treatment, 2 patients (20%) achieved partial response (PR), 4 (40%) remained stable (SD), and the rest 4 (40%) patients developed disease progression (PD). The median PFS was 97 days [95% CI (13, 180)] estimated by Kaplan-Meier method. Conclusions: These findings lend support that the combination of modified CAR T cells targeting MSLN with PD1 inhibition for solid tumors is safe. Modified CAR-T cells expressing PD-1 antibodies maybe an option to improve CAR-T efficacy as a result of refined TME. Clinical trial information: NCT03615313 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e15081-e15081
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e15081-e15081
    Abstract: e15081 Background: Anlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor (TKI) for tumor angiogenesis and tumor cell proliferation. Modulation of vascular endothelial growth factor-mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We reported results from the clinical activity and safety of anlotinib combined with anti-PD-1 antibodies in patients with advanced solid tumors. Methods: 21 patients with advanced lung, gallbladder, endometrial, gastric, pancreatic, penile cancers and melanoma were treated since January 2019. Patients received a combination of anlotinib (12mg) once daily on day 1 to day 14 (21 days as a course) plus anti-PD-1 antibodies every 3 weeks until progression or unacceptable toxicity. Radiologic imaging was performed every 6 weeks for the first year of therapy. Results: Among 21 enrolled patients, 11 tumor types were represented, with lung, gallbladder, endometrial cancers and sarcoma being the most common.Most patients had received prior systemic therapy for metastatic disease (76.2%). The objective response rate (ORR) was 19.1%, including one complete responses (CR) (4.8%) and three partial responses (PR) (14.3%) and a disease control rate (DCR = CR+PR+SD) of 81.0% (17 of 21). One CR and three PRs have lasted 4, 4, 5 and 8 months, respectively. Thirteen patients (61.9%) had stable disease (SD) that lasted 1.5 to 13 months. Treatment-related adverse events occurred in 12 patients (57.1%). Three patients (14.3%) had grade 3 treatment-related adverse events. There were no grade 4 and 5 treatment-related adverse events. Grades 3 toxicities included hand-foot syndrome (n = 1) and hypertension (n = 2). Conclusions: anlotinib can be administered combined with anti-PD-1 antibodies with acceptable toxicity and promising durable antitumor efficacy that warrant further testing in a randomized trial.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 3082-3082
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 3082-3082
    Abstract: 3082 Background: Chemotherapy-induced thrombocytopenia (CIT) contributes to treatment dose delay and/or modification, often resulting in poorer survival and disease progression. Compared with partial splenic embolization (PSE) and drugs, high-intensity focused ultrasound has the advantages as following: (1) it is a noninvasive treatment modality with potentially fewer adverse effects and complications; (2) the hospital stay and recovery time after treatment are short; (3) its cost is relatively low compared to surgery. The purpose of this work was to preliminarily investigate the efficacy and safety of high intensity focused ultrasound treatment of chemotherapy-induced thrombocytopenia (CIT) and hypersplenism. Methods: 26 patients with chemotherapy-induced thrombocytopenia and hypersplenism (15 male and 11 female; median age, 56 years; range, 51-66 years) were treated with ultrasound guided high-intensity focused ultrasound. Complications were recorded. Laboratory examination and magnetic resonance imaging were used to evaluate the efficacy. The spleen volume and ablation volume rate of the spleen were calculated by MRI after treatment. They were followed closely for at least 6 months. Results: After high-intensity focused ultrasound treatment, the MRI showed that the ablation area had turned into a non-perfused volume, the mean percent spleen ablation volume was 18.76% ± 6.1% (range, 11.17%-32.34%). After 6 months of HIFU ablation, the ablated area shrank evidently; the sunken spleen formed a lobulated shape and the splenic volume decreased. The platelet count increased 3-7 days after treatment and remained for 1-2weeks higher than baseline (53.33 ± 15.80 × 10 9 /L). The white blood cell count and platelet count of the patients were substantially improved during the follow-up period. No substantial difference was observed in RBC counts between baseline and after treatment. In addition, symptoms such as epistaxis and gingival bleeding were ameliorated or even eliminated, and the quality of life was improved. Follow-up imaging showed a nonperfused volume in the spleen. Conclusions: For the first time to our knowledge, high-intensity focused ultrasound ablation was used to treat Chemotherapy-induced thrombocytopenia (CIT) and hypersplenism. High-intensity focused ultrasound ablation of the spleen may cause damage to a certain volume of the spleen parenchyma to achieve the purpose of hypersplenism treatment. High intensity focused ultrasound may be an effective and safe alternative for treatment of CIT and hypersplenism.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e14610-e14610
    Abstract: e14610 Background: The findings on the clinical effect of the therapy with anti-PD-1 Abs plus angiogenic receptor inhibitors in the treatment of MSS/pMMR mCRC have been inconsistent. The aim of this study was to evaluate the prognostic and predictive role of NLR and IFN-γ in mCRC treated with anti-PD-1 and angiogenic receptor inhibitors. Methods: A total number of 35 patients with MSS/pMMR colorectal cancer treated with anti-PD-1 and angiogenic receptor inhibitors at Shanghai Tenth People’s Hospital (Shanghai, China) between December 2019 and January 2023 were retrospectively evaluated. We reviewed the tumor response and progression-free survival (PFS), and evaluated the associations among neutrophil-to-lymphocyte ratio (NLR), cytokines, and outcomes in the treatment of MSS/pMMR mCRC. A cut-off value of 3 was adopted to discriminate patients with low (NLR 〈 3) versus high (NLR 〉 3) NLR. A cut-off value of 2.7 was employed to discriminate patients with low (IFN-γ 〈 2.7) versus high (IFN-γ 〉 2.7) IFN-γ. Tissue samples from the mCRC patients were stained with CD4, CD8 to establish the immune status. Results: Of the remaining 25 mCRC patients, 14 received sintilimab and fruquintinib, 3 received sintilimab and regorafenib, 6 received camrelizumab and fruquintinib, and 2 received raltizumab and fruquintinib. Two patients were treated with PEG-rhG-CSF, and one patient had myelosuppression after previous chemotherapy. Thus, the NLR ratio could not be calculated in these three patients. Meanwhile, among the 25 patients, 4 patients no cytokine test had been performed before the treatment with anti-PD-1 and VEGF inhibitors. Thus, cytokine analyses were conducted only in the remaining 21 patients. Partial response and stable disease were found in 5 (20%) and 8 (32%) patients, respectively. The disease control rate was 52%. The pretreatment NLR ratio and IFN-γ level of the responder and stable patients were higher than those in progressive patients ( P = 0.0010, n = 22; P = 0.0267, n = 21, respectively). Higher baseline levels of NLR ratio and IFN-γ was associated with longer progression-free survival in mCRC patients receiving anti-PD-1 and angiogenic receptor inhibitors. NLR and IFN-γ were also positively correlated with PFS (R 2 = 0.3334, P = 0.0049; R 2 = 0.4063, P = 0.0019) respectively. Patients getting clinical benefits (PR+SD) were found CD4+ T cells infiltrated (P = 0.0074). Conclusions: Higher NLR ratio and IFN-γ level are prognostic factors associated with longer progression-free survival and better response of MSS/pMMR mCRC patients to anti-PD-1 and angiogenic receptor inhibitors. NLR ratio and IFN-γ level pretreatment could be predictive factors of the response to anti-PD-1 and angiogenic receptor inhibitors in MSS/pMMR mCRC patients. Clinical trial information: ChiCTR2300067767 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 52, No. 9 ( 2020-09), p. 969-983
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 7
    In: Psychotherapy and Psychosomatics, S. Karger AG, Vol. 90, No. 2 ( 2021), p. 127-136
    Abstract: Background: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. Objective: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. Methods: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. Results: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18–1.31; p 〈 0.01), depression (OR = 1.23; 95% CI 1.17–1.29; p 〈 0.01), somatization (OR = 1.20; 95% CI 1.14–1.25; p 〈 0.01), hostility (OR = 1.24; 95% CI 1.18–1.30; p 〈 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34–1.66; p 〈 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78–0.89; p 〈 0.01), subjective support (OR = 0.84; 95% CI 0.80–0.88; p 〈 0.01), utilization of support (OR = 0.80; 95% CI 0.72–0.88; p 〈 0.01), social support (OR = 0.90; 95% CI 0.87–0.93; p 〈 0.01), and global well-being (OR = 0.30; 95% CI 0.22–0.41; p 〈 0.01) were negatively associated. Conclusions: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.
    Type of Medium: Online Resource
    ISSN: 0033-3190 , 1423-0348
    RVK:
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    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1472321-9
    SSG: 5,2
    SSG: 15,3
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  • 8
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 94, No. 8 ( 2023-08), p. 605-613
    Abstract: To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. Methods A retrospective observational study was conducted in 121 patients (2016–2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). Results Among cohort A (male:female=79:42; median age: 42 (14–78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p 〈 0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00–5352.00) vs 700.00 (76.70–2899.00), p 〈 0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23] , p =0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0–6) vs 0 (0–3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). Conclusions Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
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    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 1480429-3
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  • 9
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 21, No. 9 ( 2012-5-1), p. 2132-2141
    Type of Medium: Online Resource
    ISSN: 1460-2083 , 0964-6906
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 1474816-2
    SSG: 12
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 7 ( 2021-03-01), p. 713-722
    Abstract: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079 ), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR) mutation-positive resected stage II-IIIA (N1-N2) non–small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively. CONCLUSION Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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