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  • 1
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2005
    In:  Clinical and Experimental Immunology Vol. 142, No. 1 ( 2005-07-28), p. 193-198
    In: Clinical and Experimental Immunology, Oxford University Press (OUP), Vol. 142, No. 1 ( 2005-07-28), p. 193-198
    Kurzfassung: The human MHC class I chain-related gene A (MICA) plays a role in regulating protective responses by intestinal epithelial Vδ1 γ δ T cells and the polymorphism of MICA were reported to be related to several autoimmune diseases. The present study aimed to investigate the association of the microsatellite polymorphisms of TM region of MICA gene with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of the MICA were genotyped in unrelated 86 Chinese patients with UC and 172 ethnically matched healthy controls by a semiautomatic fluorenscently labelled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICA-A5·1 homozygous genotype and A5·1 allele were significantly increased in UC patients compared with healthy controls (22·1%versus 7%, P = 0·0009, Pc = 0·0126, OR = 3·781, 95%CI: 1·738–8·225 and 30·2%versus 17·4%, P = 0·0014, Pc = 0·007, OR = 2·051, 95%CI: 1·336–3·148, respectively). Adjusted the effects of gender and age at onset, MICA-A5·1 homozygous genotype and A5·1 allele were also increased in the UC patients. Moreover MICA-A5·1 allele was significantly increased in frequency in the female UC patients (38·2%versus 21·0%, P = 0·0095, Pc = 0·0475, OR = 2·326, 95%CI: 1·234–4·382). Logistic regression analysis also revealed that gender was independently associated with UC patients carried MICA-A5·1 allele (P = 0·046, OR (male) = 0·511, 95% CI: 0·264–0·987). Although the UC patients with extensive colitis (32·5%versus 17·4% in the healthy controls, P = 0·005, Pc = 0·025) and the UC patients with extraintestinal manifestations (36%versus 17·4% in the healthy controls, P = 0·0039, Pc = 0·0195) were more likely to carry the MICA-A5·1 allele, EIMs was associated with extent of disease (P  & lt; 0·0001, OR (with EIMs) = 3·511, 95% CI 1·747–7·056) and MICA-A5·1 allele was not associated with UC patients with extensive colitis or with EIMs in the logistic regression analysis. Therefore, the MICA-A5·1 homozygous genotype and A5·1 allele were closely associated with UC and the MICA-A5·1 allele was positively associated with the female UC patients in Chinese population.
    Materialart: Online-Ressource
    ISSN: 1365-2249 , 0009-9104
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    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2005
    ZDB Id: 2020024-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 209, No. 2 ( 2022-07-15), p. 238-249
    Kurzfassung: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide and is characterized by lymphocytic infiltration, elevated circulating autoantibodies, and proinflammatory cytokines. The key immune cell subset changes and the TCR/BCR repertoire alterations in pSS patients remain unclear. In this study, we sought to comprehensively characterize the transcriptional changes in PBMCs of pSS patients by single-cell RNA sequencing and single-cell V(D)J sequencing. Naive CD8+ T cells and mucosal-associated invariant T cells were markedly decreased but regulatory T cells were increased in pSS patients. There were a large number of differentially expressed genes shared by multiple subpopulations of T cells and B cells. Abnormal signaling pathways, including Ag processing and presentation, the BCR signaling pathway, the TCR signaling pathway, and Epstein–Barr virus infection, were highly enriched in pSS patients. Moreover, there were obvious differences in the CD30, FLT3, IFN-II, IL-1, IL-2, IL-6, IL-10, RESISTIN, TGF-β, TNF, and VEGF signaling networks between pSS patients and healthy controls. Single-cell TCR and BCR repertoire analysis showed that there was a lower diversity of T cells in pSS patients than in healthy controls; however, there was no significant difference in the degree of clonal expansion, CDR3 length distribution, or degree of sequence sharing. Notably, our results further emphasize the functional importance of αβ pairing in determining Ag specificity. In conclusion, our analysis provides a comprehensive single-cell map of gene expression and TCR/BCR profiles in pSS patients for a better understanding of the pathogenesis, diagnosis, and treatment of pSS.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
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    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2022
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 149, No. 13 ( 2023-10), p. 11491-11498
    Kurzfassung: Currently, there is a lack of an effective strategy for the prevention of peritoneal metastasis (PM) from locally advanced gastric cancer (AGC). This randomized-controlled study aimed to evaluate the outcome of D2 radical resection with hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally AGC patients. Methods All enrolled patients were randomly assigned to receive HIPEC plus systemic chemotherapy (HIPEC group) or systemic chemotherapy alone (non-HIPEC group) after radical gastrectomy. HIPEC was performed intraperitoneally with cisplatin (40 mg/m 2 ) within 72 h after surgery, while systemic chemotherapy based on the SOX regimen (S-1 combined with oxaliplatin) was administered 4–6 weeks after radical surgery. Patterns of recurrence, adverse events, 3-year disease-free survival (DFS), and overall survival (OS) were analyzed. Results A total of 134 patients were enrolled in the present study. The 3-year DFS rate was 73.8% in the HIPEC group, which was significantly higher than that in the non-HIPEC group (61.2%, P =  0.031). The 3-year OS rate was 73.9% in the HIPEC group and 77.6% in the non-HIPEC group, with no significant difference ( P =  0.737). PM was the most common distant metastasis in both groups. The occurrence rate of PM in the HIPEC group was statistically lower than that in the non-HIPEC group (20.9% vs. 40.3%, P =  0.015). Grade 3 or 4 adverse events occurred in 19 (14.2%) patients, and there was no significant difference between the two groups. Conclusion Radical surgery followed by HIPEC combined with systemic chemotherapy is a safe and feasible strategy for locally AGC patients and could effectively improve DFS and reduce the occurrence of PM. However, more prospective randomized studies with a large sample size are warranted. Trial registration This study was registered with www.medresman.org.cn as ChiCTR2200055966 on 10/12/2016.
    Materialart: Online-Ressource
    ISSN: 0171-5216 , 1432-1335
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    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 1459285-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 20 ( 2013-10-15), p. 6277-6288
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 20 ( 2013-10-15), p. 6277-6288
    Kurzfassung: Histone lysine methyltransferase NSD2 (WHSC1/MMSET) is overexpressed frequently in multiple myeloma due to the t(4;14) translocation associated with 15% to 20% of cases of this disease. NSD2 has been found to be involved in myelomagenesis, suggesting it may offer a novel therapeutic target. Here we show that NSD2 methyltransferase activity is crucial for clonogenicity, adherence, and proliferation of multiple myeloma cells on bone marrow stroma in vitro and that NSD2 is required for tumorigenesis of t(4;14)+ but not t(4;14)− multiple myeloma cells in vivo. The PHD domains in NSD2 were important for its cellular activity and biological function through recruiting NSD2 to its oncogenic target genes and driving their transcriptional activation. By strengthening its disease linkage and deepening insights into its mechanism of action, this study provides a strategy to therapeutically target NSD2 in multiple myeloma patients with a t(4;14) translocation. Cancer Res; 73(20); 6277–88. ©2013 AACR.
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
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    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2013
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e16012-e16012
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16012-e16012
    Kurzfassung: e16012 Background: Gastric cancer is the fifth most common cancer in the world and the third leading cause of cancer death. At present, traditional chemotherapy is still the main treatment method of advanced gastric cancer, but the efficacy is limited. Immunotherapy has been identified as a treatment for chemotherapy-refractory gastric cancer, and sintilimab is a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1). This study aims to investigate the efficacy of sintilimab combined with chemotherapy in patients with inoperable metastatic gastric cancer and analyze the prognostic factors of these patients. Methods: Patients with advanced gastric cancer which were initially treated unresectable and with distant metastasis in Zhejiang Cancer Hospital from August 2018 to December 2021 were retrospectively analyzed in this research. Patients received sintilimab combined with chemotherapy (PS regimen) :sintilimab 200mg, day 1, paclitaxel was administered intravenously (150 mg/m 2 ) on day 1, and S-1 was administered orally (80 mg/m 2 /day) on days 1–14 of a 3-week cycle. The primary endpoints were treatment efficiency; and the secondary endpoint was safety and overall survival (OS) time. Results: A total of 66 patients were enrolled, including 43 males and 23 females, with an average age of 62.2 years (29-77 years). All of these patients had one or more distant metastases (liver 28 cases, peritoneum 20 cases, retroperitoneal lymph node 21 cases and ovary 5 cases). 33 patients (50%) underwent surgery, including conversion surgery (26 cases), palliative surgery (7 cases). The mean OS of patients with conversion surgery was 19.2 months (95%CI 16.5̃21.9 months), and the 2-year survival rate was 50.0%. The mean OS of non-conversion surgery was 16.9 months (95%CI 12.9̃20.1 months), and the 2-year survival rate was 29.1% (P=0.028). 24 (92.3%) cases had R0 resection. Multivariate analysis showed that postoperative CA125 level was an independent risk factor for prognosis of these gastric cancer patients. Conclusions: Sintilimab combined with chemotherapy is safe and effective, and combined with conversion surgery can improve the prognosis of patients with partially unresectable advanced gastric cancer.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2022
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 4060-4060
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4060-4060
    Kurzfassung: 4060 Background: Gastric cancer is one of the most common cancer types. Most patients were diagnosed at advanced stages and experienced poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing the gastric cancer-associated mortality. Methods: We prospectively collected a study cohort of 249 participants including 110 pathologically confirmed with stage I-II gastric cancer and 139 with non-cancerous conditions. A plasma sample was collected from each patient before conventional screening modalities for gastric cancer. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. We used these differential profiles to develop an ensemble model to identify gastric cancer patients from non-cancer individuals. We further collected a validation cohort consisting of 73 gastric cancer patients and 94 non-cancer individuals to validate the cfDNA-based assay. Additionally, we compared the performance of our assay and conventional gastroscopy in a hypothetical 100,000 screening population by Monte Carlo simulation. Results: The liquid biopsy assay that incorporated four types of cfDNA characteristics was able to identify early-stage gastric cancer patients from non-cancer individuals at an AUROC of 0.962 in the study cohort and 0.972 in the validation cohort. At a specificity of 92.1% (128/139), it achieved a sensitivity of 88.2% (97/110) in the study cohort. With this threshold, in the validation cohort, 91.5% (86/94) of healthy individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In both study and validation cohorts, the inferred probabilities of cancer showed consistent trends to increase with pathological stages in the cancer group and disease statuses in the non-cancer group. Of note, our approach detected all gastric tumors located in the cardia and fundus (100.0%, 19/19), which could be challenging for gastroscopic examination. Additionally, through in-silico simulations, we showed that our cfDNA-based non-invasive assay may detect 96.3% more gastric cancer cases than conventional gastroscopy owing to higher sensitivity and anticipated better participant compliance in a large hypothetical screening population. Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2023
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e16064-e16064
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16064-e16064
    Kurzfassung: e16064 Background: Borrmann type IV gastric cancer is highly malignant and prone to peritoneal metastasis, including peritoneal dissemination (P1) and positive peritoneal cytology (CY1) causing a dismal prognosis. This study is to compare the efficacy of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy in patients with Borrmann type IV gastric cancer and analyze the prognostic factors of these patients. Methods: According to different therapies, patients diagnosed with Borrmann type IV gastric cancer in Zhejiang Cancer Hospital from June 2010 to June 2020, were divided into two groups: neoadjuvant chemotherapy group (NCT group) and non-neoadjuvant chemotherapy group (NNCT group). Both of two groups were subjected to the propensity score matching (PSM) at a ratio of 1:2 and then the treatment completion rate and overall survival (OS) time were analyzed. Results: A total of 240 cases were included after propensity score matching and 80 patients and 160 patients were enrolled in the NCT group and NNCT group, respectively. Neoadjuvant chemotherapy and postoperative adjuvant chemotherapy were based on platinum combined with fluorouracil. For the efficacy of treatment, R0 resection was performed on 92.2% patients in the NCT group and 88.1% in the NNCT group, but there was no statistical difference (P=0.463). 3-year survival rate was 35.0% in the NCT group compared with 29.4% in the NNCT group (P=0.427), and the 5-year survival rate was 28.7% and 25.6%, respectively (P=0.460). For patients with and without R0 resection, the 3-year survival rate was 34.3% and 7.4% (P 〈 0.001), and the 5-year survival rate was 30.0% and 0%, respectively (P 〈 0.001). Hyperthermic intraperitoneal chemotherapy (HIPEC) was conducted on 40 patients (16.7%), and the survival rate of HIPEC group was better than that of non-HIPEC group (3 year survival rate: 55.0% vs 26.5%, P=0.073; 5 year survival rate: 45.0% vs 23.0%, P=0.174), but the difference was not statistically significant. Conclusions: Borrmann type IV gastric cancer was characterized by poor differentiation and high incidence of peritoneal metastasis. The efficacy of the neoadjuvant chemotherapy based on platinum combined with fluorouracil is limited. A combination of HIPEC and system chemotherapy may effectively improve the prognosis of these patients.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2022
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21616-e21616
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21616-e21616
    Kurzfassung: e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p 〈 0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p 〈 0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p 〈 0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2020
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Gastroenterology, Elsevier BV, Vol. 166, No. 5 ( 2024-05), p. S-1740-
    Materialart: Online-Ressource
    ISSN: 0016-5085
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    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2024
    Standort Signatur Einschränkungen Verfügbarkeit
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