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Article ; Online: Influence of Hypertension on the Survival of Non-Small Cell Lung Cancer Patients with Type 2 Diabetes Mellitus.

Zeng, Xianghua / Zeng, Dong / Cheng, Jianan / Xu, Cheng / Sun, Chengdu / Long, Haixia / Zhu, Bo

Medical science monitor : international medical journal of experimental and clinical research

2020 Volume 26, Page(s) e921676

Abstract: BACKGROUND Hypertension and diabetes mellitus (DM) are both the risk factors for cancer. This study aimed to explore the prognostic value of fasting blood glucose (FBG) and hypertension in type 2 DM (T2DM) patients with advanced non-small cell lung ... ...

Abstract	BACKGROUND Hypertension and diabetes mellitus (DM) are both the risk factors for cancer. This study aimed to explore the prognostic value of fasting blood glucose (FBG) and hypertension in type 2 DM (T2DM) patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy treatment. MATERIAL AND METHODS There were 181 advanced NSCLC patients with T2DM between 2010 and 2019 included in this study. Their laboratory and clinical data were retrospectively analyzed. The predictive value of FBG and hypertension was evaluated. The Kaplan-Meier method was used to evaluate progression-free survival (PFS). RESULTS The median PFS was 168.0 days (95% CI: 137.9-198.7 days) in patients with FBG ≥7 mmol/L compared to 154.0 days (95% CI: 126.7-181.3 days) for patients with FBG <7 mmol/L (hazard ratio [HR]=1.054; 95% CI: 0.7669-1.452; P=0.7447). Median PFS was longer in non-hypertensive patients than in hypertensive patients [179.0 days (95% CI: 137.3-220.7 days) versus 128.0 days (95% CI: 96.3-159.7 days); P=0.0189]. The existence of hypertension (HR=1.478; 95% CI: 1.063-2.055; P=0.020) was an independent predictor for shorter PFS in the multivariate analysis. Decreased hemoglobin was the major adverse event (over 95% patients). The incidence of all grades of adverse reactions was similar between hypertensive and non-hypertensive patients (all P>0.05) except diarrhea (P=0.020). CONCLUSIONS Complication of hypertension might confer a poor survival for advanced NSCLC patients with T2DM. Further prospective research is needed to confirm these findings.
MeSH term(s)	Aged ; Blood Glucose/metabolism ; Carcinoma, Non-Small-Cell Lung/complications ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/physiopathology ; China ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/physiopathology ; Disease-Free Survival ; Female ; Humans ; Hypertension/epidemiology ; Hypertension/physiopathology ; Incidence ; Kaplan-Meier Estimate ; Lung Neoplasms/drug therapy ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors
Chemical Substances	Blood Glucose
Language	English
Publishing date	2020-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1439041-3
ISSN	1643-3750 ; 1234-1010
ISSN (online)	1643-3750
ISSN	1234-1010
DOI	10.12659/MSM.921676
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Zs.A 4924: Show issues

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Article ; Online: Potent immunogenicity in BRCA1-mutated patients with high-grade serous ovarian carcinoma.

Dai, Ying / Sun, Chengdu / Feng, Yi / Jia, Qingzhu / Zhu, Bo

Journal of cellular and molecular medicine

2018 Volume 22, Issue 8, Page(s) 3979–3986

Abstract: High-grade serous ovarian carcinomas (HGSOCs) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors (ICIs). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise ... ...

Abstract	High-grade serous ovarian carcinomas (HGSOCs) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors (ICIs). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise immunotherapy for HGSOC patients. Here, we analysed genomic data of patients with HGSOCs to depict their immunological phenotype of tumour microenvironment (TME) and figure out the major determinants of immunogenicity. In comparison with other solid tumours, we observed the lowest levels of PD-L1, total mutation burden (TMB) and cytolytic molecules in HGSOCs. Surprisingly, TMB is not certainly positively related to tumour immune response as it failed to predict the response to ICIs in a considerable portion of patients in previous clinical trials. By a machine learning approach in search of biomarkers for immunotherapy implications for HGSOCs, we identified the ten most dominant factors determining the immunogenicity of HGSOCs. Interestingly, we found that BRCA1 mutated tumours presented a potent immunogenic phenotype, independent of TMB, meeting the criteria of both our dominant factors and the determinants of immunogenicity established before. Our findings provide evidence that BRCA1-mutation may be served as a predictive biomarker in guiding ICI therapies for the patients with HGSOCs.
Language	English
Publishing date	2018-05-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.13678
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Zs.A 5752: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Poor glycemic control might compromise the efficacy of chemotherapy in non-small cell lung cancer patients with diabetes mellitus.

Zeng, Xianghua / Xu, Cheng / Cheng, Jianan / Sun, Chengdu / Wang, Zhongyu / Gong, Zhihua / Long, Haixia / Zhu, Bo

Cancer medicine

2019 Volume 9, Issue 3, Page(s) 902–911

Abstract: Background: Previous studies indicated that type 2 diabetes mellitus (T2DM) is related to an increased lung cancer risk, but its role in the prognosis of NSCLC remains conflicting. This study investigated the impact of blood glucose control on the ... ...

Abstract	Background: Previous studies indicated that type 2 diabetes mellitus (T2DM) is related to an increased lung cancer risk, but its role in the prognosis of NSCLC remains conflicting. This study investigated the impact of blood glucose control on the outcomes in NSCLC patients with T2DM treated with platinum-based doublets. Methods: Clinicopathological and survival data from 191 T2DM patients with advanced NSCLC, who received platinum-based chemotherapy, were retrospectively analyzed. Based on the blood glucose conditions during chemotherapy, patients were classified into poor (n = 84) and good control (n = 107) groups. Progression-free survival (PFS) was assessed using the Kaplan-Meier method. Results: The median PFS among patients with good glycemic control [197.0 (95% CI: 136.3-257.7) days] was longer than that among those with poor control [132.0 (95% CI: 112.5-151.5) days] (P = .0003). Further subgroup analysis of lung squamous carcinoma and adenocarcinoma patients showed that the median PFS of the good control group was also significantly longer than that of the poor control group [179.0 (95% CI: 78.4-279.6) days vs 125.0 (95% CI: 110.9-139.1) days, P = .0014; 197.0 (95% CI: 124.3-269.7) days vs 154.0 (95% CI: 129.9-178.1) days, P = .0359; respectively]. The incidence rates of side effects were similar among patients with good glycemic control and those with poor glycemic control (all P > .05). Conclusions: Satisfactory glycemic control during platinum-based chemotherapy might provide a survival benefit to T2DM patients with NSCLC. Further studies are warranted to confirm our findings.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Blood Glucose/drug effects ; Carcinoma, Non-Small-Cell Lung/blood ; Carcinoma, Non-Small-Cell Lung/complications ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/mortality ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Female ; Glycemic Control/statistics & numerical data ; Humans ; Hypoglycemic Agents/administration & dosage ; Kaplan-Meier Estimate ; Lung/diagnostic imaging ; Lung Neoplasms/blood ; Lung Neoplasms/complications ; Lung Neoplasms/drug therapy ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Prognosis ; Progression-Free Survival ; Retrospective Studies
Chemical Substances	Blood Glucose ; Hypoglycemic Agents
Language	English
Publishing date	2019-12-12
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	2045-7634
ISSN (online)	2045-7634
DOI	10.1002/cam4.2750
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Article ; Online: Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy.

Cheng, Jia-Nan / Luo, Wen / Sun, Chengdu / Jin, Zheng / Zeng, Xianghua / Alexander, Peter B / Gong, Zhihua / Xia, Xin / Ding, Xiaofang / Xu, Shouxia / Zou, Ping / Wan, Yisong Y / Jia, Qingzhu / Li, Qi-Jing / Zhu, Bo

Science advances

2021 Volume 7, Issue 5

Abstract: The efficacy of cancer immunotherapy is dictated by ... ...

Abstract	The efficacy of cancer immunotherapy is dictated by CD8
Language	English
Publishing date	2021-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abc7609
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Article ; Online: C

Sun, Chengdu / Wang, Liming / Gao, Dan / Pan, Yuanming / Zhao, Yuliang / Chen, Chunying / Guo, Mingzhou

Nanoscale

2016 Volume 8, Issue 36, Page(s) 16332–16339

Abstract: ... ...

Abstract	C
MeSH term(s)	Angiogenesis Inhibitors/pharmacology ; Animals ; Female ; Fullerenes/pharmacology ; Gene Knockdown Techniques ; Histone Deacetylase Inhibitors/pharmacology ; Human Umbilical Vein Endothelial Cells/drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic/drug therapy ; RNA, Small Interfering ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Fullerenes ; HIF1A protein, human ; Histone Deacetylase Inhibitors ; Hypoxia-Inducible Factor 1, alpha Subunit ; RNA, Small Interfering ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; MMP2 protein, human (EC 3.4.24.24) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; fullerene C60 (NP9U26B839)
Language	English
Publishing date	2016-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2515664-0
ISSN	2040-3372 ; 2040-3364
ISSN (online)	2040-3372
ISSN	2040-3364
DOI	10.1039/c6nr04875g
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Article: Immune Landscape of Colorectal Cancer Tumor Microenvironment from Different Primary Tumor Location.

Zhang, Longhui / Zhao, Yuetao / Dai, Ying / Cheng, Jia-Nan / Gong, Zhihua / Feng, Yi / Sun, Chengdu / Jia, Qingzhu / Zhu, Bo

Frontiers in immunology

2018 Volume 9, Page(s) 1578

Abstract: To define differences in tumor microenvironment (TME) immune phenotypes between right and left colorectal cancers (CRCs) and explore their therapeutic implications. Gene expression profiling and clinical characteristics of patients with CRC were ... ...

Abstract	To define differences in tumor microenvironment (TME) immune phenotypes between right and left colorectal cancers (CRCs) and explore their therapeutic implications. Gene expression profiling and clinical characteristics of patients with CRC were retrieved from The Cancer Genome Atlas data portal. Immune cell infiltration was estimated based on single-sample gene set enrichment analysis. CRCs tissue microarrays (TMAs) containing 90 consecutive cases of surgical samples were used for validation. Expression of CD8A and VEGFA was confirmed by immunohistochemistry (IHC) analysis with TMAs, and overall survival (OS) was analyzed. Expression profiling data demonstrated that CRC immune microenvironment from right side tumor was characterized as increased infiltration of immune cells with enhanced cytotoxic function, based on higher cytotoxic activity scores (CYT) and interferon-γ signatures. Expression of VEGFA, which could be neutralized by bevacizumab, was associated with decreased levels of activated CD8
Language	English
Publishing date	2018
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.01578
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Article: Association between angiogenesis and cytotoxic signatures in the tumor microenvironment of gastric cancer.

Feng, Yi / Dai, Ying / Gong, Zhihua / Cheng, Jia-Nan / Zhang, Longhui / Sun, Chengdu / Zeng, Xianghua / Jia, Qingzhu / Zhu, Bo

OncoTargets and therapy

2018 Volume 11, Page(s) 2725–2733

Abstract: Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then ... ...

Abstract	Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer. Materials and methods: Transcriptome profiling data retrieved from The Cancer Genome Atlas (TCGA) database were used to deconvolute the feature of TME for gastric cancer (N = 375). Machine learning, correlation, and prognosis analysis were applied to elucidate the correlations between angiogenesis, cytotoxic T lymphocyte infiltration, and patient survival. Results: Substantial heterogeneous infiltration of immune cell populations among cases was observed. Furthermore, among targetable pathways, angiogenesis was identified as the dominant factor in discriminating different infiltration statuses. Most importantly, the angiogenesis pathway was negatively correlated with the amount of activated CD8 Conclusion: Our findings demonstrated a negative correlation between angiogenesis signaling and cytotoxic function in gastric cancer patients with a highly infiltrated immune niche. These data provided a rationale for potential combination strategy and further clinical investigations of ICIs plus antiangiogenesis agents for patients with gastric cancer with an inflamed TME.
Language	English
Publishing date	2018-05-10
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2495130-4
ISSN	1178-6930
ISSN	1178-6930
DOI	10.2147/OTT.S162729
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Article ; Online: Tumor Microenvironment Properties are Associated With Low CD68-positive Cell Infiltration and Favorable Disease-free Survival in EGFR-mutant Lung Adenocarcinoma.

Gong, Zhihua / Chen, Junying / Cheng, Jia-Nan / Sun, Chengdu / Jia, Qingzhu / Diao, Xinwei / Zhu, Bo

Clinical lung cancer

2018 Volume 19, Issue 5, Page(s) e551–e558

Abstract: Background: The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties ... ...

Abstract	Background: The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties between mutant and wild-type EGFR have not been fully characterized. Patients and methods: We collected 105 surgically resected (50 EGFR mutated and 55 EGFR wild-type), treatment-naïve lung adenocarcinoma tissues with clinical data to investigate the landscape and compartmentalization of tumor-infiltrating immune cells with respect to EGFR status by immunohistochemistry. The normalized FPKM values of data for 531 patients were obtained from The Cancer Genome Atlas (TCGA) Data Portal (https://portal.gdc.cancer.gov/). Results: CD68-positive cells within the tumor niche exhibited more intensive infiltration in wild-type EGFR than in mutations, and was related to lymph node invasion. In the RNA-Seq analysis, MMP9 and VEGFA showed higher levels in wild-type EGFR than in mutant cases. The EGFR mutation independently predicted a favorable disease-free survival. Conclusion: The CD68-positive cells play a crucial role in discriminating the TME between different EGFR statuses.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Adenocarcinoma/mortality ; Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/genetics ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein Kinase Inhibitors/therapeutic use ; Retrospective Studies ; Survival Rate ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Biomarkers, Tumor ; CD68 antigen, human ; Protein Kinase Inhibitors ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2018-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2145146-1
ISSN	1938-0690 ; 1525-7304
ISSN (online)	1938-0690
ISSN	1525-7304
DOI	10.1016/j.cllc.2018.03.011
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Zs.A 5893: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 440: Show issues

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Article ; Online: Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer.

Jia, Qingzhu / Wu, Wei / Wang, Yuqi / Alexander, Peter B / Sun, Chengdu / Gong, Zhihua / Cheng, Jia-Nan / Sun, Huaibo / Guan, Yanfang / Xia, Xuefeng / Yang, Ling / Yi, Xin / Wan, Yisong Y / Wang, Haidong / He, Ji / Futreal, P Andrew / Li, Qi-Jing / Zhu, Bo

Nature communications

2018 Volume 9, Issue 1, Page(s) 5361

Abstract: Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This ... ...

Abstract	Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy.
MeSH term(s)	Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Biopsy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/immunology ; Carcinoma, Non-Small-Cell Lung/pathology ; DNA Mutational Analysis ; Gene Expression Profiling ; Humans ; Lung/pathology ; Lung Neoplasms/genetics ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Mutation ; T-Lymphocytes/immunology ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology ; Exome Sequencing
Chemical Substances	Antigens, Neoplasm
Language	English
Publishing date	2018-12-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-07767-w
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