scholarly journals SERPINs in Macrophage May Be Key Inflammation Regulator and Relevant to Poor Prognosis in Adamantinomatous Craniopharyngioma

2021 ◽  
Author(s):  
Jia Yibin ◽  
Wang Guanyi ◽  
Ye Yuqin ◽  
Kang Enming ◽  
Wu JunFeng ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Brain Tumor ◽  
Poor Prognosis ◽  
Benign Tumor ◽  
Critical Role ◽  
Immune Microenvironment ◽  
Aggressive Cancer ◽  
Interesting Pattern ◽  
Tumor Inflammation ◽  
Adamantinomatous Craniopharyngioma

Abstract Craniopharyngioma is one of the most prevalent sellar tumors in children. Though normally, gross resection might be reached, while the prognosis and outcome of the patient is much more worse than any other benign tumor. Inflammation in tumor is of essential in tumor growth and progression. We found that inflammation was relevant to patient outcome and macrophages in adamantinomatous craniopharyngioma were activated in an interesting pattern. We then evaluated immune microenvironment in adamantinomatous craniopharyngioma and intended to screen out potential functional molecules for therapeutic targets and predicting prognosis. The results showed that SERPINs family, especially SERPINE1 and SERPING1 were up-regulated in adamantinomatous craniopharyngioma and might be related to patient outcome in malignant tumor. At the same time, the immune environment of adamantinomatous craniopharyngioma was similar with glioma rather than other benign brain tumors. The study firstly proposes the view that ACP might share the same characteristics with malignant brain tumor, and meanwhile preliminarily demonstrates SERPINs, especially SERPINE1 might also play a critical role in ACP, just like other aggressive cancer.

scholarly journals Bioinformatic Analyses Identify a Prognostic Autophagy-Related Long Non-coding RNA Signature Associated With Immune Microenvironment in Diffuse Gliomas

2021 ◽  
Vol 9 ◽  
Author(s):  
Shengchao Xu ◽  
Lu Tang ◽  
Zhixiong Liu ◽  
Kui Yang ◽  
Quan Cheng
Keyword(s):  
Immune Cells ◽  
Poor Prognosis ◽  
Critical Role ◽  
Diffuse Glioma ◽  
Consensus Clustering ◽  
Immune Microenvironment ◽  
Non Coding Rna ◽  
Diffuse Gliomas ◽  
Long Non Coding Rna ◽  
High Infiltration

BackgroundAutophagy and long non-coding RNA (lncRNA) play a critical role in tumor progression and microenvironment. However, the role of autophagy-related lncRNAs (ARLs) in glioma microenvironment remains unclear.MethodsA total of 988 diffuse glioma samples were extracted from TCGA and CGGA databases. Consensus clustering was applied to reveal different subgroups of diffuse gliomas. Kaplan-Meier analysis was used to evaluate survival differences between groups. The infiltration of immune cells was estimated by ssGSEA, TIMER, and CIBERSORT algorithms. The construction of ARL signature was conducted using principal component analysis.ResultsConsensus clustering revealed two clusters of diffuse gliomas, in which cluster 1 was associated with poor prognosis and enriched with malignant subtypes of gliomas. Moreover, cluster 1 exhibited high apoptotic and immune characteristics, and it had a low purity and high infiltration of several immune cells. The constructed ARL signature showed a promising accuracy in predicting the prognosis of glioma patients. ARL score was significantly elevated in the malignant subtype of glioma and the high ARL score indicated a poor prognosis. Besides, the high ARL score notably indicated low tumor purity and high infiltration of macrophages and neutrophils.ConclusionOur study developed and validated a novel ARL signature for the classification of diffuse glioma, which was closely associated with glioma immune microenvironment and could serve as a promising prognostic biomarker for glioma patients.

scholarly journals RDNA-14. RADIATION-INDUCED miR-4516 CONTRIBUTES TO RADIO-RESISTANCE AND PROMOTES AGGRESSIVE PHENOTYPE IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi209-vi210
Author(s):  
Ebin Sebastian ◽  
Tiantian Cui ◽  
Erica Hlavin Bell ◽  
Joseph McElroy ◽  
Benjamin Johnson ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cell Viability ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Radiation Treatment ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Glioblastoma Cell ◽  
Clonogenic Assays ◽  
Glioblastoma Cell Lines

Abstract BACKGROUND Glioblastoma is the most aggressive brain tumor with poor prognosis despite the best available treatment. MicroRNAs (miRNAs) are emerging as promising, novel prognostic biomarkers and therapeutic targets in glioblastoma. In a previous study, we demonstrated that miR-4516 predicts poor prognosis and functions as an oncogene in glioblastoma. Aim of the current study is to examine the role miR-4516 in radiation resistance and identify downstream targets contributing to this phenotype METHODS Radiosensitization was evaluated by cell viability and clonogenic assays. Cell apoptosis was evaluated using flow cytometry and immunoblotting. Potential targets of miR-4516 were identified using bioinformatic analysis (Targetscan and miRDB) and confirmed by luciferase reporter assays. Results were validated using immunoblotting. miR-4516 expression in glioblastoma cell lines after radiation treatment was quantified by qRT-PCR. RESULTS Expression of miR-4516 was increased up to 15 fold following radiation treatment, peaking at around 15min-60 min in primary and established glioblastoma cell lines including GBM 08-387, GBM 30 and U87-MG. Furthermore, inhibition of miR-4516 sensitized GBM 08-387, GBM30 and U87-MG cells to radiation in comparison to control groups as determined by cell viability and clonogenic assays. Further, miR-4516 inhibition induced apoptosis in these cell lines following radiation treatment. While conducting mechanistic studies, we found that the tumor-promoting function of miR-4516 was, in part, mediated by inhibition of p21 and PTPN14, two direct targets of miR-4516 CONCLUSION Our data suggest that radiation induces the expression of miR-4516 in glioblastoma cell lines. This miRNA plays a critical role in radio-resistance and promotes aggressive phenotypes in glioblastoma and therefore, functional analyses of its target pathways may uncover novel therapeutically vulnerable target(s) in glioblastoma. FUNDING: R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01(NCI), Brain Tumor Funders Collaborative Grant, and OSU-CCC (all to AC). The Ton and Patricia Bohnenn Fund for Neuro_Oncology Research (to PR).

scholarly journals Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Quan Jiang ◽  
Lingli Chen ◽  
Hao Chen ◽  
Zhaoqing Tang ◽  
Fenglin Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Independent Risk Factor ◽  
Critical Role ◽  
Tumor Biology ◽  
Integrated Analysis ◽  
Lasso Regression ◽  
Immune Microenvironment ◽  
Critical Feature ◽  
Non Coding Rnas ◽  
Gastric Cancer Patients

The immune microenvironment plays a critical role in tumor biology. As a critical feature of cancers, stemness is acknowledged as a contributor to the development of drug resistance in gastric cancers (GCs). Long non-coding RNAs (lncRNAs) have been revealed to participate in this process. In this study, we aimed to develop a stemness-related lncRNA signature (SRLncSig) with guiding significance for immunotherapy. Three cohorts (TCGA, Zhongshan, and IMvigor210) were enrolled for analysis. A list of stemness-related lncRNAs (SRlncRNAs) was collected by co-expression strategy under the threshold of coefficient value >0.35 and p-value < 0.05. Cox and Lasso regression analysis was further applied to find out the SRlncRNAs with prognosis-predictive value to establish the SRLncSig in the TCGA cohort. IPS and TIDE algorithms were further applied to predict the efficacy of SRLncSig in TCGA and Zhongshan cohorts. IMvigor210 was composed of patients with clinical outcomes of immunotherapy. The results indicated that SRLncSig not only was confirmed as an independent risk factor for GCs but also identified as a robust indicator for immunotherapy. The patient with a lower SRLncSig score was more likely to benefit from immunotherapy, and the results were highly consistent in three cohorts. In conclusion, our study not only could clarify the correlations between stemness and immunotherapy in GC patients but also provided a model to guide the applications of immunotherapy in clinical practice.

scholarly journals Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon

2021 ◽  
Vol 11 ◽  
Author(s):  
Emilie Darrigues ◽  
Benjamin W. Elberson ◽  
Annick De Loose ◽  
Madison P. Lee ◽  
Ebonye Green ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Critical Role ◽  
First Year ◽  
Histopathological Diagnosis ◽  
Next Generation ◽  
Cancer Predisposition Syndrome ◽  
Generation Sequencing

Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.

Critical Role of ABCG2 in ALA-Photodynamic Diagnosis and Therapy of Human Brain Tumor

2015 ◽  
pp. 197-216 ◽  
Author(s):  
Toshihisa Ishikawa ◽  
Yoshinaga Kajimoto ◽  
Yutaka Inoue ◽  
Yoji Ikegami ◽  
Toshihiko Kuroiwa
Keyword(s):  
Brain Tumor ◽  
Human Brain ◽  
Critical Role ◽  
Photodynamic Diagnosis ◽  
Human Brain Tumor ◽  
Diagnosis And Therapy

scholarly journals Overexpression of malignant brain tumor domain containing protein 1 predicts a poor prognosis of prostate cancer

2019 ◽  
Author(s):  
Wanhua Wu ◽  
Shoumin Bai ◽  
Dingjun Zhu ◽  
Kaiwen Li ◽  
Wen Dong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Brain Tumor ◽  
Poor Prognosis ◽  
Malignant Brain Tumor

scholarly journals M1 Macrophage and M1/M2 ratio defined by transcriptomic signatures resemble only part of their conventional clinical characteristics in breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Masanori Oshi ◽  
Yoshihisa Tokumaru ◽  
Mariko Asaoka ◽  
Li Yan ◽  
Vikas Satyananda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Clinical Characteristics ◽  
Critical Role ◽  
Immune Microenvironment ◽  
Gene Sets ◽  
M1 Macrophage ◽  
Tumor Immune Microenvironment ◽  
Cell Cycle Related Gene ◽  
High Level

Abstract Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer. In the current study, we defined “M1” macrophage and “M1”/“M2” ratio by transcriptomic signatures using xCell. We investigated the association between high level of “M1” macrophage or “M1”/“M2” ratio and the tumor immune microenvironment by analyzing the transcriptome of publicly available cohorts, TCGA and METABRIC. We found that “M1” high tumors were not associated with prolonged survival compared with “M1” low tumors, or with the response to neoadjuvant chemotherapy. “M1” high tumors were associated with clinically aggressive features and “M1” high tumors enriched the cell proliferation and cell cycle related gene sets in GSEA. At the same time, “M1” high tumors were associated with high immune activity and favorable tumor immune microenvironment, as well as high expression of immune check point molecules. Strikingly, all these results were mirrored in “M1”/“M2” ratio high tumors. In conclusion, transcriptomically defined “M1” or “M1”/“M2” high tumors were associated with aggressive cancer biology and favorable tumor immune microenvironment but not with survival benefit, which resembled only part of their conventional clinical characteristics.

scholarly journals Overexpression of IQGAP1 in advanced colorectal cancer correlates with poor prognosis-critical role in tumor invasion

2010 ◽  
pp. NA-NA ◽  
Author(s):  
Hiroyuki Hayashi ◽  
Kazuki Nabeshima ◽  
Mikiko Aoki ◽  
Makoto Hamasaki ◽  
Sotaro Enatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Invasion ◽  
Poor Prognosis ◽  
Advanced Colorectal Cancer ◽  
Critical Role

Heat Shock Protein Vaccine Therapy for Ovarian Cancer

2018 ◽  
Author(s):  
Hiroyuki Abe ◽  
Amane Sasada ◽  
Shigeki Tabata ◽  
Minako Abe
Keyword(s):  
Ovarian Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Immune Suppression ◽  
Poor Prognosis ◽  
Critical Role ◽  
Combination Immunotherapy ◽  
Protein Vaccine ◽  
Key Technologies ◽  
Method Of Production

Despite advances in chemotherapeutic regimens, ovarian cancer has a poor prognosis. Therefore important effective treatments are urgently needed. Many studies have reported that the immune system plays a critical role in disease progression and overall survival. One known effective immunotherapy is the dendritic cell (DC)-based vaccine pulsed with tumor-associated antigens. This chapter reports on a method of production of a novel DC-based vaccine. The key technologies are (a) monocyte collection without leukapheresis, (b) monocyte expansion, (c) production of dendritic cells, (d) multiple overlapping long peptides with heat shock protein 70, and (e) combination immunotherapy approach. The next generation of immunotherapy for ovarian cancer will be focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. Possible combinations which might be useful to help patients with ovarian cancer are summarized in this chapter.

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