Interleukin 37 Expression was Negatively Associated with Pathological Grading in Human Gliomas

Abstract Background: Little is known about the roles of interleukin 37 (IL-37), a newly identified cytokine, in the pathogenesis of cancer. In this study, we aimed to determine the expression of IL-37 in gliomas with different pathological grades and evaluated its effects on survival. Methods: Ninety-five participants with different pathological grades of glioma were included in this study, which were classified into grade I-II (n=27), grade III (n=30), and grade IV (n=38). Ten normal brain tissues that were resected for intracranial decompression after traumatic brain injuries served as control group. The expression of IL-37 mRNA and protein in glioma tissues was determined using Real-time PCR and immunohistochemical techniques. The association between IL-37 expression and various clinicopathologic factors was evaluated. Results: IL-37 mRNA was expressed in normal tissues and tumor tissues, and the expression of IL-37 in tumor tissues were significantly higher than normal brain tissue (p<0.05). IL-37 expression showed decline with the increase of grade level. The expression of IL-37 was significantly lower in glioma tissues of a high malignancy compared with the glioma tissues of a low malignancy. Patients with low IL-37 expression showed a shorter survival time. Conclusions: Low IL-37 expression was negatively correlated with pathological grade, rather than pathological type. Low IL-37 was positively correlated with survival time. Thus, IL-37 maybe plays an inhibitory role in glioma progression.

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Overexpression of P4HA1 Is Correlated with Poor Survival and Immune Infiltrates in Lung Adenocarcinoma

BioMed Research International ◽

10.1155/2020/8024138 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Haiting Zhou ◽

Yi He ◽

Lingling Li ◽

Cheng Wu ◽

Guoqing Hu

Keyword(s):

Lung Adenocarcinoma ◽

Clinical Decision ◽

Bioinformatic Analysis ◽

Normal Tissues ◽

Pathological Type ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cox Analysis ◽

T Classification ◽

The Relationship

Lung adenocarcinoma (LUAD) is a major pathological type of lung cancer. Understanding the mechanism of LUAD at the molecular level is important for a clinical decision. In this study, we use bioinformatic analysis to explore the prognostic value of P4HA1 in lung adenocarcinoma (LUAD) and the relationship with prognosis and tumor-infiltrating immune cells (TIICs). The results showed that the expression of P4HA1 was significantly higher in tumor tissues than in normal tissues for LUAD patients. Upregulated P4HA1 was related to stage and T classification. Kaplan-Meier analysis indicated that upregulation of P4HA1 was significantly related to worse overall survival (OS). Univariate and multivariate Cox analysis indicated P4HA1 remained to be an independent prognostic factor. GSEA showed that several cancer-related and immune-related signaling pathways exhibited prominently differential enrichment in P4HA1-high expression phenotype. In addition, the expression of P4HA1 was significantly correlated with proportion of several TIICs, particularly B cells and CD4+ T cells. In conclusion, our study confirmed that P4HA1 is a promising biomarker of poor prognosis and relates to immune infiltrates in LUAD.

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Assessment of Tumor Cells in a Mouse Model of Diffuse Infiltrative Glioma by Raman Spectroscopy

BioMed Research International ◽

10.1155/2014/860241 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Kuniaki Tanahashi ◽

Atsushi Natsume ◽

Fumiharu Ohka ◽

Hiroyuki Momota ◽

Akira Kato ◽

...

Keyword(s):

Raman Spectroscopy ◽

Structural Information ◽

Glioma Cells ◽

Principal Component ◽

Low Grade ◽

Normal Brain ◽

Spectral Difference ◽

Normal Tissues ◽

Tumor Tissues ◽

Avian Sarcoma

Glioma of infiltrative nature is challenging for surgeons to achieve tumor-specific and maximal resection. Raman spectroscopy provides structural information on the targeted materials as vibrational shifts. We utilized Raman spectroscopy to distinguish invasive tumors from normal tissues. Spectra obtained from replication-competent avian sarcoma-(RCAS-) based infiltrative glioma cells and glioma tissues (resembling low-grade human glioma) were compared with those obtained from normal mouse astrocytes and normal tissues. In cell analysis, the spectra at 950–1000, 1030, 1050–1100, 1120–1130, 1120–1200, 1200–1300, 1300–1350, and 1450 cm−1were significantly higher in infiltrative glioma cells than in normal astrocytes. In brain tissue analysis, the spectra at 1030, 1050–1100, and 1200–1300 cm−1were significantly higher in infiltrative glioma tissues than in normal brain tissues. These spectra reflect the structures of proteins, lipids, and DNA content. The sensitivity and specificity to predict glioma cells by distinguishing normal cells were 98.3% and 75.0%, respectively. Principal component analysis elucidated the significance of spectral difference between tumor tissues and normal tissues. It is possible to distinguish invasive tumors from normal tissues by using Raman spectroscopy.

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Downregulation of transcription factor EB inhibits the growth and metastasis of colorectal carcinomas

European Journal of Inflammation ◽

10.1177/2058739218805333 ◽

2018 ◽

Vol 16 ◽

pp. 205873921880533

Author(s):

Jin-Zhe Chang ◽

Shu-Dong Chen ◽

Hui Zheng ◽

Hua-Ping Zhang

Keyword(s):

Transcription Factor ◽

Western Blot ◽

Cancer Cells ◽

Migration And Invasion ◽

Control Group ◽

Normal Tissues ◽

Tumor Tissues ◽

Transcription Factor Eb ◽

Ht 29

To determine the roles of transcription factor EB (TFEB) in colorectal cancer (CRC), we collected samples of tumor tissues and normal tissues from 40 patients with CRC. The expression of TFEB in these samples was analyzed by using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Furthermore, we explored the expression of TFEB mRNA in CCD-18Co normal cells and HT-29, HCT-8, C2BBe1 cancer cells. HT-29, HCT-8, and C2BBe1 cancer cells were transfected with a TFEB-specific small interference RNA (siRNA) and scrambled siRNA, then the TFEB expression was confirmed by Western blot. The migration and invasion abilities of cells transfected with TFEB-siRNA were examined by transwell method and wound-healing assay. The subsequent effect of TFEB silencing on the tumor growth was also detected in mice xenograft model in vivo. Our study found that TFEB expression was significantly increased ( P < 0.05) in colorectal tumor tissues compared with normal tissues. Consistent with TFEB expression in tissues, compared with the normal CCD-18Co cells, TFEB mRNA expression was also significantly augmented in CRC cells. TFEB protein expression was markedly reduced in HT-29, HCT-8, and C2BBe1 cells after TFEB-siRNA transfection. In addition, inhibition of TFEB expression resulted in decrease of cells migration and invasion abilities. In vivo study, compared with the negative control group, the tumor weight, and volume were also reduced after inhibiting the TFEB expression. Our research suggested that TFEB expression is related to the occurrence and development of colorectal adenocarcinoma. The migration and invasion abilities of cancer cells, the weight and volume of tumor were all decreased when inhibiting TFEB expression. Thus, TFEB serves as an important factor in the development of CRC by modulating cancer cell migration and invasion, showing the potential therapeutic target of CRC in clinical.

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Investigating Differential Expression of mTOR1/UCA1 in Tumor Samples of Colorectal Cancer Compared with Tumor Marginal Samples

Journal of Human Genetics and Genomics ◽

10.5812/jhgg.117855 ◽

2021 ◽

Vol 3 (2) ◽

Author(s):

Maryam Alamdar ◽

Majid Sadeghizadeh

Keyword(s):

Colorectal Cancer ◽

Control Group ◽

Tissue Samples ◽

Normal Tissues ◽

Tumor Tissues ◽

Significant Difference ◽

Cancer Tumor ◽

Therapy And Diagnosis ◽

Autophagy Inhibition ◽

Stimulate Cell Proliferation

Background: Colorectal cancer (CRC) is the second and third most common cancer in men and women respectively, and the fourth cause of cancer death of individuals. Mutations in specific genes can lead to colorectal cancer. UCA1 is one of the oncogenic genes that have been shown to stimulate cell proliferation. mTOR1 is another gene that leads to the growth of cancer cells through anabolic processes and autophagy inhibition. Objectives: In this study, we evaluate the expression of these two genes in different phases of CRC, that helps the early detection of colorectal cancer which can increase the survival rate. Methods: First, we collected 25 colorectal cancer tumor tissues and 25 adjacent normal tissues as a control group. Then, RNA was extracted from tissue samples and cDNA synthesized. The UCA1 and mTOR1 expression was evaluated in CRC tissues compared to adjacent normal tissues by Real Time PCR. Results: Our results showed that the UCA1 and mTOR1 expression in the tumor tissues was significantly higher than in the adjacent normal tissues (P < 0.05). There was also a significant difference in Lynph inv and Vescu inv with mTOR1 expression (P < 0.05). Conclusions: Our results showed that UCA1/mTOR1 may be important genes involved in colorectal cancer. mTOR1 was also identified as one of the possible genes in metastasis of colorectal cancer. Thus, UCA1 and mTOR1 can probably be considered as biomarkers in CRC therapy and diagnosis.

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The Predictive Role of Biochemical Plasma Factors in Patients with Severe Traumatic Brain Injuries

Revista de Chimie ◽

10.37358/rc.19.5.7209 ◽

2019 ◽

Vol 70 (5) ◽

pp. 1754-1757

Author(s):

Marius Toma Papacocea ◽

Ioana Anca Badarau ◽

Mugurel Radoi ◽

Ioana Raluca Papacocea

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Blood Cell ◽

Brain Injuries ◽

Hematological Parameters ◽

Group Versus ◽

Public Health Problem ◽

Traumatic Brain Injuries ◽

High Rate ◽

Control Group

Traumatic brain injuries (TBI) represent a high impact public health problem due to a high rate of death , long term disability and occurrence especially in young adults. Despite several promising animal studies, several parameters were proposed as biological markers and were assessed for this aim. Our study proposes the study of the early biochemical changes in association to hematological parameters for severe TBI patients prognosis. 43 patients with acute TBI were included in study based on clinical, laboratory and imagistic findings. The severity of the TBI was established by Glasgow Coma Scale GCS 3-8. In all patients were evaluated hematologic parameters (Red blood cell count - RBC, Hematocrit, blood Hemoglobin, White blood cell - WBC, Platelet count and biochemical parameters (glucose, urea, creatinine, electrolytes). Outcome was expressed as Glasgow Outcome Scale (GOS), between 1-5. Values were compared to control group -15 cases. Significant early differences in body temperature, heart rate, and systolic blood pressure were observed in TBI group versus control (p[0.05). After correlation, laboratory findings significantly associated to severe outcome - GOS = 1, 2 - (p[0.05) were plasma Na decrease and significant glucose increase. An early increase of temperature and decrease of Na may predict a severe outcome in patients with acute TBI; association with shifts in heart rate and blood pressure, imposes aggressive treatment measures.

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Recombinant adeno-associated virus 9-mediated expression of Kallistatin suppresses lung tumor growth in mice

Current Gene Therapy ◽

10.2174/1566523220999201111194257 ◽

2020 ◽

Vol 20 ◽

Author(s):

Weihong Qu ◽

Jianguo Zhao ◽

Yaqing Wu ◽

Ruian Xu ◽

Shaowu Liu

Keyword(s):

Lung Cancer ◽

Gene Therapy ◽

Tumor Growth ◽

Lung Tumor ◽

Control Group ◽

High Dose ◽

Blank Control Group ◽

Adeno Associated Virus ◽

Tumor Tissues ◽

Subcutaneous Xenograft

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9）by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.

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Calreticulin is Differentially Expressed in Invasive Ductal Carcinoma: A Comparative Study

Current Proteomics ◽

10.2174/1570164615666180907154459 ◽

2019 ◽

Vol 16 (2) ◽

pp. 148-155

Author(s):

Asma Tariq ◽

Rana Muhammad Mateen ◽

Iram Fatima ◽

Muhammad Waheed Akhtar

Keyword(s):

Invasive Ductal Carcinoma ◽

Tumor Tissue ◽

Ductal Carcinoma ◽

Tissue Level ◽

Differentially Expressed ◽

Breast Cancer Patients ◽

Two Dimensional Gel Electrophoresis ◽

Normal Tissues ◽

Tumor Tissues ◽

Grade Ii

Objective: The aim of the present study was to build protein profiles of untreated breast cancer patients of invasive ductal carcinoma grade II at tissue level in Pakistani population and to compare 2-D profiles of breast tumor tissues with matched normal tissues in order to evaluate for variations of proteins among them. Materials & Methods: Breast tissue profiles were made after polytron tissue lysis and rehydrated proteins were further characterized by using two-dimensional gel electrophoresis. On the basis of isoelectric point (pI) and molecular weight, proteins were identified by online tool named Siena 2-D database and their identification was further confirmed by using MALDI-TOF. Results: Among identified spots, 10 proteins were found to be differentially expressed i.e.; COX5A, THIO, TCTP, HPT, SODC, PPIA, calreticulin (CRT), HBB, albumin and serotransferrin. For further investigation, CRT was selected. The level of CRT in tumors was found to be significantly higher than in normal group (p < 0.05). The increased expression of CRT level in tumor was statistically significant (p = 0.010) at a 95% confidence level (p < 0.05) as analyzed by Mann-Whitney. CRT was found distinctly expressed in high amount in tumor tissue as compared to their matched normal tissues. Conclusion: It has been concluded that CRT expression could discriminate between normal tissue and tumor tissue so it might serve as a possible candidate for future studies in cancer diagnostic markers.

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Effect of Systemic Corticosteroid Therapy on the Efficacy and Safety of Nivolumab in the Treatment of Non-Small-Cell Lung Cancer

Cancer Control ◽

10.1177/1073274820985790 ◽

2021 ◽

Vol 28 ◽

pp. 107327482098579

Author(s):

Kengo Umehara ◽

Kaori Yama ◽

Keisuke Goto ◽

Azusa Wakamoto ◽

Tae Hatsuyama ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Survival Time ◽

Cell Lung Cancer ◽

Objective Response ◽

Small Cell ◽

Control Group ◽

Small Cell Lung ◽

Corticosteroid Administration

Introduction: Corticosteroids are used to treat immune-related adverse events (irAEs) associated with nivolumab. However, patients with non-small-cell lung cancer who are administered corticosteroids before the initiation of nivolumab treatment are commonly excluded from clinical trials. The appropriate timing for corticosteroid administration in relation to nivolumab treatment, effects of corticosteroids on the efficacy of nivolumab, and resulting adverse events are not clearly understood. In this study, the effects of differences in the timing of corticosteroid administration on nivolumab efficacy and the resulting adverse events were examined. Methods: A retrospective study was conducted with 109 patients who were treated with nivolumab at Sapporo Minami-Sanjo Hospital between December 2015 and March 2018. Results: Of the 109 patients treated with nivolumab, 12 patients were administered corticosteroids before the first cycle of nivolumab (pre-CS), and 33 patients were administered corticosteroids after the first cycle of nivolumab (post-CS). These 2 groups were compared with the control group comprising 64 patients who were not administered corticosteroids (non-CS). The objective response rate in the post-CS group was significantly higher than that in the non-CS group, and the disease control rate in the pre-CS group was significantly lower than that in the non-CS group. The overall survival time and progression-free survival time in the pre-CS group were significantly shorter than those observed in the non-CS group; however, these did not differ from those in the post-CS group. Conclusions: These results suggest that corticosteroids administered to patients with non-small-cell lung cancer after initiation of nivolumab treatment did not affect the disease prognosis. Thus, corticosteroids can be administered immediately for rapid treatment of irAEs.

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EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

Neuro-Oncology ◽

10.1093/neuonc/noz175.400 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi97-vi97

Author(s):

Satoshi Suehiro ◽

Takanori Ohnishi ◽

Akihiro Inoue ◽

Daisuke Yamashita ◽

Masahiro Nishikawa ◽

...

Keyword(s):

Tumor Cells ◽

Malignant Gliomas ◽

Glioma Cells ◽

High Intensity Focused Ultrasound ◽

Control Group ◽

Normal Brain ◽

Sonodynamic Therapy ◽

Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

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Effects of LncRNA HOX Transcript Antisense RNA Targeting miRNA-761 on Cervical Cancer Cell Proliferation and Apoptosis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2725 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2081-2086

Author(s):

Bin Qiu ◽

Hui Zhong ◽

Shenqiu Ming ◽

Chunxia Zhu

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Control Group ◽

Normal Tissues ◽

Cell Clones ◽

Cervical Cancer Cells ◽

Set Up ◽

Cancer Tissues ◽

Lncrna Hotair

Abnormal LncRNA HOTAIR level is correlated with various cancers and miR-761 can inhibit cancers. LncRNA HOTAIR targets miR-761 by StarBase 2.0 analysis. Our study investigated whether LncRNA HOTAIR can affect cervical cancer cells by regulating miR-761. The control group (NC group), LncRNA HOTAIR group and LncRNA HOTAIR + miR-761 Mimics group were set up to measure LncRNA HOTAIR and miR-761 level by qRT-PCR. Dual fluorescein reporter assay assessed whether miR-761 binds LncRNA HOTAIR. Western blot was used to measure Cyclin D1, Bcl-2 and Tubulin expression and clone formation assay was to assess cell proliferation and Annexin VFITC/PI staining was to detect cell apoptosis. Compared with normal tissues, LncRNA HOTAIR level was significantly higher in cervical cancer tissues, while miR-761 was lower (P < 0.01). LncRNA HOTAIR targets miR-761. Compared with NC group, CyclinD1 and Bcl-2 in LncRNA HOTAIR group were significantly increased (P < 0.01), which were significantly lower in LncRNA HOTAIR + miR-761 Mimics group (P < 0.05). Compared to NC group, miR-761 in LncRNA HOTAIR group was significantly reduced (P < 0.01) and elevated by miR-761 Mimics. In addition, compared to NC group, the number of cell clones in LncRNA HOTAIR group was increased, cell proliferation was increased, and number of apoptotic cells was decreased, which were all reversed in the LncRNA HOTAIR + miR-761 Mimics group. LncRNA HOTAIR targets miR-761, promotes cell proliferation and reduces cell apoptosis. miR-761 mimics can partially prevent the effects of LncRNA HOTAIR.

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