scholarly journals The effect of HMGB1 on the clinicopathological and prognostic features of cervical cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Pan Li ◽  
Mengfei Xu ◽  
Hongbing Cai ◽  
Niresh Thapa ◽  
Can He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Immunohistochemical Analysis ◽  
Figo Stage ◽  
P Value ◽  
Prognostic Features ◽  
Potential Biomarker ◽  
Hmgb1 Expression

Abstract Cervical cancer is the third leading cause of cancer death among women in less-developed regions. Because of the poor survivorship of patients with advanced disease, finding new biomarkers for prognostic prediction is of great importance. In the current study, mRNA datasets (GSE9750 and GSE63514) were retrieved from Gene Expression Omnibus and was used to identify differentially expressed genes. The underlying molecular mechanisms associated with high-mobility group box 1 protein (HMGB1) were investigated using bioinformatics analysis. Immunohistochemical analysis of HMGB1 was performed on 239 cases of cervical cancer samples to investigate its possible correlation with clinicopathological characteristics and outcomes. A preliminary validation has been made to explore the possible correlation factors with HMGB1 that promote migration of cervical cancer cells. Bioinformatics analysis showed that adherens junction was significant for both P-value and enrichment scores, which was consistent with the clinical study. The underlying molecular mechanisms might be the interaction among HMGB1, RAC1, and CDC42. HMGB1 expression was significantly associated with tumor size, parametrial infiltration, the depth of cervical stromal invasion, and FIGO stage (P=0.003, 0.019, 0.013, and 0.003, respectively). FIGO stage, lymph mode metastasis, and HMGB1 expression were independent predictors of a poorer prognosis of patients with cervical cancer. Knockdown of HMGB1 inhibits migration of Siha and C33A cells in vitro. Western blot and quantitative real-time PCR (qRT-PCR) showed that the expression of RAC1 and CDC42 was positively correlated with HMGB1. HMGB1 is a useful prognostic indicator and a potential biomarker of cervical cancer. RAC1 and CDC42 may be involved in the progression of cervical cancer migration induced by HMGB1.

scholarly journals Enhanced Expression of IGFBP-3 Reduces Radiosensitivity and Is Associated with Poor Prognosis in Oral Squamous Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 494
Author(s):  
Junki Sakata ◽  
Akiyuki Hirosue ◽  
Ryoji Yoshida ◽  
Yuichiro Matsuoka ◽  
Kenta Kawahara ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Immunohistochemical Analysis ◽  
Cell Functions ◽  
Potential Biomarker ◽  
Igfbp 3

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) modulates various cell functions through IGF-dependent or independent mechanisms. However, its biological roles in the radiosensitivity of oral squamous cell carcinoma (OSCC) remain largely unknown. The purpose of this study was to determine the clinical significance and molecular mechanisms of the association between IGFBP-3 and OSCC radiosensitivity. We performed an immunohistochemical analysis of IGFBP-3 in 52 OSCC specimens from patients treated with preoperative chemoradiotherapy and surgery (phase II study). Associations between IGFBP-3 expression and clinicopathological features were also evaluated. In addition, we examined the effects of IGFBP-3 on post-X-ray irradiation radiosensitivity and DNA damage in vitro. High IGFBP-3 expression was significantly correlated with poor chemoradiotherapy responses and prognosis. With IGFBP-3 knockdown, irradiated OSCC cells exhibited significantly higher radiosensitivity compared with that of control cells. Moreover, IGFBP-3 depletion in OSCC cells reduced phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is required for DNA double-strand break repair during non-homologous end joining. These findings indicate that IGFBP-3 may have a significant role in regulating DNA repair and is be a potential biomarker for predicting clinical response to radiotherapy and prognosis in OSCC.

scholarly journals Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

2021 ◽  
Vol 22 (13) ◽  
pp. 6663
Author(s):  
Maurycy Jankowski ◽  
Mariusz Kaczmarek ◽  
Grzegorz Wąsiatycz ◽  
Claudia Dompe ◽  
Paul Mozdziak ◽  
...  
Keyword(s):  
Stem Cells ◽  
In Vitro Culture ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Marker Genes ◽  
P Value ◽  
Illumina Platform

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

scholarly journals Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds

2021 ◽  
Vol 22 (15) ◽  
pp. 7844
Author(s):  
Jason S. Holsapple ◽  
Ben Cooper ◽  
Susan H. Berry ◽  
Aleksandra Staniszewska ◽  
Bruce M. Dickson ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Immunohistochemical Analysis ◽  
Therapeutic Effects ◽  
Gene Expressions ◽  
Extracorporeal Shock Wave

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150–500 impulses, 5 Hz, 0.1 mJ/mm2). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.

hSRBC promoter CpG island hypermethylation as resistant predictive biomarker of oxaliplatin based chemotherapy in metastasic colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14609-e14609
Author(s):  
Catia Moutinho ◽  
Anna Martinez-Cardus ◽  
Cristina Santos ◽  
Valentín Navarro-Perez ◽  
Eva Martinez-Balibrea ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cpg Island ◽  
Methylation Status ◽  
Stage Iv ◽  
Predictive Biomarker ◽  
Promoter Hypermethylation ◽  
Chemotherapeutic Agents ◽  
P Value ◽  
Potential Biomarker

e14609 Background: Resistance acquisition to chemotherapeutic agents is one of the main problems that come up during cancer treatment. hSRBC is a tumor suppressor gene whose inactivation has been associated with malignant tumor progression. In a previous work, we investigated the influence of hSRBC promoter methylation alterations in oxaliplatin (OXA) resistance acquisition by using a CRC “in vitro” model, detecting an hSRBC promoter hypermethylation in OXA–resistant derived cells when compared with the sensitive counterpart. These results were validated by functional analyses in the same model. Taking this into account, our aim in the present work is to determine the role of hSRBC methylation status as a potential biomarker of OXA resistance, in metastatic CRC patients, treated at first line with fluouropirimidines plus OXA based chemotherapy. Methods: hSRBC promoter hypermethylation was analyzed in DNA extracted from paraffin embebbed tissue of 111 metastatic CRC tumors by using Methylation Specific PCR. Methylation data was correlated to overall response (OR) and progression free survival (PFS) by using F-Fisher test and Kaplan-Meyer Survival curves respectively. A multivariate analysis was carried out by Cox regression. p-values under 0.05 were considered statistic significant. Results: Two independent cohorts of stage IV CRC tumors were included. Twenty-two out of 111 patients received radical surgery for metastasis, that became to be a positive prognostic factor (p-value = 0.04). Gene hypermethylation was detected in a 33% of cases. Although OR was not associated with hSRBC methylation, we observed a significant correlation between hypermethylation of gene and a worse PFS in patients without metastasis surgery (Log Rank; p-value = 0.04). Conclusions: Remarkably, hSRBC promoter hypermethylation is associated with worse PFS in metastatic CRC patients. We suggest hSRBC methylation status as a predictive biomarker of OXA-based treatment outcome in metastatic CRC patients. However, further studies are warranted in order to elucidate the clinical application of these findings.

scholarly journals Loss of G-Protein Pathway Suppressor 2 Promotes Tumor Growth Through Activation of AKT Signaling

2021 ◽  
Vol 8 ◽  
Author(s):  
Stefanie Chan ◽  
Emma Smith ◽  
Yuan Gao ◽  
Julian Kwan ◽  
Benjamin C. Blum ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
G Protein ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Proteomic Profiling ◽  
Potential Biomarker ◽  
Regulated Gene Expression

G Protein Suppressor 2 (GPS2) is a multifunctional protein that exerts important roles in inflammation and metabolism in adipose, liver, and immune cells. GPS2 has recently been identified as a significantly mutated gene in breast cancer and other malignancies and proposed to work as a putative tumor suppressor. However, molecular mechanisms by which GPS2 prevents cancer development and/or progression are largely unknown. Here, we have profiled the phenotypic changes induced by GPS2 depletion in MDA-MB-231 triple negative breast cancer cells and investigated the underlying molecular mechanisms. We found that GPS2-deleted MDA-MB-231 cells exhibited increased proliferative, migratory, and invasive properties in vitro, and conferred greater tumor burden in vivo in an orthotopic xenograft mouse model. Transcriptomic, proteomic and phospho-proteomic profiling of GPS2-deleted MBA-MB-231 revealed a network of altered signals that relate to cell growth and PI3K/AKT signaling. Overlay of GPS2-regulated gene expression with MDA-MB-231 cells modified to express constitutively active AKT showed significant overlap, suggesting that sustained AKT activation is associated with loss of GPS2. Accordingly, we demonstrate that the pro-oncogenic phenotypes associated with GPS2 deletion are rescued by pharmacological inhibition of AKT with MK2206. Collectively, these observations confirm a tumor suppressor role for GPS2 and reveal that loss of GPS2 promotes breast cancer cell proliferation and tumor growth through uncontrolled activation of AKT signaling. Moreover, our study points to GPS2 as a potential biomarker for a subclass of breast cancers that would be responsive to PI3K-class inhibitor drugs.

scholarly journals lncRNA SNHG15 Induced by SOX12 Promotes the Tumorigenic Properties and Chemoresistance in Cervical Cancer via the miR-4735-3p/HIF1a Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Jiang Yang ◽  
Mei Yang ◽  
Huabing Lv ◽  
Min Zhou ◽  
Xiaogang Mao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Luciferase Reporter ◽  
Major Health ◽  
Tumor Tissues ◽  
High Prevalence ◽  
Reporter Assays

Cervical cancer (CC) is one of the most common malignancies in females, with high prevalence and mortality globally. Despite advances in diagnosis and therapeutic strategies developed in recent years, CC is still a major health burden worldwide. The molecular mechanisms underlying the development of CC need to be understood. In this study, we aimed to demonstrate the role of lncRNA SNHG15 in CC progression. Using qRT-PCR, we determined that lncRNA SNHG15 is highly expressed in CC tumor tissues and cells. lncRNA SNHG15 knockdown also reduces the tumorigenic properties of CC in vitro, as determined using the MTT, EdU, flow cytometry, and transwell assays. Using bioinformatics analysis, RNA pull-down, ChIP, and luciferase reporter assays, we verified the molecular mechanisms of lncRNA SNHG15 in CC progression and found that lncRNA SNHG15 expression in CC cells is transcriptionally regulated by SOX12; moreover, lncRNA SNHG15 promotes CC progression via the miR-4735-3p/HIF1a axis. This study can provide a potential target for CC diagnosis or therapeutic strategies in the future.

scholarly journals LINC00152 Acts as a Potential Marker in Gliomas and Promotes Tumor Proliferation and Invasion Through The LINC00152/miR-107/RAB10 Axis

2021 ◽  
Author(s):  
qing liu ◽  
gang peng ◽  
Jun Su ◽  
zeyou wang ◽  
songhua xiao
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Experimental Studies ◽  
Pivotal Role ◽  
Aberrant Expression ◽  
Potential Marker ◽  
Induced Apoptosis ◽  
Proliferation And Invasion

Abstract Aberrant expression of long noncoding RNAs plays a pivotal role in tumorigenesis. Recently, several studies have showed that the LINC00152 gene is upregulated in a variety of tumors and plays an oncogene role; however, its underlying molecular mechanisms in glioblastoma remain unclear. In this study, we found that LINC00152 was upregulated in gliomas and its expression was significantly associated with high tumor aggressiveness and poor outcomes for glioma patients through bioinformatics analysis. Functionally, the knockdown of LINC00152 not only inhibited malignant behaviors of glioma, such as proliferation and invasion of glioma cells and induced apoptosis in vitro but also suppressed tumorigenesis in vivo. Mechanistically, results of the bioinformatics analysis and experimental studies confirmed that LINC00152 and RAB10 as the targets of miR-107, and LINC00152 might act as a sponge for miR-107 to regulate the expression of RAB10 in glioblastoma. Additionally, silencing miR-107 reversed the effects induced by LINC00152 knockdown on glioblastoma cells both in vitro and in vivo. Taken together, our data suggested that LINC00152 is a candidate prognostic marker of glioma, and that the LINC00152/MIR-107/RAB10 axis plays a pivotal role in regulation of the glioma malignancy, and therefore, targeting the axis might be an effective therapeutic strategy to treat glioma.

Concomitant weekly carboplatin (CB) and paclitaxel (P) with pelvic radiotherapy (RT) for the treatment of advanced cervical cancer (ACC): A FNCLCC gynecologic group phase I trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5542-5542 ◽  
Author(s):  
C. Lhomme ◽  
T. Petit ◽  
R. Largillier ◽  
F. Mayer ◽  
A. Floquet ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Complete Response ◽  
Figo Stage ◽  
Primary Treatment ◽  
External Irradiation ◽  
Hematologic Toxicity ◽  
Ct Dose ◽  
Phase Ii Studies ◽  
Paraaortic Lymph Nodes

5542 Background: Standard primary treatment for locally ACC is RT with concomitant chemotherapy (CT). CB and P are radiosensitizers with in vitro synergistic action. Methods: Patients (pts) with FIGO stage IIB-IVA negative paraaortic lymph nodes cervical cancer were treated with 6 weekly cycles of CT during pelvic RT (45 Gy) and brachytherapy (BT) according to Table 1 . Each dose escalation step followed a 30-day period of observation on cohorts of 3 to 6 pts depending on dose limiting toxicity (DLT): toxic death; garde (G) 4 neutropenia > 1 week; G 4 toxicity (other hematologic or non-hematologic); any toxicity requiring = 1 week delay in RT, or > 2 dose reductions of CT, or G 3/4 hematologic toxicity > 3 weeks after treatment’s end; unendurable G 3 non hematologic toxicity. Results: 23 pts were included by 5 centers in 5 dose levels (L). Stage distribution: IIB (10), III (11), IVA (2); 20 epidermoid and 3 adenocarcinoma; ECOG: 0 (16), 1 (7). 22 pts received the 6 planned cycles. Median dose of irradiation was 45 Gy (43.2–50) with no toxicity related interruption. 17 pts underwent BT, 2 had hysterectomy and 1 received complementary external irradiation 12 Gy. CT dose reduction was necessary in 4 pts (cycle 5 or 6) and cycles postponed for 10 pts (cycle. 5 or 6). One pt experienced paclitaxel allergy at L1. G 3 anemia and/or neutropenia were reported in 11 pts and G 4 neutropenia = 1 week in 2 pts. Radiodermatitis occurred in 5 pts, asthenia in 3 and nausea in 1. One DLT was observed: unendurable G 3 asthenia + G 3 neutropenia and leucopenia at L3. Clinical and radiological complete response was obtained in 13 pts, 5 PRs and 2 SDs in 20 evaluable pts. Conclusions: Acceptable toxicity and optimal irradiation were possible at L4 in 7 pts. These doses are recommended for future phase II studies of concomitant CT/RT in ACC. [Table: see text] No significant financial relationships to disclose.

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

2020 ◽  
Author(s):  
Liang Wang ◽  
Jun Yang ◽  
Jian Huang ◽  
Zheng-Qi Wen ◽  
Ning Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Expression Level ◽  
Cancer Tissue ◽  
Potential Biomarker

Abstract Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC.Methods: The infiltration and metastasis of neutrophils in Primary colorectal cancer tissue and Paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of microRNAs were screened by using Agilent microRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using Targetscan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed microRNA using quantitative Realtime polymerase chain reaction (RT-PCR) was validated.Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 were validated in accordance with the results of RT-PCR.Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells, and provided the potential biomarker for prognosis for clinical treatment of CRC

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