scholarly journals Gene expression levels of the insulin-like growth factor family in patients with AMD before and after ranibizumab intravitreal injections

2017 ◽  
Vol Volume 12 ◽  
pp. 1401-1408 ◽  
Author(s):  
Barbara Strzalka-Mrozik ◽  
Małgorzata Kimsa-Furdzik ◽  
Adam Kabiesz ◽  
Katarzyna Michalska-Małecka ◽  
Małgorzata Nita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Intravitreal Injections ◽  
Insulin Like Growth Factor ◽  
Expression Levels ◽  
Before And After ◽  
Gene Expression Levels

scholarly journals Influence of Insulin-Like Growth Factor 1 Gene Expression in Women with Breast Cancer: A Systematic Review

2020 ◽  
Author(s):  
Danylo Rafhael Costa-Silva ◽  
Francisco Adelton Alves-Ribeiro ◽  
Maria da Conceição Barros-Oliveira ◽  
Larysse Cardoso Campos-Verdes ◽  
Renato de Oliveira Pereira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Systematic Review ◽  
Growth Factor ◽  
Expression Patterns ◽  
Insulin Like Growth Factor ◽  
Expression Levels ◽  
Cancer Support ◽  
Increased Risk ◽  
Gene Expression Levels

Abstract Background: Breast cancer, the leading cause of cancer death among women worldwide, one of the major risk factors for breast cancer is genetic changes. Changes in the expression levels of the insulin-like growth factor 1 (IGF-1) gene have been associated with increased risk and aggressiveness of breast cancer. The IGF-1 gene encodes the IGF-1 peptide that is present in most human tissues, as in the normal and neoplastic mammary gland. Here, we conducted a systematic review to investigate the influence of IGF-1 gene expression levels in women with breast cancer.Methods: PubMed, Scopus, and Web of Science databases were searched for relevant studies published between February 2 and May 15, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find association between IGF-1gene expression and breast cancer.Results: A growing number of studies in women with breast cancer support, with controversial results, the influence of IGF-1 gene expression levels on clinical-pathological factors, disease-free survival, overall survival, and resistance to tamoxifen.Conclusions: Therefore, the elucidation of IGF-1 gene expression patterns through further studies may enable the characterization of women at high risk for breast cancer, as well as the development of effective prognostic and therapeutic strategies.

scholarly journals Influence of Insulin-Like Growth Factor 1 Gene Expression in Women with Breast Cancer: A Systematic Review

2020 ◽  
Author(s):  
Danylo Rafhael Costa-Silva ◽  
Maria da Conceição Barros-Oliveira ◽  
Larysse Cardoso Campos-Verdes ◽  
Renato de Oliveira Pereira ◽  
Cleciton Braga Tavares ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Systematic Review ◽  
Growth Factor ◽  
Expression Patterns ◽  
Insulin Like Growth Factor ◽  
Expression Levels ◽  
Cancer Support ◽  
Increased Risk ◽  
Gene Expression Levels

Abstract Background: Breast cancer, the leading cause of cancer death among women worldwide, one of the major risk factors for breast cancer is genetic changes. Changes in the expression levels of the insulin-like growth factor 1 (IGF-1) gene have been associated with increased risk and aggressiveness of breast cancer. The IGF-1 gene encodes the IGF-1 peptide that is present in most human tissues, as in the normal and neoplastic mammary gland. Here, we conducted a systematic review to investigate the influence of IGF-1 gene expression levels in women with breast cancer.Methods: PubMed, Scopus, and Web of Science databases were searched for relevant studies published between February 2 and May 15, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find association between IGF-1gene expression and breast cancer.Results: A growing number of studies in women with breast cancer support, with controversial results, the influence of IGF-1 gene expression levels on clinical-pathological factors, disease-free survival, overall survival, and resistance to tamoxifen.Conclusions: Therefore, the elucidation of IGF-1 gene expression patterns through further studies may enable the characterization of women at high risk for breast cancer, as well as the development of effective prognostic and therapeutic strategies.

Gene Expression Profiling Identifies IGFBP7 as a BAALC Co-Expressed Gene with a Functional Role in Acute Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2629-2629
Author(s):  
Sandra Heesch ◽  
Cornelia Schlee ◽  
Martin Neumann ◽  
Andrea Stroux ◽  
Andrea Kühnl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Acute Leukemia ◽  
Treatment Failure ◽  
Functional Role ◽  
Human Gene ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Insulin Like Growth Factor ◽  
Expression Levels

Abstract Abstract 2629 Poster Board II-605 The human gene BAALC (Brain And Acute Leukemia, Cytoplasmic) is a molecular marker of immature hematopoietic cells. In normal hematopoiesis, BAALC is highly expressed in CD34 positive progenitors and down-regulated with cell differentiation. Moreover, high mRNA expression levels of BAALC have shown to be an adverse risk factor and were associated with chemotherapy resistance in adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) and acute T-lymphoblastic leukemia (T-ALL). While the prognostic value of BAALC expression has been validated, the function of BAALC in leukemia remains unknown. The aim of this study was to identify genes correlated with BAALC to gain further insights into the underlying pathways of the BAALC-associated chemotherapy resistant leukemic phenotype. Therefore, we generated gene expression profiles (GEP) using pre-treatment T-ALL samples (n=86) that differentiated high versus low BAALC expressers (HG-U133 Plus 2.0, Affymetrix). Samples were divided into quartiles (Q1-Q4) according to BAALC expression and QB1-3 was defined as low BAALC and QB4 as high BAALC. Differentially expressed genes between QB1–3 and QB4 were defined by a minimum expression change of three-fold (P'0.05). In order to identify BAALC-associated genes common to T-ALL, CN-AML and normal hematopoiesis we compared these BAALC-derived GEP in T-ALL with BAALC-associated profiles of CN-AML (Langer C et al, Blood 2008) and of normal CD34 positive progenitors (Komor et al, Stem Cells 2005). Only four genes (CD34, CD133, NPR3, IGFBP7) were common to the BAALC-associated GEP of all three entities (T-ALL, CN-AML, and CD34 positive progenitors). Of these genes, the human gene Insulin-like Growth Factor Binding Protein 7 (IGFBP7) was further investigated as the Insulin-like growth factor signaling plays an important role in various human cancers. Next we determined IGFBP7 expression levels by real-time RT-PCR in an independent cohort of 219 adults with newly diagnosed T-ALL, registered within the German Multicenter Acute Lymphoblastic Leukemia Study 06/99 and 07/03 protocols. In T-ALL samples, IGFBP7 showed a heterogeneous expression pattern compared to normal bone marrow (expression range: 0–79.1 vs 0.6–2.3). For correlation of IGFBP7 expression with clinical and molecular features, samples were divided into quartile groups according to IGFBP7 expression and defined as low IGFBP7 with expression levels in QI1 to QI3 (n=158) and as high IGFBP7 with expression levels in QI4 (n=53). High expression levels of IGFBP7 were associated with an immature phenotype of early T-ALL (62% of patients in QI4 showed an early T-ALL immunophenotype as compared to only 15% in QI1–3; P<0.001), high cell surface expression of CD34 (mean: 36% vs 15%; P<0.001) and CD33 (mean: 24% vs 3%; P<0.001). Moreover, high IGFBP7 expression significantly predicted a higher frequency of refractory disease (11% vs 3%; P=0.03) and an inferior overall survival (OS; 4-year OS: IGFBP7 QI4: 42% vs IGFBP7 QI1–3: 55%; P=0.03). In vitro, studies revealed that treatment with rIGFBP7 significantly inhibited proliferation of KG1a leukemic cells (65% reduction of proliferation compared to untreated cells; P<0.001) determined by Cell Proliferation Reagent WST-1. Moreover, a 26% reduction (P<0.001) of the DNA synthesis phase was detected by BrdU incorporation after rIGFBP7 treatment of KG1a cells. Taken together, we identified IGFBP7 as a lineage-independent, BAALC co-expressed gene involved in leukemia. High IGFBP7 expression was associated with stem cell features and treatment failure in T-ALL. In contrast to BAALC which likely represents only a surrogate marker of treatment failure in acute leukemias, IGFBP7 might play functional role and contribute to the molecular basis of BAALC-associated drug resistance. As rIGFBP7 inhibits proliferation of leukemic cells, secreted IGFBP7 protein may therefore promote resistance to cell cycle dependent cytostatic drugs targeting highly proliferate blast cells. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership.

scholarly journals Gene Expression Profile of Human Cytokines in Response to Burkholderia pseudomallei Infection

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Shivankari Krishnananthasivam ◽  
Harindra Darshana Sathkumara ◽  
Enoka Corea ◽  
Mohan Natesan ◽  
Aruna Dharshan De Silva
Keyword(s):  
Gene Expression ◽  
Infectious Disease ◽  
Growth Factor ◽  
Disease Susceptibility ◽  
Negative Bacterium ◽  
Gram Negative ◽  
Content Type ◽  
Expression Levels ◽  
Life Threatening ◽  
Gene Expression Levels

ABSTRACT Melioidosis is a life-threatening infectious disease caused by a soil-associated Gram-negative bacterium, B. pseudomallei. Melioidosis is endemic in Southeast Asia and northern Australia; however, the global distribution of B. pseudomallei and the disease burden of melioidosisis are still poorly understood. Melioidosis is difficult to treat, as B. pseudomallei is intrinsically resistant to many antibiotics and requires a long course of antibiotic treatment. The mortality rates remain high in areas of endemicity, with reoccurrence being common. Therefore, it is imperative to diagnose the disease at an early stage and provide vital clinical care to reduce the mortality rate. With limitations in treatment and lack of a vaccine, it is crucial to study the immune response mechanisms to this infection to get a better understanding of disease susceptibility and pathogenesis. Therefore, this study aimed to analyze the gene expression levels of important cytokines to establish useful correlations for diagnostic and therapeutic purposes. Melioidosis is an underreported infectious disease, caused by the Gram-negative bacterium Burkholderia pseudomallei. Understanding the disease susceptibility and pathogenesis is crucial for developing newer diagnostic and therapeutic strategies for this life-threatening infection. In this study, we aimed to analyze the gene expression levels of important cytokines in melioidosis patients and establish useful correlates with disease biomarkers compared to cases of sepsis infection caused by other pathogens and healthy individuals. A Qiagen common human cytokines array profiling the gene expression of 84 important cytokines by real-time quantitative PCR (RT-qPCR) was used. We analyzed 26 melioidosis cases, 5 healthy controls, and 10 cases of sepsis infection caused by other pathogens. Our results showed consistently upregulated expression of interleukins (IL) interleukin-4 (IL-4), interleukin-17 alpha (IL-17A), IL-23A, and IL-24, interferons (IFN) interferon alpha 1 (IFNA1) and interferon beta 1 (IFNB1), tumor necrosis factor (TNF) superfamily 4 (TNFSF4), transforming growth factor (TGF) superfamily, bone morphogenetic proteins 3 and 6 (BMP3 and BMP6), transforming growth factor beta 1 (TGFB1), and other growth factors, including macrophage colony-stimulating factor (M-CSF), C-fos-induced growth factor (FIGF), and platelet-derived growth factor alpha (PDGFA) polypeptide, in melioidosis patients compared to their expression in other sepsis cases, irrespective of comorbidities, duration of fever/clinical symptoms, and antibiotic treatment. Our findings indicate a dominant Th2- and Th17-type-cytokine response, suggesting that their dysregulation at initial stages of infection may play an important role in disease pathogenesis. IL-1A, interleukin-1 beta (IL-1B), and IL-8 were significantly downregulated in septicemic melioidosis patients compared to their expression in other sepsis cases. These differentially expressed genes may serve as biomarkers for melioidosis diagnosis and targets for therapeutic intervention and may help us understand immune response mechanisms. IMPORTANCE Melioidosis is a life-threatening infectious disease caused by a soil-associated Gram-negative bacterium, B. pseudomallei. Melioidosis is endemic in Southeast Asia and northern Australia; however, the global distribution of B. pseudomallei and the disease burden of melioidosisis are still poorly understood. Melioidosis is difficult to treat, as B. pseudomallei is intrinsically resistant to many antibiotics and requires a long course of antibiotic treatment. The mortality rates remain high in areas of endemicity, with reoccurrence being common. Therefore, it is imperative to diagnose the disease at an early stage and provide vital clinical care to reduce the mortality rate. With limitations in treatment and lack of a vaccine, it is crucial to study the immune response mechanisms to this infection to get a better understanding of disease susceptibility and pathogenesis. Therefore, this study aimed to analyze the gene expression levels of important cytokines to establish useful correlations for diagnostic and therapeutic purposes.

Impact of gene expression of orotate phosphoribosyl transferase for complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4566-4566
Author(s):  
T. Kajiwara ◽  
T. Nishina ◽  
I. Hyodo ◽  
T. Moriwaki ◽  
S. Endo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Predictive Factor ◽  
Complete Response ◽  
Carcinoma Of The Esophagus ◽  
Expression Levels ◽  
Gene Expression Levels

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.

Molecular Determinants of Cetuximab Efficacy

2005 ◽  
Vol 23 (15) ◽  
pp. 3536-3544 ◽  
Author(s):  
Daniel Vallböhmer ◽  
Wu Zhang ◽  
Michael Gordon ◽  
Dong Yun Yang ◽  
Jim Yun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Growth Factor ◽  
Clinical Outcome ◽  
Single Agent ◽  
Rank Test ◽  
Expression Levels ◽  
Log Rank Test ◽  
Cox 2 ◽  
Gene Expression Levels

Purpose To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. Patients and Methods Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. Results There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. Conclusion This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.

scholarly journals The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age

2015 ◽  
Vol 26 (15) ◽  
pp. 2733-2741 ◽  
Author(s):  
Flaviana Marzano ◽  
Annamaria Ventura ◽  
Mariano Francesco Caratozzolo ◽  
Italia Aiello ◽  
Francesca Mastropasqua ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Mrna Expression ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Insulin Like Growth Factor ◽  
Proliferating Cells ◽  
P53 Family ◽  
Expression Levels ◽  
Mrna Expression Levels

The regulation of insulin-like growth factor–binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood.

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