Genetic polymorphisms of EGF 5'-UTR in patients with glioma: A possible predictive marker of outcome.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13009-e13009
Author(s):  
Emanuela Vattemi ◽  
Giovanna Cipollini ◽  
Cristina Dealis ◽  
Lorena Rossi ◽  
Susanne Baier ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Direct Sequencing ◽  
Predictive Marker ◽  
Reference Sequence ◽  
Published Data ◽  
Sequencing Method ◽  
Number Of Patients ◽  
Predictive Role ◽  
Epidermal Growth

e13009 Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

Cubilin, the Intrinsic Factor-Vitamin B12 Receptor in Development and Disease

2020 ◽  
Vol 27 (19) ◽  
pp. 3123-3150 ◽  
Author(s):  
Renata Kozyraki ◽  
Olivier Cases
Keyword(s):  
Vitamin B12 ◽  
Cancer Progression ◽  
Intrinsic Factor ◽  
Basic Research ◽  
Toxic Substances ◽  
Human Pathology ◽  
Peripheral Membrane Protein ◽  
Epidermal Growth ◽  
Fgf8 Signaling

Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.

Cancer Fighting SiRNA-RRM2 Loaded Nanorobots

2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta
Keyword(s):  
Cancer Therapy ◽  
Dna Synthesis ◽  
Cancer Progression ◽  
Sirna Delivery ◽  
Predictive Marker ◽  
The Body ◽  
Tumor Site ◽  
Target Delivery ◽  
Target Effect

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

scholarly journals The Role of Canonical Wnt Signaling in Regulating Radioresistance

2018 ◽  
Vol 48 (2) ◽  
pp. 419-432 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Leilei Tao ◽  
Jun Yi ◽  
Haizhu Song ◽  
Longbang Chen
Keyword(s):  
Wnt Signaling ◽  
Cancer Progression ◽  
Wnt Signaling Pathway ◽  
Growth Factor Receptor ◽  
Cancer Resistance ◽  
Canonical Wnt Signaling ◽  
Damage Repair ◽  
Epidermal Growth ◽  
Canonical Wnt

Radioresistance is a major obstacle in radiotherapy for cancer, and strategies are needed to overcome this problem. Currently, radiotherapy combined with targeted therapy such as inhibitors of phosphoinosotide 3-kinase/Akt and epidermal growth factor receptor signaling have become the focus of studies on radiosensitization. Apart from these two signaling pathways, which promote radioresistance, deregulation of Wnt signaling is also associated with the radioresistance of multiple cancers. Wnts, as important messengers in the tumor microenvironment, are involved in cancer progression mainly via canonical Wnt signaling. Their role in promoting DNA damage repair and inhibiting apoptosis facilitates cancer resistance to radiation. Thus, it seems reasonable to target Wnt signaling as a method for overcoming radioresistance. Many small-molecule inhibitors that target the Wnt signaling pathway have been identified and shown to promote radiosensitization. Therefore, a Wnt signaling inhibitor may help to overcome radioresistance in cancer therapy.

scholarly journals Polymorphisms in FCGR2A (131H/R) and FCGR2B (232I/T) are associated with the development of inhibitors in Chinese hemophilia A patients

2020 ◽  
Author(s):  
Hong Qu ◽  
Yongfang Chen ◽  
Wenjing Zeng ◽  
Xiaohua Huang ◽  
Shuqin Cheng
Keyword(s):  
Direct Sequencing ◽  
Allele Frequencies ◽  
Chinese Han ◽  
Chi Square ◽  
Inhibitor Development ◽  
Fviii Inhibitor ◽  
Gamma Receptor ◽  
Sequencing Method ◽  
Genotype And Allele Frequencies

Abstract Background: Present study was to explore the association between gene polymorphisms in Fc gamma receptor IIa (FCGR2A) and Iib (FCGR2B) and factor VIII (FVIII) inhibitor development in patients with hemophili A (HA) in a Chinese Han population.Methods: FCGR2A (131H/R) and FCGR2B (232I/T) polymorphsims were genotyped using PCR and direct sequencing method in 108 HA patients, including 23 cases with inhibitors and 85 without inhibitors. Chi-square (c2) test was applied to compare the genotype and allele frequencies between two groups. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to indicate the relative susceptibility of HA.Results: FCGR2A 131RH genotype frequency had a significantly increased trend in inhibitor group compared with the non-inhibitor group, suggesting a momentous role of 131H/R polymorphism for inhibitor development in HA patients. Individuals carrying 131RH genotype showed higher risk to be attacked by the inhibitor development in HA patients (OR=4.929; 95%CI=1.029-23.605). However, there were no significant differences of FCGR2B (232I/T) polymorphism genotype and allele frequencies between inhibitor and non-inhibitor groups.Conclusion: FCGR2A (131H/R) was in relation to the susceptibility of FVIII inhibitors development in HA patients.

Multiple sclerosis progression and galanin receptor GALR2: is there evidence for a link?

2021 ◽  
Vol 21 (2) ◽  
pp. 107-111
Author(s):  
Victoria I. Lioudyno ◽  
Alexandr G. Ilves ◽  
Gennadij N. Bisaga ◽  
Irina N. Abdurasulova
Keyword(s):  
Structural Changes ◽  
Reference Sequence ◽  
Published Data ◽  
Study Cohort ◽  
Progression Rate ◽  
Disease Course ◽  
Galanin Receptor ◽  
Exon 2 ◽  
Disease Progression Rate

BACKGROUND: Given the recently proposed role of the rare galanin receptor-2 (GALR2) genes missense mutation (SNP rs61745847) in the etiology of MS, we genotyped rs61745847 in a group of MS patients that was enriched with an unfavorable disease course cases. MATERIALS AND METHODS: Our study cohort consisted of 100 MS patients selected based on their progressive course, high disease progression rate and pediatric onset. To determine the nucleotide sequence of GALR2 gene fragment, surrounding the rs61745847 area, Sanger sequencing of PCR amplicons was performed. RESULTS: No homozygous rs61745847 carrier was found in our cohort, and the region of exon 2 surrounding rs61745847 completely coincided with the reference sequence (Gene Bank NC_000017.11). In agreement with previously published data on Canadian and Brazilian populations of patients, our study of a Russian cohort confirmed the rarity of the rs61745847 variant, including among patients with rapidly progressive MS. CONCLUSIONS: Thus, although structural changes in the GALR2 gene associated with rs61745847 may play a significant role in individual patients carrying this rare mutation, it is unlikely that such changes determine an unfavorable disease course of MS in general.

scholarly journals The Role of HE4 in Ovarian Cancer Follow-up: A Review

2014 ◽  
Vol 24 (8) ◽  
pp. 1359-1365 ◽  
Author(s):  
Elisa Piovano ◽  
Lorenza Attamante ◽  
Chiara Macchi ◽  
Camilla Cavallero ◽  
Cesare Romagnolo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Recurrence ◽  
Ca 125 ◽  
Prognostic Role ◽  
Independent Predictive Factor ◽  
Secondary Cytoreductive Surgery ◽  
Number Of Patients ◽  
Predictive Role

ObjectiveThe aim of this review was to analyze the state of the art about HE4 and follow-up in patients treated for ovarian cancer.MethodsA literature search was conducted in the MEDLINE database using the key words “HE4” and “ovarian cancer” and “recurrence” or “relapse” or “follow up.”ResultsSeven of 28 clinical studies were selected. Four studies were prospective, and all of them were based on a small number of patients (8–73 women). A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis, thus suggesting the need of a closer follow-up. Moreover, HE4 showed better sensibility and specificity in the diagnosis of ovarian cancer recurrence with respect to CA-125, being also an earlier indicator of the relapse with a lead time of 5 to 8 months. HE4 showed a better performance in this setting if performed in association with other markers (CA-125, CA-72.4). HE4 seems to be an independent predictive factor for the surgical outcome at secondary cytoreductive surgery and to maintain its prognostic role even after the recurrence.ConclusionsThese preliminary data start to suggest a superiority of HE4 over CA-125 in the detection of ovarian cancer recurrence. Moreover, the prognostic role of HE4 could help clinicians to personalize the follow-up program, whereas its predictive role could be useful to plan the treatment of the relapse. The role of HE4 in ovarian cancer follow-up deserves to be further investigated in prospective randomized multicentric studies.

scholarly journals The histone H2B ubiquitin ligase RNF40 is required for HER2-driven mammary tumorigenesis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Florian Wegwitz ◽  
Evangelos Prokakis ◽  
Anastasija Pejkovska ◽  
Robyn Laura Kosinsky ◽  
Markus Glatzel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Ubiquitin Ligase ◽  
Transcriptional Activation ◽  
Breast Cancer Subtype ◽  
Mammary Tumorigenesis ◽  
Human Tumor ◽  
Her2 Positive ◽  
Number Of Patients

Abstract The HER2-positive breast cancer subtype (HER2+-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2+-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment strategies. Epigenetic regulators are commonly misregulated in cancer and represent attractive molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by the heterodimeric ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2+-BC. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin-cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2+-BC, revealing the H2B monoubiquitination axis as a possible tumor context-dependent therapeutic target in breast cancer.

scholarly journals M2 macrophages‐derived exosomal microRNA-501-3p promotes the progression of lung cancer via targeting WD repeat domain 82

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Lei ◽  
Peng Chen ◽  
Feng Zhang ◽  
Na Zhang ◽  
Jianfei Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Cancer Tissue ◽  
M2 Macrophages ◽  
Repeat Domain ◽  
Predictive Role ◽  
Wd Repeat ◽  
Tissue Specimens ◽  
Cancer Tissues

Abstract Background Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82). Methods Lung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed. Results TAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p. Conclusion M2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.

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