Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

Ortega, Miguel Á.; Fraile-Martínez, Óscar; García-Montero, Cielo; Ruiz-Grande, Fernando; Barrena, Silve; Montoya, Héctor; Pekarek, Leonel; Zoullas, Sofia; Álvarez-Mon, Miguel Ángel; Sáinz, Felipe; Asúnsolo, Ángel; Acero, Julio; Álvarez‐Mon, Melchor; Buján, Julia; García‐Honduvilla, Natalio; Guijarro, Luis

doi:10.1177/03000605211041275

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…Finally, immunohistochemical analysis shows that IL-10 is expressed in 6 pancreatic cancer patients, whereas 31.7% present negative expression for this cy The median survival for patients with pancreatic cancer and negative tissue expre IL-10 was 4 (4-7) months. However, in the case of patients with low-medium exp it was 11 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) months, increasing to 24 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) months in patients with a high exp (Figure 2B). Global comparisons showed that the significance value was p < 0.001 * a hazard ratio of 0.265 and a 95% confidence interval [0.142-0.500] in patients w expressions of IL-10.…”

Section: Aif-1 Il-12a and Il-18 Are Directly Related To Pancreatic Ca...mentioning

confidence: 94%

“…When the mean proportion of the labeled sample was greater than or equivalent to 5% of the entire sample, the individuals were categorized as positive. As previously described in previous works [24], this was accomplished by computing the overall percentage of marked tissue in each microscope field to produce an average of the research sample. Two researchers worked independently to observe and quantify the samples.…”

Section: Histopathological Evaluationmentioning

confidence: 99%

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Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer

Ortega,

Jiménez-Álvarez,

Fraile-Martinez

et al. 2024

CIMB

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Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan–Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC’s pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

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Section: Aif-1 Il-12a and Il-18 Are Directly Related To Pancreatic Ca...mentioning

confidence: 94%

Section: Histopathological Evaluationmentioning

confidence: 99%

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer

Ortega,

Jiménez-Álvarez,

Fraile-Martinez

et al. 2024

CIMB

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“…(1) To synthesize complementary DNA (cDNA) via reverse transcription, RNA samples were diluted to 50 ng/µL; then, 4 µL of diluted RNA was mixed with 4 µL of oligo-dT solution at 0.25 µg/µL (Thermo Fisher Scientific A., Waltham, MA, USA) and incubated at 65 • C for 10 min in a dry bath (AccuBlock™, Labnet International Inc., Edison, NJ, USA) to denature the RNA. (2) Next, the samples were put on ice, and 10 µL of a reverse transcription mixture was added to each sample in agreement with established protocols [18]. (3) Reverse transcription was performed to synthesize cDNA using a G-Storm GS1 thermocycler (G-Storm, Somerset, UK) at 37 • C for 1 h and 15 min, 70 • C for 15 min (leading to denaturation of the reverse transcriptase enzyme) and then a gradual decrease to 4 • C. (4) To verify the absence of genomic DNA contamination in the total RNA samples, negative control samples were run in parallel; in these samples, M-MLV RT was replaced with DNase-and RNase-free water.…”

Section: Analysis Of Gene Expression Using Qrt-pcrmentioning

confidence: 99%

“…( 6) qPCR was performed to quantify the levels of cDNA of our genes of interest. ( 7) Specific primers were designed de novo for the studied genes (Table 3) using Primer-BLAST (National Center for Biotechnology Information, Bethesda, MD, USA) and AutoDimer [18]. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene was used to normalize the results.…”

Section: Analysis Of Gene Expression Using Qrt-pcrmentioning

confidence: 99%

Contribution of the Elastic Component and Venous Wall Arterialization in Patients with Venous Reflux

Ortega

Fraile-Martínez

García-Montero

et al. 2022

JPM

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Chronic venous disease (CVeD) is defined as a set of disorders affecting the venous system mainly manifested in the form of varicose veins. CVeD is characterized by a sustained venous hypertension, leading to a plethora of functional and structural changes in the vein that may cause valve incompetence and pathologic reflux. In turn, venous reflux aggravates the venous hypertension and enhances the progression of CVeD into the most advanced stages. Previous studies have proposed that there are several alterations in the venous wall preceding the valve dysfunction and venous reflux. Besides, it has also been identified that young patients with CVeD present premature aging and changes in the venous wall composition that may be related to the presence of venous reflux. In this context, the aim of the present study is to examine the possible pathophysiological role of elastic fibers and their precursors in the venous wall of patients with reflux in comparison to those without reflux, considering the variable age in both groups (<50 years and ≥50 years). We performed immunohistochemical and quantitative polymerase chain reaction (PCR) in order to assess the protein and gene expression of tropoelastin, fibrillin-1, fibulins 4 and 5, lysyl oxidase and lysyl oxidase like 1, respectively. In parallel, we assessed the elastin content through histological techniques (orcein stain) in this group of patients. Our results show significant changes in elastic fibers and their precursors in young patients with pathologic reflux when compared with elder patients with reflux and young patients without reflux. These variations suggest that the venous system of young patients with venous reflux appears to present an enhanced dynamism and arterialization of the venous wall, which may be associated with a premature aging and pathological environment of the tissue.

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“…Pathophysiologically, CVeD is characterized by an ambulatory venous hypertension, which affects the venous valves, compromising the venous return, frequently in the lower limbs [ 11 , 12 ]. The persistent hypertension is a major source of local and systemic inflammation, leading to an increase in oxidative stress, endothelial dysfunction, chronic hypoxia, matrix remodeling and so on [ 13 , 14 , 15 , 16 ]. Eventually, in advanced stages of the disease, skin changes such as pigmentation, lipodermatosclerosis and ulcerations can be observed [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Venous Wall of Patients with Chronic Venous Disease Exhibits a Glycolytic Phenotype

Fraile-Martínez

García-Montero

Álvarez-Mon

et al. 2022

JPM

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Chronic venous disease (CVeD) is a rising medical condition characterized by a broad spectrum of disorders in the venous system. Varicose veins (VVs) represent a frequent clinical manifestation of CVeD, particularly in the lower limbs. Prior histopathological studies have defined a set of alterations observed in the venous wall of patients with VVs, affecting their structure and behavior. Metabolic changes in the veins appear to be a critical biological mechanism aiding our understanding of the pathogenesis of CVeD. In this sense, previous studies have identified a potential role of a glycolytic phenotype in the development of different vascular disorders; however, its precise role in CVeD remains to be fully explored. Thus, the aim of the present study was to analyze the gene and protein expression of glucose transporter 1 (GLUT-1) and the glycolytic enzymes PGK-1, ALD, GA3PDH and LDH in the VVs of patients with CVeD (n = 35) in comparison to those expressed in healthy subjects. Our results display enhanced gene and protein expression of GLUT-1, PGK-1, ALD, GA3PDH and LDH in patients with CVeD, suggesting a glycolytic switch of the venous tissue. Greater understanding of the impact of this glycolytic switch in patients with CVeD is required to define a possible pathophysiological role or therapeutic implications of these changes.

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Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

Cited by 6 publications

References 43 publications

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer

Contribution of the Elastic Component and Venous Wall Arterialization in Patients with Venous Reflux

Venous Wall of Patients with Chronic Venous Disease Exhibits a Glycolytic Phenotype

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