Sergejs Isajevs

University of Latvia

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Mārcis Leja

Riga East University Hospital

IĶ

Ilze Ķikuste

University of Latvia

Karīna Siliņa

École Polytechnique Fédérale de Lausanne

Aija Linē

Latvian Biomedical Research and Study Centre

Inta Liepniece‐Karele

Riga East University Hospital

DŠ

Daiga Šantare

University of Latvia

Ivars Tolmanis

Latvian Environment, Geology and Meteorology Centre (Latvia)

Aigars Vanags

University of Latvia

Dace Rudzīte

Riga East University Hospital

Helen Thut

University Hospital of Basel

Cooperative Institutions

University of Latvia

276

Unidad de Cirugía Artroscópica

123

Latvia University of Life Sciences and Technologies

123

Foundation for Ichthyosis and Related Skin Types

122

Riga Stradiņš University

Riga East University Hospital

Pauls Stradiņš Clinical University Hospital

Latvian Biomedical Research and Study Centre

Latvijas Organiskās Sintēzes Institūts

Institute of Organic Synthesis

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Chronic obstructive pulmonary disease is characterized with suppressed lipoxin A4 and increased lipoxin receptor expression in lungs

European Respiratory Journal (2012)

Līga Balode Darja Isajeva Agnese Kislina Sergejs Isajevs Gunta Strazda

Persistent inflammation of COPD could be influenced by disorders of arachidonic acid metabolism when synthesis of leukotrienes does not switch to lipoxin generation, and thereby promotes further inflammation process. The aim: to estimate concentration of lipoxin A4 (LXA4), leukotriene B4 (LtB4), as well as expression of LXA4 receptor (FPRL-1) in induced sputum (IS) of COPD patients and healthy controls. Materials and methods: 17 COPD patients and 7 healthy controls. LXA4 and LtB4 concentration in IS was assessed with ELISA. FPRL-1 expression was detected immunocytochemically. Results: Concentration of LXA4 in COPD patient9s IS was decreased compared to healthy controls (0,909+/-0,43 ng/ml vs 2,198+/-1,189 ng/ml; p=0,009). Ratio LtB4/LXA4 in COPD patients was three times greater compared to healthy persons (8,884+/-2,789 vs 3,328+/-2,94; p=0,0071). In COPD patient9s IS FPRL-1 positive polinuclear cells (PPC) were in greater amount compared to healthy controls (8,802+/-5,758 cells/mm2 vs 2,123+/-2,232 cells/mm2; p=0,0109). Also, in COPD patients a count of FPRL-1 positive mononuclear cells (PMC) in IS was increased compared to healthy controls (2,563+/-1,711 cells/mm2 vs 0,655+/-0,522 cells/mm2; p=0,0311). Correlation between FPRL-1 PPC and LtB4 concentration in IS (r=0,628; p=0,0013). Conclusions: Increased LtB4/LXA4 indicate a disbalance of inflammatory mediators in COPD patients that could be one of the causes of inflammation persistence. In turn, increased LXA4 receptor expression and its correlation with LtB4 concentration in COPD patients could denote mechanism of inflammation adaption that is initiated by LtB4.

Lipoxin

Leukotriene B4

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The Prevalence of Cancer-Associated Autoantibodies in Patients with Gastric Cancer and Progressive Grades of Premalignant Lesions

Cancer Epidemiology Biomarkers & Prevention (2017)

Irēna Meistere Simone Werner Pawel Zayakin Karīna Siliņa Undīne Rulle

Background: Serum autoantibodies against tumor-associated antigens (TAAs) are detectable in early-stage gastric cancer patients; however, the time point during cancerogenesis when they appear in circulation is still obscure.Methods: In this study, we developed a recombinant antigen microarray and analyzed the prevalence of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy controls from Caucasian and Asian populations, as well as 100 patients with chronic atrophic gastritis and 775 individuals staged according to different grades of intestinal metaplasia.Results: Six antigens, including CTAG1B/CTAG2, DDX53, IGF2BP2, TP53, and MAGEA3, were predominantly reacting with sera from gastric cancer patients when compared with healthy controls, and the seroreactivity was associated with intestinal-type gastric cancer, but not with patients' Helicobacter pylori status, grade, age, gender, or stage of gastric cancer. We detected gastric cancer-associated seroreactivity in 13% of patients with advanced/severe intestinal metaplasia, which was increased in comparison with mild/moderate intestinal metaplasia (5.3%) and was comparable with that seen in early-stage gastric cancer patients (12%). Moreover, by testing serum samples taken 1 to 9 years before the clinical diagnosis of 18 incident gastric cancer cases, we detected autoantibody responses against several TAAs-SOX2, MYC, BIRC5, IGF2BP1, and MUC1.Conclusions: Our results suggest that humoral immune response against TAAs is generated already during premalignant stages.Impact: Based on the obtained results, cancer-associated autoantibodies might make a valuable contribution to the stratification of high-risk patients with premalignant lesions in the stomach through enhancing the positive predictive power of existing risk models. Cancer Epidemiol Biomarkers Prev; 26(10); 1564-74. ©2017 AACR.

Intestinal metaplasia

Atrophic gastritis

Stomach cancer

10.1158/1055-9965.epi-17-0238

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Supplementary Table S1 and supplmentary figure legends. from The Prevalence of Cancer-Associated Autoantibodies in Patients with Gastric Cancer and Progressive Grades of Premalignant Lesions

Irēna Meistere Simone Werner Pawel Zayakin Karīna Siliņa Undīne Rulle

<p>Supplementary Table S1. List of recombinantly expressed antigen clones represented on the microarray. Supplementary figure legends are also available.</p>

Table (database)

10.1158/1055-9965.22437889

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Figure S4 from The Prevalence of Cancer-Associated Autoantibodies in Patients with Gastric Cancer and Progressive Grades of Premalignant Lesions

Irēna Meistere Simone Werner Pawel Zayakin Karīna Siliņa Undīne Rulle

<p>Supplementary Figure 4. ROC curve analysis of identified autoantibody signatures.</p>

10.1158/1055-9965.22437895

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Antimutagenic 1,4-Dihydropyridine AV-153 Normalizes Expression of GLUT1, GLUT4, INOS, PARP1, and Gamma H2AX Histone in Myocardium of Rats with Streptozotocin Model of Diabetes Mellitus

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences (2023)

Evita Rostoka Sergejs Isajevs Jeļizaveta Sokolovska Г. Дубурс Nikolajs Sjakste

Abstract Diabetic cardiomyopathy increases the risk of heart failure and worsens prognosis for diabetes mellitus (DM) patients. Its development depends on many factors, including modification of nitric oxide production and impaired DNA repair. The goal of the present work was to study in vivo effects of a 1,4-dihydropyridine AV-153, known as antimutagen and DNA-binder, on DNA integrity, and on the expression of several proteins involved in glucose transport, nitric oxide metabolism, and DNA repair in myocardium in diabetic rats. DM was induced in rats by streptozotocin (STZ) injection. Expression of proteins was studied by means of immunohistochemistry. Development of the STZ-induced DM significantly induced PARP1 and gamma H2AX histone, markers of DNA breakage, protein expression in heart tissue, while AV-153 administration decreased PARP1 and H2AX protein expression. In this model of diabetes, myocardial expression of iNOS was also significantly increased, but administration of AV-153 reduced it to normal levels. AV-153 also upregulated the expression of insulin-dependent GLUT4 and insulin-independent GLUT1 glucose transporters up to normal level in diabetic rats. Thus, AV-153 appears to be prospective for creation of a remedy for prevention of diabetic cardiomyopathy.

Diabetic Cardiomyopathy

GLUT4

10.2478/prolas-2023-0014

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Association of gastric cancer risk with genetic variant of HRH 2

Georgijs Moisejevs Linda Gailīte Liene Ņikitina-Zaķe Sergejs Isajevs Armands Sīviņš

Association (psychology)

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Melanoma Unknown Primary Brain Metastasis Treatment with ECHO-7 Oncolytic Virus Rigvir: A Case Report

Frontiers in Oncology (2018)

Guna Proboka Andra Tilgase Sergejs Isajevs Agnija Rasa Pēteris Alberts

Melanoma is considered an aggressive malignancy with a tendency for forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of this disease. Melanoma brain metastases have many severe side effects and unfortunately, any disease related to the brain has limited therapeutic options due to the blood brain barrier. The course of the disease after completing a treatment course, and stopping the treatment, is complicated to predict and is difficult to obtain long-lasting remission. In this report we describe a female patient with unknown primary melanoma brain metastasis being treated with the oncolytic ECHO-7 virus Rigvir® after brain surgery. The patient has been stable, as monitored by MRI, for more than 3 years with the therapy still ongoing. The median expected overall survival from the time of diagnosis is approximately five months. Additional positive effect could have been gained from use of the intranasal administration route, which is considered effective due to the direct anatomical connection between the nasal cavity and the central nervous system. However, further studies are required to fully understand this mode of drug administration.

Neuroradiology

10.3389/fonc.2018.00043

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Changes in GLUT1 expression under metformin treatment in rat models of severe and mild stretozotocin diabetes mellitus

13th European Congress of Endocrinology (2011)

Jeļizaveta Sokolovska Sergejs Isajevs Olga Sugoka Jelena Sharipova Lāsma Ļauberte

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Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcinoma

Cancer Research (2017)

Karīna Siliņa Alex Soltermann Farkhondeh Movahedian Attar Ruben Casanova Zina M. Uckeley

Abstract In solid tumors, the presence of lymph node–like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS develop in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multispectral microscopy, quantitative pathology, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation in LSCC culminating in the formation of germinal centers (GC). In untreated patients, TLS density was the strongest independent prognostic marker. Furthermore, TLS density correlated with GC formation and expression of adaptive immune response–related genes. In patients treated with neoadjuvant chemotherapy, TLS density was similar, but GC formation was impaired and the prognostic value of TLS density was lost. Corticosteroids are coadministered with chemotherapy to manage side effects in LSCC patients, so we evaluated whether they impaired TLS development independently of chemotherapy. TLS density and GC formation were each reduced in chemotherapy-naïve LSCC patients treated with corticosteroids before surgery, compared with untreated patients, a finding that we confirmed in the experimental model of lung TLS induction. Overall, our results highlight the importance of GC formation in TLS during tumor development and treatment. Significance: Corticosteroid treatment during chemotherapy negatively affects the development of tertiary lymphoid structures and abrogates their prognostic value in patients with lung cancer. Cancer Res; 78(5); 1308–20. ©2018 AACR.

10.1158/0008-5472.can-17-1987

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Addressing the importance of melanoma tumor‑infiltrating lymphocytes in disease progression and clinicopathological characteristics

Molecular and Clinical Oncology (2021)

Tatjana Zablocka Anna Nikolajeva Madara Kreišmane Dace Pjanova Sergejs Isajevs

Tumor-infiltrating lymphocytes (TILs) in primary cutaneous melanoma are considered to represent the host's antitumor immunological response; however, whether there are associations between TIL grade and histopathological characteristics and disease survival remains controversial. BRAF mutational status has been established as a routine screening method in advanced malignant melanoma, and worse prognosis rates have been demonstrated in patients harboring BRAF mutations. However, the general impact of BRAF mutational status on survival and histopathological characteristics is still debated. The aim of the present study was to compare the value of the assessment of TIL grade in stages I-II nodular and superficial spreading melanoma and BRAF mutational status, and its influence on clinicopathological characteristics. Altogether, 85 patients at stage IA-IIC who underwent melanoma surgical treatment at the Riga East University Hospital between 2012 and 2017 were retrospectively enrolled in the study. The histopathological characteristics were assessed according to the current World Health Organization and The American Joint Committee on Cancer 8th edition guidelines. The current study showed that patients with melanoma with high TIL grade had significantly better progression-free survival than patients with low TIL grade (hazard ratio, 4.9; 95% CI, 2.3-11.2; P<0.0001). BRAF mutations were observed in 52 patients (61.2%). BRAF mutational status in melanoma was associated with Clark invasion level (P=0.045), patient age (P=0.02) and TIL (P=0.04). The assessment of TIL grade in stage I-II melanoma demonstrated prognostic significance value and may help improve risk assessment in the future.

Tumor progression

10.3892/mco.2021.2417

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