Irina Kholodnyuk Holodnuka

Riga Stradins University | rsu · Institute of Microbiology and Virology

Chemokines and their receptors regulate the migration of immune cells and the dissemination of cancer cells. CCR1, CCR2, CCR3, and CCR5 all belong to a single protein homology cluster and respond to the same inflammatory chemokines. We previously reported that CCR1 and CCR2B are induced upon Epstein-Barr virus (EBV) infection of B cells in vitro. E...

Nucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for bo...

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes in patients with chronic lymphocytic leukemia (CLL) and is consi...

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 7 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted 8 in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical 9 outcomes in patients with chronic lymphocytic leukemia (CLL) and is...

Telomerase reverse transcriptase (TERT) is a classic tumor-associated antigen overexpressed in majority of tumors. Several TERT-based cancer vaccines are currently in clinical trials, but immune correlates of their antitumor activity remain largely unknown. Here, we characterized fine specificity and lytic potential of immune response against rat T...

Background and objectives: Composition of the peripheral blood (PB) cell populations and their activation state reflect the immune status of a patient. Rheumatoid arthritis (RA) is characterized by abnormal B- and T-cell functions. The objective of this study was to assess the profiles of the PB mononuclear cell (PBMC) populations in patients with...

CCR2 is the cognate receptor to the chemokine CCL2. CCR2–CCL2 signaling mediates cancer progression and metastasis dissemination. However, the role of CCR2–CCL2 signaling in pathogenesis of B-cell malignancies is not clear. Previously, we showed that CCR2B was upregulated in ex vivo peripheral blood B cells upon Epstein‒Barr virus (EBV) infection a...

The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, ar...

Aim: To study the status of the tumor growth factor beta (TGFB) pathway in chronic lymphocytic leukemia (CLL) cells and to uncover molecular details underlying CLL cell genesis. Objects and methods: The study was conducted on peripheral blood samples of patients with CLL using the following methods: RNA isolation, analysis of expression of trans...

Up to now, the immune status of chronic lymphocytic leukemia (CLL) patients in association with the expression of zeta-chain-associated protein kinase 70 (ZAP-70) in leukemic cells has not been evaluated. The aim of this work was the study of the peripheral blood (PB) T-lymphocyte phenotypes in ZAP-70-positive (ZAP-70(+)) and ZAP-70-negative (ZAP-7...

CELL-SURFACE EXPRESSION OF CHEMOKINE RECEPTORS CCR1 AND CCR2 IN PB B-LYMPHOCYTES OF PATIENTS WITH RHEUMATOID ARTHRITIS, OSTEOARTHRITIS, AND B-CELL LYMPHOPROLIFERATIVE DISORDER Kholodnyuk Holodnuka I.1, Spaka I.1, Kadisa A.1,2, Studers P.3, Vilkaite A.1, Spaks A.1, Gravelsina S.1, Rivkina A.1,2,4, Lejniece S.2,4, Lajnieks A.2,4, Murovska M.1 1A.Kirc...

Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that is located on the human chromosome 6p21.3. We discovered that overexpression of the S18-2 protein led to immortalization and de-differentiation of primary rat embryonic fibroblasts. Cells showed anchorage-independent growth pattern. Moreover, pathways characte...

Epstein-Barr virus (EBV) is involved in the pathogenesis of endemic Burkitt’s lymphoma (BL). EBV-positive BL cell lines initially maintain the original tumor phenotype of EBV infection (latency I, LatI), but most of them drift toward a lymphoblast phenotype of EBV latency III (LatIII) during in vitro culturing. The aim of this study was to characte...

Euploid chromosome balance is vitally important for normal development, but is profoundly changed in many tumors. Is each tumor dependent on its own structurally and numerically changed chromosome complement that has evolved during its development and progression? We have previously shown that normal chromosome 3 transfer into the KH39 renal cell c...

Chr3 alterations in RCC cell lines speak in favor of "Mandatory chromosomal segment copy number" model.

We have applied a functional test for tumour antagonizing genes based on human chromosome 3 (chr3)-mouse fibrosarcoma A9 MCHs that were studied in vitro and after growth as tumours in severe combined immunodeficiency (SCID) mice. Previously, we reported that 9 out of the 36 SCID-tumours maintained the transferred chr3 ("chr3+" tumours), but lost th...

Lactoferrin (LF) is one of 19 active genes in the common eliminated region 1 at 3p21.3 identified by us. LF was transfected into mouse fibrosarcoma A9. Fourteen severe combined immunodeficient (SCID) derived tumors from two PI based artificial chromosome (PAC)-transfectants containing the entire LF gene and two LF-cDNA transfectants were analyzed b...

We have previously shown that inoculation of human chromosome 3 (chr3)/A9 mouse fibrosarcoma microcell hybrids (MCHs) into severely combined immunodeficient (SCID) mice was followed by the regular elimination of certain 3p regions, whereas a 3q region was retained even after prolonged mouse passage. Using this approach, referred to as the eliminati...

Similar regions of human chromosome 3 are eliminated from, or retained in human/human and human/mouse microcell hybrids during tumor growth in SCID mice.

By passaging microcell hybrids (MCHs) containing human chromosome 3 (chr3) on A9 mouse fibrosarcoma background through severe combined immunodeficient (SCID) mice (elimination test), we have previously defined a 1-Mb-long common eliminated region 1 (CER1) at 3p21.3, a second eliminated region (ER2) at 3p21.1-p14 and a common retained region (CRR) a...

We have previously shown that inoculation of human chromosome 3 (chr3)/A9 mouse fibrosarcoma microcell hybrids (MCHs) into severe combined immunodeficient (SCID) mice was followed by the regular elimination of some 3p regions whereas a 3q region was retained even after prolonged mouse passage. Using this approach, referred to as the elimination tes...

We have developed an elimination test to identify chromosomal regions that contain tumor inhibitory genes. Monochromosomal human/mouse microcell hybrids are generated and passaged through SCID mice. Derived tumors are then analyzed for deletions on the transgenomic chromosome. Using this strategy, we have previously identified a 1.6-cM common elimi...

We have previously identified an approximately 7 cM long common eliminated region (CER), involving the 3p21.3 markers AP20R, D3S966, D3S3559, D3S1029, WI-7947, D3S2354, AFMb362wb9, and D3S32, in human chromosome 3/A9 mouse fibrosarcoma microcell hybrid (MCH) derived SCID mouse tumors. We now report the results of our more detailed analysis on 24 SC...

We have previously found that human chromosome 3 was fragmented in the course of in vivo tumor growth of monochromosomal human/mouse (A9 fibrosarcoma parent) microcell hybrids in SCID mice. Marker analysis of tumor cell lines has identified a regularly eliminated 7 cM segment on 3p21.3 referred to as the common eliminated region (CER). The same reg...

We have previously identified an approximately 7 cM long common eliminated region (CER), involving the 3p21.3 markers AP20R, D3S966, D3S3559, D3S1029, WI‐7947, D3S2354, AFMb362wb9, and D3S32, in human chromosome 3/A9 mouse fibrosarcoma microcell hybrid (MCH) derived SCID mouse tumors. We now report the results of our more detailed analysis on 24 SC...

We have previously found that human chromosome 3 was fragmented in the course of in vivo tumor growth of monochromosomal human/mouse (A9 fibrosarcoma parent) microcell hybrids in SCID mice. Marker analysis of tumor cell lines has identified a regularly eliminated 7 cM segment on 3p21.3 referred to as the common eliminated region (CER). The same reg...

We have previously shown that four markers spanning the 3p24-p21.3 region, THRB, AP20R, D3S1029, and D3S32, were regularly eliminated from three human chromosome 3 (chr3)/mouse microcell hybrids (MCHs) during tumor growth in SCID mice. In an attempt to narrow down the eliminated region, we have studied 22 new SCID mouse tumors derived from 5 MCH li...

We have examined 17 primary undifferentiated nasopharyngeal carcinoma biopsies for allelic loss on 3p, comparing the findings in tumors with those in normal lymphocyte DNA from the same patients. Ten polymorphic microsatellite markers were used between 3p13 and 3p26. Allelic loss was observed in 12 samples (70%). Two loci were most frequently affec...

Loss of heterozygosity on chromosome 3p in nasopharyngeal carcinoma.

Long-range restriction site maps are of central importance for mapping the human genome. The use of clones from linking and jumping libraries for genome mapping offers a promising alternative to the laborious procedures used up until now. In the present review, this research field is analyzed with particular emphasis on the implementation of a shot...

"Elimination test", for screening tumor suppressor loci on chromosome 3.

"SCID mouse elimination test", for screening putative tumor suppressor loci on chromosome 3.

Microcell hybrid lines of A9 mouse fibrosarcoma containing complete or partially deleted human chromosomes 3 (chr. 3) were inoculated into SCID mice. Cell lines derived from the tumors were examined by fluorescent in situ hybridization for the status of the transferred human chromosome and by PCR for marker loss. The SCID tumors arising after the i...

"SCID mouse elimination test", for screening putative tumor suppressor loci on chromosome 3

"SCID mouse elimination test", for screening putative tumor suppressor loci on chromosome 3

NotI linking clones represent valuable tools for both physical and genetic mapping. Using procedures that we have previously described, several chromosome 3-specific NotI linking libraries have been constructed. Here, we describe the construction of six independent NotI linking libraries specific for the total human genome. These libraries were mad...

To study the connection among NotI linking clones,CpG islands, and genes, the sequence surrounding 143 NotI sites was determined. These Not I linking clones were isolated from human chromosome 3-specific libraries and contain an average C + G content of 65%. These clones represent sequence-tagged sites that can be positioned onto chromosome maps an...

The aim of this study is to identify the gene(s) on the short arm of human chromosome 3, the loss of which contributes to the occurrence of kidney carcinoma and other solid tumors. The critical role of aberrations detected on the short arm of chromosome 3 have been suggested by recent cytogenetic and molecular studies with restriction fragment leng...

The antigen-independent radioimmunoassay for the detection of HBsAg is presented. The principle of this method is the inhibition of the reaction of binding idiotype antibodies and tracer anti-idiotype antibodies by the competing HBsAg. The antigen-independent competition radioimmunoassay is specific and has 80-100 ng/ml-1 of HBsAg sensitivity.