Marta Gajewska - Academia.edu (original) (raw)
Papers by Marta Gajewska
F1000Research, Dec 21, 2010
BMC Veterinary Research, Aug 3, 2022
High stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, an... more High stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, and the products of their activity, including ammonia and hydrogen sulphide, have adverse health effects. Active techniques used to reduce unfavourable environmental conditions, such as ventilation, sprinkling, bedding sorbents, and nutritional treatments, are not always sufficient to improve the animals' living environment. The current paper aims to evaluate the effect of radiant catalytic ionization (RCI) on airborne microorganisms, cage microbiological status, gaseous ammonia concentrations, and the haematological status of mice in animal houses. After one week of operation of an RCI system, the number of airborne bacteria and fungi in the experimental room decreased in comparison to the first day of the experiment (p < 0.05 and p < 0.05 respectively), as did the concentrations of ammonia (p < 0.01) and dust. At the same time, the basic health parameters of the mice, determined in the blood, were very similar between the control and experimental room. RCI seems to be an ideal solution to ensure high hygiene standards in animal rooms and houses with limited use of disinfectants or antibiotic treatment of sick animals. An additional, environmental benefit is the limited amount of nitrogen released.
Rejuvenation Research, 2021
Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of rep... more Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of repair processes in situ by paracrine mechanisms. These unique capabilities make ASCs candidates for the regenerative medicine applications, including cell-assisted lipotransfer method. ASC aging processes have been extensively researched in vitro, there is however limited information about the impact of ASC aging on their biological role in tissue regeneration in vivo. The aim of our study was the research of the possible effects of aging processes of ASCs resulting from the donor age or from in vitro aging during long-term culture (ASC expansion in bioreactors) on their capability to support survival of adipose subcutaneous transplants in rats. The supportive in vivo effects of ASCs from young donors were compared with the effects of ASCs from old donors and ASCs ''aged'' in long-term in vitro cultures. Fat grafts enriched with ASCs (regardless of their age) retain their volume longer than fat grafts without ASCs supplementation. Vascular expansion in cell-enriched fat grafts was more intense when compared with the controls. It may be concluded that the aging of ASCs does not substantially reduce their ability for the support of the survival of adipose tissue grafts.
Archives Animal Breeding, 2005
Experiment was carried out on 111 and 13-14 weeks old mice divergently selected for low (L) and h... more Experiment was carried out on 111 and 13-14 weeks old mice divergently selected for low (L) and high (C) body weight over 108 generations. In leg muscle and liver cathepsin D (CatD) was determined as pepstatin sensitive activity (PSCatD), and as pepstatin-insensitive (PIA) and leupeptin-insensitive (LIA) acid autolytic activities (AAA) were measured. In leg muscle and liver all measured activities were higher in L as compared to C and control (K) mice. The percent of inhibition of LIA was lower in L then C mice in both examined tissues. In the leg muscles, in L mice protein catabolism was mostly influenced by CatD, but in the liver CatD was mostly active in K mice. CatD, PSCatD, AAA and LIA in leg muscle of L mice as compare to K were higher in female (F) by 68 %, 68.5 %, 91.3 % and 94.5 %, respectively, and in male (M) mice by 43.4 %, 54 %, 47.1 % and 64 %, respectively. The percent of inhibition by leupeptin in AAA was higher in C mice by 61.9 % in F and by 40 % in M mice. In the liver, PIA was higher by about 45 % in L and by 28.5 % in C mice as compare to K ones. There were about 36% of 30.00-39.99 µm muscle fibrils in M mice and in males of L group 40.00-49.99 µm fibrils appeared at 25% (absent in 3 weeks mice). In female, all measured fibril diameters were in higher percent in L than in C group. RNA variables were higher by about 25% (in average) in C as compare to K and L groups. Functional cell size (FCS) was lowered in L and C group as compared to K by about 10 % (in average). These results indicate on faster proteins turnover in L than in C group of mice.
Biological Invasions, 2010
... Jörn Theuerkauf Hervé Jourdan Sophie Rouys Roman Gula Marta Gajewska Katarzyna Unru... more ... Jörn Theuerkauf Hervé Jourdan Sophie Rouys Roman Gula Marta Gajewska Katarzyna Unrug Ralph Kuehn ... A ban on the introduction of invasive species to Wallis and Futuna was voted in July 2007 (Code de l&amp;amp;amp;#x27;Environnement, Délibération n°09 bis/AT-2007). ...
Rarefraction curves from all samples on family level drawn with MEGAN5 software. (PDF 4369Â kb)
Annals of Warsaw University of Life Sciences- SGGW Animal Science, 2013
Semen quality parameters in outbred male mice from four different selected lines. Breeding of (ou... more Semen quality parameters in outbred male mice from four different selected lines. Breeding of (outbred) selective lines of laboratory mouse was initiated in Warsaw University of Life Sciences about 40 years ago. It bred Heavy (C) and Light (L) mice selected opposite for body weight at weaning (21st day of life), S mice line selected for higher testes weight, and control (K) mice without selection. All lines have identical genetic background, but different directions of selections caused diversi cation of speci c phenotypic traits between them. The purpose of this study was to compare semen quantity and quality parameters in outbred C, K, L and S male mice in the context of measurements of average body and testes weight for each line. Research materials were seminal uids squeezed out of the vas deferens from 20 outbred C, K, L and S male mice (5 males per group). Animals had been euthanized, and necropsy was performed. Body and testes weight was measured. Also sperm concentration, vi...
Rarefraction curves from all samples on family level drawn with MEGAN5 software. (PDF 4369Â kb)
Journal of Radiation Research, 2011
Radiation induced lymphoma/Radiation induced myeloid-granulocytic leukemia/Susceptibility genes/C... more Radiation induced lymphoma/Radiation induced myeloid-granulocytic leukemia/Susceptibility genes/Chromosomal abnormalities. Genetics of susceptibility to radiation-induced hematopoietic neoplasms and somatic chromosomal aberrations were analyzed in 305 backcross (CcS-17xCcS-2)xCcS-2 mice of two CcS/Dem recombinant congenic strains. Irradiated CcS-2 mice were previously shown to exhibit high frequency of myeloid neoplasms whereas irradiated CcS-17 mice were susceptible to T-cell lymphomas. Mice were exposed to four whole-body irradiation doses of 1.7 Gy at one week intervals, which resulted in 139 hematopoietic neoplasms. The hematopoietic neoplasms were classified according to the Bethesda proposals for classification of lymphoid and nonlymphoid hematopoietic neoplasms in mice. Genotyping of mice with 24 microsatellite markers and subsequent statistical analysis indicated linkage of the radiation induced T-lymphomas to two loci on chromosome 10 (D10Mit134) and chromosome 12 (D12Mit52). T-lymphoma susceptibility appeared to be linked to D10Mit134 in a sex dependent way. In contrast, the myeloidgranulocytic leukemias susceptibility is linked to combined effects of chromosome 5 (D5Mit179) and 16 (D16Mit34). Cytogenetic analysis was performed according to the standard G-bands procedure and confirmed using FISH method. We found non-random numerical and structural chromosomal changes in lymphoid neoplasms. Cytogenetic analysis indicated chromosomal aberrations presumably associated with lymphomagenesis, no specific cancer-related rearrangements were observed.
Marine Ecology Progress Series, 2013
Southern elephant seals Mirounga leonina migrate seasonally between pelagic foraging areas in the... more Southern elephant seals Mirounga leonina migrate seasonally between pelagic foraging areas in the Southern Ocean and breeding and moulting sites on subantarctic islands. Here we characterized genetic diversity of the elephant seal moulting colony from King George Island (KGI), South Shetlands Archipelago, in comparison with breeding colonies described in earlier studies. Although KGI serves as a breeding site, the numbers of elephant seals are up to 3 times higher during the moulting season, suggesting post-breeding immigration from other sites, or that large numbers of individuals skip the breeding season every year. High haplotype diversity and a high percentage of shared haplotypes is consistent with the hypothesis of immigration from other South Atlantic colonies, which is also supported by satellite tracking data from earlier studies. Estimates of effective population size at both mtDNA and microsatellite loci were unexpectedly high compared with the census size of the KGI colony, suggesting that they were elevated due to the presence of immigrants. However, we detected few immigrants and no genetic structure in the KGI colony, which could result from the genetic similarity between KGI and other breeding colonies from the South Atlantic, but could also be an effect of an insufficient sampling scheme. These results show the need for genetic monitoring of southern elephant seal colonies throughout their annual cycle to better understand the range of their seasonal movements and patterns of gene flow. The southern elephant seal serves as a model to study links between spatio-temporal environmental variability, population dynamics, and individual movements, physiology and reproductive behavior. Understanding the patterns of dispersal and gene flow in this species is essential to adequately address these general questions.
BioMed Research International, 2018
Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death w... more Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models. Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively. More than half of CRC tumors (20 out of 37, 54%) developed into a PDX. Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors. DNA sequencing identified an average of 0.14 variants per gene per sample. The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal ...
Experimental Animals, 2011
The genetic basis of the peripheral blood cell parameters is not fully elucidated. Thus, it is es... more The genetic basis of the peripheral blood cell parameters is not fully elucidated. Thus, it is essential to research the correlation between blood cell counts levels and the genome in laboratory animals and subsequently in humans. In the present study, we examined 288 F 2 mice from a cross between BALB/cW and C57BL/6J-Mpl hlb219 /J. The C57BL/6J-Mpl hlb219 /J strain is a mouse model of thrombocytopenia. We found very strong correlations for PLT counts and revealed some highly significant correlations for RBC counts. On the basis of the obtained results, we presume that genetic control of erythrocyte parameters is divided into two pathways: first, the morphological determinants responsible for the red blood cell count (RBC), hematocrit (HCT), and mean corpuscular volume (MCV), and second, the functional pathway determining the hemoglobin content (HGB). The locus on Chromosome 4 is the only detected quantitative trait locus (QTL) influencing the analyzed platelets parameters. We also detected highly significant correlations for erythrocyte parameters on Chromosome 1 (RBC, MCV, MCH), Chr 7 (HGB), Chr 9 (MCHC), Chr 11 (RBC), and Chr 17 (MCH). Finally, with regards to the given correlations, using the Mouse Genome Database resource, we proposed candidate genes with possible meaning for the level of these parameters: cytokine receptor genes (e.g., Mpl), transcription factor genes (e.g., Xbp1, Ikzf1), hemoglobin chain genes (e.g., Hbb-b1, Hbb-ar), and many others localized in the confidence intervals of found QTLs.
International Journal of Molecular Sciences
TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selec... more TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspas...
Under certain conditions small amounts of DNA can survive for long periods of time and may be use... more Under certain conditions small amounts of DNA can survive for long periods of time and may be used as substrates in the polymerase chain reaction (PCR) for the study of phylogeny and population genetics of extinct animals and plants. About 20 years ago, DNA sequences were separately described from the quagga and an ancient Egyptian individual; what made these DNA sequences exceptional was that they were derived from 140- and 2,400-year-old specimens. More recently, ancient DNA (aDNA) has been used to study phylogenetic relationships of protists, fungi, algae, plants, and higher eukaryotes such as extinct horses, cave bears, woolly mammoths, the moa, and Neanderthal. In the past few years, this approach has been extended to the study of infectious disease in ancient mummies from Egypt and South America; they suggested a butchery pattern indicative of a human population under resource stress, revealed dietary habits of ancient animals, and helped to understand how climatic change impa...
Cancer Research, 2021
The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2,... more The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase–associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition–induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM i...
Journal of Biological Chemistry, 2019
The mitochondrial amidoxime-reducing component (MARC) is a mammalian molybdenum-containing enzyme... more The mitochondrial amidoxime-reducing component (MARC) is a mammalian molybdenum-containing enzyme. All annotated mammalian genomes harbor two MARC genes, MARC1 and MARC2, which share a high degree of sequence similarity. Both molybdoenzymes reduce a variety of N-hydroxylated compounds. Besides their role in N-reductive drug metabolism, only little is known about their physiological functions. In this study, we characterized an existing KO mouse model lacking the functional MARC2 gene and fed a high-fat diet and also performed in vivo and in vitro experiments to characterize reductase activity toward known MARC substrates. MARC2 KO significantly decreased reductase activity toward several N-oxygenated substrates, and for typical MARC substrates, only small residual reductive activity was still detectable in MARC2 KO mice. The residual detected reductase activity in MARC2 KO mice could be explained by MARC1 expression that was hardly unaffected by KO, and we found no evidence of signi...
Nutrition & Metabolism, 2016
Background: Transplanting a fecal sample from lean, healthy donors to obese recipients has been s... more Background: Transplanting a fecal sample from lean, healthy donors to obese recipients has been shown to improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering a long-term, high-fat diet (HFD) supplemented with feces from lean mice through the fecal-oral route. Methods: C57BL6/W mice were allowed to adapt to a non-specific pathogen free (SFP) environment for 2 weeks before being divided into three groups of 16 animals. Animals were fed for 28 weeks with a normal diet (ND), HFD or HFD supplemented with feces from ND-fed mice (HFDS). The composition of colonizing bacteria was evaluated in droppings collected under SPF conditions at the beginning of the study and at 12 and 28 weeks using an 16S Metagenomics Kit on Ion PGM sequencer. Results: HFD and HFDS-fed mice attained (p < 0.05) greater body weights by weeks 6 and 5, respectively. HFDS-fed mice gained more weight than HFD-fed mice by week 25. Both species diversity and richness indices increased with time in HFDS mice only. Conclusions: Prolonged HFD-fed mice supplementation with feces from lean mice altered bacteria species diversity and richness, accelerated the onset of obesity, and caused increased weight gain in the later weeks of the HFD regimen.
1 Department of Genetics and Laboratory Animal Breeding, The Maria Sklodowska-Curie Memorial Canc... more 1 Department of Genetics and Laboratory Animal Breeding, The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, Roentgena 5, 02-781 Warsaw, Poland 2 Department of Clinical Chemistry, The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, Roentgena 5, 02-781 Warsaw, Poland 3 Department of Genetics and Animal Breeding, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2015
Objective. The study focuses on the comparison of tissue reaction to titanium and bioresorbable i... more Objective. The study focuses on the comparison of tissue reaction to titanium and bioresorbable implants with and without postoperative irradiation on an animal model. Materials and Methods. Thirty-nine LEW/W rats were randomly assigned to experimental or control groups. One titanium and one bioresorbable screw (polyeLelactide [PLLA] and Le and Delactide polyeL/Delactide [PDLLA]) were implanted into the left scapulas of 24 rats. Half of them received 30 Gy to the operation site and the other half received 42 Gy. In the control groups, 3 rats received 30 Gy, and 6 rats received 42 Gy to the scapula area without operation; and 6 rats had implants inserted as in the experimental group, but received no postoperative irradiation. The scapulas were removed 14 or 30 days after irradiation and a histologic analysis was performed. Results. The host tissue reaction to titanium and PLLAePDLLA screws without postoperative irradiation was of similar intensity. In irradiated animals, the inflammatory tissue reaction was more evident around the titanium screws than around the bioresorbable screws, irrespective of the radiation dose and of the time that elapsed from the irradiation. The reaction was more evident on the 14th day than on the 30th day after the last radiation dose (70 and 86 days after surgery, respectively). The intensity of the inflammatory tissue reaction, irrespective of the implant type, was more intense in the group irradiated with 42 Gy. Conclusions. PLLAePDLLA implants appear to cause less tissue reaction after irradiation and could be safer reconstructive devices than titanium implants for patients undergoing surgery and adjuvant radiotherapy for cancer. (
F1000Research, Dec 21, 2010
BMC Veterinary Research, Aug 3, 2022
High stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, an... more High stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, and the products of their activity, including ammonia and hydrogen sulphide, have adverse health effects. Active techniques used to reduce unfavourable environmental conditions, such as ventilation, sprinkling, bedding sorbents, and nutritional treatments, are not always sufficient to improve the animals' living environment. The current paper aims to evaluate the effect of radiant catalytic ionization (RCI) on airborne microorganisms, cage microbiological status, gaseous ammonia concentrations, and the haematological status of mice in animal houses. After one week of operation of an RCI system, the number of airborne bacteria and fungi in the experimental room decreased in comparison to the first day of the experiment (p < 0.05 and p < 0.05 respectively), as did the concentrations of ammonia (p < 0.01) and dust. At the same time, the basic health parameters of the mice, determined in the blood, were very similar between the control and experimental room. RCI seems to be an ideal solution to ensure high hygiene standards in animal rooms and houses with limited use of disinfectants or antibiotic treatment of sick animals. An additional, environmental benefit is the limited amount of nitrogen released.
Rejuvenation Research, 2021
Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of rep... more Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of repair processes in situ by paracrine mechanisms. These unique capabilities make ASCs candidates for the regenerative medicine applications, including cell-assisted lipotransfer method. ASC aging processes have been extensively researched in vitro, there is however limited information about the impact of ASC aging on their biological role in tissue regeneration in vivo. The aim of our study was the research of the possible effects of aging processes of ASCs resulting from the donor age or from in vitro aging during long-term culture (ASC expansion in bioreactors) on their capability to support survival of adipose subcutaneous transplants in rats. The supportive in vivo effects of ASCs from young donors were compared with the effects of ASCs from old donors and ASCs ''aged'' in long-term in vitro cultures. Fat grafts enriched with ASCs (regardless of their age) retain their volume longer than fat grafts without ASCs supplementation. Vascular expansion in cell-enriched fat grafts was more intense when compared with the controls. It may be concluded that the aging of ASCs does not substantially reduce their ability for the support of the survival of adipose tissue grafts.
Archives Animal Breeding, 2005
Experiment was carried out on 111 and 13-14 weeks old mice divergently selected for low (L) and h... more Experiment was carried out on 111 and 13-14 weeks old mice divergently selected for low (L) and high (C) body weight over 108 generations. In leg muscle and liver cathepsin D (CatD) was determined as pepstatin sensitive activity (PSCatD), and as pepstatin-insensitive (PIA) and leupeptin-insensitive (LIA) acid autolytic activities (AAA) were measured. In leg muscle and liver all measured activities were higher in L as compared to C and control (K) mice. The percent of inhibition of LIA was lower in L then C mice in both examined tissues. In the leg muscles, in L mice protein catabolism was mostly influenced by CatD, but in the liver CatD was mostly active in K mice. CatD, PSCatD, AAA and LIA in leg muscle of L mice as compare to K were higher in female (F) by 68 %, 68.5 %, 91.3 % and 94.5 %, respectively, and in male (M) mice by 43.4 %, 54 %, 47.1 % and 64 %, respectively. The percent of inhibition by leupeptin in AAA was higher in C mice by 61.9 % in F and by 40 % in M mice. In the liver, PIA was higher by about 45 % in L and by 28.5 % in C mice as compare to K ones. There were about 36% of 30.00-39.99 µm muscle fibrils in M mice and in males of L group 40.00-49.99 µm fibrils appeared at 25% (absent in 3 weeks mice). In female, all measured fibril diameters were in higher percent in L than in C group. RNA variables were higher by about 25% (in average) in C as compare to K and L groups. Functional cell size (FCS) was lowered in L and C group as compared to K by about 10 % (in average). These results indicate on faster proteins turnover in L than in C group of mice.
Biological Invasions, 2010
... Jörn Theuerkauf Hervé Jourdan Sophie Rouys Roman Gula Marta Gajewska Katarzyna Unru... more ... Jörn Theuerkauf Hervé Jourdan Sophie Rouys Roman Gula Marta Gajewska Katarzyna Unrug Ralph Kuehn ... A ban on the introduction of invasive species to Wallis and Futuna was voted in July 2007 (Code de l&amp;amp;amp;#x27;Environnement, Délibération n°09 bis/AT-2007). ...
Rarefraction curves from all samples on family level drawn with MEGAN5 software. (PDF 4369Â kb)
Annals of Warsaw University of Life Sciences- SGGW Animal Science, 2013
Semen quality parameters in outbred male mice from four different selected lines. Breeding of (ou... more Semen quality parameters in outbred male mice from four different selected lines. Breeding of (outbred) selective lines of laboratory mouse was initiated in Warsaw University of Life Sciences about 40 years ago. It bred Heavy (C) and Light (L) mice selected opposite for body weight at weaning (21st day of life), S mice line selected for higher testes weight, and control (K) mice without selection. All lines have identical genetic background, but different directions of selections caused diversi cation of speci c phenotypic traits between them. The purpose of this study was to compare semen quantity and quality parameters in outbred C, K, L and S male mice in the context of measurements of average body and testes weight for each line. Research materials were seminal uids squeezed out of the vas deferens from 20 outbred C, K, L and S male mice (5 males per group). Animals had been euthanized, and necropsy was performed. Body and testes weight was measured. Also sperm concentration, vi...
Rarefraction curves from all samples on family level drawn with MEGAN5 software. (PDF 4369Â kb)
Journal of Radiation Research, 2011
Radiation induced lymphoma/Radiation induced myeloid-granulocytic leukemia/Susceptibility genes/C... more Radiation induced lymphoma/Radiation induced myeloid-granulocytic leukemia/Susceptibility genes/Chromosomal abnormalities. Genetics of susceptibility to radiation-induced hematopoietic neoplasms and somatic chromosomal aberrations were analyzed in 305 backcross (CcS-17xCcS-2)xCcS-2 mice of two CcS/Dem recombinant congenic strains. Irradiated CcS-2 mice were previously shown to exhibit high frequency of myeloid neoplasms whereas irradiated CcS-17 mice were susceptible to T-cell lymphomas. Mice were exposed to four whole-body irradiation doses of 1.7 Gy at one week intervals, which resulted in 139 hematopoietic neoplasms. The hematopoietic neoplasms were classified according to the Bethesda proposals for classification of lymphoid and nonlymphoid hematopoietic neoplasms in mice. Genotyping of mice with 24 microsatellite markers and subsequent statistical analysis indicated linkage of the radiation induced T-lymphomas to two loci on chromosome 10 (D10Mit134) and chromosome 12 (D12Mit52). T-lymphoma susceptibility appeared to be linked to D10Mit134 in a sex dependent way. In contrast, the myeloidgranulocytic leukemias susceptibility is linked to combined effects of chromosome 5 (D5Mit179) and 16 (D16Mit34). Cytogenetic analysis was performed according to the standard G-bands procedure and confirmed using FISH method. We found non-random numerical and structural chromosomal changes in lymphoid neoplasms. Cytogenetic analysis indicated chromosomal aberrations presumably associated with lymphomagenesis, no specific cancer-related rearrangements were observed.
Marine Ecology Progress Series, 2013
Southern elephant seals Mirounga leonina migrate seasonally between pelagic foraging areas in the... more Southern elephant seals Mirounga leonina migrate seasonally between pelagic foraging areas in the Southern Ocean and breeding and moulting sites on subantarctic islands. Here we characterized genetic diversity of the elephant seal moulting colony from King George Island (KGI), South Shetlands Archipelago, in comparison with breeding colonies described in earlier studies. Although KGI serves as a breeding site, the numbers of elephant seals are up to 3 times higher during the moulting season, suggesting post-breeding immigration from other sites, or that large numbers of individuals skip the breeding season every year. High haplotype diversity and a high percentage of shared haplotypes is consistent with the hypothesis of immigration from other South Atlantic colonies, which is also supported by satellite tracking data from earlier studies. Estimates of effective population size at both mtDNA and microsatellite loci were unexpectedly high compared with the census size of the KGI colony, suggesting that they were elevated due to the presence of immigrants. However, we detected few immigrants and no genetic structure in the KGI colony, which could result from the genetic similarity between KGI and other breeding colonies from the South Atlantic, but could also be an effect of an insufficient sampling scheme. These results show the need for genetic monitoring of southern elephant seal colonies throughout their annual cycle to better understand the range of their seasonal movements and patterns of gene flow. The southern elephant seal serves as a model to study links between spatio-temporal environmental variability, population dynamics, and individual movements, physiology and reproductive behavior. Understanding the patterns of dispersal and gene flow in this species is essential to adequately address these general questions.
BioMed Research International, 2018
Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death w... more Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models. Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively. More than half of CRC tumors (20 out of 37, 54%) developed into a PDX. Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors. DNA sequencing identified an average of 0.14 variants per gene per sample. The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal ...
Experimental Animals, 2011
The genetic basis of the peripheral blood cell parameters is not fully elucidated. Thus, it is es... more The genetic basis of the peripheral blood cell parameters is not fully elucidated. Thus, it is essential to research the correlation between blood cell counts levels and the genome in laboratory animals and subsequently in humans. In the present study, we examined 288 F 2 mice from a cross between BALB/cW and C57BL/6J-Mpl hlb219 /J. The C57BL/6J-Mpl hlb219 /J strain is a mouse model of thrombocytopenia. We found very strong correlations for PLT counts and revealed some highly significant correlations for RBC counts. On the basis of the obtained results, we presume that genetic control of erythrocyte parameters is divided into two pathways: first, the morphological determinants responsible for the red blood cell count (RBC), hematocrit (HCT), and mean corpuscular volume (MCV), and second, the functional pathway determining the hemoglobin content (HGB). The locus on Chromosome 4 is the only detected quantitative trait locus (QTL) influencing the analyzed platelets parameters. We also detected highly significant correlations for erythrocyte parameters on Chromosome 1 (RBC, MCV, MCH), Chr 7 (HGB), Chr 9 (MCHC), Chr 11 (RBC), and Chr 17 (MCH). Finally, with regards to the given correlations, using the Mouse Genome Database resource, we proposed candidate genes with possible meaning for the level of these parameters: cytokine receptor genes (e.g., Mpl), transcription factor genes (e.g., Xbp1, Ikzf1), hemoglobin chain genes (e.g., Hbb-b1, Hbb-ar), and many others localized in the confidence intervals of found QTLs.
International Journal of Molecular Sciences
TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selec... more TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspas...
Under certain conditions small amounts of DNA can survive for long periods of time and may be use... more Under certain conditions small amounts of DNA can survive for long periods of time and may be used as substrates in the polymerase chain reaction (PCR) for the study of phylogeny and population genetics of extinct animals and plants. About 20 years ago, DNA sequences were separately described from the quagga and an ancient Egyptian individual; what made these DNA sequences exceptional was that they were derived from 140- and 2,400-year-old specimens. More recently, ancient DNA (aDNA) has been used to study phylogenetic relationships of protists, fungi, algae, plants, and higher eukaryotes such as extinct horses, cave bears, woolly mammoths, the moa, and Neanderthal. In the past few years, this approach has been extended to the study of infectious disease in ancient mummies from Egypt and South America; they suggested a butchery pattern indicative of a human population under resource stress, revealed dietary habits of ancient animals, and helped to understand how climatic change impa...
Cancer Research, 2021
The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2,... more The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase–associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition–induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM i...
Journal of Biological Chemistry, 2019
The mitochondrial amidoxime-reducing component (MARC) is a mammalian molybdenum-containing enzyme... more The mitochondrial amidoxime-reducing component (MARC) is a mammalian molybdenum-containing enzyme. All annotated mammalian genomes harbor two MARC genes, MARC1 and MARC2, which share a high degree of sequence similarity. Both molybdoenzymes reduce a variety of N-hydroxylated compounds. Besides their role in N-reductive drug metabolism, only little is known about their physiological functions. In this study, we characterized an existing KO mouse model lacking the functional MARC2 gene and fed a high-fat diet and also performed in vivo and in vitro experiments to characterize reductase activity toward known MARC substrates. MARC2 KO significantly decreased reductase activity toward several N-oxygenated substrates, and for typical MARC substrates, only small residual reductive activity was still detectable in MARC2 KO mice. The residual detected reductase activity in MARC2 KO mice could be explained by MARC1 expression that was hardly unaffected by KO, and we found no evidence of signi...
Nutrition & Metabolism, 2016
Background: Transplanting a fecal sample from lean, healthy donors to obese recipients has been s... more Background: Transplanting a fecal sample from lean, healthy donors to obese recipients has been shown to improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering a long-term, high-fat diet (HFD) supplemented with feces from lean mice through the fecal-oral route. Methods: C57BL6/W mice were allowed to adapt to a non-specific pathogen free (SFP) environment for 2 weeks before being divided into three groups of 16 animals. Animals were fed for 28 weeks with a normal diet (ND), HFD or HFD supplemented with feces from ND-fed mice (HFDS). The composition of colonizing bacteria was evaluated in droppings collected under SPF conditions at the beginning of the study and at 12 and 28 weeks using an 16S Metagenomics Kit on Ion PGM sequencer. Results: HFD and HFDS-fed mice attained (p < 0.05) greater body weights by weeks 6 and 5, respectively. HFDS-fed mice gained more weight than HFD-fed mice by week 25. Both species diversity and richness indices increased with time in HFDS mice only. Conclusions: Prolonged HFD-fed mice supplementation with feces from lean mice altered bacteria species diversity and richness, accelerated the onset of obesity, and caused increased weight gain in the later weeks of the HFD regimen.
1 Department of Genetics and Laboratory Animal Breeding, The Maria Sklodowska-Curie Memorial Canc... more 1 Department of Genetics and Laboratory Animal Breeding, The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, Roentgena 5, 02-781 Warsaw, Poland 2 Department of Clinical Chemistry, The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, Roentgena 5, 02-781 Warsaw, Poland 3 Department of Genetics and Animal Breeding, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2015
Objective. The study focuses on the comparison of tissue reaction to titanium and bioresorbable i... more Objective. The study focuses on the comparison of tissue reaction to titanium and bioresorbable implants with and without postoperative irradiation on an animal model. Materials and Methods. Thirty-nine LEW/W rats were randomly assigned to experimental or control groups. One titanium and one bioresorbable screw (polyeLelactide [PLLA] and Le and Delactide polyeL/Delactide [PDLLA]) were implanted into the left scapulas of 24 rats. Half of them received 30 Gy to the operation site and the other half received 42 Gy. In the control groups, 3 rats received 30 Gy, and 6 rats received 42 Gy to the scapula area without operation; and 6 rats had implants inserted as in the experimental group, but received no postoperative irradiation. The scapulas were removed 14 or 30 days after irradiation and a histologic analysis was performed. Results. The host tissue reaction to titanium and PLLAePDLLA screws without postoperative irradiation was of similar intensity. In irradiated animals, the inflammatory tissue reaction was more evident around the titanium screws than around the bioresorbable screws, irrespective of the radiation dose and of the time that elapsed from the irradiation. The reaction was more evident on the 14th day than on the 30th day after the last radiation dose (70 and 86 days after surgery, respectively). The intensity of the inflammatory tissue reaction, irrespective of the implant type, was more intense in the group irradiated with 42 Gy. Conclusions. PLLAePDLLA implants appear to cause less tissue reaction after irradiation and could be safer reconstructive devices than titanium implants for patients undergoing surgery and adjuvant radiotherapy for cancer. (