Publications by authors named "Galazka Krystyna"

56 Publications

Acute onset of necrolytic migratory erythema mimicking an erythema multiforme.

Postepy Dermatol Alergol 2020 Oct 7;37(5):817-819. Epub 2020 Nov 7.

Department of Dermatology, Stefan Żeromski Special Hospital, Krakow, Poland.

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http://dx.doi.org/10.5114/ada.2020.100495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675067PMC
October 2020

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with probable mesentery involvement with associated hemophagocytic syndrome (HPS) - how to treat it?

J Dermatolog Treat 2020 Sep 14:1-11. Epub 2020 Sep 14.

Department of Hematology, Jagiellonian University Medical College, ul. Kopernika 17, 31-501 Kraków, Poland.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare, cutaneous lymphoma involving subcutaneous adipose tissue. SPTL is associated in less than 20% with hemophagocytic syndrome (HPS). A 5-year overall survival rate is inferior in pts with SPTLand HPS (46%) as compared with 91% in pts without HPS. No standardized therapy for SPTCL has yet been established. A case of 35-year-old Caucasian man with a one-month history of B symptoms with the suspicion of Still's disease. At admission with leucopenia, high LDH, ferritin, sIl-R2, and triglycerides levels, hepatosplenomegaly, small right supraclavicular nodule, and irregular thickening of trunk subcutaneous tissue. The abdomen MRI showed generalized thickening of mesentery and colonic mucosa. In the patient diagnosis of SPTCL was established with secondary HPS. CHOEP chemotherapy and modified HLH 2014 protocol were applied with subsequent high dose chemotherapy (BEAM) supported by autologous stem cells transplantation. Treatment was complicated by pancytopenia and pneumonia. The outcome of the disease treated by intensive protocol seems to be good.
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http://dx.doi.org/10.1080/09546634.2020.1809624DOI Listing
September 2020

Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

Molecules 2020 May 27;25(11). Epub 2020 May 27.

Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.

In acute pancreatitis (AP), pancreatic damage leads to local vascular injury, manifesting as endothelial damage and activation, increased vascular permeability, leukocyte rolling, sticking and transmigration to pancreatic tissue as well as activation of coagulation. Previous studies have shown that pretreatment with heparin or acenocoumarol inhibits the development of AP. The aim of the present study was to check the impact of pretreatment with warfarin, an oral vitamin K antagonist, on the development of ischemia/reperfusion-induced AP in rats. AP was induced by pancreatic ischemia followed by reperfusion of the gland. Warfarin (90, 180 or 270 µg/kg/dose) or vehicle were administered intragastrically once a day for 7 days before induction of AP. The effect of warfarin on the severity of AP was assessed 6 h after pancreatic reperfusion. The assessment included histological, functional, and biochemical analyses. Pretreatment with warfarin given at a dose of 90 or 180 µg/kg/dose increased the international normalized ratio and reduced morphological signs of pancreatic damage such as pancreatic edema, vacuolization of acinar cells, necrosis and the number of hemorrhages. These effects were accompanied by an improvement of pancreatic blood flow and a decrease in serum level amylase, lipase, pro-inflammatory interleukin-1β and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µg/kg/dose led to an increase in severity of pancreatic damage and biochemical indicators of AP. In addition, this dose of warfarin resulted in deaths in some animals. Pretreatment with low doses of warfarin inhibits the development of AP induced by pancreatic ischemia followed by reperfusion.
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http://dx.doi.org/10.3390/molecules25112493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321200PMC
May 2020

Atypical course of infective endocarditis in a patient with complex congenital heart disease, chronic hepatitis B virus infection, and splenic marginal zone lymphoma.

Pol Arch Intern Med 2020 08 19;130(7-8):697-699. Epub 2020 May 19.

Department of Cardiac and Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland

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http://dx.doi.org/10.20452/pamw.15367DOI Listing
August 2020

Uterine myoma with massive lymphocytic infiltration - case report.

Prz Menopauzalny 2019 Jun 28;18(2):123-125. Epub 2019 Jun 28.

Department of Obstetrics and Gynaecology, Provincial Clinical Hospital No. 2 in Rzeszow, Poland.

Introduction: Uterine leiomyomas are the most common neoplasm of the uterus in women. Massive lymphocytic infiltration in a myoma is an unusual finding. It is characterised by the varying intensity of lymphocyte infiltration, the presence of scattered plasma cells, eosinophilia, and rarely, other items. We would like to call attention to such a rare lesion.

Case Description: We present the case of a 31-year-old woman who had undergone surgical excision of a uterine tumour. Grossly, it had the typical uterine smooth muscle wall consistency. The microscopic examination revealed leiomyoma with heavy infiltration composed mainly of lymphocytes. On immunohistochemistry, in the lymphocytic infiltrate the T mature (CD3+/CD5+/TdT-) lymphocytes, small and of cytotoxic (CD8+/CD56-) type, prevailed, with moderate proliferative activity (expression of Ki67 found in ca. 30-40% of the cells), whereas B lymphocytes (CD20+/CD5-/TdT-) were innumerous and present in nodular aggregates. Despite a strong suspicion of neoplastic lymphoproliferation, the histopathological diagnosis was: leiomyoma with massive lymphoid infiltration. The cause of this feature is not known, although the gonadotropin-releasing hormone agonist and post-menopausal processes may promote such transformations. In differential diagnosis, malignant lymphoma, inflammatory pseudotumour, and pyomyoma should be included.

Conclusions: Lymphocytic infiltration within the uterine myoma is rare. The recognition of its distinct histological features is important to avoid possible misdiagnosis.
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http://dx.doi.org/10.5114/pm.2019.86838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719633PMC
June 2019

Chemerin alleviates acute pancreatitis in the rat thorough modulation of NF-κB signal.

Pancreatology 2019 Apr 11;19(3):401-408. Epub 2019 Feb 11.

Department of Medical Physiology Faculty of Health Sciences, Krakow, Poland.

Objective: Chemerin, an adipokine, works as the chemoattractant for the immune cells. The role of chemerin in the inflammatory reaction is controversial. Chemerin has been shown to aggravate the inflammatory response, but other studies demonstrated its anti-inflammatory influence. This study assessed the effects of chemerin on acute pancreatitis (AP) in vivo and in vitro.

Methods: For in vivo experiments male Wistar rats were used. For in vitro study rat pancreatic AR42J cells were employed. Chemerin (1, 5 or 10 μg/kg) was given to the rats prior to the induction of AP by subcutaneous caerulein infusion (25 μg/kg). For in vitro studies cells were subjected to caerulein (10 nM) with or without chemerin (100 nM). Serum amylase activity was measured by enzymatic method, serum TNFα concentration - by ELISA kit. Western-blot was used to examine cellular proteins.

Results: AP was confirmed by histological examination. Chemerin given to AP rats decreased histological manifestations of AP, reduced serum amylase activity and TNFα concentration. In AR42J cells subjected to caerulein with addition of chemerin signal for TNFα was reduced comparing to the cultures treated with caerulein alone. Analysis of the dynamics of nuclear translocation for p50, p65 and Bcl-3 points out to NF-κB attenuation as a mechanism of observed anti-inflammatory action of chemerin.

Conclusion: Chemerin significantly alleviated severity of AP in the rat, this is possibly due to the inhibition of pro-inflammatory signaling in the pancreatic cells.
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http://dx.doi.org/10.1016/j.pan.2019.02.005DOI Listing
April 2019

Intraoral manifestation of systemic AL amyloidosis with unique microscopic presentation of intracellular amyloid deposition in striated muscles.

Pol J Pathol 2018;69(2):200-204

We report the history of a 59-year old patient with systemic AL amyloidosis of intraoral manifestation. The patient first presented with complaints about dysphagia and remarkable enlargement of the tongue with highly reduced mobility, as well as bilateral submucosal thickenings on the cheeks. Histopathological examination of the incisional biopsy of the buccal mucosa and underlying tissues revealed AL amyloidosis. The microscopic presentation was, however, unique, as the amyloid deposits were present intracellularly in the striated muscles. The subsequent bone marrow biopsy confirmed the diagnosis of primary amyloidosis/multiple myeloma - associated amyloidosis.
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http://dx.doi.org/10.5114/pjp.2018.76705DOI Listing
May 2019

Pretreatment with obestatin inhibits the development of acetic acid-induced colitis in rats.

Arch Med Sci 2018 Jun 23;14(4):920-929. Epub 2016 Mar 23.

Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.

Introduction: Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies have shown that obestatin exhibits some protective and therapeutic effects in the pancreas and stomach. The aim of this study was to examine the effect of pretreatment with obestatin on the development of acetic acid-induced colitis.

Material And Methods: Studies were performed on Wistar rats. Before induction of colitis, rats were treated intraperitoneally with saline or obestatin, administered twice at a dose of 4, 8 or 16 nmol/kg/dose. The first dose of saline or obestatin was administered 8 h before the induction of colitis, the second one 7 h after the first dose. Colitis was induced by enema with 1 ml of 4% acetic acid solution. The severity of colitis was assessed 1 or 24 h after administration of enema.

Results: Pretreatment with obestatin administered at a dose of 8 or 16 nmol/kg/dose significantly reduced the area of mucosal damage evoked by enema with acetic acid ( < 0.05). This effect was accompanied by an improvement of mucosal blood flow and DNA synthesis in the colon. Moreover, obestatin administered at a dose of 8 or 16 nmol/kg/dose significantly reduced mucosal concentration of IL-1β and activity of myeloperoxidase ( < 0.05).

Conclusions: Pretreatment with obestatin exhibited a protective effect in the colon, leading to a reduction of colonic damage in acetic acid-induced colitis. This effect was associated with an improvement of mucosal blood flow, an increase in mucosal cell proliferation, and a decrease in local inflammation.
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http://dx.doi.org/10.5114/aoms.2016.58749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040133PMC
June 2018

Comprehensive histopathological diagnostics of aggressive B-cell lymphomas based on the updated criteria of the World Health Organisation's 2017 classification.

Pol J Pathol 2018;69(1):1-19

Revision of the fourth edition of the World Health Organisation (WHO) Classification of Haematopoietic and Lymphatic Tissues, which was published in 2017, introduced important changes updating the biology, pathology, genetics, and clinical presentation of aggressive B-cell lymphomas. High grade B-cell lymphomas (HGBLs) replaced B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, the new provisional entity Burkitt-like lymphoma with 11q aberration was identified, and some categories were upgraded, e.g. EBV-positive diffuse large B-cell lymphoma, not otherwise specified. Still the histopathological diagnostics is based on morphology and immunoprofile, but to define the HGBLs evaluation of MYC, BCL2, and BCL6 gene statuses is required. According to the presented WHO criteria, in the comprehensive histopathological diagnostics of aggressive B-cell lymphomas a highly specialised diagnostic team including a pathologist, a molecular biologist, a geneticist, a haematologist, and immunophenotyping technicians is needed.
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http://dx.doi.org/10.5114/pjp.2018.75332DOI Listing
July 2018

Treatment with Obestatin-A Ghrelin Gene-Encoded Peptide-Reduces the Severity of Experimental Colitis Evoked by Trinitrobenzene Sulfonic Acid.

Int J Mol Sci 2018 Jun 1;19(6). Epub 2018 Jun 1.

Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.

Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies showed that obestatin exhibited some protective and therapeutic effects in the gut. The aim of our presented study was to examine the effect of treatment with obestatin on trinitrobenzene sulfonic acid (TNBS)-induced colitis. In rats anesthetized with ketamine, colitis was induced through intrarectal administration of 25 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Obestatin was administered intraperitoneally at doses of 4, 8, or 16 nmol/kg, twice per day for four consecutive days. The first dose of obestatin was given one day before the induction of colitis, and the last one was given two days after administration of TNBS. Fourteen days after the induction of colitis, rats were anesthetized again with ketamine, and the severity of colitis was determined. The administration of obestatin had no effect on the parameters tested in rats without the induction of colitis. In rats with colitis, administration of obestatin at doses of 8 or 16 nmol/kg reduced the area of colonic damage, and improved mucosal blood flow in the colon. These effects were accompanied by a reduction in the colitis-evoked increase in the level of blood leukocytes, and mucosal concentration of pro-inflammatory interleukin-1β. Moreover, obestatin administered at doses of 8 or 16 nmol/kg reduced histological signs of colonic damage. The administration of obestatin at a dose of 4 nmol/kg failed to significantly affect the parameters tested. Overall, treatment with obestatin reduced the severity of TNBS-induced colitis in rats. This effect was associated with an improvement in mucosal blood flow in the colon, and a decrease in local and systemic inflammatory processes.
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http://dx.doi.org/10.3390/ijms19061643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032262PMC
June 2018

Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations.

Oncotarget 2016 Jun;7(25):38180-38190

Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden.

The genetic mechanisms underlying disease progression, relapse and therapy resistance in mantle cell lymphoma (MCL) remain largely unknown. Whole-exome sequencing was performed in 27 MCL samples from 13 patients, representing the largest analyzed series of consecutive biopsies obtained at diagnosis and/or relapse for this type of lymphoma. Eighteen genes were found to be recurrently mutated in these samples, including known (ATM, MEF2B and MLL2) and novel mutation targets (S1PR1 and CARD11). CARD11, a scaffold protein required for B-cell receptor (BCR)-induced NF-κB activation, was subsequently screened in an additional 173 MCL samples and mutations were observed in 5.5% of cases. Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-κB-inhibitor lenalidomide. Genetic alterations acquired in the relapse samples were found to be largely non-recurrent, in line with the branched evolutionary pattern of clonal evolution observed in most cases. In summary, this study highlights the genetic heterogeneity in MCL, in particular at relapse, and provides for the first time genetic evidence of BCR/NF-κB activation in a subset of MCL.
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http://dx.doi.org/10.18632/oncotarget.9500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122381PMC
June 2016

Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

Int J Mol Sci 2016 Sep 1;17(9). Epub 2016 Sep 1.

Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegórzecka St., 31-531 Cracow, Poland.

Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis.
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http://dx.doi.org/10.3390/ijms17091455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037734PMC
September 2016

Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917) in the Treatment of Acetic Acid-Induced Colitis in Rats.

Gastroenterol Res Pract 2016 28;2016:3126280. Epub 2016 Jun 28.

Department of Internal Medicine II, Thuringia Clinic, Teaching Hospital of the University of Jena, Rainweg 68, 07318 Saalfeld, Germany.

Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN) administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose) and/or Mutaflor (10(9) CFU/dose) were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats.
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http://dx.doi.org/10.1155/2016/3126280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940557PMC
July 2016

Single-agent MOR208 salvage and maintenance therapy in a patient with refractory/relapsing diffuse large B-cell lymphoma: a case report.

J Med Case Rep 2016 May 14;10(1):123. Epub 2016 May 14.

Department of Hematology, Jagiellonian University, Kopernika 17, Kraków, 31-501, Poland.

Background: Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin's lymphoma. Standard first-line treatment for this aggressive subtype comprises the anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone. If patients receiving such treatment have an early relapse, or their disease is initially refractory to such treatment, standard salvage regimens may not be effective. There is therefore a high unmet clinical need for new targeted agents that might improve the outcome for such patients. CD19 is a B-lymphocyte lineage-specific cell surface antigen that is expressed by most B-cell non-Hodgkin's lymphomas. MOR208 is an fragment-crystallizable engineered humanized monoclonal antibody with enhanced antitumor activity that targets CD19 and that may consequently have clinical utility in this setting.

Case Presentation: We describe the case of a 33-year-old Caucasian man who presented with a 3-month history of general symptoms and who was admitted to our pulmonology ward with dyspnea due to pneumonia and severe anemia. A histopathological examination of an enlarged right suprasternal lymph node confirmed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma, an uncommon morphological variant of diffuse large B-cell lymphoma. Our patient had a complete response to first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone, but had an early relapse 5 months after the end of treatment. After intensive salvage therapy consolidated with an autologous stem-cell transplant, our patient again had an early relapse and was subsequently enrolled in a phase IIa trial of single-agent MOR208. Following a scheduled 3 months of weekly treatment, a partial response was confirmed and MOR208 was continued as maintenance therapy, with administration every second week. Positron emission tomography-computed tomography confirmed a complete response 9 months later. This response is ongoing, with a duration of 24 months. MOR208 was well-tolerated by our patient and his quality of life and performance status remain high. No hospitalizations were required and our patient engaged in full-time work and physical activities.

Conclusion: Third-line single-agent therapy with the CD19 antibody MOR208 was highly effective in this patient, despite a history of early relapse after standard first-line and second-line treatment regimens. These data provide support for future randomized studies of MOR208.
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http://dx.doi.org/10.1186/s13256-016-0875-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868005PMC
May 2016

IgG4-related disease in the head and neck region: report of two cases and review of the literature.

Pol J Pathol 2016;67(4):370-375

IgG4-related disease (IgG4-RD) is a rare immune-mediated condition characterized by extensive tissue fibrosis and infiltration by immunoglobulin G4 positive plasma cells in a single organ or systemic appearance. Two cases are presented including an unusual case of a 30-year-old man with IgG4-RD appearing simultaneously in the cervical lymph nodes, ethmoid, maxillary sinuses, and upper gingiva, with spontaneous loss of teeth. According to the literature, this is the first case with loss of teeth occurring in the course of the disease. The second case is a 46-year-old man suffering from IgG4-related chronic sclerosing sialadenitis of the right submandibular gland.
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http://dx.doi.org/10.5114/pjp.2016.65871DOI Listing
July 2017

Prostate cancer with different ERG status may show different FOXP3-positive cell numbers.

Pol J Pathol 2016;67(4):313-317

Prostatic carcinoma is the most frequent cancer in males in the Western world. A significant proportion of these cancers have a recurrent translocation involving ETS family genes, which leads to the overexpression of ERG transcription factor. Prostate cancers, which bear this mutation, differ in a number of features, including tumor microenvironment. One of the components of the tumor microenvironment is FOXP3 positive lymphocytes, which may participate in breaking immunosurveillance and promoting tumor growth. The aim of the study was to analyze the relationships between ERG expression, number of FOXP3 positive cells and other features of the tumor. The study group consisted of 65 cases. Tissue microarrays composed of 2 mm tissue cores were used for immunohistological evaluation. Immunohistochemistry for ERG and FOXP3 was performed according to the routinely applied protocol. The FOXP3 positive cells were counted and the results were expressed as the number of cells per mm2. The average number of FOXP3 positive cells was 33.30/mm2 for all cases, 21.43/mm2 for the ERG negative and 42.28/mm2 for the ERG positive group (p < 0.02). There were no significant relationships between FOXP3 positive cell count and any other parameters studied. Our results suggest that the immune response may differ between ERG negative and ERG positive prostatic carcinomas.
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http://dx.doi.org/10.5114/pjp.2016.65861DOI Listing
July 2017

The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats.

Biomed Res Int 2015 2;2015:718314. Epub 2015 Dec 2.

Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegórzecka Street, 31-531 Cracow, Poland.

Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin's anti-inflammatory and antioxidative properties.
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http://dx.doi.org/10.1155/2015/718314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680107PMC
September 2016

Lenalidomide in heavily pretreated refractory diffuse large B-cell lymphoma: a case report.

J Med Case Rep 2014 Oct 2;8:325. Epub 2014 Oct 2.

Department of Hematology, Jagiellonian University, Kopernika 17, Kraków 30-501, Poland.

Introduction: In diffuse large B-cell lymphoma, first-line treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; salvage with cisplatin-based regimens for relapsing patients; and autologous stem cell therapy are standards of care. Treatment approaches are less clear for patients who are refractory or who are not candidates for autologous stem cell therapy. Options may include palliative regimens or clinical trial enrollment. One therapy under investigation in diffuse large B-cell lymphoma is lenalidomide, an immunomodulatory agent with antiangiogenic activity.

Case Presentation: We present the case of a 55-year-old Caucasian male patient diagnosed with diffuse large B-cell lymphoma who had an early relapse after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. He then had a subsequent early relapse after cisplatin-based salvage consolidated with autologous stem cell therapy. The efficacy of gemcitabine-cisplatin-rituximab was limited to five months, followed by systemic and central nervous system progression. Fourth-line treatment with lenalidomide plus rituximab and involved-field radiotherapy followed by lenalidomide monotherapy greatly improved this patient's quality of life and performance status, allowing over two years of progression-free survival to date (excluding a brief relapse due to treatment interruption).

Conclusion: A lenalidomide-based regimen was highly effective in this patient with diffuse large B-cell lymphoma.
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http://dx.doi.org/10.1186/1752-1947-8-325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191682PMC
October 2014

Clinical utility of different bone marrow examination methods in the diagnosis of adults with sporadic Gaucher disease type 1.

Pol Arch Med Wewn 2014 3;124(11):587-92. Epub 2014 Sep 3.

Introduction: In the absence of a known affected family member, frequent symptoms of Gaucher disease (GD), a rare lysosomal storage disorder, such as thrombocytopenia or splenomegaly, often lead to hematological diagnostic workup.

Objectives: The aim of the study was to compare the clinical utility of aspiration biopsy of the bone marrow (ASP) with trephine biopsy (TB) for the diagnosis of GD type 1 (GD1).

Patients And Methods: Six non-Jewish patients with sporadic GD1 were initially examined with ASP and TB to establish the cause of cytopenia and splenomegaly. In the current study, samples from each patient consisted of 2 bone marrow slides. On each slide, 500 nucleated cells were counted and then averaged. The composition of bone marrow TBs was assessed using digital images analyzed on a computer.

Results: Of 6 patients, 5 carried at least 1 N370S allele with a c.1226A>G mutation in the GBA1 gene. The median number of Gaucher cells identified during cytological assessment of bone marrow smears was 4 (range, 1-18), and the median percentage of Gaucher cells was 0.4% (range, 0.1%-1.8%). The absolute proportion of Gaucher cells in histological samples ranged from 22% to 36% (median value, 28%), and the ratio of Gaucher cell infiltrate to hematopoietic tissue ranged from 34% to 54% (median value, 47%). The median value of the ratio of Gaucher cells to hematopoietic tissue was strikingly lower when using ASP compared with TB (P = 0.028).

Conclusions: Our results indicate that ASP is not a reliable diagnostic tool for the detection of GD1. Thus, patients with unclear long-lasting splenomegaly and/or thrombocytopenia, in whom bone marrow aspirate cytology is negative for Gaucher cells, should be routinely referred for an enzymatic assay for GD.
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http://dx.doi.org/10.20452/pamw.2493DOI Listing
November 2016

The analysis of metallothionein immunoreactivity in stromal fibroblasts and macrophages in cases of uterine cervical carcinoma with respect to both the local and distant spread of the disease.

Am J Reprod Immunol 2013 Sep 17;70(3):253-61. Epub 2013 Apr 17.

Department of Obstetrics and Gynecology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.

Problem: The tumor microenvironment is made up of tissue that is responsible for the growth and progression of the tumor as well as its ability to initiate metastases. The cancer cells on the front of the tumor together with the macrophages and fibroblasts help to constitute the aggressive phenotype of the tumor. The presence of this aggressive phenotype is indicated by the local infiltration of cancer cells and by the development of lymph node metastases. In cases of uterine cancer, the extent of the local and distant spread of the disease is crucial for determining the type of therapeutic strategy to be applied - surgery alone, surgery followed by radio-chemotherapy, or radio-chemotherapy alone. In the interest of trying to improve the patient's quality of life, different studies supporting the therapeutic model of surgery alone have been conducted. While the cancer cells on the tumor front together with the macrophages and the fibroblasts help to constitute the aggressive phenotype of the tumor, metallothionein (MT) has been shown to have both pro-proliferative and anti-apoptotic activities and to participate in microenvironment remodeling. The aim of the current study was to determine the levels of MT immunoreactivity in the uterine cervical cancer cells as well as in the stromal fibroblasts and macrophages of the tumor microenvironment with respect to the depth of the local invasion and the extent of the distant metastases, so that its potential predictive value as a therapeutic strategy for cervical cancer can be ascertained.

Methods: We determined the levels of immunoreactivity of MT in a total of 57 carcinoma tissue samples (in the tumor front, in its central part, and in the macrophages and fibroblasts present within the tumor microenvironment). The patients from whom the samples derived were divided into groups with respect to the presence of lymph node metastases (distant spread) and to the depth of invasion (local spread) in relation to the FIGO stage.

Results: Metallothionein immunoreactivity was observed in uterine cervical cancer cells; it was also identified in the fibroblasts and macrophages found within the microenvironments of the tumors of patients suffering from the disease. The MT immunoreactivity level significantly increased within the whole cancer nest in relation to the FIGO stage (intensity of the local spread of the disease). Similarly, the infiltration of MT-positive CAFs and TAMs statistically significantly increased in relation to the FIGO stage.

Conclusion: The level of MT immunoreactivity found in the fibroblasts and macrophages within the tumor microenvironment seems to be indicative of the intensity of the remodeled cervical tumor microenvironment, and this in turn may be related to the local advancement of the disease. Moreover, it appears that the intensity of the metallothionein immunoreactivity in the immunoreactivity profile of the cervical tumor may be linked to both the depth of the local invasion and the extent of the distant advancement of the disease.
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http://dx.doi.org/10.1111/aji.12120DOI Listing
September 2013

Enterocolic lymphocytic phlebitis: an unusual cause of abdominal complaints.

Pol J Pathol 2012 Mar;63(1):75-9

Department of Pathomorphology, Jagiellonian University, Collegium Medicum, Kraków, Poland.

Enterocolic lymphocytic phlebitis (ELP) is a rare disease of unknown etiology involving most often the intramural and mesenteric small and medium-sized veins of the gastrointestinal tract. The diagnosis of the disorder is based on the histopathological examination of a surgical specimen as endoscopically obtained diagnostic material is usually too superficial. Clinical manifestation of ELP most frequently is characterized by acute symptoms, such as acute abdomen, signs suggesting acute appendicitis, gastrointestinal hemorrhage, sometimes it manifests as chronic gastrointestinal complaints. We report, to our knowledge for the first time in Poland, a case of ELP with clinical symptoms pointing to acute appendicitis, on laparoscopy manifesting as a tumorous mass in the colonic wall with an unchanged appendix.
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March 2012

The immunohistochemical analysis of antigens such as RCAS1 and B7H4 in the cervical cancer nest and within the fibroblasts and macrophages infiltrating the cancer microenvironment.

Am J Reprod Immunol 2012 Jul 24;68(1):85-93. Epub 2012 Apr 24.

Department of Pathomorphology, Jagiellonian University, Krakow, Poland.

Introduction: The presence of the aggressive phenotype of the tumor seems to be indicated by the local infiltration of cancer cells and by the development of metastases in the lymph nodes. This phenotype is related to the intensity of the suppressive profile of the tumor microenvironment. The aim of our study has been to gather information about the expression of both RCAS1 and B7H4 proteins in the macrophages and fibroblasts present within both the microenvironment of cervical cancer tumors and the cancer cells present on the front of the cancer nest.

Methods: We analyzed the immunoreactivity levels of such antigens as B7H4 and RCAS1 in the macrophages and fibroblasts of the cancer microenvironment and within the cancer nest in the tissue samples derived from patients on whom both a radical hysterectomy and a lymphadenectomy had been performed following a diagnosis of uterine cervical carcinoma. These patients were then divided into two subgroups according to the extent of the local and distant advancement of the cancer - that is, according to the FIGO stage and the presence or absence of lymph node metastases.

Results: RCAS1 immunoreactivity levels on the front of the cancer nest statistically significantly increase according to the FIGO stage or the extent of the local spread of the disease while B7H4 immunoreactivity levels on the tumor front increase in relation to the extent of the distant spread of the disease or the presence of lymph nodes metastases.

Conclusion: The intensity of the suppressive profile of the cervical cancer microenvironment indicated by the presence of both RCAS1 and B7H4 on the front of the tumor and in the macrophages and fibroblasts infiltrating the cancer stroma seems to correlate with the extent of both the local and distant advancement of the disease.
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http://dx.doi.org/10.1111/j.1600-0897.2012.01134.xDOI Listing
July 2012

Analysis of RCAS1 immunoreactivity within hydatidiform mole cells and decidual cells according to the applied therapeutic strategy: surgery or surgery followed by chemotherapy.

Gynecol Obstet Invest 2012 24;73(2):106-12. Epub 2012 Jan 24.

Departments of Gynecology and Oncology, Lukaszczyk Oncological Center, Bydgoszcz, Poland.

Introduction: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole.

Methods: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure.

Result: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy.

Conclusion: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.
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http://dx.doi.org/10.1159/000328509DOI Listing
August 2012

Ecchordosis physaliphora - a case report and a review of notochord-derived lesions.

Neurol Neurochir Pol 2011 Mar-Apr;45(2):169-73

Department of Pathology, Jagiellonian University Medical College, Krakow.

Some notochord cells remain along the axis of the vertebral column after embryogenesis. These 'notochordal remnants' have some similarities, but their biological behaviour varies considerably. They can give rise to benign lesions such as ecchordosis physaliphora (EP) and 'benign notochordal cell tumour' (BNCT), or aggressive ones like chordoma. We review the problems of the differential diagnosis of notochordal remnants apropos of a case of the incidental autopsy finding of EP in a 78-year-old man, who died due to heart infarction. The 6-mm asymptomatic gelatinous lesion was fixed to the basilar artery on its ventral aspect. Small EPs can be easily overlooked in autopsy. Ecchordosis physaliphora and intradural chordoma share some similarities that may be misleading and may even result in the wrong diagnosis and therapy. The recently reported new entity BNCT poses a similar problem. We review the literature illustrating the most important features of notochord-derived lesions and discuss the relationships between these lesions with regard to molecular genetics.
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http://dx.doi.org/10.1016/s0028-3843(14)60029-3DOI Listing
July 2011

The immunohistochemical analysis of RCAS1, HLA-G, and B7H4-positive macrophages in partial and complete hydatidiform mole in both applied therapeutic surgery and surgery followed by chemotherapy.

Am J Reprod Immunol 2011 Feb;65(2):164-72

Gynecology, Obstetrics and Oncology of the Jagiellonian University, Krakow, Poland.

Introduction: The suppressive microenvironment developing around the implantating ovum in normal pregnant women may correlate with the development in cancer patients of a suppressive microenvironment of neoplasmatic cells derived from trophoblasts, such as occurs in molar lesions. Macrophages are suitable candidates for mediating not only the balance of the maternal defensive immune responses to external antigens, but also a tolerance to tumor cells. The aim of our study has been to gain information about the expression of RCAS1, B7H4, and HLA-G within the macrophages present in the microenvironment of the molar lesion.

Methods: We analyzed the immunoreactivity of such antigens as B7H4, RCAS1, and HLA-G on the macrophages present in tissue samples derived from patients on whom curettage was performed after a diagnosis of molar pregnancy. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure.

Results: We observed a statistically significant increase in the RCAS1-positive macrophage infiltration within the microenvironment of the molar lesions in patients with partial hydatidiform mole in comparison with those patients who exhibited complete hydatidiform mole. There were no such differences, however, in the infiltration of HLA-G- and B7H4-positive macrophages between the two groups of patients. Additionally, we showed that RCAS1- and HLA-G-positive macrophages are more distinct in those cases of complete molar pregnancy where chemotherapy was necessary after surgical treatment while no such differences with respect to B7H4-positive macrophages were observed.

Conclusion: The immune-suppressive endometrial microenvironment represented by suppressive macrophages may have an influence on the clinical course of hydatidiform mole.
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http://dx.doi.org/10.1111/j.1600-0897.2010.00897.xDOI Listing
February 2011

A diagnostically difficult case of chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA effectively treated with imatinib in accelerated phase: case report.

Pol Arch Med Wewn 2009 Dec;119(12):838-41

Department of Hematology and Internal Diseases, Rydygier Hospital, Kraków, Poland.

Chronic myeloid neoplasm with eosinophilia and abnormalities of platelet-derived growth factor receptor alpha (PDGFRA), referred to until 2008 as chronic eosinophilic leukemia, is distinguished from hypereosinophilic syndrome (HES), if accompanied by genetic abnormalities that enable to determine eosinophil clonality. Typically, HES has a benign course and glucocorticosteroids suffice to achieve remission. In chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA the FIP1L1-PDGFRA fusion gene can be detected. Its product is a protein showing tyrosine kinase activity leading to malignant proliferation of eosinophil precursors. Differential diagnosis of HES is often difficult because hypereosinophilia may also be reactive and may occur in many nonhematological as well as hematological disorders. Thus, reverse-transcription polymerase chain reaction (RT-PCR)is indicated in all patients with HES in order to detect the FIP1L1-PDGFRA transcript. Traditional treatment of chronic myeloid neoplasm with cytostatic drugs results in a short-term and transient remission or stabilization of the disease. We present the case of a 52-year-old patient with chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA, in whom acceleration occurred after a year of cytostatic therapy with hydroxyurea and was successfully treated with imatinib. It was impossible to unequivocally determine the type of bone marrow disease based on histologic criteria, and a wide spectrum of molecular tests differentiating the type of myeloid proliferation were necessary to establish the diagnosis. RT-PCR did not reveal BCR-ABL or JAK2 V617F mutation. Further molecular testing showed rearrangement involving the FIP1L1 gene, thus enabling implementation of targeted therapy.
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December 2009