FOXP1 Expression in Normal and Neoplastic Erythroid and Myeloid Cells

FOXP1 protein was firstly analyzed in normal tissues, and afterwards in different tumor tissues, mainly carcinoma and lymphoma. In B-cell malignancies, its role was well explored; its expression was shown to be connected with disease prognosis in certain B-non Hodgkin lymphomas. In this study, 16 bone marrow trephine samples from patients with no hematopoietic malignancies and 10 samples from peripheral blood of healthy individuals were immunostained with anti-FOXP1 antibody. Positive cells in bone marrows were not only lymphocytes, but also cells that are immunohistochemically positive for glycophorin C or myeloperoxidase. Peripheral blood samples showed no other positive cells, but small round lymphocytes. Additionally 60 samples from patients with myeloid lineage neoplasms were analyzed. 25 samples from patients with myelodisplastic syndrome (MDS) and 35 patients with myeloproliferative disease (MPD) were double immunostained with anti-FOXP1/anti-glycophorin C and anti-FOXP1/anti- myeloperoxidase antibodies. FOXP1 was found to be expressed in 22 cases of MDS and in none of MPD cases. Its expression in MDS was observed mostly in myeloperoxidase positive cells in contrast to gylcophorin C positive cells. Only two cases revealed both myeloperoxidase positive cells and gylcophorin C positive cells expressing FOXP1 transcription factor. Our results show that FOXP1 is present in normal cells of erythroid and myeloid linages and thus suggest its possible role in development of all hematopoetic cells as well as possible involvement in neoplasm development of myeloid disorders

Stable gastric pentadecapeptide BPC 157 may counteract myocardial infarction induced by isoprenaline in rats

We revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and centrally, which was described for the first time in isoprenaline- treated rats. BPC 157 (10 ng/kg, 10 µg/kg i.p.), L-NAME (5 mg/kg i.p.), and L-arginine (200 mg/kg i.p.) were given alone or together at (i) 30 min before or, alternatively, (ii) at 5 min after isoprenaline (75 or 150 mg/kg s.c.). At 30 min after isoprenaline 75 mg/kg s.c., we noted an early multiorgan failure (brain, heart, lung, liver, kidney and gastrointestinal lesions), thrombosis, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension, in its full presentation (or attenuated by BPC 157 therapy (given at 5 min after isoprenaline) via activation of the azygos vein). Further, we studied isoprenaline (75 or 150 mg/kg s.c.) myocardial infarction (1 challenge) and reinfarction (isoprenaline at 0 h and 24 h, 2 challenges) in rats (assessed at the end of the subsequent 24 h period). BPC 157 reduced levels of all necrosis markers, CK, CK-MB, LDH, and cTnT, and attenuated gross (no visible infarcted area) and histological damage, ECG (no ST-T ischemic changes), and echocardiography (preservation of systolic left ventricular function) damage induced by isoprenaline. Its effect was associated with a significant decrease in oxidative stress parameters and likely maintained NO system function, providing that BPC 157 interacted with eNOS and COX2 gene expression in a particular way and counteracted the noxious effect of the NOS- blocker, L-NAME

Izraženost glipikana-3, beta-katenina i CD34 u hepatocelularnom karcinomu bolesnika s transplantiranom jetrom [Expression of glypican-3, beta-catenin and CD34 in hepatocellular carcinoma in patients with orthotopic liver transplantation]

The aim of the study was to determine morphological features of HCC, clinical and laboratory data and characteristics of immunohistochemical expression of glipican-3 (GPC3), beta - catenin and CD34 in HCC, their mutual association and prognostic value, with special regard to those patient groups meeting and those exceeding milan criteria. 71 patients with primary HCC have undergone liver transplantation. Pathological tumor characteristics - number and size of tumors, architectural pattern, histological type, differentiation grade, and macro and microvascular invasion were analyzed. 30 patients meeting and 41 exceeding milan criteria. Vascular invasion was present in 14 patients. Cytoplasmatic GPC3 positivity was observed in 67.60% cases of HCC. Membrane beta-catenin was expressed in all cases of HCCs. The strong expression of CD34 was observed in all cases of HCCs. There was no significant difference between group meeting and exceeding milan criteria according to expression's characteristics of GPC3, beta-catenin and CD34. There was no difference in survival rate and recurrence between patient groups meeting and exceeding milan criteria. Vascular invasion was more frequently observed in patients group with shorter period of recurrence. Membranous, strong intensity of beta-catenin was more frequently observed in patients group with longer survival rate

Expression of glypican-3, beta-catenin and CD34 in hepatocellular carcinoma in patients with orthotopic liver transplantation

Cilj istraživanja je bio odrediti morfološke karakteristike hepatocelularnog karcinoma (HCK-a), kliničke i laboratorijske pokazatelje i imunohistokemijske karakteristike izraženosti glipikana-3 (GPC3), beta-katenina i CD34 u HCK-u, njihovu međusobnu povezanost te utjecaj na ishod bolesnika unutar i izvan milanskih kriterija. 71 bolesnik sa primarnim HCK-om, liječen je transplantacijom jetre. Analizirane su morfološke karakteristike tumora - broj i veličina, arhitekturalni tip rasta, histološki tip, stupanj diferencijacije, prisutnost makro i mikrožilne invazije. 30 bolesnika je bilo unutar milanskih kriterija i 41 bolesnik izvan milanskih kriterija. Kod 14 bolesnika je bila prisutna žilna invazija tumora. Pozitivna izraženost GPC3 je bila prisutna u 67.60% slučajeva HCK-a, citoplazmatske lokalizacije. Pozitivna izraženost beta-katenina bila je prisutna u svim HCK-a, membranske lokalizacije. Izraženost CD34 u svim slučajevima bila je jakog intenziteta. Karakteristike izraženosti biljega GPC3, beta-katenina i CD34 ne razlikuju se u skupinama bolesnika određenih milanskim kriterijima. Analizirane skupine bolesnika određene milanskim kriterijima nisu se razlikovale ukupnim preživljenjem, niti vremenom do ponovne pojave bolesti. Žilna invazija bila je značajno češće prisutna u skupini bolesnika s kraćim vremenom do ponovne pojave bolesti. Jaki intenzitet izraženosti beta-katenina bio je značajno češće prisutan u skupini bolesnika dužeg ukupnog preživljenja.The aim of the study was to determine morphological features of HCC, clinical and laboratory data and characteristics of immunohistochemical expression of glipican-3 (GPC3), beta - catenin and CD34 in HCC, their mutual association and prognostic value, with special regard to those patient groups meeting and those exceeding milan criteria. 71 patients with primary HCC have undergone liver transplantation. Pathological tumor characteristics - number and size of tumors, architectural pattern, histological type, differentiation grade, and macro and microvascular invasion were analyzed. 30 patients meeting and 41 exceeding milan criteria. Vascular invasion was present in 14 patients. Cytoplasmatic GPC3 positivity was observed in 67.60% cases of HCC. Membrane beta-catenin was expressed in all cases of HCCs. The strong expression of CD34 was observed in all cases of HCCs. There was no significant difference between group meeting and exceeding milan criteria according to expression's characteristics of GPC3, beta-catenin and CD34. There was no difference in survival rate and recurrence between patient groups meeting and exceeding milan criteria. Vascular invasion was more frequently observed in patients group with shorter period of recurrence. Membranous, strong intensity of beta-catenin was more frequently observed in patients group with longer survival rate

Expression of glypican-3, beta-catenin and CD34 in hepatocellular carcinoma in patients with orthotopic liver transplantation

Cilj istraživanja je bio odrediti morfološke karakteristike hepatocelularnog karcinoma (HCK-a), kliničke i laboratorijske pokazatelje i imunohistokemijske karakteristike izraženosti glipikana-3 (GPC3), beta-katenina i CD34 u HCK-u, njihovu međusobnu povezanost te utjecaj na ishod bolesnika unutar i izvan milanskih kriterija. 71 bolesnik sa primarnim HCK-om, liječen je transplantacijom jetre. Analizirane su morfološke karakteristike tumora - broj i veličina, arhitekturalni tip rasta, histološki tip, stupanj diferencijacije, prisutnost makro i mikrožilne invazije. 30 bolesnika je bilo unutar milanskih kriterija i 41 bolesnik izvan milanskih kriterija. Kod 14 bolesnika je bila prisutna žilna invazija tumora. Pozitivna izraženost GPC3 je bila prisutna u 67.60% slučajeva HCK-a, citoplazmatske lokalizacije. Pozitivna izraženost beta-katenina bila je prisutna u svim HCK-a, membranske lokalizacije. Izraženost CD34 u svim slučajevima bila je jakog intenziteta. Karakteristike izraženosti biljega GPC3, beta-katenina i CD34 ne razlikuju se u skupinama bolesnika određenih milanskim kriterijima. Analizirane skupine bolesnika određene milanskim kriterijima nisu se razlikovale ukupnim preživljenjem, niti vremenom do ponovne pojave bolesti. Žilna invazija bila je značajno češće prisutna u skupini bolesnika s kraćim vremenom do ponovne pojave bolesti. Jaki intenzitet izraženosti beta-katenina bio je značajno češće prisutan u skupini bolesnika dužeg ukupnog preživljenja.The aim of the study was to determine morphological features of HCC, clinical and laboratory data and characteristics of immunohistochemical expression of glipican-3 (GPC3), beta - catenin and CD34 in HCC, their mutual association and prognostic value, with special regard to those patient groups meeting and those exceeding milan criteria. 71 patients with primary HCC have undergone liver transplantation. Pathological tumor characteristics - number and size of tumors, architectural pattern, histological type, differentiation grade, and macro and microvascular invasion were analyzed. 30 patients meeting and 41 exceeding milan criteria. Vascular invasion was present in 14 patients. Cytoplasmatic GPC3 positivity was observed in 67.60% cases of HCC. Membrane beta-catenin was expressed in all cases of HCCs. The strong expression of CD34 was observed in all cases of HCCs. There was no significant difference between group meeting and exceeding milan criteria according to expression's characteristics of GPC3, beta-catenin and CD34. There was no difference in survival rate and recurrence between patient groups meeting and exceeding milan criteria. Vascular invasion was more frequently observed in patients group with shorter period of recurrence. Membranous, strong intensity of beta-catenin was more frequently observed in patients group with longer survival rate

Expression of glypican-3, beta-catenin and CD34 in hepatocellular carcinoma in patients with orthotopic liver transplantation

Cilj istraživanja je bio odrediti morfološke karakteristike hepatocelularnog karcinoma (HCK-a), kliničke i laboratorijske pokazatelje i imunohistokemijske karakteristike izraženosti glipikana-3 (GPC3), beta-katenina i CD34 u HCK-u, njihovu međusobnu povezanost te utjecaj na ishod bolesnika unutar i izvan milanskih kriterija. 71 bolesnik sa primarnim HCK-om, liječen je transplantacijom jetre. Analizirane su morfološke karakteristike tumora - broj i veličina, arhitekturalni tip rasta, histološki tip, stupanj diferencijacije, prisutnost makro i mikrožilne invazije. 30 bolesnika je bilo unutar milanskih kriterija i 41 bolesnik izvan milanskih kriterija. Kod 14 bolesnika je bila prisutna žilna invazija tumora. Pozitivna izraženost GPC3 je bila prisutna u 67.60% slučajeva HCK-a, citoplazmatske lokalizacije. Pozitivna izraženost beta-katenina bila je prisutna u svim HCK-a, membranske lokalizacije. Izraženost CD34 u svim slučajevima bila je jakog intenziteta. Karakteristike izraženosti biljega GPC3, beta-katenina i CD34 ne razlikuju se u skupinama bolesnika određenih milanskim kriterijima. Analizirane skupine bolesnika određene milanskim kriterijima nisu se razlikovale ukupnim preživljenjem, niti vremenom do ponovne pojave bolesti. Žilna invazija bila je značajno češće prisutna u skupini bolesnika s kraćim vremenom do ponovne pojave bolesti. Jaki intenzitet izraženosti beta-katenina bio je značajno češće prisutan u skupini bolesnika dužeg ukupnog preživljenja.The aim of the study was to determine morphological features of HCC, clinical and laboratory data and characteristics of immunohistochemical expression of glipican-3 (GPC3), beta - catenin and CD34 in HCC, their mutual association and prognostic value, with special regard to those patient groups meeting and those exceeding milan criteria. 71 patients with primary HCC have undergone liver transplantation. Pathological tumor characteristics - number and size of tumors, architectural pattern, histological type, differentiation grade, and macro and microvascular invasion were analyzed. 30 patients meeting and 41 exceeding milan criteria. Vascular invasion was present in 14 patients. Cytoplasmatic GPC3 positivity was observed in 67.60% cases of HCC. Membrane beta-catenin was expressed in all cases of HCCs. The strong expression of CD34 was observed in all cases of HCCs. There was no significant difference between group meeting and exceeding milan criteria according to expression's characteristics of GPC3, beta-catenin and CD34. There was no difference in survival rate and recurrence between patient groups meeting and exceeding milan criteria. Vascular invasion was more frequently observed in patients group with shorter period of recurrence. Membranous, strong intensity of beta-catenin was more frequently observed in patients group with longer survival rate

FOXP1 expression in normal and neoplastic erythroid and myeloid cells [Ekspresija FOXP1 u normalnim i neoplastičnim stanicama ertroidne i mijeloidne loze]

FOXP1 protein was firstly analyzed in normal tissues, and afterwards in different tumor tissues, mainly carcinoma and lymphoma. In B-cell malignancies, its role was well explored; its expression was shown to be connected with disease prognosis in certain B-non Hodgkin lymphomas. In this study, 16 bone marrow trephine samples from patients with no hematopoietic malignancies and 10 samples from peripheral blood of healthy individuals were immunostained with anti-FOXP1 antibody. Positive cells in bone marrows were not only lymphocytes, but also cells that are immunohistochemically positive for glycophorin C or myeloperoxidase. Peripheral blood samples showed no other positive cells, but small round lymphocytes. Additionally 60 samples from patients with myeloid lineage neoplasms were analyzed. 25 samples from patients with myelodysplastic syndrome (MDS) and 35 patients with myeloproliferative disease (MPD) were double immunostained with anti-FOXP1/anti-glycophorin C and anti-FOXP1/anti-myeloperoxidase antibodies. FOXP1 was found to be expressed in 22 cases of MDS and in none of MPD cases. Its expression in MDS was observed mostly in myeloperoxidase positive cells in contrast to gylcophorin C positive cells. Only two cases revealed both myeloperoxidase positive cells and gylcophorin C positive cells expressing FOXP1 transcription factor. Our results show that FOXP1 is present in normal cells of erythroid and myeloid linages and thus suggest its possible role in development of all hematopoetic cells as well as possible involvement in neoplasm development of myeloid disorders

Ekspresija FOXP1 u normalnim i neoplastičnim stanicama ertroidne i mijeloidne loze

FOXP1 protein was firstly analyzed in normal tissues, and afterwards in different tumor tissues, mainly carcinoma and lymphoma. In B-cell malignancies, its role was well explored; its expression was shown to be connected with disease prognosis in certain B-non Hodgkin lymphomas. In this study, 16 bone marrow trephine samples from patients with no hematopoietic malignancies and 10 samples from peripheral blood of healthy individuals were immunostained with anti-FOXP1 antibody. Positive cells in bone marrows were not only lymphocytes, but also cells that are immunohistochemically positive for glycophorin C or myeloperoxidase. Peripheral blood samples showed no other positive cells, but small round lymphocytes. Additionally 60 samples from patients with myeloid lineage neoplasms were analyzed. 25 samples from patients with myelodysplastic syndrome (MDS) and 35 patients with myeloproliferative disease (MPD) were double immunostained with anti-FOXP1/anti-glycophorin C and anti-FOXP1/anti-myeloperoxidase antibodies. FOXP1 was found to be expressed in 22 cases of MDS and in none of MPD cases. Its expression in MDS was observed mostly in myeloperoxidase positive cells in contrast to gylcophorin C positive cells. Only two cases revealed both myeloperoxidase positive cells and gylcophorin C positive cells expressing FOXP1 transcription factor. Our results show that FOXP1 is present in normal cells of erythroid and myeloid linages and thus suggest its possible role in development of all hematopoetic cells as well as possible involvement in neoplasm development of myeloid disorders.Protein FOXP1 prvo je bio istraživan u normalnom tkivu i različitim tumorskim tkivima, najviše karcinomima i limfomima. Njegova je uloga u B-staničnim neoplazmama dobro istražena, a dokazano je i da je njegova ekspresija u pojedinim B ne-Hodgkinovim limfomima vezana za prognozu. U ovom istraživanju 16 uzoraka biopsija koštanih srži uklopljenih u parafin pacijanata bez hematoloških bolesti i 10 uzoraka razmaza periferne krvi zdravih ispitanika, imunohistokemijski su obojeni anti-FOXP1 antitijelom. Pozitivne stanice u koštanim sržima nisu bili samo limfociti, već i stanice koje su imunohistokemijski pozitivne i na glikoforin C ili mijeloperoksidazu. Uzorci razmaza periferne krvi nisu pokazivali druge pozitivne stanice osim malih, okruglih limfocita. Dodatno je analizirano 60 uzoraka koštanih srži pacijenata s neoplazmama mijeloidne linije. 25 uzoraka bilo je od pacijenata s mijelodisplastičnim sindromom (MDS), a 35 s mijeloproliferativnom bolesti (MPD). Svi su uzorci obojeni dvostrukim imunohistokemijskim bojenjem korištenjem anti-FOXP1/anti-glikoforin C i anti-FOXP1/anti-mijeloperoksidaza antitijela. FOXP1 nađen je u neoplastičnim stanicama 22 uzorka MDS-a, dok tumorske stanice MPD-a nisu pokazivale njegovu ekspresiju. Neoplastične MDS stanice koje eksprimiraju FOXP1 većinom su bile pozitivne i na mijeoperoksidazu. Samo su dva uzorka pokazala ekspresiju FOXP1 proteina i u stanicama pozitivnim na glikoforin C i u stanicama pozitivnim na mijeloperoksidazu. Ovakvi rezultati pokazuju prisutnost FOXP1 proteina u normalnim razvojnim stadijima eritroidne i mijeloidne loze i ukazuju na mogućnost da je on potreban za razvoj svih hematopoetskih stanica. Isto tako ukazuju na mogućnost da FOXP1 ima ulogu u razvoju mijeloidnih neoplazmi

Ekspresija FOXP1 u normalnim i neoplastičnim stanicama ertroidne i mijeloidne loze

FOXP1 protein was firstly analyzed in normal tissues, and afterwards in different tumor tissues, mainly carcinoma and lymphoma. In B-cell malignancies, its role was well explored; its expression was shown to be connected with disease prognosis in certain B-non Hodgkin lymphomas. In this study, 16 bone marrow trephine samples from patients with no hematopoietic malignancies and 10 samples from peripheral blood of healthy individuals were immunostained with anti-FOXP1 antibody. Positive cells in bone marrows were not only lymphocytes, but also cells that are immunohistochemically positive for glycophorin C or myeloperoxidase. Peripheral blood samples showed no other positive cells, but small round lymphocytes. Additionally 60 samples from patients with myeloid lineage neoplasms were analyzed. 25 samples from patients with myelodysplastic syndrome (MDS) and 35 patients with myeloproliferative disease (MPD) were double immunostained with anti-FOXP1/anti-glycophorin C and anti-FOXP1/anti-myeloperoxidase antibodies. FOXP1 was found to be expressed in 22 cases of MDS and in none of MPD cases. Its expression in MDS was observed mostly in myeloperoxidase positive cells in contrast to gylcophorin C positive cells. Only two cases revealed both myeloperoxidase positive cells and gylcophorin C positive cells expressing FOXP1 transcription factor. Our results show that FOXP1 is present in normal cells of erythroid and myeloid linages and thus suggest its possible role in development of all hematopoetic cells as well as possible involvement in neoplasm development of myeloid disorders.Protein FOXP1 prvo je bio istraživan u normalnom tkivu i različitim tumorskim tkivima, najviše karcinomima i limfomima. Njegova je uloga u B-staničnim neoplazmama dobro istražena, a dokazano je i da je njegova ekspresija u pojedinim B ne-Hodgkinovim limfomima vezana za prognozu. U ovom istraživanju 16 uzoraka biopsija koštanih srži uklopljenih u parafin pacijanata bez hematoloških bolesti i 10 uzoraka razmaza periferne krvi zdravih ispitanika, imunohistokemijski su obojeni anti-FOXP1 antitijelom. Pozitivne stanice u koštanim sržima nisu bili samo limfociti, već i stanice koje su imunohistokemijski pozitivne i na glikoforin C ili mijeloperoksidazu. Uzorci razmaza periferne krvi nisu pokazivali druge pozitivne stanice osim malih, okruglih limfocita. Dodatno je analizirano 60 uzoraka koštanih srži pacijenata s neoplazmama mijeloidne linije. 25 uzoraka bilo je od pacijenata s mijelodisplastičnim sindromom (MDS), a 35 s mijeloproliferativnom bolesti (MPD). Svi su uzorci obojeni dvostrukim imunohistokemijskim bojenjem korištenjem anti-FOXP1/anti-glikoforin C i anti-FOXP1/anti-mijeloperoksidaza antitijela. FOXP1 nađen je u neoplastičnim stanicama 22 uzorka MDS-a, dok tumorske stanice MPD-a nisu pokazivale njegovu ekspresiju. Neoplastične MDS stanice koje eksprimiraju FOXP1 većinom su bile pozitivne i na mijeoperoksidazu. Samo su dva uzorka pokazala ekspresiju FOXP1 proteina i u stanicama pozitivnim na glikoforin C i u stanicama pozitivnim na mijeloperoksidazu. Ovakvi rezultati pokazuju prisutnost FOXP1 proteina u normalnim razvojnim stadijima eritroidne i mijeloidne loze i ukazuju na mogućnost da je on potreban za razvoj svih hematopoetskih stanica. Isto tako ukazuju na mogućnost da FOXP1 ima ulogu u razvoju mijeloidnih neoplazmi