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

Gastric pentadecapeptide BPC 157 in cytoprotection to resolve major vessel occlusion disturbances, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes. Summarized are all these arguments, in the Robert's cytoprotection concept, to substantiate the resolution of different major vessel occlusion disturbances, in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome, which was obtained by BPC 157 therapy. Conceptually, there is a new point, namely, endothelium maintenance to epithelium maintenance (the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow or bypass the occluded or ruptured vessel). In this paper, we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157, which is stable in the human gastric juice, is a membrane stabilizer and counteracts gut-leaky syndrome. As a particular target, it is distinctive from the standard peptide growth factors, involving particular molecular pathways and controlling VEGF and NO pathways. In the early 1990s, BPC 157 appeared as a late outbreak of the Robert's and Szabo's cytoprotection-organoprotection concept, like the previous theoretical/practical breakthrough in the 1980s and the brain-gut axis and gut-brain axis. As the time went on, with its reported effects, it is likely most useful theory practical implementation and justification. Meantime, several reviews suggest that BPC 157, which does not have a lethal dose, has profound cytoprotective activity, used to be demonstrated in ulcerative colitis and multiple sclerosis trials. Likely, it may bring the theory to practical application, starting with the initial argument, no degradation in human gastric juice for more than 24 h, and thereby, the therapeutic effectiveness (including via a therapeutic per-oral regimen) and pleiotropic beneficial effects

Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy

Recently, marked therapeutic effects pertaining to the recovery of injured rat spinal cords (1 min compression injury of the sacrocaudal spinal cord (S2-Co1) resulting in tail paralysis) appeared after a single intraperitoneal administration of the stable gastric pentadecapeptide BPC 157 at 10 min post-injury. Besides the demonstrated rapid and sustained recovery (1 year), we showed the particular points of the immediate effect of the BPC 157 therapy that began rapidly after its administration, (i) soon after injury (10 min), or (ii) later (4 days), in the rats with a definitive spinal cord injury. Specifically, in counteracting spinal cord hematoma and swelling, (i) in rats that had undergone acute spinal cord injury, followed by intraperitoneal BPC 157 application at 10 min, we focused on the first 10–30 min post-injury period (assessment of gross, microscopic, and gene expression changes). Taking day 4 post-injury as the definitive injury, (ii) we focused on the immediate effects after the BPC 157 intragastric application over 20 min of the post-therapy period. Comparable long-time recovery was noted in treated rats which had definitive tail paralysis: (iii) the therapy was continuously given per orally in drinking water, beginning at day 4 after injury and lasting one month after injury. BPC 157 rats presented only discrete edema and minimal hemorrhage and increased Nos1, Nos2, and Nos3 values (30 min post-injury, (i)) or only mild hemorrhage, and only discrete vacuolation of tissue (day 4, (ii)). In the day 4–30 post-injury study (iii), BPC 157 rats rapidly presented tail function recovery, and no demyelination process (Luxol fast blue staining)