scholarly journals Immunoexpression of DNA fragmentation factor 40, DNA fragmentation factor 45, and B-cell lymphoma 2 protein in normal human endometrium and uterine myometrium depends on menstrual cycle phase and menopausal status

2018 ◽  
Vol 14 (6) ◽  
pp. 1254-1262 ◽  
Author(s):  
Tomasz Banas ◽  
Kazimierz Pitynski ◽  
Krzysztof Okon ◽  
Marcin Mikos ◽  
Aleksandra I. Czerw ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
B Cell ◽  
Dna Fragmentation ◽  
Cell Lymphoma ◽  
Menopausal Status ◽  
B Cell Lymphoma ◽  
Human Endometrium ◽  
Cycle Phase ◽  
Menstrual Cycle Phase ◽  
Normal Human

scholarly journals The Normal Human Endometrium but not Myometrium Presents Menstrual Cycle-Dependent Fluctuations in the Immunoexpression of DNA Fragmentation Factor 40, DNA Fragmentation Factor 45, and B-cell Lymphoma 2 Protein.

2017 ◽  
Author(s):  
Tomasz Banas ◽  
Kazimierz Pitynski ◽  
Krzysztof Okon ◽  
Marcin Mikos ◽  
Joanna Bonior ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
B Cell ◽  
Dna Fragmentation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Human Endometrium ◽  
Proliferative Endometrium ◽  
Normal Human ◽  
Cycle Dependent ◽  
Secretory Endometrium

Abstract: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.

203 PLASMA MEMBRANE Ca2+-PUMPING ATPase 1 IS ABUNDANTLY EXPRESSED AND DISTINCTLY REGULATED BY ESTROGEN IN HUMAN ENDOMETRIUM DURING THE MENSTRUAL CYCLE

2011 ◽  
Vol 23 (1) ◽  
pp. 201
Author(s):  
H. Yang ◽  
E.-B. Jeung
Keyword(s):  
Plasma Membrane ◽  
Menstrual Cycle ◽  
Critical Role ◽  
Human Endometrium ◽  
Cycle Phase ◽  
Menstrual Phase ◽  
Menstrual Cycle Phase ◽  
Secretory Phase ◽  
Total N ◽  
High Level

Plasma membrane Ca2+-pumping ATPases (PMCA) play a critical role in maintaining cellular Ca2+ homeostasis. The PMCA mRNA are encoded on 4 genes, designated PMCA1 to PMCA4. In a previous study, we found that both PMCA1 and PMCA4 are expressed at similar levels in astrocytes and in neurons. Although PMCA1b is expressed in the uterus of rats during the oestrous cycle, the expression of PMCA1 and its potential roles has not been elucidated during the menstrual cycle in the human endometrium. Thus, in the current study, the expression pattern of PMCA1 was examined to predict its roles in the human endometrium during the menstrual cycle. Human uterine tissues (total n = 40) were separated into 3 groups according to menstrual cycle phase: menstrual phase, proliferative phase (early, mid, late), and secretory phase (early, mid, late). Using real-time PCR and Western blot analysis, uterine expression of PMCA1 mRNA and protein increased to 1.5-fold in the early-, mid- and late-proliferative phases in the endometrium of the human uterus, compared with other menstrual phases. In addition, uterine PMCA1 was abundantly localised in the cytoplasm of the luminal and glandular epithelial cells in the menstrual phases, indicating that this protein may participate in the uterine Ca balance of the human endometrium during the menstrual cycle. Taken together, these results suggest that a high level of uterine PMCA1 expression may be involved in reproductive functions during the menstrual cycle of humans.

Pre-Clinical Evaluation of a Novel DNA Crosslinking Agent, Bo-1055 in B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5483-5483 ◽  
Author(s):  
Eloisi Caldas Lopes ◽  
Fabian Correa ◽  
Elizabeth Peguero ◽  
Srikanth R. Ambati ◽  
Jae Hung Shieh ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Crosslinking Agent ◽  
B Cell Lymphoma ◽  
Water Soluble ◽  
Therapeutic Window ◽  
Hematopoietic Stem ◽  
Normal Human

Abstract Some B-cell lymphoma including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) remain incurable using conventional chemotherapeutic approaches. Therefore it is important that new treatment strategies be developed. We have evaluated the efficacy of a number of novel, third generation, DNA-directed alkylating agents that have DNA specific binding domain by linking DNA-affinic molecules to N-mustard pharmacophore via a urea, carbamate or hydrazinecarboxamide linker (Kapuriya et al. Bioorganic & Medicinal Chem. 19:471–485; 2011). One of these, the water-soluble ureidomustine BO-1055, was screened for toxicity against a panel of human lymphoma cell lines including MCL (JEKO-1, Z-138, HBL-2), DLBCL (OCILy10, OCILy19) and a spontaneous murine B-cell lymphoma. We also screened BO1055 against a panel of normal human cells including mesenchymal stromal cells (IC50 >10uM), bone marrow-derived endothelium (IC50 >10uM) lung basal epithelium, bronchial epithelium and myofibroblasts (IC50s >10uM) and purified cord blood CD34+ cells in suspension culture or colony-forming assay (for hematopoietic progenitor cells) (IC50 >10uM) and in cobblestone area-forming assay (for hematopoietic stem cells) (IC50 9.1uM). The mean IC50±SD (uM) in MCL cell lines was JEKO-1 (0.266±0.27), Z-138 (0.182±0.15), HBL2 (0.161±0.34), In DLBCL lines OCILy10 (0.117±0.21), OCILy19 (0.287±0.17) and murine B-cell lymphoma (0.463±0.39). Our results indicated that BO-1055 has a significant therapeutic window (50-100-fold) between its toxicity against human B-cell lymphomas compared to various normal human cell types. We evaluated BO-1055 cardiotoxicity in the HL-1 cardiomyocyte line and observed a 227-fold less cytotoxicity compared to Doxorubicin. Treatment with BO-1055 resulted in accumulation of cells in S-phase and up-regulation of proteins involved in DNA repair [MRE11, p-P95/NBS1 (ser343), RAD50, p-ATR (ser428)] while Bcl-6, an important B-cell lymphoma biomarker, was down-regulated. Xenograft experiments in NSG mice bearing JEKO-1 GFP/luciferase+ tumors treated with BO-1055 (30mg/kg) 3x/week showed complete tumor remission after 2 weeks of treatment as monitored by luciferase image. Our results suggest that BO-1055 has potent activity against B-cell lymphoma and present a strong rationale for its further therapeutic development as an alkylating agent due to his low toxicity against normal tissue and high toxicity against hematopoietic tumors. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ki-B5: a monoclonal antibody unrelated to CD45 recognizes normal and neoplastic human B cells in routine paraffin sections

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 809-817 ◽  
Author(s):  
ML Hansmann ◽  
HH Wacker ◽  
J Gralla ◽  
H Lumbeck ◽  
M Kossmahl ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Protein Fractions ◽  
Paraffin Sections ◽  
Human B Cells ◽  
Normal Human

In the search for immunoreagents appropriate for the histopathologic diagnosis of malignant B-cell lymphomas in routinely processed paraffin sections, a new monoclonal antibody, Ki-B5, was generated using a high- grade B-cell lymphoma as the immunogene. Ki-B5 is a mouse IgG1/kappa that recognizes five protein fractions of about 84, 82, 55, 48, and 27 Kd after biosynthetic radiolabeling and immunoprecipitation. Protein fractions with the molecular weights of approximately 84 and 82 Kd were expressed on the cell surface and show that Ki-B5 is probably unrelated to CD45. It was possible through electron microscopy to visualize the membrane-bound portion of Ki-B5. Extensive immunohistologic studies on normal human tissue and various neoplasias demonstrated the high specificity of Ki-B5 to normal human B cells and a minor subgroup of plasma cells. Except for ML-2, which is a myelomonocytic human cell line, Ki-B5 exclusively recognized the B-cell lineage, including EB-3, BALL-1, and NALM-1. All carcinomas, sarcomas, and malignant melanomas tested with Ki-B5 were negative. Although normal granulocytes and monocytes were constantly negative, three of eight myelomonocytic leukemias coreacted with this antibody. Eight of the 57 T-cell lymphomas studied were positive to Ki-B5. Five were classified as lymphoblastic, two represented T8-CLL, and one was classified as immunoblastic T-cell lymphoma. Only 3 of 126 cases of B-cell lymphoma, including rare types not considered in the current classifications, were negative to Ki-B5. Plasmacytomas were also negative, except for one case. Irrespective of the cases of lymphoblastic lymphoma and plasmacytoma, Ki-B5 represents a new monoclonal antibody appropriate for the diagnosis and immunophenotyping of malignant lymphomas in routinely processed paraffin sections.

scholarly journals DNA fragmentation factors 40 and 45 (DFF40/DFF45) and B-cell lymphoma 2 (Bcl-2) protein are underexpressed in uterine leiomyosarcomas and may predict survival

2017 ◽  
Vol Volume 10 ◽  
pp. 4579-4589 ◽  
Author(s):  
Tomasz Banas ◽  
Kazimierz Pitynski ◽  
Krzysztof Okon ◽  
Aleksandra Czerw
Keyword(s):  
B Cell ◽  
Dna Fragmentation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma

scholarly journals Ki-B5: a monoclonal antibody unrelated to CD45 recognizes normal and neoplastic human B cells in routine paraffin sections

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 809-817 ◽  
Author(s):  
ML Hansmann ◽  
HH Wacker ◽  
J Gralla ◽  
H Lumbeck ◽  
M Kossmahl ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Protein Fractions ◽  
Paraffin Sections ◽  
Human B Cells ◽  
Normal Human

Abstract In the search for immunoreagents appropriate for the histopathologic diagnosis of malignant B-cell lymphomas in routinely processed paraffin sections, a new monoclonal antibody, Ki-B5, was generated using a high- grade B-cell lymphoma as the immunogene. Ki-B5 is a mouse IgG1/kappa that recognizes five protein fractions of about 84, 82, 55, 48, and 27 Kd after biosynthetic radiolabeling and immunoprecipitation. Protein fractions with the molecular weights of approximately 84 and 82 Kd were expressed on the cell surface and show that Ki-B5 is probably unrelated to CD45. It was possible through electron microscopy to visualize the membrane-bound portion of Ki-B5. Extensive immunohistologic studies on normal human tissue and various neoplasias demonstrated the high specificity of Ki-B5 to normal human B cells and a minor subgroup of plasma cells. Except for ML-2, which is a myelomonocytic human cell line, Ki-B5 exclusively recognized the B-cell lineage, including EB-3, BALL-1, and NALM-1. All carcinomas, sarcomas, and malignant melanomas tested with Ki-B5 were negative. Although normal granulocytes and monocytes were constantly negative, three of eight myelomonocytic leukemias coreacted with this antibody. Eight of the 57 T-cell lymphomas studied were positive to Ki-B5. Five were classified as lymphoblastic, two represented T8-CLL, and one was classified as immunoblastic T-cell lymphoma. Only 3 of 126 cases of B-cell lymphoma, including rare types not considered in the current classifications, were negative to Ki-B5. Plasmacytomas were also negative, except for one case. Irrespective of the cases of lymphoblastic lymphoma and plasmacytoma, Ki-B5 represents a new monoclonal antibody appropriate for the diagnosis and immunophenotyping of malignant lymphomas in routinely processed paraffin sections.

Novel Alkylating Agent, Ureidomustine Exhibit Pre-Clinical Efficacy in B-Cell Lymphoma with Minimal Dose-Limiting Myelotoxicity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1556-1556 ◽  
Author(s):  
Eloisi Caldas Lopes ◽  
Shieh Jae-Hung ◽  
Srikanth Ambati ◽  
Su Tsann-Long ◽  
Fabian Correa ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
S Phase ◽  
Water Soluble ◽  
Lymphoma Cell ◽  
Therapeutic Window ◽  
B Cell Lymphomas ◽  
Normal Human

Abstract Many patients with B-cell lymphomas, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL), are not cured by conventional chemo-immunotherapy. One reason for this is because these drugs, while effective, are limited by their narrow therapeutic window and significant toxicities. B-cell lymphomas are highly dependent on DNA damage checkpoints, and hence are biologically responsive to drugs that trigger these checkpoints. Hence, In order to identify superior DNA damaging anti-lymphoma drugs we evaluated a series of novel, third generation, DNA-directed alkylating agents that have DNA specific binding domains chemically linked via urea, carbamate or hydrazinecarboxamide to N-mustard pharmacophores. The chemically favorable water-soluble ureidomustine (BO-1055) was evaluated for activity against 23 human lymphoma cell lines including MCL, DLBCL (GCB and ABC subtype) and a spontaneous murine B-cell lymphoma. Fifty % of these MCL and DLBCL cell lines exhibited BO-1055 IC50 values in the nanomolar range including even markedly chemo-resistant cell lines as OCI-Ly10 (IC50 0.117μM ±0.21). In marked contrast, against normal human tissues (lung fibroblast IMR90, kidney fibroblast CV1, mesenchymal stromal, bronchial epithelium, myofibroblast, bone marrow-derived endothelium) and hematopoietic cells (cord blood CD34+ cells, colony-forming assay for hematopoietic progenitors) and in cobblestone area-forming assay for hematopoietic stem cells, BO-1055 IC50s were > 10μM. Hence BO-1055 has a significant therapeutic window (50-100-fold) between its toxicity against B-cell lymphomas compared to normal human cells. We evaluated BO-1055 cardiotoxicity in the HL-1 cardiomyocyte line and observed a 227-fold less cytotoxicity compared to Doxorubicin. Drug combination studies with BO-1055 and an Hsp90 inhibitor (PU-H71), an Hsp70 inhibitor (TT46), doxorubicin and bortezomib (Velcade) demonstrated synergistic effects based on Compusyn analysis with very low combination indices in 50% of lymphoma cell lines. The synergistic effect was not observed in normal cells. Notably, BO-1055 caused downregulation of the critical lymphoma oncoproteins MYC and BCL6, but not Bcl2. BCL6 normally suppresses the ATR-driven S-phase checkpoint. Accordingly treatment with BO-1055 resulted in accumulation of cells in S-phase and up-regulation of proteins involved in DNA repair and intra-S-phase checkpoints [MRE11, p-P95/NBS1 (ser343), RAD50, p-ATR (ser428)]. Finally, xenograft experiments in NSG mice bearing MCL JEKO1 GFP/luciferase+ tumors treated with BO-1055 (30mg/kg) 3x/week showed complete tumor remission after 2 weeks of treatment as monitored by luminescent imaging. In summary, BO-1055 is emerging as a potent therapeutic agent for B-cell lymphomas, with little toxicity against normal tissues and hence potentially wider therapeutic window than current lymphoma drugs. Disclosures Caldas Lopes: BOtique Biopharm: Employment.

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