- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Viral-associated cancers and disorders
- Click Chemistry and Applications
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Cancer-related gene regulation
- 14-3-3 protein interactions
- Cancer Treatment and Pharmacology
- Sarcoma Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- Immune Cell Function and Interaction
- Apelin-related biomedical research
- Kruppel-like factors research
- HIV/AIDS drug development and treatment
- Hemoglobinopathies and Related Disorders
- Biochemical and Molecular Research
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Adenosine and Purinergic Signaling
- Hematopoietic Stem Cell Transplantation
University of Botswana
2025
Charles University
2012-2018
To investigate the roles of BCL2, MCL1, and BCL-XL in survival diffuse large B-cell lymphoma (DLBCL).Immunohistochemical analysis 105 primary DLBCL samples, Western blot 18 cell lines for expression BCL-XL. Pharmacologic targeting with ABT-199, homoharringtonine (HHT), ABT-737. Analysis clones manipulated expressions Immunoprecipitation MCL1 complexes selected lines. Experimental therapy aimed at inhibition BCL2 using ABT-199 HHT, single agent, or combination, vitro vivo on cell-based murine...
Abstract The global burden of cervical cancer is highest in low- and middle-income countries (LMICs). Women living with HIV infection are particularly impacted by despite availability adherence to antiretroviral therapy (ART). Immune profile correlates survival treatment response have not been widely explored patients without infection. This study recruited women undergoing definitive chemoradiation (CRT) Botswana. Clinical characteristics blood samples were collected. Flow cytometry was...
Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin associated with poor prognosis. Implementation high-dose cytarabine (araC) into induction therapy became standard-of-care for all newly diagnosed younger MCL patients. However, many patients relapse even after araC-based regimen. Molecular mechanisms responsible araC resistance in are unknown and optimal treatment strategy relapsed/refractory remains elusive. Five araC-resistant (R) clones were derived by long-term...
Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin (NHL) associated with poor prognosis. Animal models MCL are scarce. We established and characterized various in vivo metastatic human by tail vein injection either primary cells isolated from patients or lines (Jeko-1, Mino, Rec-1, Hbl-2, Granta-519) into immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. infiltration was assessed immunohistochemistry (tissues) flow cytometry (peripheral blood). Engraftment...
A complete series of pyrrolidine nucleotides, (3R)- and (3S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acids (3S,4R)-, (3R,4S)-, (3S,4S)-, (3R,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acids, were synthesized evaluated as potential inhibitors purine nucleoside phosphorylase (PNP) isolated from peripheral blood mononuclear cells (PBMCs) cell lines myeloid lymphoid origin. Two compounds, (S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acid (2a)...
Richter syndrome represents the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed clonally-related pleomorphic highly-aggressive mantle cell (MCL) after five cycles fludarabine-based second-line therapy for first relapse CLL. Molecular cytogenetic methods together whole-exome sequencing revealed numerous gene alterations restricted to MCL clone...
Mantle cell lymphoma (MCL) is a chronically relapsing aggressive type of B-cell non-Hodgkin considered incurable by currently used treatment approaches. Fludarabine purine analog clinically still widely in the therapy relapsed MCL. Molecular mechanisms fludarabine resistance have not, however, been studied setting MCL so far. We therefore derived fludarabine-resistant cells (Mino/FR) and performed their detailed functional proteomic characterization compared to original sensitive (Mino)....
Mantle cell lymphoma (MCL) is an aggressive subtype with dismal prognosis. New treatments are needed to improve outcome of relapsed/refractory disease. Recently, several drugs targeting at least partially the process angiogenesis have been successfully tested in therapy MCL. Molecular mechanisms that regulate MCL-induced and might represent potential new druggable targets remain, however, incompletely understood. We established two mouse models human MCL by subcutaneous xenotransplantation...
<p>To investigate whether the expression level of BCL2 proteins detected by western blot is comparable with assessed IHC analysis, we analyzed protein (by IHC) BCL2, MCL1 and BCL-XL from subcutaneous lymphoma xenografts obtained mice xenotransplanted selected DLBCL cell lines known blot).</p>
<p>Cell of origin (COO), BCL2 expression status and IC100 for ABT-199 (µM) HHT (nM) are shown.</p>
<p>(A) Comparison of the extent apopotosis induced by HHT (after 24hrs exposure) in HHT-resistant (HHT-R) clones compared to original cell lines (CTRL). (B) Western blot analysis demonstrates upregulation BCL-XL protein HHT-R CTRL lines.</p>
<p>Viability of DLBCL cell lines cultured with different concentrations HHT (nM) or ABT-199 (µM) was measured by WST-8 survival/proliferation assay for 7-14 days. Graphs indicate % viable cells, i.e. maximal absorbance untreated cells shown dashed lines. Representative example two independent experiments is shown. Standard deviations were < 5% all measurements.</p>
<p>The graphs show the extent of apoptosis DLBCL cell lines induced by different concentrations HHT, ABT-199 and ABT-737 after 24hrs exposure to particular agents.</p>
<p>Shown are examples of different levels semi-quantitative protein expression (0-3).</p>
<p>Western blot analysis showing protein expression profile of key regulators apoptosis in 18 DLBCL cell lines (12 germinal center B-cell-like (GCB) and 6 activated (ABC) lines). *UPF4D line (GCB origin) was derived our laboratory.</p>
<p>Downregulation of MYC, cFLIP or BCL6 in OCI-Ly7 and BJAB DLBCL cell lines (by western blot) after exposure to HHT.</p>
<p>To investigate whether the expression level of BCL2 proteins detected by western blot is comparable with assessed IHC analysis, we analyzed protein (by IHC) BCL2, MCL1 and BCL-XL from subcutaneous lymphoma xenografts obtained mice xenotransplanted selected DLBCL cell lines known blot).</p>
<div>Abstract<p><b>Purpose:</b> To investigate the roles of BCL2, MCL1, and BCL-XL in survival diffuse large B-cell lymphoma (DLBCL).</p><p><b>Experimental designs:</b> Immunohistochemical analysis 105 primary DLBCL samples, Western blot 18 cell lines for expression BCL-XL. Pharmacologic targeting with ABT-199, homoharringtonine (HHT), ABT-737. Analysis clones manipulated expressions Immunoprecipitation MCL1 complexes selected lines....
<div>Abstract<p><b>Purpose:</b> To investigate the roles of BCL2, MCL1, and BCL-XL in survival diffuse large B-cell lymphoma (DLBCL).</p><p><b>Experimental designs:</b> Immunohistochemical analysis 105 primary DLBCL samples, Western blot 18 cell lines for expression BCL-XL. Pharmacologic targeting with ABT-199, homoharringtonine (HHT), ABT-737. Analysis clones manipulated expressions Immunoprecipitation MCL1 complexes selected lines....
<p>Cell of origin (COO), BCL2 expression status and IC100 for ABT-199 (µM) HHT (nM) are shown.</p>