The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
Cristina Rodriguezpadilla - One of the best experts on this subject based on the ideXlab platform.
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the bovine dialysable Leukocyte Extract immunepotent crp induces immunogenic cell death in breast cancer cells leading to long term antitumour memory
British Journal of Cancer, 2021Co-Authors: Alejandra Reyesruiz, Kenny Misael Calvillorodriguez, Ana Carolina Martineztorres, Cristina RodriguezpadillaAbstract:Cancer recurrence is a serious problem in breast cancer (BC) patients, and immunogenic cell death (ICD) has been proposed as a strategy to overcome this recurrence. IMMUNEPOTENT CRP (ICRP) acts as an immunomodulator and can be cytotoxic to cancer cells. Thus, we evaluated if ICRP induces ICD in BC cells. Immunogenicity of ICRP-induced cell death was evaluated in vitro, analysing the principal biochemical characteristics of ICD in MCF-7, MDA-MB-231 and 4T1 cells. Ex vivo, we assessed the ability of killed cancer cells (KCC) obtained from ICRP-treated 4T1 cells (ICRP-KCC) to induce DC maturation, T-cell priming and T-cell-mediated cancer cytotoxicity. In vivo, we evaluated tumour establishment and antitumour immune memory after prophylactic ICRP-KCC vaccination in BALB/c mice. ICRP induced caspase-independent, ROS-dependent cell death, autophagosome formation, P-eIF2α, chaperone protein exposure, CD47 loss, ATP and HMBG1 release in BC cells. Additionally, ICRP-KCC promoted DC maturation, which triggered T-cell priming and cancer cytotoxicity. Prophylactic vaccination with ICRP-KCC prevented tumour establishment and induced long-term antitumour memory in BALB/c mice, involving DC maturation in lymph nodes, CD8+ T-cell augmentation in lymph nodes, peripheral blood and tumour site and ex vivo tumour-specific cytotoxicity by splenocytes. ICRP induces ICD in BC cells, leading to long-term antitumour memory.
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immunepotent crp plus doxorubicin cyclophosphamide chemotherapy remodel the tumor microenvironment in an air pouch triple negative breast cancer murine model
Biomedicine & Pharmacotherapy, 2020Co-Authors: Silvia Elena Santanakrimskaya, Moises Armides Francomolina, Pablo Zapatabenavides, Heriberto Pradogarcia, Diana G Zaratetrivino, Felipe Torresdelmuro, Cristina RodriguezpadillaAbstract:In 1889, Steven Paget postulated the theory that cancer cells require a permissive environment to grow. This permissive environment is known as the tumor microenvironment (TME) and nowadays it is evident that the TME is involved in the progression and response to therapy of solid cancer tumors. Triple-negative breast cancer is one of the most lethal types of cancer for women worldwide and chemotherapy remains the standard treatment for these patients. IMMUNEPOTENT CRP is a bovine dialyzable Leukocyte Extract with immunomodulatory and antitumor properties. The combination of chemotherapy and IMMUNEPOTENT CRP improves clinical parameters of breast cancer patients. In the current study, we aimed to evaluate the antitumor effect of doxorubicin/cyclophosphamide chemotherapy plus IMMUNEPOTENT CRP and its impact over the tumor microenvironment in a triple-negative breast cancer murine model. We evaluated CD8+, CD4+, T regulatory cells, memory T cells, myeloid-derived suppressor cells, CD71+, innate effector cells and molecules such as α-SMA, VEGF, CTLA-4, PD-L1, Gal-3, IDO, IL-2, IFN-γ, IL-12, IL-6, MCP-1, and IL-10 as part of the components of the TME. Doxorubicin/cyclophosphamide + IMMUNEPOTENT CRP decreased tumor volume, prolonged survival, increased infiltrating and systemic CD8+ T cells and decreased tumor suppressor molecules (such as PD-L1, Gal-3, and IL-10 among others). In conclusion, we suggest that IMMUNEPOTENT CRP act as a modifier of the TME and the immune response, potentiating or prolonging anti-tumor effects of doxorubicin/cyclophosphamide in a triple-negative breast cancer murine model.
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in vivo chemoprotective activity of bovine dialyzable Leukocyte Extract in mouse bone marrow cells against damage induced by 5 fluorouracil
Clinical & Developmental Immunology, 2016Co-Authors: Erika Evangelina Coronadocerda, Moises Armides Francomolina, Edgar Mendozagamboa, Pablo Zapatabenavides, Reyes Tamezguerra, Heriberto Pradogarcia, Lydia G Riveramorales, Maria Del Carmen Rodriguezsalazar, Diana Caballerohernandez, Cristina RodriguezpadillaAbstract:Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable Leukocyte Extract (bDLE) or IMMUNEPOTENT CRP® (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of Leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients.
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clinical and immunological assessment in breast cancer patients receiving anticancer therapy and bovine dialyzable Leukocyte Extract as an adjuvant
Experimental and Therapeutic Medicine, 2010Co-Authors: Humberto H Lara, Reyes Tamezguerra, Liliana Ixtepan Turrent, Elsa N Garzatrevino, Cristina RodriguezpadillaAbstract:Dialyzable Leukocyte Extract (DLE) is one of the immunological agents used as an adjuvant in cancer therapy; it has been associated with improved quality of life during cancer chemotherapy. Based on these previous findings and on the observed clinical benefits attributed to DLE in other types of cancer, we investigated its clinical and immunological effects as a therapy adjuvant on breast cancer patients who received only chemotherapy, as compared to patients administered bovine DLE (bDLE) as an adjuvant. This study included 43 breast cancer patients who were about to begin chemotherapy. This group was divided as follows: 25 received chemotherapy and bDLE as an adjuvant therapy, and 18 received only chemotherapy without the adjuvant. All patient clinical and immunological responses were monitored. Among patients in the group that received bDLE as adjuvant, 60% showed a complete response, 32% showed a partial response and 8% did not respond. By contrast, in the group without the adjuvant, 39% showed a complete response, 50% displayed a partial response and 11% were non-responders. In addition, bDLE treatment in combination with chemotherapy resulted in the enhancement of the Karnofsky performance scale during chemotherapy. Even though patients underwent several cycles of chemotherapy without bDLE, the lymphocyte population dropped to below the reference value. On the other hand, in patients with bDLE as adjuvant, the CD4(+) and CD8(+) lymphocytes and the B lymphocytes were maintained within the median range of the reference value. The number of natural killer cells also increased after chemotherapy treatment with bDLE as an adjuvant. In conclusion, bDLE treatment contributes to significant immunological recovery in patients that have undergone heavy chemotherapy, increasing the clinical response and quality of life during chemotherapy.
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bovine dialyzable Leukocyte Extract modulates ap 1 dna binding activity and nuclear transcription factor expression in mcf 7 breast cancer cells
Cytotherapy, 2008Co-Authors: Edgar Mendozagamboa, Moises Armides Francomolina, Pablo Zapatabenavides, Reyes Tamezguerra, Paloma Castillotello, Magda E Veragarcia, Cristina RodriguezpadillaAbstract:BackgroundWe have previously demonstrated that bovine dialyzable Leukocyte Extract (bDLE) induces death through an apoptosis mechanism in MCF-7 breast cancer cells. Depending on the cell type and stimulus, activating protein-1 (AP-1) has been shown to regulate cell proliferation and differentiation, the stress response, apoptosis and survival. It remains unknown whether AP-1 and other transcription factors are mechanisms by which bDLE induces cell death.MethodsTo determine whether bDLE modulates the AP-1 DNA binding and gene expression, MCF-7 breast cancer cells were treated with bDLE (0, 1, 5, 10 U) for 72 h and evaluated by electrophoretic mobility shift assay, reverse transcriptase-polymerase chain reaction and Western blot assays.ResultsbDLE induced inhibition of cell growth, suppressed the AP-1 DNA-binding activity, decreased c-Jun protein expression and modulated NFATx, NFATc, NFκB, c-Jun and c-Fos transcription factor gene expression in MCF-7 breast cancer cells.DiscussionThe present data indicate ...
Moises Armides Francomolina - One of the best experts on this subject based on the ideXlab platform.
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immunepotent crp plus doxorubicin cyclophosphamide chemotherapy remodel the tumor microenvironment in an air pouch triple negative breast cancer murine model
Biomedicine & Pharmacotherapy, 2020Co-Authors: Silvia Elena Santanakrimskaya, Moises Armides Francomolina, Pablo Zapatabenavides, Heriberto Pradogarcia, Diana G Zaratetrivino, Felipe Torresdelmuro, Cristina RodriguezpadillaAbstract:In 1889, Steven Paget postulated the theory that cancer cells require a permissive environment to grow. This permissive environment is known as the tumor microenvironment (TME) and nowadays it is evident that the TME is involved in the progression and response to therapy of solid cancer tumors. Triple-negative breast cancer is one of the most lethal types of cancer for women worldwide and chemotherapy remains the standard treatment for these patients. IMMUNEPOTENT CRP is a bovine dialyzable Leukocyte Extract with immunomodulatory and antitumor properties. The combination of chemotherapy and IMMUNEPOTENT CRP improves clinical parameters of breast cancer patients. In the current study, we aimed to evaluate the antitumor effect of doxorubicin/cyclophosphamide chemotherapy plus IMMUNEPOTENT CRP and its impact over the tumor microenvironment in a triple-negative breast cancer murine model. We evaluated CD8+, CD4+, T regulatory cells, memory T cells, myeloid-derived suppressor cells, CD71+, innate effector cells and molecules such as α-SMA, VEGF, CTLA-4, PD-L1, Gal-3, IDO, IL-2, IFN-γ, IL-12, IL-6, MCP-1, and IL-10 as part of the components of the TME. Doxorubicin/cyclophosphamide + IMMUNEPOTENT CRP decreased tumor volume, prolonged survival, increased infiltrating and systemic CD8+ T cells and decreased tumor suppressor molecules (such as PD-L1, Gal-3, and IL-10 among others). In conclusion, we suggest that IMMUNEPOTENT CRP act as a modifier of the TME and the immune response, potentiating or prolonging anti-tumor effects of doxorubicin/cyclophosphamide in a triple-negative breast cancer murine model.
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in vivo chemoprotective activity of bovine dialyzable Leukocyte Extract in mouse bone marrow cells against damage induced by 5 fluorouracil
Clinical & Developmental Immunology, 2016Co-Authors: Erika Evangelina Coronadocerda, Moises Armides Francomolina, Edgar Mendozagamboa, Pablo Zapatabenavides, Reyes Tamezguerra, Heriberto Pradogarcia, Lydia G Riveramorales, Maria Del Carmen Rodriguezsalazar, Diana Caballerohernandez, Cristina RodriguezpadillaAbstract:Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable Leukocyte Extract (bDLE) or IMMUNEPOTENT CRP® (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of Leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients.
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bovine dialyzable Leukocyte Extract modulates ap 1 dna binding activity and nuclear transcription factor expression in mcf 7 breast cancer cells
Cytotherapy, 2008Co-Authors: Edgar Mendozagamboa, Moises Armides Francomolina, Pablo Zapatabenavides, Reyes Tamezguerra, Paloma Castillotello, Magda E Veragarcia, Cristina RodriguezpadillaAbstract:BackgroundWe have previously demonstrated that bovine dialyzable Leukocyte Extract (bDLE) induces death through an apoptosis mechanism in MCF-7 breast cancer cells. Depending on the cell type and stimulus, activating protein-1 (AP-1) has been shown to regulate cell proliferation and differentiation, the stress response, apoptosis and survival. It remains unknown whether AP-1 and other transcription factors are mechanisms by which bDLE induces cell death.MethodsTo determine whether bDLE modulates the AP-1 DNA binding and gene expression, MCF-7 breast cancer cells were treated with bDLE (0, 1, 5, 10 U) for 72 h and evaluated by electrophoretic mobility shift assay, reverse transcriptase-polymerase chain reaction and Western blot assays.ResultsbDLE induced inhibition of cell growth, suppressed the AP-1 DNA-binding activity, decreased c-Jun protein expression and modulated NFATx, NFATc, NFκB, c-Jun and c-Fos transcription factor gene expression in MCF-7 breast cancer cells.DiscussionThe present data indicate ...
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immunepotent crp bovine dialyzable Leukocyte Extract adjuvant immunotherapy a phase i study in non small cell lung cancer patients
Cytotherapy, 2008Co-Authors: Moises Armides Francomolina, Edgar Mendozagamboa, Pablo Zapatabenavides, Reyes Tamezguerra, Paloma Castillotello, Magda E Veragarcia, Garcia A De La Fuente, R D Mendoza, R G Garza, Cristina RodriguezpadillaAbstract:BackgroundIMMUNEPOTENT CRP is a mixture of low molecular weight substances, some of which have been shown to be capable of modifying the immune response. We evaluated the response and adjuvant effect of IMMUNEPOTENT CRP on non-small cell lung cancer (NSCLC) patients in a phase I clinical trial.MethodsTwenty-four NSCLC patients were included in the study and divided into two groups. Group 1 received a conventional treatment of 5400 cGy external radiotherapy in 28 fractions and chemotherapy consisting of intravenous cisplatin (40 mg/m2) delivered weekly for 6 weeks. Group 2 received the conventional treatment plus IMMUNEPOTENT CRP (5 U) administered daily. We performed clinical evaluation by CT scan and radiography analysis, and determined the quality of life of the patients with the Karnofsky performance scale. A complete blood count (red and white blood cell tests), including flow cytometry analysis, blood work (alkaline phosphatase test) and a delayed-type hypersensitivity (DTH) skin test for PPD, Varida...
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bovine dialyzable Leukocyte Extract modulates cytokines and nitric oxide production in lipopolysaccharide stimulated human blood cells
Cytotherapy, 2007Co-Authors: Moises Armides Francomolina, Edgar Mendozagamboa, Leonardo Castilloleon, C Isazabrando, Reyes Tamezguerra, Paloma Castillotello, M Vera E Garcia, Cristina RodriguezpadillaAbstract:BackgroundIn the current study, we determined whether bovine dialyzable Leukocyte Extract (bDLE) modulates lipopolysaccharide (LPS)-induced nitric oxide and cytokine overproduction.MethodsHuman whole blood cells were treated with LPS (50 ng) + bDLE (1 U).ResultsThe bDLE treatment decreased nitric oxide as well as TNF-α, IL-6 and IL-10 (P <0.01) cytokine production. In addition, it decreased TNF-α, IL-1β and IL-6 mRNA expression and suppressed IL-10 and IL-12p40 mRNA expression, but did not modulate IL-8 mRNA expression in LPS-stimulated human blood cells.DiscussionOur results suggest that bDLE may effectively modulate the fatal symptoms of hypotensive shock associated with endotoxin (LPS)-induced nitric oxide and cytokine production, and this may offer therapeutic potential for the treatment of endotoxic shock.
Antonin Vacek - One of the best experts on this subject based on the ideXlab platform.
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ultrafiltered pig Leukocyte Extract imunor decreases nitric oxide formation and hematopoiesis stimulating cytokine production in lipopolysaccharide stimulated raw 264 7 macrophages
International Immunopharmacology, 2007Co-Authors: M Hofer, Antonin Vacek, Antonin Lojek, J Hola, D StreitovaAbstract:A low-molecular-weight (< 12 kDa) ultrafiltered pig Leukocyte Extract, IMUNOR®, was tested in experiments in vitro on non-stimulated and lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages in order to assess modulation of nitric oxide (NO) production (measured indirectly as the concentration of nitrites), hematopoiesis-stimulating activity of the supernatant of the macrophage cells (ascertained by counting cell colonies growing from progenitor cells for granulocytes and macrophages (GM-CFC) in vitro), and the release of hematopoiesis-stimulating cytokines. No hematopoiesis-stimulating activity and cytokine or NO production were found in the supernatant of non-stimulated macrophages. It was found that IMUNOR® does not influence this status. Supernatant of LPS-stimulated macrophages was characterized by hematopoiesis-stimulating activity, as well as by the presence of nitrites, interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). A key role in the hematopoiesis-stimulating activity of the supernatant of LPS-stimulated macrophages could be ascribed to G-CSF since the formation of the colonies could be abrogated nearly completely by monoclonal antibodies against G-CSF. IMUNOR® was found to suppress all the mentioned manifestations of the LPS-activated macrophages. When considering these results together with those from our previous in vivo study revealing stimulatory effects of IMUNOR® on radiation-suppressed hematopoiesis, a hypothesis may be formulated which postulates a homeostatic role of IMUNOR®, consisting in stimulation of impaired immune and hematopoietic systems but also in cutting back the production of proinflammatory mediators in cases of overstimulation which threats with undesirable consequences.
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the role of g csf and il 6 in the granulopoiesis stimulating activity of murine blood serum induced by perorally administered ultrafiltered pig Leukocyte Extract imunor
International Immunopharmacology, 2007Co-Authors: Antonin Vacek, M Hofer, J Hola, D Streitova, Lenka Weiterova, Jaroslav SvobodaAbstract:IMUNOR, a low-molecular weight (< 12 kD) ultrafiltered pig Leukocyte Extract, has been previously found to have significant stimulatory effects on murine hematopoiesis supressed by ionizing radiation or cytotoxic drugs. This communication shows data on the mechanisms of these effects. Using ELISA assay, significantly increased levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were observed. On the contrary, no detectable levels of granulocyte-macrophage colony-stimulating factor (GM-CFC) and interleukin-3 (IL-3) have been found in blood serum of IMUNOR-treated mice. Incubation of the serum from IMUNOR-treated mice with antibodies against G-CSF caused abrogation of the ability of the sera to stimulate in vitro growth of colonies originating from granulocyte-macrophage progenitor cells (GM-CFC). In contrast, incubation of the serum with antibodies against IL-6 did not change its colony-stimulating activity. It may be inferred from these findings that G-CSF is probably the main cytokine responsible for the granulopoiesis-stimulating effects of IMUNOR. When the serum from IMUNOR-treated mice with G-CSF inactivated by anti-G-CSF antibodies (but with elevated IL-6) was added to cultures of bone marrow cells together with a suboptimum concentration of IL-3, a significant increase in the numbers of GM-CFC colonies was found. Moreover, conjoint inactivation of G-CSF and IL-6 significantly decreased the numbers of GM-CFC colonies in comparison with those observed when only G-CSF was inactivated. This observation strongly suggests that though IMUNOR-induced IL-6 is not able to induce the growth of GM-CFC colonies alone, it is able to potentiate the hematopoiesis-stimulating effect of IL-3. These findings represent a new knowledge concerning the hematopoiesis-stimulating action of IMUNOR, a promising immunomodulatory agent.
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ultrafiltered pig Leukocyte Extract uple imunor potentiates hematopoiesis stimulating effects of g csf in vitro and improves the outcome of treatment of hematopoietic radiation damage in mice with g csf
Immunopharmacology and Immunotoxicology, 2005Co-Authors: Antonin Vacek, M Hofer, H Schneiderova, J SvobodaAbstract:Ultrafiltered pig Leukocyte Extract (UPLE, Imunor), a heterogeneous mixture of low molecular weight (<10 kD) substances released from disintegrated pig Leukocytes was tested from the point of view of its hematopoiesis-modulating activities using experiments in vitro and in vivo. Attention was focused especially on evaluation of the contingent ability of UPLE to potentiate the hematopoiesis-stimulating effects of recobinant human granulocyte colony-stimulating factor (G-CSF). Experiments in vitro revealed the capability of sera from mice administered UPLE perorally (p.o.) to stimulate proliferation of progenitor cells for granulocytes and macrophages (GM-CFC) in cultures of normal bone marrow cells. In addition, UPLE, as well as sera from mice given UPLE, added to the cultures in combination with G-CSF enhanced the numbers of GM-CFC significantly over those induced by sera after administration of either of the preparations alone. In in vivo experiments, UPLE was found to increase the counts of GM-CFC per femur and femoral bone marrow cellularity in sublethally irradiated mice when administered p.o. after irradiation in combination with G-CSF in comparison with the effects of G-CSF alone. These results indicate the possibility of using UPLE, a commercially available preparation, for treatment of hematopoietic suppression of various etiology.
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hemopoiesis stimulating effects and enhanced survival of irradiated mice after peroral or intraperitoneal administration of ultrafiltered pig Leukocyte Extract uple imunor
Immunopharmacology and Immunotoxicology, 2002Co-Authors: Antonin Vacek, M Hofer, J Hromas, E Luksikova, J Svoboda, H SchneiderovaAbstract:ABSTRACTUltrafiltered pig Leukocyte Extract (UPLE, IMUNOR®, ImunomedicA, Usti nad Labem, Czech Republic) administered perorally (p.o.) or intraperitoneally (i.p.) enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow of normal or sublethally irradiated mice and increased survival of mice exposed to a lethal radiation dose. In experiments in vitro, sera of mice treated with UPLE p.o. or i.p. induced GM-CFC colony formation in cultures of normal mouse bone marrow cells, i.e., produced colony-stimulating activity (CSA). UPLE alone did not induce GM-CFC colony growth, i.e., had no CSA. When UPLE alone or sera of mice administered UPLE p.o. or i.p. were added to bone marrow cultures containing suboptimal concentration of recombinant mouse interleukin-3 (rmIL-3), both UPLE and the sera increased the counts of GM-CFC colonies in comparison with cultures containing only rmIL-3, i.e., produced co-stimulating activity (CoSA). Based on the findings obtained ...
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positive effects of dialyzable Leukocyte Extract dle on recovery of mouse haemopoiesis suppressed by ionizing radiation and on proliferation of haemopoietic progenitor cells in vitro
International Journal of Immunopharmacology, 2000Co-Authors: Antonin Vacek, M Hofer, Karel Barnet, Karel Cech, Josef Pekarek, H SchneiderovaAbstract:Dialyzed Leukocyte Extract (DLE) (Immodin SEVAC, Czech Republic) was shown to enhance the recovery of the pools of hemopoietic stem cells (CFUs) and of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow in vivo, as well as to increase the numbers of Leukocytes and thrombocytes in the peripheral blood of mice exposed to a sublethal dose of gamma-rays, with an ensuing increase in the numbers of mice surviving the lethal radiation dose. In experiments performed in vitro, DLE or sera of mice administered with DLE were added to cultures of intact mouse bone marrow cells containing suboptimal concentrations of hemopoietic stimulatory cytokines, namely recombinant mouse interleukin-3 (rmIL-3) or recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF); under these experimental conditions, both DLE and sera of mice administered DLE were found to increase the counts of GM-CFC colonies in the cultures. It can be hypothesized on the basis of the findings obtained in vitro that the described co-stimulating activity (CoSA) of DLE may play a role also under in vivo conditions; the enhancement of the recovery of hemopoiesis suppressed by ionizing radiation may be due to a co-operation of the stimulatory effects of DLE with the action of cytokines endogenously produced in irradiated tissues.
Cristina Rodriguez-padilla - One of the best experts on this subject based on the ideXlab platform.
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Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines
Journal of Oncology, 2020Co-Authors: Helen Yarimet Lorenzo-anota, Ana Carolina Martínez-torres, Daniel Scott-algara, Reyes Tamez-guerra, Cristina Rodriguez-padillaAbstract:Immunotherapies strengthen the immune system to fight multiple diseases such as infections, immunodeficiencies, and autoimmune diseases, and recently, they are being used as an adjuvant in cancer treatment. IMMUNEPOTENT-CRP (I-CRP) is an immunotherapy made of bovine dialyzable Leukocyte Extract (bDLE) that has chemoprotective and immunomodulatory effects in different cellular populations of the immune system and antitumor activity in different cancer cell lines. Our recent results suggest that the antineoplastic effect of I-CRP is due to the characteristics of cancer cells. To confirm, we evaluated whether the selectivity is due to cell lineage or characteristics of cancer cells, testing cytotoxicity in T-acute lymphoblastic leukemia cells and their cell death mechanism. Here, we assessed the effect of I-CRP on cell viability and cell death. To determine the mechanism of cell death, we tested cell cycle, mitochondrial and nuclear alterations, and caspases and reactive oxygen species (ROS) and their role in cell death mechanism. Our results show that I-CRP does not affect cell viability in noncancer cells and induces selective cytotoxicity in a dose-dependent manner in leukemic cell lines. I-CRP also induces mitochondrial damage through proapoptotic and antiapoptotic protein modulation (Bax and Bcl-2) and ROS production, nuclear alterations including DNA damage (γ-H2Ax), overexpression of p53, cell cycle arrest, and DNA degradation. I-CRP induced ROS-dependent apoptosis in leukemic cells. Overall, here, we show that I-CRP cytotoxicity is selective to leukemic cells, inducing ROS-dependent apoptosis. This research opens the door to further exploration of their role in the immune system and the cell death mechanism that could potentially work in conjunction with other therapies including hematological malignances.
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RESEARCH ARTICLE Open Access
2013Co-Authors: Humberto H Lara, Liliana Ixtepan-turrent, Elsa N Garza-treviño, Jose I Badillo-almaraz, Cristina Rodriguez-padillaAbstract:Antiviral mode of action of bovine dialyzable Leukocyte Extract against human immunodeficiency virus type 1 infectio
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Antiviral mode of action of bovine dialyzable Leukocyte Extract against human immunodeficiency virus type 1 infection
BMC Research Notes, 2011Co-Authors: Humberto H Lara, Liliana Ixtepan-turrent, Elsa N Garza-treviño, Jose I Badillo-almaraz, Cristina Rodriguez-padillaAbstract:Background Bovine dialyzable Leukocyte Extract (bDLE) is derived from immune Leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays. Results The cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action. HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-β-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours. Conclusions bDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours. bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals.
M Hofer - One of the best experts on this subject based on the ideXlab platform.
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ultrafiltered pig Leukocyte Extract imunor decreases nitric oxide formation and hematopoiesis stimulating cytokine production in lipopolysaccharide stimulated raw 264 7 macrophages
International Immunopharmacology, 2007Co-Authors: M Hofer, Antonin Vacek, Antonin Lojek, J Hola, D StreitovaAbstract:A low-molecular-weight (< 12 kDa) ultrafiltered pig Leukocyte Extract, IMUNOR®, was tested in experiments in vitro on non-stimulated and lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages in order to assess modulation of nitric oxide (NO) production (measured indirectly as the concentration of nitrites), hematopoiesis-stimulating activity of the supernatant of the macrophage cells (ascertained by counting cell colonies growing from progenitor cells for granulocytes and macrophages (GM-CFC) in vitro), and the release of hematopoiesis-stimulating cytokines. No hematopoiesis-stimulating activity and cytokine or NO production were found in the supernatant of non-stimulated macrophages. It was found that IMUNOR® does not influence this status. Supernatant of LPS-stimulated macrophages was characterized by hematopoiesis-stimulating activity, as well as by the presence of nitrites, interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). A key role in the hematopoiesis-stimulating activity of the supernatant of LPS-stimulated macrophages could be ascribed to G-CSF since the formation of the colonies could be abrogated nearly completely by monoclonal antibodies against G-CSF. IMUNOR® was found to suppress all the mentioned manifestations of the LPS-activated macrophages. When considering these results together with those from our previous in vivo study revealing stimulatory effects of IMUNOR® on radiation-suppressed hematopoiesis, a hypothesis may be formulated which postulates a homeostatic role of IMUNOR®, consisting in stimulation of impaired immune and hematopoietic systems but also in cutting back the production of proinflammatory mediators in cases of overstimulation which threats with undesirable consequences.
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the role of g csf and il 6 in the granulopoiesis stimulating activity of murine blood serum induced by perorally administered ultrafiltered pig Leukocyte Extract imunor
International Immunopharmacology, 2007Co-Authors: Antonin Vacek, M Hofer, J Hola, D Streitova, Lenka Weiterova, Jaroslav SvobodaAbstract:IMUNOR, a low-molecular weight (< 12 kD) ultrafiltered pig Leukocyte Extract, has been previously found to have significant stimulatory effects on murine hematopoiesis supressed by ionizing radiation or cytotoxic drugs. This communication shows data on the mechanisms of these effects. Using ELISA assay, significantly increased levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were observed. On the contrary, no detectable levels of granulocyte-macrophage colony-stimulating factor (GM-CFC) and interleukin-3 (IL-3) have been found in blood serum of IMUNOR-treated mice. Incubation of the serum from IMUNOR-treated mice with antibodies against G-CSF caused abrogation of the ability of the sera to stimulate in vitro growth of colonies originating from granulocyte-macrophage progenitor cells (GM-CFC). In contrast, incubation of the serum with antibodies against IL-6 did not change its colony-stimulating activity. It may be inferred from these findings that G-CSF is probably the main cytokine responsible for the granulopoiesis-stimulating effects of IMUNOR. When the serum from IMUNOR-treated mice with G-CSF inactivated by anti-G-CSF antibodies (but with elevated IL-6) was added to cultures of bone marrow cells together with a suboptimum concentration of IL-3, a significant increase in the numbers of GM-CFC colonies was found. Moreover, conjoint inactivation of G-CSF and IL-6 significantly decreased the numbers of GM-CFC colonies in comparison with those observed when only G-CSF was inactivated. This observation strongly suggests that though IMUNOR-induced IL-6 is not able to induce the growth of GM-CFC colonies alone, it is able to potentiate the hematopoiesis-stimulating effect of IL-3. These findings represent a new knowledge concerning the hematopoiesis-stimulating action of IMUNOR, a promising immunomodulatory agent.
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ultrafiltered pig Leukocyte Extract uple imunor potentiates hematopoiesis stimulating effects of g csf in vitro and improves the outcome of treatment of hematopoietic radiation damage in mice with g csf
Immunopharmacology and Immunotoxicology, 2005Co-Authors: Antonin Vacek, M Hofer, H Schneiderova, J SvobodaAbstract:Ultrafiltered pig Leukocyte Extract (UPLE, Imunor), a heterogeneous mixture of low molecular weight (<10 kD) substances released from disintegrated pig Leukocytes was tested from the point of view of its hematopoiesis-modulating activities using experiments in vitro and in vivo. Attention was focused especially on evaluation of the contingent ability of UPLE to potentiate the hematopoiesis-stimulating effects of recobinant human granulocyte colony-stimulating factor (G-CSF). Experiments in vitro revealed the capability of sera from mice administered UPLE perorally (p.o.) to stimulate proliferation of progenitor cells for granulocytes and macrophages (GM-CFC) in cultures of normal bone marrow cells. In addition, UPLE, as well as sera from mice given UPLE, added to the cultures in combination with G-CSF enhanced the numbers of GM-CFC significantly over those induced by sera after administration of either of the preparations alone. In in vivo experiments, UPLE was found to increase the counts of GM-CFC per femur and femoral bone marrow cellularity in sublethally irradiated mice when administered p.o. after irradiation in combination with G-CSF in comparison with the effects of G-CSF alone. These results indicate the possibility of using UPLE, a commercially available preparation, for treatment of hematopoietic suppression of various etiology.
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hemopoiesis stimulating effects and enhanced survival of irradiated mice after peroral or intraperitoneal administration of ultrafiltered pig Leukocyte Extract uple imunor
Immunopharmacology and Immunotoxicology, 2002Co-Authors: Antonin Vacek, M Hofer, J Hromas, E Luksikova, J Svoboda, H SchneiderovaAbstract:ABSTRACTUltrafiltered pig Leukocyte Extract (UPLE, IMUNOR®, ImunomedicA, Usti nad Labem, Czech Republic) administered perorally (p.o.) or intraperitoneally (i.p.) enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow of normal or sublethally irradiated mice and increased survival of mice exposed to a lethal radiation dose. In experiments in vitro, sera of mice treated with UPLE p.o. or i.p. induced GM-CFC colony formation in cultures of normal mouse bone marrow cells, i.e., produced colony-stimulating activity (CSA). UPLE alone did not induce GM-CFC colony growth, i.e., had no CSA. When UPLE alone or sera of mice administered UPLE p.o. or i.p. were added to bone marrow cultures containing suboptimal concentration of recombinant mouse interleukin-3 (rmIL-3), both UPLE and the sera increased the counts of GM-CFC colonies in comparison with cultures containing only rmIL-3, i.e., produced co-stimulating activity (CoSA). Based on the findings obtained ...
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positive effects of dialyzable Leukocyte Extract dle on recovery of mouse haemopoiesis suppressed by ionizing radiation and on proliferation of haemopoietic progenitor cells in vitro
International Journal of Immunopharmacology, 2000Co-Authors: Antonin Vacek, M Hofer, Karel Barnet, Karel Cech, Josef Pekarek, H SchneiderovaAbstract:Dialyzed Leukocyte Extract (DLE) (Immodin SEVAC, Czech Republic) was shown to enhance the recovery of the pools of hemopoietic stem cells (CFUs) and of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow in vivo, as well as to increase the numbers of Leukocytes and thrombocytes in the peripheral blood of mice exposed to a sublethal dose of gamma-rays, with an ensuing increase in the numbers of mice surviving the lethal radiation dose. In experiments performed in vitro, DLE or sera of mice administered with DLE were added to cultures of intact mouse bone marrow cells containing suboptimal concentrations of hemopoietic stimulatory cytokines, namely recombinant mouse interleukin-3 (rmIL-3) or recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF); under these experimental conditions, both DLE and sera of mice administered DLE were found to increase the counts of GM-CFC colonies in the cultures. It can be hypothesized on the basis of the findings obtained in vitro that the described co-stimulating activity (CoSA) of DLE may play a role also under in vivo conditions; the enhancement of the recovery of hemopoiesis suppressed by ionizing radiation may be due to a co-operation of the stimulatory effects of DLE with the action of cytokines endogenously produced in irradiated tissues.