scholarly journals Synthesis and anti-tumor properties of derivatives [4- (41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[c,d]azulen-1-yl-metil]-para-tolylamine

2020 ◽  
pp. 69-77
Author(s):  
S. A. Demchenko ◽  
V. V. Sukhoveev ◽  
О. V. Моsкаlеnко ◽  
Yu. A. Fedchenkova ◽  
G. P. Potebnia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Antitumor Activity ◽  
Biologically Active ◽  
New Drugs ◽  
Antitumor Action ◽  
Experimental Conditions ◽  
System Disease ◽  
Bone Marrow Damage ◽  
Rpmi 8226

Leukemia, as a part of hemoblastosises, is a malignant blood system disease, which is characterized by bone marrow damage, caused by leukemic stem cells, which appear due to disruption of self-renewal and differentiation of hempoetic stem cells and predecessor cells. In their turn, hemoblastoses are divided into two groups: bone marrow (acute leukemia, chronical leukemia, paraproteinemic hemoblastoses) and outside bone marrow (lymphogranulomatosis, or Hodgkin lymphoma, and non-Hodgkin malignant mymphomas). Nowadays in Ukraine, different kinds of leukemia are cured by various drugs, which have many side effects. Increase in effectivity of chemotherapy of tumor disease is primarily related to creation of new antitumor drugs of selective action. Which is why search for biologically active compounds with antitumor activity is a perspective direction in creation of new drugs. Aim of this work was synthesis of compounds with potential antitumor properties in a variety of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[c,d]-azulen-1-yl-methyl]-para-tolylamin derivatives. As the objects of our studies, we have picked the derivatives of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]-azulen-1-yl-methyl]-para-tolilamin (8 and 10 a, b). [4-(41-Chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) was obtained by boiling of equimolar quantities of 3-(41-methylphenyl)aminomethyl-6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-a]azepin (5) and α-brom-4-chloracetophenon in ethylacetate. Thioamides (10 a, b) were obtained by interaction of amin (8) with corresponding arylisothiocyanates (9 а, b) in dry benzene. Antitumor activity of [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) was studied in National Cancer Institute of Health, USA within Development Therapeutic Program. In experimental conditions [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) showed ability to inhibit growth of cancerous leukemia cells of CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226 and SR lines, higher than standard – 5-fluorouracil. Towards HL-60(TB) cells [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а- triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin exceeds standard in effectivity by 64.68%. For K-562, MOLT-4, RPMI-8226 and SR cells, those numbers are equal to: 85.88%, 84.95%, 42.10% and 36.82% correspondingly. Towards CCRF-CEM cells, this compound not only inhibits cell growth and division, but also destroys them by 20.34%. Thus conducted studies confirm perceptivity of search for compounds with antitumor action on the basis of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl­methyl]-para-tolylamin.

111 EQUINE AMNIOTIC EPITHELIAL OR BONE MARROW MESENCHYMAL STEM CELLS DIFFERENTLY SUPPORT IN VITRO EMBRYO DEVELOPMENT IN A BOVINE IN VITRO CULTURE MODEL

2009 ◽  
Vol 21 (1) ◽  
pp. 156 ◽  
Author(s):  
F. Cremonesi ◽  
V. Maggio ◽  
A. Lange Consiglio
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
In Vitro Culture ◽  
Calf Serum ◽  
Biologically Active ◽  
Bovine Embryo ◽  
Epithelial Stem Cells ◽  
Marrow Mesenchymal Stem Cells

There are indications that the culture system and the medium composition can affect embryo quality. In fact, various studies have been shown that the in vitro culture environment is one of the key determinants of the blastocyst output. In light of this, recently, some studies used co-culture with mouse embryonic fibroblasts in the effort to improve the development of bovine and ovine in vitro-derived embryos. Despite the progress in equine IVM and ICSI technologies and the different culture conditions reported for preimplantation development of ICSI fertilized horse oocytes, the yield of blastocysts remained low. In the present study we investigated the benefits of co-culturing bovine embryos with equine bone marrow mesenchymal stem cells (BM-MSC) or equine amniotic epithelial stem cells (AE-SC) on blastocyst development. This study employed the bovine embryo as a model and represents the initial step towards standardization of a protocol for the culture of equine embryos in our laboratory. BM specimens were obtained aseptically from sternal aspirates of horses under local anaesthesia and layered over Hystopaque™ 1.080, then centrifuged for 20 min at 400g and 4°C. Cell pellets were resuspended in 10 mL Dulbecco Modified Earle’s Medium supplemented with 10% fetal calf serum, 1% non-essential amino acids, penicillin (100 U mL–1) and streptomycin (100 μg mL–1) and seeded in 24-well plates. Amniotic membranes were obtained from fresh placentas and, to release the AE cells, amniotic fractions were incubated at 37°C with 0.05% trypsin for 45 min. Separated AE cells were plated on 25 cm2 flask in standard culture media containing 10 ng mL–1 epidermal growth factor. Seven hundred fifty cumulus–oocyte complexes with a homogeneous cytoplasm and two or more layers of cumulus cells were used. After IVM and IVF cumulus-free presumptive zygotes were randomly transferred into one of three co-culture systems in which they were cultured for up to Day 7: 1) co-culture with granulosa cells (control); 2) co-culture with BM-MSC; 3) co-culture with AE-SC. The culture medium was TCM 199 + 10% fetal bovine serum, pyruvate and gentamicin at 38.5°C in 5% CO2. Statistical analyses was performed by chi square test. Blastocysts developmental rates were similar among control, AE-SC and BM-MSC (35%, 41% and 30%, respectively), but the co-culture with AE-SC gave a significantly greater percentage of blastocysts compared to BM-MSC (P < 0.05). In conclusion, despite the absence of a significant increment in blastocysts attainment using stem cells as feeders for embryo culture, the AE-SC monolayer create a more suitable microenvironment necessary for inducing local cell activation and proliferation of the growing embryos in comparison with BM-MSC. It can be suggested that these cells secrete biologically active substances including signaling molecules and growth factors of epithelial nature different from those of the BM cells of mesenchymal origin. Regione Lombardia is acknowledged for the “Dote Ricercatori” fellowship to V.M.

scholarly journals The effect of 5-fluorouracil on erythropoiesis

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1164-1170 ◽  
Author(s):  
IN Rich
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Normal Values ◽  
Biologically Active ◽  
Stem Cell Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Proliferative Potential ◽  
Colony Forming Unit ◽  
Kinetics Of

Abstract The effects of a single dose (150 mg/kg) of 5-fluorouracil on mature erythroid and erythropoietic and multipotential in vitro precursor populations in the bone marrow and spleen and circulating biologically (erythroid colony forming unit [CFU-E] assay) and immunologically active (enzyme-linked immunosorbent assay) erythropoietin (Epo) are described. All mature erythroid (reticulocytes, erythrocytes) and in vitro erythropoietic precursors (CFU-E, erythroid burst-forming unit [BFU-E]) are severely reduced, if not eradicated. Transient repopulation of the pure BFU-E and CFU-E populations on days 6 and 7, respectively, produces a marked reticulocytosis after day 9. Circulating Epo increases to above normal values by day 2. However, whereas biologically active Epo remains constant at this level until day 9, immunologically active Epo continually increases; by day 12, however, both assays detect circulating Epo levels of about 400 mU/mL. In vitro multipotential stem cells (BFU-E mix) are reduced to 32% on day 1, 7.6% on day 2, and return to normal values between days 4 and 5. The survival and repopulation kinetics of the BFU-E mix imply a stem cell population more mature than the high proliferative potential colony-forming cells. However, the BFU-E mix may be responsible for erythropoiesis repopulating ability.

scholarly journals The effect of 5-fluorouracil on erythropoiesis

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1164-1170
Author(s):  
IN Rich
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Normal Values ◽  
Biologically Active ◽  
Stem Cell Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Proliferative Potential ◽  
Colony Forming Unit ◽  
Kinetics Of

The effects of a single dose (150 mg/kg) of 5-fluorouracil on mature erythroid and erythropoietic and multipotential in vitro precursor populations in the bone marrow and spleen and circulating biologically (erythroid colony forming unit [CFU-E] assay) and immunologically active (enzyme-linked immunosorbent assay) erythropoietin (Epo) are described. All mature erythroid (reticulocytes, erythrocytes) and in vitro erythropoietic precursors (CFU-E, erythroid burst-forming unit [BFU-E]) are severely reduced, if not eradicated. Transient repopulation of the pure BFU-E and CFU-E populations on days 6 and 7, respectively, produces a marked reticulocytosis after day 9. Circulating Epo increases to above normal values by day 2. However, whereas biologically active Epo remains constant at this level until day 9, immunologically active Epo continually increases; by day 12, however, both assays detect circulating Epo levels of about 400 mU/mL. In vitro multipotential stem cells (BFU-E mix) are reduced to 32% on day 1, 7.6% on day 2, and return to normal values between days 4 and 5. The survival and repopulation kinetics of the BFU-E mix imply a stem cell population more mature than the high proliferative potential colony-forming cells. However, the BFU-E mix may be responsible for erythropoiesis repopulating ability.

scholarly journals Elimination of clonogenic stem cells from human multiple myeloma cell lines by a plasma cell-reactive monoclonal antibody and complement

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1482-1489 ◽  
Author(s):  
AW Tong ◽  
JC Lee ◽  
JW Fay ◽  
MJ Stone
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Cell Lines ◽  
Plasma Cell ◽  
Colony Formation ◽  
Human Multiple Myeloma ◽  
Rpmi 8226 ◽  
Marrow Cells

Abstract The monoclonal antibody (MoAb) MM4 reacts with human multiple myeloma (MM) cell lines and bone marrow from patients with plasma cell dyscrasias but not with normal peripheral blood or bone marrow cells. Treatment with MM4 and rabbit complement (C') was cytotoxic to the plasma cell-derived cell lines GM 1312, RPMI 8226, and ARH-77, as demonstrated by chromium release microcytotoxicity and trypan blue exclusion assays. The same treatment eliminated greater than 99% of clonogenic myeloma stem cell colony formation of these cell lines, with less than 20% inhibition of normal human bone marrow pleuripotent progenitor colony formation in vitro. As an experimental model to explore the efficacy of MM4 + C' in purging MM-involved bone marrow, normal marrow cells were mixed with RPMI 8226 or GM 1312 cells in the ratio of 90:10 or 50:50 (marrow:myeloma cells). Colony growth assays indicated that MM4 + C' eliminated at least 2 logs of clonogenic myeloma stem cells in both 90:10 and 50:50 preparations, while sparing the majority of normal marrow progenitors (inhibition of CFU-C:10% to 13%; BFU-E:0%). The selectivity of MM4-mediated cytotoxicity may be useful for eliminating myeloma clonogenic stem cells from bone marrow of patients with multiple myeloma.

scholarly journals EXPERIMENTAL SUBSTANTIATION OF THE USE OF MARAL DEER ANTLERS FOR COMBATING EXTREME PSYCHO-EMOTIONAL STRESS

Biomeditsina ◽  
2019 ◽  
pp. 33-40
Author(s):  
I. N. Smirnova ◽  
N. I. Suslov ◽  
I. A. Khlusov ◽  
K. V. Zaytsev ◽  
A. A. Gostyukhina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Sleep Deprivation ◽  
Hematopoietic Stem Cells ◽  
Biologically Active ◽  
Distilled Water ◽  
Hematopoietic Stem ◽  
In Vivo Experiments

This work was aimed at investigating the effect of maral antler powder on the activity of animal hematopoietic stem cells both in vivo and in vitro.For in vivo experiments based on the model of sleep deprivation, male mice of the CBA/CaLac line were used. Prior to the experiment, mice in the experimental and control groups were intragastrically administered with a water dispersion of a maral antler powder and distilled water, respectively. Subsequently, the extraction of bone marrow from the femur, cloning of erythro- and granulo-monocytopoiesis precursors and count of the number of cell colonies were performed. Experiments in vitro involved the extraction of bone marrow cells from the femur followed by their cultivation both in a culture containing a maral antler powder (experimental) and distilled water (control culture). The number of CFU was counted 7 days following the beginning of the experiment.Maral antlers are found to exhibit no noticeable modulating effect on the colony-forming activity of mouse hematopoietic stem cells in vitro. However, according to our in vivo experiments on mice, a preventive administration of an antler powder before a stressful infl uence (sleep deprivation) prevents suppression of erythropoiaesis processes, thus exhibiting a modulating effect on the activity of CFU-E and CFU-GM by increasing the number of CFU-E and reducing the number of CFU-GM by more than three times. The modulating effect of maral antlers on the activity of hematopoietic and stem cells is based on the infl uence of biologically active substances contained therein on the neuroendocrine regulation of the hematopoietic system occurring in living organisms. 

scholarly journals Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Luara de Sousa Monteiro ◽  
Katherine Xavier Bastos ◽  
José Maria Barbosa-Filho ◽  
Petrônio Filgueiras de Athayde-Filho ◽  
Margareth de Fátima Formiga Melo Diniz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Medicinal Plants ◽  
Antitumor Activity ◽  
New Technologies ◽  
Herbal Medicines ◽  
Biologically Active ◽  
New Drugs ◽  
High Morbidity ◽  
Antitumor Potential ◽  
Living Organisms

Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.

The Mechanisms Of Damage To Bone Marrow By Iron Overload In Patients With Immuno-Related Pancytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5561-5561
Author(s):  
Rong Fu ◽  
Lei Huang ◽  
Zonghong Shao
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
Iron Overload ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Bone Marrow Damage ◽  
Normal Controls ◽  
Cd4 Lymphocytes

Abstract Objective To investigate the mechanisms of iron overloading bone marrow damage in patients with immuno-related pancytopenia. Methods Forty-seven IRP patients (21 iron overloading IRP patients) and 10 normal controls were enrolled in this study. The expression of ROS, apoptosis, Bcl-2 and Caspase-3 of the bone marrow mononuclear cells (BMMNC) were analyzed by flow cytometry. Antioxidants were added to the iron overloading IRP BMMNC, and then the changes were detected by FCM. The number and apoptosis of the T lymphocytes of IRP patients were detected. Results The ROS and apoptosis of the BMMNC, myelocytes, erythrocytes and stem cells in the bone marrow were significantly higher than those of non iron overloading IRP patients and normal controls(P<0.05). The expression of Bcl-2 in BMMNC, erythrocytes and stem cells of the iron overloading IRP patients were significantly lower than those of non iron overloading IRP patients (P<0.05). The levels of Caspase-3 in myelocytes, erythrocytes and stem cells of the iron overloading IRP patients were significantly higher than those of non iron overloading IRP patients or normal controls (P<0.05). After being treated with antioxidants, the expression of ROS, Caspase-3 and apoptosis of the iron overloading IRP BMMNC significantly decreased, the opposite of the Bcl-2. The percentage of the CD4+ lymphocytes (40.86±8.74)% and CD4+/CD8+ (1.44±0.36) in PB of the iron overloading IRP patients were significantly higher than those of non iron overloading IRP patients (35.96±7.03)% and (1.13±0.37)and normal controls(28.00±6.73)% and (0.79±0.21) (P<0.05), the opposite of CD8+ lymphocytes (P<0.05). The apoptosis of CD8+ lymphocytes (27.35±10.76)% and the ratio of CD8+ apoptosis /CD4+ apoptosis (2.51±0.80) in BM were significantly higher than those of the non iron overloading IRP patients (15.47±8.99)% and (1.39±0.47) (P<0.05). The apoptosis of the erythrocytes and stem cells coated with auto-antibodies in BM of the iron overloading IRP patients were significantly higher than those of the non iron overloading IRP patients. Conclusion Iron overload damaging the bone marrow hematopoiesis might be through the following mechanisms. 1. The increased ROS induced by iron overload affected the expression of Caspase-3 and Bcl-2, which caused the higher BMMNC apoptosis; 2. The abnormal number and ratio of T lymphocytes caused by iron overload aggravate the abnormality of immunity of IRP; 3. Iron overload may increase the damage to erythrocytes and stem cells coated with auto-antibodies. Disclosures: No relevant conflicts of interest to declare.

Mesenchymal stem cells repair bone marrow damage of aging rats and regulate autophagy and aging genes

2020 ◽  
Vol 38 (6) ◽  
pp. 792-800 ◽  
Author(s):  
Zhihong Wang ◽  
Yibin Shi ◽  
Weimin Chen ◽  
Hong Wei ◽  
Jin Shang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Aging Rats ◽  
Bone Marrow Damage

scholarly journals Elimination of clonogenic stem cells from human multiple myeloma cell lines by a plasma cell-reactive monoclonal antibody and complement

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1482-1489
Author(s):  
AW Tong ◽  
JC Lee ◽  
JW Fay ◽  
MJ Stone
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Cell Lines ◽  
Plasma Cell ◽  
Colony Formation ◽  
Human Multiple Myeloma ◽  
Rpmi 8226 ◽  
Marrow Cells

The monoclonal antibody (MoAb) MM4 reacts with human multiple myeloma (MM) cell lines and bone marrow from patients with plasma cell dyscrasias but not with normal peripheral blood or bone marrow cells. Treatment with MM4 and rabbit complement (C') was cytotoxic to the plasma cell-derived cell lines GM 1312, RPMI 8226, and ARH-77, as demonstrated by chromium release microcytotoxicity and trypan blue exclusion assays. The same treatment eliminated greater than 99% of clonogenic myeloma stem cell colony formation of these cell lines, with less than 20% inhibition of normal human bone marrow pleuripotent progenitor colony formation in vitro. As an experimental model to explore the efficacy of MM4 + C' in purging MM-involved bone marrow, normal marrow cells were mixed with RPMI 8226 or GM 1312 cells in the ratio of 90:10 or 50:50 (marrow:myeloma cells). Colony growth assays indicated that MM4 + C' eliminated at least 2 logs of clonogenic myeloma stem cells in both 90:10 and 50:50 preparations, while sparing the majority of normal marrow progenitors (inhibition of CFU-C:10% to 13%; BFU-E:0%). The selectivity of MM4-mediated cytotoxicity may be useful for eliminating myeloma clonogenic stem cells from bone marrow of patients with multiple myeloma.

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