scholarly journals Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

2021 ◽  
Vol 15 (2) ◽  
pp. 15-24
Author(s):  
M. V. Popovych ◽  
◽  
Ya. R. Shalai ◽  
V. P. Hreniukh ◽  
O. R. Kulachkovskyy ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
The Body ◽  
Thiazole Derivatives ◽  
Lymphoma Cells ◽  
Thiazole Derivative ◽  
Polymeric Carriers

Background. A pronounced cytotoxic action of the thiazole derivatives complexed with polymeric carriers on tumor cells in vitro was reported earlier, while no cytotoxicity of these compounds was detected toward noncancerous cells. It was found that thiazole derivatives at concentrations of 10 and 50 µM affected lymphoma cell ultrastructure in vitro. The purpose of this work was to investigate the effect of thiazole derivative 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]- thiazolo-[3,2-a]-pyrimidin-4(2H)-one (PP2) and its complexes with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th12) and poly(PEGMA) (Th14) on the ultrastructure of lymphoma cells in vivo. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascite tumors were created by intreperitoneal inocu­lation of 1–2 mln of Nemet–Kelner lymphoma cells to mice. On the 12th day after inoculation, the body weight of animals was increased by 140–160 % mostly due to ascites growth. For treatment of ascites three solutions of the chemical compounds were prepared: PP2, PP2 + Th12, PP2 + Th14 and administered to the mice intraperitoneally for 5 days. The final concentration of PP2 was 5 mg/kg of body weight. Abdominal drainage from ascites was performed with a sterile syringe under chloroform anesthesia on the 10th day after the start of treatment. The ultrastructure of the cells was examined by electron microscopy. Results. Еlectron microscopy study showed that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, a decreased nucleus/cytoplasm ratio, a destruction of the plasma membrane and a change of mitochondria shape. The studied compound complexed with polymeric carriers caused an apoptotic-like changes in lymphoma cells. Under the action of such complexes, the nucleus/cytoplasm ratio decreased and the area of mitochondria increased. Conclusions. The obtained results suggest that the tested compounds induce apoptosis in tumor cells. Complexes of thiazole derivative with polymers do not impair the effect of the compound on lymphoma cells. The obtained data can be used to carry out further preclinical studies of thiazole derivatives complexed with polymeric carriers as potential antitumor drugs.

scholarly journals Effect of a novel thiazole derivative and its complex with polymeric carriers on the activity of antioxidant enzymes in murine lymphoma cells

2021 ◽  
Vol 15 (4) ◽  
pp. 37-48
Author(s):  
M. V. Popovych ◽  
◽  
Ya. R. Shalai ◽  
S. M. Mandzynets ◽  
N. E. Mitina ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Tumor Cells ◽  
Antioxidant Defense ◽  
Antioxidant Defense System ◽  
Defense System ◽  
Thiazole Derivatives ◽  
Lymphoma Cells ◽  
Thiazole Derivative ◽  
Polymeric Carriers

Background. Previous studies have shown a pronounced cytotoxic effect of thiazole derivatives in combination with polymeric carriers on tumor cells. At the same time, the derivatives were not cytotoxic against non-cancerous cells in vitro. It was shown that thiazole derivatives at concentrations of 10 and 50 μM affected the prooxidant and antioxidant systems of lymphoma cells in vitro. The aim of this work was to study the effect of the complex of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) in combination with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th1), poly(PEGMA) (Th3) and poly(PEGMA-co-DMM) (Th5) on the antioxidant defense system of the NK/Ly cell in vitro. Materials and Methods. The experiments were performed on white wild-type male mice with grafted NK/Ly lymphoma. Tumor cells were inoculated into mice intraperitoneally. Ascites was drained from the abdominal cavity of anaesthetized mice with a sterile syringe on the 7th-10th day after inoculation. Investigated compounds BF1, BF1 + Th1 (Th2, Th12), BF1 + Th3 (Th4, Th14), BF1 + Th5 (Th6, Th16) at a final concentration of 10 μM were added to the lymphoma samples and incubated for 10 min; the activity of antioxidant enzymes was determined according to the techniques described previously. Results. It was found that all the studied complexes based on thiazole derivative BF1 and polymeric carriers poly (VEP-co-GMA)-graft-mPEG (Th2, Th12), poly (PEGMA) (Th4, Th14) and poly (PEGMA-co-DMM) (Th6, Th16) at a concentration of 10 μm increased the activity of SOD, while the activity of CAT and GPX were reduced compared to control. Complexes Th2, Th12 and Th4 increased the significance of the BF1 influence on lymphoma cells from P <0.05 to P <0.01. Pure polymeric carriers did not affect the level of the antioxidant defense system enzymes. Conclusions. Thus, it was found that the polymeric carriers in combination with thiazole derivative BF1 increased the significance of thiazole derivative BF1 influence on the activity of the antioxidant defense system of lymphoma cells, while pure polymeric carriers did not affect the activity of SOD, CAT or GPX. The results of this work can be used for further studies of complexes of thiazole derivative and PEG-containing polymeric carriers as potential antitumor drugs.

scholarly journals Involvement of leukocyte function-associated antigen-1 (LFA-1) in the invasion of hepatocyte cultures by lymphoma and T-cell hybridoma cells.

1987 ◽  
Vol 105 (1) ◽  
pp. 553-559 ◽  
Author(s):  
E Roos ◽  
F F Roossien
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Cell Types ◽  
Hybridoma Cells ◽  
Lymphoma Cells ◽  
Hepatocyte Cultures ◽  
Leukocyte Function ◽  
Vitro Model

We studied the interaction of MB6A lymphoma and TAM2D2 T cell hybridoma cells with hepatocyte cultures as an in vitro model for in vivo liver invasion by these tumor cells. A monoclonal antibody against leukocyte function-associated antigen-1 (LFA-1) inhibited adhesion of the tumor cells to the surface of hepatocytes and consequently strongly reduced invasion. This effect was specific since control antibodies, directed against Thy.1 and against T200, of the same isotype, similar affinity, and comparable binding to these cells, did not inhibit adhesion. This suggests that LFA-1 is involved in the formation of liver metastases by lymphoma cells. TAM2D2 T cell hybridoma cells were agglutinated by anti-LFA-1, but not by control antibodies. Reduction of adhesion was not due to this agglutination since monovalent Fab fragments inhibited adhesion as well, inhibition was also seen under conditions where agglutination was minimal, and anti-LFA-1 similarly affected adhesion of MB6A lymphoma cells that were not agglutinated. The two cell types differed in LFA-1 surface density. TAM2D2 cells exhibited 400,000 surface LFA-1 molecules, 10 times more than MB6A cells. Nevertheless, the level of adhesion and the extent of inhibition by the anti-LFA-1 antibody were only slightly larger for the TAM2D2 cells.

scholarly journals FURTHER STUDIES ON EFFECTS OF TISSUE EXTRACTS ON STAPHYLOCOCCUS AUREUS

1946 ◽  
Vol 84 (3) ◽  
pp. 247-261 ◽  
Author(s):  
Leo G. Nutini ◽  
Sister Eva Maria Lynch
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
The Body ◽  
Brain Extract ◽  
Toxicity Tests ◽  
Control Series ◽  
Experimental Animals ◽  
Tissue Extracts

1. The ability of alcoholic-precipitated extracts of beef tissue—brain, spleen, heart, and kidney—to stimulate the growth of Staphylococcus aureus, in vitro, and to convert the yellow S form to a white R variant with altered biochemical characteristics conforming to those of an avirulent organism, has been confirmed. 2. The avirulence of the white R variant has been established by tests in vivo on mice. 3. Staphylococcus aureus infections induced subcutaneously, intraperitoneally, and intravenously in mice responded favorably to brain extract following subcutaneous or oral administration. The mortality was 2 per cent in 444 experimental animals and 81 per cent in 448 control animals. 4. The extracts appeared equally efficient when used therapeutically (mortality 2 per cent of 162 experimental animals and 90 per cent in the control series) or prophylactically (mortality 2 per cent of 282 experimental animals and 76 per cent in 286 control mice). Extracts of brain and spleen were more effective than those of either heart or kidney. 5. Studies concerning the mechanism of action of the tissue extracts indicate that they prevented the formation of toxin by Staphylococcus aureus, and had but little effect on toxin actions. 6. Toxicity tests revealed that the brain and spleen extracts were relatively non-toxic, dosages equivalent to 2 per cent of the body weight being well tolerated. Kidney and heart extracts were much more toxic, producing mortality in dosages as low as 0.3 per cent of the body weight.

Effective Induction of Apoptosis by Mistletoe Plant Extracts in an Acute Lymphoblastic Leukemia Model.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1880-1880
Author(s):  
Georg Seifert ◽  
Patrick Jesse ◽  
Aram Prokop ◽  
Tobias Reindl ◽  
Stephan Lobitz ◽  
...  
Keyword(s):  
Cell Death ◽  
Body Weight ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
The Body ◽  
Induction Of Apoptosis ◽  
First Time ◽  
Over Time

Abstract Mistletoe (Viscum album) is one of the most used alternative cancer therapies applied as monotherapy or in combination with conventional therapies. Anti-tumor effects of mistletoe (MT) extracts were related to cytostatic and immunomodulatory effects observed in vitro. Aqueous MT extracts contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. The MT lectins inhibit protein biosynthesis by inactivating the 60S ribosomal subunit. Mistletoe lectin-I (ML-I) is one important apoptosis inducing compound. It is a heterodimer that consists of a cytotoxic A-chain (ribosome inactivating protein, RIP type 1) linked by a carbohydrate binding B-chain for cellular lectin uptake. However, although MT is widely used, there is a lack of scientific preclinical and clinical data. Here, we describe for the first time efficacy and mechanism of MT extracts against lymphoblastic leukemia in vitro and in vivo. For this purpose, we first investigated both the cytotoxic effect and mechanism of action of two standardized aqueous MT extracts (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) and isolated ML-I, in three human acute lymphoblastic leukemia (ALL) cell lines (NALM-6, sup-B-15 and REH). MT-A, MT-P and ML-I clearly inhibited cell proliferation as determined by LDH reslease assays at very low concentrations (ML-I LD50 from 0,05 ng/ml to 10 ng/ml depending on the host tree) with MT-P being the most cytotoxic extract. The mechanism of cell death was determined by DNA-fragmentation assays. These indicated dose dependent induction of apoptosis as the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). For this purpose, mice (n=8/group) were injected i.v. with 1 × 106NALM6 cells and treated by intraperitoneal injections four times per week for 3 weeks (day 1–4; 7–11; 14–18) at varying doses (1, 5 and 50 mg/Kg (plant weight/body weight)). Mice (n=8) treated with PBS and cyclophosphamide (100 mg/kg, once on day 1) were used as negative and positive controls, respectively. Toxicity, peripheral blood counts, bodyweight and survival was determined over time. Interestingly, both MT extracts in all tested concentrations significantly improved survival (up to 55,4 days) in contrast to controls (34,6 days). Furthermore, no hematologic side effects were observed from this treatment as indicated by completely stable blood counts. Also the body weight of treated animals remained stable over time indicating a complete absence of systemic toxicity in the selected dose range. In summary, we demonstrate for the first time efficacy and mechanism of MT extracts against ALL in vitro and in vivo and hereby provide an important base line for the design of clinical trials with these compounds.

scholarly journals Repression of LKB1 by miR-17∼92 sensitizes MYC-dependent lymphoma to biguanide treatment

2019 ◽  
Author(s):  
Said Izreig ◽  
Alexandra Gariepy ◽  
Ariel O. Donayo ◽  
Gaëlle Bridon ◽  
Daina Avizonis ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Human Cancer ◽  
Tca Cycle ◽  
Mirna Cluster ◽  
Lymphoma Cells ◽  
Ampk Signaling ◽  
Potential Biomarker

AbstractCancer cells display metabolic plasticity to survive metabolic and energetic stresses in the tumor microenvironment, prompting the need for tools to target tumor metabolism. Cellular adaptation to energetic stress is coordinated in part by signaling through the Liver Kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Reducing LKB1-AMPK signaling exposes metabolic vulnerabilities in tumor cells with potential for therapeutic targeting. Here we describe that miRNA-mediated silencing of LKB1 (mediated by the oncogenic miRNA cluster miR-17∼92) confers sensitivity of lymphoma cells to mitochondrial inhibition by biguanides. Using both classic (phenformin) and novel (IM156) biguanides, we demonstrate that Myc+ lymphoma cells with elevated miR-17∼92 expression display increased sensitivity to biguanide treatment both in cell viability assays in vitro and tumor growth assays in vivo. This increased biguanide sensitivity is driven by miR-17-dependent silencing of LKB1, which results in reduced AMPK activation in response to bioenergetic stress. Mechanistically, biguanide treatment inhibits TCA cycle metabolism and mitochondrial respiration in miR-17∼92-expressing tumor cells, targeting their metabolic vulnerability. Finally, we demonstrate a direct correlation between miR-17∼92 expression and biguanide sensitivity in human cancer cells. Our results identify miR-17∼92 expression as a potential biomarker for biguanide sensitivity in hematological malignancies and solid tumors.One Sentence SummarymiR-17∼92 expression in Myc+ tumors sensitizes cancer cells to biguanide treatment by disrupting bioenergetic stability in lymphoma cells.

scholarly journals VIABILITAS BAKTERI PROBIOTIK IN-VITRO DAN PENGARUH PEMBERIAN AIR OKSIGEN TERHADAP PERTUMBUHAN BAKTERI PROBIOTIK SECARA IN-VIVO

2007 ◽  
Vol 2 (1) ◽  
pp. 22
Author(s):  
Enok Sobariah ◽  
Ali Khomsan ◽  
Ingrid S. Surono
Keyword(s):  
Body Weight ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Day Treatment ◽  
The Body ◽  
Probiotic Bacteria ◽  
Control Group ◽  
Oxygenated Water

<p class="MsoNormal" style="margin: 0cm 12.45pt 6pt 17.85pt; text-align: justify;"><span style="font-size: 10pt;" lang="en-us" xml:lang="en-us">The aim of this study were  to identify the in-vitro tolerance of pro-biotic bacteria to acid and bile salt condition; and  to prove a hypothesis that the supplementation of oxygenated water has a positive effect on the body weight of rat and on viability of pro-biotic bacteria.  The first study was carried out at PAU Laboratory of Bogor Agricultural University, while the second study was conducted at Department of Community Nutrition of Bogor Agricultural University and Microbiology Laboratory of Indonesia Institute of Technology. Forty five rats aged 6 weeks were divided into three groups, i.e., control group without probiotic (a0), Lactobacillus casei Shirota (a1), and Lactobacillus IS-7257 (a2).  Each group (consisting of 5 rats each) has three different treatments, namely, control without oxygenated water (b0), 50 ppm oxygenated water (b2), and 80 ppm oxygenated water (b2). Oxygenated water was administered to the rats twice a day in the morning (3.25 ml) and afternoon (3.00 ml). Observation was carried out on the body  weight of the rats, fecal lactic acid bacteria, coliform, and anaerob bacteria by plate counting, for 4 periods, i.e, prior to the treatment (C0), after three-day treatment (C1), after seven-day treatment (C2), and on the 10<sup>th</sup> day treatment or three days after washed out period. The results indicated that probiotic bacteria are resistant to acid and bile acid condition. Oxygen concentration in water has a significant positive influence on the body weight of rats towards viability of probiotic bacteria (p-level &lt; 0.05).  The supplementation of  oxygenated water 50 ppm significantly increase the population of viable fecal lactic acid bacteria in L. casei Shirota and Lactobacillus IS-7257 groups after 3 and 7 days of treatment.  Lactobacillus IS-7257 gave better response than L. casei Shirota. The supplementation of oxygenated water 80 ppm significantly reduces the fecal coliform in-vivo in both L. casei Shirota and Lactobacillus IS-7257 groups (p-level &lt; 0.05).</span></p>

scholarly journals Anti-obesity effect of Tamarindus indicus seed extract against a high-fat diet-induced obese model in rats

2020 ◽  
Vol 11 (2) ◽  
pp. 2083-2089
Author(s):  
Nabeel K ◽  
Asra Fathima ◽  
Farhath Khanum ◽  
Manjula S N ◽  
Mruthunjaya K ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Seed Extract ◽  
The Body ◽  
High Fat ◽  
Cell Viability Assay ◽  
Serum Triglycerides

The present study was aimed to evaluate the anti-obesity property of Tamarindus indica seed extract (TSE) on high fat-fed obese rats. TSE was prepared by cold maceration method and qualitative phytochemical studies had been carried out. In vitro cell viability assay (MTT assay) was and oil red staining for evaluating the lipid accumulation in cells was carried out using 3T3-L1 cells, and leptin levels was evaluated by ELISA. In-vivo Obesity was induced in experimental rats by administration of a high-fat diet for 04 weeks. The anti-obesity effect was screened by oral administration of TSE at two different dose levels i.e., 250 and 500mg/kg b. Wt. Along with a high-fat diet for a period of 04 weeks. The anti-obesity activity is estimated in terms of body weight gain, serum triglycerides (TG), Total cholesterol (TC). In -vitro studies revealed that the TSE has no cytotoxic effect, Administration of a high-fat diet for 04 weeks significantly increased the body weight, serum triglycerides, cholesterol. Upon treatment with TSE, a significant dose-dependent alteration in body weight, triglycerides, cholesterol levels were observed, inferring the anti-obesity property of Tamarindus seed extract.

Programming the anti-tumor immune response in vitro and its application to stop the growth of tumor cells and prolonging the lifespan of mice with carcinoma in vivo

2017 ◽  
pp. 67-73
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
О.П. Буданова ◽  
И.Ю. Малышев
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Tumor Cells ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Ec Cells ◽  
Growth Of Tumor ◽  
Immune Response In Vitro

Цель - представить доказательства правомерности гипотезы, что комбинированный пул репрограммированных in vitro макрофагов и лимфоцитов будет эффективно ограничивать пролиферацию опухолевых клеток in vitro , а при введении в организм будет существенно ограничивать развитие опухоли in vivo . Методика. Размножение опухолевых клеток инициировали in vitro путем добавления клеток карциномы Эрлиха (КЭ) в среду культивирования RPMI-1640. Развитие асцитной опухоли in vivo воспроизводили путем внутрибрюшной инъекции клеток КЭ мышам. Результаты. Установлено, что M3 макрофаги вместе с антиген-репрограммированными лимфоцитами оказывают выраженный противоопухолевый эффект и in vitro, и in vivo , который был существеннее противоопухолевого эффекта цисплатина. Заключение. Факты, свидетельствующие, что М3 макрофаги в сочетании с in vitro антиген-репрограммированными лимфоцитами значительно подавляют рост опухоли in vivo , делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли путем предварительного программирования противоопухолевого иммунного ответа «в пробирке». Aim. To test a hypothesis that a combined pool of in vitro reprogrammed macrophages and lymphocytes will effectively limit growth of tumor cells in vitro , and injections of these cells into the body will considerably limit development of a tumor in vivo . Methods. Tumor growth was initiated in vitro by addition of Ehrlich carcinoma (EC) cells to the RPMI-1640 cell culture medium and in vivo by intraperitoneal injection of EC cells into mice. Results. M3 macrophages in combination with antigen-reprogrammed lymphocytes exerted a pronounced antitumor effect both in vitro and in vivo, which was superior to the effect of cisplatin. Conclusion. M3 macrophages in combination with in vitro antigen-reprogrammed lymphocytes significantly inhibited the tumor growth in vivo . This fact justifies development of a clinical version of the tumor growth restricting biotechnology using pre-programming of the antitumor immune response in vitro .

Effects of Hwangryunjihwang-tang on In Vitro Fertilization and Ovulation in Mice Fed a High-fat Diet

2003 ◽  
Vol 31 (02) ◽  
pp. 213-223
Author(s):  
H. G. Choi ◽  
D. H. Kwak ◽  
J. Y. Kim ◽  
Y. J. Choi ◽  
B. S. Kil ◽  
...  
Keyword(s):  
Body Weight ◽  
Embryonic Development ◽  
High Fat Diet ◽  
Normal Diet ◽  
The Body ◽  
High Fat ◽  
Reproductive Dysfunction ◽  
Vitro Fertilization

It has been generally accepted that Hwangryunjihwang-tang (H-tang) is a useful prescription for treating polydipsia and to prevent obesity induced by a high-fat diet. The aim of this study was to clarify whether H-tang improved reproductive dysfunction caused by obesity in mice. Mice were fed a high density protein and lipid diet for 4 weeks, followed by administration of H-tang at 480 mg/kg body weight per day for 4 days. Thereafter, changes of body weight, ovulation rate, in vitro and in vivo fertilization, embryonic development and implantation rate were measured. H-tang markedly reduced the body weight of obese mice fed a high-fat diet, but not mice fed a normal diet. H-tang significantly improved ovulation rates, in vitro and in vivo fertilization rates and embryonic development. These results indicate pharmacological reversal of reproductive dysfunction caused by obesity, perhaps by adjusting internal secretions and metabolic functions.

scholarly journals Distribution and Excretion of BisGMA in Guinea Pigs

2008 ◽  
Vol 87 (4) ◽  
pp. 378-380 ◽  
Author(s):  
F.X. Reichl ◽  
M. Seiss ◽  
N. Kleinsasser ◽  
K. Kehe ◽  
K.H. Kunzelmann ◽  
...  
Keyword(s):  
Body Weight ◽  
Guinea Pigs ◽  
Dental Materials ◽  
The Body ◽  
Urine Level ◽  
Mammalian Tissues ◽  
Dose Levels ◽  
Adjusted Dose

Bisphenol-A-glycidyldimethacrylate (BisGMA) is used in many resin-based dental materials. It was shown in vitro that BisGMA was released into the adjacent biophase from such materials during the first days after placement. In this study, the uptake, distribution, and excretion of [14C]BisGMA applied via gastric and intravenous administration (at dose levels well above those encountered in dental care) were examined in vivo in guinea pigs to test the hypothesis that BisGMA reaches cytotoxic levels in mammalian tissues. [14C]BisGMA was taken up rapidly from the stomach and intestine after gastric administration and was widely distributed in the body following administration by each route. Most [14C] was excreted within one day as 14CO2. The peak equivalent BisGMA levels in guinea pig tissues examined were at least 1000-fold less than known toxic levels. The peak urine level in guinea pigs that received well in excess of the body-weight-adjusted dose expected in humans was also below known toxic levels. The study therefore did not support the hypothesis.

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