P02.02 Modeling of response to irradiation in recurrence glioblastoma’s cells culture

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
N Antipina ◽  
A Belyashova ◽  
G Pavlova ◽  
A Nikolaeva ◽  
E Savchenko ◽  
...  
Keyword(s):  
Experimental Data ◽  
Proliferative Activity ◽  
Dose Range ◽  
Combined Treatment ◽  
Mathematical Expression ◽  
Dose Effect ◽  
Proliferating Cells ◽  
Culture Cells ◽  
Effect Curve

Abstract BACKGROUND Radiosensitivity of glioblastoma (GB) cells of local relapses may be markedly different from the primary tumor. Optimal doses and regimes of re-irradiation GB recurrence is not determined yet. MATERIAL AND METHODS GO1 primary GB cell culture was obtained during removal of a recurrent tumor after combined treatment, including irradiation of the surgical bed. Сell’s culture was irradiated by photon beams with energy 6 MeV and dose rate 600 MU/min. Irradiation performed in 1, 3 and 5 fractions, by 10 different doses for each regime. The dose range was determined experimentally for one fraction (5–250 Gy); for other regimes it was calculated according to the biological equivalent dose conception (3 fractions: 5–450 Gy, 5 fractions: 5–550 Gy). The proliferative activity of cells was investigate by MTT test. The results were normalized to the control. Dose-effect curves were plotted for each irradiation regime.The experimental data were approximated by calculated curves obtained by selecting the optimal parameters of the LQ-model and it’s modification. RESULTS Irradiation of GO1 by 1 fraction with the dose 5–250 Gy, causes a slow decrease in proliferative activity, which reaches a minimum value of 23% at 150 Gy and then remains constant. After irradiation by 3 fractions, proliferative activity of the GO1 gradually decrease only at a total dose over 120 Gy and reaches 37% after 450 Gy. When GO1 was irradiated in 5 fractions, a similar dose-effect curve was obtained, gradual decrease was observed to a value of 52% in the range of 250–500 Gy. Thus, the experimental dose-effect curves for irradiation of recurrence GB cells for 3 and 5 fractions have the appreciable “shoulder”, which could be explained by increased radioresistance. When approximating the experimental data by fitting the parameters of the LQ-model, the use of α/β = 8 provided the slope of the curve, close to the experimental data. For reflecting the “shoulder” an additional summand was introduced into the mathematical expression for the number of proliferating cells - a 105 Gy for 3 fractions and 255 Gy for 5 fractions. CONCLUSION Modified LQ-model could be used for an adequate mathematical description of the effectiveness of fractionated irradiation in relapsed GB culture cells in vitro. It’s necessary to introduce a summand into the formula that determines the formation of a “shoulder” on the dose-effect curve for this. The research was supported financially by RFBR (Project No. 18-29-01061).

The point of transition on the dose-effect curve as a reference point in the evaluation of in vitro toxicity data

2012 ◽  
Vol 32 (10) ◽  
pp. 843-849 ◽  
Author(s):  
Salomon Sand ◽  
Joakim Ringblom ◽  
Helen Håkansson ◽  
Mattias Öberg
Keyword(s):  
Reference Point ◽  
Dose Effect ◽  
In Vitro Toxicity ◽  
Toxicity Data ◽  
Effect Curve

Effect on the Sensitivity of Lymphoid Cells to Acriflavine after « in vivo » Treatment with Heterologous Albumin Coupled with Diazotized Acriflavin

1966 ◽  
Vol 52 (3) ◽  
pp. 177-185
Author(s):  
Aurelio Di Marco ◽  
Rosella Silvestrini ◽  
Emidio Calendi
Keyword(s):  
Lymph Nodes ◽  
Proliferative Activity ◽  
Lymphoid Cells ◽  
Low Doses ◽  
Proliferating Cells ◽  
In Vivo Treatment ◽  
Albino Mice ◽  
Different Doses

The possibility that the «in vivo» treatment with heterologous albumin coupled with diazotized acriflavine may affect the sensitivity of lymphoid cells to the action of acriflavine was studied. Albino mice CFW strain were treated subcutanceusly with the coupled albumin in the presence of complete Freund adjuvant. Lymph nodes from control and immunized animals, fifteen days after the treament, were cultured «in vitro» in the presence of different doses of acriflavine (from 0.5 to 4 μg/ml). The action of acriflavine was evaluated as the growth of cultures, the percent of lymphoid cells in the different phases of differentiation and the percent of proliferating cells after incubation for 24 hours in the presence of 3H thymidine. Results show that lymphoid cells of immunized mice are less sensitive to the citotoxic activity of acriflavine than those of the controls. Acriflavine, at low doses, reduces the growth of normal cultures and the proliferative activity of immature elements. At the highest doses the proliferation area is almost completely absent and the elements still present are strongly degenerated. Acriflavine, at the concentration able to reduce or to inhibit the growth of control cultures, is ineffective in altering the ratio of immature elements in cultures of immunized animals. The ability of these elements to incorporate 3H thymidine is also unchanged.

scholarly journals "Dose – effect" calibration dependence by frequency of unstable chromosomic exchanges in human lymphocytes in acute gamma irradiation by 137Сs in low doses for biological dosimetry

2021 ◽  
Vol 22 (2) ◽  
pp. 167-173
Author(s):  
V.A. Kurochkina ◽  
◽  
L.K. Bezdrobna ◽  
T.V. Tsyganok ◽  
I.A. Khomych
Keyword(s):  
Gamma Irradiation ◽  
Human Lymphocytes ◽  
Dose Range ◽  
Dose Effect ◽  
Low Doses ◽  
Radiation Factor ◽  
Calibration Dependence ◽  
Zone Of Influence ◽  
Operation Duration

The calibration dependence of dicentrics and rings chromosomes with an accompanying fragment induction in human lymphocytes by in vitro 137Сs acute gamma irradiation of blood in the dose range of 0.09 - 1.0 Gy is presented. The application of the obtained calibration curve for estimation of “biological” doses for overexposed 9 persons from the contract staff of the Chornobyl SSE is shown. Their doses calculated by the frequency of dicentrics and centric rings with consideration of operation duration and mode in the zone of influence of the radiation factor, significantly exceeded the doses determined by the methods of physical dosimetry.

scholarly journals ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression

2021 ◽  
Vol 9 ◽  
Author(s):  
Annika Dwucet ◽  
Maximilian Pruss ◽  
Qiyu Cao ◽  
Mine Tanriover ◽  
Varun V. Prabhu ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Drug Testing ◽  
Combined Treatment ◽  
Inhibitory Effect ◽  
Additional Treatment ◽  
Metabolic Reprogramming ◽  
Cellular Viability ◽  
Extracellular Flux ◽  
Glycolysis Inhibitor

The purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in high and low c-myc-expressing medulloblastoma cells. Our data show that treatment with the imipridone ONC201/TIC10 leads to a significant inihibitory effect on the cellular viability of different medulloblastoma cells independent of c-myc expression. This effect is enhanced by glucose starvation. While ONC201/TIC10 decreases the oxidative consumption rates in D458 (c-myc high) and DAOY (c-myc low) cells extracellular acidification rates experienced an increase in D458 and a decrease in DAOY cells. Combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose led to a synergistic inhibitory effect on the cellular viability of medulloblastoma cells including spheroid models. In conclusion, our data suggest that ONC201/TIC10 has a profound anti-proliferative activity against medulloblastoma cells independent of c-myc expression. Metabolic targeting of medulloblastoma cells by ONC201/TIC10 can be significantly enhanced by an additional treatment with the glycolysis inhibitor 2-Deoxyglucose. Further investigations are warranted.

Dose Effect Curve of Somatic Mutations in Ephestia kühniella Z. for Low Dose-range (0–200 r.).

Nature ◽  
1962 ◽  
Vol 194 (4830) ◽  
pp. 783-784 ◽  
Author(s):  
I. MÜLLER ◽  
E. A. LÖBBECKE ◽  
O. OLTMANNS
Keyword(s):  
Low Dose ◽  
Somatic Mutations ◽  
Dose Range ◽  
Dose Effect ◽  
Effect Curve ◽  
Ephestia Kühniella

Combined Treatment of 4′-EPI-Doxorubicin and Radiation on Hamster Lung Cells

1986 ◽  
Vol 72 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Jasna Ban ◽  
Matija Bistrović ◽  
Željko Maričić ◽  
Krsto Kolarić
Keyword(s):  
Combined Treatment ◽  
Chinese Hamster ◽  
Drug Action ◽  
Simultaneous Action ◽  
Lung Cells ◽  
Cytotoxic Effects ◽  
Culture Cells ◽  
Tissue Culture Cells ◽  
Cell Kill

The purpose of this study was to test the type and the degree of cytotoxic effects of epirubicin and radiation in combined treatment on Chinese hamster lung cells in vitro. Experiments were performed with proliferating tissue culture cells. Cell kill was determined by colony-forming ability. The maximum killing effects were obtained when simultaneous action of drug treatment and irradiation occurred. Their interaction was synergistic. Synergism depended on time of drug incubation (epirubicin present for 1 h). Slight antagonism was noted after prolonged drug action (24 h).

LOCAL HYPERTHERMIA IN TREATMENT FOR MALIGNANT BRAIN TUMORS

2018 ◽  
Vol 64 (1) ◽  
pp. 54-61
Author(s):  
A. Ryabova ◽  
O. Gribova ◽  
V. Novikov ◽  
E. Choinzonov ◽  
Zh. Starceva ◽  
...  
Keyword(s):  
Experimental Data ◽  
Radiation Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Combined Treatment ◽  
Complex Treatment ◽  
Local Hyperthermia ◽  
Malignant Brain Tumors ◽  
Sensitizing Effect ◽  
Methods Of Treatment

Unsatisfactory results of complex treatment for malignant brain tumors stimulate search of new effective methods of treatment. Radiation therapy is an integral part of the combined treatment but often does not influence lethally on resistant tumor cells. Thereby in recent decades there has been an active search for different modifiers, which can increase the sensitivity of tumors to chemotherapy and radiotherapy. One of the universal sensitizers is the local hyperthermia. Experimental data showed that the effect of high temperatures had both a direct damaging effect on tumor cells and a sensitizing effect. The literature review given in the article provides an overview of the existing methods of the local hyperthermia for brain tumors treatment.

(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

2020 ◽  
Vol 17 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Chandrakant Dhondiram Pawar ◽  
Dattatraya Navnath Pansare ◽  
Devanand Baburao Shinde
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Thiophene Ring ◽  
Amide Group ◽  
Peptide Coupling ◽  
Ic50 Value ◽  
Important Building Block ◽  
Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

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