scholarly journals RELATIONSHIP BETWEEN GLUCOSE METABOLISM IN CANCER CELLS WITH DIFFERENT METASTATIC POTENTIAL AND CELL SENSITIVITY TO ANOIKIS

InterConf ◽  
2021 ◽  
pp. 462-468
Author(s):  
Denis Kolesnik ◽  
Olga Pyaskovskaya ◽  
Nataliia Shliakhtova ◽  
Galina Solyanik

Despite the significant intensification of research on the mechanisms of anoikis, the question of how metastatic cells avoid death upon separation from the extracellular matrix remains open. The aim of the study was to investigate in vitro glucose metabolism in the cells of two variants of Lewis lung carcinoma with different metastatic potential (highly metastatic LLC cells and low metastatic LLC/R9 cells) and to analyze the relationship between metastatic potential, glucose oxidation intensity and cell sensitivity to anoikis. A comparative analysis of the studied indices showed that in conditions of deadhesive growth (which simulated the process of dissemination of metastatically active cells) LLC/R9 cells (as opposed to LLC cells) were characterized by a decreased glycolysis intensity and decreased sensitivity to anoikis. The stability of the glycolysis intensity in LLC cells during the transition to deadhesive growth conditions determined both the resistance (at least in part) of these cells to anoikis and their high metastatic potential.

1999 ◽  
Vol 112 (16) ◽  
pp. 2785-2795
Author(s):  
F.M. Johnson ◽  
B.D. Shur

Beta1,4-Galactosyltransferase I (GalT I) is localized on the leading lamellipodia of migrating cells, where it associates with the cytoskeleton and facilitates cell spreading and migration on basal lamina matrices. It has previously been reported that a variety of highly metastatic murine and human cell lines are characterized by elevated levels of cell surface GalT I, although the intracellular biosynthetic pool is similar between cells of high and low metastatic potential. In this study, we examined whether the elevated expression of surface GalT I characteristic of metastatic cells is instructive or incidental to their metastatic behavior by altering the expression of surface GalT I and by the use of GalT I-specific perturbants. Surface GalT I levels were positively and negatively altered on murine melanoma cells by either overexpressing full-length GalT I or by homologous recombination, respectively. The consequences of altered surface GalT I expression on cell invasion in vitro and lung colonization in vivo were determined. Increasing surface GalT I expression on cells of low metastatic potential to levels characteristic of highly metastatic cells recapitulated the highly invasive phenotype in vitro. Alternatively, decreasing surface GalT I expression on highly metastatic cells to levels characteristic of low metastatic cells reduced their invasive behavior in vitro and metastatic activity in vivo. Within the physiological range of surface GalT I expression, the invasive potential of each clonal cell line correlated strongly with the level of surface GalT I expressed. As an independent means to assess the involvement of surface GalT I in metastatic behavior, cells were pretreated with two different classes of surface GalT I perturbants, a competitive oligosaccharide substrate and a substrate modifier protein. Both perturbants inhibited metastatic colonization of the lung, whereas control reagents did not. Finally, as reported by others, surface GalT I on metastatic cells selectively interacted with one glycoprotein substrate, or ligand, of approximately 100 kDa, the identity of which remains obscure. These results show that the elevated expression of surface GalT I characteristic of highly metastatic cells contributes to their invasive phenotype in vitro and to their metastatic phenotype in vivo.


Author(s):  
H.-B. Zhuang ◽  
Ch.-S. Chen ◽  
S.-Y. Lee ◽  
M.-Ch. Pan

Resonance frequency analysis (RFA) has been applied to detect the stability and boundary condition of the dental implant osseointegration in several investigations. Its clinical relating application was generally accepted. Nevertheless, these studies only presented the overall phenomena of osseointegration around the implant and were unable to diagnose the location of the bone defect. Therefore, the aim of this study refers to an effective detection technique for locating the position of bone defect surrounding the dental implant. Various in-vitro bone defect models composed of a dental implant, a healing abutment and an artificial bone block were used to perform the experimental modal analysis (EMA). The bone defect model was excited by an impacted hammer; induced vibration response was acquired by an accelerometer and processed through a spectrum analyzer. The statistical analysis was used to generalize the relationship between the obtained RF values and various bone defects from experimental results. The finding of this study indicates that RF decreases remarkably when the range and depth of defects increase. Thus, the direction of the defect is decided first by RF variations of the sound and defective side, and the position of the defect is discriminated later by RF differences of various bone defect models. This conclusion assists doctors in diagnosis after surgery.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Huimin Hou ◽  
Ying Wang ◽  
Chunshi Li ◽  
Jian Wang ◽  
Yanli Cao

Epigallocatechin-3-gallate (EGCG), a major active ingredient in green tea, has various health benefits. It affects glucose metabolism, but the mechanism is not well understood. This study aimed to identify targets of EGCG related to glucose metabolism. The core fragment of EGCG is a flavonoid. The flavonoid scaffold was used as a substructure to find proteins cocrystallized with flavonoids in the Protein Data Bank. The proteins identified were screened in PubMed for known relationships with diabetes. Dipeptidyl peptidase-4 (DPP4; PDB 5J3J) was identified following this approach. By molecular docking, the interactions of EGCG and DPP4 were assessed. To test the stability of the interactions between EGCG and DPP4, molecular dynamics simulation for 100 ns was performed using Desmond software. In vitro, the concentration of EGCG required to inhibit DPP4 activity by 50% (the IC50 value) was 28.42 μM. These data provide a theoretical basis for intervention in glucose metabolism with EGCG.


Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.


Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.


1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.


1993 ◽  
Vol 70 (06) ◽  
pp. 0998-1004 ◽  
Author(s):  
Páll T Önundarson ◽  
H Magnús Haraldsson ◽  
Lena Bergmann ◽  
Charles W Francis ◽  
Victor J Marder

SummaryThe relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.


1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.


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