Simultaneous Model Selection and Model Calibration for the Proliferation of Tumor and Normal Cells During In Vitro Chemotherapy Experiments

2018 ◽  
Vol 25 (12) ◽  
pp. 1285-1300 ◽  
Author(s):  
JosÉ M.J. Costa ◽  
Helcio R.B. Orlande ◽  
Viviane O.F. Lione ◽  
Antonio G.F. Lima ◽  
TaynÁ C.S. Cardoso ◽  
...  
Keyword(s):  
Model Selection ◽  
Model Calibration ◽  
Normal Cells ◽  
Simultaneous Model ◽  
In Vitro Chemotherapy

Immunoenzymatic demonstration of the simultaneous presence of transferrin, hemopexin and albumin in a same hepatocyte and their ultrastructural localization

1978 ◽  
Vol 36 (2) ◽  
pp. 88-89
Author(s):  
M. Kraemer ◽  
J. Foucrier ◽  
J. Vassy ◽  
M.T. Chalumeau
Keyword(s):  
Plasma Proteins ◽  
Rat Hepatocytes ◽  
Ultrastructural Localization ◽  
Carrier Proteins ◽  
Normal Cells ◽  
Adult Rat ◽  
Adult Rat Hepatocytes ◽  
Monospecific Antisera ◽  
Different Levels

Some authors using immunofluorescent techniques had already suggested that some hepatocytes are able to synthetize several plasma proteins. In vitro studies on normal cells or on cells issued of murine hepatomas raise the same conclusion. These works could be indications of an hepatocyte functionnal non-specialization, meanwhile the authors never give direct topographic proofs suitable with this hypothesis.The use of immunoenzymatic techniques after obtention of monospecific antisera had seemed to us useful to bring forward a better knowledge of this problem. We have studied three carrier proteins (transferrin = Tf, hemopexin = Hx, albumin = Alb) operating at different levels in iron metabolism by demonstrating and localizing the adult rat hepatocytes involved in their synthesis.Immunological, histological and ultrastructural methods have been described in a previous work.

Cytotoxicity Studies of Curcumin Loaded-Cockle Shell-Derived Calcium Carbonate Nanoparticles

2019 ◽  
Vol 09 ◽  
Author(s):  
Maryam Muhammad Mailafiya ◽  
Mohamad Aris Mohd Moklas ◽  
Kabeer Abubakar ◽  
Abubakar Danmaigoro ◽  
Samaila Musa Chiroma ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Safety Margin ◽  
Bone Diseases ◽  
In Vivo Studies ◽  
Normal Cells ◽  
Cytotoxicity Studies ◽  
Standard Techniques ◽  
Cockle Shell

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possess wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attentions. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at higher dose of 500 µg/ml and 40 µg/ml respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone related ailments.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

scholarly journals Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie Shinohara ◽  
Hiroshi Arakawa ◽  
Yuuichi Oda ◽  
Nobuaki Shiraki ◽  
Shinji Sugiura ◽  
...  
Keyword(s):  
Normal Cell ◽  
Human Hepatocytes ◽  
New Drugs ◽  
Intestinal Cells ◽  
Specific Gene ◽  
Gene Expressions ◽  
Normal Cells ◽  
Pneumatic Pressure ◽  
Pressure Driven

AbstractExamining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance and careful handling. Herein, we demonstrated the potential of coculturing normal cells on MPSs in the evaluation of intestine–liver interactions. To this end, we cocultured human-induced pluripotent stem cell-derived intestinal cells and fresh human hepatocytes which were isolated from PXB mice with medium circulation in a pneumatic-pressure-driven MPS with pipette-friendly liquid-handling options. The cytochrome activity, albumin production, and liver-specific gene expressions in human hepatocytes freshly isolated from a PXB mouse were significantly upregulated via coculture with hiPS-intestinal cells. Our normal cell coculture shows the effects of the interactions between the intestine and liver that may occur in vivo. This study is the first to demonstrate the coculturing of hiPS-intestinal cells and fresh human hepatocytes on an MPS for examining pure inter-organ interactions. Normal-cell coculture using the multi-organ MPS could be pursued to explore unknown physiological mechanisms of inter-organ interactions in vitro and investigate the physiological response of new drugs.

The effect of a yeast extract (PCO) on the mitotic activity of neoplastic and normal cells in vitro

1973 ◽  
Vol 5 (4) ◽  
pp. 307-314 ◽  
Author(s):  
John C. Fardon ◽  
Sister M. Eymard Poydock ◽  
Yoshiki Tsuchiya
Keyword(s):  
Mitotic Activity ◽  
Yeast Extract ◽  
Normal Cells

scholarly journals In Vitro Antitumor Activity of Endophytic Fungi Isolated From the Mexican Cactus Pachycereus Marginatus (DC.) Britton & Ros

2021 ◽  
Author(s):  
Jesica M. Ramírez-Villalobos ◽  
César I. Romo-Sáenz ◽  
Karla S. Morán Santibañez ◽  
Patricia Tamez-Guerra ◽  
Ramiro Quintanilla-Licea ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Endophytic Fungi ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Normal Cells ◽  
Human Tumor Cell Lines ◽  
Ht 29 ◽  
Mcf 7

Abstract Background: Arid zone plants such as cacti are known to harbor diverse groups of endophytic fungi, which represent potential sources of new compounds with anticancer properties. In the present study we isolated, identified, and characterized Pachycereus marginatus (DC.) Britton & Ros endophytic fungi with cytotoxic activity against murine and human tumor cell lines.Methods: Endophytic fungi were isolated from P. marginatus stems. Methanol extracts were then obtained from fungi liquid cultures and their cytotoxic activity at concentrations ranging from 31 µg/ml to 250 µg/ml against murine L5178Y-R lymphoma, human colorectal adenocarcinoma HT-29, and human breast cancer MCF-7 was evaluated by the colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction assay, using the normal cells Macacus rhesus monkey epitelial kidney MA-104 and human peripheral blood mononuclear cells (PBMC) as controls. IC50 values were obtained and the selectivity index (SI) was calculated from the IC50 ratio of cancer cells and normal cells. Furthermore, molecular identification of fungi showing cytotoxic activity was determined by the internal transcribed spacer molecular marker.Results: The Cladosporium sp. PME-H008 strain showed significant (P < 0.01) 94.3% and 36.8% cytotoxicity against L5178Y-R and HT-29 cells, respectively. The highest SI was observed by L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMC respectively. In addition, the Metarhizium anisopliae PME-H007 strain was more effective against MCF-7 with 55.8% cytotoxicity. The lowest IC50 was obtained with the Aspergillus sp. PME-H005 strain at 95.21 µg/ml against the MCF-7 cell line, followed by PME-H008 strain at 101 µg/ml against L5178Y-R cells.Conclusion: P. marginatus endophytic fungi showed in vitro cytotoxic activity against murine and human tumor cell lines, without affecting normal cells.

Abstract 246: Human Induced Pluripotent Stem Cells Reveal Mitophagy as an Essential Process Against Diabetic Cardiomyopathy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Sang-Ging Ong ◽  
Won Hee Lee ◽  
Kazuki Kodo ◽  
Haodi Wu ◽  
Joseph C Wu
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Fission ◽  
Induced Pluripotent Stem Cell ◽  
Mitochondrial Fragmentation ◽  
Normal Cells ◽  
Mitochondrial Pathology ◽  
Vitro Model ◽  
Induced Pluripotent

Diabetic cardiomyopathy is a common consequence of diabetes and associated with mitochondrial pathology. Using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as an in vitro model of diabetes, we sought to understand the role of mitophagy, a process that selectively degrades mitochondria through the autophagy-lysosome pathway as a crucial quality control pathway against diabetic cardiomyopathy. We first showed that iPSC-CMs exposed to a diabetic milieu demonstrated increased hypertrophy, impaired calcium signaling, and higher oxidative stress. Flow cytometry analysis of iPSC-CMs subjected to diabetic conditions revealed two distinct population of cells (normal and hypertrophied), suggesting a heterogeneous response to hyperglycemia. In these cells, hypertrophied iPSC-CMs were found to have reduced mitophagy compared to normal cells when exposed to hyperglycemia. In addition, we showed that mitochondrial fragmentation was also decreased in the hypertrophied iPSC-CMs compared to normal cells upon exposure to hyperglycemia, demonstrating a link between mitochondrial fragmentation and mitophagy. Surprisingly, pretreatment of iPSC-CMs with a non-selective antioxidant, N-(2-mercaptopropionyl)-glycine, not only failed to limit the deleterious effects of hyperglycemia, but actually led to increased hypertrophy and cell death. We found that mitophagy was significantly reduced in iPSC-CMs following antioxidant treatment, suggesting the need of mild oxidative stress as a trigger for mitophagy. Future studies are warranted to further investigate the association between oxidative stress, mitochondrial fragmentation, and mitochondrial fission as targets against diabetic cardiomyopathy.

In vivo effect of sodium orthovanadate on pp60c-src kinase

1987 ◽  
Vol 7 (3) ◽  
pp. 1139-1147
Author(s):  
J W Ryder ◽  
J A Gordon
Keyword(s):  
Tyrosine Kinase ◽  
Chicken Embryo ◽  
Sodium Orthovanadate ◽  
Normal Cells ◽  
Amino Terminal ◽  
Carboxyl Terminal ◽  
Embryo Fibroblasts ◽  
Chicken Embryo Fibroblasts

We have compared the tyrosine kinase activity of pp60c-src isolated from intact chicken embryo fibroblasts treated with micromolar sodium orthovanadate for 4 h and from untreated cells. We found an approximate 50% reduction in both autophosphorylation of pp60c-src and phosphorylation of casein when examined in the immune complex kinase assay. The reduction of in vitro enzymatic activity correlated with a vanadate-induced increase in in vivo phosphorylation of pp60c-src at the major site of tyrosine phosphorylation in the carboxyl-terminal half of the molecule and at serine in the amino-terminal half of the molecule. Our observations in vivo and those of Courtneidge in vitro (EMBO J. 4:1471-1477, 1985) suggest that vanadate may enhance a cellular regulatory mechanism that inhibits the activity of pp60c-src in normal cells. A likely candidate for this mechanism is phosphorylation at a tyrosine residue distinct from tyrosine 416, probably tyrosine 527 in the carboxyl-terminal sequence of amino acids unique to pp60c-src. The regulatory role, if any, of serine phosphorylation in pp60c-src remains unclear. The 36-kilodalton phosphoprotein, a substrate of pp60v-src, showed a significant phosphorylation at tyrosine after treatment of normal chicken embryo fibroblasts with vanadate. Assuming that pp60c-src is inhibited intracellularly by vanadate, either another tyrosine kinase is stimulated by vanadate (e.g., a growth factor receptor) or the 36-kilodalton phosphoprotein in normal cells is no longer rapidly dephosphorylated by a tyrosine phosphatase in the presence of vanadate.

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