Placenta‐targeted treatment in hypoxic dams improves maturation and growth of fetal cardiomyocytes in vitro via the release of placental factors

2020 ◽  
Vol 105 (9) ◽  
pp. 1507-1514 ◽  
Author(s):  
Esha Ganguly ◽  
Floor Spaans ◽  
Jude S. Morton ◽  
Raven Kirschenman ◽  
Mais M. Aljunaidy ◽  
...  
Keyword(s):  
Targeted Treatment ◽  
Fetal Cardiomyocytes

Ranolazine and TDM1 treatment: Cardioprotective effects in vitro and in vivo.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23102-e23102
Author(s):  
Nicola Maurea ◽  
Carmela Coppola ◽  
Giovanna Piscopo ◽  
Gennaro Riccio ◽  
Domenica Rea ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cell Viability ◽  
Cell Counting ◽  
In Vivo Studies ◽  
Breast Cancer Patients ◽  
Antibody Drug Conjugate ◽  
Fetal Cardiomyocytes ◽  
Covalently Linked

e23102 Background: Ado trastuzumab emtansine (TDM1) is a novel antibody–drug conjugate consisting of trastuzumab (TRAS) covalently linked to the highly potent microtubule inhibitory agent DM1 via a stable thioether linker. TDM1 is used in metastatic ErbB2 positive breast cancer patients. Although, the potential cardiotoxic effects of TDM1 have not yet been fully elucidated, they can include changes in Ca2+ regulation related to blockade of ErbB2, PI3K-Akt and MAPK pathways. Here, we aim to elucidate whether Ranolazine (R), administered after TDM1 treatment, blunts or not cardiotoxicity in vivo and in vitro. Methods: In vitro, human fetal cardiomyocytes (HFC) were treated with TDM1 for 3 days and then treated in the absence or presence of R for 3 days. Cell viability was assessed by cell counting and MTT assay. To evaluate cardiac function in vivo, C57/BL6 mice, 2-4 months old, were daily treated with TDM1 (44.4 mg/kg/day). At day 0 and after 7 days, fractional shortening (FS) and ejection fraction (EF) were measured, by M/B mode echocardiography, and radial and longitudinal strain (RS and LS) were evaluated using 2D speckle-stracking. These measurements were repeated after 5 days of R treatment (305 mg/Kg/day), started at the end of TDM1 treatment. Results: R reduces TDM1 toxicity in HFC, as evidenced by the higher percentage of viable cells treated with TDM1+ R with respect to the cells treated with TDM1 alone (p < 0.01). In in vivo studies: after 7 days with TDM1 administration, FS decreased to 53.6±0.9%, versus 61.0±0.8 % (sham), (p < 0.01), and EF decreased to 85.5±3.5 % versus 91.0±0.8% (sham), (p < 0.01). Moreover, RS decreased to 20.92±3.2 % versus 42.2±10.1% (sham) (p < 0.01), and LS decreased to -15.5±2.8 % versus -23.6±6.7% (sham), (p < 0.01).In mice treated with TDM1 and, successively treated with R for 5 days, the indices of cardiac function partially recovered: FS 58±2.4 % (p < 0.05), EF 88.8±1.7 %, (p < 0.05), RS (35.7±8.2 %, p > 0.05), whereas the alteration of LS persists even after treatment with R (-17.3±3.7 %, p > 0.05) Conclusions: Here we show that in vivo R post-treatment reduces cardiotoxic effects due to TDM1, as demonstrated by the recovery of FS, EF and RS values. As expected, R increases cell viability of HFC treated with TDM1.

Abstract 3516: EZH2 overexpression in myeloma patients shortens survival and in-vitro data supports a potential new targeted treatment strategy

2015 ◽  
Author(s):  
Charlotte Pawlyn ◽  
Martin F. Kaiser ◽  
Caleb K. Stein ◽  
Christopher P. Wardell ◽  
Veronica Macleod ◽  
...  
Keyword(s):  
Treatment Strategy ◽  
Targeted Treatment ◽  
Vitro Data ◽  
In Vitro Data

scholarly journals Unexpected maturation of PI3K and MAPK-ERK signaling in fetal ovine cardiomyocytes

2014 ◽  
Vol 307 (8) ◽  
pp. H1216-H1225 ◽  
Author(s):  
N. N. Chattergoon ◽  
S. Louey ◽  
P. J. Stork ◽  
G. D. Giraud ◽  
K. L. Thornburg
Keyword(s):  
Cell Cycle ◽  
Intracellular Signaling ◽  
Cardiac Development ◽  
Hormonal Control ◽  
Binucleated Cells ◽  
Age Related ◽  
Fetal Cardiomyocytes ◽  
Near Term ◽  
In Cells

In the first two-thirds of gestation, ovine fetal cardiomyocytes undergo mitosis to increase cardiac mass and accommodate fetal growth. Thereafter, some myocytes continue to proliferate while others mature and terminally differentiate into binucleated cells. At term (145 days gestational age; dGA) about 60% of cardiomyocytes become binucleated and exit the cell cycle under hormonal control. Rising thyroid hormone (T3) levels near term (135 dGA) inhibit proliferation and stimulate maturation. However, the degree to which intracellular signaling patterns change with age in response to T3 is unknown. We hypothesized that in vitro activation of ERK, Akt, and p70S6K by two regulators of cardiomyocyte cell cycle activity, T3 and insulin like growth factor-1 (IGF-1), would be similar in cardiomyocytes at gestational ages 100 and 135 dGA. IGF-1 and T3 each independently stimulated phosphorylation of ERK, Akt, and p70S6K in cells at both ages. In the younger mononucleated myocytes, the phosphorylation of ERK and Akt was reduced in the presence of IGF-1 and T3. However, the same hormone combination led to a dramatic twofold increase in the phosphorylation of these signaling proteins in the 135 dGA cardiomyocytes—even in cells that were not proliferating. In the older cells, both mono- and binucleated cells were affected. In conclusion, fetal ovine cardiomyocytes undergo profound maturation-related changes in signaling in response to T3 and IGF-1, but not to either factor alone. Differences in age-related response are likely to be related to milestones in fetal cardiac development as the myocardium prepares for ex utero life.

Electrophysiological and Morphological Maturation of Murine Fetal Cardiomyocytes During Electrical Stimulation In Vitro

2014 ◽  
Vol 20 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Sven Baumgartner ◽  
Marcel Halbach ◽  
Benjamin Krausgrill ◽  
Martina Maass ◽  
Sureshkumar Perumal Srinivasan ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Fetal Cardiomyocytes ◽  
Morphological Maturation

scholarly journals Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro

2007 ◽  
Vol 192 (2) ◽  
pp. R1-R8 ◽  
Author(s):  
N N Chattergoon ◽  
G D Giraud ◽  
K L Thornburg
Keyword(s):  
Thyroid Hormone ◽  
Cyclin D1 ◽  
Late Gestation ◽  
Cell Cycle Regulators ◽  
Cardiomyocyte Proliferation ◽  
Serum Free ◽  
Protein Levels ◽  
Fetal Organ ◽  
Fetal Cardiomyocytes

Thyroid hormone (T3) is a key regulator of fetal organ maturation. Premature elevations of thyroid hormone may lead to a ‘mature’ cardio-phenotype. Thyroid hormone will stimulate maturation of ovine fetal cardiomyocytes in culture by decreasing their proliferative capacity. Group 1 fetal cardiomyocytes (~135 days gestation) were incubated with T3 (1.5, 3, 10, and 100 nM) and bromodeoxyuridine (BrdU; 10 μM) for 24 and 48 h. Group 2 cardiomyocytes were cultured with T3 alone for later protein analysis of cell cycle regulators. At all concentrations, T3 decreased BrdU uptake fourfold in serum media (P<0.001 versus serum, n = 5). Following serum-free (SF) T3 treatment, BrdU uptake was inhibited when compared with serum (P<0.001 versus serum, n = 5). p21 expression increased threefold (P<0.05 versus serum free, n = 4) and cyclin D1 expression decreased twofold (P<0.05 versus serum, n = 4) in T3-treated cardiomyocytes. (1) T3 inhibits fetal cardiomyocyte proliferation, while (2) p21 protein levels increase, and (3) cyclin D1 levels decrease. Thus, T3 may be a potent regulator of cardiomyocyte proliferation and maturation in the late gestation fetus.

In vitro study of BSA gel/polyelectrolite complexes core shell microcapsules encapsulating doxorubicin for antitumoral targeted treatment

2019 ◽  
Vol 68 (1-3) ◽  
pp. 60-72 ◽  
Author(s):  
Violeta Paşcalău ◽  
Emoke Pall ◽  
Mihaela Tertis ◽  
Maria Suciu ◽  
Cecilia Cristea ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Targeted Treatment ◽  
Core Shell

In Vitro Biocompatibility of Surface-Modified Porous Alumina Particles for HepG2 Tumor Cells: Toward Early Diagnosis and Targeted Treatment

2015 ◽  
Vol 7 (33) ◽  
pp. 18600-18608 ◽  
Author(s):  
Elisabet Xifre-Perez ◽  
Sandra Guaita-Esteruelas ◽  
Malgorzata Baranowska ◽  
Josep Pallares ◽  
Lluis Masana ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Tumor Cells ◽  
Porous Alumina ◽  
Targeted Treatment ◽  
In Vitro Biocompatibility ◽  
Alumina Particles ◽  
Surface Modified

scholarly journals Immunomodulatory mAbs as Tools to Investigate on Cis-Interaction of PD-1/PD-L1 on Tumor Cells and to Set Up Methods for Early Screening of Safe and Potent Combinatorial Treatments

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2858
Author(s):  
Cinzia Vetrei ◽  
Margherita Passariello ◽  
Guendalina Froechlich ◽  
Rosa Rapuano Lembo ◽  
Nicola Zambrano ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoints ◽  
Early Screening ◽  
Programmed Death ◽  
Fetal Cardiomyocytes

Antibodies targeting Immune Checkpoints (IC) on tumor infiltrating lymphocytes improve immune responses against cancer. Recently, the expression of some ICs has also been reported on cancer cells. We used the clinically validated Ipilimumab and Nivolumab and other novel human antibodies targeting Cytotoxic T- lymphocyte-antigen 4 (CTLA-4), Programmed Death receptor-1 (PD-1) and Programmed Death Ligand 1 (PD-L1) to shed light on the functions of these ICs in cancer cells. We show here for the first time that all these antagonistic mAbs are able to reduce Erk phosphorylation and, unexpectedly, to induce a significant increase of ICs expression on tumor cells, involving a hyperphosphorylation of NF-kB. On the contrary, agonistic PD-L1 and PD-1 recombinant proteins showed opposite effects by leading to a significant reduction of PD-1 and PD-L1, thus also suggesting the existence of a crosstalk in tumor cells between multiple ICs. Since the immunomodulatory mAbs show their higher anti-tumor efficacy by activating lymphocytes against cancer cells, we also investigated whether it was possible to identify the most efficient combinations of immunomodulatory mAbs for achieving potent anti-tumor efficacy associated with the lowest adverse side effects by setting up novel simple and predictive in vitro models based on co-cultures of tumor cells or human fetal cardiomyocytes with lymphocytes. We demonstrate here that novel combinations of immunomodulatory mAbs with more potent anti-cancer activity than Ipilimumab and Nivolumab combination can be identified with no or lower cardiotoxic side effects. Thus, we propose these co-cultures-based assays as useful tools to test also other combinatorial treatments of emerging immunomodulatory mAbs against different ICs for the early screening of most potent and safe combinatorial therapeutic regimens.

scholarly journals Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e57522 ◽  
Author(s):  
Rachel A. Kudgus ◽  
Annamaria Szabolcs ◽  
Jameel Ahmad Khan ◽  
Chad A. Walden ◽  
Joel M. Reid ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Targeted Treatment
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