scholarly journals Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Romina Mancinelli ◽  
Antimo Cutone ◽  
Luigi Rosa ◽  
Maria Stefania Lepanto ◽  
Paolo Onori ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Tumor Development ◽  
In Vitro Models ◽  
Molecular Forms ◽  
Cellular Processes ◽  
Small Duct ◽  
Transferrin Receptor 1 ◽  
The Difference ◽  
Tumor Management

Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management.

scholarly journals Adipose Tissue Depot-Specific Differences in the Regulation of Hyaluronan Production of Relevance to Graves' Orbitopathy

2012 ◽  
Vol 97 (2) ◽  
pp. 653-662 ◽  
Author(s):  
Lei Zhang ◽  
Fiona Grennan-Jones ◽  
Carol Lane ◽  
D. Aled Rees ◽  
Colin M. Dayan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
In Vitro Models ◽  
Akt Inhibitor ◽  
Transcript Accumulation ◽  
Igf I ◽  
Graves Orbitopathy ◽  
The Difference ◽  
Ha Synthase ◽  
Orbital Fibroblasts

Context: Graves' orbitopathy (GO) is associated with Graves' disease, in which anti-TSH receptor (TSHR) autoantibodies (thyroid-stimulating antibodies) increase cAMP causing hyperthyroidism. Excess adipogenesis and hyaluronan (HA) overproduction [HA synthase 2 (HAS2) is the major source] expand the orbital contents causing GO. TSHR activation participates in both processes but an anti-TSHR monoclonal without TSAB activity also increased HA, suggesting the involvement of other cascades. Objective and Patients Studied: We investigated using in vitro models in which preadipocytes/fibroblasts from human orbital (n = 12) and sc (n = 10) adipose tissues were treated with IGF-I (to probe the pAkt pathway, recently identified as a positive regulator of HAS2), TSH, and/or various inhibitors. Changes in HA during in vitro-induced adipogenesis were also evaluated. Main Outcome and Results: Adipogenesis in orbital preadipocytes was accompanied by significantly increased HAS2 transcripts and HA accumulation in contrast to sc cells in which differentiation significantly decreased HAS2 mRNA and secreted HA. Surprisingly, IGF-I alone did not increase HAS2 levels, despite significantly increasing the ratio of phosphorylated to total Akt; furthermore, an Akt inhibitor increased orbital (but not sc) HAS2 transcripts. A stimulatory effect of IGF-I on HAS2 transcripts was revealed by addition of rapamycin in sc but by a MAPK kinase inhibitor in orbital fibroblasts. Conclusions: The results have several possible explanations including a phosphorylation-dependent repressor of HAS2 transcript accumulation, exclusively in the orbit. The difference in control of HAS2 expression allows the activation of one of the mechanisms underlying GO, adipogenesis, to be linked biologically with the second, HA overproduction.

scholarly journals The Biochemical and Molecular Analysis of Changes in Melanogenesis Induced by UVA-Activated Fluoroquinolones—In Vitro Study on Human Normal Melanocytes

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2900
Author(s):  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
...  
Keyword(s):  
Transcription Factor ◽  
In Vitro Study ◽  
Skin Lesions ◽  
Cellular Level ◽  
Tyrosinase Activity ◽  
Cellular Processes ◽  
Uva Irradiation ◽  
The Difference ◽  
Uva Radiation

Fluoroquinolones cause phototoxic reactions, manifested as different types of skin lesions, including hyperpigmentation. The disturbances of melanogenesis indicate that fluoroquinolones may affect cellular processes in melanocytes. It has been reported that these antibiotics may bind with melanin and accumulate in pigmented cells. The study aimed to examine the changes in melanogenesis in human normal melanocytes exposed to UVA radiation and treated with lomefloxacin and moxifloxacin, the most and the least fluoroquinolone, respectively. The obtained results demonstrated that both tested fluoroquinolones inhibited melanogenesis through a decrease in tyrosinase activity and down-regulation of tyrosinase and microphthalmia-associated transcription factor production. Only lomefloxacin potentiated UVA-induced melanogenesis. Under UVA irradiation lomefloxacin significantly enhanced melanin content and tyrosinase activity in melanocytes, although the drug did not cause an increased expression of tyrosinase or microphthalmia-associated transcription factor. The current studies revealed that phototoxic activity of fluoroquinolones is associated with alterations in the melanogenesis process. The difference in phototoxic potential of fluoroquinolones derivatives may be connected with various effects on UVA-induced events at a cellular level.

The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2564-2570 ◽  
Author(s):  
Hanqian Carlson ◽  
An-Sheng Zhang ◽  
William H. Fleming ◽  
Caroline A. Enns
Keyword(s):  
Transferrin Receptor ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Cell Types ◽  
Single Amino Acid ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Transferrin Receptor 1 ◽  
A Cell

AbstractHereditary hemochromatosis (HH) is an autosomal recessive disease that leads to parenchymal iron accumulation. The most common form of HH is caused by a single amino acid substitution in the HH protein, HFE, but the mechanism by which HFE regulates iron homeostasis is not known. In the absence of transferrin (Tf), HFE interacts with transferrin receptor 1 (TfR1) and the 2 proteins co-internalize, and in vitro studies have shown that HFE and Tf compete for TfR1 binding. Using a cell line lacking endogenous transferrin receptors (TRVb cells) transfected with different forms of HFE and TfR1, we demonstrate that even at low concentrations Tf competes effectively with HFE for binding to TfR1 on living cells. Transfection of TRVb cells or the derivative line TRVb1 (which stably expresses human TfR1) with HFE resulted in lower ferritin levels and decreased Fe2+ uptake. These data indicate that HFE can regulate intracellular iron storage independently of its interaction with TfR1. Earlier studies found that in HeLa cells, HFE expression lowers Tf-mediated iron uptake; here we show that HFE lowers non–Tf-bound iron in TRVb cells and add to a growing body of evidence that HFE may play different roles in different cell types.

scholarly journals The NMD Pathway Regulates GABARAPL1 mRNA during the EMT

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1302
Author(s):  
Timothée Baudu ◽  
Chloé Parratte ◽  
Valérie Perez ◽  
Marie Ancion ◽  
Stefania Millevoi ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tumor Development ◽  
A549 Cells ◽  
Cancer Therapies ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Promising Target ◽  
Anti Cancer ◽  
Lung Adenocarcinomas

EMT is a reversible cellular process that is linked to gene expression reprogramming, which allows for epithelial cells to undergo a phenotypic switch to acquire mesenchymal properties. EMT is associated with cancer progression and cancer therapeutic resistance and it is known that, during the EMT, many stress response pathways, such as autophagy and NMD, are dysregulated. Therefore, our goal was to study the regulation of ATG8 family members (GABARAP, GABARAPL1, LC3B) by the NMD and to identify molecular links between these two cellular processes that are involved in tumor development and metastasis formation. IHC experiments, which were conducted in a cohort of patients presenting lung adenocarcinomas, showed high GABARAPL1 and low UPF1 levels in EMT+ tumors. We observed increased levels of GABARAPL1 correlated with decreased levels of NMD factors in A549 cells in vitro. We then confirmed that GABARAPL1 mRNA was indeed targeted by the NMD in a 3′UTR-dependent manner and we identified four overlapping binding sites for UPF1 and eIF4A3 that are potentially involved in the recognition of this transcript by the NMD pathway. Our study suggests that 3′UTR-dependent NMD might be an important mechanism that is involved in the induction of autophagy and could represent a promising target in the development of new anti-cancer therapies.

scholarly journals In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

2020 ◽  
Vol 21 (16) ◽  
pp. 5747
Author(s):  
Sandra Clara-Trujillo ◽  
Gloria Gallego Ferrer ◽  
José Luis Gómez Ribelles
Keyword(s):  
Tissue Engineering ◽  
Drug Resistance ◽  
Cell Fate ◽  
Tumor Biology ◽  
Tumor Development ◽  
In Vitro Models ◽  
Matrix Composition ◽  
Composition Material ◽  
Natural Interactions

In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.

Yangambin Cytotoxicity: A Pharmacologically Active Lignan Obtained from Ocotea duckei Vattimo (Lauraceae)

2008 ◽  
Vol 63 (9-10) ◽  
pp. 681-686 ◽  
Author(s):  
Rubens L. Monte Neto ◽  
M. A. Sousa ◽  
Celidarque S. Dias ◽  
José M. Barbosa Filho ◽  
Márcia R. Oliveira
Keyword(s):  
Trypan Blue ◽  
Inhibitory Effect ◽  
In Vitro Models ◽  
In Vitro Cytotoxicity ◽  
Blue Dye ◽  
Reduction Assay ◽  
Mtt Reduction ◽  
The Difference ◽  
Pharmacologically Active

The in vitro cytotoxic potential of yangambin was evaluated. Yangambin is a pharmacologically active furofuran lignan obtained from the leaves of Ocotea duckei. It is the major compound from the lignoids fraction. Yangambin presented low cytotoxicity in all in vitro models analyzed. Its cytotoxicity to murine macrophages was measured by the Trypan blue dye exclusion test and MTT reduction assay, resulting in high CC50 values of 187.0 μg/mL (383.3 μm) and 246.7 μg/mL (504.3 μm), respectively. The difference obtained in the inhibitory concentrations aforementioned can be explained, at least in part, by the different principles of the methods. While the MTT reduction assay evaluates the ability of yangambin to inhibit the activity of the mitochondrial enzyme succinate dehydrogenase, the Trypan blue dye exclusion test evaluates possible damages to the integrity of the cytoplasmic membrane which result in cell death. The capacity of yangambin to inhibit the sea urchin embryonic development showed that it has low antimitotic and teratogenic potential, once continued exposure of embryos to concentrations up to 500 μg/mL (1.025 μm) did not result in an inhibitory effect on the first egg cleavages. Such low in vitro cytotoxicity is correlated with the low acute toxicity previously studied. All these data, together with the various therapeutic properties of yangambin, make this lignan a promising one for a new drug.

Analysis and applicability of different in vitro models of Glioblastoma multiforme

2014 ◽  
Vol 226 (06) ◽  
Author(s):  
D William ◽  
M Linnebacher ◽  
CF Classen
Keyword(s):  
Glioblastoma Multiforme ◽  
In Vitro Models

On the Role of Transferrin in 67Ga Uptake by Tumor Cells

1988 ◽  
Vol 27 (04) ◽  
pp. 151-153
Author(s):  
P. Thouvenot ◽  
F. Brunotte ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Specific Binding ◽  
Subcellular Fractionation ◽  
Animal Blood ◽  
Tumor Bearing ◽  
Cell Structures ◽  
The Difference ◽  
Sarcoma Cells ◽  
In Vitro Uptake

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about ii/io of 67Ga and 1/5o of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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