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12:00 – 12:30 Alihamze Fathinajafabadi 

Multilevel action of AP-1 transcription factors in lung tumor microenvironment

Abstract: AP-1, a group of dimeric transcriptional complexes composed of combinations of JUN, FOS, ATF and MAF family members, plays a central role in the physiology of both individual cells and the entire organism, including embryo development and tissue homeostasis. It is involved in many cellular processes such as differentiation, proliferation, and apoptosis. Dysregulation of AP-1 protein levels and their post-translationally activated states have been implicated in various pathologies, notably tumor development. Lung cancer, particularly lung adenocarcinoma, exhibits significant involvement of AP-1 members, with the overexpression of FOSL1 and FOSL2 associated with adverse patient survival.

In our laboratory, we are investigating the multilevel actions of AP-1 activity in the lung adenocarcinoma microenvironment. Employing a combination of microscopic analysis of patient samples and in vitro approaches using related cell lines, we are assessing the protein expression patterns and intracellular localization of FRA1 (encoded by FOSL1), FRA2 (encoded by FOSL2), and JUNB. Preliminary results reveal a distinct expression pattern for these three proteins, dependent on the specific cell type within the tumor tissue. This observed differential distribution suggests a spatial-temporal coordination orchestrated by FRA1, FRA2, and JUNB between tumoral cells and specific subtypes of resident leukocytes in the tumor microenvironment, such as TANs (Tumor-Associated Neutrophils). Consequently, our findings propose a multilevel control exerted by specific AP-1 members within the tumoral context, shedding light on the intricate interplay within the lung adenocarcinoma microenvironment.

Repurposing drug delivery systems for diagnostics

Speaker: Prof. Joern Dengjel
Institution: Faculté de Pharmacie, Université de Montréal, Montréal, Canada
Place: Jerónimo Forteza conference room, CIPF

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In the last two decades, a number of drug delivery systems were repurposed for diagnostic applications. Traditional uses of diagnostic delivery systems are nanocarriers of diagnostic cargo (e.g., contrast agents) with controlled release kinetics or active targeting properties. In this seminar, I will demonstrate how established delivery systems can be used for diagnostics in less conventional ways. First, I will present the development of an enzyme-loaded vesicular reaction compartment for the quantification of lactate in whole blood. Isolating the lactate-sensing reaction in the liposomal lumen allowed this reaction to occur in whole blood as interfering substances were incapable of crossing the membrane. This vesicular reaction compartment forms the basis of a novel blood lactate assay for bedside use in sepsis. The fluorescence assay was tested in fresh human blood in an Institutional Review Board-approved study and successfully combined with a portable fluorometer. This system highlighted how the selectively permeable membrane of liposomes could be utilized to isolate an enzymatic reaction in order to enable it in a prohibiting matrix. Second, I will present the development of a series of novel non-releasing hydrogels for diagnostic applications. Hydrogels are widely used in tissue engineering and drug delivery, and their localization is tied to their function. As means for hydrogel localization in the body are limited, we developed a new and broadly applicable method to track hydrogels by encapsulating a clinically used oil-based contrast agent. This non-releasing system was visualized in mice using computed tomography. Another example of a non-releasing hydrogel is a pH-sensing diagnostic wound dressing for chronic wounds. Hydrogels loaded with pH-sensitive fluorescent microparticles were developed and sensed the pH in a clinically relevant range on dorsal mouse wounds. The dye was highly retained on microparticles in the presence of biological fluids to minimize the risk of wound exposure to the dye. These liposomal and hydrogel systems highlight the high versatility and usefulness of drug delivery systems for diagnostic applications.

PATROCINADO POR: 

With support from the Generalitat Valenciana, AMPER-02/2023 and CIAORG/2022/035

12:00 – 12:30 Javier Martínez Latorre

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12:30 – 13:00 Carlos Camps

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12:00 – 12:30 Verónica Llorens

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12:30 – 13:00 Jose Luís López

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