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The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor
2021
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …
Models for preterm cortical development using non invasive clinical EEG
2017
AbstractThe objective of this study was to evaluate the piglet and the mouse as model systems for preterm cortical development. According to the clinical context, we used non invasive EEG recordings. As a prerequisite, we developed miniaturized Ag/AgCl electrodes for full band EEG recordings in mice and verified that Urethane had no effect on EEG band power. Since mice are born with a “preterm” brain, we evaluated three age groups: P0/P1, P3/P4 and P13/P14. Our aim was to identify EEG patterns in the somatosensory cortex which are distinguishable between developmental stages and represent a physiologic brain development. In mice, we were able to find clear differences between age groups wit…
Immaturity for gestational age of microvasculature and placental barrier in term placentas with high weight
2017
Abstract Objective Villous immaturity for gestational age is a multifactorial developmental deviation associated with unexpected placental insufficiency, fetal hypoxia and term fetal death. In our previous work we have shown that immature CD15+/CD31+/CD34+ endothelial cells were an important indicator of placental villous immaturity and chronic insufficiency. The aim of this study was to perform a comparative analysis of CD15-marked immaturity in the vessel walls between normal and pathological term placentas of clinically and structurally heterogenous groups with normal, low and high weight. Study design 165 clinically normal and pathological placentas of gestational age 39–42 with normal …
Behavioural and structural interventions in cancer prevention: towards the 2030 SDG horizon
2020
Interventions in individual lifestyles have often been viewed as the main component of cancer prevention strategies. However, environmental factors may facilitate or impede healthy behaviours. The behavioural‐structural dichotomy of cancer prevention can only be resolved by incorporating the ‘Health in All Policies’ perspective at multiple levels (legislation, promotion of healthy choices, health support groups, health education).
ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
2018
AbstractPurpose: This study aimed to identify biomarkers of resistance to endocrine therapy in estrogen receptor–positive (ER+) breast cancers treated with prolonged neoadjuvant letrozole.Experimental Design: We performed targeted DNA and RNA sequencing in 68 ER+ breast cancers from patients treated with preoperative letrozole (median, 7 months).Results: Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC > 1, FDR < 0.03) in letrozole-resistant tumors with transcription-binding data showed significant overlap with 20 E2F4-regulated genes (P =…
Molecular, Biological and Structural Features of VL CDR-1 Rb44 Peptide, Which Targets the Microtubule Network in Melanoma Cells
2019
Microtubules are important drug targets in tumor cells, owing to their role in supporting and determining the cell shape, organelle movement and cell division. The complementarity-determining regions (CDRs) of immunoglobulins have been reported to be a source of anti-tumor peptide sequences, independently of the original antibody specificity for a given antigen. We found that, the anti-Lewis B mAb light-chain CDR1 synthetic peptide Rb44, interacted with microtubules and induced depolymerization, with subsequent degradation of actin filaments, leading to depolarization of mitochondrial membrane-potential, increase of ROS, cell cycle arrest at G2/M, cleavage of caspase-9, caspase-3 and PARP, …
AP2α controls the dynamic balance between miR-126&126* and miR-221&222 during melanoma progression
2016
Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumor suppressors miR-126&126∗ in melanoma development and progression. According to the inverse correlation between endogenous miR-221&222 and miR-126&126∗, respectively increasing or decreasing with malignancy, their enforced expression or silencing was sufficient for a reciprocal regulation. In line with the opposite roles of these miRs, protein analyses confirmed the reverse ex…
Cytokeratins in the Histological Diagnosis of Malignant Tumors
1994
Cytokeratins, which comprise a multigene family of 20 related polypeptides (CKs 1–20), are constituents of the intermediate filaments of epithelial cells, in which they are expressed in various combinations depending on the epithelial type and the degree of differentiation. Of these, CK 19 (400 amino acids; 44.1 kilodaltons) is an example of a widely distributed CK, being expressed in various epithelia, including many simple epithelia. In contrast, the recently identified CK 20 (424 amino acids; 48.6 kilodaltons) is essentially confined to gastrointestinal epithelia, the urothelium and Merkel cells. The differential expression of individual CKs in various types of carcinomas makes them use…
Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities
2021
Simple Summary The growing interest in immunotherapy for the treatment of multiple myeloma demands a deep knowledge of the complex interactions between malignant and immune cells within the bone marrow. Indeed, understanding the cellular and molecular mechanisms underlying this network should represent the basis for the design of novel patient-oriented biological therapeutic approaches. Here, we describe the role of the main immune components of the myeloma niche along disease evolution and their implication in impairing/improving the response to anti-cancer treatments. Additionally, we provided an overview of the potential weakness of this pro-tumor interplay, evidencing novel therapeutic …
Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?
2016
Irreversible functional deficits in multiple sclerosis (MS) are directly correlated to axonal damage and loss. Neurodegeneration results from immune-mediated destruction of myelin sheaths and subsequent axonal demyelination. Importantly, oligodendrocytes, the myelinating glial cells of the central nervous system, can be replaced to some extent to generate new myelin sheaths. This endogenous regeneration capacity has so far mainly been attributed to the activation and recruitment of resident oligodendroglial precursor cells. As this self-repair process is limited and increasingly fails while MS progresses, much interest has evolved regarding the development of remyelination-promoting strateg…