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Simple Summary: For the first time, we hypothesized an inverse correlation and almost mutual exclusivity between RKIP and EGFR expression in different solid tumors. In silico, cervical cancer was the third tumor type in which this inverse correlation was strong, a result that we validated in a series of 202 patient samples. Importantly, we highlight the importance of this axis by demonstrating its strong association with patient prognosis. Using in vitro functional assays, we showed that RKIP can control EGFR mRNA expression as well as its phosphorylation status, while EGFR activation can also interfere with RKIP protein expression levels. Therefore, the discovery of this novel putative RKIP/EGFR loop opens the door for several interesting future studies in many other tumor types, mainly those in which EGFR has a crucial oncogenic role. Raf Kinase Inhibitor Protein (RKIP) is recognized as a bona fide tumor suppressor gene, and its diminished expression or loss is associated with the progression and poor prognosis of various solid tumors. It exerts multifaceted roles in carcinogenesis by modulating diverse intracellular signaling pathways, including those governed by HER receptors such as MAPK. Given the significance of HER receptor overexpression in numerous tumor types, we investigated the potential oncogenic relationship between RKIP and HER receptors in solid tumors. Through a comprehensive in silico analysis of 30 TCGA PanCancer Atlas studies encompassing solid tumors (10,719 samples), we uncovered compelling evidence of an inverse correlation between RKIP and EGFR expression in solid tumors observed in 25 out of 30 studies. Conversely, a predominantly positive association was noted for the other HER receptors (ERBB2, ERBB3, and ERBB4). In particular, cervical cancer (CC) emerged as a tumor type exhibiting a robust inverse association between RKIP and EGFR expression, a finding that was further validated in a cohort of 202 patient samples. Subsequent in vitro experiments involving pharmacological and genetic modulation of EGFR and RKIP showed that RKIP depletion led to significant upregulation of EGFR mRNA levels and induction of EGFR phosphorylation. Conversely, EGFR overactivation decreased RKIP expression in CC cell lines. Additionally, we identified a common molecular signature among patients depicting low RKIP and high EGFR expression and demonstrated the prognostic value of this inverse correlation in CC patients. In conclusion, our findings reveal an inverse association between RKIP and EGFR expression across various solid tumors, shedding new light on the underlying molecular mechanisms contributing to the aggressive phenotype associated with RKIP and EGFR in cervical cancer. [ABSTRACT FROM AUTHOR]

The widespread adoption of digital technologies in educational systems has been globally reflecting a shift in pedagogic content delivery that seems to fit modern generations of students while tackling relevant challenges faced by the current scholar context, e.g., progress traceability, pedagogic content fair access and intuitive visual representativeness, mobility issue mitigation, and sustainability in crisis situations. Among these technologies, augmented reality (AR) emerges as a particularly promising approach, allowing the visualization of computer-generated interactive data on top of real-world elements, thus enhancing comprehension and intuition regarding educational content, often in mobile settings. While the application of AR to education has been widely addressed, issues related to performance interaction and cognitive performance are commonly addressed, with lesser attention paid to the limitations associated with setup complexity, mostly related to experiences configurating tools, or contextual range, i.e., technical/scientific domain targeting versatility. Therefore, this paper introduces ARPocketLab, a digital, mobile, flexible, and scalable solution designed for the dynamic needs of modern tutorship. With a dual-interface system, it allows both educators and students to interactively design and engage with AR content directly tied to educational outcomes. Moreover, ARPocketLab's design, aimed at handheld operationalization using a minimal set of physical resources, is particularly relevant in environments where educational materials are scarce or in situations where remote learning becomes necessary. Its versatility stems from the fact that it only requires a marker or a surface (e.g., a table) to function at full capacity. To evaluate the solution, tests were conducted with 8th-grade Portuguese students within the context of Physics and Chemistry subject. Results demonstrate the application's effectiveness in providing didactic assistance, with positive feedback not only in terms of usability but also regarding learning performance. The participants also reported openness for the adoption of AR in pedagogic contexts. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression—a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma. [ABSTRACT FROM AUTHOR]

Raf kinase inhibitor protein (RKIP), an important modulator of intracellular signalling pathways, is commonly downregulated in multiple cancers. This reduction, or loss of expression, is correlated not only with the presence of metastasis, contributing to RKIP's classification as a metastasis suppressor, but also with tumour aggressiveness and poor prognosis. Recent findings suggest a strong involvement of RKIP in the modulation of tumour microenvironment components, particularly by controlling the infiltration of specific immune cells and secretion of pro-metastatic factors. Additionally, RKIP interaction with multiple signalling molecules seems to potentiate its function as a regulator of inflammatory processes, mainly through stimulation of anti- or pro-inflammatory cytokines. Furthermore, RKIP is involved in the modulation of immunotherapeutic drugs response, through diverse mechanisms that sensitize cells to apoptosis. In the present review, we will provide updated information about the role of RKIP as an inflammatory and immune modulator and its potential implications in cancer will be addressed. [ABSTRACT FROM AUTHOR]

Lung cancer is the most deadly neoplasm with the highest incidence in both genders, with non-small cell lung cancer (NSCLC) being the most frequent subtype. Somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are key drivers of NSCLC progression, with EGFR inhibitors being particularly beneficial for patients carrying the so-called "EGFR-sensitizing mutations". However, patients eventually acquire resistance to these EGFR inhibitors, and a better knowledge of other driven and targetable proteins will allow the design of increasingly accurate drugs against patients' specific molecular aberrations. Raf kinase inhibitory protein (RKIP) is an important modulator of relevant intracellular signaling pathways, including those controlled by EGFR, such as MAPK. It has been reported that it has metastasis suppressor activity and a prognostic role in several solid tumors, including lung cancer. In the present review, the potential use of RKIP in the clinic as a prognostic biomarker and predictor of therapy response in lung cancer is addressed. [ABSTRACT FROM AUTHOR]