Application of Nanoparticles in Cancer Treatment: A Concise Review

Timely diagnosis and appropriate antitumoral treatments remain of utmost importance, since cancer remains a leading cause of death worldwide. Within this context, nanotechnology offers specific benefits in terms of cancer therapy by reducing its adverse effects and guiding drugs to selectively target cancer cells. In this comprehensive review, we have summarized the most relevant novel outcomes in the range of 2010–2023, covering the design and application of nanosystems for cancer therapy. We have established the general requirements for nanoparticles to be used in drug delivery and strategies for their uptake in tumor microenvironment and vasculature, including the reticuloendothelial system uptake and surface functionalization with protein corona. After a brief review of the classes of nanovectors, we have covered different classes of nanoparticles used in cancer therapies. First, the advances in the encapsulation of drugs (such as paclitaxel and fisetin) into nanoliposomes and nanoemulsions are described, as well as their relevance in current clinical trials. Then, polymeric nanoparticles are presented, namely the ones comprising poly lactic-coglycolic acid, polyethylene glycol (and PEG dilemma) and dendrimers. The relevance of quantum dots in bioimaging is also covered, namely the systems with zinc sulfide and indium phosphide. Afterwards, we have reviewed gold nanoparticles (spheres and anisotropic) and their application in plasmon-induced photothermal therapy. The clinical relevance of iron oxide nanoparticles, such as magnetite and maghemite, has been analyzed in different fields, namely for magnetic resonance imaging, immunotherapy, hyperthermia, and drug delivery. Lastly, we have covered the recent advances in the systems using carbon nanomaterials, namely graphene oxide, carbon nanotubes, fullerenes, and carbon dots. Finally, we have compared the strategies of passive and active targeting of nanoparticles and their relevance in cancer theranostics. This review aims to be a (nano)mark on the ongoing journey towards realizing the remarkable potential of different nanoparticles in the realm of cancer therapeutics.info:eu-repo/semantics/publishedVersio

Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Predictive biomarkers are crucial in clarifying the best strategy to use poly(ADP-ribose) polymerase inhibitors (PARPi) for the greatest benefit to ovarian cancer patients. PARPi are specifically lethal to cancer cells that cannot repair DNA damage by homologous recombination (HR), and HR deficiency is frequently associated with BRCA1/2 mutations. Genetic tests for BRCA1/2 mutations are currently used in the clinic, but results can be inconclusive due to the high prevalence of rare DNA sequence variants of unknown significance. Most tests also fail to detect epigenetic modifications and mutations located deep within introns that may alter the mRNA. The aim of this study was to investigate whether quantitation of BRCA1/2 mRNAs in ovarian cancer can provide information beyond the DNA tests. Using the nCounter assay from NanoString Technologies, we analyzed RNA isolated from 38 ovarian cancer specimens and 11 normal fallopian tube samples. We found that BRCA1/2 expression was highly variable among tumors. We further observed that tumors with lower levels of BRCA1/2 mRNA showed downregulated expression of 12 additional HR genes. Analysis of 299 ovarian cancer samples from The Cancer Genome Atlas (TCGA) confirmed the coordinated expression of BRCA1/2 and HR genes. To facilitate the routine analysis of BRCA1/2 mRNA in the clinical setting, we developed a targeted droplet digital PCR approach that can be used with FFPE samples. In conclusion, this study underscores the potential clinical benefit of measuring mRNA levels in tumors when BRCA1/2 DNA tests are negative or inconclusive.This research was funded by the Fundação para a Ciência e a Tecnologia, Portugal (PTDC/MED-ONC/29469/2017) and an unrestricted grant from AstraZeneca to M.C.-F. R.S. was a recipient of an EMBO Long-Term Fellowship (EMBO ALTF 101-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 842695.info:eu-repo/semantics/publishedVersio

Approximate confidence intervals for a linear combination of binomial proportions: A new variant

We propose a new adjustment for constructing an improved version of theWald interval for linear combinations of binomial proportions, which addresses the presence of extremal samples. A comparative simulation study was carried out to investigate the performance of this new variant with respect to the exact coverage probability, expected interval length, and mesial and distal noncoverage probabilities. Additionally, we discuss the application of a criterion for interpreting interval location in the case of small samples and/or in situations in which extremal observations exist. The confidence intervals obtained from the new variant performed better for some evaluation measures

Quality Criteria for Educational Games

The development of software products in general and educational games in particular is a very demanding process involving costly resources for long periods of time. Evaluating its quality throughout the development lifecycle contributes to the early identification of imperfections and to improved efficiency. In this paper we discuss a set of quality criteria and a method to assess the quality of educational games. These quality criteria are based on the functional requirements of the system and structured into two groups: general and specific. General criteria refer to the set of criteria that are common to all educational games in a given study area. Specific criteria refer to those criteria particularly addressing a specific educational purpose. We also present a quality model that is based on the software engineering paradigms. This model, called Quantitative Evaluation Framework, provides a quantitative measure for the quality of an educational game

Ensino a distância no Politécnico de Lisboa: necessidades de formação

No contexto da situação pandémica associada à COVID-19, o Politécnico de Lisboa (IPL) criou a Unidade de Ensino a Distância (EaD@IPL), que tem como principal objetivo promover a inovação pedagógica e a competência digital, em permanente sintonia com os avanços da ciência e da tecnologia da comunicação.N/

Conservation, divergence and functions of centromeric satellite DNA families in the Bovidae.

Repetitive satellite DNA (satDNA) sequences are abundant in eukaryote genomes, with a structural and functional role in centromeric function. We analysed the nucleotide sequence and chromosomal location of the five known cattle (Bos taurus) satDNA families in seven species from the tribe Tragelaphini (Bovinae subfamily). One of the families (SAT1.723) was present at the chromosomes' centromeres of the Tragelaphini species, as well in two more distantly related bovid species, Ovis aries and Capra hircus. Analysis of the interaction of SAT1.723 with centromeric proteins revealed that this satDNA sequence is involved in the centromeric activity in all the species analysed and that it is preserved for at least 15-20 My across Bovidae species. The satDNA sequence similarity among the analysed species reflected different stages of homogeneity/heterogeneity, revealing the evolutionary history of each satDNA family. The SAT1.723 monomer-flanking regions showed the presence of transposable elements, explaining the extensive shuffling of this satDNA between different genomic regions

Bovine satellite DNAs – a history of the evolution of complexity and its impact in the Bovidae family

Despite the many questions regarding satellite DNA sequences and their cellular roles, the evolutionary history of eukaryotic genomes seems to have been largely influenced by this dynamic and multifaceted genomic component. The bovine genome is highly rich in diverse satDNA sequences that differ in monomer sequence and length, complexity, chromosomal location and abundance, as well as in their sequences’ evolutionary mechanisms. In the evolution of the Bovidae family, the genomes’ repetitive fraction played a central role in karyotype reorganisation, and in the last few decades several studies have demonstrated and reinforced an association between centromeric satDNAs and the process of chromosome evolution in remodelling genomes of Bovidae species. Here, we review different aspects of the molecular nature and genome behaviour of all the satDNA families identified in the bovine genome, including their organisation, abundance, chromosome localisation, variation in sequence, and evolutionary history in the Bovidae family and in particular in the Bovinae subfamily, taking an integrative perspective. “Evolution and satDNA” can be addressed through two complementary views: the satDNA sequence evolution per se, and genome evolution promoted by the satDNA dynamism. SatDNA both provides phylogenetic information and is a critical genomic component that enables sequence and chromosome evolution – features arising from its presence, absence or alteration

Bovine satellite DNAs–a history of the evolution of complexity and its impact in the Bovidae family

Despite the many questions regarding satellite DNA sequences and their cellular roles, the evolutionary history of eukaryotic genomes seems to have been largely influenced by this dynamic and multifaceted genomic component. The bovine genome is highly rich in diverse satDNA sequences that differ in monomer sequence and length, complexity, chromosomal location and abundance, as well as in their sequences’ evolutionary mechanisms. In the evolution of the Bovidae family, the genomes’ repetitive fraction played a central role in karyotype reorganisation, and in the last few decades several studies have demonstrated and reinforced an association between centromeric satDNAs and the process of chromosome evolution in remodelling genomes of Bovidae species. Here, we review different aspects of the molecular nature and genome behaviour of all the satDNA families identified in the bovine genome, including their organisation, abundance, chromosome localisation, variation in sequence, and evolutionary history in the Bovidae family and in particular in the Bovinae subfamily, taking an integrative perspective. “Evolution and satDNA” can be addressed through two complementary views: the satDNA sequence evolution per se, and genome evolution promoted by the satDNA dynamism. SatDNA both provides phylogenetic information and is a critical genomic component that enables sequence and chromosome evolution–features arising from its presence, absence or alteration