Segui questo link per vedere altri tipi di pubblicazioni sul tema: Composés antitumoraux.
Articoli di riviste sul tema "Composés antitumoraux"
Cita una fonte nei formati APA, MLA, Chicago, Harvard e in molti altri stili
Vedi i top-41 articoli di riviste per l'attività di ricerca sul tema "Composés antitumoraux".
Accanto a ogni fonte nell'elenco di riferimenti c'è un pulsante "Aggiungi alla bibliografia". Premilo e genereremo automaticamente la citazione bibliografica dell'opera scelta nello stile citazionale di cui hai bisogno: APA, MLA, Harvard, Chicago, Vancouver ecc.
Puoi anche scaricare il testo completo della pubblicazione scientifica nel formato .pdf e leggere online l'abstract (il sommario) dell'opera se è presente nei metadati.
Vedi gli articoli di riviste di molte aree scientifiche e compila una bibliografia corretta.
1
Romeiro, Camila Fernanda Rodrigues, Lucas Villar Pedrosa da Silva Pantoja e Marcieni Ataíde de Andrade. "Compostos bioativos identificados em Ayapana triplinervis: Uma revisão sobre mecanismos antitumorais". Research, Society and Development 11, n. 6 (17 aprile 2022): e0811628478. http://dx.doi.org/10.33448/rsd-v11i6.28478.
Testo completoAbstract (sommario):
O câncer está entre as principais causas de morte no mundo. Disfunções mitocondriais – relacionadas a mutação ou não –, estresse oxidativo e ativação de células imunes se relacionam à fisiopatologia do câncer, em função da indução por múltiplas vias de fatores oncogênicos. Até o momento, a produção e o desenvolvimento de drogas antitumorais para o tratamento do câncer ainda se configura como uma barreira, até que a formulação esteja disponível em condições seguras aos pacientes. Nesse contexto, a abordagem com plantas de uso tradicional relatado, como a Ayapana triplinervis passou a chamar a atenção tendo a vista o grande potencial observado de seus metabólitos secundários e o uso amplamente difundido. Fitosteróis e flavonóides são amplamente consumidos como nutracêuticos e possuem ações antioxidantes e anti-inflamatórias relatadas. Assim, a presente revisão integrativa objetivou reunir os mecanismos pelos quais compostos anteriormente identificados em A. triplinervis desempenham atividade antitumoral, além disso, buscou-se apresentar aspectos toxicológicos atribuídos a essas moléculas. A partir da análise crítica da literatura selecionada, a presente revisão reúne dados que evidenciam que os metabólitos β-sitosterol, estigmasterol e kaempferol desempenham significativo papel antitumoral por meio de disfunção mitocondrial, rotas oxidativas e modulação gênica. Quanto aos aspectos toxicológicos dessas moléculas, o presente estudo chama atenção para a necessidade de delineamentos experimentais em modelos in vivo, haja vista a necessidade da realização de cálculos assertivos de doses efetivas – para atividade antitumoral – e tóxicas desses compostos.
2
Sekaki, A., M. Gardès-Albert, C. Houée-Levin, C. Ferradini, C. Rivalle, E. Bisagni e B. Hickel. "Oxydation monoélectronique d’un composé antitumoral dérivé de l’ellipticine : le BD84". Journal de Chimie Physique 88 (1991): 977–85. http://dx.doi.org/10.1051/jcp/1991880977.
Testo completo
3
Benazeth, S., D. Bazin, B. Viossat, H. Dexpert, P. Lamelle e Nguyen-Huy Dung. "Composés du Pt(II) à visée antitumorale, dérivés de l’ellipticine et de ses analogues". Journal de Chimie Physique 86 (1989): 1635–42. http://dx.doi.org/10.1051/jcp/1989861635.
Testo completo
4
Ferreira, Wagner Andrade, Gabriella Salles Aguiar, Heloisa Rodrigues Pessoa, Danielly Cristiny Ferraz da Costa e Lilia Zago. "Potencial antitumoral dos compostos fenólicos de produtos da oliveira (Olea europaea L.): uma revisão integrativa da literatura". Research, Society and Development 10, n. 13 (3 ottobre 2021): e22101320733. http://dx.doi.org/10.33448/rsd-v10i13.20733.
Testo completoAbstract (sommario):
Os compostos fenólicos de produtos da oliveira (Olea europaea L.) apresentam potencial antitumoral devido a prevenção da gênese e de supressão tumoral em diferentes modelos de câncer. Este artigo tem por objetivo realizar uma análise da literatura, por meio de uma revisão integrativa, sobre o potencial antitumoral dos compostos fenólicos dos produtos da oliveira. Trata-se de uma revisão integrativa da literatura, de caráter qualitativo e exploratório, baseada em estudos pré-clínicos, in vitro e in vivo, publicados em periódicos indexados em bases de dados que abordam a temática. A busca, sem restrição de data, foi realizada nas bases de dados Web of Science, PUBMED e Scopus. As evidências sugerem que compostos fenólicos de produtos da oliveira (oleuropeína, hidroxitirosol, tirosol e oleocantal) podem exercer efeitos de inibição da gênese tumoral, como a reparação e a proteção contra danos do estresse oxidativo e da inflamação crônica, e dessa maneira, poderiam auxiliar na redução do risco de câncer, postergando o desenvolvimento, a progressão ou recorrência de diversos tipos de tumores. A análise dos estudos demonstrou potencial antitumoral dos compostos fenólicos da oliveira por apresentarem atividade anticâncer por meio da diminuição do crescimento e da viabilidade celular, inibição da proliferação, migração e invasão celular, modulação nas fases do ciclo celular e indução da apoptoses em diferentes modelos tumorais.
5
Bisanção, Vitória Roberto, Julio Cesar Polonio e Halison Correia Golias. "COGUMELOS BASIDIOMYCOTA: FONTES DE COMPOSTOS COM ATIVIDADE ANTICÂNCER". Arquivos do Mudi 26, n. 2 (22 agosto 2022): 29–46. http://dx.doi.org/10.4025/arqmudi.v27i2.63571.
Testo completoAbstract (sommario):
Os cogumelos silvestres são fascinantes pela formação de seus corpos de frutificação e sua aplicação na indústria alimentícia e medicinal, apresentando-se como uma grande fonte de extração de metabólitos secundários com propriedades farmacológicas. Esta revisão tem como objetivo fornecer informações sobre a produção de compostos com atividade anticancerígena por cogumelos do filo Basidiomycota, apresentando diferentes moléculas obtidas desses organismos e como elas atuam no combate às células tumorais. Dentre os principais medicamentos produzidos a partir desses fungos, destacam-se os utilizados para o tratamento do câncer. Os principais metabólitos primários extraídos deste grupo e aplicados em atividades farmacológicas são os polissacarídeos da família das beta-glucanas. Esses compostos são encontrados nas paredes dos fungos, que podem atuar no tratamento de atividades antitumorais, pois estimula o funcionamento do sistema imunológico aumentando o bloqueio da imunidade celular.
6
Cristina Novaes dos Reis, Roberta, Gustavo Alves de Castro, Gustavo Henrique Souza Oliveira, Lara Cristina Pereira Malaquias, Alessandro Del’Duca Teixeira, Cassiano Fonseca e Adilson David da Silva. "Potenciais aplicações medicinais de compostos 1,2,3-triazólicos: uma revisão". HU Revista 48 (11 agosto 2022): 1–15. http://dx.doi.org/10.34019/1982-8047.2022.v48.36662.
Testo completoAbstract (sommario):
Introdução: Os 1,2,3-triazóis são compostos de origem sintética e são relevantes para a química medicinal, além de poderem atuar como uma conexão entre duas ou mais substâncias de interesse, em uma estratégia de hibridação molecular. Objetivo: Abordar algumas aplicações farmacológicas dos derivados 1,2,3-triazólicos. Material e Métodos: Uma busca na base de dados Scopus utilizando o termo “1,2,3 triazole” (janeiro de 2021), foi realizada, além de uma pesquisa nos bancos de dados eletrônicos público. Resultados: Foram encontrados 5.760 resultados para os últimos dez anos sobre 1,2,3-triazóis, bem como várias publicações referentes a derivados 1,2,3-triazólicos de interesse farmacológico. Conclusão: Os compostos 1,2,3-triazólicos têm adquirido cada vez mais atenção e visibilidade no que se refere as suas potenciais atividades farmacológicas, tais como antiviral, antitumoral, antifúngica, antiparasitária e antimicrobiana.
7
Santos, Viviane Martins Rebello dos, Claudio Luis Donnici, João Batista Neves DaCosta e Janaína Marques Rodrigues Caixeiro. "Compostos organofosforados pentavalentes: histórico, métodos sintéticos de preparação e aplicações como inseticidas e agentes antitumorais". Química Nova 30, n. 1 (febbraio 2007): 159–70. http://dx.doi.org/10.1590/s0100-40422007000100028.
Testo completo
8
Scheller, S., W. Krol, K. Skirmuntt, G. Zydowicz e J. Shani. "Antitumoral Effect of Bleomycin + Dolomite Combination Treatment, in Mice Bearing Ehrlich Ascites Carcinoma". Zeitschrift für Naturforschung C 48, n. 9-10 (1 ottobre 1993): 818–20. http://dx.doi.org/10.1515/znc-1993-9-1023.
Testo completoAbstract (sommario):
Abstract Dolomite, a mineral composed of magnesium and calcium carbonates, potentiates the antitumoral activity of bleomycin: While 40 days after inoculation, no mice survived the Ehrlich ascites tumor burden, 44% of them survived it after bleomycin treatment, and 63% after a simultaneous treatment of bleomycin and dolomite. The beneficial antitumor effect of dolomite is probably related to its high content (12.8%) of magnesium
9
Oliveira, Bruno Hanrry Melo, Luiz André Araujo Silva, Fernando Ferreira Leite, Gabrielly Diniz Duarte, Sâmia Sousa Duarte, Daiana Karla Frade Silva, Marianna Vieira Sobral e Luis Cézar Rodrigues. "Síntese e avaliação antitumoral do (±)-4-O-demethylKadsurenin M um composto natural e seus análogos". Brazilian Journal of Development 5, n. 10 (2019): 19109–23. http://dx.doi.org/10.34117/bjdv5n10-144.
Testo completo
10
Bouyahya, A., J. Abrini, Y. Bakri e N. Dakka. "Les huiles essentielles comme agents anticancéreux : actualité sur le mode d’action". Phytothérapie 16, n. 5 (ottobre 2018): 254–67. http://dx.doi.org/10.3166/s10298-016-1058-z.
Testo completoAbstract (sommario):
Le cancer est une maladie complexe qui présente un réel problème de santé publique à travers le monde et cause statiquement sept millions de décès chaque année. Au cours des dernières décennies, la thérapie anticancéreuse a connu un réel bouleversement et un foisonnement de découvertes fondamentales. Plusieurs études accumulatives ont révélé l’activité antitumorale des substances naturelles isolées à partir de plantes. Les huiles essentielles (HE) et leurs constituants ont montré des activités anticancéreuses puissantes in vitro et in vivo. Cependant, les mécanismes d’action sont encore peu étudiés et moins connus. Par ailleurs, leur application dans l’industrie pharmaceutique nécessite une spécificité– sélectivité pharmacodynamique absolue. Dans le présent travail, nous présentons une synthèse des travaux réalisés sur les mécanismes d’actions anticancéreuses des HE et leurs composés bioactifs.
11
da Silva, Tereza Cristina, Bruno Cogliati, Andréia Oliveira Latorre, Gokithi Akisue, Márcia Kazumi Nagamine, Mitsue Haraguchi, Daiane Hansen, Daniel Soares Sanches e Maria Lúcia Zaidan Dagli. "Pfaffosidic Fraction fromHebanthe paniculataInduces Cell Cycle Arrest and Caspase-3-Induced Apoptosis in HepG2 Cells". Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/835796.
Testo completoAbstract (sommario):
Hebanthe paniculataroots (formerlyPfaffia paniculataand popularly known as Brazilian ginseng) show antineoplastic, chemopreventive, and antiproliferative properties. Functional properties of these roots and their extracts are usually attributed to the pfaffosidic fraction, which is composed mainly by pfaffosides A–F. However, the therapeutic potential of this fraction in cancer cells is not yet entirely understood. This study aimed to analyze the antitumoral effects of the purified pfaffosidic fraction or saponinic fraction on the human hepatocellular carcinoma HepG2 cell line. Cellular viability, proliferation, and apoptosis were evaluated, respectively, by MTT assay, BrdU incorporation, activated caspase-3 immunocytochemistry, and DNA fragmentation assay. Cell cycle was analyzed by flow cytometry and the cell cycle-related proteins were analyzed by quantitative PCR and Western blot. The cells exposed to pfaffosidic fraction had reduced viability and cellular growth, induced G2/M at 48 h or S at 72 h arrest, and increased sub-G1 cell population via cyclin E downregulation,p27KIP1overexpression, and caspase-3-induced apoptosis, without affecting the DNA integrity. Antitumoral effects of pfaffosidic fraction fromH. paniculatain HepG2 cells originated by multimechanisms of action might be associated with cell cycle arrest in the S phase, by CDK2 and cyclin E downregulation andp27KIP1overexpression, besides induction of apoptosis through caspase-3 activation.
12
SILVA, L. E., R. A. REIS, E. A. MOURA, W. AMARAL e P. T. SOUSA Jr. "Plantas do Gênero Xylopia: Composição Química e Potencial Farmacológico". Revista Brasileira de Plantas Medicinais 17, n. 4 suppl 1 (2015): 814–26. http://dx.doi.org/10.1590/1983-084x/14_076.
Testo completoAbstract (sommario):
RESUMO A família Annonaceae possui representantes de grande interesse medicinal e o gênero Xylopia é um dos que merecem destaque. Composta por aproximadamente 160 espécies distribuídas na América do Sul, América central, África e Ásia, as espécies desse gênero podem ser arbustivas ou arbóreas. No Brasil são encontradas nas regiões Norte, Nordeste, Centro-Oeste e Centro Sul. Este gênero produz uma variedade de metabólitos incluindo alcalóides, amidas, lignóides, acetogeninas e terpenóides e têm sido investigados como fonte potencial de acetogeninas, compostos esses que apresentam uma ampla variedade de propriedades biológicas com destaque para: citotóxica, antitumoral, antiparasitária, antimicrobial, inseticida e antimalarial. Neste estudo, efetuou-se uma revisão das principais espécies de Xylopiaencontradas no Brasil, já estudadas e descritas na literatura, abordando os aspectos químico-farmacológicos, destacando os constituintes químicos isolados bem como a ação farmacológica evidenciada.
13
Mojsilovic, Sonja S., Slavko Mojsilovic, Victor H. Villar e Juan F. Santibanez. "The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?" Analytical Cellular Pathology 2021 (14 agosto 2021): 1–12. http://dx.doi.org/10.1155/2021/5523055.
Testo completoAbstract (sommario):
Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.
14
Formaggio, Daniela M. D., Jéssica A. Magalhães, Vitor M. Andrade, Katia Conceição, Juliana M. Anastácio, Gabrielli S. Santiago, Denise C. Arruda e Dayane B. Tada. "Co-Functionalization of Gold Nanoparticles with C7H2 and HuAL1 Peptides: Enhanced Antimicrobial and Antitumoral Activities". Pharmaceutics 14, n. 7 (23 giugno 2022): 1324. http://dx.doi.org/10.3390/pharmaceutics14071324.
Testo completoAbstract (sommario):
The functionalization of nanoparticles with therapeutic peptides has been pointed out as a promising strategy to improve the applications of these molecules in the field of health sciences. Peptides are highly bioactive but face several limitations such as low bioavailability due to the difficulty of overcoming the physiological barriers in the body and their degradation by enzymes. In this work, gold nanoparticles (AuNPs) were co-functionalized with two therapeutic peptides simultaneously. The peptides from the complementary determining region of monoclonal antibodies, composed of the amino acid sequences YISCYNGATSYNQKFK (C7H2) and RASQSVSSYLA (HuAL1) were chosen for having exhibited antitumor and antimicrobial activity before. The peptides-conjugated AuNPs were characterized regarding size, morphology, and metal concentration by using TEM, dynamic light scattering, and ICP-OES techniques. Then, peptides-conjugated AuNPs were evaluated regarding the antimicrobial activity against E. coli, P. aeruginosa, and C. albicans. The antitumoral activity was evaluated in vitro by cell viability assays with metastatic melanoma cell line (B16F10-Nex2) and the cytotoxicity was evaluated against human foreskin fibroblast (Hs68) cell line. Finally, in vivo assays were performed by using a syngeneic animal model of metastatic melanoma. Our findings have highlighted the potential application of the dual-peptide AuNPs in order to enhance the antitumor and antimicrobial activity of peptides.
15
Moreira, João de Brito, Naíra Assunção De Sá Holanda, Sarah Raquel Silveira Da Silva Santiago, Elzalina Ribeiro Soares, Richardson Alves De Almeida, Ketlen Christine Ohse e Paulo Alexandre Lima Santiago. "LEVANTAMENTO BIBLIOGRÁFICO DOS COMPOSTOS QUÍMICOS COM ATIVIDADE ANTIOXIDANTE E ANTIMICROBIANA PRESENSTES EM Arrabidaea chica (HUMB. & BONPL.) B. VERLOT (BIGNONIACEAE)". REVISTA FOCO 17, n. 1 (19 gennaio 2024): e4141. http://dx.doi.org/10.54751/revistafoco.v17n1-073.
Testo completoAbstract (sommario):
A espécie vegetal Arrabidaea chica, popularmente como pariri, cipó-pau ou crajiru, destaca-se por suas diversas propriedades medicinais. Dentre elas, a possibilidade de uso no tratamento de inflamações uterinas, sífilis, leucemia, conjuntivites, diarreias, cólicas intestinais, psoríase, impigens, úlceras, prevenção contra cáries dentre outros. Apesar de ser um organismo amplamente estudado, o número de monografias, dissertações, teses e artigos que abordam essa espécie nos últimos dez anos não ultrapassa cinquenta e cinco, e essa quantidade é ainda menor no Amazonas. Nesse contexto, este estudo tem como objetivo analisar, por meio de levantamento bibliográfico, os compostos químicos presentes nas folhas e hastes da A. chica responsáveis pelas atividades antimicrobiana e antioxidante. O método empregado baseia-se em pesquisa exploratória-descritiva de artigos disponíveis nas bases SciELO e Google Acadêmico, abrangendo o período de 2004 a 2022, com enfoque em atividade antimicrobiana e antioxidante. Foram identificados 20 artigos que indicam a predominância de substâncias da classe dos flavonoides, os quais exibem atividade antioxidante e antimicrobiana contra diversos patógenos, incluindo Trichophyton mentagrophytes, Candida albicans, Staphylococcus aureus e Pseudomonas aeruginosa. Além disso, relatam-se atividades antianêmicas, anti-hipertensivas, anti-hepatotóxicas, antioxidantes, antitumorais, anti-inflamatórias, diuréticas e cicatrizantes. Dentre os flavonoides que são mencionados na literatura, têm-se a carajurina, carajurona, 6,7,3’-triidroxi-5,4’-dimetoxiflavílio, 6,7,3,4’-triidroxi-5-metoxiflavílio, 4’,7-diidroxi-5-metoxiflavona, 4’-hidroxi-3,7-dimetoxiflavona, carajuflavona, luteolina, kaempferol, vicentina-2 e acacetina. A partir do levantamento de dados realizado no presente estudo, almeja-se promover a disseminação do conhecimento e incentivar pesquisas biológicas e químicas sobre a A. chica na região do Alto Solimões no Estado do Amazonas.
16
Vedeanu, Nicoleta Simona, Cristian Lujerdean, Marius Zăhan, Daniel Severus Dezmirean, Lucian Barbu-Tudoran, Grigore Damian e Răzvan Ștefan. "Synthesis and Structural Characterization of CaO-P2O5-CaF:CuO Glasses with Antitumoral Effect on Skin Cancer Cells". Materials 15, n. 4 (18 febbraio 2022): 1526. http://dx.doi.org/10.3390/ma15041526.
Testo completoAbstract (sommario):
Copper is one of the most used therapeutic metallic elements in biomedicine, ranging from antibacterial approaches to developing new complexes in cancer therapy. In the present investigation, we developed a novel xCuO∙(100 − x) [CaF2∙3P2O5∙CaO] glass system with 0 ≤ x ≤ 16 mol% in order to determine the influence of doping on the composition structure of glasses. The samples were characterized by dissolution tests, pH measurements, Fourier-transform infrared spectroscopy (FT-IR), electron paramagnetic resonance (EPR), Scanning Electron Microscopy with energy dispersive spectroscopy (SEM-EDX) and afterward, their antitumor character was assessed. The glasses were mostly soluble in the aqueous medium, their dissolution rate being directly proportional to the increase in pH and the level of doping up to x = 8 mol%. FT-IR spectra of glass samples show the presence of all structural units characteristic to P2O5 in different rates and directly depending on the depolymerization process. SEM-EDX results revealed the presence of an amorphous glass structure composed of P, O, Ca, and Cu elements. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay showed strong cytotoxicity for tumoral cells A375 even in low concentrations for Cu-treatment. In contrast, the copper-free matrix (without Cu) determined a proliferative effect of over 70% viability for all concentrations used.
17
Nunes, Higor Lopes, Katiuska Tuttis, Juliana Mara Serpeloni, Cláudia Quintino da Rocha e Ilce Mara de Syllos Cólus. "Efeito necrótico de brachydin A, um composto de origem vegetal, em células humanas de próstata normais e tumorais". Semina: Ciências Biológicas e da Saúde 38, n. 1supl (16 febbraio 2018): 158. http://dx.doi.org/10.5433/1679-0367.2017v38n1suplp158.
Testo completoAbstract (sommario):
Para combater efeitos genotóxicos de agentes químicos, aditivos de alimentos e medicamentos que causam danos no DNA, estudos sobre quimioprevenção são desenvolvidos com o propósito de reverter ou suprimir lesões pré-malignas ou malignas por meio da utilização de compostos químicos naturais ou sintéticos. Os fitoterápicos têm sido uma alternativa para quimioprevenção de doenças crônicas. Entre as plantas utilizadas na medicina popular brasileira destaca-se o gênero Arrabidaea (família Bignoniaceae). Diversas espécies deste gênero têm sido utilizadas na medicina tradicional com função antioxidante, antimicrobiana, antitumoral, anti-inflamatória e adstringente. O presente estudo teve como objetivo avaliar os possíveis efeitos citotóxicos de quatro concentrações (0,96; 1,50; 3,84 e 6,00 ?M) de brachydin A, um composto extraído das raízes de Arrabidaea brachypoda (DC) Bureau, em relação ao processo de morte celular em linhagens celulares humanos de próstata normais (PNT2) e tumorais (PC-3). O conhecimento dessa atividade biológica, somado aos resultados de outras investigações sobre este composto poderá contribuir para que futuramente este possa ser recomendado como medicamento fitoterápico. O processo de apoptose ocorre normalmente durante o desenvolvimento e envelhecimento celular, também como um mecanismo homeostático para controlar a população celular ou como um mecanismo de defesa. A necrose, considerada um processo tóxico, degradativo, pode danificar células adjacentes. O ensaio de apoptose/necrose utilizando corantes fluorescentes permite a diferenciação dos distintos tipos de morte celular. No presente estudo uma mistura de fluorocromos (Hoescht + diacetato de fluoresceína + iodeto de propídio, adicionados a tampão fosfato salino) foi feita para o ensaio de apoptose/necrose. O composto brachydin A induziu necrose na concentração de 6 ?M em ambos os tipos celulares após 24 horas de tratamento. Estes resultados corroboram dados do laboratório de Mutagênese e Oncogenética ainda não publicados, onde o extrato etanólico das folhas de A. brachypoda induziu necrose em células primárias de estômago normais (GAS) e tumorais (ACP02). Como brachydin A foi obtido a partir de extratos da mesma planta, a análise conjunta dos resultados reforça o efeito necrótico de compostos presentes nesta planta para células humanas in vitro.
18
Lucas, Mariana, Marisa Freitas, Artur M. S. Silva, Eduarda Fernandes e Daniela Ribeiro. "Styrylchromones: Biological Activities and Structure-Activity Relationship". Oxidative Medicine and Cellular Longevity 2021 (22 dicembre 2021): 1–47. http://dx.doi.org/10.1155/2021/2804521.
Testo completoAbstract (sommario):
Styrylchromones (SC) are a group of oxygen-containing heterocyclic compounds, which are characterized by the attachment of a styryl group to the chromone core. SC can be found in nature or can be chemically synthesized in the laboratory. As their presence in nature is scarce, the synthetic origin is the most common. Two types of SC are known: 2-styrylchromones and 3-styrylchromones. However, 2-styrylchromones are the most common, being more commonly found in nature and which chemical synthesis is more commonly described. A wide variety of SC has been described in the literature, with different substituents in different positions, the majority of which are distributed on the A- and/or B-rings. Over the years, several biological activities have been attributed to SC. This work presents a comprehensive review of the biological activities attributed to SC and their structure-activity relationship, based on a published literature search, since 1989. The following biological activities are thoroughly revised and discussed in this review: antioxidant, antiallergic, antiviral, antibacterial, antifungal, anti-inflammatory, and antitumoral, affinity and selectivity for A3 adenosine receptors, neuroprotective, and α-glucosidase inhibition. In general, SC are composed by a promising scaffold with great potential for the development of new drugs.
19
Pieretti, Joana C., Jordan Beurton, Julián Munevar, Luiz C. C. M. Nagamine, Alain Le Faou, Amedea B. Seabra, Igor Clarot e Ariane Boudier. "The Impact of Multiple Functional Layers in the Structure of Magnetic Nanoparticles and Their Influence on Albumin Interaction". International Journal of Molecular Sciences 22, n. 19 (28 settembre 2021): 10477. http://dx.doi.org/10.3390/ijms221910477.
Testo completoAbstract (sommario):
In nanomedicine, hybrid nanomaterials stand out for providing new insights in both the diagnosis and treatment of several diseases. Once administered, engineered nanoparticles (NPs) interact with biological molecules, and the nature of this interaction might directly interfere with the biological fate and action of the NPs. In this work, we synthesized a hybrid magnetic nanostructure, with antibacterial and antitumoral potential applications, composed of a magnetite core covered by silver NPs, and coated with a modified chitosan polymer. As magnetite NPs readily oxidize to maghemite, we investigated the structural properties of the NPs after addition of the two successive layers using Mössbauer spectroscopy. Then, the structural characteristics of the NPs were correlated to their interaction with albumin, the major blood protein, to evidence the consequences of its binding on NP properties and protein retention. Thermodynamic parameters of the NPs–albumin interaction were determined. We observed that the more stable NPs (coated with modified chitosan) present a lower affinity for albumin in comparison to pure magnetite and magnetite/silver hybrid NPs. Surface properties were key players at the NP–biological interface. To the best of our knowledge, this is the first study that demonstrates a correlation between the structural properties of complex hybrid NPs and their interaction with albumin.
20
De Oliveira, Brenner Kássio Ferreira, Eloiza de Oliveira Silva, Rosa Mery Oliveira e Oliveira, Waldireny Rocha Gomes e Maria de Fátima Fernandes Vattimo. "Ação farmacológica e uso etnofarmacológico da Abuta grandifolia e outras plantas do gênero na medicina popular amazônica: revisão de escopo". Brazilian Journal of Health Review 6, n. 2 (10 aprile 2023): 7158–76. http://dx.doi.org/10.34119/bjhrv6n2-215.
Testo completoAbstract (sommario):
O gênero Abuta é encontrado nas florestas tropicais, tendo maior diversidade na Amazônia. Os caules, folhas e raízes dessas espécies são utilizados para tratamento de doenças, mas também a partir deles extraem-se produtos naturais com ampla variedade de propriedades medicinais. O uso corriqueiro para tratamento de afecções urinárias e renais em comunidades ribeirinhas da Amazônia tem despertado interesse por suas propriedades farmacológicas. Esta revisão tem o objetivo de mapear dados etnofarmacológicos e farmacológicos descritos na literatura para espécies do gênero Abuta. Usou-se a combinação mnemônica PCC (P: Population – não incluída; C: concept – aspectos etnofarmacológicos e farmacológicos; C: Contexto – fitoterapia). O levantamento bibliográfico ocorreu nas bases de dados da Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SCIELO), National Library of Medicine (PUBMED), MEDLINE, SCOPUS e Google Scholar em período atemporal. A amostra final foi composta de 32 artigos, dos quais, 12 foram elencados com indicações etnofarmacológicas e 20 com dados farmacológicos. Estudos de validação dos dados etnofarmacológicos confirmaram inúmeras indicações populares para diversas espécies de Abuta, incluindo atividades atuantes no sistema neurológico, antihiperglicêmica, antimalárica, antimicrobiana, antitumoral e imunomoduladora, justificando o uso destas espécies na medicina popular, entretanto, não há estudos farmacológicos sobre a sua atuação sobre umas das formas de uso popular contra doenças renais.
21
Solano, Alfredo Amaury Bautista, Gloria Dávila-Ortiz, María de Jesús Perea-Flores e Alma Leticia Martínez-Ayala. "Optimization and Synthesis of Nano-Niosomes for Encapsulation of Triacontanol by Box–Behnken Design". Molecules 29, n. 18 (18 settembre 2024): 4421. http://dx.doi.org/10.3390/molecules29184421.
Testo completoAbstract (sommario):
Triacontanol is a long-chain primary alcohol derived from policosanol, known for its diverse biological activities, including functioning as a plant growth regulator and exhibiting anti-inflammatory and antitumoral effects. However, its application is limited due to its high hydrophobicity, resulting in poor absorption and reduced therapeutic effectiveness. A potential solution to this problem is the use of niosomes. Niosomes are carriers composed of non-ionic surfactants, cholesterol, charge-inducing agents, and a hydration medium. They are effective in encapsulating drugs, improving their solubility and bioavailability. The objective of this study was to optimize and synthesize nano-niosomes for the encapsulation of triacontanol. Niosomes were synthesized using a thin-film hydration method combined with ultrasonication, following a Box–Behnken design. Niosomes were characterized using various techniques including dynamic light scattering, Fourier-transform infrared spectroscopy (FTIR), confocal microscopy, high-resolution scanning electron microscopy, and transmission electron microscopy (TEM). Formulation 14 of niosomes achieved the desired size, polydispersity index (0.198 ± 0.008), and zeta potential (−31.28 ± 1.21). FTIR analysis revealed a characteristic signal in the 3400–300 cm−1 range, indicating intermolecular interactions due to a bifurcated hydrogen bond between cholesterol and S60. Confocal microscopy confirmed the presence of triacontanol through Nile Red fluorescence. TEM revealed the spherical structure of niosomes.
22
Paíno, Teresa, Antonio Garcia-Gomez, Lorena González-Méndez, Laura San-Segundo, Montserrat Martín-Sánchez, Susana Hernández-García, Mercedes Garayoa, Enrique M. Ocio e Jesús F. San-Miguel. "Dual Antitumoral and Bone Antiresorptive Effect Of The Pan-Pim Kinase Inhibitor, LGH447, In Multiple Myeloma". Blood 122, n. 21 (15 novembre 2013): 4435. http://dx.doi.org/10.1182/blood.v122.21.4435.4435.
Testo completoAbstract (sommario):
Introduction Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM) and is closely associated with osteolytic lesions, in part due to an increase in the bone-resorptive activity and number of osteoclasts (OCs). The activation of survival pathways in myeloma cells could be the cause of treatment failure rendering the disease incurable. Pim kinases are a family of survival serine/threonine kinases composed of three members (Pim1, Pim2 and Pim3) that are overexpressed in MM cells and may have a role in MM pathogenesis. However, little is known about the role of Pim kinases in OCs and its involvement in myeloma bone disease. Here, we have evaluated the preclinical activity of a new pan-Pim kinase inhibitor, LGH447, on MM cells and OCs. Cell lines, primary samples, material and methods LGH447 was provided by Novartis Pharmaceuticals. The human MM cell lines MM1S, MM1R, RPMI-8226 (or RPMI-8226-luc), RPMI-LR5, MM144, NCI-H929, OPM-2, U266, U266-Dox4 and U266-LR7 were employed. PBMCs from healthy volunteers were used to generate OCs, whereas primary mesenchymal stromal cells (MSCs) were obtained from bone marrow aspirates of MM patients. Cell viability was studied using MTT colorimetric assay or bioluminescence. Apoptosis was measured by annexin-V staining. For cell cycle analysis, propidium iodide staining was used. OC formation was assessed by enumeration of multinucleated (≥3) TRAP-positive cells and OC resorption was assessed on calcium-coated slides. Immunoblotting, quantitative PCR and immunofluorescence were used to further investigate the mechanism of action of LGH447. Results All MM cell lines expressed the three isoforms of Pim kinases with higher levels of Pim2. The dose-response curves to LGH447 after a 48 hour treatment revealed two groups of MM cell lines with regard to sensitivity to this drug: high sensitive, with IC50 values ranging from 0.2 to 3.3 µM (MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929); and low sensitive, with IC50 values >7 µM (OPM-2, RPMI-LR5, U266-Dox4 and U266-LR7). Our results indicated that LGH447 promoted apoptosis in myeloma cells as shown by the increase in annexin-V positive cells and by the cleavage of initiator (caspases 8 and 9) and effector caspases (caspases 3 and 7) and of PARP. LGH447 also blocked the cell cycle in MM cells as demonstrated by the increase in G0-G1 and the decrease in S-G2-M phases. Importantly, LGH447 was also able to overcome the growth advantage conferred to RPMI-8226-luc cells by co-culture with MSCs or OCs. Regarding the mechanisms involved in these effects, LGH447 inhibited the mTOR pathway, demonstrated by a decreased phosphorylation of the downstream mTOR effectors, 4EBP1 and S6 in residues Thr37/46 and Ser235/236, respectively. Interestingly, LGH447 also inhibited OC formation and resorption activity. LGH447 treatment of human pre-OCs diminished the expression of key molecules involved in OC differentiation (p-Erk1/2 and NFATc1) and function [CAII (carbonic anhidrase II), CLCN7 (chloride channel 7), ATP6V1A (vacuolar-H+-ATPase catalytic subunit A1) and MMP9 (matrix metalloproteinase 9)] and also disrupted the F-actin ring necessary for OC effective resorption. Conclusion Overall, our results demonstrate that both MM cells and OCs are targets of the pan-Pim kinase inhibitor, LGH447. Therefore, the inhibition of Pim kinases could potentially provide a dual benefit in myeloma patients as a consequence of cytotoxic effects exerted on MM cells and an anti-resorptive activity on bone. This work was supported by funding from the Fundación Española de Hematología y Hemoterapia (AG-G), Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, the RTICC-Hematology Group (RD12/0036/0058), Spanish FIS (PI12/02591) and the Junta de Castilla y León, Gerencia Regional de Salud (GRS 862/A/13). Disclosures: Off Label Use: LGH447 is a pan-Pim kinase inhibitor (Novartis Pharmaceuticals). It has been used for pre-clinical studies in multiple myeloma.
23
Corrêa, Anna, Mauricio Vericimo, Andriy Dashevskiy, Patricia Pereira e Vania Paschoalin. "Liposomal Taro Lectin Nanocapsules Control Human Glioblastoma and Mammary Adenocarcinoma Cell Proliferation". Molecules 24, n. 3 (29 gennaio 2019): 471. http://dx.doi.org/10.3390/molecules24030471.
Testo completoAbstract (sommario):
The search for natural anticancer agents and nanocarrier uses are a part of the current strategies to overcome the side effects caused by chemotherapeutics. Liposomal nanocapsules loaded with purified tarin, a potential immunomodulatory and antitumoral lectin found in taro corms, were produced. Liposomes were composed by 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine, cholesterylhemisuccinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000 prepared by thin-film hydration. Small unilamellar vesicles were achieved by sonication and extrusion. Scanning electron microscopy evidenced round-shaped nanocapsules presenting a smooth surface, 150 nm diameter and polydispersity index <0.2, estimated by dynamic light scattering. Tarin entrapment rates were over 80% and leakage of ~3% under 40 days of storage at 4 °C. Entrapped tarin exhibited an 83% release after 6 h at pH 4.6–7.4 and 36 °C. Both free and encapsulated tarin exhibited no in vitro toxicity against healthy mice bone marrow and L929 cells but stimulated the production of fibroblast-like and large round-shaped cells. Encapsulated tarin resulted in inhibition of human glioblastoma (U-87 MG) and breast adenocarcinoma (MDA-MB-231) proliferation, with an IC50 of 39.36 and 71.38 µg/mL, respectively. The effectiveness of encapsulated tarin was similar to conventional chemotherapy drugs, such as cisplatin and temozolide. Tarin liposomal nanocapsules exhibited superior pharmacological activity compared to free tarin as a potential chemotherapy adjuvant.
24
Yang, Haijun, Xiang Li, Ning Zhang, Qingqi Zeng, Qiping Yu e Shihuai Ke. "HPLC Method for the Simultaneous Determination of Ten Annonaceous Acetogenins after Supercritical Fluid CO2 Extraction". International Journal of Biomedical Science 6, n. 3 (15 settembre 2010): 202–7. http://dx.doi.org/10.59566/ijbs.2010.6202.
Testo completoAbstract (sommario):
Annonaceous acetogenins (ACGs) isolated from Annonaceaeplants exhibited a broad range of biological bioactivities such as cytotoxic, antitumoral, antiparasitic, pesticidal and immunosuppresive activities. However, their structures were liable to change at more than 60°C and their extraction yields were low using traditional organic solvent extraction. In the present study, all samples from Annona genus plant seeds were extracted by supercritical carbon dioxide under optimized conditions and a high-performance liquid chromatography (HPLC) method was established for simultaneously determining ten ACGs. All of the ten compounds were simultaneously separated on reversed-phase C18 column (250 mm × 4.6 mm, 5 μm) with the column temperature at 30°C. The mobile phase was composed of (A) methanol and (B) distilled water, the flow rate was 1.0 ml/min and the detection wavelength was set at 220 nm. All calibration curves showed good linear regression (γ>0.9995) within the test range. The established method showed good precision and accuracy with overall intra-day and inter-day variations of 0.99-2.56% and 1.93-3.65%, respectively, and overall recoveries of 95.16-105.01% for the ten compounds analyzed. The established method can be applied to evaluate the intrinsic quality of Annonaceae plant seeds. The determination results recover the content-variation regularities of various ACGs in different species, which are helpful to choose the good-quality Annonaceae plant seeds for anticancer lead compound discovery.
25
Sosa-Lochedino, Arianna, María Belén Hapon e Carlos Gamarra-Luques. "A Systematic Review About the Contribution of The Genus Tessaria (Asteraceae) To Cancer Study and Treatment". Uniciencia 36, n. 1 (1 giugno 2022): 1–17. http://dx.doi.org/10.15359/ru.36-1.30.
Testo completoAbstract (sommario):
Belonging to the Asteraceae family, Tessaria (Ruiz & Pavon, 1753) is a genus of shrubs or small trees distributed in various habitats located from Argentina to the southwestern United States of America. The taxa are composed of five confirmed species, which have been previously reported for their ethnopharmacological uses as hypocholesterolemiant, hypoglycemic, antitussive, anti-inflammatory, anticancer, and abortifacient agent; it also has been used in hepatic, renal, pulmonary, and rheumatic diseases. Up to the present, T. absinthioides, T. ambigua, T. dodoneifolia, T. fastigiata and T. integrifolia have been chemically analyzed. While decoctions, infusions, methanolic, and hydromethanolic extracts are the most studied botanical compounds, its most recognized phytochemical constituents are caffeoylquinic acid, eupatorin, naringenin, protocatechuic, and quercetin. Scientifically, several biomedical properties such as virucidal, antibacterial, leishmanicidal, insecticidal, gastroprotective, antiasthmatic, hypoglycemic, and antiatherogenic were attributed to the genus. Concerning oncologic research, the chemicals produced by Tessaria have antitumor activities interfering with carcinogenesis, cell proliferation, metastasis, and angiogenesis. In addition, the natural extracts obtained from Tessaria species have biological activities closely related to cancer, acting as antioxidants and anti-inflammatories. In particular, it has been reported that T. absinthioides resulted cytotoxic against several cancer cell lines and acts as an antitumoral compound in murine models. Due to the aforementioned antecedents, the Tessaria species are considered undervalued within the oncological field; the goal of the current systematic review is to summarize the information available on the genus, relevant for cancer research and treatment.
26
Moya-Lopez, Carmen, Alberto Juan, Murillo Donizeti, Jesus Valcarcel, José A. Vazquez, Eduardo Solano, David Chapron et al. "Multifunctional PLA/Gelatin Bionanocomposites for Tailored Drug Delivery Systems". Pharmaceutics 14, n. 6 (27 maggio 2022): 1138. http://dx.doi.org/10.3390/pharmaceutics14061138.
Testo completoAbstract (sommario):
A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect. The nanoparticles generated were successfully formulated with two different antitumoral compounds (doxorubicin and dasatinib) possessing different structures to prove the loading versatility of the drug delivery system. The bionanocomposites were characterized by several techniques (SEM, DLS, RAMAN, DSC, SAXS/WAXS and rheology) as well as their reversible sol–gel transition upon thermal treatment that occurs during the drug delivery system preparation and the thermal annealing step. In addition, the local applicability of the drug delivery system was assessed by the so-called “syringe test” to validate both the storage capability and its flow properties at simulated physiological conditions. Finally, the drug release profiles of the doxorubicin from both the PLA nanoparticles or the bionanocomposites were analyzed and correlated to the nanostructure of the drug delivery system.
27
Yu, Chunxiao, Kurt Shanebeck, Shiguang Yu, Jeanine Ruiz, Shichang Li, Stone D. H. Shi, Hong Ma e Yuefeng Lu. "Abstract 2474: Antitumoral efficacy of ASKG812, a Smartkine® based bifunctional PD-1-eIL-2 molecule, through enhancing T effector cis agonism". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 2474. http://dx.doi.org/10.1158/1538-7445.am2024-2474.
Testo completoAbstract (sommario):
Abstract Cytokines are potent molecules, yet their broad application as therapeutics has been significantly hampered due to short PK, severe systemic toxicity, and narrow therapeutic window. To improve the developability of cytokines, AskGene has invented a proprietary cytokine platform (Smartkine®) to achieve its overarching objective of modulating immune reactions at a disease site in a selective and controlled manner. Several antibody-cytokine fusion molecules using the SmartKine® platform have been moving into preclinical and clinical development. ASKG812 is a unique fusion molecule composed of anti-PD-1 antibody and engineered IL-2 (eIL-2). The eIL-2 moiety also comprises a specific mask such that the eIL-2 molecule binding biases towards PD-1+ T effector cells in a cis agonism manner for improved efficacy and therapeutic window. In ex vivo human PBMC assays, we demonstrated that ASKG812 significantly reduced activity in PD-1− T and NK cells, and enhanced activity in PD-1+ T cells judged by levels of pSTAT5, Ki67 and Granzyme B. In a cytotoxicity assay, ASKG812 can efficiently induce PBMC-mediated killing of MDA-MB-231 tumor cells in a dose-dependent manner. Moreover, in both anti-PD-1 therapy responsive and non-responsive syngeneic mouse tumor models, ASKG812 showed robust efficacy; without noticeable toxicity compared to a reference anti-PD-1-IL-2v fusion molecule. In conclusion, these findings provide the basis for the development of this new generation of PD-1 cis-targeted IL-2R agonists with enhanced therapeutic potential for the clinical treatment of cancer. Citation Format: Chunxiao Yu, Kurt Shanebeck, Shiguang Yu, Jeanine Ruiz, Shichang Li, Stone D.-H Shi, Hong Ma, Yuefeng Lu. Antitumoral efficacy of ASKG812, a Smartkine® based bifunctional PD-1-eIL-2 molecule, through enhancing T effector cis agonism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2474.
28
Dieu-Nosjean, Marie-Caroline, Martine Antoine, Claire Danel, Didier Heudes, Marie Wislez, Virginie Poulot, Nathalie Rabbe et al. "Long-Term Survival for Patients With Non–Small-Cell Lung Cancer With Intratumoral Lymphoid Structures". Journal of Clinical Oncology 26, n. 27 (20 settembre 2008): 4410–17. http://dx.doi.org/10.1200/jco.2007.15.0284.
Testo completoAbstract (sommario):
Purpose It has been established that the immune system plays an important role in tumor rejection. There is also compelling evidence that immune responses can develop independently of secondary lymphoid organs in tertiary lymphoid structures. We studied the presence and the correlation of tertiary lymphoid structures with clinical outcome in non–small-cell lung cancer (NSCLC), as the prognostic value of these structures in patients with cancer had not yet been established. Patients and Methods This retrospective study was performed by immunohistochemistry on paraffin-embedded tissue specimens from 74 patients with early-stage NSCLC. Results Tertiary lymphoid structures were detected in some tumors but not in nontumoral lungs. Thus we called these structures tumor-induced bronchus-associated lymphoid tissue (Ti-BALT). As in lymph nodes, Ti-BALTs were composed of mature dendritic cell (DC)/T-cell clusters adjacent to B-cell follicles and had features of an ongoing immune response. Because the quantitative counting of Ti-BALT was difficult to achieve, we used mature DCs that homed exclusively in Ti-BALT as a specific marker of these structures. Univariate analysis showed that the density of mature DCs was highly associated with a favorable clinical outcome (overall, disease-specific, and disease-free survival), suggesting that Ti-BALT may participate in antitumoral immunity. The density of tumor-infiltrating lymphocytes, in particular, CD4+ and T-bet+ Th1 T cells, was profoundly decreased in tumors weakly infiltrated by mature DCs. Conclusion The density of mature DCs was found to be a better predictor of clinical outcome than the other parameters tested. The number of tumor-infiltrating mature DCs may identify patients with early-stage NSCLC who have a high risk of relapse.
29
Bessede, Thomas, Clara Freixinos, Jennifer Barrat, Véronique Garambois, Nadia Vie, Henri-Alexandre Michaud, Julien Faget et al. "Abstract B045: Sensitizing the PDAC tumor microenvironment to immune checkpoint therapies: characterization of a PDAC 3D model to decipher immune infiltration". Cancer Research 84, n. 17_Supplement_2 (15 settembre 2024): B045. http://dx.doi.org/10.1158/1538-7445.pancreatic24-b045.
Testo completoAbstract (sommario):
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal solid tumor with an unfavorable prognosis, often resistant to conventional treatments due to its dense stroma rich in Cancer- Associated Fibroblasts (CAFs). Limited T cell infiltration and prevalence of immunosuppressive cells within the tumor hinder the efficacy of immune checkpoint inhibitors (ICIs). The objective of our project is to modify immune landscape of PDAC tumor microenvironment (TME) to induce ICIs sensitization. We thus develop novel therapeutic strategies combining an immunomodulatory cytokine Interleukine-15 (IL15), with conventional chemotherapies (Gemcitabine or Folfirinox). To accurately replicate the complex cancer-stroma interactions within the pancreatic tumor microenvironment, we constructed a three-dimensional in vitro heterospheroid model composed of xenograft-derived tumor cells from PDAC patients, both primary or immortalized CAFs, and peripheral blood mononuclear cells (PBMCs) from healthy donors. Human 3D models were first set up and characterized by cytometry, imaging mass spectrometry and immunohistochemistry. We showed that, CAFs produce components of the extracellular matrix, promote tumor cell growth, improve resistance to chemotherapy and are able to down-regulate immune cell infiltration and modulate the nature of infiltrated immune cells. Spatial analysis of spheroids using imaging mass cytometry show that CAF influences the distribution of immune cells in our models. Interestingly, Interleukine 15 treatment prompted robust infiltration of PBMCs into heterospheroids. Immunophenotyping experiments revealed a substantial shift in the nature of immune infiltration, marked by a pronounced increase in CD4+ and CD8+ T lymphocytes, gDelta T cell and NK cell populations. When combined with Gemcitabine and IL15, immune effector cell infiltration is remarkably increased, resulting in antitumoral effects and control of tumor cell growth. Moreover, therapeutic combinations induce activation of infiltrated immune effector cells with an increase of activation, degranulation and cytotoxic markers, such as IFNγ, CD107a, and Granzyme B respectively. Thus, the heterotypic spheroids described in our study are a suitable in vitro model to both characterize the influence of CAF on therapeutic effects and the mechanisms that drives immune suppressive microenvironment. Moving forward, the next steps will consist to conduct in vivo experiments using a syngeneic PDAC orthotopic model to assess whether this combined therapeutic approach sensitize the PDAC microenvironment to anti-PD1 therapies. Citation Format: Thomas Bessede, Clara Freixinos, Jennifer Barrat, Véronique Garambois, Nadia Vie, Henri-Alexandre Michaud, Julien Faget, Nathalie Bonnefoy, Céline Gongora, Bruno Robert, Laurent Gros, Christel Larbouret. Sensitizing the PDAC tumor microenvironment to immune checkpoint therapies: characterization of a PDAC 3D model to decipher immune infiltration [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B045.
30
Bessede, Thomas, Clara Freixinos, Jennifer Barrat, Véronique Garambois, Nadia Vie, Henri-Alexandre Michaud, Julien Faget et al. "Abstract B046: Sensitizing the PDAC tumor microenvironment to immune checkpoint therapies: characterization of a PDAC 3D model to decipher immune infiltration". Cancer Research 84, n. 17_Supplement_2 (15 settembre 2024): B046. http://dx.doi.org/10.1158/1538-7445.pancreatic24-b046.
Testo completoAbstract (sommario):
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal solid tumor with an unfavorable prognosis, often resistant to conventional treatments due to its dense stroma rich in Cancer- Associated Fibroblasts (CAFs). Limited T cell infiltration and prevalence of immunosuppressive cells within the tumor hinder the efficacy of immune checkpoint inhibitors (ICIs). The objective of our project is to modify immune landscape of PDAC tumor microenvironment (TME) to induce ICIs sensitization. We thus develop novel therapeutic strategies combining an immunomodulatory cytokine Interleukine-15 (IL15), with conventional chemotherapies (Gemcitabine or Folfirinox). To accurately replicate the complex cancer-stroma interactions within the pancreatic tumor microenvironment, we constructed a three-dimensional in vitro heterospheroid model composed of xenograft-derived tumor cells from PDAC patients, both primary or immortalized CAFs, and peripheral blood mononuclear cells (PBMCs) from healthy donors. Human 3D models were first set up and characterized by cytometry, imaging mass spectrometry and immunohistochemistry. We showed that, CAFs produce components of the extracellular matrix, promote tumor cell growth, improve resistance to chemotherapy and are able to down-regulate immune cell infiltration and modulate the nature of infiltrated immune cells. Spatial analysis of spheroids using imaging mass cytometry show that CAF influences the distribution of immune cells in our models. Interestingly, Interleukine 15 treatment prompted robust infiltration of PBMCs into heterospheroids. Immunophenotyping experiments revealed a substantial shift in the nature of immune infiltration, marked by a pronounced increase in CD4+ and CD8+ T lymphocytes, gDelta T cell and NK cell populations. When combined with Gemcitabine and IL15, immune effector cell infiltration is remarkably increased, resulting in antitumoral effects and control of tumor cell growth. Moreover, therapeutic combinations induce activation of infiltrated immune effector cells with an increase of activation, degranulation and cytotoxic markers, such as IFNγ, CD107a, and Granzyme B respectively. Thus, the heterotypic spheroids described in our study are a suitable in vitro model to both characterize the influence of CAF on therapeutic effects and the mechanisms that drives immune suppressive microenvironment. Moving forward, the next steps will consist to conduct in vivo experiments using a syngeneic PDAC orthotopic model to assess whether this combined therapeutic approach sensitize the PDAC microenvironment to anti-PD1 therapies. Citation Format: Thomas Bessede, Clara Freixinos, Jennifer Barrat, Véronique Garambois, Nadia Vie, Henri-Alexandre Michaud, Julien Faget, Nathalie Bonnefoy, Céline Gongora, Bruno Robert, Laurent Gros, Christel Larbouret. Sensitizing the PDAC tumor microenvironment to immune checkpoint therapies: characterization of a PDAC 3D model to decipher immune infiltration [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B046.
31
Pattarini, Lucia, Marina Pavlidou, Aizea Kastresana Morales, Janet Peper-Gabriel, Matthieu Riviere, Didier Demarles, Alix Scholer-Dahirel, Veronique Blanc e Shane Olwill. "Abstract LB220: The anticalin-antibody bispecific PRS-352/S095025 strongly stimulates human CD4+ T cells in a PD-L1-dependent manner". Cancer Research 82, n. 12_Supplement (15 giugno 2022): LB220. http://dx.doi.org/10.1158/1538-7445.am2022-lb220.
Testo completoAbstract (sommario):
Abstract Background: OX40, a member of the tumor necrosis factor receptor superfamily, is a costimulatory molecule promoting survival and cytokine release by effector T cells and inhibiting human regulatory T-cell activity. OX40 activation has been explored as a potential treatment for solid malignancies, using mainly agonistic anti-OX40 antibodies. These antibodies rely on Fc gamma receptor (FcγR)-mediated crosslinking to activate the OX40 pathway and have shown so far only limited antitumoral efficacy in clinical settings. One underlying hypothesis is that FcγR crosslinking of these antibodies may not allow optimal activation of the OX40 pathway to fully exploit the potential of this target for immunotherapy of cancer. To overcome this limitation, we designed PRS-352/S095025, a strong PD-L1-dependent OX40 agonistic bispecific molecule, that allows combination of OX40 costimulation and PD-L1 blockade. Methods: We generated an Anticalin protein that binds with high affinity to human OX40. Anticalin® proteins are approximately 18-20 kDa protein therapeutics derived from human lipocalins that can be engineered to bind with high affinity and specificity to different targets. The PRS-352/S095025 bispecific fusion protein was obtained by genetic fusion of OX40-targeting Anticalin protein to a PD-L1-targeting monoclonal antibody with a modified IgG4 backbone, allowing an optimal activation of OX40 in the presence of PD-L1, but not FcγRs. Results: We showed that PRS-352/S095025 retains binding to PD-L1 like the anti PD-L1 antibody backbone alone and binds with high affinity to both human and cynomolgus OX40. We showed that PRS-352/S095025 inhibited the PD-1/PD-L1 pathway, as the parental PD-L1 targeting antibody and an approved anti PD-L1 antibody. In addition to its PD-L1 blocking properties, we showed that PRS-352/S095025 activates OX40, and that this activity is dependent on the expression of PD-L1 and not on FcγR, consistent with the desired mechanism of action. Furthermore, we demonstrated that PRS-352/S095025 activity is superior to both PD-L1 benchmark antibodies and to the combination of clinically relevant OX40 and PD-L1 benchmark antibodies. We could also show that PRS352/S095025 strongly stimulated human CD4 T cells. In vivo, we showed that PRS-352/S095025 has a PK profile similar to that of the PD-L1 antibody alone. Conclusions: We provide here the preclinical characterization of the fusion protein PRS-352/S095025, a bispecific molecule composed of a PD-L1 blocking moiety and an Anticalin protein agonizing OX40. In vitro, this molecule showed the desired MoA, PD-L1 blocking and potent OX40 agonism driven by binding to PD-L1, with superior activity to a clinical stage OX40 agonist. Citation Format: Lucia Pattarini, Marina Pavlidou, Aizea Kastresana Morales, Janet Peper-Gabriel, Matthieu Riviere, Didier Demarles, Alix Scholer-Dahirel, Veronique Blanc, Shane Olwill. The anticalin-antibody bispecific PRS-352/S095025 strongly stimulates human CD4+ T cells in a PD-L1-dependent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB220.
32
Lenz, Heinz-Josef, Thibaud Koessler, Paul Oberstein, Eric Van Cutsem, Sunnie Kim, Ralph Fritsch, Hans Prenen et al. "Abstract CT570: KISIMA-01: A first-in-human trial of the heterologous prime-boost vaccine ATP128/VSV-GP128 with ezabenlimab (BI 754091) in patients with stage IV colorectal cancer". Cancer Research 82, n. 12_Supplement (15 giugno 2022): CT570. http://dx.doi.org/10.1158/1538-7445.am2022-ct570.
Testo completoAbstract (sommario):
Abstract Background: Most microsatellite stable/mismatch repair proficient (MSS/MMRp) stage IV colorectal cancers (CRC) do not respond to PD-1 inhibition. ATP128, based on the KISIMA platform, is a single chimeric fusion protein, composed of 3 elements essential to generate potent antitumoral cellular immunity: a proprietary cell-penetrating peptide (CPP) for antigen delivery, a proprietary Toll-like receptor (TLR)-peptide agonist with self-adjuvant properties and a modulable multi-antigenic domain (Mad), where the Mad for CRC includes 3 antigens: carcinoembryonic antigen (CEA), Survivin, Achaete-scute complex homolog 2 (ASCL2). VSV-GP128 is a recombinant vesicular stomatitis virus (VSV) carrying the glycoprotein (GP) of a non-neurotropic strain of lymphocytic choriomeningitis virus (LCMV) instead of the native VSV-GP. The GP of the LCMV abrogates neurotoxicity. As viral vector, VSV-GP128 expresses a Mad with identical sequence to ATP128 integrated in a linear, negative-sense, single-stranded RNA genome. Preclinical data have shown that priming with KISIMA vaccine followed by VSV-GP boost induced a large pool of polyfunctional and persistent antigen-specific cytotoxic T cells in the periphery as well as within the tumor in several tumor models. Combining heterologous vaccination with a PD-1 inhibitor further improved its therapeutic efficacy (Das et al., Nature Communication 2021). Methods: KISIMA-01 (NCT04046445) is an open-label, multi-center Phase 1b umbrella trial to investigate the safety, tolerability and immunogenicity of the heterologous prime-boost vaccine AT128/VSV-GP128 in combination with the anti-PD1 ezabenlimab in patients with stage IV MSS CRC. Two different patient cohorts are investigated: 1) maintenance setting (during a chemotherapy free period) after a minimum of 4 months of 1st line standard chemotherapy with clinical benefit (defined as PR or SD) (n=30); 2) resectable liver-limited disease (n=15). ATP128 is given subcutaneously on day 1 (prime); VSV-GP128 is administered intravenously on day 15 as the heterologous boost. ATP128 is again administered on day 29 (injection 3) and then every 4 weeks for the last 3 immunizations. Ezabenlimab is administered every 3 weeks starting with the first ATP128 administration. Blood and tissue samples are collected before, during and after ATP128/VSV-GP128 treatment to monitor the induction of a tumor associated antigen-specific immune response and immune-related changes. Immunogenicity will be analyzed in the peripheral blood using ELISpot, and in the tumor microenvironment by immunohistochemical assessment of tumor-infiltrating lymphocytes (TILs). Clearance of ctDNA is analyzed as an exploratory endpoint. The heterologous prime-boost cohorts (ATP128/VSV-GP128) of the KISIMA-01 trial are recruiting in the US, Switzerland and Belgium. Citation Format: Heinz-Josef Lenz, Thibaud Koessler, Paul Oberstein, Eric Van Cutsem, Sunnie Kim, Ralph Fritsch, Hans Prenen, Michael Morse, Delphine Gani, Madiha Derouazi, Thomas Bogenrieder, Scott Kopetz. KISIMA-01: A first-in-human trial of the heterologous prime-boost vaccine ATP128/VSV-GP128 with ezabenlimab (BI 754091) in patients with stage IV colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT570.
33
Skov, Vibe, Thomas Stauffer Larsen, Mads Thomassen, Caroline Riley, Morten Krogh Jensen, Ole Weis Bjerrum, Torben A. Kruse e Hans Carl Hasselbalch. "Increased Expression of Proteasome-Related Genes In Patients with Primary Myelofibrosis". Blood 116, n. 21 (19 novembre 2010): 4117. http://dx.doi.org/10.1182/blood.v116.21.4117.4117.
Testo completoAbstract (sommario):
Abstract Abstract 4117 Introduction: The proteasome is an ubiquituous enzyme complex that plays a critical role in the degradation of many proteins involved in cell cycle regulation, apoptosis, and angiogenesis. Since these pathways and functions are often deregulated in cancer cells, inhibition of the proteasome is an attractive potential anticancer therapy. Bortezomib (Velcade, formerly PS-341) is an extremely potent and selective proteasome inhibitor that shows strong activity against many solid and hematologic tumor types. Moreover, bortezomib, mainly by inhibition of the NF-kappaB pathway, has a chemosensitizing effect when administered together with other antitumoral drugs. Bortezomib is a well-established treatment in multiple myeloma and studies are focusing in the potential benefit of bortezomib in other haematological malignancies, including malignant lymphomas. Since the NF-kappaB pathway is considered to be implicated in the abnormal release of cytokines in primary myelofibrosis (PMF), the proteasome inhibitor bortezomib might be a potential therapy. In a murine model, bortezomib has been demonstrated to inhibit thrombopoietin (TPO)-induced NF-kappaB activation in megakaryocytes and to reduce myeloproliferation induced by high TPO levels. Accordingly, from in vitro studies it was concluded that bortezomib might be a promising therapy for future treatment of PMF patients. Surprisingly, however, these encouraging results have not been achieved in clinical trials testing bortezomib in patients with myelofibrosis. We have performed gene expression profiling of patients with PMF and in patients with other chronic myeloproliferative neoplasms (CMPNs) in order to describe aberrant genes in the proteasome pathway in PMF. Materials and methods: The HG-U133 Plus 2.0 microarray from Affymetrix was used to profile expression of 38500 genes in whole blood from 70 patients with CMPNs, including 9 patients with PMF and 61 patients with other CMPNs. All patients were diagnosed according to the WHO criteria of a CMPN (ET=19, PV=41, PMF=9). The patients were diagnosed and followed in two institutions. Most patients were studied on cytoreductive therapy, which for the large majority included hydroxyurea. Total RNA was purified from whole blood and amplified to biotin-labeled aRNA and hybridized to microarray chips. Differences in gene expression between the two groups were calculated for each gene in the dataset by using Welch two sample t test, and the Benjamini Hochberg method was applied to control for multiple hypothesis testing (false discovery rate (FDR) < 0.05). Data were integrated with biological pathways and networks using Gene Microarray Pathway Profiler (GenMAPP 2.1) and Cytoscape 2.6.3, respectively. Hypothesis driven discovery was used to find significantly differentially expressed genes and pathways associated with PMF. Results: Single gene analysis demonstrated significantly elevated expression of seventeen proteasomal subunit genes in patients with PMF (PSMA1, PSMA2, PSMA6, PSMA7, PSMB4, PSMB5, PSMB6, PSMB7, PSMC2, PSMC3, PSMD10, PSMD14, PSMD4, PSMD8, PSMD9, PSMG1, and PSMG3 (FDR < 0.05). Only one gene, PSMB4, was significantly downregulated (FDR < 0.05). Global pathway analysis showed a significant upregulation of the proteasome degradation pathway (adjusted P < 0.03), and the network analysis revealed a significant subnetwork only composed of upregulated genes (CDC25A, CDC6, CDT1, GMNN, ORC1L, PSMA6, PSMA7, PSMB5, PSMB6, PSMB7, PSMC3, PSMD5, PSMD8, PSMD9, PSMD14) of which 10 were proteasomal genes (Z=2.6). Conclusion: In this study, we have for the first time described the gene signature of the proteasome in peripheral blood cells from patients with myelofibrosis and patients with ET and PV. Using single gene analysis, global pathway and network analysis, we found significant upregulation of the proteasomal transcriptome in patients with PMF as compared to patients with ET and PV as a group. This study has added new important information of the genes involved in the upregulation of the proteasome degradation pathway in these patients. Disclosures: No relevant conflicts of interest to declare.
34
Silva, Mariane. "O promissor potencial dos compostos canabinóides no tratamento ao câncer." Ensaios USF 7, n. 1 (1 agosto 2023). http://dx.doi.org/10.24933/e-usf.v7i1.232.
Testo completoAbstract (sommario):
Este trabalho teve como principal objetivo despertar o interesse na busca de novas alternativas de tratamento para os mais variados tipos de câncer, considerando o grande volume de acometimentos desta doença em âmbito mundial, e pelo alto grau de letalidade que ela acarreta. Como os tratamentos convencionais não vêm alcançando resultados desejados na maior parte da população diagnosticada, pois impõem manifestações físicas adversas severas aos pacientes e em determinados tipos de tumores não são capazes de interromper o processo de proliferação do câncer, por estas razões, novas opções de terapias para controle da doença se fazem necessárias. No sentido de buscar tratamentos que possam contribuir para melhorar a qualidade de vida destes pacientes, e até mesmo a interrupção do processo tumoral, ampliam-se os estudos e pesquisas no cenário internacional, que vêm demonstrando um alto potencial terapêutico para substâncias derivadas do cânhamo, denominadas compostos canabinóides, que são interpretadas pelo sistema nervoso central, através do sistema endocanabinóide e seus receptores, que em recentes estudos vêm apontando a capacidade destas substâncias de induzir a apoptose em células tumorais de uma grande variedade de linhas de câncer. Desta forma este trabalho realizou uma revisão bibliográfica sobre o potencial antitumoral dos compostos canabinóides.
35
Cavararo, Carollyne Dos Santos, Jorge Pinho Silva Jr, Josiane Roberto Domingues e Claudete Corrêa de Jesus Chiappini. "DESENVOLVIMENTO E ACEITAÇÃO SENSORIAL DE KEFIR COM GELEIA DE GOIABA E AVALIAÇÃO DE COMPOSTOS BIOATIVOS". DEMETRA: Alimentação, Nutrição & Saúde 13, n. 2 (13 luglio 2018). http://dx.doi.org/10.12957/demetra.2018.31290.
Testo completoAbstract (sommario):
Introdução: Compostos bioativos são definidos como nutrientes ou não nutrientes que possuem ação metabólica ou fisiológica específica no organismo, como as ações antitumoral, antifúngica, antibacteriana, imunomoduladora, anti-inflamatória e antioxidante. Os probióticos presentes nos leites fermentados e os carotenoides presentes nas frutas são descritos, na literatura, como benéficos à saúde. Objetivo: Desenvolver, avaliar a aceitação sensorial, a atividade antioxidante e determinados compostos bioativos de kefir com geleia de goiaba. Metodologia: O kefir foi desenvolvido e sua aceitação avaliada pelo teste de escala hedônica; a composição centesimal foi determinada pelos métodos oficiais; a atividade antioxidante foi avaliada pelo ensaio ORAC; os compostos fenólicos totais e os carotenoides totais foram determinados por método espectrofotométrico. Resultados: A adição dos 30% de geleia de goiaba elevou a atividade antioxidante, os compostos fenólicos e os carotenoides totais do kefir. O produto elaborado foi bem aceito pelos consumidores, que também comprariam o produto caso este fosse comercializado. Conclusão: Concluiu-se que adição de geleia contribuiu para o aumento dos compostos bioativos avaliados e a bebida fermentada poderia contribuir para a saúde dos consumidores.DOI: 10.12957/demetra.2018.31290
36
Dobaño-López, Cèlia, Juan García Valero, Ferran Araujo-Ayala, Ferran Nadeu, Fabien Gava, Carla Faria, Marine Norlund et al. "Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target". Blood Cancer Journal 14, n. 1 (2 maggio 2024). http://dx.doi.org/10.1038/s41408-024-01041-7.
Testo completoAbstract (sommario):
AbstractFollicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.
37
Xue, Wenjing, Caili Xu, Kaiqi Zhang, Lu Cui, Xiting Huang, Yanyang Nan, Dianwen Ju, Xusheng Chang e Xuyao Zhang. "Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer". Cell Death Discovery 10, n. 1 (3 settembre 2024). http://dx.doi.org/10.1038/s41420-024-02167-0.
Testo completoAbstract (sommario):
AbstractClaudin18.2 (CLDN18.2) is overexpressed in cancers of the digestive system, rendering it an ideal drug target for antibody-drug conjugates (ADCs). Despite many CLDN18.2-directed ADCs undergoing clinical trials, the inconclusive underlying mechanisms pose a hurdle to extending the utility of these agents. In our study, αCLDN18.2-MMAE, an ADC composed of an anti-CLDN18.2 monoclonal antibody and the tubulin inhibitor MMAE, induced a dose-dependent apoptosis via the cleavage of caspase-9/PARP proteins in CLDN18.2-positive gastric cancer cells. It was worth noting that autophagy was remarkably activated during the αCLDN18.2-MMAE treatment, which was characterized by the accumulation of autophagosomes, the conversion of autophagy marker LC3 from its form I to II, and the complete autophagic flux. Inhibiting autophagy by autophagy inhibitor LY294002 remarkably enhanced αCLDN18.2-MMAE-induced cytotoxicity and caspase-mediated apoptosis, indicating the cytoprotective role of autophagy in CLDN18.2-directed ADC-treated gastric cancer cells. Combination with an autophagy inhibitor significantly potentiated the in vivo antitumoral efficacy of αCLDN18.2-MMAE. Besides, the Akt/mTOR pathway inactivation was demonstrated to be implicated in the autophagy initiation in αCLDN18.2-MMAE-treated gastric cancer cells. In conclusion, our study highlighted a groundbreaking investigation into the mechanism of the CLDN18.2-directed ADC, focusing on the crucial role of autophagy, providing a novel insight to treat gastric cancer by the combination of CLDN18.2-directed ADC and autophagy inhibitor.
38
Gremski, Luiza Helena, Fernando Hitomi Matsubara, Nayanne Louise Costacurta Polli, Bruno Cesar Antunes, Pedro Henrique de Caires Schluga, Hanna Câmara da Justa, João Carlos Minozzo, Ana Carolina Martins Wille, Andrea Senff-Ribeiro e Silvio Sanches Veiga. "Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs". Frontiers in Molecular Biosciences 8 (17 giugno 2021). http://dx.doi.org/10.3389/fmolb.2021.706704.
Testo completoAbstract (sommario):
Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism. Systemic loxoscelism, such as hematological abnormalities and renal injury, are less frequent but more lethal. Some Loxosceles venom toxins have already been isolated and extensively studied, such as phospholipases D (PLDs), which have been recombinantly expressed and were proven to reproduce toxic activities associated to the whole venom. PLDs have a notable potential to be engineered and converted in non-toxic antigens to produce a new generation of antivenoms or vaccines. PLDs also can serve as tools to discover inhibitors to be used as therapeutic agents. Other Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). All these toxins were produced as recombinant molecules and are biologically active molecules that can be used as tools for the potential development of chemical candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies. In addition, these recombinant toxins may be useful to develop a rational therapy for loxoscelism. This review summarizes the main candidates for the development of drugs and biotechnological inputs that have been described in Brown spider venoms.
39
Matos, Aline da Rocha, Braulia Costa Caetano, João Luiz de Almeida Filho, Jéssica Santa Cruz de Carvalho Martins, Michele Gabrielle Pacheco de Oliveira, Thiago das Chagas Sousa, Marco Aurélio Pereira Horta, Marilda Mendonça Siqueira e Jorge Hernandez Fernandez. "Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity". Frontiers in Microbiology 13 (10 febbraio 2022). http://dx.doi.org/10.3389/fmicb.2022.828984.
Testo completoAbstract (sommario):
The COVID-19 pandemic has had an unprecedented impact on the global economy and public health. Its etiologic agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible, pathogenic and has a rapid global spread. Currently, the increase in the number of new confirmed cases has been slowed down due to the increase of vaccination in some regions of the world. Still, the rise of new variants has influenced the detection of additional waves of rising cases that some countries have experienced. Since the virus replication cycle is composed of many distinct stages, some viral proteins related to them, as the main-protease (Mpro) and RNA dependent RNA polymerase (RdRp), constitute individual potential antiviral targets. In this study, we challenged the mentioned enzymes against compounds pre-approved by health regulatory agencies in a virtual screening and later in Molecular Mechanics/Poisson–Bolzmann Surface Area (MM/PBSA) analysis. Our results showed that, among the identified potential drugs with anti-SARS-CoV-2 properties, Hypericin, an important component of the Hypericum perforatum that presents antiviral and antitumoral properties, binds with high affinity to viral Mpro and RdRp. Furthermore, we evaluated the activity of Hypericin anti-SARS-CoV-2 replication in an in vitro model of Vero-E6 infected cells. Therefore, we show that Hypericin inhibited viral replication in a dose dependent manner. Moreover, the cytotoxicity of the compound, in cultured cells, was evaluated, but no significant activity was found. Thus, the results observed in this study indicate that Hypericin is an excellent candidate for repurposing for the treatment of COVID-19, with possible inhibition of two important phases of virus maturation.
40
Rosato, Francesca, Rajeev Pasupuleti, Jana Tomisch, Ana Valeria Meléndez, Dajana Kolanovic, Olga N. Makshakova, Birgit Wiltschi e Winfried Römer. "A bispecific, crosslinking lectibody activates cytotoxic T cells and induces cancer cell death". Journal of Translational Medicine 20, n. 1 (9 dicembre 2022). http://dx.doi.org/10.1186/s12967-022-03794-w.
Testo completoAbstract (sommario):
Abstract Background Aberrant glycosylation patterns play a crucial role in the development of cancer cells as they promote tumor growth and aggressiveness. Lectins recognize carbohydrate antigens attached to proteins and lipids on cell surfaces and represent potential tools for application in cancer diagnostics and therapy. Among the emerging cancer therapies, immunotherapy has become a promising treatment modality for various hematological and solid malignancies. Here we present an approach to redirect the immune system into fighting cancer by targeting altered glycans at the surface of malignant cells. We developed a so-called “lectibody”, a bispecific construct composed of a lectin linked to an antibody fragment. This lectibody is inspired by bispecific T cell engager (BiTEs) antibodies that recruit cytotoxic T lymphocytes (CTLs) while simultaneously binding to tumor-associated antigens (TAAs) on cancer cells. The tumor-related glycosphingolipid globotriaosylceramide (Gb3) represents the target of this proof-of-concept study. It is recognized with high selectivity by the B-subunit of the pathogen-derived Shiga toxin, presenting opportunities for clinical development. Methods The lectibody was realized by conjugating an anti-CD3 single-chain antibody fragment to the B-subunit of Shiga toxin to target Gb3+ cancer cells. The reactive non-canonical amino acid azidolysine (AzK) was inserted at predefined single positions in both proteins. The azido groups were functionalized by bioorthogonal conjugation with individual linkers that facilitated selective coupling via an alternative bioorthogonal click chemistry reaction. In vitro cell-based assays were conducted to evaluate the antitumoral activity of the lectibody. CTLs, Burkitt´s lymphoma-derived cells and colorectal adenocarcinoma cell lines were screened in flow cytometry and cytotoxicity assays for activation and lysis, respectively. Results This proof-of-concept study demonstrates that the lectibody activates T cells for their cytotoxic signaling, redirecting CTLs´ cytotoxicity in a highly selective manner and resulting in nearly complete tumor cell lysis—up to 93%—of Gb3+ tumor cells in vitro. Conclusions This research highlights the potential of lectins in targeting certain tumors, with an opportunity for new cancer treatments. When considering a combinatorial strategy, lectin-based platforms of this type offer the possibility to target glycan epitopes on tumor cells and boost the efficacy of current therapies, providing an additional strategy for tumor eradication and improving patient outcomes.
41
Carbone, Maria Luigia, Alessia Capone, Marika Guercio, Sofia Reddel, Domenico Alessandro Silvestris, Daniela Lulli, Carmela Ramondino et al. "Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy". Frontiers in Immunology 14 (23 agosto 2023). http://dx.doi.org/10.3389/fimmu.2023.1197630.
Testo completoAbstract (sommario):
IntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor.