Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab). Such mutations in the TP53 gene are often accompanied by changes in the conformation of the p53 protein. Small molecules that restore the wild-type conformation of p53 and, consequently, rebuild its proper function have been identified. These promising agents include PRIMA-1, MIRA-1, and several derivatives of the thiosemicarbazone family. In addition to mutations in p53 itself, p53 activity may be also be impaired due to alterations in p53s regulating proteins such as MDM2. MDM2 functions as primary cellular p53 inhibitor and deregulation of the MDM2/p53-balance has serious consequences. MDM2 alterations often result in its overexpression and therefore promote inhibition of p53 activity. To deal with this problem, a judicious approach is to employ MDM2 inhibitors. Several promising MDM2 inhibitors have been described such as nutlins, benzodiazepinediones or spiro-oxindoles as well as novel compound classes such as xanthone derivatives and trisubstituted aminothiophenes. Furthermore, even naturally derived inhibitor compounds such as a-mangostin, gambogic acid and siladenoserinols have been discovered. In this review, we discuss in detail such small molecules that play a pertinent role in affecting the p53-MDM2 signaling axis and analyze their potential as cancer chemotherapeutics.

Current advances in CRC treatment have led to significant but slight improvements in patient survival with curative outcomes only seen in earlier stage cancers. Consequently, much effort is being put into developing completely novel therapies that fulfil a number of criteria including greater efficacy and fewer side effects. Many of these conditions are met by the wide range of gene therapy strategies currently in pre-clinical or clinical trial phases. Gene therapy approaches may be broadly broken down into three main areas: Following a few tragic events in the context of clinical gene therapy studies, safety is currently the prime concern. Further progress in the field is expected from the combination of the described approaches with conventional treatment modalities.

O presente trabalho teve por objetivo avaliar a seletividade do herbicida bentazon para crotalária consorciado com milho e avaliar a produtividade do milho e a massa seca de crotalária cultivados em consórcio. O delineamento utilizado foi o de blocos casualizados (DBC), com 4 repetições e 5 tratamentos assim constituídos:  Milho sem aplicação de herbicida; Milho + Crotalaria spectabilis sem aplicação de herbicida; Milho + Crotalaria spectabilis com aplicação de herbicida bentazon na dose de 0,5 L ha-1; Milho + Crotalaria spectabilis com aplicação de herbicida bentazon na dose de 1 L ha-1; Milho + Crotalaria spectabilis com aplicação de herbicida bentazon na dose de 1,5 L ha-1. O experimento foi implantado no dia 16 de novembro de 2017. A semeadura do milho foi simultânea a da crotalária, com previa gradagem do solo. O híbrido utilizado foi o CD 3410 PW®, da empresa Coodetec, tratado industrialmente com o inseticida Poncho® da DuPont Pioneer (600g/l) enquanto para a crotalária foram utilizadas sementes comuns sem tratamento. De acordo com a análise de variância não houve diferença significativa (P < 0,05) para a produção de massa seca da crotalária em função das doses de herbicida aplicadas; bem como para os componentes da produtividade: altura de planta, diâmetro de colmo, altura de inserção da primeira espiga, diâmetro de espiga, comprimento de espiga, massa de 1000 grãos. O herbicida bentazon nas três dosagens testadas foi seletivo para a Crotalaria spectabilis, não prejudicando o seu desenvolvimento e nem sua produção de massa seca. O milho em monocultivo produziu em torno de 1,5 toneladas ha-1 a mais que o milho consorciado com a Crotalaria spectabilis.