RESUMO
Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
Assuntos
Antineoplásicos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Terapia de Alvo Molecular , Neoplasias , Animais , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the long-term clinical and radiographic outcomes of dental implant placed using osteotome sinus floor elevation (OSFE) without bone grafts, and to analyze the potential influence factors of implant survival and endo-sinus bone remodeling. MATERIAL AND METHODS: A retrospective study design was adopted. The clinical and radiographic data of 96 implants in 80 patients were collected after 4-9 (mean 5.40) years follow-up. Implant failures, peri-implant marginal bone loss (MBL), and endo-sinus bone remodeling on the radiographs were evaluated. A life-table analysis was used to assess the implant survival. Statistical models were established to investigate the potential influence factors of implant survival and endo-sinus bone gain (ESBG). RESULTS: In total, nine implants in seven patients failed, giving the 9-year cumulative survival rates of 90.6% and 91.3% for implant-based analysis and patient-based analysis, respectively. The mean MBL between implant installation and the 4- and 9-year follow-up visit was 0.46 ± 0.88 and 0.50 ± 1.69 mm, respectively. The average ESBG on radiographs was 2.95 ± 1.25 and 2.16 ± 1.13 mm at the 4- and 9-year follow-up. The final ESBG was found to be positively correlated to implant protrusion length after surgery without any other factors related. The implant survival rate was significantly lower in severe atrophic site (residual bone height <5 mm). CONCLUSION: Osteotome sinus floor elevation without bone grafts is a predictable treatment modality in the long run. But it should be used with caution when the initial bone height of the edentulous site is lower than 5 mm. The final endo-sinus bone height was found to be positively correlated to implant protrusion length measured on radiographs immediately after implant installation.
Assuntos
Implantação Dentária Endóssea , Implantes Dentários , Levantamento do Assoalho do Seio Maxilar/métodos , Adulto , Idoso , Remodelação Óssea , Falha de Restauração Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Owing to their unique physical and chemical properties and remarkable biological activities, marine biological resources are emerging as important sources of raw materials for producing health products, food, and cosmetics. Collagen accounts for approximately 70% of the sea cucumber body wall, and its hydrolysis produces small-molecule collagen polypeptides with diverse biological functions, such as anticancer, antihypertensive, immune-enhancing, memory-enhancing, and cartilage tissue repairing effects. Notably, the potential of sea cucumber polypeptides in combination with anticancer therapy has garnered considerable attention. Determining the composition and structure of sea cucumber polypeptides and exploring their structure-activity relationships will aid in obtaining an in-depth understanding of their diverse biological activities and provide scientific insights for the development and utilization of these polypeptides. Therefore, this review focuses on the amino acid structures and activities of sea cucumber polypeptides of varying molecular weights. This study also provides an overview of the biological activities of various sea cucumber polypeptides and aims to establish a scientific basis for their development.