RESUMEN
A number of conditions and factors can cause the transformation of normal cells in the body into malignant tissue by changing the normal functions of a wide range of regulatory, apoptotic, and signal transduction pathways. Despite the current deficiency in fully understanding the mechanism of cancer action accurately and clearly, numerous genes and proteins that are causally involved in the initiation, progression, and metastasis of cancer have been identified. But due to the lack of space and the abundance of details on this complex topic, we have emphasized here more recent advances in our understanding of the principles implied tumor cell transformation, development, invasion, angiogenesis, and metastasis. Inhibition of angiogenesis is a significant strategy for the treatment of various solid tumors, that essentially depend on cutting or at least limiting the supply of blood to micro-regions of tumors, leading to pan-hypoxia and pan-necrosis inside solid tumor tissues. Researchers have continued to enhance the efficiency of anti-angiogenic drugs over the past two decades, to identify their potential in the drug interaction, and to discover reasonable interpretations for possible resistance to treatment. In this review, we have discussed an overview of cancer history and recent methods use in cancer therapy, focusing on anti-angiogenic inhibitors targeting angiogenesis formation. Further, this review has explained the molecular mechanism of action of these anti-angiogenic inhibitors in various tumor types and their limitations use. In addition, we described the synergistic mechanisms of immunotherapy and anti-angiogenic therapy and summarizes current clinical trials of these combinations. Many phase III trials found that combining immunotherapy and anti-angiogenic therapy improved survival. Therefore, targeting the source supply of cancer cells to grow and spread with new anti-angiogenic agents in combination with different conventional therapy is a novel method to reduce cancer progression. The aim of this paper is to overview the varying concepts of cancer focusing on mechanisms involved in tumor angiogenesis and provide an overview of the recent trends in anti-angiogenic strategies for cancer therapy.
Asunto(s)
Inhibidores de la Angiogénesis , Neoplasias , Neovascularización Patológica , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/irrigación sanguínea , Neoplasias/patología , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/farmacología , Neovascularización Patológica/tratamiento farmacológico , AnimalesRESUMEN
BACKGROUND: After total knee arthroplasty (TKA), patients have limited knee range of motion (ROM), trophic changes and pain. Cryotherapy and compression are recommended in the literature, but no study has shown that cryotherapy and compression combined leads to better results than cryotherapy alone. The primary objective was to compare knee ROM after 21 days of rehabilitation post-TKA between patients who underwent rehabilitation with compressive cryotherapy with those who had cryotherapy alone. The secondary objectives were to compare other trophic, pain and functional outcomes. METHODS: Forty patients were randomized into two groups: Standard Cryotherapy (SC = 20, median age 77 years), which applied cold packs along with their rehabilitation; and Compressive Cryotherapy (CC = 20, median age 76 years), which received cold compression. Knee joint's passive and active ROM (primary outcome) were measured with a goniometer. Knee's circumference, fluctuation test, pain at rest and during activity, 6-minute walking test (6MWT) and KOOS questionnaire were secondary outcomes. The groups were compared on D1 (baseline) and D21 of rehabilitation. A survival analysis has compared the groups on D1, D8, D15, D21. RESULTS: All subjects had a significant improvement in all the parameters on D21 relative to D1 (p < .05), except for pain at rest (p = .065 for CC and p = .052 for SC). On D21, the CC group had a significantly larger improvement in the joint effusion (p = .002), pain during activity (p = .005), 6MWT (p = .018) and KOOS (p = .004) than the SC group. Based on the survival analysis, the CC group had significantly faster improvement in the joint ROM (p = .011 for flexion and p = .038 for extension) and knee circumference (p = .013) than the SC group. CONCLUSIONS: Both cryotherapy methods improved joint ROM, trophic changes, pain and function. Adding dynamic compression to a cryotherapy protocol provided further benefits: a significantly faster improvement in passive knee flexion ROM, a greater reduction of swelling, and pain during activity. Similarly, walking distance and KOOS questionnaire were significantly better for CC. TRIALS REGISTRATION: The study was registered in the ClinicalTrials.gov database on 14/09/2023 (identifier: NCT06037824).
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Humanos , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/rehabilitación , Resultado del Tratamiento , Articulación de la Rodilla/cirugía , Dolor Postoperatorio/etiología , Rango del Movimiento Articular , Crioterapia/métodos , Edema/etiologíaRESUMEN
Hackathons are collaborative events that bring together diverse groups to solve predefined challenges. The COVID-19 pandemic caused by SARS-CoV-2 has emphasized the need for portable and reproducible genomics analysis pipelines to study the genetic susceptibility of the human host and investigate human-SARS-CoV-2 protein interactions. To build and strengthen institutional capacities in OMICS data analysis applied to host-pathogen interaction (HPI), the PHINDaccess project organized two hackathons in 2020 and 2021. These hackathons are aimed at developing bioinformatics pipelines related to the SARS-CoV-2 viral genome, its phylodynamic transmission, and the identification of human genome host variants, with a focus on addressing global health challenges, particularly in low- and middle-income countries (LMIC). This paper outlines the preparation, proceedings, and lessons learned from these hackathons, including the challenges faced by participants and our recommendations based on our experience for organizing hackathons in LMIC and beyond.
Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2/genética , Países en Desarrollo , Pandemias , Interacciones Huésped-Patógeno/genéticaRESUMEN
Angiogenesis plays an important role in the development of cancer since it allows for the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination to distant organs. Inhibition of angiogenesis is an important strategy for the prevention of multiple solid tumors that depend on cutting or at least reducing the blood supply to tumor micro-regions, resulting in pan-hypoxia and pan-necrosis within solid tumor tissues. These drugs are an important part of treatment for some types of cancer. As a stand-alone therapy, inhibition of tumor angiogenesis can arrest or halt tumor growth, but will not eliminate the tumor. Therefore, anti-angiogenic drugs in combinations with another anti-cancer treatment method, like chemotherapy, lead to being critical for optimum cancer patient outcomes. Over the last two decades, investigations have been made to improve the efficacy of anti-angiogenic drugs, recognize their potential in drug interactions, and come up with plausible explanations for possible treatment resistance. This review will offer an overview of the varying concepts of tumor angiogenesis, several important angiogenic factors; focus on the role of anti-angiogenesis strategies in cancer treatment.
Asunto(s)
Inmunoterapia/métodos , Neoplasias/patología , Neovascularización Patológica/metabolismo , HumanosAsunto(s)
Artritis Psoriásica/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Proteínas del Citoesqueleto/genética , Predisposición Genética a la Enfermedad , Humanos , Interleucina-1/genética , PPAR gamma/genética , Pirina , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVE: There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls. METHODS: Two SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor). RESULTS: Both SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1 × 10(-5) OR 1.33, rs20541 ptrend = 8.0 × 10(-4) OR 1.27), but neither SNP was significantly associated with susceptibility to PsV. CONCLUSIONS: This study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA.