34 research outputs found
Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma
PURPOSE: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance. METHODS: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance. RESULTS: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance. CONCLUSIONS: We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and lowâmiddle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of âsingle-useâ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for lowâmiddle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both highâ and lowâmiddleâincome countries
Challenges and achievements of liquid biopsy technologies employed in early breast cancer
Breast cancer is the most common cancer type in women worldwide and its early detection is crucial to curing the disease. Tissue biopsy, currently the method of choice to obtain tumour molecular information, is invasive and might be affected by tumour heterogeneity rendering it incapable to portray the complete molecular picture. Liquid biopsy permits to study disease features in a more comprehensive manner by sampling biofluids and extracting tumour components such as circulating-tumour DNA (ctDNA), circulating-tumour cells (CTCs), and/or circulating-tumour RNA (ctRNA) amongst others in a monitoring-compatible manner. In this review, we describe the recent progress in the utilization of the circulating tumour components using early breast cancer samples. We review the most important analytes and technologies employed for their study.ICM's contract is funded by the Spanish Association Against Cancer (AECC). AAB is contracted by the âGarantĂa Juvenil en I+D+i Subprograma Estatal de Incorporacionâ by the Ministry of Science and Innovation (Spanish Government). MIQO contract is supported by the âMiguel Servet Type IIâ program (CPI13/00003), ISCIII, Spain and cofunded by the "Fondo Europeo de Desarrollo Regional-(FEDER)", and by the âNicolas Monardesâ research program from the "ConsejerĂa de Salud" (C-0030-2018), Andalusian Gobernment, Spain.Ye
Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma
PURPOSE: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance. METHODS: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance. RESULTS: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance. CONCLUSIONS: We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies
Effect of aflibercept plus FOLFIRI and potential efficacy biomarkers in patients with metastatic colorectal cancer: the POLAF trial.
Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135âng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. In total, 101 patients were followed for a median of 12 (6-17) months. The 1941âpg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was This study supports aflibercept plus FOLFIRI benefits, suggesting VEGF-A as a potential biomarker to predict better outcomes
Narration and the production of meaning in neomodernism
This essay analyzes the narration strategies and methods of making meanings in neo-modernism movement. Filmmakers, who are its representatives, prefer the opposite model of cinematic communication which is commonly used in mainstream movies. The article begins with the definition of neo-modernism and description of key components that provide specific forms of narration and reception. Moreover, there were presented main terms related to the modernism and co-called slow cinema. In main fragments of the essay the author focused on some neo-modernist crime stories, which have been created through different, than in traditional cinema, methods of making meaning. Then, there were analyzed such elements of cinematic style as: use of off-screen space and non-conventional concepts of narrative ellipsis.Zadaniem artykuĆu jest przeprowadzenie analizy narracji i sposobĂłw produkcji znaczeĆ w filmowym neomodernizmie. Podejmowane w ramach tej formacji strategie inscenizacyjne stanowiÄ
rewers metod powszechnie uĆŒywanych w kinowym mainstreamie. Esej rozpoczyna prĂłba zdefiniowania, czym jest neomodernizm oraz czym siÄ charakteryzuje â zarĂłwno na pĆaszczyĆșnie narracyjnej, jak teĆŒ odbiorczej. WaĆŒnym elementem opisu staĆo siÄ wprowadzenie terminologii zwiÄ
zanej z filmowym modernizmem i tzw. slow-cinema. W gĆĂłwnych fragmentach eseju zostaĆy poddane analizie neomodernistyczne kryminaĆy, oparte na odrÄbnej, niĆŒ dzieje siÄ w tradycyjnym kinie, produkcji znaczeĆ. Potem opisane zostaĆy kluczowe strategie inscenizacyjne, w ktĂłrych priorytetowymi zadaniami byĆo przeniesienie waĆŒnych fabularnie zdarzeĆ w przestrzeĆ pozakadrowÄ
i niekonwencjonalny sposĂłb wprowadzania elips czasoprzestrzennych