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141.
Tuhina Khan Nicola Relitti Margherita Brindisi Stefania Magnano Daniela Zisterer Sandra Gemma Stefania Butini Giuseppe Campiani 《Medicinal research reviews》2020,40(3):1002-1060
Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC. 相似文献
142.
María N. Pizzi Elisa Franquet Santiago Aguadé-Bruix Begoña Manso Jaume Casaldáliga Gemma Cuberas-Borrós Guillermo Romero-Farina Josep Pinar Joan Castell-Conesa David García-Dorado Jaume Candell-Riera 《Pediatric cardiology》2014,35(2):197-207
The arterial switch operation (ASO) is the preferred technique for correcting transposition of the great arteries, but translocation and reimplantation of the coronary arteries can produce myocardial ischemia. This report aims to describe the authors’ experience with exercise single-photon emission computed tomography (SPECT) used to evaluate myocardial perfusion. Exercise-rest gated-myocardial perfusion SPECT was performed for 69 patients (49 boys; median age, 9 years; 5th percentile [6.4 years] to 95th percentile [15.6 years]), 64 of whom were asymptomatic 9.98 ± 3.20 years after ASO. During exercise testing, the patients reached 9.85 ± 3.05 metabolic equivalents (METs) and a median heart rate of 160 beats per minute (bpm), 5th percentile (106 bpm) to 95th percentile (196 bpm). Whereas 61 patients (88.41 %) had normal myocardial perfusion, 2 patients (2.9 %) had reversible defects, and 6 patients (8.7 %) had fixed defects. All the patients with perioperative ischemic complications (4/4, 100 %) had myocardial perfusion defects, whereas four patients (4/65, 6.15 %) without ischemic complications had abnormal perfusion (p = 0.0005). Age at the time of surgery did not differ significantly (p = 0.234) between the patients with perfusion defects and those with normal study results. No significant difference was observed between the patients who had an A coronary pattern (left coronary artery originating from the left sinus and the right coronary artery originating from the right sinus, n = 47) and those who had a non-A coronary pattern (n = 22) (p = 1). The high rate for normality of exercise myocardial perfusion in our study suggests that myocardial perfusion gated-SPECT should be reserved for patients who have experienced perioperative ischemic complications or those with symptoms, at least during the first 10 years after the surgery. 相似文献
143.
Gemma Rojo Christian Castillo Juan Duaso Ana Liempi Daniel Droguett Norbel Galanti Juan Diego Maya Rodrigo López-Muñoz Ulrike Kemmerling 《Acta tropica》2014
Nifurtimox (Nfx) and Benznidazole (Bnz) are the only available drugs in use for the treatment of Chagas disease. These drugs are recommended but not fully validated in evidence-based medicine and reports about the differential toxicity of both drugs are controversial. Here, we evaluated the toxic and therapeutic effects of Nfx and Bnz on human placental chorionic villi explants (HPCVE) during ex vivo infection of Trypanosoma cruzi, performing histopathological, histochemical, immunohistochemical as well as immunofluorescence analysis of the tissue. Additionally, we determined the effect of both drugs on parasite load by real time PCR. Bnz prevents the parasite induced tissue damage in ex vivo infected HPCVE compared to Nfx, which is toxic per se. The presence of T. cruzi antigens and DNA in infected explants suggests that these drugs do not impair parasite invasion into the HPCVE. Additionally, our results confirm reports suggesting that Bnz is less toxic than Nfx and support the need for the development of more effective and better-tolerated drugs. 相似文献
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147.
Rintaro Noro Kazufumi Honda Kengo Nagashima Noriko Motoi Shinobu Kunugi Jun Matsubayashi Susumu Takeuchi Hideaki Shiraishi Tetsuya Okano Ayumi Kashiro Xue Meng Yukihiro Yoshida Shunichi Watanabe Jitsuo Usuda Tatsuya Inoue Huang Wilber Norihiko Ikeda Masahiro Seike Akihiko Gemma Kaoru Kubota 《Cancer science》2022,113(3):1002
Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non‐small‐cell lung cancer (NSCLC) in Japan, only one‐third of cases has received adjuvant chemotherapy (ADJ) according to real‐world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence‐free survival (RFS) were carried out. Formalin‐fixed, paraffin‐embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety‐nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4‐positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009‐0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4‐negative cases (all ages: HR, 1.214; 95% CI, 0.848‐1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side‐effects of ADJ, and saving medical costs. 相似文献
148.
Ruth Ponsford Jo Crichton Rebecca Meiksin Tara Tancred Gemma Morgan Nerissa Tilouche Rona Campbell Chris Bonell 《Lancet》2018
Background
There is increasing emphasis on involving intended beneficiaries and other stakeholders in the development of public health interventions to maximise acceptability and remove barriers to adoption, implementation, and maintenance before costly implementation. Yet the processes whereby key actors are engaged in intervention development are rarely reported, and frameworks for carrying out such work remain limited. We outline our approach to involving stakeholders in the optimisation of two school-based relationships and sex education programmes (Project Respect and Positive Choices) and reflect on the challenges of co-producing with teachers, students, and other partners.Methods
Systematic optimisation of both interventions involved a review of existing literature on effective approaches; consultation with staff and students on intervention content and delivery; drafting of intervention materials; further consultation with schools; and then intervention refinement in preparation for a pilot. Seven focus groups took place in southeast and southwest England involving 75 students aged 13–15 years and 22 school staff. A group of young people trained to advise on public health research were consulted on two occasions and a wide range of sexual health and sex education practitioners and policy makers shared their views at a stakeholder event.Findings
Consultation provided useful insights to inform intervention adaption in relation to who should deliver the programmes in schools; whether lessons should be taught in single sex classes; the format that guidance and lesson plans should take; the relevance and acceptability to students and teachers; and the need for the flexibility for materials to adapt to different school contexts. Genuine consultation and incorporation of school stakeholder views was challenging where stakeholder availability was limited and intervention development and implementation timelines were tight. Challenges also arose in relation to the weight to give divergent opinions among stakeholders and between stakeholders and researchers.Interpretation
Carrying out structured stakeholder engagement activities can yield valuable insights that can improve the applicability of interventions to local contexts before they are formally trialled. To genuinely engage stakeholders in intervention development requires sufficient time to both consult and adapt. In such consultations, it is important to attend not just to the voices of those who are the loudest and most powerful.Funding
National Institute for Health Research (NIHR). 相似文献149.