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1.
NPJ Breast Cancer ; 10(1): 35, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734703

RESUMO

BRCA1 plays a suppressive role in breast tumorigenesis. Ubiquitin-dependent degradation is a common mechanism that regulates BRCA1 protein stability, and several ubiquitin ligases involved have been identified. However, the deubiquitinating enzyme for BRCA1 remains less defined. Here, we report that the deubiquitinase USP4 interacts with, deubiquitinates and stabilizes BRCA1, maintaining the protein level of BRCA1. USP4 knockdown results in a decreased BRCA1 protein level, impairment in homologous recombination mediated double-stranded break repair, and increased genome instability, and confers resistance to DNA damage-inducing agents and PARP inhibitors. Ectopic expression of USP4 stabilizes BRCA1 and reverse the effects caused by USP4 knockdown. Moreover, USP4 is low expressed in human breast cancer tissues and its low expression correlates with poorer survival of patients. Furthermore, we identified several loss-of-function mutations of USP4 in human gynecological cancers, the catalytic activity of which or their interaction with BRCA1 is disrupted. Together, we reveal that USP4 is a deubiquitinase for BRCA1. USP4 positively regulates the stability and function of BRCA1 through de-ubiquitination, and plays important role in the suppression of breast cancer.

2.
Eur J Med Res ; 29(1): 207, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549156

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a complex malignancy characterized by diverse molecular profiles, clinical outcomes, and limited precision in prognostic markers. Addressing these challenges, this study utilized multi-omics data to define consensus molecular subtypes in CRC and elucidate their association with clinical outcomes and underlying biological processes. METHODS: Consensus molecular subtypes were obtained by applying ten integrated multi-omics clustering algorithms to analyze TCGA-CRC multi-omics data, including mRNA, lncRNA, miRNA, DNA methylation CpG sites, and somatic mutation data. The association of subtypes with prognoses, enrichment functions, immune status, and genomic alterations were further analyzed. Next, we conducted univariate Cox and Lasso regression analyses to investigate the potential prognostic application of biomarkers associated with multi-omics subtypes derived from weighted gene co-expression network analysis (WGCNA). The function of one of the biomarkers MID2 was validated in CRC cell lines. RESULTS: Two CRC subtypes linked to distinct clinical outcomes were identified in TCGA-CRC cohort and validated with three external datasets. The CS1 subtype exhibited a poor prognosis and was characterized by higher tumor-related Hallmark pathway activity and lower metabolism pathway activity. In addition, the CS1 was predicted to have less immunotherapy responder and exhibited more genomic alteration compared to CS2. Then a prognostic model comprising five genes was established, with patients in the high-risk group showing substantial concordance with the CS1 subtype, and those in the low-risk group with the CS2 subtype. The gene MID2, included in the prognostic model, was found to be correlated with epithelial-mesenchymal transition (EMT) pathway and distinct DNA methylation patterns. Knockdown of MID2 in CRC cells resulted in reduced colony formation, migration, and invasion capacities. CONCLUSION: The integrative multi-omics subtypes proposed potential biomarkers for CRC and provided valuable knowledge for precision oncology.


Assuntos
Neoplasias Colorretais , Neoplasias , Humanos , Microambiente Tumoral/genética , Multiômica , Medicina de Precisão , Prognóstico , Biomarcadores , Neoplasias Colorretais/genética
3.
Cancer Lett ; 577: 216440, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37838281

RESUMO

Radiotherapy is the standard adjuvant treatment for esophageal squamous cell carcinoma (ESCC), yet radioresistance remains a major obstacle leading to treatment failure and unfavorable prognosis. Previous reports have demonstrated the involvement of astrocyte elevated gene-1 (AEG-1) in tumorigenesis and progression of multiple malignancies. Nevertheless, the precise role of AEG-1 in the radioresistance of ESCC remains elusive. Here, we unveiled a strong correlation between aberrant AEG-1 gene overexpression and malignant progression as well as adverse prognosis in ESCC patients. Moreover, both in vitro and in vivo investigations revealed that AEG-1 significantly alleviated irradiation-induced DNA damage and enhanced radiation resistance in ESCC cells. Mechanistically, AEG-1 recruited the deubiquitinase USP10 to remove the K48-linked polyubiquitin chains at the Lys425 of PARP1, thus preventing its proteasomal degradation. This orchestrated process facilitated homologous recombination-mediated DNA double-strand breaks (DSBs) repair, culminating in mitigated DNA damage and acquired radioresistance in ESCC cells. Notably, PARP1 overexpression reversed the radiosensitizing effect caused by AEG-1 deficiency. Collectively, these findings shed new light on the mechanism of ESCC radioresistance, providing potential therapeutic targets to enhance the efficacy of radiotherapy in ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Astrócitos , Tolerância a Radiação/genética , Linhagem Celular Tumoral , Reparo do DNA , Reparo de DNA por Recombinação , Dano ao DNA , Ubiquitina Tiolesterase/genética , Poli(ADP-Ribose) Polimerase-1/genética
4.
Hepatobiliary Surg Nutr ; 12(4): 534-544, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37601001

RESUMO

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

5.
Sci Rep ; 13(1): 13339, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587214

RESUMO

There is uncertainty regarding the benefits and drawbacks of various radiation protocols for the treatment of left-sided breast cancer. To address this issue, we conducted a Bayesian network analysis. First, we searched several electronic databases for eligible literature. Next, we pooled the data from twelve studies concerning three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), combined with either deep inspiratory breath-holding (DIBH) or free-breathing (FB) modalities. The integrated cardiac and pulmonary dosimetric indexes for all included treatments were compared using Bayesian networks. A direct meta-analysis indicated that for the two methods of 3D-CRT and IMRT, DIBH technology was more effective than FB in reducing the radiation dose to the heart and lungs. Additionally, according to the network results, DIBH was superior to FB in all six treatment options, regardless of whether the plan was 3D-CRT, IMRT, or VMAT. Besides, the combined data indicated that the FB-3D-CRT regimen had the weakest dosimetric advantage of all the treatments. Excluding FB-3D-CRT, each of the other five treatments had its own specific benefits. This is the first Bayesian study of several radiotherapy regimens for breast cancer patients on the left side, and the findings can be used to select appropriate radiotherapy programs for breast cancer patients.


Assuntos
Neoplasias da Mama , Radioterapia (Especialidade) , Neoplasias Unilaterais da Mama , Humanos , Feminino , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias da Mama/radioterapia , Teorema de Bayes , Protocolos Clínicos
6.
Gland Surg ; 12(6): 749-766, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37441012

RESUMO

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

7.
Sci Rep ; 13(1): 8673, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248363

RESUMO

Radiotherapy benefits patients with advanced esophageal squamous cell carcinoma (ESCC) in terms of symptom relief and long-term survival. In contrast, a substantial proportion of ESCC patients have not benefited from radiotherapy. This study aimed to establish and validate an artificial neural network-based radiomics model for the pretreatment prediction of the radiotherapy response of advanced ESCC by using integrated data combined with feasible baseline characteristics of computed tomography. A total of 248 patients with advanced ESCC who underwent baseline CT and received radiotherapy were enrolled in this study and were analyzed by two types of radiomics models, machine learning and deep learning. As a result, the Att. Resnet50 pretrained network model indicated superior performance, with AUCs of 0.876, 0.802 and 0.732 in the training, internal validation, and external validation cohorts, respectively. Similarly, our Att. Resnet50 pretrained network model showed excellent calibration and significant clinical benefit according to the C index and decision curve analysis. Herein, a novel pretreatment radiomics model was established based on deep learning methods and could be used for radiotherapy response prediction in advanced ESCC patients, thus providing reliable evidence for therapeutic decision-making.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Radioterapia (Especialidade) , Humanos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/radioterapia , Área Sob a Curva , Redes Neurais de Computação , Estudos Retrospectivos
8.
Cochrane Database Syst Rev ; 4: CD010956, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-37058421

RESUMO

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.


Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Dabigatrana/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Trombose Venosa/complicações , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/prevenção & controle , Hemorragia/induzido quimicamente
9.
Cochrane Database Syst Rev ; 1: CD010185, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629152

RESUMO

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a vascular condition with significant risk attached, particularly if they rupture. Therefore, it is critical to identify and repair these as an elective procedure before they rupture and require emergency surgery. Repair has traditionally been an open surgical technique that required a large incision across the abdomen. Endovascular abdominal aortic aneurysm repairs (EVARs) are now a common alternative. In this procedure, the common femoral artery is exposed via a cut-down approach and a graft is introduced to the aneurysm in this way. This Cochrane Review examines a totally percutaneous approach to EVAR. This technique gives a minimally invasive approach to femoral artery access that may reduce groin wound complication rates and improve recovery time. However, the technique may be less applicable in people with, for example, groin scarring or arterial calcification. This is an update of the previous Cochrane Review published in 2017. OBJECTIVES: To evaluate the benefits and harms of totally percutaneous access compared to cut-down femoral artery access in people undergoing elective bifurcated abdominal endovascular aneurysm repair (EVAR). SEARCH METHODS: We used standard, extensive Cochrane search methods The latest search was 8 April 2022. SELECTION CRITERIA: We included randomised controlled trials in people diagnosed with an AAA comparing totally percutaneous versus surgical cut-down access endovascular repair. We considered all device types. We only considered studies investigating elective repairs. We excluded studies reporting emergency surgery for ruptured AAAs and those reporting aorto-uni-iliac repairs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. short-term mortality, 2. failure of aneurysm exclusion and 3. wound infection. Secondary outcomes were 4. major complications (30-day or in-hospital); 5. medium- to long-term (6 and 12 months) complications and mortality; 6. bleeding complications and haematoma; and 7. operating time, duration of intensive treatment unit (ITU) stay and hospital stay. We used GRADE to assess the certainty of evidence for the seven most clinically relevant primary and secondary outcomes. MAIN RESULTS: Three studies with 318 participants met the inclusion criteria, 189 undergoing the percutaneous technique and 129 treated by cut-down femoral artery access. One study had a small sample size and did not adequately report the method of randomisation, allocation concealment or preselected outcomes. The other two larger studies had few sources of bias and good methodology; although one study had a high risk of bias in selective reporting. We observed no clear difference in short-term mortality between groups, with only one death occurring overall, in the totally percutaneous group (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.06 to 36.18; 2 studies, 181 participants; low-certainty evidence). One study reported failure of aneurysm exclusion. There was one failure of aneurysm exclusion in the surgical cut-down femoral artery access group (RR 0.17, 95% CI 0.01 to 4.02; 1 study, 151 participants; moderate-certainty evidence). For wound infection, there was no clear difference between groups (RR 0.18, 95% CI 0.01 to 3.59; 3 studies, 318 participants; moderate-certainty evidence). There was no clear difference between percutaneous and cut-down femoral artery access groups in major complications (RR 1.21, 95% CI 0.61 to 2.41; 3 studies, 318 participants; moderate-certainty evidence), bleeding complications (RR 1.02, 95% CI 0.29 to 3.64; 2 studies, 181 participants; moderate-certainty evidence) or haematoma (RR 0.88, 95% CI 0.13 to 6.05; 2 studies, 288 participants). One study reported medium- to long-term complications at six months, with no clear differences between the percutaneous and cut-down femoral artery access groups (RR 0.82, 95% CI 0.25 to 2.65; 1 study, 135 participants; moderate-certainty evidence). We detected differences in operating time, with the percutaneous approach being faster than cut-down femoral artery access (mean difference (MD) -21.13 minutes, 95% CI -41.74 to -0.53 minutes; 3 studies, 318 participants; low-certainty evidence). One study reported the duration of ITU stay and hospital stay, with no clear difference between groups. AUTHORS' CONCLUSIONS: Skin puncture may make little to no difference to short-term mortality. There is probably little or no difference in failure of aneurysm exclusion (failure to seal the aneurysms), wound infection, major complications within 30 days or while in hospital, medium- to long-term (six months) complications and bleeding complications between the two groups. Compared with exposing the femoral artery, skin puncture may reduce the operating time slightly. We downgraded the certainty of the evidence to moderate and low as a result of imprecision due to the small number of participants, low event rates and wide CIs, and inconsistency due to clinical heterogeneity. As the number of included studies was limited, further research into this technique would be beneficial.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Infecção dos Ferimentos , Humanos , Aneurisma da Aorta Abdominal/cirurgia , Correção Endovascular de Aneurisma , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Artéria Femoral/cirurgia , Virilha/cirurgia , Hematoma , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Clin Epidemiol ; 155: 1-12, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574532

RESUMO

OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.

11.
Biochem Biophys Res Commun ; 611: 107-113, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35487060

RESUMO

BARD1 is a tumor suppressor that is necessary for the functioning and stability of BRCA1, with which it forms a heterodimer and participates in the repair of DNA double-strand breaks. The cellular level of BARD1 and its interaction with BRCA1 are crucial for BRCA1/BARD1 function in homologous recombination and tumor suppression. However, the regulatory mechanism underpinning the stability of BARD1 is largely unclear. In this study, we identified DCAF8L2, a DDB1-Cullin associated factor (DCAF) associated with CRL4 E3 ligase, as a negative regulator of BARD1. Mechanistically, DCAF8L2 interacts with and targets BARD1 for ubiquitination and degradation. In addition, the interaction of DCAF8L2 with BARD1 through the RING domain could compete with the dimerization of BRCA1 and BARD1, leading to increased cellular uncoupling of BARD1 and BRCA1, subjecting the latter to degradation. The overexpression of DCAF8L2 compromises the homologous recombination process and confers cells with increased sensitivity to DNA damage. Furthermore, DCAF8L2 was aberrantly expressed in breast cancer cell lines. Our findings suggest that DCAF8L2 may play an oncogenic role in the pathogenesis of breast cancer, possibly by negative regulation of BARD1.


Assuntos
Neoplasias da Mama , Receptores de Interleucina-17 , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Proteína BRCA1/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Recombinação Homóloga , Humanos , Receptores de Interleucina-17/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
12.
Gland Surg ; 10(8): 2591-2599, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34527570

RESUMO

BACKGROUND: Standardized and transparent reporting of surgical technique is the cornerstone of effective dissemination, implementation and improvement. However, current reporting of surgical techniques is inadequate. The existing guidelines potentially applied to guide surgical technique reporting are with a minimal highlight of the surgical technique, lack requirements explaining what extent and dimensions need to be described in detail, or are unlikely to extrapolate to a wide range of surgical techniques. This study aims to formulate a rigorous protocol to develop a surgical technique reporting checklist and standards (SUPER) that defines what a clear, comprehensive and detailed surgical technique report should be contained. METHODS: This protocol is designed following the classic guidance for developing reporting guidelines recommended by the EQUATOR network. RESULTS: The development team will consist of surgeons (~80%), methodologists, and journal editors. The draft checklist sources will include a scoping review of existing reporting guidelines related to surgical technique, surgical technique articles from 15 top journals published in the last year, and brainstorming by the multidisciplinary development team. The final SUPER checklist will be formed after three rounds of Delphi surveys, one round of face-to-face meeting, and a month-long pilot test. The SUPER checklist will be published as open-access and be used in combination with existing reporting guidelines related to surgical techniques (e.g., IDEAL). This protocol will steer the SUPER checklist's development, allowing us to further elaborate surgical technique reporting for all surgical specialties, and enabling a more favorable experience for surgeons, nurses, medical students, residents, editors, and reviewers. TRIAL REGISTRATION: This trial is registered at the EQUATOR network on December 18th, 2020. Available at: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/.

13.
Gland Surg ; 10(7): 2325-2333, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422603

RESUMO

BACKGROUND: The reporting of surgical techniques is of mixed quality, with most at a very minimal level. Reporting guidelines that could be applied to guide surgical technique reporting vary in methodology for development, discipline coverage, dimension coverage and detail requested. However, a scoping review that could indicate the gaps and efforts needed in surgical technique reporting guidelines is lacking and warranted. This study aims to design a methodological rigour protocol to guide the development of a scoping review of surgical technique reporting guidelines. METHODS: This protocol is designed following the 2020 manual proposed by the Joanna Briggs Institute. To further ensure the soundness of the protocol, we also included multidisciplinary professionals (including methodologists, clinicians, and journal editors) to refine the protocol. DISCUSSION: Seven key steps for developing the scoping review are identified and presented in detail, including (I) identifying the research questions; (II) inclusion criteria; (III) search strategy; (IV) source of evidence selection; (V) data extraction; (VI) analysis of the evidence; and (VII) presentation of the results. Guided by this protocol, the subsequent scoping review will inform us the overview of surgical technique reporting guidelines and precisely guide our direction and next steps in improving surgical technique reporting guidelines. TRIAL REGISTRATION: This protocol is not registered as the PROSPERO database only accepts registration of systematic review protocols while does not accept registration of scoping review protocols.

14.
Ann Transl Med ; 9(13): 1088, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34423000

RESUMO

BACKGROUND: The International Reporting Items for Practice Guidelines in Health Care (RIGHT) statement is a set of recommendations for the reporting in clinical practice guidelines (CPGs). We aimed to assess the reporting quality of CPGs for pancreatic cancer following the RIGHT checklist. METHODS: Guidelines for pancreatic cancer were identified by searching electronic databases, guideline databases, and medical society websites. The reporting quality was evaluated by calculating the adherence to the items of the RIGHT checklist and summarizing them over the seven domains and the entire checklist. We also present results stratified by selected characteristics. RESULTS: A total of 22 guidelines were found eligible. Mean overall adherence to the RIGHT items was 60.0%. All guidelines adhered to the RIGHT items 3, 7a, 13a, while no guidelines reported the items 14c or 18b, which are some of the topics dealing with rationale for recommendations and funding source, respectively. Of the seven domains of the RIGHT checklist, "Review and quality assurance" and "Funding and declaration and management of interests" had the lowest reporting rates (25.0% and 43.2%, respectively); the remaining five domains had reporting rates >50%. CPGs that reported funding support, were published in higher-impact journals, and that applied a grading system for the quality of evidence, tended to have higher reporting rates. CONCLUSIONS: Our results show that reporting quality of pancreatic cancer CPGs still needs to be improved. The use of the RIGHT statement should be encouraged when developing new guidelines.

15.
Ann Transl Med ; 9(14): 1172, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430613

RESUMO

BACKGROUND: The International Reporting Items for Practice Guidelines in Healthcare (RIGHT) instrument was launched in 2016 to improve the reporting of clinical practice guidelines (CPGs). We aimed to systematically evaluate the reporting quality of CPGs on melanoma using RIGHT. METHODS: We systematically searched electronic databases, guideline databases and medical society websites until November 2020 to identify guidelines for melanoma published since 2018. The reporting quality of included guidelines was assessed by calculating the percentages of the 35 items of the RIGHT checklist that were appropriately reported. We stratified the results by selected characteristics to describe the correlation of these factors with reporting quality. RESULTS: A total of 20 guidelines were identified and analyzed. The mean reporting rate was greater than 50% in five of the seven domains of the RIGHT checklist; the remaining two domains (Other information, Review and quality assurance) both had a mean reporting rate of 35.0%. The mean overall reporting rate was 63.7%. No CPG considered equity, feasibility or acceptability of the recommendations (item 14c), and only one CPG described the role of funders (item 18b). Guidelines that reported funding or were published in higher-impact journals tended to have a higher reporting quality, whereas the reporting rate in the one included Chinese-language CPG was low. CONCLUSIONS: Reporting quality of melanoma CPGs tends to be relatively good. The CPGs developed in China were however an exception. The use of the 2016 RIGHT tool in guideline development should be encouraged to support rigorous and transparent reporting.

16.
Ann Transl Med ; 9(14): 1173, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430614

RESUMO

BACKGROUND: The International Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement is a set of recommendations for reporting in clinical practice guidelines (CPGs). We aimed to use RIGHT to evaluate the reporting quality of CPGs on prostate cancer. METHODS: We systematically searched literature databases and websites from January 1, 2018 to December 1, 2020 to identify CPGs on prostate cancer. Two investigators reviewed the identified articles and assessed the reporting quality independently by using the RIGHT checklist. We reported the proportions of guidelines that complied with each of the 35 RIGHT checklist item and the mean reporting compliance percentages for each of the seven domains of RIGHT. RESULTS: A total of 38 CPGs were included. The mean overall reporting rate over the included CPGs was 51.6%. Eighteen items were reported by more than half of the guidelines four items (1a 3, 7a and 13a) were reported by all guidelines. Items 7b (10.5%), 13b (10.5%), 14c (13.2%), and 18b (7.9%) had the lowest reporting proportions. The mean reporting rates in each RIGHT domain were 74.6% for "Basic Information", 26.3% for "Review and quality assurance", 59.9% for "Background", 43.7% for "Evidence", 43.2% for "Recommendations", 43.4% for "Funding and declaration and management of interests", and 43.0% for "Other information". CONCLUSIONS: The overall adherence of CPGs on prostate cancer to RIGHT checklist is poor. Following the RIGHT checklist during the development of the guideline could improve the quality of reporting in the future.

17.
Ann Transl Med ; 9(14): 1175, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430616

RESUMO

BACKGROUND: Clinical practice guidelines are an essential tool for translating evidence into practice. Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist assists to guide the reporting in guidelines. We used RIGHT to assess the reporting completeness and quality of guidelines on colorectal cancer (CRC). METHODS: We searched the electronic databases Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) from January 1st, 2018 to December 1st, 2020 for guidelines on CRC. Websites of guideline development organizations were also searched. Two investigators assessed the reporting quality of the included guidelines, and calculated the numbers of guidelines that were compliant with each RIGHT checklist item and the mean proportions of reported items for each of the seven RIGHT checklist domains. RESULTS: Twenty-seven colorectal guidelines were included. The proportions of reported items in each RIGHT domain were 71.0% for Basic information, 66.2% for Background, 45.9% for Evidence, 68.8% for Recommendations, 24.1% for Review and quality assurance, 33.3% for Funding and declaration and management of interests, and 40.7% for Other information. CONCLUSIONS: The reporting quality of colorectal guidelines was moderate. A systematic use of the RIGHT checklist during the development process could improve the reporting quality of guidelines in the future.

18.
Ann Transl Med ; 9(14): 1174, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430615

RESUMO

BACKGROUND: Breast cancer is the most frequent type of cancer in women. The methodological quality of clinical practice guidelines (CPGs) on breast cancer has been shown to be heterogeneous. The aim of our study was to evaluate the quality of breast cancer CPGs published in years 2018-2020, using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. METHODS: We searched Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) as well as websites of guideline organizations for CPGs on breast cancer published between 2018 and 2020. We used the RIGHT checklist to evaluate the reporting quality of the included guidelines by assessing whether the CPGs adhered to each item of the checklist and calculated the proportions of appropriately reported RIGHT checklist items. We also presented the adherence reporting rates for each guideline and the mean rates for each of the seven domains of the RIGHT checklist. RESULTS: A total of 45 guidelines were included. Eighteen (40.0%) guidelines had an overall reporting rate below 50% and only three (6.7%) reported more than 80% of the items. The domains "Basic information" and "Background" had the highest reporting rates (75.9% and 62.5%, respectively). The mean reporting rates of the domains "Evidence", "Recommendation", "Review and quality assurance", "Funding and declaration and management of interests" and "Other information" were 42.7%, 53.0%, 33.3%, 45.0%, and 44.4%, respectively. CONCLUSIONS: The reporting quality varied among guidelines for breast cancer, showing the need for improvement in reporting the contents. Guideline developers should pay more attention to reporting the evidence, review and quality assurance, and funding and declaration and management of interests in future.

19.
Ann Transl Med ; 9(12): 1002, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277802

RESUMO

BACKGROUND: The reporting quality of clinical practice guidelines (CPGs) for gliomas has not yet been thoroughly assessed. The International Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement developed in 2016 provides a reporting framework to improve the quality of CPGs. We aimed to estimate the reporting quality of glioma guidelines using the RIGHT checklist and investigate how the reporting quality differs by selected characteristics. METHODS: We systematically searched electronic databases, guideline databases, and medical society websites to retrieve CPGs on glioma published between 2018 and 2020. We calculated the compliance of the CPGs to individual items, domains and the RIGHT checklist overall. We performed stratified analyses by publication year, country of development, reporting of funding, and impact factor (IF) of the journal. RESULTS: Our search revealed 20 eligible guidelines. Mean overall adherence to the RIGHT statement was 54.6%. Eight CPGs reported more than 60% of the items, and five reported less than 50%. All guidelines adhered to the items 1a, 3, 7a, 13a, while no guidelines reported the items 17 or 18b (see http://www.right-statement.org/right-statement/checklist for a description of the items). Two of the seven domains, "Basic information" and "Background", had mean reporting rates above 60%. The "Review and quality assurance" domain had the lowest mean reporting rate, 12.5%. The reporting quality of guidelines published in 2020, guidelines developed in the United States, and guidelines that reported funding tended to be above average. CONCLUSIONS: The reporting quality of CPGs on gliomas is low and needs improvement. Particular attention should be paid on reporting the external review and quality assurance process. The use of the RIGHT criteria should be encouraged to guide the development, reporting and evaluation of CPGs.

20.
Ann Transl Med ; 9(12): 1003, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277803

RESUMO

BACKGROUND: Gastric cancer is the fifth most common type of cancer globally. We aimed to evaluate the reporting quality of clinical practice guidelines in the field of gastric cancer. METHODS: We searched Medline (via PubMed), China Biology Medicine, Chinese National Knowledge Infrastructure and WanFang databases and the websites of the main guideline development organizations from 2018 to 2020 for guidelines on gastric cancer. Data were extracted and the reporting quality evaluated by two researchers independently using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. We assessed the compliance of the guidelines to each of the 35 items of RIGHT and summarized the reporting proportions of the seven domains of RIGHT. RESULTS: Eighteen guidelines were included. The mean proportion of appropriately reported RIGHT items was 52.4%. Among the seven domains of the RIGHT checklist, Basic information had the highest reporting rate (78.7%), and Review and quality assurance domain the lowest rate (16.7%). The domains Evidence (40.0%), Funding and declaration and management of interests (43.1%), and Other information (31.5%) had also reporting rates below 50%. Two RIGHT items (17 and 19b) were not reported by any of the guidelines. CONCLUSIONS: The reporting quality of gastric cancer guidelines published in the years 2018-2020 was suboptimal, especially regarding the reporting of review, quality assurance and evidence. Guideline developers should pay attention on rigorous reporting following international standard to improve the quality of guidelines.

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