Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 159
Filtrar
1.
Transl Lung Cancer Res ; 11(11): 2318-2331, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36519017

RESUMO

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the Chinese Guidelines on Video-assisted Thoracoscopy, and the National Comprehensive Cancer Network (NCCN) guidelines on the management of pulmonary lesions. Each of the statements was discussed and agreed upon with a unanimous consensus amongst the panel. A total of 6 consensus statements were developed. Fluorescence-guided thoracoscopy has unique advantages in the visualization of pulmonary nodules, and recognition and resection of the anterior plane of the pulmonary segment. The expert panel agrees that fluorescence-guided thoracoscopic surgery has the potential to become a routine operation for the treatment of pulmonary lesions.

2.
Commun Biol ; 5(1): 1355, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494488

RESUMO

Circular RNAs (CircRNAs) are a class of noncoding RNAs formed by backsplicing during cotranscriptional and posttranscriptional processes, and they widely exist in various organisms. CircRNAs have multiple biological functions and are associated with the occurrence and development of many diseases. While the biogenesis and biological function of circRNAs have been extensively studied, there are few studies on circRNA degradation and only a few pathways for specific circRNA degradation have been identified. Here we outline basic information about circRNAs, summarize the research on the circRNA degradation mechanisms and discusses where this field might head, hoping to provide some inspiration and guidance for scholars who aim to study the degradation of circRNAs.


Assuntos
RNA Circular , RNA , RNA Circular/genética , RNA/genética , RNA/metabolismo , Estabilidade de RNA
4.
J Thorac Dis ; 14(9): 3277-3284, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36245591

RESUMO

Background: Definitive chemoradiation is the preferred treatment for cervical esophageal carcinoma (CEC), per the National Comprehensive Cancer Network (NCCN) guidelines. However, in treatment failures, salvage surgery poses significant technical challenges. If non-responders could be identified, prior to chemoradiation, these patients may benefit from primary esophagectomy. Programmed cell death protein 1 (PD-1) inhibitor is widely used and recognized as an effective treatment method in various cancers including esophageal cancer. Therefore, we propose to screen for treatment response to neoadjuvant immunotherapy plus chemotherapy to select patients who are radiosensitive and potential candidates for laryngeal preservation. While non-responders are likely to be insensitive to chemoradiation would be offered radical esophagectomy. Methods: A total of 36 patients with histopathologically-confirmed locally advanced CEC have been enrolled in our study. All participants will receive 2 cycles of induction therapy, which was tislelizumab combined with paclitaxel and carboplatin. Patients will be classified into 3 groups according to their response to induction therapy: a remarkable response (RR) group, limited partial response (LPR) group, and poor response (POR) group. Stratified patients will receive the following follow-up treatments: those in the RR group will receive dCRT, and those in the LPR and POR groups will undergo radical surgery. Then, participants in the RR group will be administrated with tislelizumab alone for 1 year. The choice of postoperative treatment for patients in the LPR and POR groups will depend on the patient's condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint of the study is the 2-year event-free survival (EFS). The secondary endpoints are disease-free survival (DFS), regression-free survival (RFS), objective response rate (ORR), and 5-year overall survival (OS). At the same time, we will assess the patient's quality of life (QoL). Conclusions: Screening CEC patients after immune-induction therapy combined with chemotherapy using different treatment strategies might lead to improvements in their QoL and OS time. No relevant double-endpoint studies have been reported until now. Our study is the first multicenter, prospective, exploratory study to seek the optimal treatment for locally advanced CEC patients. The results may offer high-level evidence for future CEC treatment. Trial Registration: Chictr.Org identifier: ChiCTR2200057732.

5.
Cell Oncol (Dordr) ; 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36223033

RESUMO

PURPOSE: Macrophages (MΦs) play a dual role in the promotion and suppression of lung adenocarcinoma (LUAD), the function of which is influenced by the metabolic status. The role of protein tyrosine phosphatase receptor type F (PTPRF) in cancer has not been elucidated, and its role in MΦs remains to be seen. METHODS: The Seahorse XFe 96 Cell Flow Analyzer detected glucose metabolism in tumor cells and macrophages. The expressions of FSCN1, M-CSF, IL4, PTPRF and IGF1 in macrophages were detected by Western blotting and qRT-PCR. Binding of FSCN1 and IGF1R was detected by co-immunoprecipitation. The tumor status in animals was observed using the IVIS Lumina III imaging system. RESULTS: We found that Fascin Actin-Bundling Protein 1 (FSCN1) activates the PI3K-AKT and JAK-STAT signaling pathways in LUAD cells via binding to IGF-1R, thereby promoting the secretion of cytokines such as IL4 and M-CSF. IL4 and M-CSF promote the expression of PTPRF in MΦs, leading to M2 polarization of MΦs by increasing glucose intake and lactate production. In return, M2-type MΦs act on LUAD cells by secreting cytokines such as IGF-1, CCL2, and IL10, which ultimately promote tumor progression. In vivo experiments proved that the knockdown of FSCN1 in A549 cells and PTPRF in MΦs greatly reduced LUAD proliferative and metastatic capacity, which was consistent with the in vitro findings. CONCLUSIONS: This study investigated the reprogramming effects of FSCN1 and PTPRF on inflammatory cytokines in the LUAD microenvironment, revealing potential mechanisms by which FSCN1 and PTPRF promote tumor progression and providing a new experimental basis for LUAD treatment.

6.
Respir Res ; 23(1): 269, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183124

RESUMO

BACKGROUND: The defects and imbalance in lung repair and structural maintenance contribute to the pathogenesis of chronic obstructive pulmonary diseases (COPD), yet the molecular mechanisms that regulate lung repair process are so far incompletely understood. We hypothesized that cigarette smoking causes glycocalyx impairment and endothelial apoptosis in COPD, which could be repaired by the stimulation of fibroblast growth factor 10 (FGF10)/FGF receptor 1 (FGFR1) signaling. METHODS: We used immunostaining (immunohistochemical [IHC] and immunofluorescence [IF]) and enzyme-linked immunosorbent assay (ELISA) to detect the levels of glycocalyx components and endothelial apoptosis in animal models and in patients with COPD. We used the murine emphysema model and in vitro studies to determine the protective and reparative role of FGF10/FGFR1. RESULTS: Exposure to cigarette smoke caused endothelial glycocalyx impairment and emphysematous changes in murine models and human specimens. Pretreatment of FGF10 attenuated the development of emphysema and the shedding of glycocalyx components induced by CSE in vivo. However, FGF10 did not attenuate the emphysema induced by endothelial-specific killing peptide CGSPGWVRC-GG-D(KLAKLAK)2. Mechanistically, FGF10 alleviated smoke-induced endothelial apoptosis and glycocalyx repair through FGFR1/ERK/SOX9/HS6ST1 signaling in vitro. FGF10 was shown to repair pulmonary glycocalyx injury and endothelial apoptosis, and attenuate smoke-induced COPD through FGFR1 signaling. CONCLUSIONS: Our results suggest that FGF10 may serve as a potential therapeutic strategy against COPD via endothelial repair and glycocalyx reconstitution.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Animais , Apoptose/fisiologia , Enfisema/complicações , Fator 10 de Crescimento de Fibroblastos , Glicocálix/metabolismo , Glicocálix/patologia , Humanos , Camundongos , Enfisema Pulmonar/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/uso terapêutico , Tabaco
7.
Nature ; 608(7923): 513-517, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35978124

RESUMO

High pressure induces dramatic changes and novel phenomena in condensed volatiles1,2 that are usually not preserved after recovery from pressure vessels. Here we report a process that pressurizes volatiles into nanopores of type 1 glassy carbon precursors, converts glassy carbon into nanocrystalline diamond by heating and synthesizes free-standing nanostructured diamond capsules (NDCs) capable of permanently preserving volatiles at high pressures, even after release back to ambient conditions for various vacuum-based diagnostic probes including electron microscopy. As a demonstration, we perform a comprehensive study of a high-pressure argon sample preserved in NDCs. Synchrotron X-ray diffraction and high-resolution transmission electron microscopy show nanometre-sized argon crystals at around 22.0 gigapascals embedded in nanocrystalline diamond, energy-dispersive X­ray spectroscopy provides quantitative compositional analysis and electron energy-loss spectroscopy details the chemical bonding nature of high-pressure argon. The preserved pressure of the argon sample inside NDCs can be tuned by controlling NDC synthesis pressure. To test the general applicability of the NDC process, we show that high-pressure neon can also be trapped in NDCs and that type 2 glassy carbon can be used as the precursor container material. Further experiments on other volatiles and carbon allotropes open the possibility of bringing high-pressure explorations on a par with mainstream condensed-matter investigations and applications.

8.
Langenbecks Arch Surg ; 407(7): 2673-2680, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36006505

RESUMO

PURPOSE: Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy. METHODS: Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes in pulmonary function, operative data, and pulmonary complications were compared between the 2 groups. RESULTS: A total of 71 patients were randomized and underwent MIE after receiving CT (n = 34) or CRT (n = 37). Baseline clinical characteristics were comparable between the 2 groups. The CRT group experienced a greater decrease of forced expiratory volume at 1 s (FEV1) (2.66 to 2.18 L, p = 0.023) and diffusion capacity of the lung for carbon monoxide divided by the mean alveolar volume (DLCO/Va) (17.3%, p < 0.001) than the CT group (FEV1 2.53 to 2.41 L; DLCO/Va 4.8%). The incidence of pulmonary complications was higher in the CRT group (13.51 vs. 8.82%), but the difference was not significant (p = 0.532). CONCLUSIONS: Preoperative CRT affects pulmonary function more than CT alone, but does not increase the risk of pulmonary complications in patients undergoing MIE.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Esofagectomia/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Esofágicas/cirurgia , Quimiorradioterapia/efeitos adversos , Pulmão/diagnóstico por imagem
9.
Artigo em Inglês | MEDLINE | ID: mdl-35907612

RESUMO

Studies have shown that tumors with ground-glass opacity (GGO) components are associated with favorable outcomes. However, this view should be confirmed in an international cohort. We aimed to verify the impact of a GGO component on clinical (c)-stage IA lung adenocarcinoma and to describe the biological discrepancies between the part-solid and pure-solid groups. We evaluated 1333 cases of surgically resected c-stage IA lung adenocarcinomas, including 484 part-solid and 849 pure-solid tumors. Furthermore, we matched the solid size between the 2 groups and examined 470 patients. We compared the prognoses between the 2 groups before and after matching. The prognostic and biological differences were described before and after matching. Compared with the pure-solid group, the part-solid group was associated with favorable outcomes [5-year overall survival (OS) 99.4% vs 87.6%, P < 0.001; 5-year recurrence-free survival (RFS) 96.9% vs 82.2%, P < 0.001]. Similar results were obtained after matching (5-year OS 98.9% vs 92.2%, P = 0.012; 5-year RFS 95.0% vs 88.5%, P = 0.007). Multivariable analyses revealed that GGO component appearance was a factor of better OS and RFS. The part-solid tumor, regardless of the size of the solid component, had a similar outcome to the pure-solid tumor of c-stage T1a classification. Also, more epidermal growth factor receptor, human epidermal growth factor receptor-2 mutations, and receptor tyrosine kinase ROS-1-positive were observed in the part-solid group. In comparison, more wild types and Kirsten-Ras were observed in the pure-solid group. Adenocarcinomas with a GGO component were associated with superior outcomes. The GGO component should be considereda new clinical T descriptor. Early-stage lung adenocarcinomas with and without a GGO component may be 2 distinct tumor types.

10.
Ann Surg Oncol ; 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838904

RESUMO

BACKGROUND: The appropriate approach for video-assisted thoracic surgery for early-stage thymoma remains debatable. The current study compared the safety and feasibility between subxiphoid-approach thoracoscopic thymectomy (SATT) and lateral intercostal-approach thoracoscopic thymectomy (LATT) for Masaoka-Koga stages 1 and 2 thymoma. METHODS: The study retrospectively enrolled 461 patients without myasthenia gravis who underwent SATT or LATT at the Zhongshan Hospital of Fudan University between 2016 and 2020. A 1:1 propensity score-matching (PSM) analysis was performed to control for selection bias. A series of perioperative outcomes, including surgical outcomes, inflammatory factors, morbidity and mortality, pain assessment, and quality of life, were compared. RESULTS: Each group consisted of 144 patients after PSM. The results showed that the SATT group had a significantly higher rate of exposure to the bilateral phrenic nerves (SATT [98.6 %] vs. LATT [77.1 %]; p < 0.001) as well as a larger maximum length (9.20 ± 3.08 vs. 7.52 ± 3.44 cm; p < 0.001) and width (6.13 ± 1.81 vs. 5.04 ± 1.77 cm; p < 0.001) of resected tissue than the LATT group. In addition, the SATT group had lower postoperative high-sensitivity C-reactive protein (hs-CRP) levels (9.37 ± 2.17 vs. 12.69 ± 2.13 mg/L; p < 0.001), better postoperative days 1, 3, and 7 visual analog pain scale (VAS) scores (p < 0.001), and better postoperative days 30 and 90 quality of life (p < 0.05). However, the two groups showed no significant increase in surgical time, estimated blood loss, total drainage time, postoperative total drainage volume, complications, or postoperative hospital stays. CONCLUSIONS: The study results suggest that the SATT is feasible and safe for Masaoka-Koga stages 1 and 2 thymoma.

11.
Surg Endosc ; 36(12): 9113-9122, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35773604

RESUMO

BACKGROUND: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. RESULTS: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2-3] days vs. 3 [3-4] days, p = 0.001), but comparable LOS (10 [9-11.25] days vs. 10 [9-13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). CONCLUSIONS: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Esofagectomia/métodos , Fístula Anastomótica/cirurgia , Resultado do Tratamento , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/complicações , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
12.
Dis Esophagus ; 35(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35649396

RESUMO

Immune checkpoint inhibitors (ICIs) have shown a powerful benefit in the neoadjuvant therapy for esophageal cancer, but evidence for its safety and efficacy is limited and may not reflect real-world practice. We retrospectively reviewed the database of treatment-naive patients from 15 esophageal cancer centers in China who received ICIs as neoadjuvant treatment for locally advanced esophageal cancer from May 2019 to December 2020. The primary endpoints were rate and severity of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs). Secondary endpoints included pathologically complete response (pCR) rate, R0 resection rate, mortality and morbidity. Among the 370 patients, 311 (84.1%) were male with a median age of 63 (range: 30-81) years and stage III or IVa disease accounted for 84.1% of these patients. A total of 299 (80.8%) patients were treated with ICIs and chemotherapy. TRAEs were observed in 199 (53.8%) patients with low severity (grade 1-2, 39.2%; grade 3-4, 13.2%; grade 5, 1.4%), and irAEs occurred in 24.3% of patients and were mostly of grade 1-2 severity (21.1%). A total of 341 (92.2%) patients had received surgery and R0 resection was achieved in 333 (97.7%) patients. The local pCR rate in primary tumor was 34.6%, including 25.8% of ypT0N0 and 8.8% of ypT0N+. The rate of postoperative complications was 41.4% and grade 3 or higher complications occurred in 35 (10.3%) patients. No death was observed within 30 days after surgery, and three patients (0.9%) died within 90 days postoperatively. This study shows acceptable toxicity of neoadjuvant immunotherapy for locally advanced esophageal cancer in real-world data. Long-term survival results are pending for further investigations.


Assuntos
Neoplasias Esofágicas , Terapia Neoadjuvante , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Terapia Neoadjuvante/métodos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas/tratamento farmacológico
13.
BMC Cancer ; 22(1): 650, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698100

RESUMO

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .


Assuntos
Neoplasias Esofágicas , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Humanos , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Ann Transl Med ; 10(7): 422, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530957

RESUMO

Background: Anatomically, the esophagus is located within the mediastinum, and thus it potentially a transcervical approach for esophagectomy, which avoids thoracic manipulation, could be an alternative to transthoracic esophagectomy for the surgical resection of esophageal cancer. A modified transcervical minimally invasive esophagectomy (MIE), laparo-gastroscopic esophagectomy (LGE), was recently introduced using an integrated gastroscope to mobilize the esophagus. As such, a randomized controlled trial (RCT) is necessary to validate its value compared to transthoracic MIE, which carries a high risk of morbidity due to thoracic manipulation. Methods: This prospective study plans to enroll patients with resectable esophageal cancer with a pathological diagnosis of squamous cell carcinoma or adenocarcinoma patients over a 2-year period. Patients will be randomly assigned to one of 2 groups in a 1:1 ratio: patients in Group A will radical LGE and patients in Group B will receive radical laparo-thoracoscopic esophagectomy (LTE). Perioperative and long-term outcomes of all patients will be collected and analyzed. The primary end point will be perioperative morbidity, and the secondary end points will include 5-year overall survival (OS) and disease-free survival (DFS) and quality of life (QOL) score. Other data that will be collected and compared between the groups include the number of harvested lymph nodes, surgical Apgar score, and duration of operation. Discussion: Transthoracic MIE is the most widely accepted approach for treating esophageal cancer. In this RCT, transthoracic MIE and transcervical LGE will be compared with respect to oncological and surgical outcomes (oncological none-inferiority and surgical superiority). Trial Registration: This study is registered in Chinese Clinical Trial Registry (ChiCTR2200055312) with the name of 'Transcervical versus Transthoracic Minimally Invasive Esophagectomy: A Randomized and Controlled Trial' on January 6, 2022. Details can be found on http://www.chictr.org.cn/showproj.aspx?proj=133224.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35579357

RESUMO

OBJECTIVES: The aim of this study was to determine the prevalence of nontherapeutic thymectomy and define a clinical standard to reduce it. METHODS: From 2016 to 2020, consecutive patients who underwent thymectomy were retrospectively reviewed. Univariable and multivariable analyses were used to identify the correlation factors of nontherapeutic thymectomy. A receiver operating characteristic curve was analysed to assess the cut-off threshold of factors correlated with nontherapeutic thymectomy. RESULTS: A total of 1039 patients were included in this study. Overall, 78.4% (n = 814) of thymectomies were therapeutic and 21.6% (n = 225) were nontherapeutic. Thymoma (57.9%, n = 602) was the most common diagnosis in therapeutic thymectomy. Among those of nontherapeutic thymectomy, thymic cysts (11.9%, n = 124) were the most common lesion. Compared with therapeutic thymectomy, patients with nontherapeutic thymectomy were more likely to be younger (median age 50.1 vs 55.6 years, P < 0.001) with a smaller precontrast and postcontrast computed tomography (CT) value (P < 0.001, P < 0.001), as well as ΔCT value [10.7 vs 23.5 Hounsfield units (HU), P < 0.001]. Multivariable analysis indicated that only age and ΔCT value were significantly different between therapeutic and nontherapeutic thymectomy groups. Receiver operating characteristic curve analysis showed that cut-off values of age and ΔCT value were 44 years and 6 HU, respectively. Patients with age ≤44 years and a ΔCT value ≤6 HU had a 95% probability of nontherapeutic thymectomy. CONCLUSIONS: Surgeons should be cautious to perform thymectomy for patients with age ≤44 years and ΔCT value ≤6 HU. This simple clinical standard is helpful to reduce the rate of nontherapeutic thymectomy.


Assuntos
Cisto Mediastínico , Timoma , Neoplasias do Timo , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Timectomia
16.
BMC Cancer ; 22(1): 506, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524205

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240). METHODS: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events. DISCUSSION: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021. TRIAL REGISTRATION: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Terapia Neoadjuvante , Estudos Prospectivos
17.
Mol Ther Nucleic Acids ; 28: 366-386, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35505963

RESUMO

Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. Combination chemotherapy with cisplatin (CDDP) plus pemetrexed (PEM) remains the predominant therapeutic regimen; however, chemoresistance greatly limits its curative potential. Here, through CRISPR-Cas9 screening, we identified miR-6077 as a key driver of CDDP/PEM resistance in LUAD. Functional experiments verified that ectopic overexpression of miR-6077 desensitized LUAD cells to CDDP/PEM in both cell lines and patient-derived xenograft models. Through RNA sequencing in cells and single-cell sequencing of samples from patients with CDDP/PEM treatments, we observed CDDP/PEM-induced upregulation of CDKN1A and KEAP1, which in turn activated cell-cycle arrest and ferroptosis, respectively, thus leading to cell death. Through miRNA pull-down, we identified and validated that miR-6077 targets CDKN1A and KEAP1. Furthermore, we demonstrated that miR-6077 protects LUAD cells from cell death induced by CDDP/PEM via CDKN1A-CDK1-mediated cell-cycle arrest and KEAP1-NRF2-SLC7A11/NQO1-mediated ferroptosis, thus resulting in chemoresistance in multiple LUAD cells both in vitro and in vivo. Moreover, we found that GMDS-AS1 and LINC01128 sensitized LUAD cells to CDDP/PEM by sponging miR-6077. Collectively, these results imply the critical role of miR-6077 in LUAD's sensitivity to CDDP/PEM, thus providing a novel therapeutic strategy for overcoming chemoresistance in clinical practice.

18.
J Transl Med ; 20(1): 171, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410350

RESUMO

OBJECTIVES: Platinum-based chemotherapies are currently the first-line treatment of non-small cell lung cancer. This study will improve our understanding of the causes of resistance to cisplatin, especially in lung adenocarcinoma (LUAD) and provide a reference for therapeutic decisions in clinical practice. METHODS: Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA) and Zhongshan hospital affiliated to Fudan University (zs-cohort) were used to identify the multi-omics differences related to platinum chemotherapy. Cisplatin-resistant mRNA and miRNA models were constructed by Logistic regression, classification and regression tree and C4.5 decision tree classification algorithm with previous feature selection performed via least absolute shrinkage and selection operator (LASSO). qRT-PCR and western-blotting of A549 and H358 cells, as well as single-cell Seq data of tumor samples were applied to verify the tendency of certain genes. RESULTS: 661 cell lines were divided into three groups according to the IC50 value of cisplatin, and the top 1/3 (220) with a small IC50 value were defined as the sensitive group while the last 1/3 (220) were enrolled in the insensitive group. TP53 was the most common mutation in the insensitive group, in contrast to TTN in the sensitive group. 1348 mRNA, 80 miRNA, and 15 metabolites were differentially expressed between 2 groups (P < 0.05). According to the LASSO penalized logistic modeling, 6 of the 1348 mRNAs, FOXA2, BATF3, SIX1, HOXA1, ZBTB38, IRF5, were selected as the associated features with cisplatin resistance and for the contribution of predictive mRNA model (all of adjusted P-values < 0.001). Three of 6 (BATF3, IRF5, ZBTB38) genes were finally verified in cell level and patients in zs-cohort. CONCLUSIONS: Somatic mutations, mRNA expressions, miRNA expressions, metabolites and methylation were related to the resistance of cisplatin. The models we created could help in the prediction of the reaction and prognosis of patients given platinum-based chemotherapies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Proteínas de Homeodomínio , Humanos , Fatores Reguladores de Interferon , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Aprendizado de Máquina , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/uso terapêutico
19.
Pharmgenomics Pers Med ; 15: 235-247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35321090

RESUMO

Background: The σ1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population. Methods: A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P<0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step. Results: AP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers. Conclusion: AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.

20.
Nat Commun ; 13(1): 617, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105875

RESUMO

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.


Assuntos
Detecção Precoce de Câncer/métodos , Lasers , Nanoestruturas/química , Neoplasias/classificação , Neoplasias/diagnóstico , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , China , Estudos de Coortes , Feminino , Humanos , Aprendizado de Máquina , Masculino , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...