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1.
Acad Radiol ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508939

RESUMO

RATIONALE AND OBJECTIVES: To evaluate the diagnostic performance of dual-energy CT (DECT) parameters and quantitative-semantic features for differentiating the invasiveness of lung adenocarcinoma manifesting as ground glass nodules (GGNs). MATERIALS AND METHODS: Between June 2022 and September 2023, 69 patients with 74 surgically resected GGNs who underwent DECT examinations were included. CT numbers on virtual monochromatic images were calculated at 40-130 keV generated from DECT. Quantitative morphological measurements and semantic features were evaluated on unenhanced CT images and compared between pathologically confirmed adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA) and invasive lung adenocarcinoma (IAC). Multivariable logistic regression analysis was used to identify independent predictors. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC) and compared using DeLong's test. RESULTS: Monochromatic CT numbers at 40-130 keV were significantly higher in IAC than in AIS-MIA (all P < 0.05). Multivariate logistic analysis revealed that CT number of 130 keV (odds ratio [OR] = 1.02, P = 0.013), maximum cross-sectional long diameter (OR =1.40, P = 0.014), deep or moderate lobulation sign (OR =19.88, P = 0.005), and abnormal intranodular vessel morphology (OR = 25.57, P = 0.017) were independent predictors of IAC. The combined prediction model showed a favorable differentiation performance with an AUC of 0.966 (95.2% sensitivity, 94.3% specificity, 94.8% accuracy), which was significantly higher than that for each risk factor (AUC = 0.791-0.822, all P < 0.05). CONCLUSION: A multi-parameter combined prediction model integrating monochromatic CT numbers from DECT and quantitative-semantic features is promising for the preoperative discrimination of IAC and AIS-MIA in GGN-predominant lung adenocarcinoma.

2.
Med. oral patol. oral cir. bucal (Internet) ; 29(1): e27-e35, Ene. 2024. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-229185

RESUMO

Background: The relationship between the impacted mandibular third molar (IMTM) and the external root re-sorption (ERR) of the mandibular second molar (MSM) was analysed with cone-beam computed tomography(CBCT). The risk factors affecting the ERR of the MSM were examined to provide a reference.Material and Methods: A total of 327 patients (total: 578 teeth) admitted to the Affiliated Hospital of YanbianUniversity for IMTM extraction from January 2017 to December 2019 was chosen and divided according togender and age. The correlation between the IMTM and ERR of MSM was analysed, including inclination angle,impaction direction and depth. The relationship of mandibular ascending ramus classification with ERR of MSMwas also analysed. In addition, the correlation between the MTM impaction type and the severity of ERR wasanalysed.Results: The incidence of ERR of MSM in male patients was higher than in females (27.9% vs.17.6%, p = 0.018).The occurrence and the site of ERR showed statistical differences in the inclination angle [(≤20°, 3.6%) vs. (21°-40°, 27.1%) vs. (41°-60°, 27.6%) vs. (61°-80°, 25.6%) vs. (>80°, 31.7%), p <0.001], impaction direction [(Vertical,1.1%) vs. (Mesial, 32.7%) vs. (Horizontal, 25.3%), p <0.001] and depth of MTM [(Low position, 38.6%) vs. (Medi-an position, 32.0%) vs. (High position, 13.7%), p <0.001]. Also, there was a significant difference in the mandib-ular ascending ramus type [(Class I, 17.4%) vs. (Class II, 32.3%) vs. (Class III, 44.9%), p <0.001]. In addition, theseverity of ERR showed statistical differences in the mesial (40.9%, p<0.05), lower impaction (54.5%, p<0.05)depth of MTM and type III of mandibular ascending ramus (63.6%, p<0.05).Conclusions: The inclination angle, impaction direction, and depth of MTM were the influencing factors for theoccurrence and site of ERR.(AU)


Assuntos
Humanos , Masculino , Feminino , Dente Serotino/cirurgia , Tomografia Computadorizada de Feixe Cônico , Dente Impactado , Reabsorção da Raiz , Mandíbula/diagnóstico por imagem , Odontologia , Medicina Bucal , Saúde Bucal
3.
Int J Gen Med ; 16: 5225-5234, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021056

RESUMO

Purpose: To compare the clinical repair effects of leaving the defect empty and using Platelet-Rich Fibrin (PRF) combined with BIO-GENE artificial bone powder in patients with bone defects 6 months after jaw cystectomy. Patients and Methods: From June 2021 to June 2022, 70 patients who were admitted to the Department of Stomatology, Affiliated Hospital of Yanbian University, and were diagnosed with jaw cysts postoperatively were selected. All of the patients were divided into two groups according to random method, among which 35 patients who underwent cystectomy alone were recorded as group A, which served as blank control; 35 patients who underwent cystectomy and PRF combined with BIO-GENE artificial bone meal repaired bone defects during the same period were recorded as group B. 3D Slicer 5.0.3 software was used to reconstruct Cone Beam Computed Tomography (CBCT) after operation. In this study, the preoperative and postoperative CBCT data of the patients were analyzed using 3D Slicer 5.0.3 software in DICOM format to calculate the cleft volume before surgery and the newly formed bone volume after surgery. The osteogenesis rate was measured based on these calculations.The bone formation percentage in the bone defect area was recorded at 6 months, and the clinical curative effects of the two groups were compared. Results: After 6 months of surgery, the patients showed varying degrees of restoration in the jaw cyst area.The osteogenesis rate at 6 months in group A was 76.06±13.38%, while group B had a rate of 92.87±5.72%.The CBCT values in group B were higher than those in group A at 6 months post-surgery (P<0.05), t=-6.84.Group A and Group B showed a statistically significant difference. Conclusion: Compared with simple cystectomy, PRF combined with BIO-GENE artificial bone powder has a better effect on the speed of bone repair after cystectomy within 6 months and provides more favorable effects for the repair of postoperative dentition defects, and provides support to repair teeth after defects such as dental implants.

4.
J Xray Sci Technol ; 31(5): 981-999, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424490

RESUMO

BACKGROUND: Pulmonary granulomatous nodules (GN) with spiculation or lobulation have a similar morphological appearance to solid lung adenocarcinoma (SADC) under computed tomography (CT). However, these two kinds of solid pulmonary nodules (SPN) have different malignancies and are sometimes misdiagnosed. OBJECTIVE: This study aims to predict malignancies of SPNs by a deep learning model automatically. METHODS: A chimeric label with self-supervised learning (CLSSL) is proposed to pre-train a ResNet-based network (CLSSL-ResNet) for distinguishing isolated atypical GN from SADC in CT images. The malignancy, rotation, and morphology labels are integrated into a chimeric label and utilized to pre-train a ResNet50. The pre-trained ResNet50 is then transferred and fine-tuned to predict the malignancy of SPN. Two image datasets of 428 subjects (Dataset1, 307; Dataset2, 121) from different hospitals are collected. Dataset1 is divided into training, validation, and test data by a ratio of 7:1:2 to develop the model. Dataset2 is utilized as an external validation dataset. RESULTS: CLSSL-ResNet achieves an area under the ROC curve (AUC) of 0.944 and an accuracy (ACC) of 91.3%, which was much higher than that of the consensus of two experienced chest radiologists (77.3%). CLSSL-ResNet also outperforms other self-supervised learning models and many counterparts of other backbone networks. In Dataset2, AUC and ACC of CLSSL-ResNet are 0.923 and 89.3%, respectively. Additionally, the ablation experiment result indicates higher efficiency of the chimeric label. CONCLUSION: CLSSL with morphology labels can increase the ability of feature representation by deep networks. As a non-invasive method, CLSSL-ResNet can distinguish GN from SADC via CT images and may support clinical diagnoses after further validation.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Tomografia Computadorizada por Raios X/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Aprendizado de Máquina Supervisionado
5.
J Comput Assist Tomogr ; 47(2): 220-228, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36877755

RESUMO

OBJECTIVES: The objective of this study is to preoperatively investigate the value of multiphasic contrast-enhanced computed tomography (CT)-based radiomics signatures for distinguishing high-risk thymic epithelial tumors (HTET) from low-risk thymic epithelial tumors (LTET) compared with conventional CT signatures. MATERIALS AND METHODS: Pathologically confirmed 305 thymic epithelial tumors (TETs), including 147 LTET (Type A/AB/B1) and 158 HTET (Type B2/B3/C), were retrospectively analyzed, and were randomly divided into training (n = 214) and validation cohorts (n = 91). All patients underwent nonenhanced, arterial contrast-enhanced, and venous contrast-enhanced CT analysis. The least absolute shrinkage and selection operator regression with 10-fold cross-validation was performed for radiomic models building, and multivariate logistic regression analysis was performed for radiological and combined models building. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC of ROC), and the AUCs were compared using the Delong test. Decision curve analysis was used to evaluate the clinical value of each model. Nomogram and calibration curves were plotted for the combined model. RESULTS: The AUCs for radiological model in the training and validation cohorts were 0.756 and 0.733, respectively. For nonenhanced, arterial contrast-enhanced, venous contrast-enhanced CT and 3-phase images combined radiomics models, the AUCs were 0.940, 0.946, 0.960, and 0.986, respectively, in the training cohort, whereas 0.859, 0.876, 0.930, and 0.923, respectively, in the validation cohort. The combined model, including CT morphology and radiomics signature, showed AUCs of 0.990 and 0.943 in the training and validation cohorts, respectively. Delong test and decision curve analysis showed that the predictive performance and clinical value of the 4 radiomics models and combined model were greater than the radiological model ( P < 0.05). CONCLUSIONS: The combined model, including CT morphology and radiomics signature, greatly improved the predictive performance for distinguishing HTET from LTET. Radiomics texture analysis can be used as a noninvasive method for preoperative prediction of the pathological subtypes of TET.


Assuntos
Neoplasias Epiteliais e Glandulares , Radiologia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem
6.
Int J Clin Pract ; 2023: 9563476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36694610

RESUMO

Objective: To analyze differences in the positional relationships between the mandibular third molar (MTM) and the mandibular canal in Korean and Han patients using cone-beam computed tomography (CBCT) and to provide a basis for preoperative risk assessments. Materials and Methods: The CBCT imaging data of 260 Korean and Han patients were collected. The patients' genders, ages, impaction types and depths, relative positions between the MTMs and the mandibular nerve canals, and the shortest distances and shapes at the root tips and cortical bones were all recorded and analyzed. All data were compared using the nonparametric test, ordered logistic regression analysis, a chi-square test, and Fisher's exact test. Results: The relationship between the mandibular canal and the relative position of the MTM differed between Korean and Han patients, mainly in the different types of impactions, and the difference was statistically significant (P < 0.05). The shortest distance between the mesioangular and horizontally impacted mandibular canals and the buccal side of the MTM in Korean patients was less than in Han patients, and the difference was statistically significant (P < 0.05). For horizontal impactions, the probability of cortical bone interruption was 1.980 times greater in Korean patients than in Han patients, and the difference was statistically significant (P < 0.05). The significance threshold was set at 0.05. Conclusion: There are some differences in the positional relationship between the mandibular canal in the MTM region and the rate of cortical bone disruption between Koreans from the Yanbian area and the Hans. This should gain clinical attention.


Assuntos
Canal Mandibular , Dente Serotino , Feminino , Humanos , Masculino , Tomografia Computadorizada de Feixe Cônico/métodos , População do Leste Asiático , Mandíbula/diagnóstico por imagem , Canal Mandibular/diagnóstico por imagem , Dente Serotino/diagnóstico por imagem , Dente Serotino/cirurgia
7.
Biomater Sci ; 7(9): 3855-3865, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31305807

RESUMO

Fluorogens with aggregation-induced emission (AIE) characteristics (AIEgens) possess unique optical properties, design flexibility, and multi-functional capabilities and have established their niche as smart materials since their discovery in 2001. In recent years, AIEgens have found varied applications in sensing, imaging, and therapy in biomedical research. In this work, we systematically and comprehensively investigate the in vitro anticancer activity of AIEgens. We report the high cytotoxicity of AIEgens against cancer cells, especially against cancer stem cells (CSCs) which show high resistance to existing therapeutic drug regimens. Furthermore, we explore the role of AIEgens as novel image-guided chemotherapy agents that offer a new avenue for efficient cancer treatment.


Assuntos
Antineoplásicos/química , Corantes Fluorescentes/química , Fármacos Fotossensibilizantes/química , Estilbenos/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Hemólise , Humanos , Invasividade Neoplásica , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Imagem Óptica/métodos , Fotoquimioterapia , Estilbenos/farmacologia , Nanomedicina Teranóstica
9.
Org Biomol Chem ; 16(32): 5764-5770, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30004546

RESUMO

Antimicrobial peptides (AMPs) are short cationic peptides with a high affinity for membranes and emerged as a promising therapeutic approach with potential for treating infectious diseases. Chemical stabilization of short peptides proved to be a successful approach for enhancing their bio-physical properties. Herein, we designed and synthesized a panel of conformationally constrained antimicrobial peptides with either α-helical or ß-hairpin conformation using templating strategies. These synthetic short constrained peptides possess different topological distributions of hydrophobic and hydrophilic residues and displayed distinct antimicrobial activity. Notably, the conformationally constrained α-helical peptides displayed a faster internalization into the bacteria cells compared to their ß-hairpin analogues. These synthetic short constrained peptides showed killing effects on a broad spectrum of microorganisms mainly through pore formation and membrane damage which provided a potentially promising skeleton for the next generation of stabilized antimicrobial peptides.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Desenho de Fármacos , Antibacterianos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Bactérias/citologia , Infecções Bacterianas/tratamento farmacológico , Humanos , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Secundária de Proteína
10.
J Thorac Dis ; 10(Suppl 7): S790-S796, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29780625

RESUMO

BACKGROUND: Preinvasive lesions, such as atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), usually appear as pure ground-glass nodules (pGGNs) on thin-section computed tomography (TSCT). AAH is usually less than 5 mm wide on imaging and pathological examinations. We aimed to determine whether a 5-mm cut-off value was appropriate for the diagnosis of AAH and AIS. METHODS: We retrospectively analyzed the performance of TSCT in evaluating 80 pathologically confirmed preinvasive lesions (33 AAH lesions in 31 patients and 47 AIS lesions in 45 patients). We compared the following characteristics between the AAH and AIS groups: lesion diameter, density, rim, lobulation, spiculation, vacuole sign, aerated bronchus sign, pleural indentation sign, and pathological findings. RESULTS: All 80 lesions appeared as pGGNs. On TSCT, the average diameter of AAH lesions (6.0±1.64 mm) was significantly smaller than that of AIS lesions (8.7±3.16 mm; P<0.001). The area under the curve (AUC) for diameter was 0.792, and the best diagnostic cut-off value was 6.99 mm. On gross pathological examination, the average diameter of AAH lesions (4.6±1.99 mm) was significantly smaller that of AIS lesions (6.8±2.06 mm; P<0.001). The AUC was 0.794, and the best diagnostic cut-off value was 4.5 mm. The vacuole sign was common in AIS (P=0.021). AAH did not significantly differ from AIS (P>0.05) in terms of average CT value, uniformity of density, morphology, rim, lobulation, spiculation, pleural indentation sign, and aerated bronchus sign. CONCLUSIONS: Lesion size and the vacuole sign were beneficial in the diagnosis of AAH and AIS. The vacuole sign was common in AIS. The best diagnostic cut-off value of nodular diameter for differentiating between AAH and AIS was 6.99 mm on TSCT and 4.5 mm on gross pathology.

11.
J Thorac Dis ; 10(Suppl 7): S797-S806, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29780626

RESUMO

BACKGROUND: The differentiation of benign and malignant solitary pulmonary nodules (SPNs), especially subsolid nodules, is still challenging because of the small size, slow growth, and atypical imaging characteristics of these nodules. We aimed to determine the significance of mass growth rate (MGR) and mass doubling time (MDT) at follow-up CT of malignant SPNs. METHODS: This retrospective study included 167 patients (169 SPNs, diameter 8-30 mm). Among the 169 SPNs, 114 malignant SPNs were classified into three types: pure ground-glass nodules (pGGNs), part-solid nodules (pSNs), and solid nodules (SNs). These patients were followed up for at least 3 months. Three-dimensional manual segmentation was performed for all these nodules, and the intra- and inter-observer variabilities of diameter, volume, and mass measurement were assessed. From initial and follow-up CT scans, growth rates of the diameter, volume, and mass of the SPNs were compared. MDT and volume doubling time (VDT) were calculated and were compared among groups. RESULTS: Mass measurements had the best inter-observer consistency and intra-observer repeatability; the coefficients of variation of the mass measurements were the smallest. The mean growth rates of the diameter, volume, and mass of pGGNs, pSNs, and SNs significantly differed at different time points (P<0.001). Mean MDTs and VDTs of pGGNs, pSNs, and SNs were 655 vs. 848 days, 462 vs. 598 days, and 230 vs. 267 days, respectively (P<0.05). CONCLUSIONS: Mass measurements are an objective and accurate indicator in SPN assessment. During a 2-year follow-up, the mean growth rates of the diameter, volume, and mass of pGGNs, pSNs, and SNs differed at different time points, the greatest difference was observed in mean MGR. Mean MDT of malignant SPNs is less than the mean VDT.

12.
Chem Sci ; 9(12): 3227-3232, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29844896

RESUMO

We have developed a general peptide macrocyclization strategy that involves a facile and chemoselective methionine bis-alkylation/dealkylation process. This method provides a straightforward and easy approach to generate cyclic peptides with tolerances of all amino acids (including Cys), variable loop sizes, and different linkers. The Met bis-alkylation we apply in this strategy yields two additional on-tether positive charges that could assist in the cellular uptake of the peptides. Notably, the bis-alkylated peptide could be reduced to release the original peptide both in vitro and within cellular environments. This strategy provides an intriguing and facile traceless post-peptide-synthesis modification with enhanced cellular uptakes. Peptides constructed with this method could be utilized to zero in on various protein targets or to achieve other goals, such as drug delivery.

13.
Theranostics ; 7(18): 4566-4576, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29158845

RESUMO

Inhibition of the interaction between p53 and MDM2/MDMX has attracted significant attention in anticancer therapy development. We designed a series of in-tether chiral center-induced helical stabilized peptides, among which MeR/PhR effectively reactivated p53. The activation of p53 inhibits cell proliferation and induces apoptosis in both the MCF-7 normal tumor cell line and the PA-1 pluripotent cancer cell line with only minimal cellular toxicity towards normal cells or cancer cell lines with p53 mutations. The in vivo bioactivity study of the peptide in the ovarian teratocarcinoma (PA-1) xenograft model showed a tumor growth rate inhibition of 70% with a dosage of 10 mg/kg (one injection every other day). This is the first application of a stabilized peptide modulator targeting stem-like cancer cell both in vitro and in vivo and provides references to cancer stem cell therapy.


Assuntos
Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Feminino , Células HCT116 , Humanos , Imunoprecipitação , Células MCF-7 , Microscopia Confocal , Mutação/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Ubiquitinação
14.
Chem Commun (Camb) ; 53(75): 10452-10455, 2017 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-28884757

RESUMO

The helical peptide KLA (KLAKLAKKLAKLAK) is a well-known inducer of cellular apoptosis, acting to disrupt the mitochondrial membrane. However, its weak cellular uptake impedes development of any further applications. Here, we have utilized a novel in-tether chiral center induced helicity strategy (CIH) to develop a potent apoptosis inducer based on this KLA sequence. Notably, for the two resulting epimers of the CIH-KLA peptide, the CIH-KLA-(R) epimer exhibited superior cellular uptakes and special mitochondrial targeting when compared with its S counterpart. This work provides a promising and versatile method to modify the KLA peptide and a proof-of-concept application for the CIH strategy in modifying bioactive peptides.


Assuntos
Apoptose/efeitos dos fármacos , Peptídeos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Mitocôndrias/efeitos dos fármacos , Peptídeos/química , Relação Estrutura-Atividade
15.
Chembiochem ; 18(21): 2087-2093, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-28876512

RESUMO

Stapled peptides have emerged as a new class of targeting molecules with high binding affinity and specificity for intracellular undruggable targets. Their ability to penetrate cell membranes is exceptionally intriguing but remains elusively and controversially discussed. To understand the effect of stapling architectures on their physiochemical properties and to aid in promoting their cell permeability, we report herein a comparative study on the physiochemical properties and cell permeability of stapled α-helical peptides with different types of crosslinks. We highlight the decisive impact of the intrinsic properties of the crosslinks on cell permeability rather than the helical contents of the peptides in model amphipathic sequences targeting estrogen receptor-coactivator interaction. We envision this finding to shed further light on the chemical optimization of stapled α-helical peptides or macrocyclic cell-penetrating peptides for enhanced cell penetration.


Assuntos
Permeabilidade da Membrana Celular , Peptídeos/química , Físico-Química , Humanos , Peptídeos/síntese química , Peptídeos/farmacocinética , Estrutura Secundária de Proteína , Células Tumorais Cultivadas
16.
Bioorg Med Chem ; 25(6): 1756-1761, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-27919612

RESUMO

Thanks to their large binding interfaces, peptides are attractive ligands targeting protein-protein interactions compared with small molecules. Various strategies to improve peptides' pharmaceutical properties have been developed to constrain peptides into their functional three-dimensional structures. In our previous work, we reported that an in-tether chiral center could modulate peptides' biophysical properties. Herein, we applied this concept to construct a chiral sulfoxide center into the N-terminal end-cap system. We proved that this in-tether sulfoxide chiral center influences the structure of this N-capped template. In addition, longer peptides targeting estrogen receptor were also synthesized and we revealed that this chiral center could also modulate binding affinity to estrogen receptor alpha with enhanced protease resistance.


Assuntos
Oligopeptídeos/química , Sulfóxidos/química , Biofísica , Cromatografia Líquida de Alta Pressão , Receptor alfa de Estrogênio/química , Ligantes , Estereoisomerismo
17.
J Thorac Dis ; 9(12): 5335-5344, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29312743

RESUMO

BACKGROUND: Studies have reported that up to 8% of non-small cell lung cancers (NSCLC) involve multiple lesions; no detailed study has assessed the prognosis of early synchronous multiple primary non-small cell lung cancer (SMPNSCLC) (T1N0M0, T2aN0M0). We aimed to assess the spiral CT manifestations of SMPNSCLC during stage I and evaluate the effect of TNM staging with the 7th and 8th editions on the prognosis. METHODS: We retrospectively analyzed the data of patients who were examined, operated, and pathologically confirmed as having NSCLC from January 1, 2009, to December 31, 2010, and were followed-up for 5 years. The number of cases with stage I SMPNSCLC and solitary primary NSCLC (SPNSCLC) was 36 and 133 as per the 7th edition TNM staging system and 34 and 111 as per the 8th edition TNM staging system, respectively. The relationship between sex, age, smoking history, emphysema, surgical procedure, pathological type, tumor location, and tumor size was evaluated between the two groups, along with the correlation between prognosis and TNM staging with the 7th and 8th editions. RESULTS: A total of 1,948 cases of NSCLC underwent surgery, including 36 cases of stage I SMPNSCLC (77 lesions; 1.85%) with an age of onset of 44-86 years (median age, 60 years). The tumors primarily included adenocarcinoma (93.5%), with a diameter of 0.4-4.5 cm (median, 2.3 cm). CT indicated round/oval tumors in 81.8% cases, lobulation in 79.2% cases, spiculation sign in 70.1% cases, bronchial truncation sign in 31.2% cases, and pleural indentation in 75.3% cases. Moreover, CT indicated the presence of 36 (46.8%) solid nodules and 41 (53.2%) sub-solid nodules. With the 7th edition TNM staging system, the 5-year overall survival (OS) and disease-free survival (DFS) rates for stage ISMPNSCLC were 86.1% and 72.2%, respectively, which did not significantly differ from the prognosis of 133 cases of stage I SPNSCLC (P=0.587, P=0.273). With the 8th edition TNM staging system, the 5-year OS and DFS rates for stage I SMPNSCLC were 88.2% and 73.5%, respectively, which also did not significantly differ with the prognosis of 111 cases of stage I SPNSCLC (P=0.413, P=0.235). CONCLUSIONS: Adenocarcinoma was the main pathological type among the cases with stage I SMPNSCLC. Multiple synchronous lesions almost had the malignant characteristics of primary lung cancer, particularly the presence of single or multiple sub-solid nodules. Moreover, stage I SMPNSCLC has a similar prognosis as stage I SPNSCLC. The postoperative outcomes of stage I SMPNSCLC patients remained consistent regardless of whether the 7th or 8th edition TNM staging system was used for staging.

18.
Chem Sci ; 8(11): 7576-7581, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29568420

RESUMO

Due to their enhanced stability and cell permeability, cyclic cell-penetrating peptides have been widely used as delivery vectors for transporting cell-impermeable cargos into cells. In this study, we synthesized a panel of conformationally constrained peptides with either α-helix or ß-hairpin conformations. We tuned the amphiphilicity of these constrained peptides with different distributions of charged or hydrophobic residues and compared their cellular uptake efficiencies in different cell lines. We found that the amphipathicity of these conformationally constrained peptides correlates well with their cellular uptake efficiency. We proposed that peptides with larger hydrophobic moments (HMs) have stronger binding affinities with the cell membrane which further accelerates the endocytosis process. This finding should provide an approach towards the design of more potent conformationally constrained cell-penetrating peptides for biomedical applications.

19.
J Comput Assist Tomogr ; 40(4): 584-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27434787

RESUMO

OBJECTIVE: The aim of this study was to evaluate the computed tomography (CT) manifestations and expression of the excision cross-complementation group 1 (ERCC1) and their correlation with prognosis in stage I non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 133 patients with stage I NSCLC with complete 3- and 5-year disease-free survival (DFS) and overall survival (OS) data, who underwent thoracic CT and pathological examination, were included. Expression of ERCC1 in tumor samples was evaluated using semiquantitative immunohistochemical analysis. RESULTS: The 3- and 5-year DFS rates for the 133 patients were 72.2% and 60.9%, respectively, and the 3- and 5-year OS rates were 89.5% and 82.0%, respectively. Significant differences in the 3- and 5-year DFS occurred (P = 0.003 and P = 0.001, respectively), whereas no significant differences in the 3- and 5-year OS were found (P = 0.099 and P = 0.062, respectively) between high and low ERCC1 protein expression. Patients with high expression of ERCC1 had a better prognosis. There was a significant correlation between tumors with an irregular edge and signs of spiculation on CT and low expression of ERCC1 evaluated using logistic regression analysis (P < 0.05). CONCLUSIONS: It was concluded that patients with stage I NSCLC with high ERCC1 expression had superior survival rates relative to those with low ERCC1 expression. Tumors with an irregular edge and signs of spiculation on CT were significantly correlated with low expression of ERCC1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Tomografia Computadorizada por Raios X/métodos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Estatística como Assunto , Análise de Sobrevida
20.
Chem Commun (Camb) ; 52(59): 9275-8, 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-27357119

RESUMO

We report herein a proline-derived transannular N-cap as a helix nucleating template in diverse bio-related peptide sequences via macrolactamization on resin. This approach takes advantage of synergistic stabilization effects of both N-capping properties of proline and substitution of a main chain hydrogen bond with a covalent bond.


Assuntos
Peptídeos/química , Prolina/química , Estrutura Secundária de Proteína , Ligação de Hidrogênio , Conformação Molecular
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