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1.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(1): 79-85, 2022 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-35038803

RESUMO

Objective: To investigate the effectiveness of free peroneal artery chimeric perforator flap in repairing the defect after advanced local lesions resection in parotid gland carcinoma (PGC). Methods: Between June 2010 and June 2020, 32 patients with advanced local lesions of PGC were treated with extended radical resection. After that, 17 patients were repaired with the free peroneal artery chimeric perforator flaps (trial group) and another 15 patients were repaired with the pedicled pectoralis major myocutaneous flaps (control group). There was no significant difference in gender, age, disease type, histopathological classification, clinical stage, and pathological stage between groups ( P>0.05). The size of skin flap in trial group ranged from 7 cm×6 cm to 12 cm×8 cm and the size of soleus muscle flap ranged from 5 cm×3 cm to 6 cm×4 cm. The donor sites were repaired with skin grafting. The size of the pedicled pectoralis major myocutaneous flaps in control group ranged from 9 cm×6 cm to 14 cm×7 cm. The donor sites were sutured directly. The operation time, survival rate of flap, and postoperative survival of patients were recorded and compared between groups. At 1 year after operation, the University of Washington quality of life (UW-QOL) questionnaire was used to evaluate the quality of life of patients in the two groups, including appearance, shoulder movement, sociability, masticatory function, speech function, and mood. Results: The operations completed successfully. The operation time was (6.19±0.72) hours in trial group and (6.41±0.71) hours in control group, showing no significant difference between groups ( t=-0.863, P=0.395). The survival rate of flap in trial group was 94.1% (16/17); and 1 patient suffered from vascular crisis after operation and was replaced with the pedicled pectoralis major myocutaneous flap. The survival rate of flap in control group was 100%. All grafts survived and the incisions healed by first intention in the two groups. All patients were followed up. The follow-up time was 6-60 months (median, 60 months) in trial group and 7-60 months (median, 60 months) in control group. Cumulative survival rates of patients at 1, 3, and 5 years after operation were 94.1%, 64.7%, and 58.8% in trial group, respectively; 86.7%, 66.7%, and 53.3% in control group, respectively. There was no significant difference in the cumulative survival rate between groups ( χ 2=0.090, P=0.762). According to the UW-QOL questionnaire at 1 year after operation, the scores of appearance, shoulder movement, sociability, and mood in trial group were significantly higher than those in control group ( P<0.05); and there was no significant difference in masticatory function and speech function scores between groups ( P>0.05). Conclusion: The peroneal artery perforator has an invariable anatomical relationship. Each perforator emits the muscular branch that nourishes the soleus muscle. Therefore, personalized free peroneal artery chimeric perforator flap can be designed according to the tissue defect, and used to repair the defect after advanced local lesions resection in PGC.

2.
Chemistry ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837718

RESUMO

Electron-transferable oxidants such as B(C 6 F 5 ) 3 / n BuLi, B(C 6 F 5 ) 3 /LiB(C 6 F 5 ) 4 , B(C 6 F 5 ) 3 /LiHBEt 3 , Al(C 6 F 5 ) 3 /( o -RC 6 H 4 )AlH 2 (R = N(CMe 2 CH 2 ) 2 CH 2 ), B(C 6 F 5 ) 3 /AlEt 3 , Al(C 6 F 5 ) 3 , Al(C 6 F 5 ) 3 / n BuLi, Al(C 6 F 5 ) 3 /AlMe 3 , (CuC 6 F 5 ) 4 , and Ag 2 SO 4 , respectively were employed for reactions with (L) 2 Si 2 C 4 (SiMe 3 ) 2 (C 2 SiMe 3 ) 2 (L = PhC(N t Bu) 2 , 1 ). The stable radical cation [ 1 ] +· was formed and paired with the anions  [ n BuB(C 6 F 5 ) 3 ]- (in 2 ), [B(C 6 F 5 ) 4 ]- (in 3 ), [HB(C 6 F 5 ) 3 ]- (in 4 ), [EtB(C 6 F 5 ) 3 ]- (in 5 ), {[(C 6 F 5 ) 3 Al] 2 ( µ -F)]- (in 6 ), [ n BuAl(C 6 F 5 ) 3 ]- (in 7 ), and [Cu(C 6 F 5 ) 2 ]- (in 8 ), respectively. The stable dication [ 1 ] 2+ was also generated with the anions [EtB(C 6 F 5 ) 3 ]- ( 9 ) and [MeAl(C 6 F 5 ) 3 ]- ( 10 ), respectively. In addition, the neutral compound [(L) 2 Si 2 C 4 (SiMe 3 ) 2 (C 2 SiMe 3 ) 2 ][ µ -O 2 S(O) 2 ] ( 11 ) was obtained. Compounds 2 - 11 are characterized by UV-vis absorption spectroscopy, X-ray crystallography, and elemental analysis. Compounds 2 - 8 are analyzed by EPR spectroscopy and compounds 9 - 11 by NMR spectroscopy. The structure features are discussed on the central Si 2 C 4 -rings of 1 , [ 1 ] + ˙, [ 1 ] 2+ , and 11, respectively.

3.
Transl Oncol ; 15(1): 101268, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34800914

RESUMO

OBJECTIVES: This study aimed to explore factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer (aNSCLC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: A total of 101 patients with aNSCLC receiving ICIs were included. The association between clinical factors and multiple endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) were investigated by multivariate analyses. RESULTS: Multivariate logistic analyses revealed that clinical stage, lactate dehydrogena (LDH), and any grade immune-related adverse events (irAEs) were independent predictors of ORR, while LDH and ICIs treatment type were independent predictors of DCR. In Multivariate Cox analysis, Eastern Cooperative Oncology Group performance status (ECOG PS), LDH, albumin (Alb), platelet to lymphocyte ratio (PLR), and any grade irAEs were independent factors for OS. Similarly, clinical stage, LDH, Alb, and any grade irAEs were independent factors for PFS. Pre-treatment prognostic score was established based on clinical stage, ECOG PS, LDH, Alb and PLR to classify patients into three groups: the good group (0-1 score), the intermediate group (2 scores) and the poor group (3-4 scores). The immunotherapy response was significantly different in various prognostic groups. Subset analyses showed pre-treatment prognostic score ≥ 3 tended to have a strong negative impact on survival among patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 50%. CONCLUSIONS: Pre-treatment prognostic score based on clinical stage, ECOG PS, LDH, Alb and PLR may help to identify aNSCLC patients who may benefit from ICIs.

4.
BMC Cancer ; 21(1): 1216, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774014

RESUMO

BACKGROUND: Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. METHODS: Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan-Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). RESULTS: SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297-2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = - 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. CONCLUSION: Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.

5.
J Cancer ; 12(23): 6964-6978, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729099

RESUMO

Objective: Cyclin-dependent kinase regulatory subunit 2 (CKS2) plays a vital role in regulation of the cell cycle and cancer progression. However, the role of CKS2 in lung adenocarcinoma (LUAD) remains unkonwn. Here, we examined the prognostic value and biological functions of CKS2 in LUAD by using omics data of 1,235 LUAD samples from TCGA, GEO, and our own cohort as well as data of in vitro experiments. Methods: Kaplan-Meier was conducted to evaluate the prognostic value of CKS2 expression. The association between CKS2 expression level and tumor immune infiltration was explored using the single-sample Gene Set Enrichment Analysis (ssGSEA) and TIMER database. Functional enrichment analyses were performed to annotate the biological functions of CKS2 in LUAD. Furthermore, a series of in vitro experiments and immunohistochemistry were performed for validation. Results: CKS2 overexpression was correlated with the advanced stage, TP53 status, PD-L1 expression, and DNA hypomethylation. Moreover, patients with LUAD and high CKS2 expression exhibited poor overall survival. Functional enrichment analysis indicated that CKS2 was involved in cell division, cell cycle, DNA replication. Experiments in vitro indicated that CKS2 knockdown decreased the invasion and proliferation of LUAD cells and facilitated their apoptosis. ssGSEA and TIMER analysis revealed a negative correlation between CKS2 expression and the immune cell infiltration. Conclusions: In summary, High CKS2 expression was associated with poor prognosis and low levels of infiltrating immune cells in LUAD as well as with malignant phenotypes. Therefore, CKS2 may be a promising prognostic biomarker and therapeutic target in LUAD.

6.
Anal Bioanal Chem ; 413(28): 7031-7041, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34661725

RESUMO

Salinomycin (SAL) and lasalocid (LAS) are widely used as ionophore antibiotics for coccidiosis control. However, their common use as feed additives has led to the occurrence of feed cross-contamination, which has toxic effects on non-target animals. There have been few reports on multiple-residue detection for SAL and LAS in recent years. In this study, two single-chain antibody fragments (scFvs) capable of specifically recognizing SAL and LAS were constructed. Using LAS-scFv and SAL-scFv as parent antibodies, a complete bispecific single-chain diabody (scDb) against both LAS and SAL was built using splicing by overlap extension polymerase chain reaction (SOE-PCR). In addition, the key amino acid sites and interaction energy of antibody variable regions for small-molecule recognition were preliminarily studied by homology modeling and molecular docking. Finally, IC50 values of 12.9 and 8.6 ng/mL, with a linear range of 6.9-24.0 and 4.7-16.0 ng/mL, were obtained for LAS-scFv and SAL-scFv, respectively. An indirect competitive enzyme-linked immunosorbent assay (icELISA) method was established using scDb to obtain an IC50 of 3.5 ng/mL for LAS and 4.1 ng/mL for SAL, which showed better sensitivity and specificity than those of the parent scFv antibodies. The recoveries of LAS and SAL in chicken liver were 89.2-92.7%(CV<4.7%) and 88.6-90.2% (CV<6.8%)), respectively.

7.
Radiat Oncol ; 16(1): 207, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717670

RESUMO

OBJECTIVE: There is still no definitely therapeutic evidence of a beneficial effect of chemotherapy with radiotherapy for older patients with esophageal squamous cell carcinoma (ESCC). We aim to determine the influence of chemoradiotherapy (CRT) and radiotherapy (RT) alone in patients aged 65 years or older with locally advanced ESCC. METHODS: We retrospectively analyzed 581 ESCC patients who underwent CRT and RT alone. Univariate and multivariate Cox regression analysis was used to analyze the impact of clinical factors on long-term overall survival (OS) and progression-free survival (PFS). Finally, we compared the toxicity rates of these patients. RESULTS: The median OS and PFS of the overall population were 23.2 months (2.0-162.6 months) and 18.6 months (1.1-159.6 months). Multivariate Cox regression analysis showed that chemotherapy (p < 0.05), tumor thickness (p < 0.01), and N stage (p < 0.05) were independent prognostic factors associated with both OS and PFS. In the chemotherapy subgroup, patients who received 2-8 cycles of chemotherapy had better OS than those who received 1 cycle (p = 0.015). The results also revealed that the CRT group has better OS and PFS than RT alone group for patients aged 65-74 years (both p < 0.01). However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone (both p > 0.05). Besides, higher staged ESCC has the inferior OS and PFS than lower staged ESCC for patients received RT alone and aged 65-74 years (both p < 0.05). Finally, there were significantly more severe hematologic toxicities in the CRT group than in those treated with RT alone in this study (p < 0.001). CONCLUSIONS: The present study suggested that CRT for locally advanced ESCC in patients aged 65 years or older had a significant benefit over RT alone in terms of OS and PFS. However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone. CRT should be performed with special attention in patients aged 75 years or older.

8.
JAMA ; 326(10): 916-925, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519801

RESUMO

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Método Duplo-Cego , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Placebos , Intervalo Livre de Progressão , Qualidade de Vida , Análise de Sobrevida
9.
Chem Asian J ; 16(21): 3453-3461, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473912

RESUMO

Reactions of N,P-Ligands as Ph2 P(o-NMe2 C6 H4 ) (1 L), 2,6-iPr2 C6 H3 NHC(Ph)=NC6 H4 (o-PPh2 ) (2 L), and Ph2 PN(R)PPh2 (R=iPr (3 L), cyclo-C6 H11 (4 L), tBu (5 L), CH2 C4 H7 O (6 L)) each with dicobalt octacarbonyl produced complexes [1 LCo(CO)3 ]2 (1), [2 LCo(CO)(µ-CO)2 Co(CO)3 ] (2), [3 LCo(CO)3 ]+ [Co(CO)4 ]- (3), [3 LCo(CO)2 ]2 (4), [4 LCo(CO)2 ]2 (5), [5 LCo(CO)2 ]+ [Co(CO)4 ]- (6), and [6 LCo(CO)2 ]+ [Co(CO)4 ]- (7). Complexes 1-7 have all been structurally characterized by X-ray crystallography, IR and NMR spectroscopies, and elemental analysis. Catalytic tests on transformation of ethylene oxide (EO), CO and MeOH into methyl 3-hydroxypropionate (3-HMP) indicate that complexes 1-7 are active, where ion-pair complexes 3 and 6-7 behave more excellently (by achieving 88.4-93.6% 3-HMP yields) than the neutral species 1-2 and 4-5 (35.0-46.5% 3-HMP yields) when the reactions are all operated at 2 MPa CO pressure and 50 °C in MeOH solvent. Density functional theory (DFT) study by selecting 3 as a model suggests a cooperative catalytic reaction mechanism by [Co(CO)4 ]- and its counter cation [3 LCo(CO)3 ]+ . The cobalt-homonuclear ion-pair catalyzed hydroalkoxycarbonylation of EO is present herein.

10.
JAMA Oncol ; 7(10): 1459-1466, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34351356

RESUMO

Importance: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. Objective: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. Design, Setting, and Participants: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. Interventions: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. Main Outcomes and Measures: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. Results: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. Conclusions and Relevance: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02813967.

11.
Onco Targets Ther ; 14: 4415-4426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408438

RESUMO

Introduction: The aim of this study was to investigate the role and mechanism of long non-coding RNA (lncRNA) TRG-AS1 in mediating the proliferation, invasion and migration of lung cancer cells as well lung tumor growth. Methods: Firstly, the expression levels of TRG-AS1, miR-224-5p in lung cancer tissues or cells were quantified by quantitative real-time PCR. Western blot analysis was conducted to measure the expression levels of protein SMAD4. CCK-8 assay, wound healing assay and transwell assay were conducted to evaluate cell proliferation, migration and invasion, respectively. The interaction between TRG-AS1 and miR-224-5p was predicted by bioinformatics analysis. Dual-luciferase assay and RNA pull-down assay were performed to further confirm their interaction. In addition, the interaction between miR-224-5p and SMAD4 was detected by RIP assay. Results: The results showed that TRG-AS1 was highly upregulated and miR-224-5p was downregulated in lung cancer. A negative correlation was found between TRG-AS1 and miR-224-5p. Furthermore, upregulation of TRG-AS1 promoted cell proliferation and invasion, while overexpression of miR-224-5p attenuated the effects of TRG-AS1. The downstream protein SMAD4 played an important role. In vivo study showed that knockdown of TRG-AS1 effectively retarded tumor growth. Discussion: Our data suggested that the TRG-AS1/miR-224-5p/SMAD4 axis may be a potential therapeutic target in lung cancer.

12.
Future Oncol ; 17(31): 4081-4089, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34269067

RESUMO

Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcÉ£R binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.

13.
Artigo em Chinês | MEDLINE | ID: mdl-34304532

RESUMO

Objective:To investigate the treatment effect of oral and oropharyngeal cancer resection through oral approach. Methods:Forty-eight patients who with oral and oropharyngeal cancer were admitted to the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Bengbu Medical College from January 2015 to January 2018, and all received preoperative chemotherapy, surgical treatment and postoperative radiotherapy. Among them, twenty-four patients who were treated with tumor resection through oral approach in the experimental group, the other twenty-four patients were treated with tumor resection by external approach in the control group. During the operation, both groups of patients were underwent selective neck lymph node dissection and free skin flap transplantation, and preventive radiotherapy were performed after the operation. The operation time, blood loss, and the positive rate of the wound around the wound and the undercut margin of the two groups were compared, and the survival rate of the skin flap was analyzed. The Kaplan-Meier method was used to calculate the survival rate after 3 years of regular follow-up after surgery, and the difference between the curves of the two surgical methods were compared by the Log-rank test, and the quality of life of patients in one year after operation was investigated and analyzed by Washington University students'quality questionnaire 4. Results:The operation time and blood loss of the experimental group were less than the control group, but the difference was not statistically significant(P>0.05). The positive rate of frozen margins in both groups was 0. The flap survival rate was 95.8% in the experimental group and 91.7% in the control group, there was no significant difference between the two groups(P>0.05), the overall flap survival rate in the two groups was 93.8%. The survival rates of the experimental group were 91.7%, 83.3%, and 74.8% in the 1-, 2-, and 3-years after surgery, and 87.5%, 79.2%, and 75.0% in the control group, there was no statistically significant difference between the experimental group and the control group(P>0.05). The 1-year, 2-year and 3-year overall survival rates of the two groups were 93.1%, 83.7% and 78.8% respectively. Compared with the control group, the scores of appearance, activity, recreation, swallowing, chewing, speech and mood in the experimental group were significantly higher(P<0.05). Conclusion:Resection of oral cancer tumors through the oral approach with free skin flap repair is in line with the concept of minimally invasive surgery, which improves the quality of life of patients after surgery while ensuring the survival rate, and is worthy of clinical application and promotion.


Assuntos
Retalhos de Tecido Biológico , Neoplasias Orofaríngeas , Humanos , Esvaziamento Cervical , Neoplasias Orofaríngeas/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Transplante de Pele , Resultado do Tratamento
14.
Front Oncol ; 11: 687035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249736

RESUMO

Objective: Radiation esophagitis (RE) is common in patients treated with radiotherapy (RT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aim to construct a nomogram predicting the severe RE (grade ≥2) in patients with ESCC receiving definitive chemoradiotherapy (dCRT). Materials and Methods: Logistic regression was performed to evaluate the risk factors in predicting RE. Nomogram was built based on the multivariate analysis result. The model was validated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analyses (DCA). Spearman correlation analysis was used to evaluate the correlation between inflammation indexes. Results: A total of 547 patients with stage II-IVA ESCC treated with dCRT from the retrospective study were included. Two hundred and thirty-two of 547 patients (42.4%) developed grade ≥2 RE. Univariate analysis indicated that gender (p = 0.090), RT dose (p < 0.001), targeted therapy (p = 0.047), tumor thickness (p = 0.013), lymphocyte-monocyte ratio (LMR, p = 0.016), neutrophil-lymphocyte ratio (NLR, p < 0.001), and platelet-lymphocyte ratio (PLR, p < 0.001) were the significant factors for a higher incidence of RE. In multivariate analysis, RT dose [p < 0.001; odds ratio (OR), 4.680; 95% confidence interval (CI), 2.841-6.709], NLR (p < 0.001; OR, 0.384; 95% CI, 0.239-0.619), and PLR (p < 0.001; OR, 3.539; 95% CI: 2.226-5.626) were independently associated grade ≥2 RE and were involved in the nomogram. ROC curves showed the AUC of the nomogram was 0.714 (95% CI, 0.670-0.757), which was greater than each factor alone (RT dose: 0.615; NLR: 0.596; PLR: 0.590). Calibration curves showed good consistency between the actual observation and the predicted RE. DCA showed satisfactory positive net benefits of the nomogram among most threshold probabilities. Conclusions: The study demonstrated that RT dose, NLR, and PLR were independent risk factors for grade ≥2 RE in patients with locally advanced ESCC receiving dCRT. A predictive model including all these factors was built and performed better than it based on each separately. Further validation in large patient populations is still warranted.

15.
Sci Rep ; 11(1): 13281, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168239

RESUMO

GREB1L is a protein-coding gene that is an important paralog of GREB1. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of GREB1L in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between GREB1L and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, HPA, TIMER, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, GREB1L expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high GREB1L expression levels were correlated with a poor OS in LUAD. Additionally, GREB1L expression was independently associated with OS through a multivariate Cox analysis. GSEA analysis revealed enrichment in cell cycle, immune regulation, and methylation. Moreover, high GREB1L expression was associated with poor survival. We also found that the methylation and genetic alteration level was associated with prognosis in patients with LUAD. Finally, an analysis of immune infiltration showed that GREB1L is correlated with immune cell infiltration, PD-1, and PD-L1. In summary, these results indicate that GREB1L is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Proteínas de Neoplasias/metabolismo , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Idoso , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
16.
Gene ; 790: 145689, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-33964375

RESUMO

OBJECTIVE: GALNT2/14 are members of the glycosyltransferase protein family, which initiate mucin-type O-glycosylation of peptides in the Golgi apparatus. However, the correlation between GALNT2/14 and disease prognosis and methylation in lung adenocarcinoma (LUAD) remains unclear. Thus, we sought to identify their potential values in LUAD. METHODS: GALNT2/14 expressions were analyzed using publicly-available datasets. The association between GALNT2/14 and disease prognosis was evaluated. In addition, gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of GALNT2/14. The correlation between the copy number variations and methylation level of GALNT2/14 and their mRNA expressions was analyzed via cBioPortal. Finally, we explored the prognostic value of the GALNT2/14 methylation levels by MethSurv in LUAD. RESULTS: GALNT2/14 were highly expressed in LUAD tumor tissue than normal tissue (P < 0.001). Multivariate analysis showed that high GALNT2/14 expressions were both an independent prognostic factor. GSEA found that GALNT2/14 expressions were associated with the methylation, gene silencing, and cell division, whereas immune analysis showed that GALNT2/14 expressions positively correlated with the expression level of PD-L1. Finally, the methylation levels of GALNT2/14 negatively correlated with the GALNT2/14 expressions (R = -0.26 and -0.36, P < 0.001, respectively), and patients with GALNT2/14 hypomethylation had worse overall survival than patients with high methylation (P < 0.05). CONCLUSIONS: This study demonstrated that the overexpression of GALNT2/14 in LUAD can serve as biomarkers for poor prognosis. The biological functions of GALNT2/14 are potentially related to methylation, gene silencing, tumorigenesis, and cell division. These findings help elucidate the role of GALNT2/14 in tumorigenesis and provide additional insight for therapy and prognosis of LUAD.


Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , N-Acetilgalactosaminiltransferases/genética , Adenocarcinoma de Pulmão/genética , Variações do Número de Cópias de DNA , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Prognóstico , Taxa de Sobrevida
17.
Nat Commun ; 12(1): 2989, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34017000

RESUMO

The allogeneic transplantation of primordial germ cells (PGCs) derived from somatic cells overcomes the limitation of avian cloning. Here, we transdifferentiate chicken embryo fibroblasts (CEFs) from black feathered Langshan chickens to PGCs and transplant them into White Plymouth Rock chicken embryos to produce viable offspring with characteristics inherited from the donor. We express Oct4/Sox2/Nanog/Lin28A (OSNL) to reprogram CEFs to induced pluripotent stem cells (iPSCs), which are further induced to differentiate into PGCs by BMP4/BMP8b/EGF. DNA demethylation, histone acetylation and glycolytic activation elevate the iPSC induction efficiency, while histone acetylation and glycolytic inhibition facilitate PGCs formation. The induced PGCs (iPGCs) are transplanted into the recipients, which are self-crossed to produce 189/509 somatic cells derived chicken with the donor's characteristics. Microsatellite analysis and genome sequencing confirm the inheritance of genetic information from the donor. Thus, we demonstrate the feasibility of avian cloning from somatic cells.


Assuntos
Transdiferenciação Celular/genética , Clonagem de Organismos/métodos , Células Germinativas/transplante , Células-Tronco Pluripotentes Induzidas/fisiologia , Criação de Animais Domésticos/métodos , Animais , Proteína Morfogenética Óssea 4/genética , Células Cultivadas , Embrião de Galinha/citologia , Galinhas , Fator de Crescimento Epidérmico/genética , Estudos de Viabilidade , Fibroblastos/fisiologia , Células Germinativas/fisiologia , Proteína Homeobox Nanog/genética , Fator 3 de Transcrição de Octâmero/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição SOXB1/genética , Transplante Homólogo/métodos
18.
J Am Chem Soc ; 143(22): 8244-8248, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34037391

RESUMO

Two silylene molecules oxidatively react under formal [1 + 2 + 1]-cycloaddition to the C≡N bond of nitriles to yield 1-aza-2,4-disilabicyclo[1.1.0]butanes (L)(Cl)Si[µ-η1,2-NC(p-RC6H4)]Si(Cl)(L) (L = PhC(NtBu)2, R = CF3 (2), F (3), Cl (4), Br (5)). The strongly folded bicyclic SiCNSi cores in 2-5 feature inverted bridgehead carbon atoms and superelongated C-N bonds [1.745(12) to 1.801(2) Å], exceeding the lengths of C-N single bonds in known silaaziridines by up to 23%. Detailed bonding analysis discloses C-N bonding interactions, sharing far-reaching similarities with the central C-C bond in [1.1.1]propellane.

19.
Opt Lett ; 46(9): 2115-2118, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929431

RESUMO

In this Letter, we design and realize a hybrid-cavity laser with single- or dual-mode lasing states and study the nonlinear states of the laser under external optical feedback (EOF). The laser at a dual-mode state easily and directly enters the chaotic state without periodic oscillation states and display chaos for a much wider range of the EOF magnitude than the laser at a single-mode state. A flat chaotic signal is obtained for the laser at a dual-mode lasing state under a weak EOF benefitting from the low-frequency energy enhancement caused by mode competition between the dual modes.

20.
Int J Radiat Oncol Biol Phys ; 110(5): 1396-1406, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33677048

RESUMO

PURPOSE: To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. METHODS AND MATERIALS: Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. RESULTS: With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). CONCLUSION: Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Radioterapia de Intensidade Modulada/métodos , Idoso , China , Cisplatino/uso terapêutico , Intervalos de Confiança , Fracionamento da Dose de Radiação , Esquema de Medicação , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/radioterapia , Estudos de Viabilidade , Feminino , Fluoruracila/uso terapêutico , Humanos , Linfonodos/diagnóstico por imagem , Irradiação Linfática , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/uso terapêutico , Estudos Prospectivos , Fatores de Tempo , Falha de Tratamento
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