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1.
Cancer Immunol Immunother ; 73(10): 189, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093404

RESUMO

BACKGROUND: The interplay between regulatory T cells (Tregs) and neighboring cells, which is pivotal for anti-tumor immunity and closely linked to patient prognosis, remains to be fully elucidated. METHODS: Tissue microarrays of 261 operable NSCLC patients were stained by multiplex immunofluorescence (mIF) assay, and the interaction between Tregs and neighboring cells in the tumor microenvironment (TME) was evaluated. Employing various machine learning algorithms, we developed a spatial immune signature to predict the prognosis of NSCLC patients. Additionally, we explored the interplay between programmed death-1/programmed death ligand-1 (PD-1/PD-L1) interactions and their relationship with Tregs. RESULTS: Survival analysis indicated that the interplay between Tregs and neighboring cells in the invasive margin (IM) and tumor center was associated with recurrence in NSCLC patients. We integrated the intersection of the three algorithms to identify four crucial spatial immune features [P(CD8+Treg to CK) in IM, P(CD8+Treg to CD4) in IM, N(CD4+Treg to CK) in IM, N(CD4+Tcon to CK) in IM] and employed these characteristics to establish SIS, an independent prognosticator of recurrence in NSCLC patients [HR = 2.34, 95% CI (1.53, 3.58), P < 0.001]. Furthermore, analysis of cell interactions demonstrated that a higher number of Tregs contributed to higher PD-L1+ cells surrounded by PD-1+ cells (P < 0.001) with shorter distances (P = 0.004). CONCLUSION: We dissected the cell interplay network within the TME, uncovering the spatial architecture and intricate interactions between Tregs and neighboring cells, along with their impact on the prognosis of NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Linfócitos T Reguladores , Microambiente Tumoral , Humanos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linfócitos T Reguladores/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Microambiente Tumoral/imunologia , Recidiva Local de Neoplasia/imunologia , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo
2.
Nat Commun ; 15(1): 5150, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886387

RESUMO

Nanoplasmas induced by intense laser fields have attracted enormous attention due to their accompanied spectacular physical phenomena which are vigorously expected by the community of science and industry. For instance, the energetic electrons and ions produced in laser-driven nanoplasmas are significant for the development of compact beam sources. Nevertheless, effective confinement on the propagating charged particles, which was realized through magnetic field modulation and target structure design in big facilities, are largely absent in the microscopic regime. Here we introduce a reliable scheme to provide control on the emission direction of protons generated from surface ionization in gold nanoparticles driven by intense femtosecond laser fields. The ionization level of the nanosystem provides us a knob to manipulate the characteristics of the collective proton emission. The most probable emission direction can be precisely steered by tuning the excitation strength of the laser pulses. This work opens new avenue for controlling the ion emission in nanoplasmas and can vigorously promote the fields such as development of on-chip beam sources at micro-/nano-scales.

3.
Int J Biol Macromol ; 261(Pt 1): 129584, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246443

RESUMO

Disulfidptosis, a recently identified mode of cellular demise marked by excess SLC7A11-reliant cystine, has been proved to affect the development and resilience of tumor cells through the production of glutathione from cystine. Glutathione synthesis plays a crucial role in chemotherapy resistance and the survival of liver cancer cells. Thus, understanding the relationship between disulfidptosis and hepatocellular carcinoma (HCC) is imperative. A molecular typing approach was employed to classify patients with HCC into two distinct subtypes, namely disulfidptosis and disulfide-homeostasis, based on the expression of genes associated with disulfidptosis. Patients with disulfidptosis exhibited a longer survival time, improved immune status, and heightened sensitivity to conventional chemotherapeutic drugs and immunotherapy. Patients with disulfide-homeostasis demonstrated an immunosuppressive microenvironment, drug resistance, and unfavorable prognosis. A prognostic model was constructed utilizing the significant prognostic variables of the disulfidptosis-regulated genes. A real-world cohort was subjected to multiplex immunofluorescence to validate the clinical outcomes and immune context. Ultimately, our study delved into the prognostic relevance of disulfidptosis in HCC and provides insights into potential avenues for future research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Cistina , Microambiente Tumoral/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Dissulfetos , Glutationa
4.
J Transl Med ; 22(1): 27, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183111

RESUMO

BACKGROUND: Tissue-resident memory T (TRM) cells can reside in the tumor microenvironment and are considered the primary response cells to immunotherapy. Heterogeneity in functional status and spatial distribution may contribute to the controversial role of TRM cells but we know little about it. METHODS: Through multiplex immunofluorescence (mIF) (CD8, CD103, PD-1, Tim-3, GZMB, CK), the quantity and spatial location of TRM cell subsets were recognized in the tissue from 274 patients with NSCLC after radical surgery. By integrating multiple machine learning methods, we constructed a TRM-based spatial immune signature (TRM-SIS) to predict the prognosis. Furthermore, we conducted a CD103-related gene set enrichment analysis (GSEA) and verified its finding by another mIF panel (CD8, CD103, CK, CD31, Hif-1α). RESULTS: The density of TRM cells was significantly correlated with the expression of PD-1, Tim-3 and GZMB. Four types of TRM cell subsets was defined, including TRM1 (PD-1-Tim-3-TRM), TRM2 (PD-1+Tim-3-TRM), TRM3 (PD-1-Tim-3+TRM) and TRM4 (PD-1+Tim-3+TRM). The cytotoxicity of TRM2 was the strongest while that of TRM4 was the weakest. Compare with TRM1 and TRM2, TRM3 and TRM4 had better infiltration and stronger interaction with cancer cells. The TRM-SIS was an independent prognostic factor for disease-free survival [HR = 2.43, 95%CI (1.63-3.60), P < 0.001] and showed a better performance than the TNM staging system for recurrence prediction. Furthermore, by CD103-related GSEA and mIF validation, we found a negative association between tumor angiogenesis and infiltration of TRM cells. CONCLUSIONS: These findings reveal a significant heterogeneity in the functional status and spatial distribution of TRM cells, and support it as a biomarker for the prognosis of NSCLC patients. Regulating TRM cells by targeting tumor angiogenesis may be a potential strategy to improve current immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Receptor Celular 2 do Vírus da Hepatite A , Células T de Memória , Receptor de Morte Celular Programada 1 , Prognóstico , Linfócitos T CD8-Positivos , Microambiente Tumoral
5.
Pediatr Surg Int ; 40(1): 34, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214758

RESUMO

PURPOSE: To evaluate the feasibility of single-site laparoscopic orchiopexy for palpable undescended testes in children. METHODS: We prospectively studied patients with undescended testes between July 2021 and June 2022. In total, 223 patients were included in our study: 105 underwent single-site laparoscopic orchiopexy and 118 underwent conventional laparoscopic orchiopexy. During single-site laparoscopic orchiopexy, 3 ports were inserted within the umbilicus. RESULTS: No differences were observed between the groups in terms of age and laterality. For unilateral undescended testes, the operating time was longer in the single site group than in the conventional group at the early stages (55.31 ± 12.04 min vs. 48.14 ± 14.39 min, P = 0.007), but it was similar to the conventional group at the later stages (48.82 ± 13.49 min vs. 48.14 ± 14.39 min, P = 0.78). Testicular ascent occurred in one patient from each group. There was no significant difference in the success rate between the single-site group and the conventional group (99.0% vs. 99.2%, P = 0.93). In the single-site group, no visible abdominal scarring was observed, while in the conventional group, there were two noticeable scars on the abdomen. CONCLUSION: Single-site laparoscopic orchiopexy offers superior cosmetic results and comparable success rates compared to conventional laparoscopic orchiopexy for palpable undescended testes.


Assuntos
Cavidade Abdominal , Criptorquidismo , Laparoscopia , Criança , Masculino , Humanos , Lactente , Criptorquidismo/cirurgia , Orquidopexia/métodos , Testículo/cirurgia , Estudos Prospectivos , Laparoscopia/métodos , Resultado do Tratamento
6.
BMC Cancer ; 23(1): 549, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37322434

RESUMO

BACKGROUND: Immune-related genes (IRGs) have been confirmed to play an important role in tumorigenesis and tumor microenvironment formation in hepatocellular carcinoma (HCC). We investigated how IRGs regulates the HCC immunophenotype and thus affects the prognosis and response to immunotherapy. METHODS: We investigated RNA expression of IRGs and developed an immune-related genes-based prognostic index (IRGPI) in HCC samples. Then, the influence of the IRGPI on the immune microenvironment was comprehensively analysed. RESULTS: According to IRGPI, HCC patients are divided into two immune subtypes. A high IRGPI was characterized by an increased tumor mutation burden (TMB) and a poor prognosis. More CD8 + tumor infiltrating cells and expression of PD-L1 were observed in low IRGPI subtypes. Two immunotherapy cohorts confirmed patients with low IRGPI demonstrated significant therapeutic benefits. Multiplex immunofluorescence staining determined that there were more CD8 + T cells infiltrating into tumor microenvironment in IRGPI-low groups, and the survival time of these patients was longer. CONCLUSIONS: This study demonstrated that the IRGPI serve as a predictive prognostic biomarker and potential indicator for immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Imunoterapia , Prognóstico , Linfócitos T CD8-Positivos , Microambiente Tumoral/genética
7.
J Transl Med ; 21(1): 320, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173705

RESUMO

BACKGROUND: Anti-PD-(L)1 immunotherapy has been recommended for non-small cell lung cancer (NSCLC) patients with lymph node metastases (LNM). However, the exact functional feature and spatial architecture of tumor-infiltrating CD8 + T cells remain unclear in these patients. METHODS: Tissue microarrays (TMAs) from 279 IA-IIIB NSCLC samples were stained by multiplex immunofluorescence (mIF) for 11 markers (CD8, CD103, PD-1, Tim3, GZMB, CD4, Foxp3, CD31, αSMA, Hif-1α, pan-CK). We evaluated the density of CD8 + T-cell functional subsets, the mean nearest neighbor distance (mNND) between CD8 + T cells and neighboring cells, and the cancer-cell proximity score (CCPS) in invasive margin (IM) as well as tumor center (TC) to investigate their relationships with LNM and prognosis. RESULTS: The densities of CD8 + T-cell functional subsets, including predysfunctional CD8 + T cells (Tpredys) and dysfunctional CD8 + T cells (Tdys), in IM predominated over those in TC (P < 0.001). Multivariate analysis identified that the densities of CD8 + Tpredys cells in TC and CD8 + Tdys cells in IM were significantly associated with LNM [OR = 0.51, 95%CI (0.29-0.88), P = 0.015; OR = 5.80, 95%CI (3.19-10.54), P < 0.001; respectively] and recurrence-free survival (RFS) [HR = 0.55, 95%CI (0.34-0.89), P = 0.014; HR = 2.49, 95%CI (1.60-4.13), P = 0.012; respectively], independent of clinicopathological factors. Additionally, shorter mNND between CD8 + T cells and their neighboring immunoregulatory cells indicated a stronger interplay network in the microenvironment of NSCLC patients with LNM and was associated with worse prognosis. Furthermore, analysis of CCPS suggested that cancer microvessels (CMVs) and cancer-associated fibroblasts (CAFs) selectively hindered CD8 + T cells from contacting with cancer cells, and were associated with the dysfunction of CD8 + T cells. CONCLUSION: Tumor-infiltrating CD8 + T cells were in a more dysfunctional status and in a more immunosuppressive microenvironment in patients with LNM compared with those without LNM.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Estado Funcional , Linfócitos do Interstício Tumoral/patologia , Linfócitos T CD8-Positivos , Prognóstico , Microambiente Tumoral
8.
Opt Express ; 31(6): 9678-9687, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157532

RESUMO

The near-field enhancement effect in nanoparticles dominates the dynamical response of the atoms and molecules within the nanosystem when interacting with ultrashort laser pulses. In this work, using the single-shot velocity map imaging technique, the angle-resolved momentum distributions of the ionization products from surface molecules in gold nanocubes have been obtained. The far-field momentum distributions of the H+ ions can be linked with the near field profiles demonstrated by a classical simulation considering the initial ionization probability and the Coulomb interactions among the charged particles. This research provides an approach to look at the nanoscale near field distribution in the extreme interactions of femtosecond laser pulses and nanoparticles, paving the way for exploring the complex dynamics.

9.
Cancer Immunol Immunother ; 72(7): 2015-2027, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36738309

RESUMO

PURPOSE: To explore the relationship between the spatial interaction of programmed death-ligand 1(PD-L1)-positive tumor cell and T cell with specific functions and the recurrence of non-small cell lung cancer (NSCLC) and optimize prognostic stratification. MATERIALS AND METHODS: This study retrospectively included 104 patients with locally advanced NSCLC who underwent radical surgery. Tissue microarrays were constructed including tumor center (TC) and invasion margin (IM), and CK/CD4/CD8/PD-L1/programmed death-1 (PD-1) was labeled using multiplex immunofluorescence to decipher the counts and spatial distribution of tumor cells and T cells. The immune microenvironment and recurrence stratification were characterized using the Mann-Whitney U test and Cox proportional hazards model. RESULT: Compared with the IM, the proportion of tumor cells (especially PD-L1+) was increased in the TC, while T cells (especially PD-1+) were decreased. An increase in TC PD-1+ CD8 T cells promoted relapse (HR = 2.183), while PD-L1+ tumor cells alone or in combination with T cells had no predictive value for relapse. In addition, in both TC and IM, CD8 were on average closer to PD-L1+ tumor cells than CD4, especially exhausted CD8. The effective density and percentage of PD-1+ CD4 T cells interacting with PD-L1+ tumor cells in the IM were both associated with recurrence, and the HRs increased sequentially (HRs were 2.809 and 4.063, respectively). Patients with low PD-1+CD4 count combined high PD-1+CD4 effective density showed significantly poorer RFS compared to those with high PD-1+CD4 count combined low PD-1+CD4 effective density, in both the TC and IM regions (HRs were 5.810 and 8.709, respectively). CONCLUSION: Assessing the relative spatial proximity of PD-1/PD-L1 contributes to a deeper understanding of tumor immune escape and generates prognostic information in locally advanced NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Estudos Retrospectivos , Receptor de Morte Celular Programada 1 , Recidiva Local de Neoplasia/patologia , Prognóstico , Linfócitos T CD8-Positivos , Linfócitos do Interstício Tumoral , Microambiente Tumoral
10.
Front Endocrinol (Lausanne) ; 13: 980582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157447

RESUMO

Dedifferentiated thyroid cancer is the major cause of mortality in thyroid cancer and is difficult to treat. Hence, the essential molecular mechanisms involved in dedifferentiation should be thoroughly investigated. Several studies have explored the biomolecular modifications of dedifferentiated thyroid cancer such as DNA methylation, protein phosphorylation, acetylation, ubiquitination, and glycosylation and the new targets for radiological imaging and therapy in recent years. Novel radionuclide tracers and drugs have shown attractive potential in the early diagnosis and treatment of dedifferentiated thyroid cancer. We summarized the updated molecular mechanisms of dedifferentiation combined with early detection by molecular modification-based imaging to provide more accurate diagnosis and novel therapeutics in the management of dedifferentiated thyroid cancer.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Imagem Molecular , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética
11.
Phys Rev Lett ; 129(5): 057402, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35960578

RESUMO

Exciton polaritons have shown great potential for applications such as low-threshold lasing, quantum simulation, and dissipation-free circuits. In this paper, we realize a room temperature ultrafast polaritonic switch where the Bose-Einstein condensate population can be depleted at the hundred femtosecond timescale with high extinction ratios. This is achieved by applying an ultrashort optical control pulse, inducing parametric scattering within the photon part of the polariton condensate via a four-wave mixing process. Using a femtosecond angle-resolved spectroscopic imaging technique, the erasure and revival of the polariton condensates can be visualized. The condensate depletion and revival are well modeled by an open-dissipative Gross-Pitaevskii equation including parametric scattering process. This pushes the speed frontier of all-optical controlled polaritonic switches at room temperature towards the THz regime.

12.
Phys Rev Lett ; 128(24): 243201, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35776471

RESUMO

Rotational dynamics of D_{2} molecules inside helium nanodroplets is induced by a moderately intense femtosecond pump pulse and measured as a function of time by recording the yield of HeD^{+} ions, created through strong-field dissociative ionization with a delayed femtosecond probe pulse. The yield oscillates with a period of 185 fs, reflecting field-free rotational wave packet dynamics, and the oscillation persists for more than 500 periods. Within the experimental uncertainty, the rotational constant B_{He} of the in-droplet D_{2} molecule, determined by Fourier analysis, is the same as B_{gas} for an isolated D_{2} molecule. Our observations show that the D_{2} molecules inside helium nanodroplets essentially rotate as free D_{2} molecules.

13.
Quant Imaging Med Surg ; 12(5): 2658-2671, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35502390

RESUMO

Background: We developed and validated novel radiomics-based nomograms to identify epidermal growth factor receptor (EGFR) mutations and the Ki-67 proliferation index of non-small cell lung cancer. Methods: We enrolled 132 patients with histologically verified non-small cell lung cancer from four hospital institutions who underwent computed tomography (CT) scans. EGFR mutations and the Ki-67 proliferation index were measured from tumor tissues. A total of 1,287 radiomic features were extracted, and a three-stage feature selection method was implemented to acquire the most valuable radiomic features. Finally, the radiomic scores and nomograms of the two tasks were established and tested. Receiver operating characteristic curves, calibration curves, and decision curves were used to evaluate their prediction performance and clinical utility. Results: In task [1], smoking status and histological type were significantly associated with EGFR mutations. After feature selection, 10 features were used to establish radiomic score, which showed good performance [area under the curve (AUC) =0.800] in the validation cohort. The radiomic nomogram had an AUC of 0.798 (95% CI: 0.664 to 0.931) with a C-index of 0.798 in the validation cohort. In task [2], gender, smoking status, histological type, and stage showed a significant correlation with Ki-67 proliferation index expression. A total of 28 features were selected to develop a radiomic score, with an AUC of 0.820 in the validation cohort. The final nomogram showed an AUC of 0.828 (95% CI: 0.703 to 0.953) with a C-index of 0.828 in the validation cohort. Conclusions: EGFR mutations and Ki-67 proliferation index in non-small cell lung cancer can be predicted efficiently by the novel radiomic scores and nomograms.

14.
J Phys Condens Matter ; 34(22)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35290965

RESUMO

Based on ZnO microcavities with high quality factors, where the gain medium exhibits confinement of wave packets due to the intrinsically formed whispering gallery microcavity, strong coupling between excitons and cavity photons can be obtained at room temperature resulting in hybrid quasiparticles, e.g. exciton polaritons. In this work, polariton condensation is induced under the non-resonant excitation by linearly polarized femtosecond laser pulses with different polarization directions. The dynamical angle-resolvedk-space spectra of the photoluminescence emission of polariton condensates are measured with sub-picosecond resolution by the self-developed femtosecond angle-resolved spectroscopic imaging technique. Our results show that the ultrafast dynamics of polariton condensation is sensitive to the polarization direction of the excitation pulses which can be explained qualitatively by the combined effect of selective excitation of distinct exciton modes in the sample and the effective coupling strength of the excitation pulses in the ZnO microcavity for various polarization directions. This work strengthened the understanding of the condensation process for cavity exciton polaritons at room temperature.

15.
Nano Lett ; 22(5): 2023-2029, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35200029

RESUMO

Whispering gallery modes in a microwire are characterized by a nearly equidistant energy spectrum. In the strong exciton-photon coupling regime, this system represents a bosonic cascade: a ladder of discrete energy levels that sustains stimulated transitions between neighboring steps. Here, by using a femtosecond angle-resolved spectroscopic imaging technique, the ultrafast dynamics of polaritons in a bosonic cascade based on a one-dimensional ZnO whispering gallery microcavity are explicitly visualized. Clear ladder-form build-up processes from higher to lower energy branches of the polariton condensates are observed, which are well reproduced by modeling using rate equations. Remarkably, a pronounced superbunching feature, which could serve as solid evidence for bosonic cascades, is demonstrated by the measured second-order time correlation factor. In addition, the nonlinear polariton parametric scattering dynamics on a time scale of hundreds of femtoseconds are revealed. Our understandings pave the way toward ultrafast coherent control of polaritons at room temperature.

16.
Int J Biol Sci ; 18(2): 522-535, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35002507

RESUMO

Background: Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in lung adenocarcinoma have not been fully elucidated. Methods: We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1α expression, degradation, and its binding to VHL. Moreover, an in vivo subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD. Results: Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells in vivo and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines in vitro and in vivo, and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1α degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1α and glycolysis-related genes in vivo. Conclusion: Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1α/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients.


Assuntos
Adenocarcinoma de Pulmão/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , Efeito Warburg em Oncologia , Células A549 , Adenocarcinoma de Pulmão/patologia , Animais , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Acad Radiol ; 29 Suppl 2: S53-S61, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33308945

RESUMO

RATIONALE AND OBJECTIVES: To develop and validate a computed tomography (CT)-based radiomics nomogram for predicting locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: A total of 141 patients with locally advanced NSCLC treated with definitive CRT from January 2014 to December 2017 were included and divided into testing cohort (n = 100) and validation (n = 41) cohort. Radiomics features were extracted from pretreatment contrast enhanced CT. The least absolute shrinkage and selection operator logistic regression was processed to select predictive features from the testing cohort and constructed a radiomics signature. Clinical characteristics and the radiomics signature were analyzed using univariable and multivariate Cox regression. The radiomics nomogram was established with the radiomics signature and independent clinical factors. Harrell's C-index, calibration curves and decision curves were used to assess the performance of the radiomics nomogram. RESULTS: The radiomics signature, which consisted of eight selected features, was an independent factor of LRF. The clinical predictors of LRF were the histologic type and clinical stage. The radiomics nomogram combined with the radiomics signature and clinical prognostic factors showed good performance with C-indexes of 0.796 (95% confidence interval [CI]: 0.709-0.883) and 0.756 (95% CI: 0.674-0.838) in the testing and validation cohorts respectively. Additionally, the combined nomogram resulted in better performance (p < 0.001) for the estimation of LRF than the nomograms with the radiomics signature (C-index: 0.776; 95% CI: 0.686-0.866) or clinical predictors (C-index: 0.641; 95% CI: 0.542-0.740) alone. CONCLUSION: The radiomics nomogram provided the best performance for LRF prediction in patients with locally advanced NSCLC, which may help optimize individual treatments.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Nomogramas , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
18.
Front Immunol ; 13: 1022638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685566

RESUMO

Background: The anti-tumoral or pro-tumoral roles of CD4+ and CD8+ T cells typify the complexity of T cell subsets function in cancer. In the non-small cell lung cancer (NSCLC), the density and topology of distinct T cell phenotypes at the tumor center (TC) versus the invasive margin (IM) are largely unknown. Here, we investigated T cell subsets density and distribution within TC and IM regions in NSCLC and its impact on the prognosis. Methods: We performed multiplex immunofluorescence using a tissue microarray of samples from 99 patients with locally advanced NSCLC to elucidate the distributions of tumor cell, T cell subpopulations (CD4/conventional CD4/regulatory CD4/CD8/cytotoxic CD8/pre-dysfunctional CD8/dysfunctional CD8), microvessel density (MVD), cancer-associated fibroblasts (CAFs) and hypoxia-inducible factor-1α (HIF-1α) in TC and IM tissues. Cell-to-cell nearest neighbor distances and interactions were analyzed using the phenoptrreports R package. Cox regression was used to evaluate the associations between T cell subsets density and proximity to tumor cells and recurrence-free survival (RFS). Correlations between different cell subsets were examined by Spearman's or Kruskal-Wallis tests. Results: In the locally advanced NSCLC, the proportion of tumor cells and CAFs in IM is lower than in the TC, while MVD, CD4+, and CD8+ T lymphocytes were increased, and tumor cells were closer to T lymphocytes and their subsets. The density and proximity of CD4+ and CD8+ T cells in the TC and IM regions were not associated with RFS, but in the IM area, increased density of dysfunctional CD8 and closer regulatory CD4 to tumor cells were independent risk factors for recurrence (HR were 3.536 and 2.884, respectively), and were positively correlated with HIF-1α+CD8 (r = 0.41, P = 0.000) and CAFs (P = 0.017), respectively.s. Conclusions: In locally advanced NSCLC, the functional status of T cells in the IM region is closely related to recurrence. The density of dysfunctional CD8 and the proximity of regulatory CD4 to tumor cells were independent risk factors for recurrence, and are positively correlated with the hypoxia response of CD8+ T cells and CAFs. Targeting hypoxia or CAFs is expected to further sensitize therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos/patologia , Microambiente Tumoral , Estado Funcional , Subpopulações de Linfócitos T/patologia
19.
J Phys Condens Matter ; 34(2)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34614483

RESUMO

In this work, by using femtosecond angle-resolved spectroscopic imaging technique, the ultrafast dynamics of confined exciton-polaritons in an optical induced potential well based on a ZnO whispering-gallery microcavity is explicitly visualized. The sub-picosecond transition between succeeding quantum harmonic oscillator states can be experimentally distinguished. The landscape of the potential well can be modified by the pump power, the spatial distance and the time delay of the two input laser pulses. Clarifying the underlying mechanism of the polariton harmonic oscillator is interesting for the applications of polariton-based optoelectronic devices and quantum information processing.

20.
Opt Express ; 29(20): 31240-31248, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615224

RESUMO

Rather than being freed to the continuum, the strong-field tunneled electrons can make a trajectory driven by the remaining laser fields and have certain probability to be captured by the high lying Rydberg states of the parent atoms or molecules. To explore the effect of molecular orbital on Rydberg state excitation, the ellipticity dependence of Rydberg state yields of N2 and O2 molecules are experimentally investigated using cold target recoil ion momentum spectroscopy and are compared with their counterpart atoms Ar and Xe with comparable ionization potentials. We found the generation probability of the neutral Rydberg fragment O2* was orders of magnitude higher than that of Xe* due to the butterfly-shaped highest occupied molecular orbital of O2. Meanwhile, our experimental and simulation results reveal that it is the initial momentum distribution (determined by the detailed characteristics of orbitals) that finally leads to the tendency that the Rydberg state yield of O2 (Ar) decreased slower than that obtained for Xe (N2) when the ellipticity of the excitation laser field is increased.

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