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1.
J Phys Chem A ; 128(12): 2366-2375, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38489755

RESUMO

Accurate spectroscopic data of carbon dioxide are widely used in many important applications, such as carbon monitoring missions. Here, we present comb-locked cavity ring-down saturation spectroscopy of the second most abundant isotopologue of CO2, 13C16O2. We determined the positions of 88 lines in three vibrational bands in the 1.6 µm region, 30011e/30012e/30013e-00001e, with an accuracy of a few kHz. Based on the analysis of combination differences, we obtained for the first time the ground-state rotational energies with kHz accuracy. We also provide a set of hybrid line positions for 150 13C16O2 transitions. The rotational energies (J < 50) in the 30013e vibrational state can be fitted by a set of rotational and centrifugal constants with deviations within a few kHz, indicating that the 30013e state is free of perturbations. These precise isotopic line positions will be utilized to improve the Hamiltonian model and quantitative remote sensing of carbon dioxide. Moreover, they will help to track changes in the carbon source and sink through isotopic analysis.

2.
Anal Chem ; 95(13): 5652-5660, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36940417

RESUMO

Accurate and sensitive detection of multicomponent trace gases below the parts-per-million (ppm) level is needed in a variety of medical, industrial, and environmental applications. Raman spectroscopy can identify multiple molecules in the sample simultaneously and has excellent potential for fast diagnosis of various samples, but applications are often limited by its sensitivity. In this contribution, we report the development of a cavity-enhanced Raman spectroscopy instrument using a narrow-line width 532 nm laser locked with a high-finesse cavity through a Pound-Drever-Hall locking servo, which allows continuous measurement in a broad spectral range. An intracavity laser power of up to 1 kW was achieved with an incident laser power of about 240 mW, resulting in a significant enhancement of the Raman signal in the range of 200-5000 cm-1 and a sub-ppm sensitivity for various molecules. The technique is applied in the detection of different samples, including ambient air, natural gas, and reference gas of sulfur hexafluoride, demonstrating its capability for the quantitative measurement of various trace components.

3.
Mol Med ; 26(1): 88, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942985

RESUMO

BACKGROUND: Patients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies. To improve outcomes, we retrospectively investigated whether the application of a more comprehensive genetic test of tumor biopsies samples from LABM patients could provide the basis for treatment with more effective tyrosine kinase inhibitors (TKIs) regimens. METHODS: Fine needle biopsies were taken from the primary tumor (PT) and a secondary bone metastasis (BM) of 17 LABM patients before treatment. Simple genetic profiles for selecting therapies were initially obtained using an ARMS-PCR test for EGFR and ALK fusion mutations. More detailed genetic profiles of somatic exon SNVs and CNVs in 457 cancer-related genes were retrospectively derived using capture single molecule amplification and resequencing technology (capSMART). RESULTS: ARMS-PCR identified 14 EGFR positive, 3 EGFR negative and 1 ALK fusion positive patient. A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively. With the exception of two patients, molecular profiling of matching PT and BM biopsies identified a highly shared somatic variant fingerprint, although the BMs exhibited additional genomic instability. In six of 13 EGFR positive patients and in all three EGFR negative patients, examination of the genetic profiles identified additional clinically significant mutations that are known or experimental drug targets for treatment of lung cancer. CONCLUSION: Our findings firstly suggest that treatment regimens based on comprehensive genetic assessment of newly diagnosed LABM patients should target both the PT and secondary BMs, including rogue clones with potential to form new BMs. Second, the additional information gained should allow clinicians to design and implement more personalized treatment regimens and potentially improve outcomes for LABM patients.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Ósseas/secundário , Segunda Neoplasia Primária/etiologia , Transcriptoma , Idoso , Biomarcadores Tumorais , Biópsia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/tratamento farmacológico
4.
Phys Chem Chem Phys ; 22(5): 2841-2848, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31967121

RESUMO

Quantitative determination of atmospheric CO2 concentration by remote sensing relies on accurate line parameters. Lamb dips of the lines up to J'' = 72 in the 30013-00001 band at 1605 nm were measured using a comb-locked cavity ring-down spectrometer, and the positions were determined with an accuracy of a few kHz. A simple effective Hamiltonian model can fit the rotational energies in the 30013 state ideally within the experimental accuracy, indicating that the vibrational state is well-isolated and can be regarded as free from perturbations. From a comparison between other bands using a similar analysis, we conclude that the transitions in the 30013-00001 band could be more suitable as reference lines for sensing applications with the potentially improved line parameter accuracy.

5.
J Clin Lab Anal ; 34(4): e23150, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31923333

RESUMO

BACKGROUND: Early screening and diagnosis of radiation-induced heart disease (RIHD) is difficult in patients with chest radiation exposure. sST-2 is involved in myocardial stress or injury. We evaluated the relationship between heart dose parameters and sST-2 changes in chest malignant tumor patients who received chest radiation. METHODS: We prospectively collected thoracic malignancy cancer patients who had received chest radiotherapy. Heart dosimetry parameters were extracted from the treatment planning system. sST-2 was measured at baseline, the middle stage, and after radiotherapy (recorded as pre-ST-2, mid-ST-2, and post-ST-2). sST-2 change rate was calculated. Scatter plots showed the relationship between cardiac dose parameters and ST-2 change rate. Multiple regression was used to analyze the relationship between cardiac dose parameters and ST-2 change rate. RESULTS: Totally, 60 patients were enrolled. The mean V5 , V10 , V20 , V30 , V40 , and MHD was 60.93 ± 27.79%, 51.43 ± 25.44%, 39.17 ± 21.75%, 28.07 ± 17.15%,18.66 ± 12.18%, and 18.60 ± 8.63 Gy, respectively. The median M-LAD was 11.31 (IQR 3.33-18.76) Gy. The mean pre-ST-2, mid-ST-2, and post-ST-2 was 5.1 ± 3.8, 6.4 ± 3.9, and 7.6 ± 4.4, respectively. sST-2 was elevated with thoracic irradiation (P < .001). Multivariate linear regression analyses showed that V5 , V10 , V20 , and MHD were independently and positively associated with ST-2 change rate (ß = .04, .04, .04, and .10, respectively, all P < .05). CONCLUSION: Serum sST-2 levels were elevated over time during radiotherapy. V5 , V10 , V20 and MHD were independently and positively associated with the elevated ST-2 change rate.


Assuntos
Coração/efeitos da radiação , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Radiometria , Neoplasias Torácicas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Relação Dose-Resposta à Radiação , Feminino , Coração/fisiopatologia , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Solubilidade , Volume Sistólico , Neoplasias Torácicas/sangue
6.
BMC Cancer ; 17(1): 254, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28399835

RESUMO

BACKGROUND: The standard treatment for esthesioneuroblastoma, a rare malignant nasal vault neoplasm, is not established. METHODS: We retrospectively assessed the clinicopathological features, prognostic factors and treatment methods for 187 patients with esthesioneuroblastoma treated in China between 1981 and 2015. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank tests. RESULTS: Twenty-three (12.3%), 48 (25.7%) and 113 (60.4%) patients had Kadish stage A, B and C esthesioneuroblastoma; 3 (1.6%) had unknown stage. Overall, 117 (62.6%) patients received surgery and combined radiotherapy with or without chemotherapy; 35 (18.7%) received radiotherapy with or without chemotherapy; 32 (17.1%) received surgery alone; and 3 (1.6%) received palliative treatment. Three-year OS and DFS for the entire cohort were 66.7% and 57.5%, respectively. Three-year OS for stage A, B and C were 91.3%, 91.2% and 49.5% (P < 0.0001). Three-year OS was 16.7% and 66.7% for patients with and without distant metastasis (P < 0.0001). Surgery and combined radiotherapy with or without chemotherapy led to better OS and DFS than other treatment modes (both P < 0.0001). Univariate and multivariate analysis showed distant metastasis (hazard ratio [HR] = 2.162, 95% confidence interval [CI] = 1.145, 4.082, P = 0.017) and not receiving a combined modality treatment (HR = 2.391, 95% CI = 1.356, 4.218, P = 0.003) were independent prognostic factors for poor OS and DFS. CONCLUSIONS: This study indicates surgery and combined radiotherapy may currently be the optimal treatment for esthesioneuroblastoma.


Assuntos
Estesioneuroblastoma Olfatório/patologia , Estesioneuroblastoma Olfatório/terapia , Cavidade Nasal/patologia , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
7.
BMC Cancer ; 17(1): 131, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28196505

RESUMO

BACKGROUND: Due to the uncommon nature of primary spinal epidural lymphomas (PSELs), there has been little research looking at prognostic indicators for the tumor. To our knowledge, this is the largest study to evaluate possible clinical and pathologic prognostic factors in PSEL patients. METHODS: We retrospectively reviewed 130 cases of PSEL, including 36 Chinese patients and 94 published case reports from 1985 to 2015. Patient treatment regimens included surgery (S; n = 119), surgery followed by chemotherapy (S + CT; n = 25), surgery followed by radiotherapy (S + RT; n = 26), and surgery followed by chemotherapy and radiotherapy (S + CT + RT; n = 50). RESULTS: Review of the most recent case follow-up data (time varied) found 51 patients (47%) alive and tumor-free, 10 patients (9%) alive with tumor present, and 47 patients (44%) deceased. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 81.1% and 46.3%, respectively. Favorable prognostic factors found by univariate analysis were female sex, B-cell lymphoma diagnosis, cervical spine location, and combined modality treatment. Furthermore, multivariate analysis revealed that thoracic spine location (HR = 4.629, 95% CI = [1.911, 31.667], P = 0.042 for OS) and the lack of combined modality treatment (HR = 12.697, 95% CI = [2.664, 48.612], P < 0.0001 for DFS) were associated with poor survival in PSEL patients. CONCLUSIONS: PSEL demonstrates specific clinical features and is associated with a relatively good prognosis. Thoracic spine location is a significant poor prognostic factor, and combined modality treatment is associated with improved disease-free survival, but not overall survival.


Assuntos
Terapia Combinada/métodos , Linfoma/terapia , Adolescente , Adulto , Idoso , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Criança , Pré-Escolar , Espaço Epidural/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
8.
J Chem Phys ; 147(9): 091103, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28886636

RESUMO

Precise molecular transition frequencies are needed in various studies including the test of fundamental physics. Two well isolated ro-vibrational transitions of 12C16O at 1.57 µm, R(9) and R(10) in the second overtone band, were measured by a comb-locked cavity ring-down spectrometer. Despite the weakness of the lines (Einstein coefficient A≃0.008 s-1), Lamb-dip spectra were recorded with a signal-to-noise ratio over 1000, and the line positions were determined to be 191 360 212 761.1 and 191 440 612 662.2 kHz, respectively, with an uncertainty of 0.5 kHz (δν/ν=2.6×10-12). The present work demonstrates the possibility to explore extensive molecular lines in the near-infrared with sub-kHz accuracy.

9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(4): 971-4, 2015 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-26197585

RESUMO

A cavity ring-down spectrometer (CRDS) was built based on telecom distributed feedback (DFB) diode lasers. The ring down cavity was formed by mirrors of 99. 997% reflectivity with a separation of 130 cm, with an empty ring down time of about 150 µs. A minimum detectable absorption coefficient of 5 x 10(-12) cm(-1) was obtained by averaging about 1,000 recorded spectra. The ring down cavity is thermo-isolated, and used as an interferometer to calibrate the recorded spectrum. A feedback control scheme was applied to step scan the laser frequency, successively matching each of the longitudinal modes of the cavity. By measuring the CO contents in a standard gas sample, the quantitative capability of the CRDS instrument was demonstrated, and a CO detection limit of 4 ppb was achieved. The instrument was applied to monitor the CO concentration in ambient air.

10.
J Transl Med ; 12: 200, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25082261

RESUMO

BACKGROUND: Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC. METHODS: We used immunohistochemical analysis to determine the expression of Aurora-A protein in 102 NSCLC patients treated by surgery and adjuvant cisplatin-based chemotherapy. The prognostic significances were assessed by Kaplan-Meier survival estimates and Cox models. The potential role of Aurora-A in the regulation of cisplatin resistance in NSCLC cells was examined by transfections using expression vector and small interfering RNA or using small-molecule inhibitors. RESULTS: Aurora-A expression was significantly associated with clinical stage (p = 0.018), lymph node metastasis (p = 0.038) and recurrence (p = 0.005), and was an independent prognostic parameter in multivariate analysis. High level of Aurora-A expression predicted poorer overall survival (OS) and progression-free survival (PFS). In vitro data showed that Aurora-A expression was elevated in cisplatin-resistant lung cancer cells, and overexpression or knockdown of Aurora-A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora-A reversed the migration ability of cisplatin-resistant cells. CONCLUSIONS: The current findings suggest that high Aurora-A expression is correlated with cisplatin-based chemotherapeutic resistance and predicts poor patient survival in NSCLC. Aurora-A might serve as a predictive biomarker of drug response and therapeutic target to reverse chemotherapy resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aurora Quinase A/fisiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Aurora Quinase A/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Células Tumorais Cultivadas
11.
BMC Cancer ; 14: 140, 2014 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-24575810

RESUMO

BACKGROUND: Small cell cervical carcinoma (SCCC) is a rare, aggressive tumor with a poor prognosis. However, information in relation to its treatment is scarce due to the limited numbers of patients. The aim of this study was to establish whether platinum-based combination chemotherapy may by beneficial in this patient population. METHODS: We carried out a multicenter, retrospective study comprising of 72 Chinese patients with SCCC. The patients were treated between 1995 and 2010 at Sun Yat-sen Memorial Hospital or the Cancer Center of Sun Yat-Sen University, and at the First Affiliated Hospital of Shantou University Medical College, China. RESULTS: Of the 72 patients, 46/72 (63.9%) had Federation of Gynecology and Obstetrics (FIGO) stage Ia-Ib2 and 26/72 (36.1%) had stage IIa-IV disease. Surgery was performed in 63/72 (87.5%) patients, 61/72 (84.7%) patients received chemoradiotherapy and 35/72 (48.6%) received radiotherapy. The 3-year overall survival (OS) and disease-free survival (DFS) rates were as follows: Ia (100%, 100%); Ib1 (62%, 57%); Ib2 (53%, 48%); IIa (36%, 23%); IIb (29%, 21%); IIIb (50%, 50%); and IV (0%, 0%), respectively. The estimated 3-year OS and DFS rates in patients who received platinum-based combination chemotherapy (etoposide + cisplatin [EP], or paclitaxel + cisplatin [TP]) as part of their adjuvant treatment were 64.8% and 63.0%, respectively, compared to 25.2% and 22.0% in those who did not (P = 0.0003; P = 0.0003). Univariate analysis showed that platinum-based combination chemotherapy was associated with improved survival compared to other chemotherapy techniques or no chemotherapy (OS: HR = 0.227; 95% CI, 0.099-0.524; P = 0.001; DFS: HR = 0.210; 95% CI, 0.087-0.506; P = 0.001). Multivariate analysis identified FIGO stage, lymphatic metastasis and platinum-based combination chemotherapy as independent prognostic factors for improved survival in patients with SCCC. CONCLUSIONS: Platinum-based combination chemotherapy (with EP or TP) can improve the 3-year survival outcomes in patients with SCCC. Therefore, it should be considered an important component in a future standardized treatment strategy for SCCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Povo Asiático , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Povo Asiático/etnologia , Carcinoma de Células Pequenas/etnologia , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Paclitaxel , Estudos Retrospectivos , Taxoides/administração & dosagem , Neoplasias do Colo do Útero/etnologia , Adulto Jovem
12.
Gynecol Oncol ; 133(3): 616-23, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24667250

RESUMO

OBJECTIVE: The identification and investigation of cancer-associated long non-coding RNAs are important for understanding the molecular biology of cancer. The aim of the present study was to examine the expression pattern of lncRNA XLOC_010588 in cervical cancer and to evaluate its biological role and clinical significance in tumor progression. METHODS: We examined the expression of XLOC_010588 in 218 cervical cancer tissues and matched 218 adjacent normal tissues using real-time qRT-PCR. Over-expression and RNA interference approaches were used to investigate the biological functions of XLOC_010588. The effect of XLOC_010588 on proliferation was evaluated by MTT and BrdU assays. Western blot assays were used to investigate the molecular mechanism by which XLOC_010588 increases cervical cancer cell proliferation. RESULTS: The results showed that XLOC_010588 expression in cervical cancer was significantly downregulated. Decreased XLOC_010588 expression was correlated with FIGO stage, tumor size and SCC-Ag. Moreover, cervical cancer patients with XLOC_010588 lower expression have shown poorer prognosis. Multivariate Cox regression analyses showed that XLOC_010588 expression served as an independent predictor for overall survival. Ectopic expression of XLOC_010588 inhibited the proliferation of HeLa and SiHa cells. By contrast, knockdown of XLOC_010588 promoted the growth of HCC94 cells. Western blot assays confirmed that XLOC_010588 physically associates with c-Myc, consequently decreasing the expression of c-Myc. The expression of XLOC_010588 and c-Myc is strongly correlated in cervical cancer tissues. CONCLUSION: These results suggested that XLOC_010588 plays a pivotal role in cervical cancer cell proliferation via decreasing c-Myc expression and implicated the potential application of XLOC_010588 in cervical cancer therapy.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/patologia , Adulto , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Células HeLa , Humanos , Prognóstico , RNA Longo não Codificante/fisiologia , Regulação para Cima , Neoplasias do Colo do Útero/patologia
13.
Appl Opt ; 53(32): 7716-23, 2014 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-25402995

RESUMO

A cavity ring-down spectrometer is built for trace gas detection using telecom distributed feedback (DFB) diode lasers. The longitudinal modes of the ring-down cavity are used as frequency markers without active-locking either the laser or the high-finesse cavity. A control scheme is applied to scan the DFB laser frequency, matching the cavity modes one by one in sequence and resulting in a correct index at each recorded spectral data point, which allows us to calibrate the spectrum with a relative frequency precision of 0.06 MHz. Besides the frequency precision of the spectrometer, a sensitivity (noise-equivalent absorption) of 4×10-11 cm-1 Hz-1/2 has also been demonstrated. A minimum detectable absorption coefficient of 5×10-12 cm-1 has been obtained by averaging about 100 spectra recorded in 2  h. The quantitative accuracy is tested by measuring the CO2 concentrations in N2 samples prepared by the gravimetric method, and the relative deviation is less than 0.3%. The trace detection capability is demonstrated by detecting CO2 of ppbv-level concentrations in a high-purity nitrogen gas sample. Simple structure, high sensitivity, and good accuracy make the instrument very suitable for quantitative trace gas analysis.


Assuntos
Gases/análise , Microquímica/instrumentação , Análise Espectral/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Calibragem , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Arch Gynecol Obstet ; 290(4): 717-23, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24748337

RESUMO

PURPOSE: The long noncoding RNA HOTAIR has been reported to be a good biomarker for poor prognosis in a variety of human cancers. However, whether HOTAIR could serve as novel biomarker to predict prognosis in cervical cancer or not is unknown. The aim of the present study was to examine the expression of HOTAIR in cervical cancers and to investigate the relationship between this lncRNA expression levels and existing clinicopathological factors and patient survival. METHODS: We examined the expression of HOTAIR in 218 cervical cancer tissues and matched 218 adjacent normal tissues using quantitative real-time RT-PCR and analyzed its correlation with the clinical parameters. RESULTS: The results showed that HOTAIR expression in cervical cancer tissues was significantly upregulated compared with the matched nontumorous tissues (P < 0.0001). Increased HOTAIR expression was significantly correlated with FIGO stage (P < 0.0001), lymph node metastasis (P < 0.0001), depth of cervical invasion (P < 0.0001), tumor size (P = 0.006) and age (P = 0.020), but not other clinical characteristics. Moreover, cervical cancer patients with HOTAIR higher expression have shown significantly poorer overall survival (P < 0.0001) and disease-free survival (P < 0.0001) than those with lower HOTAIR expression. Univariate (P < 0.0001, HR = 4.566, 95 % CI 2.122-9.825) and multivariate (P = 0.012, HR = 2.863, 95 % CI 1.263-76.490). Cox regression analyses showed that HOTAIR expression served as an independent predictor for overall survival. CONCLUSIONS: our data indicate that high expression of HOTAIR is involved in cervical cancer progression and could be a potential target for diagnosis and gene therapy.


Assuntos
Expressão Gênica , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Marcadores Genéticos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Neoplasias do Colo do Útero/patologia
15.
Cancer Cell ; 42(9): 1598-1613.e4, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39255777

RESUMO

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Mutação , Sequenciamento de Nucleotídeos em Larga Escala/métodos
17.
Discov Med ; 35(176): 321-331, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37272099

RESUMO

OBJECTIVE: Anti-angiogenic therapy has proven effective in non-small-cell lung cancer (NSCLC) patients. The purpose of this study was to evaluate the efficacy of programmed cell death protein 1 (PD-1) inhibitors combined with anti-angiogenic therapy in patients with driver gene mutation negative NSCLC and brain metastases (BMs). METHODS: A retrospective analysis was performed on NSCLC BMs in patients without driver gene mutations who received PD-1 inhibitors. Two groups, receiving either PD-1 inhibitor monotherapy or PD-1 inhibitor plus anti-angiogenesis therapy, were identified. The primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS). The secondary endpoints were safety, intracranial objective response rate (iORR) and intracranial disease control rate (iDCR). RESULTS: 113 NSCLC patients were included, 51 (45.1%) in the PD-1 inhibitor monotherapy group and 62 (54.9%) in the PD-1 inhibitor plus anti-angiogenesis therapy group. The median follow-up time was 26.2 months. OS was higher in the combination therapy cohort than in the monotherapy cohort (OS: 21.4 vs. 11.8 months; p = 0.004), with no significant difference in iPFS (p = 0.088). Moreover, the PD-1 inhibitor + anti-angiogenic therapeutic regimen exhibited the preferred iDCR (p = 0.005) but not the iORR (p = 0.121). There was no significant difference in the incidence of grade 3-4 adverse events between the two groups. In multivariate Cox regression analysis, PD-1 inhibitor therapy combined with anti-angiogenic treatment (p = 0.003) was an independent prognostic indicator of OS. CONCLUSIONS: Combining PD-1 inhibitor therapy with anti-angiogenic treatment significantly improves the OS of driver gene mutation negative NSCLC patients with BMs.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Mutação
18.
J Clin Oncol ; 41(3): 651-663, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36206498

RESUMO

PURPOSE: The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS: At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION: Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
19.
J Phys Chem A ; 115(6): 1040-6, 2011 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-21265547

RESUMO

Complicated high-resolution spectral structures are often observed for molecules doped in solid molecular hydrogen. The structures can result from miscellaneous effects and are often interpreted differently in references. The spectrum of the ν(3) band of CO(2) in solid para-H(2) presents a model system which exhibits rich spectral structures. With the help of the potential energy simulation of the CO(2) molecule doped in para-hydrogen matrix, and extensive experiments with different CO(2) isotopologues and different ortho-hydrogen concentrations in the matrix, the spectral features observed in p-H(2) matrix are assigned to the CO(2)···(o-H(2))(n) clusters and also to energy level splitting that is due to different alignments of the doped CO(2) molecules in the matrix. The assignments are further supported by the dynamics analysis and also by the spectrum recorded with sample codoped with O(2) which serves as catalyst transferring o-H(2) to p-H(2) in the matrix at 4 K temperature. The observed spectral features of CO(2)/pH(2) can potentially be used as an alternative readout of the temperature and orthohydrogen concentration in the solid para-hydrogen.

20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(3): 835-8, 2011 Mar.
Artigo em Zh | MEDLINE | ID: mdl-21595251

RESUMO

A cavity ring-down spectrometer was built up using a CW tunable Ti: sapphire laser. The experiments show that not only the spectral resolution is up to the 10(-4) cm(-1) level, but the detecting sensitivity also exceeds 10(-10) cm(-1). With the measurements of the absorption spectroscopy of C2H2 near 12,696.4 cm(-1), the quantitative capability of the instrument was demonstrated. Through the spectroscopy of the samples mixed with trace C2H2 in N2 gas, the detection limit of C2H2 was determined to be 0.2 ppm.

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