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1.
Nat Immunol ; 21(9): 1107-1118, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32788748

RESUMEN

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.


Asunto(s)
Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Interferón Tipo I/metabolismo , Neumonía Viral/inmunología , Receptores Inmunológicos/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Humanos , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/virología , RNA-Seq , Receptores Inmunológicos/genética , Receptores Inmunológicos/inmunología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Análisis de la Célula Individual
2.
Lab Invest ; 104(8): 102090, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38830579

RESUMEN

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

3.
Anal Chem ; 96(11): 4570-4579, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38441542

RESUMEN

Ferroptosis, as a new form of regulated cell death, is implicated in various physiological and pathological processes. Developing a single probe for an independent analysis of multiple analytes related to ferroptosis can provide more accurate information and simplify the detection procedures, but it faces great challenges. In this work, we develop a fluorescent probe for the simultaneous detection of GSH through ratiometric fluorescence response and microviscosity via a fluorescence lifetime model. Based on the reversible Michael addition reaction between GSH and unsaturated C═C bond, the probe responds reversibly to GSH with a ratiometric fluorescence variation and a fast response time (t1/2 = 4.7 s). At the same time, the probe is sensitive to environmental viscosity by changing its fluorescence lifetimes. The probe was applied to monitor the drug-induced ferroptosis process through both the classical Xc-/GSH/GPX4- and DHODH-mediated defense mechanisms. We hope that the probe will provide a useful molecular tool for the real-time live-cell imaging of GSH dynamics, which is benefit to unveiling related physiological and pathological processes.


Asunto(s)
Ferroptosis , Viscosidad , Colorantes Fluorescentes/química , Microscopía Fluorescente/métodos , Imagen Óptica , Glutatión/análisis
4.
Org Biomol Chem ; 22(18): 3740-3745, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38651658

RESUMEN

An efficient and practical method for the synthesis of 3-alkenylquinoxalinones containing the SCF3 group has been readily developed through a three-component radical cascade reaction involving quinoxalinones, alkynes and AgSCF3. The reaction was found to be compatible with a variety of substrates and exhibited a high functional group tolerance and complete E-selectivity. The preliminary study suggests the involvement of a SCF3 radical in the transformation.

5.
Dig Dis Sci ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879737

RESUMEN

OBJECTIVE: Gastric cancer is a malignant tumor with high morbidity and mortality all around the world. Because of its poor prognosis and low survival rate, the treatment of gastric cancer has received extensive attention. Cinnamaldehyde (CA) is the main single active component of the Chinese herbal medicine cinnamon, which has a variety of pharmacological effects. The inhibitory effect of CA on the growth of some tumor cells has been proven, but its therapeutic effect on gastric cancer has rarely been reported. METHODS: Through network pharmacology, bioinformatics methods, and molecular docking technology, we predicted the interaction targets of CA and gastric cancer. Moreover, we found that apoptosis is an important mode of action of CA on gastric cancer cells. Subsequently, we validated it in gastric cancer cell lines cultured in vitro. RESULTS: The results showed that in the presence of CA, the Jak2/Stat3 pathway was inhibited, the ratio of Bcl-2/Bax decreased, and the apoptosis of gastric cancer cells was promoted in a concentration-dependent. CONCLUSION: In conclusion, CA can promote the apoptosis of gastric cancer cells by inhibiting the activity of the Jak2/Stat3 pathway, which may achieve the effect of treating gastric cancer.

6.
Gut ; 72(1): 153-167, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35361683

RESUMEN

OBJECTIVE: A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure. DESIGN: We performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation. RESULTS: Both IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell-cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores. CONCLUSION: Our study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.


Asunto(s)
Linfocitos T CD8-positivos , Hígado , Humanos , Hígado/patología , Antivirales , Linfocitos T Reguladores , Análisis de Secuencia de ARN , Virus de la Hepatitis B
7.
J Vis ; 23(13): 2, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37917052

RESUMEN

Although visual feature estimations are accurate and precise, overall estimation errors (i.e., the difference between estimates and actual values) tend to show systematic patterns. For example, estimates of orientations are systematically biased away from horizontal and vertical orientations, showing an oblique illusion. Additionally, many recent studies have demonstrated that estimations of current visual features are systematically biased toward previously seen features, showing a serial dependence. However, no study examined whether the overall estimation errors were correlated with the serial dependence bias. To address this question, we enrolled three groups of participants to estimate orientation, motion speed, and point-light-walker direction. The results showed that the serial dependence bias explained over 20% of overall estimation errors in the three tasks, indicating that we could use the serial dependence bias to predict the overall estimation errors. The current study first demonstrated that the serial dependence bias was not independent from the overall estimation errors. This finding could inspire researchers to investigate the neural bases underlying the visual feature estimation and serial dependence.


Asunto(s)
Ilusiones , Percepción Visual , Humanos , Sesgo , Movimiento (Física)
8.
Cancer ; 128(4): 708-718, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35076939

RESUMEN

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited. METHODS: This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years. RESULTS: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS (HR, 3.04; 95% CI, 1.22-7.58; P = .012). During surveillance after surgery, longitudinal ctDNA-positive patients (37 of 119; 31.1%) had significantly shorter RFS (HR, 3.46; 95% CI, 1.59-7.55; P < .001) and significantly shorter OS (HR, 9.99; 95% CI, 1.17-85.78; P = .010) in comparison with longitudinal ctDNA-negative patients. Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 8.71 months. CONCLUSIONS: These results suggest that perioperative ctDNA analyses can predict recurrence and survival, and serial ctDNA analyses can identify disease recurrence/metastasis earlier than routine radiologic imaging in patients with resectable NSCLC. LAY SUMMARY: The utility of serial circulating tumor DNA (ctDNA) monitoring for predicting disease recurrence and survival for early-stage non-small cell lung cancer (NSCLC) has not been well characterized. The detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence and long-term patient outcomes for resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than routine radiologic imaging. ctDNA analyses can detect minimal residual disease for resectable NSCLC and thus can facilitate early intervention.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , ADN Tumoral Circulante , Neoplasias Pulmonares , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/cirugía , ADN Tumoral Circulante/sangre , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos
9.
Chem Biodivers ; 17(5): e2000106, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32212241

RESUMEN

Three new indole diketopiperazine alkaloids, 11-methylneoechinulin E and variecolorin M, and (+)-variecolorin G, along with 12 known analogs, were isolated from a soft coral-associated epiphytic fungus Aspergillus sp. EGF 15-0-3. The structures of the new compounds were unambiguously established by extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR spectroscopy and optical rotation measurements. The absolute configurations of (+)- and (-)-variecolorin G were determined by experimental and quantum-chemical ECD investigations and single-crystal X-ray diffraction analysis. Variecolorin G is a pair of enantiomeric mixtures with a ratio of 1 : 2. Moreover, (+)-neoechinulin A is firstly reported as a natural product. The cytotoxic activities of all the isolated compounds against NCI-H1975 gefitinib resistance (NCI-H1975/GR) cell lines were preliminarily evaluated by MTT method.


Asunto(s)
Alcaloides/farmacología , Antineoplásicos/farmacología , Aspergillus/química , Dicetopiperazinas/farmacología , Indoles/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Dicetopiperazinas/química , Dicetopiperazinas/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indoles/química , Indoles/aislamiento & purificación , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad
10.
Chem Biodivers ; 17(6): e2000182, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32298046

RESUMEN

Phytochemical investigation of Sargassum fusiforme (Harv.) Setch. led to the discovery of fifteen secondary metabolites, including three sterols, three monoterpenes, five nitrogenous compounds, two fatty acids, and two others. Among them, two compounds are new, while the other thirteen compounds were isolated from S. fusiforme for the first time. The structures of the two new compounds were identified by NMR and HR-ESI-MS data analyses, and the absolute configurations were established by comparing the calculated and experimental ECD spectroscopic data.


Asunto(s)
Sargassum/química , Dicroismo Circular , Ácidos Grasos/química , Ácidos Grasos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Conformación Molecular , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Sargassum/metabolismo , Esteroles/química , Esteroles/aislamiento & purificación
11.
J Cell Biochem ; 120(6): 9193-9202, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30506723

RESUMEN

Immunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO-296 [2-(6-chlorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO-296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO-296 did not affect the expression of cluster of differentiation (CD)-25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO-296 inhibited interleukin (IL)-6, IL-17, and interferon gamma expression but had no effect on IL-2, IL-4, or IL-10. Yet, importantly, PO-296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mitogen-activated protein kinase pathway. In conclusion, these findings indicate that PO-296 inhibits human activated T-lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO-296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.


Asunto(s)
Benzoxazoles/química , Benzoxazoles/farmacología , Activación de Linfocitos/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Transcripción STAT5/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Humanos , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Linfocitos T/citología
12.
Zhongguo Zhong Yao Za Zhi ; 42(23): 4510-4513, 2017 Dec.
Artículo en Zh | MEDLINE | ID: mdl-29376245

RESUMEN

Notopterol, isoimperatorin, volatile oil and extract (water and ethanol) were used as the research objects in this study to investigate the effects of different softening method, slice thickness and drying methods on the quality of Notopterygii Rhizoma et Radix slices, and the experimental data were analyzed by homogeneous distance evaluation method. The results showed that different softening, cutting and drying processes could affect the content of five components in Notopterygii Rhizoma et Radix incisum. The best processing technology of Notopterygii Rhizoma et Radix slices was as follows: non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 1/8 volume of water was sprayed for every 1 kg of herbs every 2 h; upper part of herbs covered with clean and moist cotton, and cut into thick slices (2-4 mm) after 12 h moistening until appropriate softness, then received blast drying for 4 h at 50 ℃, and turned over for 2 times during the drying. The process is practical and provides the experimental basis for the standardization of the processing of Notopterygii Rhizoma et Radix, with great significance to improve the quality of Notopterygii Rhizoma et Radix slices.


Asunto(s)
Apiaceae/química , Medicamentos Herbarios Chinos/normas , Extractos Vegetales/normas , Desecación , Aceites Volátiles/química , Raíces de Plantas/química , Rizoma/química
13.
Zhongguo Zhong Yao Za Zhi ; 42(23): 4503-4509, 2017 Dec.
Artículo en Zh | MEDLINE | ID: mdl-29376244

RESUMEN

Study on the standardization of Chinese materia medica is an important action for modernization and globalization for traditional Chinese medicine. Standardization on the processing of Chinese herbal pieces is an important part in the study on standardization of Chinese materia medica, so it is of great significance to establish the technical processing standards of Angelicae Sinensis Radix pieces for improving its quality. In this study, single factor experiment was designed to optimize the softening, cutting and drying processes of Angelicae Sinensis Radix. With ferulic acid, Angelicae Sinensis Radix polysaccharide, volatile oil and extracts (water and ethanol) content as the quality index, the effects of different softening, cutting and drying processes on the contents of the five components in Angelicae Sinensis Radix were analyzed, and the normalized distance evaluation method was used to analyze the experimental data. The results showed that the content of five components in Angelicae Sinensis Radix was affected by different softening methods and drying temperature, but the thickness of slice had little effect on the content. The best preparation process for Angelicae Sinensis Radix was as follows: Non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 125 mL water was sprayed for every 1 kg of herbs every 2.5 h; upper part of herbs covered with clean and moist cotton, and cut into thin slices (1-2 mm) after 15 h moistening until appropriate softness, with disk thickness of 1-2 cm, then received blast drying for 6 h at 55 ℃, and turned over for 2 times during the drying.


Asunto(s)
Angelica sinensis/química , Medicamentos Herbarios Chinos/normas , Extractos Vegetales/normas , Desecación , Medicina Tradicional China , Aceites Volátiles/química , Raíces de Plantas/química , Polisacáridos/química , Estándares de Referencia
14.
Cancer ; 122(5): 740-7, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26700505

RESUMEN

BACKGROUND: The objective of this phase 2 trial was to assess the efficacy and safety of induction bevacizumab plus chemotherapy followed by surgery in patients with unresectable stage III lung adenocarcinoma. METHODS: The authors investigated induction bevacizumab (7.5 mg/kg) plus pemetrexed (500 mg/m(2) and carboplatin (area under the receiver operating characteristic curve = 5) followed by surgery for patients with unresectable stage III lung adenocarcinoma ages 18 to 65 years. The patients received neoadjuvant therapy every 3 weeks for 4 cycles. Surgery was scheduled 3 to 4 weeks after the last neoadjuvant therapy; then, the medical team assessed each patient's resectability status. The primary endpoint was the resectability rate. RESULTS: From April 2012 to April 2014, 42 patients were enrolled and received bevacizumab plus pemetrexed and carboplatin. Grade 3 or 4 induction-related AEs included fatigue in 5 patients, neutropenia in 4 patients, hypertension in 1 patient, anemia in 1 patient, and thrombocytopenia in 1 patient. One patient achieved a complete response, 22 achieved a partial response, 17 had stable disease, and 2 had progressive disease. After neoadjuvant therapy, 31 patients (73.8%) underwent surgery, including 11 who underwent pneumonectomy. Complete (R0) resection was achieved in 22 patients (52.4%). Reoperation was required in 1 patient because of a bleeding intercostal artery. No perioperative thromboembolic events or wound-healing problems were observed. The median event-free survival was 15.4 months, and the 1-year event-free survival rate was 56.1%. CONCLUSIONS: Treatment with neoadjuvant bevacizumab in combination with pemetrexed and carboplatin followed by surgery appears to be feasible and safe in patients with unresectable stage III lung adenocarcinoma. Cancer 2016;122:740-747. © 2015 American Cancer Society.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neumonectomía/estadística & datos numéricos , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Anemia/inducido químicamente , Bevacizumab/administración & dosificación , Carboplatino/administración & dosificación , Fatiga/inducido químicamente , Femenino , Humanos , Hipertensión/inducido químicamente , Quimioterapia de Inducción , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Pemetrexed/administración & dosificación , Tasa de Supervivencia , Trombocitopenia/inducido químicamente
15.
Ann Surg Oncol ; 23(6): 2115-22, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26887852

RESUMEN

BACKGROUND: This study aimed to investigate the association of epidermal growth factor receptor (EGFR) mutation status with treatment outcome for patients with stage 3 non-small cell lung cancer (NSCLC) who had undergone a complete (R0) resection. METHODS: The study identified 3445 NSCLC patients tested for EGFR mutations between September 2001 and December 2011 at the Sun Yat-Sen University Cancer Center. Of these patients, 224 were stage 3 patients who had undergone R0 resections. RESULTS: These 224 R0-resected, pathologic stage 3A and 3B patients included 150 patients with wild-type EGFR and 74 patients with EGFR mutations. During a median follow-up period of 42 months (range, 4-133 months), pathologic stage was shown to be the only prognostic factor. The 3-year overall survival (OS) rates did not differ significantly from the OS rates for the wild-type and mutant EGFR groups (62.0 vs 67.2 %; p = 0.789). Multivariate analyses indicated that the patients in the mutant EGFR group with EGFR exon 19 mutations had a better OS rate (73.0 vs 61.1 %; p = 0.026). CONCLUSIONS: Cancer stage remained the significant prognostic factor in R0-resected stage 3 NSCLC patients. The presence of an EGFR mutation is more likely to be a predictive marker for the response to treatment with tyrosine kinase inhibitors. In the EGFR mutant group, the patients with an exon 19 mutation had better 3-year OS rates. These findings might be considered in future study designs.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutación , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
16.
Chin J Cancer ; 34(10): 475-82, 2015 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-26411553

RESUMEN

BACKGROUND: A positive association between the ABO blood types and survival has been suggested in several malignancies. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1, 2005 and December 31, 2009. The relationship between the ABO blood types and survival was investigated. In addition, univariate and multivariate analyses were performed. RESULTS: Group 1 (patients with the blood type O or B) had significantly prolonged overall survival (OS) compared with group 2 (patients with the blood type A or AB), with a median OS of 74.9 months versus 61.5 months [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.72-0.96; P = 0.015]. Additionally, group 1 had significantly longer disease-free survival (DFS; HR 0.86; 95% CI 0.76-0.98; P = 0.022) and locoregional relapse-free survival (LRFS; HR 0.79; 95% CI 0.64-0.98; P = 0.024) than group 2. The association was not significantly modified by other risk factors for NSCLC, including smoking status, pathologic tumor-node-metastasis stage, pT category, pN category, and chemotherapy. CONCLUSIONS: There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. Patients with the blood type O or B had significantly prolonged OS, DFS, and LRFS compared with those with the blood type A or AB.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Carcinoma de Pulmón de Células no Pequeñas , Pronóstico , Factores de Riesgo , Pueblo Asiatico , Supervivencia sin Enfermedad , Humanos , Análisis Multivariante , Recurrencia Local de Neoplasia , Estudios Retrospectivos
17.
Cancer ; 120(9): 1379-86, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24481719

RESUMEN

BACKGROUND: The current study was undertaken to investigate the efficacy and safety of erlotinib versus pemetrexed as second-line therapy for patients with advanced epidermal growth factor receptor (EGFR) wild-type and EGFR fluorescence in situ hybridization (FISH)-positive lung adenocarcinoma. METHODS: In this open-label, randomized, phase 2 study, patients with EGFR wild-type and EGFR FISH-positive adenocarcinoma who had developed disease progression after 1 prior platinum-based chemotherapy were randomly assigned (1:1) to receive erlotinib or pemetrexed until the time of disease progression or death, unacceptable toxicity, or a request for discontinuation by the patient. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 123 patients were enrolled (61 in the erlotinib arm and 62 in the pemetrexed arm). The median PFS was 4.1 months (95% confidence interval [95% CI], 1.6 months-6.6 months) in the erlotinib group versus 3.9 months (95% CI, 2.7 months-5.1 months) in the pemetrexed group. The difference in PFS between the 2 treatment groups was not significant (hazard ratio, 0.92; 95% CI, 0.62-1.37 [P= .683]). The objective response rate appeared to be higher among patients receiving erlotinib compared with those receiving pemetrexed (19.7% vs 8.1%; P= .062). The 3 most commonly recorded adverse events were rash (54.1%), fatigue (19.7%), and diarrhea (16.4%) in the erlotinib group and fatigue (25.8%), nausea (24.2%), and anorexia (14.5%) in the pemetrexed group. CONCLUSIONS: There were no significant differences noted with regard to efficacy between erlotinib and pemetrexed in the second-line setting for patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma. Both regimens appear to be effective treatment options for these patients.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/enzimología , Antimetabolitos Antineoplásicos/uso terapéutico , Receptores ErbB/biosíntesis , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Receptores ErbB/genética , Clorhidrato de Erlotinib , Femenino , Dosificación de Gen , Glutamatos/efectos adversos , Guanina/efectos adversos , Guanina/uso terapéutico , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/efectos adversos
18.
Ann Surg Oncol ; 21(6): 2091-6, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24585406

RESUMEN

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown. METHODS: In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5), administered every 21 days for 4 cycles, followed with or without gefitinib (250 mg/day) for 6 months. The primary end point was disease-free survival (DFS). RESULTS: From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95 % confidence interval (CI) 0.16-0.85; P = 0.014; median, 39.8 vs. 27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI 0.12-1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated. CONCLUSIONS: The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Receptores ErbB/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Quinazolinas/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/secundario , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Gefitinib , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Pemetrexed , Neumonectomía , Estudios Prospectivos , Quinazolinas/efectos adversos , Tasa de Supervivencia
19.
Front Pharmacol ; 15: 1417576, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989138

RESUMEN

Organoids are in vitro 3D models that maintain their own tissue structure and function. They largely overcome the limitations of traditional tumor models and have become a powerful research tool in the field of oncology in recent years. Gynecological malignancies are major diseases that seriously threaten the life and health of women and urgently require the establishment of models with a high degree of similarity to human tumors for clinical studies to formulate individualized treatments. Currently, organoids are widely studied in exploring the mechanisms of gynecological tumor development as a means of drug screening and individualized medicine. Ovarian, endometrial, and cervical cancers as common gynecological malignancies have high morbidity and mortality rates among other gynecological tumors. Therefore, this study reviews the application of modelling, drug efficacy assessment, and drug response prediction for ovarian, endometrial, and cervical cancers, thereby clarifying the mechanisms of tumorigenesis and development, and providing precise treatment options for gynecological oncology patients.

20.
RSC Adv ; 14(20): 14465-14469, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38699687

RESUMEN

A general, efficient and practical protocol for Ts2O promoted deoxygenative dithiocarbamation of quinoline N-oxides with in situ generated dithiocarbamic acids from CS2 and amines is reported. The reaction proceeded well under transition-metal free conditions to obtain a variety of novel quinoline-dithiocarbamate compounds with wide functional group tolerance and good to high yields.

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