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1.
Front Oncol ; 14: 1380195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224807

RESUMEN

Objective: The aim of this study was to compare hematological parameters pre- and early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN). Methods: Patients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve. Results: The study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (-0.02, CI: -0.88 to 3.48 vs. -0.04, CI: -0.83 to 2.24). Among hematological parameters, lower post-chemotherapy lymphocyte count (OR 0.942, CI: 0.934-0.949), change percentage of platelet (OR 0.965, CI: 0.955-0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011-1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002-1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275. Conclusion: Peri-chemotherapy hematological markers improve the prediction of FN.

2.
Molecules ; 29(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474681

RESUMEN

Z-scheme heterojunction Bi2WO6/g-C3N4 was obtained by a novel hydrothermal process; its photocatalysis-persulfate (PDS) activation for tetracycline (TC) removal was explored under solar light (SL). The structure and photoelectrochemistry behavior of fabricated samples were well characterized by FT-IR, XRD, XPS, SEM-EDS, UV-vis DRS, Mott-Schottky, PL, photocurrent response, EIS and BET. The critical experimental factors in TC decomposition were investigated, including the Bi2WO6 doping ratio, catalyst dosage, TC concentration, PDS dose, pH, co-existing ion and humic acid (HA). The optimum test conditions were as follows: 0.4 g/L Bi2WO6/g-C3N4 (BC-3), 20 mg/L TC, 20 mg/L PDS and pH = 6.49, and the maximum removal efficiency of TC was 98.0% in 60 min. The decomposition rate in BC-3/SL/PDS system (0.0446 min-1) was 3.05 times higher than that of the g-C3N4/SL/PDS system (0.0146 min-1), which might be caused by the high-efficiency electron transfer inside the Z-scheme Bi2WO6/g-C3N4 heterojunction. Furthermore, the photogenerated hole (h+), superoxide (O2•-), sulfate radical (SO4•-) and singlet oxygen (1O2) were confirmed as the key oxidation factors in the BC-3/SL/PDS system for TC degradation by a free radical quenching experiment. Particularly, BC-3 possessed a wide application potential in actual antibiotic wastewater treatment for its superior catalytic performance that emerged in the experiment of co-existing components.

3.
Radiother Oncol ; 189: 109946, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37806560

RESUMEN

BACKGROUND AND PURPOSE: This study tested the hypothesis that a novel combination of stereotactic ablation radiotherapy (SABR) and a cancer vaccine against fibroblast activation protein-alpha (FAPα) can suppress established tumor growth and impede potential metastasis. METHODS: The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were randomly assigned to five treatment groups: (1) untreated control, (2) FAPα-based cancer vaccine, (3) SABR, (4) SABR + pCDH (lentiviral control vector), (5) SABR + FAPα-based cancer vaccine (SABR/FAPα-Vax). FAPα-based cancer vaccine were administered subcutaneously every week for a total of three treatments. SABR was delivered to the primary tumor by 3 × 8 Gy after the first vaccination. RESULTS: Consistent with the poorly immunogenic nature of 4T1, tumor-bearing mice receiving FAPα-based cancer vaccine or SABR monotherapy showed a modest reduction in tumor volume and increased animal lifespan. In contrast, SABR/FAPα-Vax was well-tolerated, significantly reduced tumor burden, and increased survival compared to monotherapy. The increased survival correlated with inhibition of extracellular matrix (ECM) production, tumor vascularization and lymphangiogenesis. SABR/FAPα-Vax also resulted in an abscopal effect capable of eliminating lung metastases. SABR/FAPα-Vax recruited and activated CD8 + T cells to attack tumor cells and FAPα + stromal cells, and initiated suppressor cell reprogramming, including facilitating macrophage polarization toward an anti-tumor (M1) state, as well as depleting myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). CONCLUSION: These findings provide a novel therapeutic combination of radiation and FAPα-based cancer vaccine with promising results against poorly immunogenic metastatic cancer. This study may pave the way to overcome the therapeutic resistance caused by FAPα + CAFs.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias Pulmonares , Radiocirugia , Animales , Ratones , Vacunas contra el Cáncer/farmacología , Endopeptidasas , Proteínas de la Membrana
4.
Front Oncol ; 13: 1094040, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37182156

RESUMEN

Objective: To investigate the predicting prognosis and guiding postoperative chemoradiotherapy (POCRT) value of preoperative mean platelet volume (MPV) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: We proposed a blood biomarker, MPV, for predicting disease-free survival (DFS) and overall survival (OS) in LA-ESCC patients who underwent surgery (S) alone or S+POCRT. The median cut-off value of MPV was 11.4 fl. We further evaluated whether MPV could guide POCRT in the study and external validation groups. We used multivariable Cox proportional hazard regression analysis, Kaplan-Meier curves, and log-rank tests to ensure the robustness of our findings. Results: In the developed group, a total of 879 patients were included. MVP was associated with OS and DFS defined by clinicopathological variables and remained an independent prognostic factor in the multivariate analysis (P = 0.001 and P = 0.002, respectively). For patients with high MVP, 5-year OS and 0DFS were significantly improved compared to those with low MPV (P = 0.0011 and P = 0.0018, respectively). Subgroup analysis revealed that POCRT was associated with improved 5-year OS and DFS compared with S alone in the low-MVP group (P < 0.0001 and P = 0.0002, respectively). External validation group analysis (n = 118) showed that POCRT significantly increased 5-year OS and DFS (P = 0.0035 and P = 0.0062, respectively) in patients with low MPV. For patients with high MPV, POCRT group showed similar survival rates compared with S alone in the developed and validation groups. Conclusions: MPV as a novel biomarker may serve as an independent prognosis factor and contribute to identifying patients most likely to benefit from POCRT for LA-ESCC.

5.
Boundary Layer Meteorol ; 188(1): 159-183, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215487

RESUMEN

This study developed a backward-Eulerian footprint modelling method based on an adjoint equation for atmospheric boundary-layer flows. In the proposed method, the concentration footprint can be obtained directly by numerical simulation with the adjoint equation, and the flux footprints can be estimated using the adjoint concentration based on the gradient diffusion hypothesis. We first tested the proposed method by estimating the footprints for an ideal three-dimensional boundary layer with different atmospheric stability conditions based on the Monin-Obukhov profiles. It was indicated that the results were similar to the FFP method (Kljun et al. in Boundary-Layer Meteorol 112:503-523, 2004, 10.1023/B:BOUN.0000030653.71031.96; Geosci Model Dev 8:3695-3713, 2015, 10.5194/gmd-8-3695-2015) for convective conditions and the K-M method (Kormann and Meixner in Boundary-Layer Meteorol 99:207-224, 2001, 10.1023/A:1018991015119) for stable conditions. The proposed method was then coupled with the Reynolds averaged Navier-Stokes model to calculate the footprints for a block-arrayed urban canopy. The results were qualitatively compared to the results from the Lagrangian-Large-Eddy-Simulation (LL) method (Hellsten et al. in Boundary-Layer Meteorol 157:191-217, 2015, 10.1007/s10546-015-0062-4). It was shown that the proposed method reproduced the main features of footprints for different sensor positions and measurement heights. However, it is necessary to simulate the adjoint equation with a more sophisticated turbulence model in the future to better capture turbulent effects in the footprint modelling.

6.
J Pharm Anal ; 13(11): 1296-1308, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38174116

RESUMEN

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/ß ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

7.
Nucl Med Commun ; 43(12): 1239-1246, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36345769

RESUMEN

OBJECTIVES: To assess the prognostic value of PET/computed tomography-based parameters in patients with locally advanced esophageal squamous cell carcinoma (ESSC). METHODS: Sixty-seven patients with ESSC undergoing definitive chemoradiotherapy (dCRT) were retrospectively enrolled. PET/CT parameters (maximum standardized uptake value (SUVmax) metabolic tumor volume (MTV), and total glycolysis (TLG) were obtained from 18F-fluorodeoxyglucose (18F-FDG) PET/CT studies. The correlation between overall survival and PET/CT parameters was analyzed using a Cox proportional hazards model. RESULTS: There were no differences in TLG, MTV, and SUVmax values across age, sex, tumor location, and lymph node status. However, for patients with cT3-4 disease, TLG and SUVmax were significantly higher (P = 0.019 and P = 0.018, respectively), and MTV showed an increasing trend (P = 0.068). There were significant correlations among TLG, MTV and SUVmax. According to the receiver-operating curve, the cutoff values of TLG, MTV and SUVmax dichotomized by survival status at 2 years were 64.00 g, 9.63 ml and 9.97 g/ml, respectively. In univariate analysis, increased TLG, MTV and SUVmax were significant negative prognostic factors for OS. However, in multivariate analysis, only SUVmax was an independent prognostic factor for overall survival (hazard ratios = 2.857, 95% confidence intervals: 1.837-4.442; P = 0.017). CONCLUSIONS: PET/CT is a useful tool for predicting the prognoses in patients with locally advanced ESSC treated with dCRT. Future prospective studies with a large number of samples should be conducted to confirm these results.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/terapia , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Fluorodesoxiglucosa F18/metabolismo , Carga Tumoral , Quimioradioterapia , Glucólisis , Radiofármacos
8.
Cancer Manag Res ; 14: 103-106, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35023973

RESUMEN

Pulmonary carcinosarcoma (PC) is a rare and highly malignant type of non-small cell lung cancer (NSCLC) that is insensitive to radiotherapy and chemotherapy and has a poor prognosis. Here, we report a case of an 88-year-old patient with inoperable PC and a history of cerebral infarction who was treated with first-line anlotinib combined with stereotactic body radiation therapy (SBRT). The therapeutic response has sustained for 10 months. Our work suggests that SBRT combined with anlotinib may be a safe and effective treatment strategy for octogenarians with PC.

9.
Future Oncol ; 17(20): 2647-2657, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34008415

RESUMEN

Aim: To explore the clinical utility of the systemic immune-inflammation index (SII) for predicting the prognosis of esophageal squamous cell carcinoma (ESCC). Patients & methods: After calculating the SII in 180 patients with ESCC, the relationship between SII values and the pre-/post-radiotherapy SII ratio and overall survival was determined. Results: The median overall survival was 649 days for the entire group and 909 and 466 days for the high and low pre-/post-radiotherapy SII ratio groups, respectively. Multivariate analysis identified Karnofsky performance status (p = 0.045), lymphatic metastasis (p = 0.032), mid-radiotherapy SII (p < 0.001) and pre-/post-radiotherapy SII ratio (p = 0.003) as independent prognostic factors. Conclusion: The pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.


Lay abstract The systemic immune-inflammation index (SII) is calculated from the counts of peripheral blood platelets (P), neutrophils (N) and lymphocytes (L) per liter according to the formula SII = P × N/L. The SII is associated with poor survival in certain cancer types. However, some reports have examined the prognostic value of the SII in patients with esophageal squamous cell carcinoma (ESCC) who were undergoing radiotherapy or radical chemoradiotherapy. As such, the current study sought to investigate the clinical prognostic value of the SII during radiotherapy and the ratio of the SII before and after radiotherapy in patients with ESCC who were undergoing chemoradiotherapy or radiotherapy. The study found that the pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.


Asunto(s)
Plaquetas/inmunología , Quimioradioterapia/estadística & datos numéricos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Linfocitos/inmunología , Neutrófilos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia/métodos , Toma de Decisiones Clínicas , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/terapia , Estudios de Factibilidad , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Estimación de Kaplan-Meier , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Selección de Paciente , Recuento de Plaquetas , Pronóstico , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Análisis de Supervivencia , Resultado del Tratamiento
10.
Environ Res ; 194: 110706, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33417910

RESUMEN

A line is a common geometry for pollution sources, e.g., outdoor traffic pollution, and is thus useful for developing a suitable source term estimation (STE) method. Most existing methods regard the source as a single point that only includes location and strength parameters; however, limited attention has been paid to the geometric information of the source. This negligence may cause errors, or even failure, in the STE. Therefore, this paper proposes a line source estimation method that combines Bayesian inference with the super-Gaussian function. This function can approximate the shape of sources with several intuitive coefficients, which are adjusted to their true value through Bayesian inference. The performance of the proposed method was evaluated through estimation of a line source in two cases: an ideal urban boundary layer, via simulation, and a complex urban square, via a wind tunnel experiment. The results demonstrate that this method is capable of identifying the source information without any prior geometric information regarding the source. Moreover, it was confirmed that the conventional point-based assumption method leads to failure in estimating the line source, which implies that geometry estimation is necessary for STE.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Ambientales , Contaminantes Atmosféricos/análisis , Teorema de Bayes , Simulación por Computador , Monitoreo del Ambiente
11.
Artif Cells Nanomed Biotechnol ; 47(1): 4182-4193, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31722575

RESUMEN

The clinical benefit of cancer immunotherapy, including tumour vaccines, is influenced by immunosuppressive factors in the tumour microenvironment. Among these factors, cancer-associated fibroblasts (CAFs) and their products, such as fibroblast activation protein-α (FAPα), greatly affect tumourigenesis, development, metastasis and treatment tolerance, which make them promising immunotherapy targets for cancer patients. Our previous study reported that a whole cell tumour vaccine (WCTV) expressing FAPα inhibited tumour growth by simultaneously attacking cancer cells and CAFs. This study aimed to improve WCTVs with xenoantigens to end immune tolerance and to further activate the adaptive immune system. In the present study, we designed a WCTV by transducing a vector encoding human FAPα (hFAPα) into murine tumour cells and evaluated its efficacy in multiple solid tumour models. Immunotherapy with this WCTV effectively delayed tumour growth and prevented recurrence. The anti-tumour responses were clearly linked to antigen-specific cytotoxic T cells, whereas CD4(+) T lymphocytes also played a role. Humoural immune responses were activated because the adoptive transfer of immunoglobulins induced abscopal anti-tumour effects, and autoantibodies against FAPα were specifically detected in the sera of immunized mice. Moreover, an increased number of apoptotic tumour cells along with a reduced number of CAFs within the tumours suggest that xenogeneic FAPα-based WCTV has the potential to drive T cell and antibody responses against cancer cells and CAFs. This finding could offer an advanced strategy to treat multiple solid tumours with individualized cancer immunotherapy techniques.


Asunto(s)
Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Gelatinasas/genética , Proteínas de la Membrana/genética , Serina Endopeptidasas/genética , Inmunidad Adaptativa/inmunología , Animales , Autoanticuerpos/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Endopeptidasas , Fibroblastos/metabolismo , Fibroblastos/patología , Expresión Génica , Humanos , Inmunidad Celular/inmunología , Ratones , Seguridad
12.
Mol Clin Oncol ; 8(4): 603-608, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29541471

RESUMEN

A meta-analysis was performed to evaluate the accuracy of optical coherence tomography (OCT) for diagnostic accuracy studies in bladder cancer patients. English language studies reporting the diagnostic accuracy of OCT for bladder cancer were retrieved from the PubMed, EMBASE and Cochrane Library databases in December 2014. Histopathology was a reference standard. Sensitivities, specificities, positive likelihood ratios and negative likelihood ratios were calculated, and summary receiver operating characteristic curves were drawn to determine the diagnostic accuracy of OCT. Finally, 9 eligible studies (468 patients) were included in our meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of OCT were 0.96 [95% confidence interval (CI): 0.94-0.98], 0.82 (95% CI: 0.80-0.85), 6.83 (95% CI: 3.24-14.1) and 0.05 (95% CI: 0.02-0.16), respectively. The summary diagnostic odds ratio was 138.88 (95% CI: 29.63-650.89) and the overall area under the curve was 0.9735. These results suggest that OCT has excellent diagnostic performance in patients with bladder cancer and recurrent lesions.

13.
J Evid Based Med ; 11(1): 56-63, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29380525

RESUMEN

AIM: Found some new methods that can be used to obtain values such as true positives (TP), false negatives (FN), false positives (FP), and true negatives (TN) which did not provide in diagnostic meta-analysis indirectly. METHODS: Using mathematical deduction and programming calculus. RESULTS: We have succeeded in increasing the number of articles that can be used from two(228 patients) to five(469 patients) by using our new method. CONCLUSION: Using these methods, it can greatly increase the number of the inclusion articles, as well as the number of inclusion patients, which will contribute to improve the persuasiveness and comprehensiveness of diagnostic meta-analysis.


Asunto(s)
Metaanálisis como Asunto , Reacciones Falso Negativas , Reacciones Falso Positivas
14.
PLoS One ; 11(7): e0159860, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27459193

RESUMEN

PURPOSE: The aim of this study is to evaluate the diagnostic accuracy of Raman spectroscopy system in the detection of malignant breast lesions through a systemic review and meta-analysis of published studies. METHODS: We conducted a comprehensive literature search of PubMed and Embase from 2000 to June 2015. Published studies that evaluated the diagnostic performance of Raman spectroscopy in distinguishing malignant breast lesions from benign lesions and normal tissues were included in our study. The pooled sensitivity, specificity, diagnostic odds ratio, and the area under the curve of summary receiver-operating characteristic curves was derived. A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies guidelines was used to assess the quality of included studies. RESULTS: The initial search produced a total of 157 articles after removing duplicates. Nine studies (8 in vitro and 1 in vivo) were eligible in this meta-analysis. We analyzed the eight in vitro studies with 1756 lesions, the pooled sensitivity and specificity of Raman spectroscopy system for the diagnosis of malignant breast lesions were 0.92 (95% CI 0.86-0.96) and 0.97 (97% CI 0.93-0.98), respectively. Diagnostic odds ratio was 266.70 (95% CI 89.38-795.79), and the area under the curve of summary receiver-operating characteristic curves was 0.98 (95% CI 0.97-0.99). Significant heterogeneity was found between studies. There was no evidence of considerable publication bias. CONCLUSIONS: Raman spectroscopy system is an optical diagnostic technology with great value for detecting malignant breast lesions. At the same time, it has advantages of being non-invasive, real-time, and easy to use. Thus it deserves to be further explored for intra-operatory breast tumor margin detection.


Asunto(s)
Neoplasias de la Mama/patología , Técnicas de Diagnóstico Molecular/normas , Espectrometría Raman/normas , Femenino , Humanos , Metástasis de la Neoplasia , Sensibilidad y Especificidad
15.
Sci Rep ; 6: 23262, 2016 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-26979925

RESUMEN

Advanced or metastatic breast cancer is an incurable disease with high mortality rate worldwide and about 20% of breast cancers overexpress and amplify the human epidermal growth factor receptor 2 (HER2). Achievements in targeted therapy have benefited people during the past decades. Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate playing a powerful role in anti-tumor activity, not only blocks the HER2 signaling pathways, but also disturbs the microtubule dynamics. To access the efficacy and safety of T-DM1, we analyzed 9 clinical trials on T-DM1. Results showed that fatigue (0.604, 95% CI 0.551, 0.654), nausea (0.450, 95% CI 0.365, 0.537), increased transaminases (0.425, 95% CI 0.353, 0.500) and thrombocytopenia (0.383, 95% CI 0.322, 0.448) occurred more frequently in participants with single T-DM1. In controlled trials, increased transaminases (OR = 4.040, 95% CI 1.429, 11.427), thrombocytopenia (OR = 8.500, 95% CI 3.964, 18.226) and fatigue (OR = 1.288, 95% CI 1.041, 1.593) were statistically significant. Only thrombocytopenia appeared as severe adverse event (grade ≥ 3) in single-arm and control-arm studies. Meanwhile, T-DM1 stabilized cancer and prolonged life with notable improved progression-free survival (PFS) and overall survival (OS). In conclusion, it is a safe and effective agent in advanced or metastatic breast cancer, but should be carefully applied on patients with severe hepatic and neurological disease.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Maitansina/análogos & derivados , Receptor ErbB-2/metabolismo , Ado-Trastuzumab Emtansina , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Maitansina/efectos adversos , Maitansina/uso terapéutico , Modelos de Riesgos Proporcionales , Trastuzumab , Resultado del Tratamiento
16.
Cancer Biomark ; 16(1): 71-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26835707

RESUMEN

BACKGROUND: The Hedgehog (Hh) signaling pathway has recently been reported to be associated with the prognosis of digestive system cancers. However, the results are inconsistent. OBJECTIVE: This study aimed to investigate the association between Hh pathway components and survival outcomes in patients with digestive system cancers. METHODS: We conducted a comprehensive retrieval in PubMed, EMBASE and Cochrane library for relevant literatures until May 1st, 2015. The pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) with 95% confidence intervals (CIs) were calculated to clarify the prognostic value of Hh pathway components, including Shh, Gli1, Gli2, Smo and Ptch1. RESULTS: A total of 16 eligible articles with 3222 patients were included in the meta-analysis. Pooled HR suggested that over-expression of Shh and Gli1 were both associated with poor OS (HR = 1.87, 95% CI: 1.14-3.07 and HR = 1.96, 95% CI: 1.66-2.32, respectively) and DFS (HR = 2.37, 95% CI: 1.19-4.72 and HR = 2.18, 95% CI: 1.61-2.96, respectively). In addition, over-expression of Smo was associated with poor DFS (HR = 1.38, 95% CI: 1.08-1.75). CONCLUSIONS: This study reveals that over-expressed Hh pathway components, including Shh, Gli1 and Smo, are associated with poor prognosis in digestive system cancer patients. Hh signaling pathway may become a potential therapeutic target in digestive system cancers.


Asunto(s)
Neoplasias del Sistema Digestivo/metabolismo , Neoplasias del Sistema Digestivo/mortalidad , Proteínas Hedgehog/metabolismo , Transducción de Señal , Biomarcadores , Neoplasias del Sistema Digestivo/genética , Expresión Génica , Proteínas Hedgehog/genética , Humanos , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Pronóstico , Sesgo de Publicación , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptor Smoothened , Transactivadores/genética , Transactivadores/metabolismo , Proteína con Dedos de Zinc GLI1
17.
J Clin Ultrasound ; 44(4): 199-209, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26402325

RESUMEN

PURPOSE: The use of contrast-enhanced sonography (CEUS) has yielded promising results in the differentiation of thyroid nodules. We conducted this meta-analysis to assess its performance in identifying and distinguishing between benign and malignant thyroid nodules. METHODS: PubMed, Medline, Embase, and the Cochrane Library were searched for studies published through the end of December 2013. Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve were calculated. RESULTS: A total of 13 studies were included in this meta-analysis. For the diagnosis of malignant thyroid nodules worldwide, the overall mean rates of sensitivity and specificity of CEUS were 90% (95% confidence interval [CI], 88-93%) and 86% (95% CI, 83-89%), respectively. The summary diagnostic odds ratio was 52.83 (95% CI, 21.71-128.55), and the area under the curve for the summary receiver operating characteristic curve was 0.94 (95% CI, 0.90-0.98). CONCLUSIONS: This meta-analysis indicates that CEUS may be a valuable supplemental method, with high rates of sensitivity and specificity, to use for identifying and distinguishing between benign and malignant thyroid nodules.


Asunto(s)
Medios de Contraste/farmacología , Glándula Tiroides/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico , Ultrasonografía/métodos , Diagnóstico Diferencial , Humanos , Reproducibilidad de los Resultados
18.
Sci Rep ; 5: 16427, 2015 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-26553557

RESUMEN

Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.


Asunto(s)
Adyuvantes Inmunológicos , Vacunas contra el Cáncer/inmunología , Células Dendríticas/inmunología , Neoplasias/inmunología , Ácido Úrico , Traslado Adoptivo , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Citocinas/metabolismo , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Femenino , Inmunización , Inmunoglobulinas/administración & dosificación , Interferón gamma , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Activación de Linfocitos/inmunología , Ratones , Neoplasias/metabolismo , Neoplasias/mortalidad , Neoplasias/terapia , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Ácido Úrico/administración & dosificación , Ácido Úrico/inmunología , Ácido Úrico/metabolismo
19.
Ultrasound Med Biol ; 41(3): 659-68, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25619783

RESUMEN

This meta-analysis was aimed at assessing the performance of oral/microbubble contrast-enhanced ultrasound (CEUS) in the detection of active Crohn's disease (CD). A literature search of PubMed, Medline, the China National Knowledge Infrastructure and the Cochrane Library was conducted. Published articles that evaluated the diagnostic potency of CEUS in CD were included in the study. A total of eight articles, which included 428 patients, were finally analyzed. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve were calculated to examine the diagnostic accuracy of CEUS. The pooled sensitivity and specificity of CEUS for active CD were 93% (95% confidence interval: 89%-95%) and 87% (81%-91%), respectively. The summary diagnostic odds ratio was 80.35 (30.93-208.73), and the area under the curve was 0.9633. In conclusion, this meta-analysis pooled results from previous studies to evaluate the accuracy of CEUS in the detection of CD. We found that CEUS has high accuracy in the detection of active CD using endoscopy/biopsy or clinical index as the reference standard. In the future, CEUS may also be widely used in other diseases, reducing the necessity for invasive diagnostic procedure.


Asunto(s)
Medios de Contraste , Enfermedad de Crohn/diagnóstico por imagen , Humanos , Sensibilidad y Especificidad , Ultrasonografía
20.
Int J Clin Exp Med ; 8(10): 17333-42, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26770325

RESUMEN

PURPOSE: This meta-analysis aimed to evaluate the performance of diffusion-weighted magnetic resonance imaging (DWI) in identification of colorectal cancer. METHODS: A systematic literature search was performed for studies that evaluated the diagnostic accuracy of DWI in identification of colorectal cancer. Methodological quality was assessed by Quality Assessment for Studies of Diagnostic Accuracy 2 (QUADAS 2) tool. After extracting data, we estimated the pooled sensitivity, specificity, likelihood ratios, and constructed summary receiver operating characteristics (SROC) curve. RESULTS: Ten studies involving 367 malignant lesions and 178 benign lesions were considered eligible after full-text review. The pooled sensitivity and specificity were 0.95 (95% CI: 0.90-0.97) and 0.93 (95% CI: 0.85-0.97), respectively. Positive likelihood ratio and negative likelihood ratio were 12.8 (95% CI: 5.99-27.4) and 0.06 (95% CI: 0.03-0.11), respectively. The area under SROC curve was 0.98. CONCLUSIONS: Our meta-analysis indicates that DWI is a highly accurate diagnostic method in identification of colorectal cancer.

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