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2.
IEEE J Biomed Health Inform ; 24(1): 292-299, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30969934

RESUMO

Human activity recognition has been widely used in healthcare applications such as elderly monitoring, exercise supervision, and rehabilitation monitoring. Compared with other approaches, sensor-based wearable human activity recognition is less affected by environmental noise and therefore is promising in providing higher recognition accuracy. However, one of the major issues of existing wearable human activity recognition methods is that although the average recognition accuracy is acceptable, the recognition accuracy for some activities (e.g., ascending stairs and descending stairs) is low, mainly due to relatively less training data and complex behavior pattern for these activities. Another issue is that the recognition accuracy is low when the training data from the test subject are limited, which is a common case in real practice. In addition, the use of neural network leads to large computational complexity and thus high power consumption. To address these issues, we proposed a new human activity recognition method with two-stage end-to-end convolutional neural network and a data augmentation method. Compared with the state-of-the-art methods (including neural network based methods and other methods), the proposed methods achieve significantly improved recognition accuracy and reduced computational complexity.

3.
J Neural Eng ; 17(1): 016025, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31476743

RESUMO

OBJECTIVE: Electroencephalography (EEG) motor imagery classification has been widely used in healthcare applications such as mobile assistive robots and post-stroke rehabilitation. Recently, EEG motor imagery classification methods based on convolutional neural networks (CNNs) have been proposed and have achieved relatively high classification accuracy. However, these methods use single convolution scale in the CNN, while the best convolution scale differs from subject to subject. This limits the classification accuracy. Another issue is that the classification accuracy degrades when training data is limited. APPROACH: To address these issues, we have proposed a hybrid-scale CNN architecture with a data augmentation method for EEG motor imagery classification. MAIN RESULTS: Compared with several state-of-the-art methods, the proposed method achieves an average classification accuracy of 91.57% and 87.6% on two commonly used datasets, which outperforms several state-of-the-art EEG motor imagery classification methods. SIGNIFICANCE: The proposed method effectively addresses the issues of existing CNN-based EEG motor imagery classification methods and improves the classification accuracy.

4.
IEEE Trans Biomed Circuits Syst ; 13(5): 1112-1121, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31329129

RESUMO

Wearable intelligent ECG monitoring devices can perform automatic ECG diagnosis in real time and send out alert signal together with abnormal ECG signal for doctor's further analysis. This provides a means for the patient to identify their heart problem as early as possible and go to doctors for medical treatment. For such system the key requirements include high accuracy and low power consumption. However, the existing wearable intelligent ECG monitoring schemes suffer from high power consumption in both ECG diagnosis and transmission in order to achieve high accuracy. In this work, we have proposed an energy-efficient wearable intelligent ECG monitor scheme with two-stage end-to-end neural network and diagnosis-based adaptive compression. Compared to the state-of-the-art schemes, it significantly reduces the power consumption in ECG diagnosis and transmission while maintaining high accuracy.

5.
World J Gastroenterol ; 25(15): 1828-1839, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057297

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression. AIM: To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α (HIF1α) are prognostic and predictive biomarkers in GC. METHODS: A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC. RESULTS: Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases , deeper infiltration depth and later tumor-node-metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC. CONCLUSION: LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metástase Linfática/patologia , Proteína-Lisina 6-Oxidase/metabolismo , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/análise , Carcinogênese/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína-Lisina 6-Oxidase/análise , RNA Mensageiro/isolamento & purificação , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Estômago/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Microambiente Tumoral
6.
Onco Targets Ther ; 12: 861-867, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774373

RESUMO

Objective: PD-1 inhibitors have improved efficacy in many cancers. There are currently no reports of the use of PD-1 inhibitors, such as nivolumab, for metastatic biliary tract cancer (mBTC). This study reviewed the efficacy and safety of nivolumab for mBTC with the aim of exploring ways to improve efficacy and survival. Methods: Thirty patients with mBTC were voluntarily treated with nivolumab at the PLA General Hospital. Nivolumab 3 mg/kg was administered. Progression-free survival (PFS) and overall survival were evaluated by Kaplan-Meier and univariate and multivariate analyses were carried out for clinical characteristics. Objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs) were also evaluated. Results: The median treatment cycle is four cycles. One case was complete response, 5 cases partial response, 12 cases stable, and 12 cases progression. ORR was 20%, DCR was 60%, and PFS was 3.1 months (95% CI: 2.13-4.06). The AEs of nivolumab monotherapy were fatigue (three cases), fever (two cases), hypothyroidism (one case), skin reaction (one case), and liver injury (one case). Nivolumab combined with chemotherapy related grade 1-2 hematologic toxicity were leukopenia (five cases) and thrombocytopenia (two cases), and grade 3-4 were leukopenia (three cases). Non-hematologic toxicity grade 1-2 were nausea and vomiting (four cases), fatigue (four cases), fever (three cases), peripheral neurotoxicity (three cases), and hypothyroidism (one case). Univariate analysis showed that PFS of nivolumab combined with chemotherapy was statistically significant compared with that of nivolumab monotherapy (4.1 vs 2.3 months, P=0.031). Programmed death-ligand 1 (PD-L1) expression positively has no relationship with better PFS in contrast with PD-L1 negatively (3.6 vs 3.0 months P>0.05). Multivariate analysis show nivolumab combined with chemotherapy was only the independent factor for longer PFS (HR: 0.432, P<0.05). Conclusion: The safety of nivolumab in mBTC is controllable. Further selection of superior populations is needed to improve the efficacy of nivolumab in mBTC.

7.
J Hematol Oncol ; 12(1): 16, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764882

RESUMO

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

8.
Dis Markers ; 2019: 6812045, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30805037

RESUMO

Background: Previously, it was demonstrated that serum levels of tumor markers, CEA and CA19-9, correlated with chemotherapy. Consequently, it has been hypothesized that dynamic monitoring of changes in these markers may predict the shrinkage or growth of colorectal cancers. To test this hypothesis, we analyzed CEA and CA19-9 serum levels in patients with advanced colorectal cancer who received cetuximab in combination with chemotherapy. These levels were evaluated at various time points to identify their potential to serve as early efficacy predictors during treatment and early predictors of disease progression. Patients and Methods: Measurements of tumor markers, CEA and CA 19-9, in patients with metastatic colorectal cancer (n = 73) who received cetuximab plus folinic acid, fluorouracil, and oxaliplatin or irinotecan (FOLFOX4/FOLFIRI) as a first-line treatment at our center were retrospectively analyzed. These levels were also compared with objective responses according to the World Health Organization criteria. Initially, 65 patients had elevated CEA levels (>5 ng/ml), and 59 patients had elevated levels of CA19-9 (>37 U/ml). A total of 172 cycles and 165 cycles of computed tomography/magnetic resonance imaging observations were available for review from these two patient groups. Results: After completing three cycles of treatment, the best diagnosis of cetuximab resistance was achieved when CEA increased by 35% (efficacy, 83.33%; sensitivity, 75.41%) and when CA19-9 increased by 28% (efficacy, 80.00%; sensitivity, 84.31%). Next, the efficacy of cetuximab at the time of diagnosis (at the first imaging examination/after three cycles of treatment) was evaluated after the first cycle of chemotherapy. When CEA decreased by 60% from its baseline level, the best effective rate and sensitivity were observed (63.64% and 80.95%, respectively). Similarly, when CA19-9 was 45% lower than its baseline level, the best effective rate and sensitivity were observed (84.21% and 93.18%, respectively). To evaluate progression-free survival (PFS), levels of both CEA and CA19-9 were evaluated after the third cycle of chemotherapy. Increases of 35% and 28%, respectively, resulted in a shorter PFS period compared with the other patients (3.15 months vs. 9.10 months, respectively; P < 0.0001). Conversely, when the evaluation was performed after the first cycle of chemotherapy, patients exhibiting a 60% decrease in CEA and a 45% decrease in CA19-9 had a longer PFS period (11.13 months vs. 8.10 months, respectively; P = 0.0395). Conclusions: CEA and CA19-9 are useful indicators of therapeutic curative effect from cetuximab combined with first-line chemotherapy. These markers also helped assess cetuximab resistance and served as early predictors of initial treatment effectiveness. Furthermore, a simultaneous increase or decrease in the levels of both indicators was consistent with the observed differences in PFS.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Camptotecina/análogos & derivados , Cetuximab/uso terapêutico , Neoplasias Colorretais/sangue , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Intervalo Livre de Progressão
9.
Technol Cancer Res Treat ; 18: 1533033818824367, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30803368

RESUMO

The aim of this study was to evaluate the safety and clinical efficacy of a combined preoperative regimen consisting of volumetric modulated arc therapy-simultaneous integrated boost and capecitabine chemotherapy for distal rectal cancer. A total of 26 patients with locally advanced distal rectal cancer were enrolled from March 2015 to May 2016. The radiation dose fractionation was 58.75 Gy/25 fractions (2.35 Gy/fraction) for rectal tumor and pelvic lymph node metastasis and 50 Gy/25 fractions for pelvic lymph node stations, accompanied with simultaneous capecitabine chemotherapy. Completion of the simultaneous chemotherapy was ensued by 1 week of rest and then another cycle of induction chemotherapy with capecitabine. A radical rectal cancer surgery was performed 6 to 8 weeks after the simultaneous chemoradiotherapy. The primary end points were the complete pathological response rate and the postoperative sphincter preservation rate. All 26 patients completed the neoadjuvant chemoradiotherapy, among which 25 received surgical treatment. The postoperative complete pathological response rate was as high as 32% (8/25), while the sphincter preservation rate was 60% (15/25), the overall tumor/node (T/N) downstaging rate was 92% (23/25), and the R0 resection rate was 100%. During the chemoradiation, the most common adverse events were grade 1 and 2; grade 3 radiodermatitis occurred in 2 cases but no occurrence of acute adverse events occurred that were grade 4 and above. After the surgery, there was one case of ureteral injury and one case of intestinal obstruction, but no perioperative deaths occurred. In conclusion, the chemoradiation regimen of preoperative volumetric modulated arc therapy-simultaneous integrated boost (VMAT-SIB58.75Gy) and a single cycle of induction chemotherapy with capecitabine for patients with distal rectal cancer is safe and feasible with a satisfactory complete pathological response rate, sphincter preservation rate, and R0 resection rate.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/terapia , Radioterapia de Intensidade Modulada/métodos , Neoplasias Retais/terapia , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Cuidados Pré-Operatórios , Prognóstico , Dosagem Radioterapêutica , Neoplasias Retais/patologia , Adulto Jovem
10.
J Clin Oncol ; 36(30): 3031-3039, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30199311

RESUMO

PURPOSE: Cetuximab in combination with chemotherapy is a standard-of-care first-line treatment regimen for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC); however, the efficacy of cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX) has never before been proven in a controlled and randomized phase III trial. To our knowledge, the TAILOR trial ( ClinicalTrials.gov identifier: NCT01228734) is the first randomized, multicenter, phase III study of the addition of cetuximab to first-line FOLFOX prospectively choosing a RAS wt population and thus providing confirmative data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone. PATIENTS AND METHODS: TAILOR is an open-label, randomized (1:1), multicenter, phase III trial in patients from China comparing FOLFOX-4 with or without cetuximab in RAS wt (KRAS/NRAS, exons 2 to 4) mCRC. The primary end point of TAILOR was progression-free survival time; secondary end points included overall survival time, overall response rate, and safety and tolerability. RESULTS: In the modified intent-to-treat population of 393 patients with RAS wt mCRC, adding cetuximab to FOLFOX-4 significantly improved the primary end point of progression-free survival time compared with FOLFOX-4 alone (hazard ratio, 0.69; 95% CI, 0.54 to 0.89; P = .004; median, 9.2 v 7.4 months, respectively), as well as the secondary end points of overall survival time (current assessment after 300 events: hazard ratio, 0.76; 95% CI, 0.61 to 0.96; P = .02; median, 20.7 v 17.8 months, respectively) and overall response rate (odds ratio, 2.41; 95% CI, 1.61 to 3.61; P < .001; 61.1% v 39.5%, respectively). Treatment was well tolerated, and there were no new or unexpected safety findings. CONCLUSION: The TAILOR study met all of its objectives and relevant clinical end points, confirming cetuximab in combination with FOLFOX as an effective standard-of-care first-line treatment regimen for patients with RAS wt mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Cetuximab/efeitos adversos , China , Neoplasias Colorretais/mortalidade , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Intervalo Livre de Progressão , Adulto Jovem
11.
Exp Cell Res ; 372(1): 35-42, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30205088

RESUMO

Recent studies have demonstrated that higher expression of follicular helper T cell (Tfh)-associated genes is associated with better prognosis in breast cancer and colorectal cancer (CRC), but the underlying mechanisms remain unclear. In this study, we compared the function of Tfh cells in non-cancer (NC) controls and in CRC patients between stages II and IV. Data showed that the level of CD4+CXCR5+ Tfh cells were significantly upregulated in stage II CRC patients but was progressively reduced in stage III and stage IV patients. The frequency of PD-1+ cells in CD4+CXCR5+ Tfh cells, on the other hand, was progressively increased from NC patients to CRC patients with increasing severity. Interestingly, the CD4+CXCR5+PD-1- Tfh cells, but not the CD4+CXCR5+PD-1+ Tfh cells, promoted the CD107a expression and IFN-γ expression by CD8+ T cells. This CD8+ T cell-promoting capacity was dependent on the expression of IL-21, as this capacity was significantly impaired by IL-21 neutralization. Tfh cells from CRC patients with advanced stages presented gradual reduction in the capacity to stimulate CD8+ T cells and the capacity to produce IL-21. In addition, treatment with autologous PD-L1-expressing tumor cells further suppressed the IL-21 expression by PD-1+ Tfh cells. Together, these data demonstrated that Tfh cells potently enhanced the effector functions of CD8+ T cells in an IL-21-dependent pathway; however, this role of Tfh cells was limited in CRC patients due to PD-1/PD-L1-mediated suppression.


Assuntos
Antígeno B7-H1/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Interleucinas/genética , Receptor de Morte Celular Programada 1/genética , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adolescente , Adulto , Idoso , Antígeno B7-H1/imunologia , Estudos de Casos e Controles , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Imunofenotipagem , Interferon gama/genética , Interferon gama/imunologia , Interleucinas/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/genética , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/imunologia , Receptores CXCR5/genética , Receptores CXCR5/imunologia , Transdução de Sinais , Linfócitos T Citotóxicos/patologia , Linfócitos T Auxiliares-Indutores/patologia
12.
Biomed Pharmacother ; 105: 18-26, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29843041

RESUMO

Special targeted therapy like endothelial growth factor receptor (EGFR) targeted therapy is available for the treatment of advanced non-small cell lung cancer (NSCLC). Biodegradable core-shell lipid-polymer hybrid nanoparticles (LPNs) can combine the beneficial properties of lipid and polymeric NPs for controlled drug delivery. In the present study, epidermal growth factor (EGF) conjugated LPNs were fabricated to co-deliver docetaxel (DTX) and resveratrol (RSV). In vitro and in vivo studies demonstrated that EGF DTX/RSV LPNs have significant synergistic effects, best tumor inhibition ability and the lowest systemic toxicity. The results indicate that EGF DTX/RSV LPNs may be a promising strategy for treatment of NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Portadores de Fármacos/química , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Fatores de Crescimento Endotelial/química , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Polietilenoglicóis/química , Resveratrol , Ácidos Esteáricos/química , Estilbenos/administração & dosagem , Estilbenos/uso terapêutico , Propriedades de Superfície , Taxoides/administração & dosagem , Taxoides/uso terapêutico
13.
Clin Epigenetics ; 10: 69, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29796120

RESUMO

Background: Reduced expression of retinoic acid-induced 2 (RAI2) was found in breast cancer. The regulation and function of RAI2 in human colorectal cancer (CRC) remain unclear. Methods: Eight CRC cell lines and 237 cases of primary CRC were analyzed. Methylation-specific PCR (MSP), flow cytometry, xenograft mouse model, and shRNA technique were employed. Results: RAI2 was completely methylated in RKO, LOVO, and HCT116 cells; partially methylated in HT29 cells; and unmethylated in SW480, SW620, DLD1, and DKO cells. RAI2 was methylated in 53.6% (127/237) of primary colorectal cancer. Methylation of RAI2 was significantly associated with gender (P < 0.001), TNM stage (P < 0.001), and lymph node metastasis (P < 0.001). Analyzing by the Kaplan-Meier method, methylation of RAI2 was significantly associated with poor 5-year overall survival (OS) (P = 0.0035) and 5-year relapse-free survival (RFS) (P = 0.0062). According to Cox proportional hazards model analysis, RAI2 methylation was an independent poor prognostic marker for 5-year OS (P = 0.002) and poor 5-year RFS (P = 0.022). RAI2 suppressed cell proliferation, migration, and invasion and induced cell apoptosis in CRC. In addition, RAI2 inhibited AKT signaling in CRC cells and suppressed human CRC cell xenograft growth in mice. Conclusion: RAI2 is frequently methylated in human CRC, and the expression of RAI2 is regulated by promoter region methylation. Methylation of RAI2 is an independent poor prognostic marker of CRC. RAI2 suppresses CRC cell growth both in vitro and in vivo. RAI2 suppresses CRC by inhibiting AKT signaling.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Metilação de DNA , Regulação para Baixo , Proteínas/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Metástase Linfática , Masculino , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Análise de Sobrevida
14.
Onco Targets Ther ; 11: 1285-1292, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29563807

RESUMO

Background: To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. Materials and methods: Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. Results: The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P=0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV (P<0.001) and TNM stage III (P<0.001). Moreover, Kaplan-Meier survival analysis showed that c-kit (P<0.001) expression was correlated with reduced disease-free survival (DFS). Multivariate analysis identified c-kit as an independent poor prognostic factor of DFS in HCC patients (P<0.001). Conclusion: Increased c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.

15.
Sci Rep ; 8(1): 4602, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29545575

RESUMO

No definitive treatment strategy has been established for patients with metastatic colorectal cancer (mCRC) who experienced progression after three or more lines of chemotherapy. A total of 36 mCRC patients were enrolled in this retrospective study who received apatinib therapy under non-clinical trial setting after progression in People's liberation army general Hospital from March 2015 and August 2017. Progression free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR) and treatment-related adverse events (AEs) were reviewed and evaluated. Five patients achieved partial response (PR), and 25 achieved stable disease (SD), and 6 achieved progression disease (PD), illustrating a DCR of 83.3% and an ORR of 13.9%. Median PFS was 3.82 m and median OS was not reached. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 adverse event incidence of 27.8%. The most common grade 3/4 adverse events were hypertension (n = 4, 11.1%), liver function damage (n = 3, 8.3%) and hand-foot syndrome (n = 2, 5.6%). No drug-related death occurred. Apatinib therapy provides a reasonable option with an acceptable safety profile for Chinese mCRC patients failed to prior chemotherapy.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Humanos , Hipertensão/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
16.
Cancer Med ; 7(4): 997-1005, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29532995

RESUMO

Chemotherapy-induced neutropenia (CIN) has been shown to be associated with improved clinical outcomes in patients with various solid tumors. This study retrospectively assessed the association between timing of CIN and prognosis in 321 patients with advanced gastric cancer (AGC) who finished at least one cycle of chemotherapy with oxaliplatin and capecitabine (XELOX). Primary landmark analyses were restricted to 274 patients who received four cycles of chemotherapy and lived for more than 4 months. CIN was categorized as early-onset and non-early-onset. The correlation between timing of CIN with survival was analyzed by the Kaplan-Meier method and a Cox proportional hazards model. Relative to patients with non-early-onset CIN, those with early-onset CIN had significantly longer times to disease progression (hazard ratio [HR] 0.574; 95% confidence interval [CI] 0.453-0.729, P < 0.001) and death (HR: 0.607; 95% CI: 0.478-0.770, P < 0.001), consistent with results from the landmark group. In conclusion, timing of CIN may be a potential prognostic biomarker in patients with AGC receiving first-line chemotherapy with XELOX. Early-onset CIN predicts better survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/diagnóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Neutropenia Febril Induzida por Quimioterapia/etiologia , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento
17.
BMC Cancer ; 17(1): 885, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29273007

RESUMO

BACKGROUND: This phase II bridging study assessed the safety and efficacy of nab-paclitaxel/gemcitabine (Metastatic Pancreatic Adenocarcinoma Clinical Trial [MPACT] regimen) in Chinese patients with metastatic pancreatic cancer (MPC). METHODS: This 3-part sequential study evaluated nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. Part 1 evaluated safety. Part 2 evaluated efficacy using Simon's optimal 2-stage design: if >2 responses were observed in Stage 1 (n = 28), 54 additional patients would be enrolled in Stage 2. If >9 responses were observed, the study was complete. Otherwise, nab-paclitaxel/gemcitabine would be compared with gemcitabine alone in Part 3. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), overall survival (OS), and safety. RESULTS: Eighty-three patients were treated. The prespecified primary endpoint was met: the independently assessed ORR in Stages 1 + 2 was 35% (95% CI, 24.8-46.2); therefore, Part 3 was not initiated. The median DOR was 8.9 months (95% CI, 6.01-8.94). The median OS and progression-free survival were 9.2 (95% CI, 7.6-11.1) and 5.5 (95% CI, 5.29-7.16) months, respectively. The 12-month OS rate was 30%. In an updated analysis, the median OS was 9.3 months and the 12-month OS rate was 32%. Longer OS was observed in patients with baseline neutrophil-to-lymphocyte ratio ≤ 5 vs > 5. The most common grade ≥ 3 adverse events were leukopenia (35%), neutropenia (34%), anemia (15%), thrombocytopenia (10%), and fatigue (13%). Grade 3 peripheral neuropathy occurred in 7% of patients (no grade 4 reported). CONCLUSIONS: The MPACT regimen of nab-paclitaxel/gemcitabine is efficacious in Chinese patients with MPC. No new safety signals were observed. TRIAL REGISTRATION: NCT02135822 , May 8, 2014.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Albuminas/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Prognóstico , Segurança , Taxa de Sobrevida
18.
Oncotarget ; 8(54): 92401-92410, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29190925

RESUMO

This single-arm, phase II trial is to investigate efficacy and safety of nab-paclitaxel plus S-1 as first-line treatment in advanced pancreatic cancer. Nab-paclitaxel was administered at 120 mg/m2 intravenously on day 1 and 8, S-1 was given twice a day orally on day 1-14 of each 21-day cycle, for 6 cycles. The primary endpoint was objective response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. The ORR in intent-to-treat population (N=60) by either blinded independent review (BIR) or investigator assessment was 50.0%. Median PFS (mPFS) by BIR and median OS (mOS) were 5.6 months (95%CI, 4.6 to 6.6 m) and 9.4 months (95%CI, 8.0 to 10.8m), respectively. The most common grade 3 or 4 toxicities were leukopenia/neutropenia (35%) and fatigue (8.3%). Subgroup analyses based on BIR showed a remarkable ORR (>70%) was achieved in patients with female gender, ≥ 50% decline from baseline CA19-9, and developed grade 3 or 4 leukopenia/neutropenia. Remarkable survival benefit was statistically significant in female (mPFS: 7.7m, mOS: 18.2m), ≥ 50% decline from baseline CA19-9 (mPFS: 6.8m, mOS: 11.8m), objective responders (mPFS: 6.9m, mOS: 12.2m), and ECOG of 0 at baseline (mPFS: 7.5m, mOS: 16.1m). Nab-paclitaxel plus S-1 showed encouraging ORR and manageable toxicities, which is an effective alternative treatment regimen for advanced pancreatic cancer. (https://clinicaltrials.gov/ number, NCT02124317).

19.
Cochrane Database Syst Rev ; 11: CD012035, 2017 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-29178132

RESUMO

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is defined as a peripheral platelet count less than 100×109/L, with or without bleeding in cancer patients receiving myelosuppressive chemotherapy. CIT is a significant medical problem during chemotherapy, and it carries the risk of sub-optimal overall survival and bleeding. Alternative interventions to platelet transfusion are limited. Different stages of preclinical and clinical studies have examined the thrombopoietin receptor agonists (TPO-RAs) for CIT in patients with solid tumours. OBJECTIVES: To assess the effects of TPO-RAs to prevent and treat CIT in patients with solid tumours:(1) to prevent CIT in patients without thrombocytopenia before chemotherapy, (2) to prevent recurrence of CIT, and (3) to treat CIT in patients with thrombocytopenia during chemotherapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, to 28 September 2017), MEDLINE (from 1950 to 28 September 2017), as well as online registers of ongoing trials (Clinical Trials, Chinese Clinical Trial Register, Australian New Zealand Clinical Trial Registry, WHO ICTRP Search Portal, International Standard Randomised Controlled Trial Number registry, GlaxoSmithKline Clinical Study Register, and Amgen Clinical Trials) and conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Society of Medical Oncology, and Conference Proceedings Citation Index-Science, from 2002 up to September 2017) for studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing TPO-RAs alone, or in combination with other drugs, to placebo, no treatment, other drugs, or another TPO-RAs for CIT in patients with solid tumours. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard methodological methods expected by Cochrane. MAIN RESULTS: We identified six trials eligible for inclusion, of which two are ongoing, and one awaiting classification study. The three included trials were conducted at many different sites in Europe, America, and Asia. All of the three studies recruited adult and elder participants (no children were included) with solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs alone, or in combination with other drugs, to no treatment, or other drugs, or another TPO-RAs.We judged the overall risk of bias as high as we found a high risk for detection bias. We assessed the risk of bias arising from inadequate blinding of outcome assessors as high for number and severity of bleeding episodes (one of the primary outcomes).To prevent CIT: We included two trials (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral administration with chemotherapy) with placebo. The use of TPO-RAs may make little or no difference to the all-cause mortality at 33 weeks of follow-up (RR 1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22 to 1.78; two trials, 206 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06 to 2.06; two trials, 206 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life.To prevent recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs (romiplostim, single-dose subcutaneous administration with chemotherapy) with placebo. There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 2.80, 95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (no severe/life-threatening bleeding episodes; one trial, 62 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), it is planned to give TPO-RAs (romiplostim, subcutaneous administration with chemotherapy) to participants, but to date this trial has not reported any outcomes.To treat CIT: We found one ongoing study (expected recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag, seven days orally) to participants when their platelet counts are less than 75×109/L during chemotherapy. This trial was originally planned to complete in March 2017, however, the completion date has passed and no results are reported.The one awaiting classification study included patients without thrombocytopenia before chemotherapy (to prevent CIT), patients with thrombocytopenia during chemotherapy (to prevent recurrence of CIT), and other patients during chemotherapy (uncertain whether CIT had happened). There was no evidence for a difference in the number of patients with at least one bleeding episode of any severity (RR 0.27, 95% CI 0.07 to 1.02; one trial, 75 participants). There was no evidence for a difference in the number of patients with at least one severe/life-threatening bleeding episode (RR 0.44, 95% CI 0.03 to 6.77; one trial, 75 participants). This study did not address overall survival or quality of life. AUTHORS' CONCLUSIONS: No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. There was no evidence to support the use of TPO-RAs for treating CIT in patients with solid tumours.


Assuntos
Antineoplásicos/efeitos adversos , Benzoatos/administração & dosagem , Hidrazinas/administração & dosagem , Pirazóis/administração & dosagem , Receptores Fc/administração & dosagem , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/administração & dosagem , Trombocitopenia/tratamento farmacológico , Trombocitopenia/prevenção & controle , Trombopoetina/administração & dosagem , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade
20.
Sci Rep ; 7(1): 14368, 2017 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29085005

RESUMO

This study aims to investigate the efficacy of bevacizumab-combined chemotherapy (BCC) in Chinese stage IV colorectal cancer (CRC), and analyze the relationship between clinicopathological features with survival. Patients with stage IV CRC treated with BCC were analyzed retrospectively. 217 metastatic CRC (mCRC) patients were collected, out of which79 were right-sided CRCs and 138 were left-sided ones. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2, single agent chemotherapy, poor/mucous/signet ring cell component, second-and further-line of bevacizumab administration, multiple metastasis sites had comparatively worse survival. Among 141 patients with known KRAS status, 55 patients harbored KRAS mutation and 86 had wild type KRAS. The ORR and DCR were 41.9% and 78.9%, respectively, in patients with wild type KRAS, while ORR and DCR was 38.7% and 77.9%, respectively, in patients with KRAS mutation. The median PFS of patients with wild type and mutant KRAS were 8.38, and9.59 months, respectively; whereas the OS was 23.00 and 21.26 months, respectively for mCRC patients with wild-type and mutant KRAS. Cumulatively, our study indicated that BCC was effective and beneficial for Chinese stage IV CRC patients. KRAS mutation status and tumor location were not a prognostic factor for survival.


Assuntos
Bevacizumab/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Bevacizumab/uso terapêutico , China , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Retais/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Proteínas ras/genética
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