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Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.
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BACKGROUND: Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical fields, we attempt to integrate a well-trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images. MATERIALS AND METHODS: Open-source data sets and multicenter data sets have been used in this study. A three-dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results. RESULTS: The sensitivity and specificity of this well-trained model were found to be 84.4% (95% confidence interval [CI], 80.5%-88.3%) and 83.0% (95% CI, 79.5%-86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10-30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three-dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment. CONCLUSION: Under the companion diagnostics, the three-dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices. IMPLICATIONS FOR PRACTICE: The three-dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice.
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Aprendizado Profundo , Neoplasias Pulmonares/diagnóstico , Redes Neurais de Computação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Algoritmos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Esophageal squamous cell carcinoma (ESCC) is the leading pathologic type in China. miR-145 has been reported to be downregulated in multiple tumors. This study was aimed to investigate the role of miR-145 in ESCC. miR-145 expression was investigated in 65 ESCC samples as well as four ESCC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Targetscan 6.2 website (http://www.targetscan.org/) was used to predict the targets of miR-145. Expression of phospholipase C epsilon 1 (PLCE1) messenger RNA and protein was detected by qRT-PCR or Western blot. MTT and wound healing assay were conducted to explore the effects of miR-145 on the proliferation and migration of ESCC cell lines, respectively. miR-145 was significantly decreased in ESCC tissues. An inverse correlation between miR-145 and invasion depth and TNM stage were observed. PLCE1 was a direct target of miR-145, and the expression of PLCE1 was inversely correlated with miR-145 expression in ESCC tissues. In addition, overexpression of miR-145 suppressed cell proliferation and migration in ESCC cells. The enforced expression of PLCE1 partially reversed the suppressive effect of miR-145. These results prove that miR-145 may perform as a tumor suppressor in ESCC by targeting PLCE1.
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Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fosfoinositídeo Fosfolipase C/genética , Idoso , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosfoinositídeo Fosfolipase C/antagonistas & inibidores , Fosfoinositídeo Fosfolipase C/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
BACKGROUND AND PURPOSE: Several case reports and studies have suggested that there is an increased survival rate for patients who undergo resection of solitary adrenal metastasis from non-small cell lung cancer (NSCLC). This study aimed to investigate whether NSCLC patients with solitary adrenal metastasis could gain a higher survival rate after adrenalectomy (ADX) when compared with those patients undergoing nonsurgical treatment, and to investigate the potential prognostic factors. PATIENTS AND METHODS: A total of 1,302 NSCLC inpatients' data from 2001 to 2015 were retrospectively reviewed to identify those with solitary adrenal metastasis. Overall survival for those who underwent both primary resection and ADX was compared to those patients with conservative treatment using the log-rank test. Potential prognostic variables were evaluated with univariate and multivariate analyses including clinical, therapeutic, pathologic, primary and metastatic data. RESULTS: A total of 22 NSCLC patients with solitary adrenal metastasis were identified, with an overall median survival of 11 months (95% confidence interval: 9.4-12.6 months) and a 1-year survival rate of 51.4% (95% confidence interval: 29.6%-73.2%). All of the patients had died by 30 months. There was no significant survival difference between patients who underwent primary and metastasis resection (n=10) and those treated conservatively (n=12), (P=0.209). Univariate analysis identified Eastern Cooperative Oncology Group performance status (ECOG PS) as the significant predictor of survival (P=0.024). Age (<65 vs ≥65 years), sex, pathologic type, mediastinal lymph node stage (N2 vs N0/N1), primary tumor size (<5 vs ≥5 cm), primary location (central vs peripheral), metastatic tumor size (<5 vs ≥5 cm), metastasis laterality, synchronous metastasis, and metastatic field radiotherapy were not identified as potential prognostic factors in relation to survival rate. In multivariate analysis, a stepwise selection procedure allowed both ECOG PS (P=0.007, relative risk =3.57) and pathologic type (P=0.069) to enter the Cox's hazard function. CONCLUSION: Primary and metastatic radical resection may not prolong the survival of NSCLC patients with solitary adrenal metastasis. ECOG PS and pathologic type might be the prognostic factors for these patients.
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Interleukin (IL)-10-producing B cells (B10 cells) plays an important role in the tumor tolerance. High frequency of peripheral B10 cell was reported in patients with lung cancer recently. Micro RNA (miR) regulates some gene expression. This study test a hypothesis that miR-98 suppresses the expression of IL-10 in B cells of subjects with lung cancer. The results showed that the levels of miR-98 were significantly less in peripheral B cells of patients with lung cancer than that in healthy subjects. IL-10 mRNA levels in peripheral B cells were significantly higher in lung cancer patients as compared with healthy controls. A negative correlation was identified between miR-98 and IL-10 in peripheral B cells. Serum IL-13 was higher in lung cancer patients than that in healthy controls. The levels of IL-13 were also negatively correlated with IL-10 in B cells. Exposure B10 cells to IL-13 in the culture or over expression of miR-98 reduced the expression of IL-10 in B cells. Administration with miR-98-laden liposomes inhibited the lung cancer growth in a mouse model. In conclusion, up regulation of miR-98 inhibits the expression of IL-10 in B cells, which may contribute to inhibit the lung cancer tolerance in the body.
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Linfócitos B/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Interleucina-10/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Adulto , Idoso , Animais , Linfócitos B/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lipossomos/farmacologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/farmacologia , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Differentiation of anomalous systemic artery to the left lower lobe (ASALLL) from pulmonary sequestration (PS) is essential, as ASALLL can be corrected by anastomosis, embolization, or ligation of the anomalous artery. PURPOSE: To compare computed tomography (CT) findings of ASALLL and PS in the left lower lobe (LLL). MATERIALS AND METHODS: This study included 16 patients with ASALLL and 25 patients with PS in LLL confirmed by operative and pathologic findings. RESULTS: Cough and sputum were more common in PS (84% and 60%, respectively) than in ASALLL (25% and 12.5%, respectively) (P < 0.05). Hemoptysis was more common in ASALLL (100%) than in PS (24%) (P < 0.05). The frequency of ground glass opacity (GGO), normal bronchial distribution, dilated left inferior pulmonary veins, and absence of the interlobar artery distal to the origin of the superior segmental artery in LLL differed significantly between ASALLL and PS. Mass was less common in ASALLL (0%) than in PS (88%) (P < 0.01). The mean diameter of the anomalous artery (11.88 ± 1.13 mm) in ASALLL was significantly larger than that (5.96 ± 0.98 mm) in PS (P < 0.01). The presence of anomalous artery arising from thoracic aorta was not different between ASALLL (100%) and PS (72%). CONCLUSION: Radiographic indications of ASALLL differ from those of PS in the LLL. Indications that may suggest ASALLL include an enlarged anomalous systemic artery arising from the thoracic aorta, dilated left inferior pulmonary veins, absence of the interlobar artery distal to the origin of the superior segmental artery, normal bronchial distribution, and GGO in the LLL.
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Sequestro Broncopulmonar/diagnóstico por imagem , Artéria Pulmonar/anormalidades , Tomografia Computadorizada por Raios X/métodos , Adulto , Sequestro Broncopulmonar/cirurgia , Meios de Contraste , Feminino , Humanos , Iohexol/análogos & derivados , Masculino , Pneumonectomia , Veias Pulmonares/anormalidadesRESUMO
Skewed CD8(+) T cell responses are important in airway inflammation. This study investigates the role of the airway epithelial cell-derived insulin-like growth factor 1 (IGF1) in contributing to CD8(+) T cell polarization. Expression of IGF1 in the airway epithelial cell line, RPMI2650 cells, was assessed by quantitative real time RT-PCR and Western blotting. The role of IGF1 in regulating CD8(+) T cell activation was observed by coculture of mite allergen-primed RPMI2650 cells and naïve CD8(+) T cells. CD8(+) T cell polarization was assessed by the carboxyfluorescein succinimidyl ester-dilution assay and the determination of cytotoxic cytokine levels in the culture medium. Exposure to mite allergen, Der p1, increased the expression of IGF1 by RPMI2650 cells. The epithelial cell-derived IGF1 prevented the activation-induced cell death by inducing the p53 gene hypermethylation. Mite allergen-primed RPMI2650 cells induced an antigen-specific CD8(+) T cell polarization. We conclude that mite allergens induce airway epithelial cell line, RPMI2650 cells, to produce IGF1; the latter contributes to antigen-specific CD8(+) T cell polarization.
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Linfócitos T CD8-Positivos/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Antígenos de Dermatophagoides/farmacologia , Proteínas de Artrópodes/farmacologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cisteína Endopeptidases/farmacologia , Metilação de DNA/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/isolamento & purificação , Fator de Crescimento Insulin-Like I/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury (IR). However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium dynamics in rat myocardial IR model in vivo. A microdialysis system was involved, and the time delay of the system and recovery time was introduced and tested with a fluids switching method. Twelve SD rats were divided into IR or control group. Myocardial IR was induced by ligating (20 min) then releasing (60 min) the suture underlying left anterior descending branch. Mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area for occlusion. Dialysate samples were collected every 10 min. Dialysate calcium concentration was detected with an atomic absorption spectrophotometer. Recovery time for the microdialysis system was 20 min, and recovery rate was 16%. Dialysate calcium concentration showed no changes during ischemia, descended immediately after reperfusion, reached the lowest level (67% of baseline value) 20 min after reperfusion, then escalated slowly. Recovery time was an important parameter for mycrodialysis technique, and it should not be neglected and needed to be tested. Our data suggest that interstitial calcium concentration in rats with myocardial IR in vivo kept steady in ischemia, descended rapidly at the initial reperfusion, then rebounded slowly. In conclusion, we introduced the concept of recovery time for microdialysis and provided a simple testing method.
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Cálcio/metabolismo , Soluções para Diálise/metabolismo , Microdiálise/métodos , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Espaço Intracelular/metabolismo , Cinética , Masculino , Ratos , Ratos Sprague-Dawley , Espectrofotometria Atômica , Fatores de TempoRESUMO
Lung adenocarcinoma (AC) is one of the most deadly malignancies. The disease has a low five-year survival rate; therefore, the identification of novel therapeutic agents is required. This study aimed to investigate the effect of small interfering RNA (siRNA) targeting hypoxiainducible factor 1α (HIF1α) on the growth of AC A549 cells. A549 cells were transfected with various concentrations of HIF1α or control siRNA, and the effect on HIF1α expression was analyzed using quantitative polymerase chain reaction and western blot analysis. The effects of HIF-1α siRNA on growth inhibition and apoptosis were then assessed using standard methods. HIF1α siRNA treatment significantly reduced HIF1α mRNA and protein expression in A549 cells. Furthermore, the downregulation of HIF-1α expression inhibited the growth of A549 cells and induced apoptosis of A549 cells by upregulating caspase-3 expression. The present in vitro study demonstrates that the downregulation of HIF1α is capable of suppressing AC A549 cell growth, through the induction of apoptosis. This suggests that HIF1α inhibition may represent a promising strategy for the treatment of AC.
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Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interferência de RNA , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Regulação para CimaRESUMO
The therapeutics of lung cancer (LC) is unsatisfactory. The pathogenesis of LC remains unclear. Protease-activated receptors (PAR) are involved in the immunoregulation. The present study aims to investigate the activation of PAR2 in regulation of the expression of EGFR and apoptosis of LC cells. The results showed that exposure to tryptase increased EGFR expression in A549 cells and suppressed the cell apoptosis. Tryptase also decreased the expression of Bax and increased Bcl-xL levels in A549 cells. We conclude that activation of PAR2 by tryptase can decrease the ratio of Bax/Bcl-xL and reduce the LC cell line, A549 cells, and apoptosis.
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Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Receptor PAR-2/agonistas , Triptases/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Interferência de RNA , RNA Mensageiro/metabolismo , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Transfecção , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismoRESUMO
BACKGROUND: Microdialysis is a specific and local sampling method to collect free molecules from the extracellular fluid, however, there are no reports on time delay issues of microdialysis applications. AIMS: This study was to check the time gap between the start of target molecule changes in detected fluid and corresponding stable concentration formation in the sampled dialysate. MATERIALS AND METHODS: A designated microdialysis system for free calcium ion was set up in vitro and perfused with saline. The dialysate was diluted synchronously, and collected in a vial every 10 min. The free calcium concentration [Ca++] of the sample was measured by an atomic absorption spectrophotometer. A signal-switching method was introduced to mimic the target molecule [Ca++] changes in the detected fluid, standard calcium solution and saline. RESULTS: There was a notable lag in dialysates [Ca++] for both uprising and down going course in spite of instant switching between the detected fluids. The recovery time (RT) of the microdialysis system was extrapolated to be 20 min for [Ca++] detection. CONCLUSIONS: With 10 min sampling interval, [Ca++] time delay of the microdialysis system existed, and could not be estimated precisely beforehand. The signal-switching method was applicable for RT calibration in vitro with a dedicated microdialysis system.
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The epidermal growth factor receptor (EGFR) has a close relation to lung cancer; its role in the pathogenesis of lung cancer is to be further elucidated. The results of this study indicate that about 80% exosomes purified from the LC biopsies contained EGFR; only about 2% exosomes contained EGFR in the samples from chronic lung inflammation. The purified exosomes induced tolerogenic DCs. Coculture of the tolerogenic DCs and Th0 cells generated the tumor antigen-specific regulatory T cells (Treg). The Tregs could suppress the tumor antigen specific CD8+ T cells.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/metabolismo , Exossomos/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos T Reguladores/imunologia , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/fisiologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/imunologia , Exossomos/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Pneumonia/metabolismoRESUMO
Recently, the prognostic value of cancer-related inflammatory response has been revealed. Previous studies showed that peripheral neutrophils and lymphocytes had significant impact on the prognosis of advanced and early-node-negative non-small-cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic value of preoperative lymphocyte and neutrophil counts in patients with NSCLC who underwent lobectomy and lymph node dissection and adjuvant chemotherapy. Retrospective analyses were performed to examine the impact of preoperative peripheral lymphocyte and neutrophil counts on disease-free survival (DFS) and overall survival (OS) and to analyze the relationships of these factors to clinicopathological factors. A total of 142 patients with NSCLC were evaluated of which 57 (40.1 %) patients had local recurrence or metastasis. Multivariate analyses revealed that peripheral lymphocyte count was an independent favorable prognostic factor of DFS (hazard ratio 0.548; 95 % confidence interval 0.351-0.857; P = 0.008) but not OS (P = 0.164). The maximum logrank statistical value was 9.504 (P = 0.002) when the cutoff value of lymphocyte was 1,800 mm(-3). The median DFS was 318.0 days (95 % confidence interval 226.0-410.0) for lymphocyte ≤1,800 mm(-3) group and 669.0 days (95 % confidence interval 0.0-1,431.0) for lymphocyte >1,800 mm(-3) group. Low lymphocyte count was related with lymphatic invasion (P = 0.012) and recurrence of NSCLC (P = 0.022). Peripheral neutrophil count had no impact on DFS or OS when analysis included all the 142 patients. Preoperative peripheral lymphocyte count, which is related with lymphatic invasion, is an independent favorable prognostic factor of DFS in patients with NSCLC who underwent lobectomy and lymph node dissection and adjuvant chemotherapy.
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Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Linfócitos do Interstício Tumoral/patologia , Adolescente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: To investigate whether XRCC1 and ADPRT polymorphisms might be associated with outcomes of breast cancer. METHODS: A prospective study was conducted with a total of 335 breast cancer patients undergoing chemotherapy consecutively collected from Jan. 2005 to Jan. 2008. Genotyping of XRCC1 and ADPRT polymorphisms was conducted by PCR-RFLP assay. RESULTS: All 335 patients were followed up until death or the end of Jan. 2012, with a median follow-up period of 38.8 (2-64) months. It was shown that the variant genotype of XRCC1 399Gln/Gln was strongly significantly associated with a decreased risk of death from breast cancer, with an HR (95% CI) of 0.52 (0.28-0.91). Similarly, individuals carrying the ADPRT 762Ala/Ala demonstrated longer survival compared to ADPRT 762 Val/ Val, with an HR (95% CI) of 0.58 (0.31-0.97). Individuals with combination genotypes of XRCC1 399Gln allele and ADPRT 762Ala/Ala presented with a longer survival, the HR (95% CI) being 0.56 (0.32-0.97). CONCLUSION: We found a significant association between XRCC1399Gln/ Gln and ADPRT 762Ala/Ala polymorphisms and clinical outcomes. These two genotypes could be used as a surrogate markers of clinical outcome in glioma cases receiving chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Proteínas de Ligação a DNA/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo Genético/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Poli(ADP-Ribose) Polimerase-1 , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
INTRODUCTION: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-1α siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. MATERIALS AND METHODS: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-1α siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-1α mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. RESULTS: In our nude mice model, HIF-1α siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-1α mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-1α siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF- 1α siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-1α siRNA-treated groups (P<0.05). CONCLUSIONS: Down-regulated HIF-1α expression induced by siRNA could effectively suppress the growth of transplanted ESCC in vivo. HIF-1α siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.
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Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Neoplasias Esofágicas/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , RNA Interferente Pequeno/genética , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Citometria de Fluxo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas Imunoenzimáticas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
Effects of photoperiod and cold exposure on diapause termination, post-diapause development and reproduction in Loxostege sticticalis were examined. Larvae were reared at diapause inducing condition (22 degrees C, L:D 12:12) consistently or transferred to long day photoperiod (L:D 16:8) and darkness (L:D 0:24) respectively, after entering into diapause. Diapause was terminated in approximately 40% of the larvae after 36 days, and no significant differences were observed between photoperiods, suggesting larval diapause was terminated spontaneously without being induced by photoperiods. Cold exposure significantly hastened diapause termination. The diapause termination incidence increased significantly with peaks of 98% at both 5 degrees C and 0 degrees C exposure for 30 days, as compared to 42% in controls not exposed to cold, while the mortality and number of days required for diapause termination decreased dramatically. The optimal low temperature exposure periods under 5 degrees C or 0 degrees C were 20 days and 30 days, showing a higher termination incidence and shorter time for diapause termination. This suggests that the low temperatures in winter play an important role in diapause termination under natural conditions. The threshold temperatures for post-diapause development in prepupae and pupae were 9.13 degrees C and 10.60 degrees C respectively, with corresponding accumulations of 125 and 200 degree-days. Adults that experienced larval diapause significantly delayed their first oviposition, oviposition period was prolonged, and the lifetime number of eggs laid was decreased, however both males and females have significantly longer longevity. The field validation of diapause termination, the degree-days model, and the relationship between diapause and migration in L. sticticalis were also discussed.
Assuntos
Aclimatação/fisiologia , Temperatura Baixa , Mariposas/crescimento & desenvolvimento , Oviposição/fisiologia , Fotoperíodo , Estações do Ano , Análise de Variância , Animais , China , Feminino , Larva/crescimento & desenvolvimento , Masculino , Modelos Biológicos , Reprodução/fisiologia , Fatores de TempoRESUMO
OBJECTIVE: To study the reasonable dosage for paraplatin according to different dosage calculations. METHODS: A prospective, randomized, single-blinded study on 54 patients with advanced non-small-cell lung cancer (NSCLC) treated with paraplatin was conducted. Patients were divided to 2 groups. In group A, paraplatin dosage was calculated according to patients' body surface, and in group B, it was calculated according to the area under the curve (AUS). Hematological toxicity, response rate and survival rate in the two groups of patients were compared. RESULTS: Neutropenia in group A and group B was seen in 77.8% and 37.0% (P < 0.05), and thrombocytopenia in 18.5% and 3.7% (P > 0.05) of patients, respectively. Hemoglobin decrease was seen in 48.2% of patients in both groups. The average quantity of paraplatin given in one cycle of treatment was 535.93 +/- 106.71 mg and 398.52 +/- 71.72 mg (P < 0.01) respectively. The average time interval between treatment cycles was 27.04 +/- 5.30 d and 22.85 +/- 2.80 d (P < 0.05). The response rate and survival rate of patients in group A and B were 22.2% versus 48.2% (P < 0.05), and 40.7% versus 44.4% (P > 0.05) respectively, but the median survival time was identical (12 months) in the two groups. CONCLUSION: NSCLC patients given paraplatin with dosages calculated on the basis of AUC have higher response rate and less severe hematological toxicity than those given paraplatin with dosages on the basis of body surface. However, the median survival time and survival rate have no statistical differences between the two groups of patients.
Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Área Sob a Curva , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Prospectivos , Método Simples-Cego , Taxa de Sobrevida , Trombocitopenia/induzido quimicamenteRESUMO
OBJECTIVE: To study the clinical application of needle video-assisted thoracoscopic biopsy in the pathologic diagnosis and staging for advanced lung cancer. METHODS: Ninety-four patients were diagnosed as having advanced lung cancer staged IIIa-IV by chest X-ray, computed tomography and magnetic resonance imaging, for which a pathologic diagnosis was not made by sputum and pleural effusion cytology or bronchoscopic examination. Needle video-assisted thoracoscopic biopsy was performed for primary lesions, mediastinal lymph nodes, metastatic lesions in the lungs and the chest wall. RESULTS: Pathologic samples were obtained in 89 of the 94 patients by needle video-assisted thoracoscopic surgery. The successful rate was 95%. After operation, the pathologic diagnosis was confirmed to be lung cancer in all the 89 patients. Adenocarcinoma was found in 47 patients, squamous carcinoma in 23, adenosquamous carcinoma in 12, and small cell lung cancer in 7. Compared to the clinical diagnosis before operation, the pathologic diagnosis post-operation was changed in 15 patients. Pneumothorax and mild haemoptysis occurred in 4 patients and 2 of the cases respectively. All the patients were followed for 8 - 18 months with computed tomography and physical examination. No implantation metastasis was found. CONCLUSION: Needle video-assisted thoracoscopic biopsy is an effective diagnostic measure for patients with advanced lung cancer for which pathologic diagnosis, typing and staging are not determined by routine examinations.