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PURPOSE: This study investigated the physical fitness and oxygen uptake kinetics (τ[Formula: see text]) along with the O2 delivery and utilization (heart rate kinetics, τHR; deoxyhemoglobin/[Formula: see text] ratio, ∆[HHb]/[Formula: see text]) adaptations of untrained female participants responding to 4 weeks of high-intensity interval training (HIIT) and 2 weeks of detraining. METHODS: Participants were randomly assigned to HIIT (n = 11, 4 × 4 protocol) or nonexercising control (n = 9) groups. Exercising group engaged 4 weeks of treadmill HIIT followed by 2 weeks of detraining while maintaining daily activity level. Ramp-incremental (RI) tests and step-transitions to moderate-intensity exercise were performed. Aerobic capacity and performance (maximal oxygen uptake, [Formula: see text]; gas-exchange threshold, GET; power output, PO), body composition (skeletal muscle mass, SMM; body fat percentage, BF%), muscle oxygenation status (∆[HHb]), [Formula: see text], and HR kinetics were assessed. RESULTS: HIIT elicited improvements in aerobic capacity ([Formula: see text], + 0.17 ± 0.04 L/min; GET, + 0.18 ± 0.05 L/min, P < 0.01; PO-[Formula: see text], ± 23.36 ± 8.37 W; PO-GET, + 17.18 ± 3.07 W, P < 0.05), body composition (SMM, + 0.92 ± 0.17 kg; BF%, - 3.08% ± 0.58%, P < 0.001), and speed up the τ[Formula: see text] (- 8.04 ± 1.57 s, P < 0.001) significantly, extending to better ∆[HHb]/[Formula: see text] ratio (1.18 ± 0.08 to 1.05 ± 0.14). After a period of detraining, the adaptation in body composition and aerobic capacity, as well as the accelerated τ[Formula: see text] were maintained in the HIIT group, but the PO-[Formula: see text] and PO-GET declined below the post-training level (P < 0.05), whereas no changes were reported in controls (P > 0.05). Four weeks of HIIT induced widespread physiological adaptations in females, and the majority of improvements were preserved after 2 weeks of detraining except for power output corresponding to [Formula: see text] and GET.
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Treinamento Intervalado de Alta Intensidade , Humanos , Feminino , Treinamento Intervalado de Alta Intensidade/métodos , Cinética , Consumo de Oxigênio/fisiologia , Músculo Esquelético/fisiologia , Oxigênio/metabolismoRESUMO
PURPOSE: This study investigated the physical fitness and oxygen uptake kinetics ([Formula: see text]) along with the exercise-onset O2 delivery (heart rate kinetics, τHR; changes in normalized deoxyhemoglobin/[Formula: see text] ratio, Δ[HHb]/[Formula: see text]) adaptations of individuals with different physical activity (PA) backgrounds responding to 4 weeks of high-intensity interval training (HIIT), and the possible effects of skeletal muscle mass (SMM) on training-induced adaptations. METHODS: Twenty subjects (10 high-PA level, HIIT-H; 10 moderate-PA level, HIIT-M) engaged in 4 weeks of treadmill HIIT. Ramp-incremental (RI) test and step-transitions to moderate-intensity exercise were performed. Cardiorespiratory fitness, body composition, muscle oxygenation status, VO2 and HR kinetics were assessed at baseline and post-training. RESULTS: HIIT improved fitness status for HIIT-H ([Formula: see text], + 0.26 ± 0.07 L/min; SMM, + 0.66 ± 0.70 kg; body fat, - 1.52 ± 1.93 kg; [Formula: see text], - 7.11 ± 1.05 s, p < 0.05) and HIIT-M ([Formula: see text], 0.24 ± 0.07 L/min, SMM, + 0.58 ± 0.61 kg; body fat, - 1.64 ± 1.37 kg; [Formula: see text], - 5.48 ± 1.05 s, p < 0.05) except for visceral fat area (p = 0.293) without between-group differences (p > 0.05). Oxygenated and deoxygenated hemoglobin amplitude during the RI test increased for both groups (p < 0.05) except for total hemoglobin (p = 0.179). The Δ[HHb]/[Formula: see text] overshoot was attenuated for both groups (p < 0.05) but only eliminated in HIIT-H (1.05 ± 0.14 to 0.92 ± 0.11), and no change was observed in τHR (p = 0.144). Linear mixed-effect models presented positive effects of SMM on absolute [Formula: see text] (p < 0.001) and ΔHHb (p = 0.034). CONCLUSION: Four weeks of HIIT promoted positive adaptations in physical fitness and [Formula: see text] kinetics, with the peripheral adaptations attributing to the observed improvements. The training effects are similar between groups suggesting that HIIT is effective for reaching higher physical fitness levels.
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Aptidão Cardiorrespiratória , Treinamento Intervalado de Alta Intensidade , Humanos , Adulto , Aptidão Física/fisiologia , Exercício Físico , Hemoglobinas , Consumo de OxigênioRESUMO
Low concentrations of gelatin methacrylate (GelMA) microfibers are more favorable for cellular activity compared with high concentrations. However, applying low-concentration GelMA microfibers as building blocks for higher-order cellular assembly remains challenging owing to their poor mechanical properties. Herein, we report a new template-based method to solve this problem. GelMA microfibers (5%, w/v) containing magnetic nanoparticles were synthesized by a microfluidic spinning method. A 9 × 9 micropillar array surrounded by a magnetic substrate was constructed to form 8 × 8 microgaps arranged in a crisscross pattern as a magnetic template. In DMEM solution, magnetic attraction facilitated efficient arrangement of the microfibers according to the template with micron assembly accuracy, with a microgrid-like construct (microGC) generated after removing all micropillars. MicroGCs were shown to effectively support the activities of surface seeded or encapsulated cells and be flexibly constructed with various organized spatial patterns. Owing to the low mechanical property requirements of assembled microfibers and the easy-to-implement operation, the proposed method provides a versatile pathway for the assembly of various microfluidic spun microfibers. Furthermore, the resulting 3D microgrid-like cellular constructs with organized spatiotemporal composition offer a convenient platform for the study of tissue engineering.
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Alginatos/química , Gelatina/química , Nanopartículas de Magnetita/química , Metacrilatos/química , Animais , Proliferação de Células , Sobrevivência Celular , Células Hep G2 , Humanos , Fenômenos Magnéticos , Camundongos , Microfluídica , Células NIH 3T3RESUMO
To identify a panel of tumor associated autoantibodies which can potentially be used as biomarkers for the early diagnosis of non-small cell lung cancer (NSCLC). Thirty-five unique and in-frame expressed phage proteins were isolated. Based on the gene expression profiling, four proteins were selected for further study. Both receiver operating characteristic curve analysis and leave-one-out method revealed that combined measurements of four antibodies produced have better predictive accuracies than any single marker alone. Leave-one-out validation also showed significant relevance with all stages of NSCLC patients. The panel of autoantibodies has a high potential for detecting early stage NSCLC.
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Anticorpos Antineoplásicos/sangue , Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Detecção Precoce de Câncer , Proteínas da Matriz Extracelular/biossíntese , Proteínas da Matriz Extracelular/imunologia , Humanos , Receptores de Hialuronatos/biossíntese , Receptores de Hialuronatos/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Proteínas Nucleares/biossíntese , Proteínas Nucleares/imunologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/biossíntese , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/imunologia , Biblioteca de Peptídeos , Fosfoproteínas/biossíntese , Fosfoproteínas/imunologia , RNA Longo não Codificante , RNA não Traduzido/biossíntese , RNA não Traduzido/imunologia , Poliamina OxidaseRESUMO
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths in the world and often diagnosed at an advanced stage, so it is urgent to explore the pathogenesis and new diagnostic biomarkers. Accumulated evidences suggested that small nucleolar RNAs (snoRNAs) played a key role in the development and progression of NSCLC. To examine differential expression snoRNA profile and identify snoRNAs with clinical significance in lung adenocarcinoma (LUAD), The Cancer Genome Atlas (TCGA) LUAD RNA sequencing dataset was used to investigate differential expression snoRNA signatures and compared with snoRNA PCR array analysis in pair-matched LUAD tissues. The diagnostic ability of SONRD60 was assessed using a receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to plot survival curves. Univariate and multivariate Cox regression analyses were used to investigate the prognostic effect of SNORD60 expression on LUAD. The results showed that SNORD60 was a significantly upregulated snoRNA after intersection analysis in LUAD cases. SNORD60 has 74.2% sensitivity and 75.3% specificity for the diagnosis of LUAD. Increased SNORD60 expression was linked with lymph node metastases and the TNM stage (P < 0.05). Pathological T category and lymph node metastases were independent prognostic factors for overall survival in a multivariate Cox regression study. Our findings demonstrated that SNORD60, a small nucleolar RNA, has an oncogenic function in LUAD and might be used as a new early diagnostic biomarker for LUAD.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Metástase Linfática , Prognóstico , RNA Nucleolar Pequeno/genéticaRESUMO
OBJECTIVE: To explore the significance of CYP3A4 and CYP3A5 genetic polymorphisms in achieving personalized fentanyl application in patients undergoing thoracoscopic operation. METHODS: This was a retrospective study. One hundred patients with lung cancer received thoracoscopic surgery operation under the conditions of general anesthesia. According to the results of individualized analgesia guided by CYP3A4/5 polymorphisms, the patients were assigned into three groups: group I (the wild-type homozygote, the induced dosage of fentanyl: 6 µg/kg, the background infusion rate of patient-controlled intravenous analgesia (PCIA): 2 mL/h), group II (the heterozygote, the induced dosage of fentanyl: 5 µg/kg, the background infusion rate of PCIA: 1.5 mL/h), and group III (the mutant homozygote, the induced dosage of fentanyl: 4 µg/kg, the background infusion rate of PCIA: 1 mL/h). The locking-time was 15 min. A visual analog scale (VAS) score less than 3 points suggested effective analgesia. The times of operation and recovery were examined. Surgical plethysmography index (SPI), blood glucose levels, VAS and bruggemann comfort scale (BCS) scores at different time points were recorded, respectively. Total consumption of fentanyl, the effective time of PCIA compression, and the incidence of adverse drug reactions were also recorded. RESULTS: There were no statistical differences in SPI, blood glucose level, VAS, BCS scores and incidence of adverse reactions among the three groups. In term of intraoperative, postoperative fentanyl doses and the amount of effective PCA, significant differences were found among the groups (P < 0.05). CONCLUSION: According to the genotype of CYP3A4/CYP3A5, an individualized application of fentanyl is feasible.
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Lumbar spine surgery is one of the most widespread types of surgery for treating back and leg pain. However, the postoperative period always presents with severe pain due to the removal of skin, subcutaneous tissues, bones, and ligaments. Patients usually require high doses of opioids to relieve pain during the initial three days after operation, as well as experience drug-related complications and prolonged length of stay in hospital. We found that Erector spinae plane block significantly reduced postoperative opioid consumption and pain scores. The present systematic review revealed that ESPB was effective and safe for postoperative analgesia.
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BACKGROUND: Although video-assisted thoracoscopy has a smaller incision than traditional surgery, the postoperative pain is still severe. Ultrasound-guided pectoral nerve block (PECS) II is a new technique that can reduce pain in patients, and it had not been reported in the analgesia after thoracoscopic lobectomy. METHODS: 40 patients scheduled for thoracoscopic lobectomy were randomly divided into two groups. Patients in the PECS II group received 0.5% ropivacaine 25 ml before the general anesthesia, while patients in the placebo group received 0.9% saline. Thirty minutes after the block was performed, a pin-prick test was used to analyze the sense of pain of T2-T6 segments. The primary endpoint was the total consumption of fentanyl. Data were collected in the postanesthesia care unit (PACU) and in the ward within 24 hours after operation. RESULTS: The total consumption of fentanyl and the consumption of fentanyl in the intravenous analgesia pump within 24 hours after the operation were significantly lower in the PECS II group compared to the placebo group (p < 0.05). The implementation rate of rescue analgesia during operation and in PACU in the PECS II group was significantly lower than that in the placebo group (p < 0.05). The numerical rating scale (NRS) in 1 and 4 h after operation was lower in the PECS II group (p < 0.05). Mean arterial pressure (MAP) and heart rate (HR) of the PECS II group at chest entering (T1) were significantly lower than those in the placebo group (p < 0.05). CONCLUSION: Preconditioning of PECS II can stabilize the intraoperative circulation and significantly reduce pain and the consumption of opioids after operation.
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Pulmão/cirurgia , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Nervos Torácicos/cirurgia , Toracoscopia/efeitos adversos , Analgesia , Pressão Arterial , Método Duplo-Cego , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , PlacebosRESUMO
Circumferential alignment of vascular smooth muscle cells (vSMCs) is critical to form an in vivo-like vascular smooth muscle layer in vitro. Although many techniques to elicit such an alignment on 3D substrates have been demonstrated, it remains a challenge to recapitulate the circumferential cellular alignment of vascular smooth muscle tissues in 3D hydrogels. Here, we propose a spring-like gelatin methacrylate (GelMA) structure formed by semi-automated reeling of a core-shell microfiber at the micro-scale. The resulting structures facilitate circumferential alignment and self-organization of encapsulated human mesenchymal stem cells (MSCs) into multilayer spring-like cellular structures. Based on the permeable tubular lumens of these structures, a perfusion culture micro-system is developed to further facilitate the vSMC differentiation of MSCs under the effect of TGF-ß1. We also evaluated the MSC contraction-induced shrinkage of the resulting cellular structures. These results demonstrate the successful in vitro regeneration of vascular smooth muscle (vSM)-like tissues in 3D environments. Compared with the substrate surface, the porous structure in hydrogels is more similar to cell microenvironments in vivo. Thus, this approach may be used to develop an in vitro model for the study of vascular tissue regeneration and the mechanism of vascular remolding during hypertension.
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Hidrogéis , Músculo Liso Vascular , Gelatina , Humanos , Miócitos de Músculo Liso , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Tissue rings with incorporated microscaffolds have been engineered as promising building blocks for constructing biological tubes from the bottom up. However, the microscaffolds available for incorporation are very limited at present. In this paper we provide an efficient strategy to first incorporate microfluidic spun Ca-alginate microfibres encapsulating magnetic nanoparticles into self-assembled fibroblast micro-rings. Based on the surface modification, microfibres with a size of â¼40 µm allowed fibroblasts to spread and proliferate along the long axis. The optimal cell seeding density was obtained by evaluating the degree of coverage of fibroblasts on microfibres after 3 days of culture. Then we designed a magnetically guided culture apparatus with multiple annular micro-wells to facilitate cell-driven assembly of microfibres. A manipulation strategy dependent on surface tension was used to pattern microfibres along the micro-wells prior to cell seeding, and magnetic attraction further kept the patterned microfibres from being deposited in the micro-wells during cultivation. Within 3 days of culture, microfibre-incorporated tissue micro-rings were formed in the micro-wells. Quantitative analysis of the formation process revealed liquid-like aggregating behaviours, and incorporated microfibres showed the potential to promote the directed organization of cells in tissue micro-rings. Furthermore, magnetically driven manipulation was used robotically to assemble the micro-rings on a micropillar inserted into the centre of the culture apparatus. After 5 days of culture to allow cell fusion, a biological tubular microstructure was achieved. Microfluidic spinning can generate fibres with a variety of shapes, geometries, and compositions; therefore, our proposed method greatly enriches the variety of microscaffolds available for incorporation into tissue rings to engineer complex artificial organs for tissue engineering and regenerative medicine.
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Fibroblastos/citologia , Microtecnologia , Engenharia Tecidual/métodos , Animais , Agregação Celular , Proliferação de Células , Fenômenos Magnéticos , Camundongos , Células NIH 3T3RESUMO
BACKGROUND: Percutaneous infrazygomatic radiofrequency (PIR) is a common approach used to block isolated maxillary nerve (V2) pain through the foramen rotundum (FR) in patients with trigeminal neuralgia (TN). Nevertheless, when using this method, there is a risk of accidental penetration of the superior orbital fissure (SOF) and the optic canal (OC) that may result in the injury of the vessels and nerves in that area, and in some severe cases may lead to blindness. According to the blocking of the external orifice of the FR and whether a curved needle was used, combined angle deviation from the path of percutaneous infrazygomatic approach, the FR to the SOF or the OC in the treatment of V2 pain, in which no research has reported the angle, we analyzed the value and application of personalized needle modification in PIR in isolated maxillary nerve pain through the FR. OBJECTIVES: The following study examined the relationship between the FR and the SOF, and analyzed the clinical significance of personalized needle modification in computed tomography (CT)-guided PIR ablation of the maxillary nerve through the FR in patients with TN. STUDY DESIGN: Randomized, review, clinical research study. SETTING: Department of Anesthesiology and Pain Medical Center, Jiaxing, China. METHODS: Three-dimensional reconstruction was performed in 88 patients and 136 patients with PIR ablation in isolated maxillary nerve pain through the FR. According to the blocking of the external orifice of the FR and whether a curved needle was used, patients were divided into 4 groups: curved-needle blocking group (CB), straight-needle blocking group (SB), straight needle no-blocking group (SN), and curved-needle no-blocking group (CN). RESULTS: The results obtained revealed minimum H (shortest diameter of the FR) = 1.0 mm and minimum L (length of the FR tubes) = 3.7 mm. The distance between the external orifice of the FR and the SOF (FS) was 5.16 ± 1.33 mm. The angle A (between the radiofrequency needle and the sagittal plane) was 39 ± 3.95°; the angle between the canthomeatal line and the CT scan line (ACT) was 58.99 ± 6.23°; the puncture depth (LS) was 63.99 ± 4.24 mm; the deviation angle of the misplacement into the SOF (SAF) was 2.96 ± 0.71°; the deviation angle of the misplacement into the OC (OAF) was 4.95 ± 0.73°. In addition, the postoperative Numeric Rating Scale scores in the CB group were significantly lower compared with the SB group, whereas the probability of entering the SOF in the CB group was significantly lower compared with the SB group. The total number of punctures in the SN group was less than that in the CN group. LIMITATIONS: Additional clinical data should be collected to preserve the results in future work. CONCLUSIONS: The distance between the FR and the SOF or the OC was only few millimeters, and slight angle error could lead to the SOF and the OC. For patients with blockage in the path, the treatment of radiofrequency with personalized needle modification could improve the curative effect and reduce the risk of accidental SOF penetration. KEY WORDS: Trigeminal neuralgia, foramen rotundum, superior orbital fissure, radiofrequency, personalized needle modification.
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Nervo Maxilar/diagnóstico por imagem , Agulhas , Terapia por Radiofrequência/instrumentação , Terapia por Radiofrequência/métodos , Neuralgia do Trigêmeo/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients. METHODS: Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated. RESULTS: Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 109/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%). CONCLUSION: Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.
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Leucemia Mieloide Aguda , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/análogos & derivados , Citarabina , Decitabina , Feminino , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective To screen the differentially expressed key molecules of HAb18G/CD147 signal transduction pathway in human hepatoma cells. Methods The total RNA was extracted from SMMC-7721 and T7721 cells, which were stably transfected and overexpressed HAb18G/CD147, and then detected by signal transduction-related microarray to identify differentially expressed key molecules. Results The microarray data indicated that there were 13 differentially expressed genes between T7721 and SMMC-7721 cells. In T7721 cell line which overexpressed HAb18G/CD147, the down-regulated genes included bone morphogenetic protein-2 (BMP-2), BMP-5, endothelin-1 (ET-1), Wnt1-induced signaling proteins-2/CCN5 (WISP-2), cysteine-rich 61/CCN1 (Cyr61), prostate stem cell antigen (PSCA), and the up-regulated genes included interleukin-10 receptor α (IL-10Rα), IL-6, IL-8, CXCL2, mitochondrial superoxide dismutase 2 (SOD2), B factor and ßig-h3.Conclusion The study identified totally 13 differentially expressed genes which were related to HAb18G/CD147 signal transduction pathway. These genes are involved in the regulation of various hepatoma biological processes, such as immune microenvironment remolding, angiogenesis, cell proliferation, invasion and metastasis.
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Basigina/fisiologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Transdução de Sinais/fisiologia , Carcinoma Hepatocelular/etiologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/etiologiaRESUMO
Radiation enteropathy is a common complication in cancer patients following radiation therapy. Thus, there is a need for agents that can protect the intestinal epithelium against radiation. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to induce differentiation and/or apoptosis in multiple cell lines and primary cells. In the current report, we studied the function of TPA in radiation induced enteropathy in cultured rat intestinal epithelial cell line IEC-6 after ionizing radiation (IR) and in mice after high dose total-body gamma-IR (TBI). In IEC-6 cells, there were reduced apoptosis and cell cycle arrest in TPA treated cells after IR. We detected a four-fold increase in crypt cell survival and a two-fold increase in animal survival post TBI in TPA treated mice. The beneficial effects of TPA were accompanied by upregulation of stem cells markers and higher level of proteins that are involved in PKC signaling pathway. In addition, TPA also decreased the TBI-augmented levels of the DNA damage indicators. The effects were only observed when TPA was given before irradiation. These results suggest that TPA has the ability to modulate intestinal crypt stem cells survival and this may represent a promising countermeasure against radiation induced enteropathy.
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Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Mucosa Intestinal/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/efeitos da radiação , Acetato de Tetradecanoilforbol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase C/metabolismo , Lesões por Radiação/genética , Lesões por Radiação/metabolismo , Lesões por Radiação/mortalidade , Lesões por Radiação/patologia , Protetores contra Radiação/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Células-Tronco/metabolismoRESUMO
The purpose of this study was to investigate the correlation between EGFR-mutation status and treatment efficacy for advanced lung adenocarcinoma patients. A total of 47 patients receiving erlotinib as first-line therapy were divided into two groups: the EGFR gene mutation group included 19 patients with known EGFR-sensitive mutations, and the EGFR-mutation status-unknown group comprised 28 patients with unknown EGFR-mutation status. Both objective response rate and disease-control rate were significantly higher in the EGFR-mutation group compared with the EGFR-unknown group (42.1% vs 14.2%, P=0.032; 94.7% vs 57.1%, P=0.005). Age, sex, smoking history, stage of disease, and tissue-sample source were not significantly correlated with the distributions of mutation status. In conclusion, it is important for advanced lung adenocarcinoma patients to undergo gene analysis before being assigned a molecularly targeted drug as first-line treatment.
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BACKGROUND: Lung cancer is the leading cause of cancer death in both men and women worldwide. Tumor metastasis is an essential aspect of lung cancer progression and patient death. The nm23-H1 gene has been extensively investigated as a metastasis suppressor gene. Our previous studies have revealed: that a significant relationship exists between the low-level expression nm23-H1 in primary non-small cell lung cancer (NSCLC) with increased metastasis and a poor prognosis; that L9981-nm23-H1 cells (a nm23-H1 transfactant cell) exhibited lower cell proliferation rates, more G0/G1 phase growth, and an increase in apoptosis with a dramatic decrease in the tumor cells' ability to invade than L9981 cells did; and that L9981- nm23-H1 cells also demonstrated a significantly reduced lymph node and distant metastatic capacity in vivo than L9981 cells did in nude mice. METHODS: In this study, we construct a plasmid containing the nm23-H1 gene, which was driven by the human telomerase reverse transcriptase (hTERT) promoter. We evaluated the anti-invasion and anti-metastatic effects of pGL3-hTP-nm23 on L9981, a human large cell lung cancer cell line with nm23-H1 negative expression, by transwell assay in vitro and bioluminescence in nude mice models. The toxicity of pGL3-hTP-nm23 and its effects on tumor growth were evaluated in nude mice models after gene therapy. The cell cycles, apoptosis, and proliferation of the nm23-H1 transfactant were also detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and flow cytometry (FCM). RESULTS: The results showed that the hTERT-promoter dramatically drives nm23-H1 gene expression, and induces inhibition of cell growth and migration in L9981-luc cells and MRC-5 cells in vitro. nm23-H1 also significantly inhibited the tumorigenesis and distant metastasis of L9981-luc cell in vivo. Moreover, no obvious side effect was detected in normal mouse tissues after intratumoral injection of the vector. CONCLUSION: The treatment of the nm23-H1 gene driven by hTERT promoter appears to be a promising approach for the gene therapy of nm23-H1 low-expressed tumors.
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BACKGROUND: It has been confirmed that nm23-H1 gene is one of the tumor metastasis suppressor genes. Up to now, the exact mechanism of nm23-H1 gebe is uncertain. The aim of this study the mechanism of metastasis suppressor gene nm23-H1 involving in the Ras signaling of lung cancer. METHODS: The wild and mutant type of pEGFP-nm23-H1 plasmids [WT (wild type), H118F, S120G, P96S, S44A] were transfected into the L9981 lung cancer cell lines through liposome method, and the complex of KSR and nm23-H1 was detected through co-immunoprecipitation and Western blot assay. RESULTS: The human KSR could be detected in the nm23-H1 immunoprecipitations in all the trasfected L9981 lung cancer cell lines. But no significant difference of KSR expression was found in the wild and mutant nm23-H1 trasfected cell lines (F =0.190, P =0.938). CONCLUSIONS: There was a close interaction between nm23-H1 and KSR, which was independent of the nm23-H1 mutation. Nm23-H1 involving in the Ras signaling of lung cancer may be through the KSR gene.