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To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. SIGNIFICANCE STATEMENT: Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Antineoplásicos/efectos adversos , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Citocromo P-450 CYP2C9RESUMEN
The ability to identify strange conspecifics in societies is supported by social memory, which is vital for gregarious animals and humans. The function of hippocampal principal neurons in social memory has been extensively investigated; however, the nonprincipal neuronal mechanism underlying social memory remains unclear. Here, we first observed parallel changes in the ability for social recognition and the number of parvalbumin interneurons (PVIs) in the ventral CA1 (vCA1) after social isolation. Then, using tetanus toxin-mediated neuronal lesion and optogenetic stimulation approaches, we revealed that vCA1-PVIs specifically engaged in the retrieval stage of social memory. Finally, through the in vivo Ca2+ imaging technique, we demonstrated that vCA1-PVIs exhibited higher activities when subjected mice approached a novel mouse than to a familiar one. These results highlight the crucial role of vCA1-PVIs for distinguishing novel conspecifics from other individuals and contribute to our understanding of the neuropathology of mental diseases with social memory deficits.
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Hipocampo/fisiología , Interneuronas/fisiología , Memoria/fisiología , Parvalbúminas/fisiología , Conducta Social , Animales , Región CA1 Hipocampal/fisiología , Calcio/metabolismo , Ratones , OptogenéticaRESUMEN
To observe the effect of Astragali Radix polysaccharides (APS) on the learning and memory functions of aged rats, in order to explore its mechanism for improving the learning and memory functions. Natural aging female SD rats were selected in the animal model and randomly divided into the control group, the APS low-dose group (50 mg x kg(-1)), the APS high-dose group (150 mg x kg(-1)) and the piracetam-treated group (560 mg x kg(-1)). They were orally administered with the corresponding drugs for consecutively 60 days. Besides, a young control group was set. The learning and memory functions of the rats were tested by the open-field test and the Morris water maze task. The Western-blot method was used to observe the levels of relevant neural plasticity protein N-methyl-D-aspartate receptor (NMDA receptor) in hippocampus, calcium/calmodulin dependent protein kinase II (CaMK II), protein kinase (PKA), the phosphorylation level of CAMP response element binding protein (CREB) and the protein expression of brain derived neurotrophic factor(BDNF). In this study, the authors found that the learning and memory functions and the hippocampus neural plasticity protein expression of the aged rat group were much lower than that of the young control group (P < 0.01). Compared with the aged rat group, the APS group showed the significant improvement in the impaired learning and memory functions of aged rats and the up-regulation in the hippocampus neural plasticity protein expression. The results showed that APS may improve the learning and memory functions of aged rats by increasing the expressions of relevant neural plasticity proteins.
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Envejecimiento/psicología , Medicamentos Herbarios Chinos/farmacología , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Polisacáridos/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Planta del Astrágalo/química , Astragalus propinquus , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Medicamentos Herbarios Chinos/química , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
BACKGROUND: Thymic carcinoma or advanced thymoma is a rare cancer of the thymus gland that tends to be aggressive and infiltrate neighbouring organs, making total resection very difficult. Induction or adjuvant chemotherapy, or both, are often used in a multimodality approach to treat people affected by this condition, but the effectiveness of chemotherapy for thymic carcinoma or advanced thymoma remains uncertain. OBJECTIVES: To assess the role of chemotherapy in adults with thymic carcinoma or advanced thymoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7), MEDLINE (accessed via Ovid from 1966 to July 2012), EMBASE (accessed via Ovid, from 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS), the Chinese Biological Medicine Database (CBM, 1978 to July 2012), China National Knowledge Infrastructure (CNKI, 1980 to July 2012) and the Chinese scientific periodical database VIP Information (VIP, 1989 to July 2012). There was no language restriction in searching for studies. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) of trials using chemotherapy (either single-agent or combination chemotherapy plus surgery, radiotherapy or not) for thymic carcinoma and/or advanced thymoma. We planned to include all adults (aged 18 years and over) diagnosed with thymic carcinoma and/or with Masaoka stage III or IV thymic tumours. The intended primary outcomes were overall survival (OS) and progression-free survival (PFS). DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated the search results according to the inclusion and exclusion criteria. There were no studies identified for inclusion and therefore no data extraction was completed. MAIN RESULTS: No RCTs were eligible for inclusion in this review. We report details of excluded prospective studies in an additional table and try to provide some useful evidence regarding current practice. AUTHORS' CONCLUSIONS: There were no RCTs eligible for inclusion in this review. In current practice the most common regimen for adult patients with thymic carcinoma or advanced thymoma is cisplatin-based chemotherapy. Considering the condition is rare, it is suggested that an international group is set up to organise and evaluate prospective collection of data from cohorts of patients to inform current clinical practice.
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Antineoplásicos/uso terapéutico , Timoma/tratamiento farmacológico , Neoplasias del Timo/tratamiento farmacológico , Adulto , Humanos , Estudios Prospectivos , Timoma/patología , Neoplasias del Timo/patologíaRESUMEN
Interoception is the sensation of the physiological state inside one's body. Growing evidence suggests that visual feedback of interoception improves body self-consciousness (BSC) and reduces pain perception among patients with chronic pain. However, whether the integration of exteroception and interoception influences pain processing in healthy individuals remains largely unknown. To examine this question, we combined the rubber hand illusion (RHI) paradigm with visualized interoception -flashing of an LED light on the rubber hand synchronously or asynchronously with participants' real-time heartbeats. Under these conditions, we tested pain thresholds and corresponding event-related potentials. The interoceptive visual feedback inhibited the P2 component of pain, and the RHI inhibited pre-stimulus alpha-band brain activity. BSC had no significant effect on the processing of pain. These findings demonstrate that interoceptive signals with visual feedback inhibit pain processing, and that this psychophysiological process is largely independent of reported self-consciousness, in healthy individuals.
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Dolor Agudo , Ilusiones , Interocepción , Imagen Corporal , Mano/fisiología , Humanos , Ilusiones/fisiología , Interocepción/fisiología , Percepción Visual/fisiologíaRESUMEN
The physical properties of a single cell, such as mass, volume, and density, are important indications of the cell's metabolic characteristics and homeostasis. Precise measurement of a single cell's mass has long been a challenge due to its minute size. It is only in the past 10 years that a variety of instruments for measuring living cellular mass have emerged with the development of MEMS, microfluidics, and optics technologies. In this review, we discuss the current developments of physical cytometry for quantifying mass-related physical properties of single cells, highlighting the working principle, applications, and unique merits. The review mainly covers these measurement methods: single-cell mass cytometry, levitation image cytometry, suspended microchannel resonator, phase-shifting interferometry, and opto-electrokinetics cell manipulation. Comparisons are made between these methods in terms of throughput, content, invasiveness, compatibility, and precision. Some typical applications of these methods in pathological diagnosis, drug efficacy evaluation, disease treatment, and other related fields are also discussed in this work.
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MicrofluídicaRESUMEN
The present study aimed to investigate the efficacy of a myeloid dendritic cell (mDCs) and plasmacytoid (p)DC combined vaccine loaded with heat-treated cancer cell lysates against lung cancer cells. The mDCs and pDCs were selected using magnetic bead sorting. Antigen loading was performed by adding heat-treated Lewis lung cancer cell lysates to mDC, pDC or mDC+pDC (1:1). Surface expression of CD80, CD86, CD40 and major histocompatibility complex (MHC)-II molecules were determined using flow cytometry, and the secretion of cytokines IL-12, IL-6 and TNF-α were assessed using ELISA assays. The effect of the mDC and pDC vaccine on cytotoxic T lymphocytes (CTLs) against tumor cells was investigated. Tumor-bearing nude mice were intravenously injected with the mDC and pDC combined vaccine. Tumor tissues were collected for hematoxylin and eosin and TUNEL staining. Loading with tumor cell lysate significantly upregulated the surface expression of costimulatory molecules MHC-II on DCs and enhanced secretions of IL-6, IL-12 and TNF-α by DCs. In addition, the tumor cell lysate-loaded mDC and pDC combined vaccine significantly promoted lymphocyte proliferation and enhanced CTL-mediated cytotoxicity against Lewis lung cancer cells compared with mDC or pDC treatment alone. Furthermore, intravenous injection of the mDC and pDC combined vaccine into tumor-bearing nude mice significantly inhibited subcutaneous tumor growth and induced necrosis and apoptosis within the tumor tissue. Overall, the pDC and mDC combination vaccine loaded with heat-treated Lewis lung cancer cell lysate had a synergistic effect on the induction of T lymphocyte proliferation and antitumor efficacy, which may be associated with the upregulation of co-stimulatory molecules and cytokine secretions.
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Primary thymic atypical carcinoid (TAC) is a kind of neuroendocrine tumors of the mediastinum, which has a poor prognosis due to its invasive behavior, metastasis and postoperative recurrence. We present a relatively rare case who came to hospital because of chest pain and tightness from a large mediastinal mass of 115 mm × 95 mm compressing left brachiocephalic veins, pericardium and upper-lobe of left lung. Although the operation was rather challenging, we performed complete resection including local lymph node dissection by open median sternotomy. The pathology of combining hematoxylin/eosin staining and immunohistochemical was confirmed to be primary TAC, grade 2 according to 2015 WHO Classification of Tumors of the Thymus. After radical surgery, the case underwent 6 cycles of platinum-based adjuvant chemotherapy. To date, the man has survived over 11 months without recurrence and distant metastasis. In conclusion, open surgery is a safe and effective method for locally advanced TAC and radical resection combination with adjuvant chemotherapy may lead to a long-term survival.
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BACKGROUND: Dedifferentiated liposarcoma in the mediastinum is an extremely rare malignant neoplasm. A few previous case reports indicate that surgical resection is the major treatment, but frequent recurrence occurs locally. Due to its rarity, its clinical characteristics, optimal treatment and clinical outcomes remain unclear. Here, we report a case of multifocal recurrent dedifferentiated liposarcoma in the posterior mediastinum treated by combining surgery with 125I brachytherapy, and summarize its clinical features, treatment and prognosis. CASE SUMMARY: A 75-year-old man was admitted to our hospital with a history of gradual dysphagia for one year and aggravated dysphagia for 3 mo. Contrast-enhanced computed tomography (CT) revealed several large cystic-solid masses with lipomatous density, and calcification in the posterior-inferior mediastinum. The patient received a wide excision by video-assisted thoracoscopic surgery. Pathological analysis confirmed the tumors were dedifferentiated liposarcomas. The tumor locally relapsed 24 mo later, and another operation was performed by video-assisted thoracoscopic surgery. Fifteen months after the second surgery, the tumor recurred again, and the patient received CT-guided radioactive seeds 125I implantation. After 8 mo, follow-up chest CT showed an enlarged tumor. Finally, his condition exacerbated with severe dysphagia and dyspnea, and he died of respiratory failure in July 2018. CONCLUSION: We reviewed the literature, and suggest that surgical resection provides beneficial effects for dedifferentiated liposarcoma in the mediastinum, even in cases with local recurrence. 125I brachytherapy may be beneficial for recurrent unresectable patients.
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The therapeutic goals of patients with chronic pain are not only to relieve pain but also to improve the quality of life. Chronic pain negatively affects various aspects of daily life, such as by decreasing the motivation to work and reward sensitivity, which may lead to difficulties in daily life or even unemployment. Human and animal studies have shown that chronic pain damages reward processing; the exploration of associated internal mechanisms may aid the development of treatments to repair this damage. Incentive salience theory, used widely to describe reward processing, divides this processing into "liking" (reward-induced hedonic sensory impact) and "wanting" (reward-induced motivation) components. It has been employed to explain pathological changes in reward processing induced by psychiatric disorders. In this review, we summarize the findings of studies of reward processing under chronic pain and examine the effects of chronic pain on "liking" and "wanting." Evidence indicates that chronic pain compromises the "wanting" component of reward processing; we also discuss the neural mechanisms that may mediate this effect. We hope that this review aids the development of therapies to improve the quality of life of patients with chronic pain.
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Dolor Crónico/psicología , Calidad de Vida/psicología , Recompensa , Animales , Emociones , Humanos , MotivaciónRESUMEN
RATIONALE: Primary schwannoma is extremely rare in the trachea, and its optimal treatment has not yet been established. Previous literature have indicated that traditional resection by thoracotomy is an effective surgical procedure but with huge trauma, and endoscopic excision is a minimally invasive surgical method but with possibility of recurrence. Window resection was usually utilized for selected patients with trachea invasion by thyroid carcinoma, but video-assisted thoracoscopic window resection for trachea schwannoma has not been reported previously. PATIENT CONCERNS: A 23-year-old woman was admitted to hospital due to dyspnea, coughing and wheezing that had persisted for 2 months with aggravation for 1 week. DIAGNOSES: Chest computed tomography (CT) scan revealed a well-circumscribed soft-tissue mass located on the right lateral posterior wall of the trachea. Bronchofibroscopy (BFS) showed a whitish, smooth and round mass with a wide base in the trachea. Immunohistochemical staining demonstrated cells labeled with Vim (+), S-100 (+), SOX-10 (+), SMA (-), CK (-). Histopathological examinations showed that the mass was a schwannoma. INTERVENTIONS: The tumor was nearly completely excised via BFS, but relapsed 2 times at 12 days and 3 weeks after endoscopic resection. Finally, the patient underwent video-assisted thoracoscopic window resection of trachea. OUTCOMES: The patient recovered rapidly and no recurrence was observed over 6 months of follow-up. LESSONS: The treatment of tracheal schwannoma depends on the characteristics of tumor and the condition of patient. Surgical resection is a preferred alternative for sessile or transmural tumors and recurrence after endoscopic excision. Tracheal window resection by video-assisted thoracoscopy is beneficial for some appropriate patients with a small and sessile tumor.
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Neurilemoma/cirugía , Cirugía Torácica Asistida por Video/métodos , Neoplasias de la Tráquea/cirugía , Femenino , Humanos , Neurilemoma/diagnóstico , Neurilemoma/patología , Tomografía Computarizada por Rayos X , Tráquea/patología , Tráquea/cirugía , Neoplasias de la Tráquea/diagnóstico , Neoplasias de la Tráquea/patología , Adulto JovenRESUMEN
BACKGROUND: This study aimed to evaluate the clinical efficacy and safety of endoscopic thoracic sympathicotomy and to explore strategies to decrease the incidence of transfer hyperhidrosis (TH). METHODS: From January 2003 to July 2016, 10,275 patients with primary palmar hyperhidrosis underwent endoscopic thoracic sympathicotomy in 15 different institutions. We carried out a retrospective analysis of these patients who were grouped into group A, those with nonretained R2 (R2, R2-3, or R2-4 ablation), and group B, those with retained R2 (single R3 or R4 ablation). RESULTS: All procedures were performed successfully. Both hands of all patients became warm and dry immediately after endoscopic thoracic sympathicotomy. Pneumothorax occurred in 146 patients, and 39 patients had intraoperative bleeding. Follow-up was carried out from 6 months to 13 years. A total of 531 patients (5.2%) were lost to follow-up. The effective rate for primary palmar hyperhidrosis was 100%. Palmar hyperhidrosis recurred in 73 patients (0.7%). Transfer hyperhidrosis appeared in 7,678 patients (78.8%). For groups A and B, the incidence of TH was 80.4% and 78.5%, respectively (P > .05), but the incidence of grade III+IV TH in group B (1.6%) was less than that in group A (4.8%; P < .001). CONCLUSION: Endoscopic thoracic sympathicotomy is a minimally invasive, safe, and effective therapeutic method for primary palmar hyperhidrosis. Although the overall incidence of TH is high, the incidence of grade III to IV TH can be decreased by reserving R2, lowering the level of thoracic sympathicotomy, and single severing of R3 or R4.
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Hiperhidrosis/cirugía , Complicaciones Posoperatorias/epidemiología , Simpatectomía/efectos adversos , Nervios Torácicos/cirugía , Cirugía Torácica Asistida por Video/efectos adversos , Adolescente , Adulto , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , China , Electrocoagulación/efectos adversos , Electrocoagulación/métodos , Femenino , Estudios de Seguimiento , Mano/inervación , Humanos , Hiperhidrosis/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/etiología , Recurrencia , Estudios Retrospectivos , Simpatectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
The Gan-Mai-Da-Zao (GMDZ) decoction is one of the most famous Chinese medicine prescriptions to treat emotional diseases in China. Here we examined the anxiolytic-like effects of the GMDZ decoction in mice. The mice were orally administered with GMDZ decoction (1, 2, and 4 g/kg, respectively) for 7 days, diazepam (2 mg/kg, p.o.) and buspirone (5 mg/kg, p.o.) were used as positive controls. Then, elevated plus maze (EPM) test, light/dark box (LDB) test, and marble burying (MB) test, open field (OF) test and rota-rod test were performed. We found that GMDZ treatment (2 and 4 g/kg) significantly increased the percentage of open arm entries and time spent on the open arms in EPM as compared to the control. GMDZ treatment also significantly increased the time spent in the light box and the number of light box entries in LDB and reduced the number of marbles buried in MB. Similarly to those observed with diazepam and buspirone. In contrast, GMDZ did not affect the locomotor activity in the OF and motor coordination in the rota-rod test. Furthermore, the anxiolytic-like effects induced by GMDZ were inhibited by the γ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil and 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635. These results showed that GMDZ possesses anxiolytic-like effects in animal models, and its mechanism of action might be modulated by 5-HT1A and GABAA receptors.
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Cell microinjection is a technique of precise delivery of substances into cells and is widely used for studying cell transfection, signaling pathways, and organelle functions. Microinjection of the embryos of zebrafish, the third most important animal model, has become a very useful technique in bioscience. However, factors such as the small cell size, high cell deformation tendency, and transparent zebrafish embryo membrane make the microinjection process difficult. Furthermore, this process has strict, specific requirements, such as chorion softening, avoiding contacting the first polar body, and high-precision detection. Therefore, highly accurate control and detection platforms are critical for achieving the automated microinjection of zebrafish embryos. This article reviews the latest technologies and methods used in the automated microinjection of zebrafish embryos and provides a detailed description of the current developments and applications of robotic microinjection systems. The review covers key areas related to automated embryo injection, including cell searching and location, cell position and posture adjustment, microscopic visual servoing control, sensors, actuators, puncturing mechanisms, and microinjection.
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That specific immunotherapy can inhibit cancer growth has been recognized; its efficiency is to be improved. This study aimed to inhibit lung cancer (LC) growth in a mouse model by using an LC-specific vaccination. In this study, a LC mouse model was created by adoptive transplantation with LC cells. The tumor-bearing mice were vaccinated with LC cell extracts plus adjuvant TNBS or adoptive transplantation with specific CD8(+) CD196(+) T cells. The results showed that the vaccination with LC extracts (LCE)/TNBS markedly inhibited the LC growth and induced CD8(+) CD196(+) T cells in LC tissue and the spleen. These CD8(+) CD196(+) T cells proliferated and produce high levels of perforin upon exposure to LCE and specifically induced LC cell apoptosis. Exposure to TNBS induced RAW264.7 cells to produce macrophage inflammatory protein-3α; the latter activated signal transducer and activator of transcription 3 and further induced perforin expression in the CD8(+) CD196(+) T cells. Adoptive transfer with specific CD8(+) CD196(+) T cells suppressed LC growth in mice. In conclusion, immunization with LC extracts and TNBS can induce LC-specific CD8(+) CD196(+) T cells in LC-bearing mice and inhibit LC growth.
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Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/inmunología , Inmunoterapia Adoptiva/métodos , Neoplasias Pulmonares/terapia , Animales , Apoptosis , Linfocitos T CD8-positivos/trasplante , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Neoplasias Pulmonares/inmunología , Proteínas Inflamatorias de Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Perforina/metabolismo , Células RAW 264.7 , Receptores CCR6/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
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.
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Antineoplásicos/administración & dosificación , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Anciano , Antineoplásicos/efectos adversos , Área Bajo la Curva , Carboplatino/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Estudios Prospectivos , Método Simple Ciego , Tasa de Supervivencia , Trombocitopenia/inducido químicamenteRESUMEN
PURPOSE: We aimed at assessing the overall efficacy of angiogenesis inhibitor (AI)-containing regimens in the treatment of advanced non-small-cell lung cancer (NSCLC) according to histological types. METHODS: Studies from PubMed and Web of Science, and abstracts presented at American Society of Clinical Oncology (ASCO) meeting up to October 31, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating AIs in advanced NSCLC with survival data according to patients' histologies. The endpoints were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 10,035 patients with advanced NSCLC from 13 RCTs were identified for analysis. The pooled results demonstrated that AI-containing regimens significantly improved the PFS (HR, 0.84, 95% confidence interval (CI): 0.78-0.91, P<0.001) and OS (HR, 0.92, 95% CI: 0.85-0.99, P=0.017) in lung adenocarcinoma when compared to non-AI-containing regimens. Additionally, there was a significantly improved PFS (HR, 0.87, 95% CI: 0.77-0.98, P=0.027) for AI-containing regimens in squamous cell lung carcinoma, but it did not translated into OS benefit (HR, 1.02, 95% CI: 0.92-1.15, P=0.68). For NSCLC patients with other histological types, the use of AIs did not significantly improve PFS (HR, 0.90, 95% CI: 0.75-1.09, P=0.27) and OS (HR, 0.90, 95% CI: 0.76-1.08, P=0.19). CONCLUSION: The findings of this study suggest that the addition of AIs to the treatment therapies for patients with lung adenocarcinoma offers improved survival benefits. Prospective clinical trials investigating the role of AIs in this setting are recommended.
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Angiotensin receptor blockers (ARBs) are the most commonly used blood pressure-lowering drugs in the world. However, the preventive value of ARBs on lung cancer is still controversial. Therefore, it was necessary for us to perform a meta-analysis to evaluate the value of ARBs on lung cancer risk. We searched the PubMed database as well as the Web of Science database. The overall effect was measured by odds ratio (OR) and corresponding 95% confidence intervals (CI). The significance of the pooled ORs was determined by the Z test with a P value less than 0.05 considering statistically significant. In this meta-analysis, we found ARBs could decrease the lung cancer risk (OR=0.81, 95% CI 0.69-0.54). The stability of the results was tested by sensitivity analysis. The result was not a significant change, suggesting that the result of our meta-analysis was stable. In conclusion, our meta-analysis demonstrated that ARBs was significantly associated with lower lung cancer.
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Cancer-associated fibroblasts (CAFs) are the main component of tumor stroma which support tumor progression. Here, we set out to determine the factors that may be involved in dramatic alteration of microRNAs (miRNAs) expression pattern in CAFs. miRNAs analyses identified differential expression of 15 microRNAs, with miR-101 being the most downregulated miRNA in CAFs which were different from the normal fibroblasts. We examined several putative miR-101 target genes identified by microarray analysis and demonstrated that miR-101 directly targets CXCL12, which play important roles in CAFs. Overexpression of miR-101 significantly impaired the ability of CAFs to stimulate tumor cell proliferation, sphere formation migration and invasion, and enhanced apoptosis. Further research showed that the cellular biological behavior was regulated by miR-101 targeting CXCL12. These findings provide new insights miR-101 down-regulation in CAFs could inhibit lung cancer proliferation and metastasis via targeting CXCL12.
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Quimiocina CXCL12/genética , Fibroblastos/metabolismo , Neoplasias Pulmonares/patología , MicroARNs/genética , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Fibroblastos/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Análisis por Micromatrices , Invasividad Neoplásica/genéticaRESUMEN
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.