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The extraordinary adaptability and dispersal abilities have allowed Hyphantria cunea to expand its range, posing a great threat to urban landscapes and natural ecosystems. Searching for safe, efficient, and low-cost control methods may provide new strategies for pest management in H. cunea spread areas. In this study, based on the attraction of insects by preferred hosts, it was found that the response rates of virgin H. cunea female adults to Salix matsudana, Juglans mandshurica and Ulmus pumila were 89.17%, 97.92% and 93.98%, respectively. It was further found that this significant preference was mainly related to the volatiles m-xylene, o-xylene, dodecane and tetradecane found in the three species. Even though all four compounds at 10 µL/mL and 100 µL/mL had significant attractive effects on the virgin H. cunea female adults, m-xylene and dodecane at 100 µL/mL elicited significant EAG responses and tending behaviors by stimulating the olfactory receptor neurons (ORN A) of females, with response rates of 83.13% and 84.17%, while also having significant attractive effects on virgin male adults with rates of 65.74% and 67.51%. Therefore, both m-xylene and dodecane which at concentrations of 100 µL/mL had strong attractions to adults, could be used as the first choice of attractants for both sexes of H. cunea. This has important practical significance in reducing the frequency of H. cunea generations, limiting their population, controlling their spread range, and improving the efficiency of pest management in epidemic areas.
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Compuestos Orgánicos Volátiles , Animales , Femenino , Masculino , Compuestos Orgánicos Volátiles/farmacología , JuglansRESUMEN
CBP/p300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (CITED1) is a transcriptional activator belonging to the non-DNA-binding transcription co-regulator family. It regulates diverse pathways, including the transforming growth factor/bone morphogenetic protein/SMAD, estrogen, Wnt-ß-catenin, and androgen-AR signaling pathways, by binding to CBP/p300 co-activators through its conserved transactivation domain CR2. CITED1 plays an important role in embryonic development and a certain regulatory role in the occurrence and development of various tumors. In this article, the biological characteristics, expression regulation, participating signaling pathways, and potential roles of CITED1 in the clinical diagnosis and treatment of tumors are reviewed.
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Proteínas Reguladoras de la Apoptosis , Neoplasias , Transactivadores , Humanos , Estrógenos , Neoplasias/genética , Factores de Transcripción , Proteínas Reguladoras de la Apoptosis/genética , Transactivadores/genéticaRESUMEN
The aim of the present study was to investigate the cytotoxic effects and underlying molecular mechanisms of nitidine chloride (NC) in hepatocellular carcinoma cells via quantitative proteomics. MTT assays were used to detect the inhibitory effects of NC in Bel-7402 liver cancer cells, and the number of apoptotic cells was measured by flow cytometry. Quantitative proteomics technology based on iTRAQ was used to discover differential expressed proteins after NC treatment, and bioinformatic techniques were further used to screen potential targets of NC. Molecular docking was applied to evaluate the docking activity of NC with possible upstream proteins, and their expression was detected at the mRNA and protein levels by quantitative reverse transcription PCR and western blotting. NC inhibited the proliferation of Bel-7402 cells after 24 h of treatment and stimulated apoptosis in vitro. The proteomics experiment showed that NC triggers mitochondrial damage in HCC cells and transcription factor AP-1 (c-Jun) may be a potential target of NC (fold change = 4.36 ± 0.23). Molecular docking results revealed the highest docking score of NC with c-Jun N-terminal kinase (JNK), one of the upstream proteins of c-Jun. Moreover, the mRNA and protein expression of c-Jun and JNK were significantly increased after NC treatment (p < 0.05). These findings indicate that NC significantly induced mitochondrial damage in HCC cells, and induced apoptosis by activating JNK/c-Jun signaling.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Factor de Transcripción AP-1/metabolismo , Proteómica , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Apoptosis , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , ARN MensajeroRESUMEN
In Chinese, the graphic units are Chinese characters, most of which are compound characters. Since a compound character can be different from another one in being regarded as composed of components (compositionality), readers might have developed a compositionality awareness of the constituent characters in two-character word (2C-word) recognition. Two experiments were conducted in a lexical decision task on the same set of 2C-words, the first constituent characters of which were manipulated in compositionality. Given that a Chinese character is more difficult to recognize when it is presented upside-down than when it is presented in an upright orientation and that it is inevitable to perceive the constituent characters in 2C-word recognition, we manipulated the first constituent characters' presentation orientation to increase the task difficulty. The two constituent characters of a 2C-word target were displayed simultaneously in a trial in Experiment 1 but were shown sequentially in Experiment 2. Participants were two cohorts of adult Chinese native speakers (CNS1s and CNS2s). CNS1s had a significantly lower level of reading proficiency than CNS2s. The influence of orientation was observed in both CNS1s and CNS2s' performance across the two experiments, but only CNS2s' reaction times seemed to have indicated the effect of compositionality in Experiment 2. Skilled readers are more likely than less skilled readers to be conscious of compositionality of the first constituent characters, which are presented separately from the second ones, in 2C-word recognition.
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Reconocimiento Visual de Modelos , Lectura , Adulto , China , Humanos , Tiempo de Reacción , Reconocimiento en PsicologíaRESUMEN
Dysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases. In the present study we investigated the effects of known K2P channel modulators on TWIK2 channel expressed in a heterologous system. In order to increase plasma membrane expression and thus TWIK2 currents, a mutant channel with three mutations (TWIK2I289A/L290A/Y308A) in the C-terminus was expressed in COS-7 cells. TWIK2 currents were assessed using whole-cell voltage-clamp recording. Among 6 known K2P channel modulators tested (DCPIB, quinine, fluoxetine, ML365, ML335, and TKDC), ML365 was the most potent TWIK2 channel blocker with an IC50 value of 4.07 ± 1.5 µM. Furthermore, ML365 selectively inhibited TWIK2 without affecting TWIK1 or THIK1 channels. We showed that ML365 (1, 5 µM) concentration-dependently inhibited ATP-induced NLRP3 inflammasome activation in LPS-primed murine BMDMs, whereas it did not affect nigericin-induced NLRP3, or non-canonical, AIM2 and NLRC4 inflammasomes activation. Knockdown of TWIK2 significantly impaired the inhibitory effect of ML365 on ATP-induced NLRP3 inflammasome activation. Moreover, we demonstrated that pre-administration of ML365 (1, 10, 25 mg/kg, ip) dose-dependently ameliorated LPS-induced endotoxic shock in mice. In a preliminary pharmacokinetic study conducted in rats, ML365 showed good absolute oral bioavailability with F value of 22.49%. In conclusion, ML365 provides a structural reference for future design of selective TWIK2 channel inhibitors in treating related inflammatory diseases.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Adenosina Trifosfato/metabolismo , Animales , Proteínas de Unión al ADN , Inflamasomas/metabolismo , Inflamación , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , RatasRESUMEN
Anti-γ-aminobutyric acid type ß receptor (anti-GABABR) antibody-associated encephalitis is a type of autoimmune encephalitis. According to current literature, its pathogenesis is reported to be closely related to tumor factors. However, diagnosis can be difficult because of the rarity of cases, limited clinical understanding, and a lack of specificity in clinical manifestation and imaging presentation. Clinical trials have demonstrated that immunotherapy can prolong the survival of patients with small cell lung cancer; however, in some cases, immunotherapy may induce anti-GABABR antibody-associated encephalitis. Patients who develop this encephalitis during immunotherapy often delay treatment because the cause is not clearly identified. In this study, we report a case of a 61-year-old man with a confirmed diagnosis of small cell lung cancer who had acute onset of cognitive impairment and seizures after two cycles of durvalumab (AstraZeneca UK Limited) combination chemotherapy. This reaction was initially considered as an immune-related adverse event (irAE) caused by durvalumab treatment, and the patient was eventually considered to have a paraneoplastic neurological disorder caused by the primary tumor. This report raises awareness of the symptoms of cognitive impairment and seizures in patients with small cell lung cancer, and the possible adverse events associated with immunotherapy. This case also highlights the importance of detecting anti-GABABR antibodies in patients with small cell lung cancer.
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BRAF mutations, primarily sensitizing mutations, such as BRAFV600E , have been proven to response to the BRAF inhibitor, Dabrafenib combined with trametinib therapy, but there have been no data demonstrating that it has activity against NSCLC-related brain metastases (BM). How patients harboring BRAFS365L mutation (a rare mutation following BRAFV600E -inhibitor treatment) in NSCLC is unknown. Vemurafenib, another BRAF inhibitor, can reverse the resistance that develops with the BRAFS365L mutation following dabrafenib combined with trametentinib treatment in melanoma, but none has been reported in NSCLC. Lung papillary cancer, as a rare typing, occupies about 4% of NSCLC. Hence, we reported the first case of a patient with BM of lung papillary carcinoma harboring a BRAFV600E mutation who benefited from dabrafenib combined with trametinib, and following the development of the BRAFS365L mutation, vemurafenib remained an effective therapeutic option. Moreover, we found that the next-generation sequencing (NGS) of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) may potentially provide more accurate information about intracranial lesions than ctDNA in the blood serum, which will be a better detection method.
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BACKGROUND: More accurate predictive factors for colorectal cancer (CRC) are urgently needed. This study aimed to assess the potential prognostic roles of circulating tumor cells (CTCs), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in CRC patients. METHODS: Between 2014 and 2017, 118 CRC patients newly diagnosed at the Affiliated Zhongshan Hospital of Dalian University were retrospectively analyzed, including 72 (61%) patients that underwent radical resection (resectable CRC) and 46 (39%) advanced patients with metastatic CRC (mCRC). The CellSearch System was used to detect CTCs, and Spearman's correlation analyses tested the correlations between CTC counts and both NLR and PLR. Statistical analyses were performed using the Kaplan-Meier method, log-rank tests, and Cox proportional hazards models. RESULTS: Of the resectable cohort, 24% were positive for CTCs. Of the advanced cohort, 49% were positive for CTCs. The presence of CTCs was associated with advanced age (≥63 years old; P=0.037), a high PLR value (P=0.008), and a high NLR value (P=0.034). Additionally, baseline NLR [hazard ratio (HR) =0.423; 95% confidence intervals (CI), 0.223-0.803; P=0.008], PLR (HR =0.513; 95% CI, 0.276-0.954; P=0.035), and CTC counts (HR =2.155; 95% CI, 1.152-4.032; P=0.016) were significantly associated with progression-free survival (PFS) in a univariate analysis of mCRC patients that received chemotherapy. Multivariate analysis further showed that NLR (P=0.044) and CTCs (P=0.047) were independent prognostic factors for mCRC patients. CONCLUSIONS: This study provided evidence that NLR and CTC counts could serve as robust prognostic factors for patients with mCRC.
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Cabozantinib has been shown to have potent anti-ROS1 activity in many solid malignancies, particularly against those with solvent-front resistance mutations following crizotinib therapy. With regard to the most common CD74-ROS1 fusion, the efficacy of cabozantinib has only been demonstrated in vitro. Therefore, we evaluate the efficacy of cabozantinib in a patient with advanced non-small-cell lung cancer (NSCLC) harboring a CD74-ROS1 fusion in the present study. A 40-year-old female patient presented with 1-month history of cough, white sputum and chest pain. Chest CT scan revealed a consolidation in the middle lobe of the right lung together with multiple cavity lesions spreading in both lungs. Histopathological analysis of biopsy samples from the lesion in the middle lobe of the right lung suggested lung adenocarcinoma. After two lines of chemotherapy and EGFR-TKI therapy, a CD74-ROS1 rearrangement was detected and the patient was administered with cabozantinib for 1.5 years. Since cabozantinib resistance developed, crizotinib therapy was applied and demonstrated clinical effectiveness until now. Together, we report the first case of cabozantinib effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient. Crizotinib remained as an effective therapeutic option following the acquisition of cabozantinib resistance.
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BACKGROUND: The activation of inflammation and coagulation cascades plays an essential role in the development of various malignancies, including metastatic breast cancer (MBC). This retrospective study aimed to investigate the prognostic role of the combination of fibrinogen and the inflammation-based index in patients with MBC. METHODS: A total of 176 patients with MBC were retrospectively reviewed. The clinical and pathological data of included patients were followed-up and analyzed. The plasma fibrinogen concentration (FIB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. Dynamic variations in the FIB, NLR, and PLR values were collected from 56 MBC patients before and after first-line therapy. Receiver operating characteristic (ROC) curves were constructed to assess the optimal cut-off values. Correlations between FIB and NLR or PLR were evaluated using Spearman correlation analysis. The Kaplan-Meier method, two-tailed log-rank test, and Cox proportional hazard model were used for statistical analysis. RESULTS: Baseline FIB was positively correlated with NLR and PLR values in MBC patients (P<0.05). Additionally, multivariable analysis proved that the ERBB2 + subtype (P=0.023), basal-like subtype (P=0.032), targeted therapy (P=0.033), other regimens (P=0.005), and baseline FIB level (P=0.004) were independent prognostic variables for progression-free survival (PFS) in MBC patients. Furthermore, ERBB2+, basal-like subtypes, and baseline hyperfibrinogenemia were independent factors for poor prognosis in MBC patients [hazard ratio (HR): 3.717, 95% confidence interval (CI): 1.561-8.851, P=0.003; HR: 3.245, 95% CI: 1.368-7.698, P=0.008; HR: 2.069, 95% CI: 1.352-3.167, P=0.001, respectively]. Most importantly, the FIB level increased significantly after first-line therapy in patients with disease progression (3.73±0.63 vs. 5.32±0.52 g/L, P=0.042) and also decreased markedly in stable disease (3.42±1.05 vs. 3.03±0.73 g/L, P=0.036). However, PFS and overall survival (OS) were not significantly correlated with the dynamic changes of FIB and the inflammation-based index. CONCLUSIONS: The present study provided evidence that baseline FIB combined with NLR and PLR could serve as prognostic predictors for MBC patients. Dynamic change of FIB before and after first-line therapy could also be used as a potential predictor of therapeutic response in MBC patients.
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K2P potassium channels stabilize the resting membrane potential in nearly all cells and have been implicated in several neuronal, cardiovascular, and immune diseases. DCPIB, a known specific and potent inhibitor of volume-regulated anion channels (VRAC), has been reported to activate TREK1 and TREK2 in astrocytes and in vitro recently. In the present study, we demonstrated DCPIB also voltage dependently activated TRAAK besides TREK1/TREK2, showing DCPIB activated all TREK subfamily members. In contrast, the compound potently inhibited several other K2P channels with no voltage dependence, including TRESK, TASK1, and TASK3. DCPIB displayed superior selectivity toward TRESK with an IC50 of 0.14 µM, demonstrating at least 100-fold higher affinity over TREK1/TRAAK channels. Furthermore, the impaired ion selectivity filter region greatly impaired the activating effect of DCPIB on TREK1 but not the inhibitory effect of DCPIB on TRESK. This indicates distinct molecular determinants underlying the effect of DCPIB on TREK1 or TRESK channels. Our results showed that DCPIB played diverse effects on K2P channels and could be a useful tool for further investigating structure-function studies of K2P channels.
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Ciclopentanos/farmacología , Indanos/farmacología , Canales de Potasio de Dominio Poro en Tándem/efectos de los fármacos , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Animales , Células COS , Chlorocebus aethiops , HumanosRESUMEN
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure. In this study, we designed and synthesized eight alkanol amine derivatives, and assessed their effects on HCN channels expressed in COS7 cells using a whole-cell patch clamp method. Among them, compound 4e displayed the most potent inhibitory activity with an IC50 of 2.9 ± 1.2 µM at - 120 mV on HCN2 channel expressed in COS7 cells. Further analysis revealed that application of compound 4e (10 µM) caused a slowing of activation and a hyperpolarizing shift (ΔV1/2 = - 30.2 ± 2.9 mV, n = 5) in the voltage dependence of HCN2 channel activation. The inhibitory effect of compound 4e on HCN1 and HCN4 channel expressed in COS7 cells was less potent with IC50 of 17.2 ± 1.3 and 7.3 ± 1.2 µM, respectively. Besides, we showed that application of compound 4e (10 µM) inhibited Ih and action potential firing in acutely dissociated mouse small dorsal root ganglion neurons. Our study provides a new strategy for the design and development of potent HCN channel inhibitors.
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Amino Alcoholes/farmacología , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/antagonistas & inhibidores , Moduladores del Transporte de Membrana/farmacología , Potenciales de Acción/efectos de los fármacos , Amino Alcoholes/síntesis química , Amino Alcoholes/química , Animales , Células COS , Chlorocebus aethiops , Humanos , Masculino , Moduladores del Transporte de Membrana/síntesis química , Moduladores del Transporte de Membrana/química , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Canales de PotasioRESUMEN
Osimertinib is commonly used in pulmonary adenocarcinoma patients who are resistant to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and carry the T790M mutation. However, the use of osimertinib may result in the development of further resistance, most commonly via the cis-C797S mutation. Herein, we report a case of a lung cancer patient harboring triple EGFR mutations of L858R, T790M, and cis-C797S who was treated with a combination of osimertinib, bevacizumab, and brigatinib. The above 3 mutations were detected by circulating tumor DNA analysis after osimertinib treatment. Subsequently, the patient received combination therapy of osimertinib and bevacizumab; the partial relief obtained was negated by later disease progression. The regimen was then changed to osimertinib, bevacizumab, and brigatinib combination therapy. Partial remission was observed, and a significant reduction in EGFR mutations was detected. This case represents the first evidence that 1) bevacizumab combined with osimertinib can significantly relieve tumor growth and respiratory symptoms in non-small-cell lung cancer patients with osimertinib resistance and 2) the clinical use of osimertinib, bevacizumab, and brigatinib is effective as combination therapy for pulmonary adenocarcinoma in the presence of triple EGFR mutations of L858R, T790M, and cis-C797S. These combination therapies may provide potential novel treatment options for pulmonary adenocarcinoma patients.
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Most of the existing chemotherapeutic drugs have plenty of side effects. Chinese herbal medicine has been used for pharmaceutical and dietary therapy for thousands of years with more effective and fewer side effects. Cestrum nocturnum (CN) has long been used to treat digestive diseases for centuries in China. Our previous study first proved that the n-butanol part isolated from the flowers of CN produced an inhibitory effect on the proliferation of malignant cells. However, the fractions responsible for the antiproliferation effect of n-butanol part from CN flowers and related mechanisms remain unknown. Thus, in this study, we extracted fractions C4 and C5 from n-butanol part of CN flowers and investigated their immune toxicity and antitumor activities. It was found that fractions C4 and C5 exhibited great cytotoxicity to cancer cell lines but had low immune toxicity towards T and B lymphocytes in vitro. The tested fractions also attenuated proliferation and induced apoptosis at G0/G1 and G2/M phases in Bel-7404 cells through inducing DNA damage and inhibiting topoisomerase II relaxation activity. These results suggest that fractions C4 and C5 may represent important sources of potential antitumor agents due to their pronounced antitumor effects and low immune toxicity.
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Gastric carcinoma (GC) is one of the most common malignant tumors and is mainly treated by invasive surgeries. The present study aimed to investigate the treatment potential of Trametes robiniophila on GC using the human GC cell line MKN-45. Cells were incubated with Trametes robiniophila at a concentration of 0, 5 and 10 mg/ml for 24 h. The apoptosis of the cell line was examined with acridine orange/ethidium bromide staining and flow cytometry. The expression of B-cell lymphoma (Bcl)-2, Fas, caspase-3, matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed using reverse transcription-polymerase chain reaction and western blotting. With increasing drug concentrations, the proportion of apoptotic and necrotic cells increased. For a certain concentration, the apoptotic ratio also increased with increasing response times. Compared with the control group, the Bcl-2, MMP-2 and MMP-9 expression levels in the MKN-45 cell line decreased, while the expression levels of Fas and caspase-3 increased (P<0.05), and the expression patterns were strengthened with increasing drug concentrations. The present study revealed that Trametes robiniophila had treatment potential on GC, and it may act on gastric cells through apoptotic induction and MMPs expression inhibition. Based on the present results, Trametes robiniophila may be considered as an alternative approach for noninvasive therapy of GC. However, future studies should be performed to clarify this further.
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BACKGROUND: The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established. METHODS: Male BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n=15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15+20, 15+10, and 15+5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment. RESULTS: The endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property. CONCLUSIONS: The combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components.
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Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias del Colon/tratamiento farmacológico , Ciclofosfamida/farmacología , Endostatinas/farmacología , Microvasos/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Animales , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Western Blotting , Línea Celular Tumoral , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Ciclofosfamida/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Endostatinas/uso terapéutico , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Reacción en Cadena de la Polimerasa , Distribución Aleatoria , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of the present study was to investigate mutation status of the c-Kit gene (KIT) and PDGFRA in patients with a gastrointestinal stromal tumor (GIST). In total, 93 patients with a GIST were included in the study, in which polymerase chain reaction amplification and gene sequencing were used to detect the sequences of exons 9, 11, 13 and 17 in KIT and exons 12 and 18 in PDGFRA. KIT mutations were detected in 64 cases (68.82%), of which exon 11 mutations were detected in 56 cases (60.22%), exon 13 mutations were detected in three cases (3.23%) and one case (1.08%) was shown to have a mutation in exon 17. The most common mutation in exon 11 was a deletion, which accounted for 55.36% (31/56) of the cases, followed by a point mutation observed in 26.79% (15/56) of the cases, while an insertion (tandem repeats) was identified in 14.29% (8/56) of the cases, and 3.57% (2/56) of the exon 11 mutations were deletions associated with a point mutation. The majority of the mutations were heterozygous, with only a few homozygous mutations. Mutational analysis revealed the mutations to be more concentrated in the classic hot zone at the 5'-end, followed by the tandem repeat frame at the 3'-end. In four cases, a mutation was detected in exon 18 of PDGFRA, of which one was associated with a mutation in KIT. The remaining three cases (10.34%, 3/29) were not associated with mutations in KIT and accounted for 37.5% (3/8) of the CD117-negative GIST cases. Therefore, the majority of the GIST cases were characterized by mutations in KIT or PDGFRA, which were directly associated with the disease. Pairs of different mutations in the same exon of KIT, or KIT mutations coupled with pairs of mutations in PDGFRA, were detected in a small number of patients. Imatinib is a small molecule tyrosine kinase inhibitor and is the first line targeted treatment for GIST, resulting in markedly improved survival rates. Thus, gene mutation genotyping may provide inspiration and guidance for imatinib-based targeted cancer therapy.
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MicroRNAs are involved in several biological processes including cell apoptosis and proliferation, stress resistance, and fat metabolism, and act as tumor suppressors by malignant transformation of human cells. The aim of this study was to identify the associations of single nucleotide polymorphisms (SNPs) rs11614913 and rs3746444 with lung cancer risk. In this meta-analysis with 2,219 cases and 2,232 controls for SNP rs11614913 and 1,685 cases and 1,690 controls for SNP rs3746444, we summarized five case-control studies by searching databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI). Lung cancer risk associated with the two SNPs was estimated by odd ratios (ORs) with 95% confidence intervals (CIs). SNP rs11614913 (OR 0.88, 95% CI 0.78-1.00 for TT vs. CT + CC) was found to be potentially associated with a decreased risk of lung cancer. However, we found no association between SNP rs3746444 and lung cancer risk. In the subgroup analysis by ethnicity, a negative association was also observed in Asians for SNP rs11614913, but a nonsignificant association for SNP rs3746444. Our meta-analysis provides evidence for potential protective effects on lung cancer risk associated with SNP rs11614913, particularly in Asian populations. Further, larger studies are necessary to validate the findings.
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Predisposición Genética a la Enfermedad/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Humanos , Oportunidad Relativa , Factores de RiesgoRESUMEN
OBJECTIVE: To observe the antitumor effects of extracts from Cestrum nocturnum (CN) in vivo. METHODS: The S180-mice model was used to observe the tumor-inhibition rate of CN and the H22-mice model was used to test the survival time. RESULTS: The experiment in S180-mice demonstrated that the n-butanol and polysaccharides extracts from CN had obvious effects on tumor inhibition. Its inhibitory rates were 52.30%, 46.75%, 42.28%, 43.19%, 37.96% and 31.82% respectively in the mice administrated the n-butanol and polysaccharides extracts from CN with 30 mg/kg, 20 mg/kg and 15 mg/kg weight dosage. It was noted that tumor formation postponed in mice treated with the n-butanol and polysaccharides extracts from CN compared with the control panel and tumor growth became slower; The n-butanol and polysaccharides extracts from CN could also greatly enhance the life span of mice with H22 ascitic tumors by 116.43%, 44.52%, 20.54%, 109.52%, 112.61% and 115.01%, respectively. The inhibit effects of n-butanol fraction extracts from CN had direct relationship with dose, while the polysaccharides fraction extracts from CN had no obvious relationship with dose. CONCLUSION: The n-butanol and polysaccharides extracts of CN are able to inhibit tumor growth and prolong the lifetime of the tumor-bearing mice in a dose-dependent pattern.