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AbstractObjective: To establish an acquired aplastic anemia animal model for investigating the function of T lymphocyte and the pathogenesis and treatment of aplastic anemia(AA). METHODS: To establish the acquired aplastic anemia mouse model through the X-ray irradiation in combination with lymphocytes injection. AA Group: the purified Pan T lymphocytes from the spleen of C57BL/6J mice were enriched and injected to the mice through tail vein(5×106), the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation; TBI Group: the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation, and were injected with the same volume of PBS buffer; Control group: the CB6F1 mice were only injected with the same volume of PBS buffer. The peripheral blood routine was examined and the number of nucleated cells in bone marrow were calculatedï¼the hematopoiesis changes in bone marrow was examinedï¼flow cytometry was used to examine the distribution of T lymphocytes in bone marrow, and it also used to examine the apoptosis of bone marrow cells and the differentiation of spleen T lymphocytes. RESULTS: Compared with 4, 5 Gy irradiated mice in AA groups, the survival time of 3 Gy irradiated AA groups was significantly prolonged. 3, 4 and 5 Gy X-ray irradiation combined with Pan T lymphocyte injection could successfully induced severe reduction of red blood cells, blood neutrophils, and platelets, severe reduction of bone marrow nucleated cells, severe bone marrow hematopoietic failure, and the significant expansion of T lymphocytes ratio in the bone marrow. CD4+ and CD8+ T cells were both increased, but mainly on CD8+ T cells, and could promote the differentiation of T cells from naïve T cells to effector memory T cells. CONCLUSION: 3, 4 and 5 Gy X-ray irradiation combined with 5×106 pan-T cell injection could successfully induce acquired aplastic anemia through T lymphocyte hyperfunction. Compared with 4, 5 Gy irradiated AA group, the 3 Gy irradiated AA group shows significantly longer survival time, and the peripheral blood routine profile closely resembles the clinical manifestations of AA patients.
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Anemia Aplástica , Animais , Medula Óssea , Células da Medula Óssea , Linfócitos T CD8-Positivos , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE@#This study aimed to investigate the role of protein kinase D (PKD)1 in regulating the growth, apop-tosis, and drug sensitivity of the squamous carcinoma cell line SCC-25.@*METHODS@#The SCC-25 cell line was transfected with either the control-shRNA or PKD1-shRNA plasmids. The stable transfected cells were selected, and the efficiency of PKD1 knockdown was detected by Western blot. The growth and apoptosis of SCC-25 were analyzed with a cell counting kit-8 (CCK8) and flow cytometry. The 50% inhibitory concentrations (IC50) of paclitaxel in the control and PKD1 knockdown cell lines were detected by CCK-8. The expression levels of Bax, Bcl-2, and P-gp were detected by Western blot.@*RESULTS@#PKD1 was constitutively expressed and phosphorylated in various cancer cell lines. Inhibiting the expression of PKD1 in SCC-25 cells by RNA interference could inhibit the growth and promote the apoptosis of SCC-25 cells via downregulating Bcl-2 expression. Additionally, inhibiting PKD1 expression could downregulate the expression of P-gp, thereby decreasing both the IC50 and resistance index of paclitaxel.@*CONCLUSIONS@#PKD1 plays an important role in regulating the biobehavior of SCC-25. It is a potential therapeutic target for oral squamous carcinoma.
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Humanos , Apoptose , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias BucaisRESUMO
OBJECTIVE@#To observe the effect of protein kinase D1 (PKD1) on the growth and metabolism of oral squamous cell carcinoma HSC-4 cells and related molecular mechanisms in the tumor microenvironment.@*METHODS@#HSC-4 cell lines were transfected with shRNA plasmids. Three groups (Wild, control-shRNA, and PKD1-shRNA) were cultured under acidic or hypoxic environment for a certain time. Western blot was used to detect the expression of autophagy-related and glycolytic-related proteins. The proliferation changes were detected by CCK-8 kits.@*RESULTS@#The PKD1-knockdown HSC-4 cell line was established. PKD1 silencing increased autophagy activity. Under hypoxic and acidic conditions, the PKD1-knockdown HSC-4 cells showed lower proliferation than the parental cells. PKD1-knockdown also decreased the expression of hypoxia induciblefactor 1α (HIF-1α) and pyruvate kinase M2 (PKM2).@*CONCLUSIONS@#Under hypoxic and acidic conditions, PKD1 gene silencing can increase apoptotic autophagy activity. Downregulated PKD1 gene expression can reduce the glycolysis of oral squamous cell carcinoma cells and inhibit tumor cell proliferation. This study revealed the important role of PKD1 in the metabolism and growth of oral squamous cell carcinoma, making it a possible target for the treatment of oral squamous cell carcinoma.
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Humanos , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Bucais , Proteínas Quinases , Microambiente TumoralRESUMO
Based on literature data from Wanfang Med Online and VIP database,the paper grabs keywords of literature to establish the keywords network,in which the relation in cardiovascular adverse drugs reaction ontology is imbedded,visualizes the network,and lists cases to verify the feasibility of keywords network-based domain resources aggregation and knowledge discovery methods in the adverse drugs reaction domain.
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AIM:To study the effect of ClC-3 gene over-expression on thyroid structure and function in mice. METHODS:Three-months-old FVB mice were used to study the difference of thyroid structure and function between wild-type(WT)mouse and ClC-3 transgene mice.The expression and distribution of ClC-3 in the thyroid of mice were deter-mined by the methods of qPCR,Western blot and immunofluorescence.Behavioral monitoring was performed on the daily activities of mice.Serum concentrations of total triiodothyronine(TT3), total thyroxine(TT4)and thyrotropin(TSH) were measured by ELISA.RESULTS:Compared with the WT group,the expression of ClC-3 in the thyroid of ClC-3 trans-gene group was significantly increased(P<0.05).The thyroid gland showed obvious hyperplasia and the folliculi glandu-lae thyreoideae was significantly bigger in ClC-3 transgene mice(P<0.05).The weight loss was increased in ClC-3 trans-gene mice(P<0.05).The expression of TT3 and TT4 were significantly higher than that of WT group(P<0.05),but the change of TSH was not obvious.CONCLUSION:ClC-3 over-expression results in thyroid hyperplasia and thyroid hor-mone secretion.This study suggests that ClC-3 is likely to be involved in the synthesis of thyroid hormones.
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Aim To study the effects of L-borneol on the chloride channel and cell volume of human umbili-cal vein endothelial cells (HUVECs). Methods Whole-cell patch-clamp technique was used to record chloride currents. The expression of ClC-3 protein was down-regulated by siRNA interference technique. The cell volume was measured by dynamic image analysis. Results 20 nmol·L-1L-borneol significantly activa-ted chloride current in HUVEC (79.59 ± 4.90) pA/pF, which could be inhibited by chloride channel blockers,NPPB and DIDS. The outward current inhib-itory rate of NPPB was (95.57 ± 2.57)%, while that of DIDS was (97.28 ± 6.36)%. The chloride current activated by L-borneol significantly decreased after the silence of ClC-3 (27.03 ± 3.89) pA/pF. Cell volume was markedly reduced by L-borneol (14.38 ± 1.58)%,which was inhibited after NPPB appliance. Conclusion L-borneol can activate ClC-3 chloride channel in HUVECs, which induces Cl- outflow then cell volume decrease.
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Objective · To explore the perceptions and current practice barriers of Chinese physicians who engage in cancer diagnosis and treatment from third-grade Class A hospitals regarding cancer patients' perceptions of fertility preservation (FP).Methods · A study was conducted in physicians from 4 third-grade Class A hospitals with different clinical specialties assisting cancer patients through a structured self-report questionnaire between January 2017 and December 2017.A total of 179 medical oncologists,77 radiation oncologists and 79 surgeons were included.Their information on gender,age,title,education background and perceptions of FP was obtained.Logistic regression analysis was used to examine the correlation between the recommendation of FP and risk factors.Results· There were 335 physicians,including 88 male physicians and 247 female physicians,with an average age of (35.94±6.27) years (range from 23-59 years) in the current study.Although 96.4% of the physicians knew that chemotherapy and radiation had a profound effect on impairment of fertility and 85.1% of them thought it was necessary to recommend FP,only 28.1% of them gave FP-related recommendations to the cancer patients.The oncologists and surgeons,female physicians,and those with higher professional titles and education background were more likely to make the FP recommendation.Among 63.3% of the physicians knowing male FP,only 37.9% and 21.2% of them noted the exact methods and place for FP,respectively.Similarly,for the 65.1% of the physicians knowing female FP,the percentage was 49.9% and 24.5%,respectively.When it came to the barriers of FP decision-making,32.8% of the oncologists reported their concerns on whether cancer patients were suitable to reproduce.Secondly,the physicians honestly admitted that they lacked expertise in FP and worried about that FP would delay cancer treatment.Conclusion· Physicians who engage in cancer diagnosis and treatment lack the awareness and knowledge background of FP recommendation for cancer patients.It is important to improve the perceptions of cancer patients' FP through standardize training.
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OBJECTIVE@#The aim of this study was to investigate the effect of saliva of patients with chronic periodontitis (CPD) on the differentiation, activation, and secretion of osteoclast-maturing mediators of macrophages.@*METHODS@#A total of 40 saliva samples were collected from healthy donors (n=20) and severe periodontitis patients (n=20). Peripheral blood mononuclear cells (PBMCs) and THP-1 monocyte line cells were challenged with 15% saliva for 5 days. The phenotype, surface marker, and phagocytosis of macrophages were analyzed by flow cytometry and microscopy. Osteoclast-maturing mediators were assayed by using enzyme-linked immunosorbent assay (ELISA) kits.@*RESULTS@#When PBMCs were treated with CPD saliva for 5 days, 61.25%±11.33% of cells were transformed into large granular cells; 86.78%±13.69% of large granular cells were identified as CD14⁺⁺CD16⁺ macrophages. When THP-1 cells were treated with CPD saliva, most cells attached to the bottom of cell culture plates, thereby exhibiting macrophage morphology and releasing additional osteoclast-maturing mediators. Furthermore, the phagocytosis of THP-1 cells considerably increased in the presence of CPD saliva (66.35%±9.67%) compared with medium control (33.33%±7.52%), or healthy saliva (40.71%±3.52%).@*CONCLUSIONS@#Saliva from patients with CPD can induce macrophage differentiation, activate phagocytose microorganisms, and secrete osteoclast-maturing mediators.
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Humanos , Diferenciação Celular , Leucócitos Mononucleares , Macrófagos , Monócitos , Periodontite , Alergia e Imunologia , SalivaRESUMO
Objective To explore the application of de-correlation algorithm to laser speckle blood flow imaging technique and study the blood flow velocity.Methods The principle and algorithm were analyzed for de-correlation laser speckle blood flow imaging.A laser speckle imaging platform was established,and de-correlation laser speckle blood flow imaging algorithm was used to execute microfluidic target experiment and animal experiment.De-correlation algorithm was applied to obtaining blood flow image and velocity curve of microfluidic target.Cross-correlation curve on the original speckle images were got with cross-correlation algorithm,and the original images corresponding to the peak points were selected to undergo computation with de-correlation algorithm,so that the minute information could be augmented on the blood vessel.Results The de-correlation laser speckle blood flow imaging algorithm could be used to obtain the blood flow information and velocity information during microfluidic target experiment and the animal experiment.Conclusion The de-correlation laser speckle blood flow imaging algorithm is feasible in laser speckle imaging,and has good application prospects.
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Objective To estimate the health risk due to the consumption of aquatic products contaminated by Vibrio parahaemolyticus in Shanghai , and provide the basis for control of foodborne diseases associated with this pathogen . Methods According to the guidelines provided by Codex Alimentarius Commission ( CAC) , we performed a quantitative microbial risk assessment model with four steps :hazard identification , hazard characterization , exposure assessment and risk characterization .The surveillance data of Vibrio parahaemolyticus concentration in aquatic products from Shanghai during 2011 and 2013 and Shanghai residents ’ aquatic products consumption data were added in the model .And the parameters were set in this model based on the FAO/WHO scientific literature .A Monte Carlo simulation method was employed to analyze the increase of Vibrio parahaemolyticus concentration in aquatic products from market to table, and quantify the exposure and health risk of Vibrio parahaemolyticus by consuming aquatic products in Shanghai . Results The mean value of probability of infectious illness caused by aquatic products contaminated by Vibrio parahaemolyticus in Shanghai was 1.2 ×10 -6 .That indicated the number of infectious illnesses associated with Vibrio parahaemolyticus in Shanghai might reach 10 746 cases every year based on the population data from Shanghai Statistical Yearbook in 2014 . Conclusion There is the certain health risk of suffering from the disease due to the consumption of aquatic products contaminated by Vibrio parahaemolyticus in Shanghai .Decreasing the occurrence of eating raw aquatic products and controlling the temperature and time of aquatic products processing and storage were determined as the critical factors for suppressing foodborne diseases caused by Vibrio parahaemolyticus.
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The aim of this study was to investigate the relationship between the acetylcholine concentration in the blood and gelsenicine-induced death in mice. Kunming mice were given intraperitoneal injections of normal saline, gelsenicine or different doses of acetylcholine chloride. Atropine was given to the mice which received gelsenicine or medium dose acetylcholine chloride injection. The blood was sampled immediately when the mice died or survived for 20 min after injection. The acetylcholine concentration and acetylcholinesterase activity in the blood were measured by the testing kits, and the mortality was calculated and analyzed. The results showed that half lethal dose of gelsenicine (0.15 mg/kg) reduced the acetylcholinesterase activity and increased the blood acetylcholine concentration. The blood acetylcholine concentration of the dead mice in the gelsenicine group was increased to 43.0 μg/mL (from 31.1 μg/mL in the control), which was lower than that (53.9 μg/mL) of the dead mice in the medium dose acetylcholine chloride group, but almost equal to that (42.7 μg/mL) of the survival mice in the medium dose acetylcholine chloride group. Atropine could successfully rescue the mice from acetylcholine poisoning, but its efficiency of rescuing the mice from gelsenicine intoxication was weak. These results suggest that gelsenicine can inhibit acetylcholinesterase activity and increase blood acetylcholine concentration, but the accumulation of acetylcholine may not be the only or main cause of the death induced by gelsenicine in mice.
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Animais , Camundongos , Acetilcolina , Morte , Alcaloides IndólicosRESUMO
BACKGROUND: Colorectal cancer (CRC) is a major health problem in China and around the world. It is one of the leading causes of cancer-related deaths. Research groups are thus searching for novel and more efficient anti-CRC agents. RESULTS: Here we demonstrated that ABC294640, a novel SphK2 inhibitor, induced growth inhibition and apoptosis in transformed and primary CRC cells. The SphK activity was remarkably inhibited by ABC294640, accompanied by sphingosine-1-phosphate (S1P) depletion and ceramide incensement in CRC cells. Exogenously-added S1P inhibited ABC294640-induced HT-29 cell lethality. While C6 ceramide and SphK1 inhibitor SKI-II facilitated ABC294640-induced cytotoxicity against HT-29 cells. ABC294640 inhibited AKT-S6K1, but activated JNK signaling in transformed and primary CRC cells. JNK inhibitors (SP600125 and JNKi-II) alleviated ABC294640-induced CRC cell apoptosis. Moreover, a low concentration of ABC294640 sensitized the activity of 5-FU and cisplatin in vitro. In vivo, ABC294640 oral administration dramatically inhibited HT-29 xenografts growth in nude mice. CONCLUSIONS: Targeting of SphK2 by ABC294640 potently inhibits CRC cell growth both in vitro and in vivo, ABC294640 could be developed as a novel therapeutic for the treatment of CRC.
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Adamantano/análogos & derivados , Antineoplásicos/farmacologia , Neoplasias Colorretais/enzimologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Piridinas/farmacologia , Adamantano/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/farmacologia , Células HCT116 , Células HT29 , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether the extracellular signal PI3K/AKT pathway was involved in the Pue-induced PASMC apoptosis. With the serum starvation group (SD group) as the control group, the MTT colorimetry method, Annexin V-FITC apoptosis detection kit and Western blot were used to detect Pue's effect on apoptosis of rat PASMCs. The protein immunoblot assay was used to detect whether PI3K/AKT pathway was involved in the inhibition of hypoxia-induced PASMC apoptosis process. The results show that under normoxic conditions, Pue had no effect on PASMC apoptosis; Under hypoxia conditions, Pue can inhibit PASMC apoptosis; Under normoxic and hypoxic conditions, Pue had no effect on TNF-α expression. Pue can reverse hypoxia-induced Bcl-2 (P <0.01), up-regulate it and down-regulated Bax (P <0.01). Under normoxic conditions, Pue had no effect on P-AKT expression. Both LY294002 and Pue can inhibit hypoxia-induced Bcl-2, up-regulation of P-AKT expression and down-regulation of Bax expression. Compared with the hypoxia + Pue group or the hypoxia + LY294002 group, the hypoxia + Pue + LY294002 group showed more significantly changes in Bcl-2, Bax, P-AKT expressions. The results show that, Pue can inhibit the hypoxic-induced PASMC apoptosis, which may be regulated through PI3K/AKT pathway.
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Animais , Ratos , Apoptose , Células Cultivadas , Cromonas , Farmacologia , Isoflavonas , Farmacologia , Morfolinas , Farmacologia , Miócitos de Músculo Liso , Fosfatidilinositol 3-Quinases , Fisiologia , Proteínas Proto-Oncogênicas c-akt , Fisiologia , Artéria Pulmonar , Biologia Celular , Ratos Wistar , Transdução de SinaisRESUMO
To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether its mechanism is achieved by regulating reactive oxygen. PASMCs of primarily cultured rats (2-5 generations) were selected in the experiment. MTT, Western blot, FCM and DCFH-DA were used to observe Pue's effect the proliferation of PASMCs. The Western blot was adopted to detect whether ROS participated in Pue's effect in inhibiting PASMC proliferation. The PASMCs were divided into five groups: the normoxia group, the hypoxia group, the hypoxia + Pue group, the hypoxia + Pue + Rotenone group and the hypoxia + Rotenone group, with Rotenone as the ROS blocker. According to the results, under the conditions of normoxia, Pue had no effect on the PASMC proliferation; But, under the conditions of hypoxia, it could inhibit the PASMC proliferation; Under the conditions of normoxia and hypoxia, Pue had no effect on the expression of the tumor necrosis factor-α (TNF-α) among PASMCs, could down-regulate the expression of hypoxia-induced cell cycle protein Cyclin A and proliferative nuclear antigen (PCNA). DCFH-DA proved Pue could reverse ROS rise caused by hypoxia. Both Rotenone and Pue could inhibit the up-regulated expressions of HIF-1α, Cyclin A, PCNA caused by anoxia, with a synergistic effect. The results suggested that Pue could inhibit the hypoxia-induced PASMC proliferation. Its mechanism may be achieved by regulating ROS.
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Animais , Masculino , Ratos , Ciclo Celular , Proliferação de Células , Células Cultivadas , Hipóxia , Patologia , Isoflavonas , Farmacologia , Miócitos de Músculo Liso , Fisiologia , Antígeno Nuclear de Célula em Proliferação , Artéria Pulmonar , Biologia Celular , Ratos Wistar , Espécies Reativas de Oxigênio , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of cutaneous regressing/regressed melanoma.</p><p><b>METHODS</b>Histopathologic evaluation and immunohistochemical study by EnVision method were performed in 8 cases of cutaneous regressing/regressed melanoma. The clinical presentation, treatment and follow-up data were analyzed.</p><p><b>RESULTS</b>The age of the patients ranged from 40 to 69 years (mean 58 years). The male-to-female ratio was 3: 1. Tumors were located on the back (4 cases), sole of the foot (2 cases), ventral aspect of the toes (1 case), and the forearm (1 case). Clinically, 6 patients presented with progressive black mole of the skin, followed by subsequent focal hypopigmentation, even scarring. Two patients presented with multiple foci of dark-brown pigmentation. Microscopically, 3 cases were completely regressed malignant melanoma. Tumoral melanosis was found in 1 of 3 cases. The other 5 cases were melanoma with severe regression. The extent of regression ranged from 75% to 90%. The Breslow depth of the tumors ranged from 0.5 to 1.0 mm. Immunohistochemically, both metastatic and primary tumor cells were diffusely positive for S-100, HMB45 and Melan A, while melanophages were positive for CD68. Follow-up data were available in 8 patients, ranging from 8 to 27 months. Five patients were alive with no evidence of disease, 1 patient was alive with stable disease and 2 patients died of metastatic melanoma.</p><p><b>CONCLUSIONS</b>Correlation between clinical presentation and pathologic features is important for diagnosis of cutaneous regressing/regressed melanoma. Thin melanoma with extensive regression ( ≥ 75%) should not been regarded as low metastatic risk and wide excision combined with sentinel lymph node biopsy is recommended.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos CD , Metabolismo , Antígenos de Diferenciação Mielomonocítica , Metabolismo , Dorso , Patologia , Seguimentos , Pé , Patologia , Metástase Linfática , Antígeno MART-1 , Metabolismo , Melanoma , Metabolismo , Patologia , Cirurgia Geral , Antígenos Específicos de Melanoma , Metabolismo , Melanose , Patologia , Proteínas S100 , Metabolismo , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas , Metabolismo , Patologia , Cirurgia Geral , Dedos do Pé , Patologia , Resultado do TratamentoRESUMO
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Capecitabina , China , Cisplatino , Desoxicitidina , Neoplasias Esofágicas , Tratamento Farmacológico , Patologia , Junção Esofagogástrica , Fluoruracila , Seguimentos , Náusea , Estadiamento de Neoplasias , Neutropenia , Receptor ErbB-2 , Metabolismo , Indução de Remissão , Estudos Retrospectivos , Neoplasias Gástricas , Tratamento Farmacológico , Patologia , Taxa de Sobrevida , Trastuzumab , VômitoRESUMO
<p><b>BACKGROUND</b>Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.</p><p><b>METHODS</b>In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.</p><p><b>RESULTS</b>Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.</p><p><b>CONCLUSIONS</b>We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais Humanizados , Usos Terapêuticos , Antineoplásicos , Usos Terapêuticos , Bevacizumab , Neoplasias da Mama , Tratamento Farmacológico , Genética , Metabolismo , Hidrocarbonetos Aromáticos com Pontes , Usos Terapêuticos , Receptor ErbB-2 , Genética , Metabolismo , Taxoides , Usos TerapêuticosRESUMO
ENHANCIN is an enhancing protein chiefly found in insect baculoviruses. One ENHANCIN homologue was identified, by blast method, in Agrotis Segetum granulovirus (AgseGV) genome, named enhancin-like. Sequence analysis indicated that this gene includes the conserved domains, conserved in other ENHANCIN, and it has no signal peptide or a-transmembrane helix. A proline-rich domain, which is similar to those of mammals, is present at its C-terminal. To analyze the synergistic function of AgseGV enhancin-like gene, prokaryotic expression vectors of its whole gene and the 5'-truncated fragment (1, 017bp) were constructed. Expression product of truncated fragment was purified by chromatography, and then it was used to prepare antibody. The expression product of whole gene was identified by Western blot with specific antibody and anti-His-Tag antibody. Bioassay proved that the expression product of whole gene can increase the mortality with 16.25% to 3th instar larvae of Helicoverpa armigera (HaNPV: 1.17 x 10(2) PIBS/mL), while the truncated fragment has no obvious synergistic function.
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Animais , Sequência de Aminoácidos , Baculoviridae , Genética , Metabolismo , Expressão Gênica , Controle de Insetos , Larva , Dados de Sequência Molecular , Mariposas , Controle Biológico de Vetores , Proteínas Virais , Genética , Metabolismo , ToxicidadeRESUMO
<p><b>OBJECTIVE</b>To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.</p><p><b>METHODS</b>Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.</p><p><b>RESULTS</b>The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02).</p><p><b>CONCLUSIONS</b>The patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.</p>
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma , Sangue , Tratamento Farmacológico , Patologia , Adenocarcinoma Mucinoso , Sangue , Tratamento Farmacológico , Patologia , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Doenças da Medula Óssea , Neoplasias do Colo , Sangue , Tratamento Farmacológico , Patologia , Diarreia , Intervalo Livre de Doença , Fluoruracila , Sangue , Farmacocinética , Usos Terapêuticos , Leucovorina , Usos Terapêuticos , Mucosite , Estadiamento de Neoplasias , Compostos Organoplatínicos , Usos Terapêuticos , Distribuição Aleatória , Neoplasias Retais , Sangue , Tratamento Farmacológico , Patologia , Indução de Remissão , Taxa de SobrevidaRESUMO
The present study aimed to investigate the effects of ursolic acid on the chloride channels and cell volume in nasopharyngeal carcinoma cells (CNE-2Z). The whole-cell patch clamp technique was used to detect the current, and cell imaging technique was applied to measure cell volume. The properties of the currents induced by ursolic acid were investigated by changing the extracellular osmotic pressure, replacing the extracellular anions and applying chloride channel blockers. The results showed that, under isotonic conditions, the background current was weak and stable. When perfusing the cells with ursolic acid (100 nmol/L), a large current (-59.86 pA/pF ± 4.86 pA/pF at -80 mV, 78.92 pA/pF ± 6.39 pA/pF at +80 mV) was induced. The chloride current showed outward rectification and negligible time- and voltage-dependent inactivation. The reversal potential (-4.83 mV ± 0.30 mV) of the current was close to the calculated equilibrium potential for Cl⁻ (-0.9 mV). The permeabilities of the channel to different anions were ranked in order as follows: Cl⁻ = I⁻ > Br⁻ > gluconate. Hypertonic solutions inhibited the current induced by ursolic acid. The chloride channel blockers, tamoxifen (20 μmol/L) and 5-nitro-2-(3-phenylpro-pylamino) benzoic acid (NPPB, 100 μmol/L), suppressed the current. Furthermore, ursolic acid decreased the cell volume by (11.78 ± 1.20)% in 1 h, and the effect was inhibited by NPPB. These results suggest that ursolic acid can activate chloride channels, resulting in outflow of Cl⁻ and decrease of cell volume in nasopharyngeal carcinoma cells.