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OBJECTIVE: To investigate the clinical efficacy of ibrutinib combined with venetoclax in the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), and to analyze the factors affecting efficacy and prognosis. METHODS: Clinical data of 62 R/R DLBCL patients admitted to our hospital from August 2017 to July 2022 were retrospectively analyzed. All patients were treated with ibrutinib combined with venetoclax. The clinical efficacy and drug safety were evaluated. The effects of clinical features on short-term efficacy and overall survival (OS) were analyzed. RESULTS: The objective response rate (ORR) of 62 patients was 48.39%. The extranodal lesions, intermediate-high/high risk of NCCN-IPI, intermediate-high/high risk of IPI, progression or recurrence time <12 months were the risk factors affecting the short-term efficacy of chemotherapy in R/R DLBCL patients (all P < 0.05). The most common adverse effect was neutropenia (75.19%), and the incidence of grade â ¢-â £ neutropenia was 52.71%. The 1-year and 2-year OS rates of 62 patients were 48.51% and 31.56%, respectively, and the median OS time was 12 months. Multivariate analysis showed that objective remission after chemotherapy [HR =0.080 (95%CI: 0.028-0.235)] was a protective factor for OS in R/R DLBCL patients, and intermediate-high/high risk of NCCN-IPI [HR =4.828 (95%CI : 1.546-15.080)] was an independent risk factor affecting the prognosis of R/R DLBCL patients. CONCLUSION: Ibrutinib combined with venetoclax can be used as an effective treatment regimen for R/R DLBCL, and NCCN-IPI can be used as a prognostic indicator. Objective remission after chemotherapy is beneficial for R/R DLBCL patients to achieve better OS.
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Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes , Linfoma Difuso de Grandes Células B , Piperidinas , Sulfonamidas , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Sulfonamidas/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Piperidinas/administração & dosagem , Adenina/análogos & derivados , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Feminino , Masculino , Pirimidinas , Taxa de Sobrevida , Resultado do Tratamento , Pessoa de Meia-Idade , Pirazóis , Recidiva Local de Neoplasia , AdultoRESUMO
BACKGROUND: Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages. CASE SUMMARY: We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura, which was not taken seriously enough. As the disease progressed, pleural effusion gradually appeared, and after systematic diagnosis and treatment, she was diagnosed with "primary light chain amyloidosis". She achieved rapid hematological remission after treatment with a daratumumab + bortezomib + cyclophosphamide + dexamethasone regimen. CONCLUSION: Periorbital purpura can be the only initial symptom of primary light chain amyloidosis; we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.
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To investigate the effects of purified humic acid (PHA) on the growth and nitrogen metabolism of cucumber under different levels of nitrogen stress and to explore the mechanism of PHA's alleviation on abiotic stress, we examined the effects of PHA on 'Xintaimici' cucumber growth and nitrogen metabolism under low nitrogen (1.0 mmol·L-1 NO3-) stress and high nitrogen (101 mmol·L-1 NO3-) stress in hydroponics compared with normal level (11 mmol·L-1 NO3-). The results showed that the growth of cucumber seedlings was inhibited under nitrogen stress treatments. Plant height, stem diameter, leaf area and dry matter accumulation under nitrogen stress were lower than that at normal nitrogen level. Dry matter accumulation under the normal nitrogen level and low nitrogen stress were significantly increased by PHA, but there was no significant difference under high nitrogen stress. The absorption of NO3- in cucumber seedlings was affected by PHA, showing increased nitrate content in cucumber seedlings under low nitrogen stress and decreased under high nitrogen stress. PHA significantly decreased ammonium content in roots and leaves under low and high nitrogen stress. Compared with normal level of nitrogen (CK), NR, GS, GOGAT, GDH activity in roots and leaves and NiR activity in roots significantly decreased under low and high nitrogen stress. PHA increased the activities of NR, NiR, GS, GOGAT, and GDH to different extents. PHA increased amino acid and soluble protein content in cucumber seedling roots and leaves. In summary, PHA addition alleviated the inhibitory effect of nitrogen stress on the growth of cucumber seedlings.
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Cucumis sativus , Substâncias Húmicas , Nitrogênio/metabolismo , Aminoácidos , Nitratos , Folhas de Planta , Raízes de Plantas , PlântulaRESUMO
The effects of iron deficiency and NO3- stress on the growth and the iron absorption cha-racteristic of tomato seedlings were investigated under suboptimal temperature (18 â/12 â (day/night)). The results indicated that the growth was significantly inhibited under suboptimal temperature compared with appropriate temperature treatment; the plant heights, leaf areas and dry matter accumulations were markedly decreased. The effects of iron deficiency under suboptimal temperature on the growth of tomato seedlings were larger than that of under appropriate temperature treatments. Under suboptimal temperature, the plant heights of tomato seedlings in iron deficiency and/or NO3- stress treatments were not significantly different from no stress treatment, but leaf areas and leaf chlorophyll content of tomato seedlings were decreased obviously. The leaf electrolytic leakage, root activity and Fe3+ reductase activity of tomato seedlings were markedly increased under suboptimal temperature, but chlorophyll content, total root length, root surface area, root tip number and root volume were obviously reduced. The iron contents in roots, stems and leaves of tomato seedlings were also remarkably decreased. The NO3- stress and the combined stress of iron deficiency and NO3- stress under suboptimal temperature aggravated the reduction of dry matter, leaf electrolytic leakage and the inhibition of iron ion absorption in tomato seedlings. The iron ion absorption showed the antagonistic impact on the absorption of potassium and calcium ion, but showed different effects among different organs. The iron deficiency symptom of tomato seedlings was aggravated by reducing the concentration of iron ion in the nutrient solution.
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Deficiências de Ferro , Plântula , Solanum lycopersicum , Folhas de Planta , Raízes de Plantas , TemperaturaRESUMO
The solution culture method was used to study the effects of sodium nitroprusside (SNP) on plant growth, nutrient uptake and antioxidant enzyme activities of tomato seedlings under iron deficiency and NO3- stress. The results indicated that after 7 d of treatment, iron deficiency inhibited the tomato seedling growth, decreased chlorophyll (a and b) and carotenoid contents, and led to obvious chlorosis; iron deficiency also reduced the activity of SOD, POD and CAT, resulting in significant accumulation of MDA contents and higher electrolytic leakage; proline and soluble sugar contents were not significantly changed; contents of N, P, K, Ca, Mg and Fe in both leaves and roots of tomato seedlings were decreased under iron deficiency in varying degrees. The combined stress of NO3- stress and iron deficiency promoted the inhibition of plant growth, decreased chlorophyll (a and b), carotenoid contents and the activities of SOD, POD and CAT; electrolytic leakage MDA, proline and soluble sugar contents of N, P, Mg, Fe in both leaves and roots of tomato seedlings were much lower, but the contents of K and Ca were significantly increased. Compared to the treatment without SNP, adding 0.1 mmol·L-1 SNP could alleviate the growth inhibition of stressed tomato seedlings. Adding 0.1 mmol·L-1 SF (sodium ferrocyanide) also showed alleviating or promoting effect on some above indexes including the activity of SOD, POD and CAT to some degree, but the other physiological indexes were not significantly changed because iron was contained in SF.
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Nitroprussiato , Solanum lycopersicum , Clorofila , Ferro , Folhas de Planta , Plântula , Estresse Fisiológico , Superóxido DismutaseRESUMO
Enteropathy-associated T-cell lymphoma (EATL) is a rare gastrointestinal non-Hodgkin's lymphoma, originating from intraepithelial T-lymphocyte, which is specifically associated with celiac disease. EATL most commonly presents in the sixth and seventh decades of life. We report a unique case of type I EATL in the colon with liver metastasis, which was presented with nonspecific radiological findings and at a very young age (29 years old) compared with previously published data. We suggest that EATL should be regarded as part of differential diagnosis in any patient presenting with abdominal pain, diarrhea, weight loss, and malabsorption because delay in treatment can result in an irreversible clinical outcome.
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'Jinyan No. 4'cucumber was used as experimental material. The growth of cucumber radicles treated with different concentrations of p-hydroxybenzoic acid (0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5 and 20 mmol·L-1) was investigated firstly, and 10 mmol·L-1 p-hydroxybenzoic acid was chosen for the further experiment. To investigate if melatonin alleviate p-hydroxybenzoic acid stress on cucumber radical elongation, 0, 1, 10, 25, 50, 75 and 100 µmol·L-1 melatonin were used to pretreat cucumber seeds for 24 h before 10 mmol·L-1 p-hydroxybenzoic acid treatment. The results suggested that exogenous melatonin could alleviate the radicle growth inhibition induced by p-hydroxybenzoic acid, and 75 µmol·L-1 melatonin showed the best effect. The growth of cucumber radical was significantly inhibited with an increase in p-hydroxybenzoic acid concentration, which was accompanied with lower activity of amylase. The melatonin pretreatment could significantly increase the activities of amylase and antioxidant enzymes in cucumber seeds resulting in lower accumulation of O2-·, H2O2 and MDA. Exogenous melatonin effectively reduced the PHBA stress on cucumber germination, which might be due to its function in decreasing oxidative stress and promoting starch catabolism.
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Cucumis sativus/efeitos dos fármacos , Melatonina/farmacologia , Parabenos/farmacologia , Antioxidantes , Cucumis sativus/crescimento & desenvolvimento , Germinação , Peróxido de Hidrogênio , Hidroxibenzoatos , Estresse OxidativoRESUMO
Taking 'Xintaimici' and 'Jinyou 1' as experimental cucumber cultivars, this paper studied the effects of watering purified humic acid (PHA) at different levels (0, 50, 100, 150, 200 mg·L-1) on growth and nutrient absorption of cucumber seedlings under low nitrogen stress (1 mmol·L-1 NO3-) in sand culture pots. The results showed that, under low N condition, PHA could significantly increase the total root length, root surface area, root tip number and root volume of cucumber seedlings, and promote plant height, stem diameter and leaf area. Proline and soluble sugar contents in cucumber leaves were significantly increased by PHA. The absorption of N, P, K, Ca, Mg, Fe in cucumber seedlings was promoted. According to the response of the two cucumber cultivars to PHA under low N stress, some traits of two cultivars showed different sensitivity to PHA level. The comprehensive analysis of the above results inferred that the PHA level from 100 mg·L-1 to 150 mg·L-1 could significantly enhance the growth and nutrient absorption of cucumber seedlings.
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Cucumis sativus/crescimento & desenvolvimento , Substâncias Húmicas , Nitrogênio/fisiologia , Plântula/crescimento & desenvolvimento , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Estresse Fisiológico , ÁguaRESUMO
To investigate the effect of calcium and ABA on photosynthesis and the activities of antioxidant enzymes in cucumber seedlings under drought stress, the cucumber was used as the expe-riment materials, normal nutrient solution culture was considered as the control, and PEG-6000 application in the nutrient solution simulated the drought stress. There were five different treatments which were spraying water, ABA, CaCl2+ABA, LaCl3(calcium channel inhibitor)+ABA and EGTA (calcium ion chelating agent)+ABA under drought stress. The results showed that drought stress inhibited the growth of cucumber seedlings, and reduced the activities of antioxidant enzymes, nitrate reductase, net photosynthetic rate and fluorescence parameters of the cucumber seedlings leaves. The application of ABA reduced the inhibition of activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX), photosynthesis (Pn, gs) and the fluorescence parameters (Fv'/Fm', qP and ETR), and decreased the damage of drought stress on plant. Spraying CaCl2+ABAsignificantly promoted the positive effect of ABA, while EGTA+ABA and LaCl3 +ABA didn't show the promoting effect.
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Cálcio/química , Cucumis sativus/fisiologia , Secas , Fotossíntese , Antioxidantes , Ascorbato Peroxidases , Catalase , Cucumis sativus/enzimologia , Peroxidases , Folhas de Planta , Plântula , Superóxido DismutaseRESUMO
The control effects of Eupolyphaga (Eupolyphaga sinensis Walker) frass and its extracts on Meloidogyne incognita were studied through laboratory assays and pot experiments, and the organic volatile compounds and oligochitosan contents in the frass were analyzed. The results indicated that the nematode immobility and mortality was significantly increased with increasing the extract concentration and treatment time. Compared with the control, egg hatching was significantly inhibited when the extract concentration was beyond 20%. Pot experiment indicated that root galling of tomato seedlings was reduced and the relative control effect was significantly improved with the increasing frass application. Meanwhile, plant height, stem diameter and leaf number of tomato increased with the increasing dosage of eupolyphaga frass. The ingredients analysis showed that the content of oligochitosan was about 4.35% and there were 9 categories and 110 kinds of volatile compounds in the frass.
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Baratas , Controle Biológico de Vetores , Doenças das Plantas/prevenção & controle , Infecções por Secernentea/prevenção & controle , Solanum lycopersicum/parasitologia , Tylenchoidea , Animais , Doenças das Plantas/parasitologia , Raízes de Plantas/parasitologiaRESUMO
INTRODUCTION: Radix Glycyrrhiza has been used in China for thousand years to treat cancer. However, focus on its tumor-suppressing mechanism has been concentrated on its effect on tumor cell growth and apoptosis. OBJECTIVES: With the aid of a panel of human breast cancer cell lines, we reveal that glycyrrhetinic acid (GA), a major component of Radix Glycyrrhiza, is actually a significantly more potent agent to suppress invasion than cell survival. RESULTS: GA effectively inhibits breast cancer cell MMP-2/MMP-9 expression; GA-induced reduction in the MMP-2/9 expression is apparently mediated by GA's ability to specifically inhibit the p38 MAPK activity and its downstream AP1 activation. Moreover, we show that GA down regulates the levels of Fra-1 and c-Jun, two main components of AP1 transcription complex in invasive breast cancer cells and that AP1-specific inhibitor abrogates breast cancer cell invasion. These results suggest that GA impairs the p38 MAPK-AP1 signaling axis, leading to the repression of breast cancer cell invasion. Finally, we demonstrate that GA effectively suppresses breast tumor outgrowth and pulmonary metastasis without causing animal weight loss or eliciting liver/kidney toxicity to the recipient animals. CONCLUSION: This study indicates that GA represents a good candidate compound for the potential development of therapeutic drug.
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Neoplasias da Mama/tratamento farmacológico , Ácido Glicirretínico/farmacologia , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Glycyrrhiza/química , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal-Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p<0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p<0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p<0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway.
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Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Mitomicina/farmacologia , Animais , Antineoplásicos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Flavonoides/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/efeitos dos fármacos , Transplante HeterólogoRESUMO
Cucumber cultivar 'Jinyan 4' was subjected to suboptimal temperature treatment of 18/12 degrees C (day/night) in the growth chambers. A solution culture experiment was conducted to study the effect of exogenously spraying 5 mg x L(-1) chlorophyllin-iron solution on plant growth, the content of proline, soluble sugar, MDA and activity of peroxidase in the leaves of cucumber seedling under suboptimal temperature. Application of chlorophyllin-iron showed prominent effects on mitigating the stress of suboptimal temperature on growth of the cucumber seedlings, significantly increasing the plant height, leaf area, shoot dry mass, the contents of soluble sugar and proline and the activities of SOD, POD, CAT and APX. Exogenously spraying chlorophyllin-iron could promote the accumulation of proline and soluble sugar, raise the activities of antioxidant enzymes, decrease the membrane lipid peroxidation and improve the adaptability of cucumber seedlings under suboptimal temperature.
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Clorofilídeos/química , Cucumis sativus/enzimologia , Ferro/química , Temperatura , Antioxidantes/metabolismo , Catalase/metabolismo , Peroxidação de Lipídeos , Peroxidase/metabolismo , Folhas de Planta/enzimologia , Plântula/enzimologia , Superóxido Dismutase/metabolismoRESUMO
Herbal formulas based on the traditional Chinese medicine (TCM) syndrome (ZHENG) have been used as alternative treatments for breast cancer. However, there is a lack of the experimental animal ZHENG model for the evaluation of the herbal formulas. In this study, we have established 4T1 mouse breast cancer with Liver Fire Invading Stomach Syndrome model (4T1 LFISS mice) and investigated the effects of the herbal formula, Zuo-Jin Wan (ZJW). Our results showed that 4T1 LFISS mice have the features of LFISS including irritability, loss of appetite, yellow urine, chow, and a tail hot. Compared to untreated 4T1 LFISS mice, ZJW significantly reduced tumor weight and volume (P < 0.05), although it was weaker than Cisplatin. However, ZJW significantly increased the body weight and food intake of 4T1 LFISS mice and decreased serum ALT, AST, Cr, and BUN levels and ZHENG score (P < 0.05), while Cisplatin reduced the food intake, and body weight and increased serum ALT, AST, Cr, and BUN levels in 4T1 LFISS mice. Our study has provided a mouse breast cancer ZHENG model and showed that ZJW suppresses tumor growth and improves LFISS and kidney and liver functions in the 4T1 LFISS mice.
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By using solution culture method, this paper studied the effects of exogenous nitric oxide (NO) on the antioxidants and antioxidases in the ascorbate-glutathione (AsA-GSH) cycle in tomato (Lycopersicon esculentum Mill. ) seedling roots under copper stress.Exogenous NO could affect the metabolic cycle of AsA-GSH in tomato roots under copper stress. Applying appropriate amount of exogenous NO increased the AsA and GSH contents, AsA/DHA and GSH/GSSG ratios, and decreased the DHA and GSSG contents in tomato roots under copper stress. With the addition of 100 micro mol L-1 of BSO, exogenous NO increased the AsA content, AsA/DHA ratio, and the AAO, MDHAR, and DHAR activities, and decreased the DHA, GSH, and GSSG contents and the APX and GR activities. When 250 micro mol L-1 of BSO was added, exogenous NO increased the contents of AsA, GSH, and GSSG, AsA/DHA ratio, and the activities of APX and GR, and decreased the DHA content and the AAO, DHAR and MDHAR activities. It was suggested that exogenous NO could affect the metabolic cycle of AsA-GSH in tomato roots under copper stress, and mitigate the damage of copper stress to tomato roots via regulating the AsA/DHA and GSH/GSSG ratios to alleviate oxidative stress.
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Ácido Ascórbico/metabolismo , Cobre/toxicidade , Glutationa/metabolismo , Óxido Nítrico/farmacologia , Solanum lycopersicum/metabolismo , Solanum lycopersicum/fisiologia , Estresse Oxidativo , Raízes de Plantas/metabolismo , Plântula/metabolismo , Plântula/fisiologia , Estresse FisiológicoRESUMO
OBJECTIVE: To evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS). METHODS: The 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS. RESULTS: The key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH. CONCLUSIONS: T, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.
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Modelos Animais de Doenças , Análise Fatorial , Deficiência da Energia Yang/fisiopatologia , Animais , Estradiol/análise , Hormônio Foliculoestimulante/análise , Hidrocortisona/análise , Hormônio Luteinizante/análise , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Testosterona/análise , Tireotropina/análise , Tiroxina/análiseRESUMO
Cancer metastasis is refractory to most forms of chemotherapy. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target metastatic cancer cells. In this study, we investigated the effects of PC-SPESII, an herbal formulation, on the migration, invasion, and metastasis of an experimental human breast cancer cell line in vivo and in vitro. PC-SPESII suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast cancer xenografts without affecting body weight, liver function, and kidney function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasion in vitro in a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and MMP-9, proteins associated with extracellular matrix degradation, was reduced in response to PC-SPESII treatment. Western blot analysis of whole-cell extracts revealed that the levels of proteolytic proteins associated with matrix and base membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC-PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype. Our results indicate that PC-PSESII impairs human breast cancer metastasis by regulating proteolytic enzymes and matrix dynamics through the p38MAPK and SAPK/JNK pathway.
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Breast cancer remains the leading cause of cancer-related deaths among women. Owing to high efficiency and low toxic effects, further exploration of natural compounds from Chinese herbal medicine may be an efficient approach for breast cancer drug discovery. In this study, we investigated the effects of evodiamine on the growth and metastasis of MDA-MB-231 human breast cancer cells in vitro and in vivo. In vitro, evodiamine inhibited cell migration and invasion abilities through downregulation of MMP-9, urokinase-type plasminogen activator (uPA) and uPAR expression. Evodiamine-induced G0/G1 arrest and apoptosis were associated with a decrease in Bcl-2, cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression and an increase in Bax and p27Kip1 expression. Moreover, evodiamine regulated p-ERK and p-p38 MAPK expression. Evodiamine-induced apoptosis was enhanced by its combination with the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580. Evodiamine-inhibited metastasis was partly blocked by combination with PD98059 or SB203580. In vivo, the administration of evodiamine (10 mg/kg) significantly reduced tumor growth and pulmonary metastasis. These results demonstrate that evodiamine possesses antitumor activities via inhibition of cell migration and invasion, arrest of the cell cycle and induction of cell apoptosis in MDA-MB-231 cells.
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Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Quinazolinas/farmacologia , Animais , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fase G1/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Metastasis is the major cause of death in breast cancer patients. In this study, we investigated the effects of baicalin, a natural compound, on cell migration, invasion and metastasis using human breast cancer MDA-MB-231 cell line as model system. Baicalin not only dose-dependently inhibited MDA-MB-231 cells migration and in vitro invasion, but also suppressed the tumor outgrowth and the pulmonary metastasis of MDA-MB-231 cells in xenograft model. Importantly, treatment of baicalin caused little change in body weight, liver and kidney function of recipient animals. Tumorigenesis-inhibitory effect is likely linked to the capability of baicalin to downregulate metalloproteinase (MMP)-2, MMP-9, urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) expression in MDA-MB-231 cells. As baicalin blocked p38 mitogen-activated protein kinase (MAPK) activity and treatment of p38MAPK inhibitor SB203580 led to the reduction of MMP-2, MMP-9, uPA and uPAR expressions, we concluded that baicalin suppresses the tumorigenecity of MDA-MB-231 cells by down-regulating MMP-2, MMP-9, uPA and uPAR expressions through the interruption of p38MAPK signaling pathway.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Flavonoides/uso terapêutico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Mama/efeitos dos fármacos , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inibidores Enzimáticos , Feminino , Flavonoides/química , Flavonoides/farmacologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Nus , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Scutellaria baicalensis/química , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the clinical results of arthroscopic single and double-bundle ACLs reconstructions. METHODS: From January 2009 to May 2010,45 patients with anterior cruciate ligament tear were divided into two groups. In the first group,the anterior cruciate ligament were anatomical reconstructed with double-bundle semitendinous tendon, and in the second group the anterior cruciate ligaments were anatomical reconstrucated with single bundle semitendinous tendon. There were 22 patients (15 males and 7 females) in double-bundle group, with an average age of (27.04 +/- 3.68) years; 18 patients (13 males and 5 females) in single bundle group, with an average age of (28.16 +/- 4.76) years. Therapeutic effects between two groups were compared according to the IKDC, Lysholm scoring standards and Lachman test, knee pivot shift test, KT-1000. RESULTS: Twenty-two patients in double-bundle group and 18 patients in single-bundle group were followed-up, and the mean duration was 12 months. The IKDC score of patients in single-bundle group improved from preoperative 41.40 +/- 6.30 to postoperatively 95.70 +/- 3.10, Lysholm score increased from preoperative 47.20 +/- 6.30 to postoperative 94.20 +/- 2.40. And the IKDC score of patients in double-bundle group improved from preoperative 40.90 +/- 6.10 to postoperative 96.10 +/-3.40, Lysholm score increased from preoperative 48.10 +/- 6.50 to postoperative 95.10 +/- 2.49. There was no statistically significant difference between the two groups. The Lachman test was positive in 2 patients (1 patient in double-bundle group and 1 patient in single-bundle group); and pivot shift test was positive in 2 patients (1 patient in double-bundle group and 1 patient in single-bundle group). KT-1000 of patients in double-bundle group was (1.5 +/- 1.2) mm, and (1.9 +/- 1.5) mm in single-bundle group, there were no statistically significant differences between the two groups. CONCLUSION: Arthroscopic single-bundle reconstruction and double-bundle anterior cruciate ligament reconstruction have no significant differences in clinical effects.