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1.
Ann Hematol ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012517

RESUMO

This study aimed to assess the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) in patients with relapsed multiple myeloma (MM). Fifty-one consecutive patients with relapsed MM were enrolled in this retrospective study. 18F-FDG parameters based on the Italian Myeloma Criteria for PET Use (IMPeTUs) and clinical data were analyzed for overall survival (OS) and progression-free survival (PFS). The Cox proportional risk model was used for univariate and multivariate analysis, and Kaplan-Meier survival curves were used for survival analysis. The median length of follow-up was 20 months (IQR, 5-29 months), the median PFS for the entire cohort was 8 months (IQR, 3-17 months) and the median OS was 21 months (IQR, 8-49 months). Multivariate survival analysis demonstrated that the Deauville score of BM > 3 [HR 2.900, 95% CI (1.011, 8.319), P = 0.048] and the presence of EMD [HR 3.134, 95% CI (1.245, 7.891), P = 0.015] were independent predictors of poor PFS. The presence of EMD [HR 12.777, 95% CI (1.825, 89.461), P = 0.010] and the reduced platelets count [HR 7.948, 95% CI (1.236, 51.099), P = 0.029] were adversely associated with OS. 18F-FDG PET/CT parameters based on IMPeTUs have prognostic significance in patients with relapsed MM.

2.
Acta Pharmacol Sin ; 42(6): 871-884, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34002042

RESUMO

Stroke is a common cause of death and disability. Allisartan isoproxil (ALL) is a new angiotensin II receptor blocker and a new antihypertensive drug discovered and developed in China. In the present study we investigated the therapeutic effects of ALL in stroke-prone renovascular hypertensive rats (RHR-SP) and the underlying mechanisms. The model rats were generated via two-kidney two-clip (2K2C) surgery, which led to 100% of hypertension, 100% of cerebrovascular damage as well as 100% of mortality 1 year after the surgery. Administration of ALL (30 mg · kg-1 · d-1 in diet, for 55 weeks) significantly decreased stroke-related death and prolonged lifespan in RHR-SP, but the survival ALL-treated RHR-SP remained of hypertension and cardiovascular hypertrophy compared with sham-operated normal controls. In addition to cardiac, and aortic protection, ALL treatment for 10 or 12 weeks significantly reduced cerebrovascular damage incidence and scoring, along with a steady reduction of blood pressure (BP) in RHR-SP. Meanwhile, it significantly decreased serum aldosterone and malondialdehyde levels and cerebral NAD(P)H oxidase expressions in RHR-SP. We conducted 24 h continuous BP recording in conscious freely moving RHR-SP, and found that a single intragastric administration of ALL produced a long hypotensive effect lasting for at least 12 h on systolic BP. Taken together, our results in RHR-SP demonstrate that ALL can be used for stroke prevention via BP reduction and organ protection, with the molecular mechanisms related to inhibition of angiotensin-aldosterone system and oxidative stress. This study also provides a valuable scoring for evaluation of cerebrovascular damage and drug efficacy.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doenças da Aorta/prevenção & controle , Compostos de Bifenilo/uso terapêutico , Transtornos Cerebrovasculares/prevenção & controle , Imidazóis/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Aldosterona/metabolismo , Animais , Aorta/efeitos dos fármacos , Doenças da Aorta/complicações , Doenças da Aorta/mortalidade , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/patologia , Coração/efeitos dos fármacos , Hipertensão/complicações , Hipertensão/mortalidade , Estimativa de Kaplan-Meier , Rim/efeitos dos fármacos , Rim/patologia , Rim/cirurgia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade
3.
Artigo em Inglês | MEDLINE | ID: mdl-32081422

RESUMO

BACKGROUND AND OBJECTIVES: Formononetin has protective effect against ischemic stroke. It's unclear whether it can restore the nerve functions after stroke. METHODS: SD rats were subjected with middle cerebral artery occlusion (MCAO), and divided into sham, model and formononetin (30 mg/kg) groups. Neurobehavioral tests (modified Neurological Severity Score [mNSS] and rotarod) were performed before and at 1, 3, 7 and 14 days after MCAO. Then, the rats were sacrificed and the brain sections were processed for neuronal differentiation and synaptic plasticity. RESULTS: Compared with the sham group, the scores of mNSS were significantly increased, and the residence time on the rotating drum was significantly decreased in the MCAO rats. Compared with the model group, the scores of mNSS were significantly decreased, and the residence time on the rotating drum was increased in the formononetin (30 mg/kg) group. Formononetin significantly increased the number of neuronal dendritic spines and the expression of ß III-tubulin, GAP-43, NGF, BDNF, p-Trk A, p-Trk B, p-AKT and p-ERK 1/2. CONCLUSIONS: Formononetin recovered injured nerve functions after ischemic stroke. PI3K/AKT/ERK pathway might involve in the beneficial effect of formononetin on the neuronal differentiation and synaptic plasticity.

4.
J Cardiovasc Pharmacol ; 75(4): 314-320, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32040035

RESUMO

BACKGROUND: The current light transmission aggregation method is a recognized conventional method for platelet function evaluation, but it is time-consuming and poor in parallelism and cannot simultaneously monitor multiple inducers at multiple levels. The microtiter plate method has been established because of the high-throughput characteristic, but it needs more practical applications. OBJECTIVES: To evaluate the microtiter plate method by using aspirin and clopidogrel in vivo and in vitro. METHODS: In vitro, the platelet aggregations inhibited by aspirin (0.3, 1, 3, 10, 30, 90 µM) and clopidogrel (1, 3, 10, 30, 100, 300 µM) were evaluated with the presence of arachidonic acid (AA) and adenosine diphosphate (ADP) agonists. Using the combination index (CI), the effect of the combination of aspirin and clopidogrel on platelet aggregation was evaluated. In vivo, New Zealand rabbits (n = 18) were randomly divided into 3 groups, aspirin group (5 mg/kg, intragastrical gavage [i.g.]), clopidogrel group (14 mg/kg at the first day, followed by 4 mg/kg, i.g.), and the combination of these two drugs, administered (i.g.) continuously for 7 days. Then, the blood was collected to measure platelet aggregation. RESULTS: Different concentrations of AA (12.5, 25, 50, 100 µM) and ADP (1.25, 2.5, 5, 10 µM) could promote platelet aggregation in concentration-dependent manner, and the most stable induction concentrations of AA and ADP were 50 and 5 µM. In vitro, with the above optimized detection system, aspirin and clopidogrel alone or in combination had concentration-dependent antiplatelet aggregation. The combination of aspirin and clopidogrel also showed synergistic inhibition effect within the concentration range studied. In vivo, aspirin and clopidogrel alone or in combination inhibited platelet aggregation induced by multiple concentrations of AA and ADP agonists, and the combined inhibition was more significant during the administration than aspirin or clopidogrel alone. CONCLUSIONS: The improved microtiter plate method combining the use of multiple levels of multiple agonists avoids the variation of the effective inducer concentrations due to individual different response of platelets to agonists. It may be a potential approach in the detection of platelet aggregation.


Assuntos
Aspirina/farmacologia , Clopidogrel/farmacologia , Monitoramento de Medicamentos/instrumentação , Ensaios de Triagem em Larga Escala/instrumentação , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/instrumentação , Animais , Relação Dose-Resposta a Droga , Terapia Antiplaquetária Dupla , Humanos , Masculino , Valor Preditivo dos Testes , Coelhos , Fatores de Tempo
5.
J Pharmacol Sci ; 140(1): 79-85, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31178326

RESUMO

Bone marrow failure is a disease syndrome with the disability to produce mature blood cells. Pancytopenia is the most common manifestation of bone marrow failure. Sirt1 is important for the function of hematopoietic stem cells, we hypothesized that Sirt1 activation may improve hematopoiesis. The Sirt1 heterozygous and wild type mice were exposed to lethal 6.5 Gy 60Co-γ rays. The survival time and hematopoietic indexes were evaluated. The survival time of Sirt1 deficiency mice was significantly decreased. The numbers of platelets (PLT), reticulocytes (RET) and white blood cells (WBC) were significantly decreased. C57BL/6 mice were exposed to 6.5 Gy 60Co-γ rays then administrated with resveratrol (20 mg/kg/d) or vehicle. Resveratrol increased the survival time and protective against irradiation induced hematopoietic damage. Resveratrol also significantly increased the numbers of PLT, RET and WBC of mice. It also increased the hematopoietic area and karyocytes number. In HEK293T cells, the expression of LKB1 was significantly increased in cytoplasm but not in nuclei when treated with resveratrol (50 µM). These results suggest that Sirt1 deficiency might aggravate bone marrow failure. Resveratrol corrected this hematopoietic defect and LKB1 might involve in the protective effect on bone marrow failure.


Assuntos
Raios gama/efeitos adversos , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Pancitopenia/sangue , Pancitopenia/etiologia , Exposição à Radiação/efeitos adversos , Protetores contra Radiação/farmacologia , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Animais , Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Contagem de Leucócitos , Camundongos Knockout , Contagem de Plaquetas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Contagem de Reticulócitos , Sirtuína 1/deficiência , Sirtuína 1/fisiologia , Estimulação Química
6.
Clin Exp Pharmacol Physiol ; 45(6): 514-524, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29193272

RESUMO

This study was designed to investigate the possible synergism of amlodipine and candesartan on the reduction of blood pressure (BP) in hypertensive rats. The end organ protection was also observed. In acute experiment, spontaneously hypertensive rats (SHRs) were treated with intragastric administration of amlodipine (0.5, 1, 2, 3 mg/kg), candesartan (1, 2, 3, 4, 6, 8 mg/kg), and 14 different combinations to find the possible ratio of synergistic interaction. In two kidneys, one clip (2K1C) rats, the effects of amlodipine (1 mg/kg), canderastan (2 mg/kg) and their combination on BP reduction were also observed. In chronic study, SHRs were treated with amlodipine (1 mg/kg), candesartan (2 mg/kg), and their combination for 5 months. Organ damage evaluation was performed after BP recording. The probability sum test (q test) was used to evaluate the synergistic action. There is a synergistic interaction between amlodipine and candesartan on BP reduction. The optimal dose ratio is 1:2. The synergistic effect was also confirmed by 2K1C hypertensive rats. In chronic study, this combination (1:2) possessed an obvious synergism on the reduction of BP and BP variability (BPV) and protection on end organs. Multiple regression analysis showed that heart and aortic hypertrophy indexes and glomerular damage parameters were positively related to BP and BPV. In conclusion, combination of amlodipine and candesartan exhibited a potent antihypertensive effect and possessed an obvious synergism on BP reduction and organ protection in hypertension. The optimal proportion was 1:2. BP and BPV reduction may both importantly contribute to end organ protection.


Assuntos
Anlodipino/efeitos adversos , Anlodipino/farmacologia , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia , Animais , Compostos de Bifenilo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
7.
Dig Dis Sci ; 59(3): 614-22, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24271118

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease and the third leading cause of cancer-related deaths worldwide. Level of the 82-kDa ATP-dependent DNA helicase II (Ku86) increases in some tumors, but its clinical use as a marker for HCC is rare. AIMS: To examine the relationship between increases in Ku86 and the development of hepatitis B virus (HBV)-related HCC to define the relationship between Ku86 and HCC. METHODS: Expression of Ku86 in tumor tissue, para-tumor tissue, and normal tissue was examined by immunohistochemistry, and Ku86 antibody titers in patient serum collected pre- and post-operatively were measured by ELISA. Long-term survival of the patients was also monitored. RESULTS: Ku86 staining in tumors was much stronger than in para-tumor and normal tissues. The expression of Ku86 was related to the tumor size, TNM stage, and tumor differentiation but not to gender, age, Child-Pugh score, tumor number, or α-fetoprotein levels. The long-term survival of patients with low Ku86 expression was longer. Patients with HCC had higher pre-operative Ku86 antibody levels. After surgical intervention, Ku86 antibody levels in patients with HCC declined significantly. Survival analysis showed that double-positive patients had the lowest survival rate, double-negative patients had the highest. Receiver operating characteristic curve analysis showed no significant difference between the AFP and Ku86 antibody. Multivariate analysis showed that Ku86 protein and Ku86 antibodies were independent prognostic factors of overall survival. CONCLUSIONS: Ku86 and Ku86 antibodies are promising tumor markers for early detection and prognosis prediction of HBV-related HCC.


Assuntos
Autoanticorpos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , DNA Helicases/metabolismo , Hepatite B Crônica/complicações , Neoplasias Hepáticas/diagnóstico , Fígado/enzimologia , Idoso , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Autoantígeno Ku , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Análise de Sobrevida
8.
Eur Heart J ; 34(30): 2412-20, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21849351

RESUMO

AIMS: Angiogenesis is critical for re-establishing blood supply to ischaemic myocardium after myocardial infarction (MI). Human studies have associated arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI. The present work was designed to examine whether ABR deficiency affects angiogenesis in MI rats. METHODS AND RESULTS: Baroreflex sensitivity (BRS) was determined in conscious rats at 1 month after occlusion of the left anterior descending coronary artery. The survival time was significantly shorter in Sprague-Dawley rats with BRS <0.60 ms/mmHg vs. those with BRS ≥0.60 ms/mmHg. Sinoaortic denervation destroyed ABR, and decreased capillary density, regional blood flow and vascular endothelial growth factor (VEGF) concentration after MI. Ketanserin (0.6 mg/kg/day) enhanced BRS, and increased capillary density, regional blood flow, and VEGF. Sinoaortic denervation also reduced the expression of vesicular acetylcholine (ACh) transporter and α7-nicotinic ACh receptor (α7-nAChR). Angiogenesis after MI was significantly attenuated in α7-nAChR knockout mice. In contrast, increase in endogenous ACh with cholinesterase inhibitor pyridostigmine (30 mg/kg/day) increased angiogenesis after MI. In cultured cardiac microvascular endothelial cells, ACh stimulated the expression of VEGF, phosphorylation of VEGF receptor 2, and tube formation in a manner dependent upon α7-nAChR. CONCLUSION: Our results demonstrated that ABR deficiency could attenuate angiogenesis in ischaemic myocardium. These findings provide further mechanistic basis for enhancing baroreflex function in the treatment of MI.


Assuntos
Acetilcolina/fisiologia , Barorreflexo/fisiologia , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica/fisiologia , Receptor Nicotínico de Acetilcolina alfa7/fisiologia , Acetilcolina/farmacologia , Indutores da Angiogênese/farmacologia , Animais , Pressão Sanguínea/fisiologia , Capilares/fisiologia , Agonistas Colinérgicos/farmacologia , Inibidores da Colinesterase/farmacologia , Vasos Coronários/fisiologia , Denervação/métodos , Ketanserina/farmacologia , Camundongos , Camundongos Knockout , Brometo de Piridostigmina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
9.
Acta Pharmacol Sin ; 34(12): 1508-14, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24241347

RESUMO

AIM: Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction (MI). Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketanserin improves the post-MI cardiac function and to explore the possible mechanism involved. METHODS: Spontaneously hypertensive rats (SHR) were treated with ketanserin (0.3 mg·kg(-1)·d(-1)). Two weeks later, blood pressure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of vesicular acetylcholine transporter (VAChT) and α7 nicotinic acetylcholine receptor (α7-nAChR) in ischemic myocardium, angiogenesis, cardiac function, and left ventricular (LV) remodeling were evaluated subsequently. RESULTS: Ketanserin significantly improved baroreflex sensitivity (0.62±0.21 vs 0.34±0.12 ms/mmHg, P<0.01) and vagal tonic activity (heart rate changes in response to atropine, 54.8±16.2 vs 37.6±13.4 bpm, P<0.01) without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin prominently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and α7-nAChR in ischemic myocardium. CONCLUSION: Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of MI.


Assuntos
Barorreflexo/efeitos dos fármacos , Coração/efeitos dos fármacos , Ketanserina/farmacologia , Infarto do Miocárdio/fisiopatologia , Acetilcolina/metabolismo , Animais , Barorreflexo/fisiologia , Ensaio de Imunoadsorção Enzimática , Coração/fisiopatologia , Infarto do Miocárdio/metabolismo , Ratos , Ratos Endogâmicos SHR , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Heart Surg Forum ; 16(4): E219-24, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23958536

RESUMO

BACKGROUND: We reviewed the experience of An Zhen and Fu Wai Hospital for congenital sinus of Valsalva aneurysm (SVA) to determine risk factors for aortic valve replacement (AVR) and postoperative progression of aortic regurgitation (AR). METHODS: Over a 7-year period, 255 patients underwent surgical repair of an SVA. Aneurysms originated from the right sinus and the noncoronary sinus in 212 patients (83.1%) and 38 patients (14.9%), respectively, and protruded into the right ventricle and right atrium in 171 patients (67.1%) and 80 patients (31.4%), respectively. AR presented in 142 patients (55.7%), 60 patients underwent AVR, and 13 patients underwent aortic valvuloplasty (3 patients eventually received AVR for valvuloplasty failure). RESULTS: All patients survived the operation. Late death occurred in 2 patients (0.8%), and 2 patients (0.8%) experienced anticoagulation-related complications. Logistic regression analysis revealed that infective endocarditis, the cardiothoracic ratio, and a nonruptured SVA were risk factors for AVR. Late follow-up of 150 patients by echocardiographic assessment revealed that AR improved in 17 patients and worsened in 20 patients. Cox regression analysis revealed AR at discharge to be an independent risk factor for AR aggravation at late follow-up. CONCLUSIONS: SVA can be repaired with low mortality and excellent long-term results. AR at discharge is an important factor in determining AR aggravation at late follow-up after the operation. We recommend early diagnosis and aggressive treatment for SVA.


Assuntos
Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/cirurgia , Insuficiência da Valva Aórtica/mortalidade , Insuficiência da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/mortalidade , Complicações Pós-Operatórias/mortalidade , Seio Aórtico/cirurgia , Adolescente , Adulto , Idoso , Aneurisma Aórtico/diagnóstico , Insuficiência da Valva Aórtica/diagnóstico , Causalidade , Criança , Pré-Escolar , China/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
11.
Zhonghua Fu Chan Ke Za Zhi ; 48(8): 595-601, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-24199925

RESUMO

OBJECTIVE: To investigate the clinic-pathological characteristics and prognosis of 48 female cases with peritoneal pseudomyxoma(PMP). METHODS: The clinicopathologic features and follow-up data of 48 female patients with PMP diagnosed in the General Hospital of People's Liberation Army from Jan.1982 to Dec.2011 were retrospectively reviewed. The relationship between clinic-pathological characteristics and prognosis were analyzed using log-rank test and Cox proportional hazards model. RESULTS: (1) Clinicopathologic features: the mean age of the 48 cases was 58.8 years (range from 24 to 79 years). SYMPTOMS: abdominal distention and abdominal discomfort were the main symptoms. Imaging examinations showed nonspecific abdominal and pelvic lesions in most cases. TREATMENT: all the 48 patients underwent laparotomy and cytoreductive surgery (CRS), in which 15(31%) patients with completeness of the cancer resection (CCR) -1, 24(50%) cases with CCR-2, and CCR-3 in 9(19%) cases. Six (12%) cases were treated by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, 20(42%) patients were treated with different options postoperative adjuvant chemotherapy. Pathological types:the cases were histologically classified into 3 subcategories:disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D), which were 22(46%) cases, 9 (19%)cases and 17 (35%)cases, respectively. Appendiceal tumors: 44(92%) cases underwent appendectomy, in which 38 cases presented appendiceal tumors (including 20 cases of low-grade appendiceal mucinous adenoma and 18 cases of appendiceal mucinous adenocarcinoma), 2 cases were diagnosed as appendicitis, 4 cases with unknown pathologic diagnosis. And the other 4(8%) cases, who didn't undergo appendectomy at the first operation, presented peritoneal tumor recurrence and appendiceal mucinous tumors 1, 11, 32 and 85 months after surgery, respectively. Parenchymal organs involved: ovarian involving was happened in 34 (71%) patients including 15 cases with the right ovary involving, 13 cases in both sides, and 6 cases involving the left side. The other parenchymal organs in 10(21%) cases. (2) Prognostic factors: 11 patients died, 31 survived and 6 cases were lost to follow-up. The mean survival time was 99 months(ranged from 1 to 312 months). The 3-year, 5-year and 10-year survival rates were 73.3%, 68.0% and 46.6%, respectively. Univariate statistical analysis showed that age, pathological type and parenchymal involvement were significantly relationship with the survival time (all P < 0.05). But the operation times, appendiceal tumor type, ovarian involvement, CCR, intraperitoneal HIPEC and post-operative adjuvant chemotherapy were not significantly correlate with survival time (all P > 0.05). Multivariate analysis showed that age and pathologic type were independent prognostic factors(P < 0.05). CONCLUSIONS: No specific clinical features presented in PMP. CRS with HIPEC should the recommended treatment. Both ovaries exploration and appendectomy should be carried out routinely in CRS. The 10-year overall survival of PMP is low. Age, pathological type and parenchymal organs involvement other than ovarian are correlated with the prognosis. And the pathological type and age are independent prognostic factors of PMP.


Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias do Apêndice/patologia , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/terapia , Adulto , Fatores Etários , Idoso , Apendicectomia , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/terapia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Prognóstico , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/terapia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Pharmacol Res Perspect ; 11(2): e01064, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36810974

RESUMO

This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood pressure reduction in vivo by both SynergyFinder 3.0 and probability sum test. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (0.5, 1, 2, and 4 mg/kg), telmisartan (4, 8, and 16 mg/kg), candesartan (1, 2, and 4 mg/kg), nine combinations for amlodipine and telmisartan, and nine combinations for amlodipine and candesartan. The control rats were treated by 0.5% carboxymethylcellulose sodium. Blood pressure was recorded continuously up to 6 h after administration. Both SynergyFinder 3.0 and the probability sum test were used to evaluate the synergistic action. The synergisms calculated by SynergyFinder 3.0 are consistent with the probability sum test both in two different combinations. There is an obviously synergistic interaction between amlodipine and telmisartan or candesartan. The combinations of amlodipine and telmisartan (2 + 4 and 1 + 4 mg/kg) and amlodipine and candesartan (0.5 + 4 and 2 + 1 mg/kg) might exert an optimum synergism against hypertension. Compared with the probability sum test, SynergyFinder 3.0 is more stable and reliable to analyze the synergism.


Assuntos
Anlodipino , Hipotensão , Ratos , Animais , Telmisartan/farmacologia , Pressão Sanguínea , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Anti-Hipertensivos/farmacologia , Ratos Endogâmicos SHR
13.
Cancer Med ; 12(3): 3101-3111, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36271592

RESUMO

BACKGROUND: The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. METHODS: We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens. RESULTS: The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS. CONCLUSION: Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Idoso , Idoso de 80 Anos ou mais , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Agentes de Imunomodulação , Intervalo Livre de Doença , Transplante Autólogo , Resultado do Tratamento , Fatores Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica
14.
Oncogene ; 42(47): 3491-3502, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37828220

RESUMO

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.


Assuntos
Neoplasias Ovarianas , Proteínas Quinases , Feminino , Humanos , Receptores de Esfingosina-1-Fosfato/genética , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Senescência Celular/genética , Proliferação de Células/genética
15.
Front Oncol ; 12: 922039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865475

RESUMO

Objective: To use machine learning methods to explore overall survival (OS)-related prognostic factors in elderly multiple myeloma (MM) patients. Methods: Data were cleaned and imputed using simple imputation methods. Two data resampling methods were implemented to facilitate model building and cross validation. Four algorithms including the cox proportional hazards model (CPH); DeepSurv; DeepHit; and the random survival forest (RSF) were applied to incorporate 30 parameters, such as baseline data, genetic abnormalities and treatment options, to construct a prognostic model for OS prediction in 338 elderly MM patients (>65 years old) from four hospitals in Beijing. The C-index and the integrated Brier score (IBwere used to evaluate model performances. Results: The 30 variables incorporated in the models comprised MM baseline data, induction treatment data and maintenance therapy data. The variable importance test showed that the OS predictions were largely affected by the maintenance schema variable. Visualizing the survival curves by maintenance schema, we realized that the immunomodulator group had the best survival rate. C-indexes of 0.769, 0.780, 0.785, 0.798 and IBS score of 0.142, 0.112, 0.108, 0.099 were obtained from the CPH model, DeepSurv, DeepHit, and the RSF model respectively. The RSF model yield best scores from the fivefold cross-validation, and the results showed that different data resampling methods did affect our model results. Conclusion: We established an OS model for elderly MM patients without genomic data based on 30 characteristics and treatment data by machine learning.

16.
J Cardiovasc Pharmacol ; 57(3): 308-16, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21266915

RESUMO

AIM: This study was designed to investigate the effects of telmisartan and amlodipine on reduction of blood pressure (BP), myocardial hypertrophy, and renal injury in hypertensive rats. METHOD: In acute experiments, the BP was measured in conscious freely moving rats. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (1, 2, 4 mg/kg), telmisartan (4, 8, 12, 16, 20 mg/kg), and their different combinations (4 + 4, 2 + 4, 4 + 8, 4 + 12, 1 + 4, 2 + 8, 4 + 16, 2 + 12, 1 + 8, 2 + 16, 2 + 20, 1 + 12, 1 + 16, 1 + 20 mg/kg). The probability sum test (q test) was used to evaluate the synergistic action on BP reduction. In two-kidney, one-clip rats, the effects of amlodipine (1 mg/kg), telmisartan (6 mg/kg) and their combination on BP reduction were observed. In the chronic study, spontaneously hypertensive rats were treated with amlodipine (1 mg/kg), telmisartan (6 mg/kg), and their combination for 4 months. Histopathologic examinations were performed after the determination of BP and BP variability. RESULTS: There is a synergistic interaction between amlodipine and telmisartan on BP reduction. The optimal dose ratio was found at 1:6. The synergistic effect of this dose ratio (1:6) was also seen in two-kidney, one-clip rats. Long-term treatment with this combination results in a beneficial effect on the reduction of BP and BP variability. The end-organ damage, including myocardial hypertrophy, glomerular atrophy, and fibrosis, was significantly attenuated by this combination. CONCLUSION: The optimal dose ratio of amlodipine and telmisartan on BP was 1:6. This combination is beneficial for the BP and BP variability reduction and end-organ damage prevention.


Assuntos
Anlodipino/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiotônicos/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Nefropatias/prevenção & controle , Glomérulos Renais/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Telmisartan , Fatores de Tempo
17.
Zhonghua Bing Li Xue Za Zhi ; 40(7): 440-3, 2011 Jul.
Artigo em Zh | MEDLINE | ID: mdl-22088368

RESUMO

OBJECTIVE: To investigate the clinical and pathological features of the mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. METHODS: Seven cases of MTSCC were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD10, CK7, CK18, CK19, Villin, EMA, P504S and vimentin. The literature on this tumor was reviewed to discuss the histological features of MTSCC and its clinical behavior. RESULTS: Three of 7 cases were male and the other 4 were female. The mean age of the patients was 48.2 years old, with a range from 39 to 61 years. All the patients presented no symptom and their tumors were found by health examination. Tumors averaged 5.5 cm in greatest dimension (range from 4.0 cm to 9.0 cm). The tumors were well-circumscribed without capsules, and the cut surfaces were solid and soft with white-tan color. By light microscopy, tumors were composed of tightly packed, small, elongated tubules with transitions to spindle cell components. Five cases had mucinous stroma. Clear cell clusters, focal sarcomatoid differentiation, papillations and foamy macrophages were seen in several cases. Immunohistochemically, all 7 cases showed positive for CK7, five of 5 cases positive for EMA, CK18 and P504S, four of 5 cases positive for CK19, but heterogeneous for CD10, villin and vimentin expression. No evidence of local recurrence or distant metastases was identified in the 5 patients with follow-up information. CONCLUSIONS: The mucinous tubular and spindle cell carcinoma is a low-grade and polymorphic neoplasm. The morphology of these tumors may not be uniform with a wide histological spectrum. The tumors can be tubular predominant or spindle cells predominant with scant to abundant mucinous stroma, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, necrosis and sarcomatoid differentiation. Immunohistochemically, MTSCC can express the markers from the proximal convoluted tubules to collecting tubules.


Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma/patologia , Carcinoma/patologia , Neoplasias Renais/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/cirurgia , Adenoma/patologia , Adulto , Carcinoma/metabolismo , Carcinoma/cirurgia , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Queratina-18/metabolismo , Queratina-7/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Mucina-1/metabolismo , Nefrectomia , Prognóstico , Racemases e Epimerases/metabolismo
18.
Drug Des Devel Ther ; 15: 3543-3560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429584

RESUMO

PURPOSE: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models. METHODS: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5'-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways. RESULTS: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR. CONCLUSION: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.


Assuntos
Aspirina/farmacologia , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Animais , Ácido Araquidônico/metabolismo , Aspirina/administração & dosagem , Cromatografia Líquida de Alta Pressão , AMP Cíclico/metabolismo , Sinergismo Farmacológico , Ginkgo biloba , Masculino , Espectrometria de Massas , Extratos Vegetais/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Glicoproteínas da Membrana de Plaquetas/metabolismo , Coelhos , Receptores Acoplados a Proteínas G/metabolismo , Tromboxano B2/metabolismo
19.
Acta Pharmacol Sin ; 31(9): 1055-64, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20729874

RESUMO

Stroke is the second most common cause of death and the most common cause of disability in developed countries. Stroke is a multi-factorial disease caused by a combination of environmental and genetic factors. Numerous epidemiologic studies have documented a significant genetic component in the occurrence of strokes. Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for stroke. Although a large group of candidate genes have been studied, most of the epidemiological results are conflicting. Studies of stroke as a monogenic disease have made huge progress, and animal models serve as an indispensable tool to dissect the complex genetics of stroke. In the present review, we provide insight into the role of in vivo stroke models for the study of stroke genetics.


Assuntos
Isquemia Encefálica/genética , Hemorragias Intracranianas/genética , Acidente Vascular Cerebral/genética , Animais , Isquemia Encefálica/etiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Humanos , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/metabolismo , Acidente Vascular Cerebral/etiologia
20.
Clin Exp Pharmacol Physiol ; 37(2): 265-71, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19566841

RESUMO

1. Stroke is a major cause of disability and death worldwide. It is preferable to prevent stroke rather than to treat it and, for the prevention of stroke, all risk factors relating to stroke need to be understood. The present paper reviews potential new strategies for the prevention of stroke based on findings of new risk factors, as well as classical risk factors. 2. Recently, new risk factors related to stroke were reported, including dysfunction of the arterial baroreflex, pro-inflammatory cytokines, vitamins and hormone deficiency. Correspondingly, therapies targeting these risk factors where shown to significantly reduce the incidence and/or severity of stroke. 3. Because the genesis of stroke is multifactorial, the prevention of stroke should not target one risk factor only. Combination therapies with drugs acting on different risk factors may be more effective in the prevention of stroke.


Assuntos
Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Bebidas Alcoólicas/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Barorreflexo/fisiologia , Citocinas/fisiologia , Feminino , Deficiência de Ácido Fólico/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Progestinas/uso terapêutico , Fatores de Risco , Prevenção do Hábito de Fumar , Acidente Vascular Cerebral/etiologia , Deficiência de Vitamina D/prevenção & controle
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