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1.
Zhonghua Nei Ke Za Zhi ; 60(7): 630-636, 2021 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-34619840

RESUMO

Objective: To evaluate the efficacy and safety of anti-programmed cell death 1 (PD-1) receptor monoclonal antibody (MoAb) in patients with advanced hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitor (TKI). Methods: From February 2019 to February 2020, 56 HCC patients who relapsed after TACE-TKI treatment in Department of Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University were enrolled. All patients received anti-PD-1 MoAb (sintilimab injection) and followed up every 6 weeks. According to mRECIST, the curative effect was evaluated as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Objective response rate (ORR) and disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs) were recorded. Univariate analysis by Chi-square test and binary logistic regression model was used to determine the influencing factors of DCR. The Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the survival data. Results: A total of 48 patients were enrolled in this study including 42 males and 6 females, with a median age of 55 years (29-71 years). ECOG scores comprised of 0 in 24 cases, 1-2 in 24 cases. Thirty-six patients were in Child-Pugh grade A of liver function and 12 cases were grade B. The median follow-up time was 4.5 months. There were 2 patients achieved CR, 12 patients with PR and 16 with SD. ORR was 29.2%, DCR was 62.5%. The independent influencing factors of DCR was ECOG score and AFP level (P=0.031, P=0.012). Median PFS was 4.1 months (95%CI 2.7-5.4 months), and ECOG score was the independent influencing factor of PFS (P=0.042). Treatment-related adverse events were reported in 70.8% (34/48) patients. Incidence of grade Ⅲ-Ⅳ TRAEs was 22.9% (11/48). Conclusion: In patients with HCC who relapse from TACE and TKI treatment, anti-PD-1 monoclonal antibody is efficacious safe especially in those with ECOG 0 score.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Inibidores Enzimáticos/uso terapêutico , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
2.
Naunyn Schmiedebergs Arch Pharmacol ; 357(2): 126-32, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9521485

RESUMO

BDF 9148, a positive cardiac inotrope, relaxes the rat isolated portal vein and the KCl-contracted rat aorta. The aims of our study were to determine the mechanism of action of BDF 9148, and to ascertain whether the relaxing effect of BDF 9148 was maintained in the presence of the hypertrophy associated with hypertension, by investigating the effects of BDF 9148 on the contractility and electrophysiology of aortae of Wistar Kyoto normo-tensive rats (WKY) and Spontaneously Hypertensive Rats (SHRs). High concentrations of veratridine contracted the quiescent rat aorta. BDF 9148 had no effect on the quiescent, but relaxed the KCl-contracted WKY and SHR aorta by a tetrodotoxin insensitive mechanism, and these relaxations decreased with age but were not greatly altered by hypertrophy. The verapamil relaxations of the KCl-contracted aorta were not altered by age or hypertrophy. The ability of KCl to depolarise the aorta was reversed by verapamil, but not by BDF 9148. On the contracted rat aorta, the relaxant responses to acetylcholine were abolished by removal of the endothelium but potentiated by IBMX (10[-6] M), and the responses to isoprenaline were inhibited by propranolol (10[-6] M) but potentiated by forskolin (10[-7] M). The relaxation responses of the KCl-contracted aorta to BDF 9148 were not altered by removal of the endothelium, or by propranolol, forskolin and IBMX. In summary, the effects of verapamil and BDF 9148 on the aorta are different, and thus it is unlikely that the relaxant responses to BDF 9148 on the aorta are due to calcium channel blocking activity. The mechanism of the relaxant effect of BDF 9148 on the aorta remains unknown, but we have shown the response is endothelium-independent, and not mediated by sodium channel opening, hyperpolarization, beta-adrenoceptors, or by stimulating adenylate cyclase or guanylate cyclase.


Assuntos
Aorta Torácica/efeitos dos fármacos , Azetidinas/farmacologia , Cardiotônicos/farmacologia , Hipertensão/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Eletrofisiologia , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Verapamil/farmacologia
4.
J Biomech Eng ; 120(1): 112-7, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9675689

RESUMO

Microcracks have been associated with age-related bone tissue fragility and fractures. The objective of this study was to develop a simple osteonal cortical bone model and apply linear elastic fracture mechanics theory to understand the micromechanics of the fracture process in osteonal cortical bone and its dependence on material properties. The linear fracture mechanics of our composite model of cortical bone, consisting of an osteon and interstitial bone tissue, was characterized in terms of a stress intensity factor (SIF) near the tip of a microcrack. The interaction between a microcrack and an osteon was studied for different types of osteons and various spacing between the crack and the osteon. The results of the analysis indicate that the fracture mechanics of osteonal cortical bone is dominated by the modulus ratio between the osteon and interstitial bone tissue: A soft osteon promotes microcrack propagation toward the osteon (and cement line) while a stiff one repels the microcrack from the osteon (and cement line). These findings suggest that newly formed, low-stiffness osteons may toughen cortical bone tissue by promoting crack propagation toward osteons. A relatively accurate empirical formula also was obtained to provide an easy estimation of the influence of osteons on the stress intensity factor.


Assuntos
Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Fraturas Espontâneas/fisiopatologia , Ósteon/fisiopatologia , Fenômenos Biomecânicos , Tecido Conjuntivo/fisiopatologia , Elasticidade , Consolidação da Fratura/fisiologia , Humanos , Modelos Teóricos , Resistência à Tração
5.
Biochem Mol Biol Int ; 36(3): 689-94, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7549969

RESUMO

To study the regulation of hormone-sensitive lipase gene in pigs, we amplified and sequenced partial porcine hormone-sensitive lipase cDNA. Nucleotide analysis indicated that porcine hormone-sensitive lipase cDNA was 86% homologous with the rat. In agreement with the rat, a 3.3 kb mRNA transcript was detected in adipose tissue but not in skeletal muscle of pigs by Northern hybridization. With more sensitive PCR method, hormone-sensitive lipase mRNA was found in adipose tissue, liver, heart, skeletal muscle, testis, and spleen. The gene expression in adipose tissue and liver was elevated after 2 days of fasting, and refeeding for another 2 days decreased the mRNA abundance. In contrast, the levels in skeletal muscle were not altered during identical nutritional transition. Combined evidences suggest that differential control may occur in porcine hormone-sensitive lipase gene in a tissue-specific fashion.


Assuntos
Tecido Adiposo/enzimologia , Fígado/enzimologia , Músculo Esquelético/enzimologia , Esterol Esterase/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Dieta , Regulação Enzimológica da Expressão Gênica , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Esterol Esterase/biossíntese , Suínos
6.
Gen Comp Endocrinol ; 70(3): 382-94, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3417113

RESUMO

Specific [3H]estradiol-17 beta ([3H]E2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds [3H]E2 with high affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of [3H]E2 binding activity in both cytosolic and nuclear fractions. The exchange between [3H]E2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species.


Assuntos
Estradiol/metabolismo , Fígado/metabolismo , Receptores de Estrogênio/metabolismo , Tartarugas/metabolismo , Animais , Núcleo Celular/análise , Citosol/análise , Feminino , Ligantes , Fígado/citologia , Fígado/ultraestrutura , Métodos , Receptores de Estrogênio/análise , Tiocianatos/farmacologia , Trítio
7.
Artigo em Inglês | MEDLINE | ID: mdl-3816355

RESUMO

Serum IgG, IgM, IgA, C3, C4 concentrations and circulating immune complexes (CIC) were measured in a series of 46 patients with oral lichen planus (LP). This investigation revealed a significant increase in the level of serum IgG in patients with oral LP as compared with 36 healthy subjects. In erosive LP, serum IgM was also elevated as compared with healthy subjects and patients with the non-erosive type. The results of this study did not support the suggestion that a humoral immunodeficiency underlies oral LP. Elevated serum level of IgM may be considered to represent secondary oral infection during mucosal erosion. The study also demonstrated a significant reduction in serum C4 in both variants of oral LP, but the C3 level was normal. A 3% polyethylene glycol precipitation (PEG-ppt) method was used, no significant amount of CIC could be detected in the patients. It is tempting to speculate that oral LP reflects an immunologic disorder in which serum IgG and C4 is disturbed. However, further investigation is needed to clarify the pathogenesis of oral LP.


Assuntos
Complexo Antígeno-Anticorpo/análise , Proteínas do Sistema Complemento/análise , Imunoglobulinas/análise , Líquen Plano/imunologia , Doenças da Boca/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Gen Comp Endocrinol ; 67(1): 119-25, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3623065

RESUMO

Employing a hydroxylapatite batch assay, estrogen-binding activities (EBAs) were demonstrated in the cytosol and nuclear extract of the testis of the anadromous sea lamprey, Petromyzon marinus. The lamprey testicular EBAs are sensitive to trypsin digestion and bind [3H]estradiol-17 beta with high affinities (cytosolic Kd = 0.52 nM; nuclear Kd = 0.39 nM) and limited capacities (cytosolic: 56.2 fmol/g tissue; nuclear: 68.2 fmol/g tissue). Androgens, progesterone, and corticosterone displayed little affinities for lamprey EBAs. Thus, lamprey testicular EBA possessed many definitive properties of an estrogen receptor as described in amphibian, reptilian, and mammalian studies. No specific binding to androgens was detected in either testicular subcellular fraction. The presence of a putative estrogen receptor in lamprey testis suggests a functional role of estrogen in testicular regulation in this ancient vertebrate.


Assuntos
Peixes/fisiologia , Lampreias/fisiologia , Receptores de Estrogênio/metabolismo , Testículo/metabolismo , Animais , Ligação Competitiva , Núcleo Celular/metabolismo , Citosol/metabolismo , Cinética , Masculino
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