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1.
Medicine (Baltimore) ; 98(52): e18513, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876741

RESUMO

BACKGROUND: This study evaluated the efficacy and safety of docetaxel combined with lobaplatin, relative to docetaxel combined with gemcitabine, for treating patients with recurrent metastatic breast cancer (rMBC). METHODS: Patients with rMBC received ≥2 cycles (21 days each) of either docetaxel and lobaplatin (DL; n = 21), or docetaxel and gemcitabine (DG; n = 22). On day 1 of each cycle, all patients were given 75 mg/m intravenous docetaxel. Patients in DL and DG were also given, respectively, 35 mg/m intravenous lobaplatin (day 2) or 1000 mg/m intravenous gemcitabine (days 1, 8). RESULTS: Five (11.6%) and 16 (37.2%) patients achieved complete remission and partial response, respectively; rates of response and disease control were 48.8%. The response rates of the groups were comparable (47.6%, 50.0%). The median survival times after relapse and metastasis of the DL group (18 months) were significantly less than that of the DG group (25 months). Median progression-free survivals after relapse and metastasis were similar (12 cf. 14 months). The main toxic side reaction was grade 2, with no treatment-related deaths. Rates of the following were comparable between DG and DL: grade 3 or 4 white blood cells (23.8%, 31.8%) and digestive tract toxicity (4.8%, 4.5%); neutropenia (28.6%, 22.7%); anemia (4.8%, nil); and thrombocytopenia (19.0%, 13.6%). Other toxicities included hepatic toxicity, myalgia, infection, and fatigue. CONCLUSIONS: Both the DL and DG regimens were associated with encouraging benefits, while treatment-related toxicity was manageable. Therefore, these regimens are effective options for treatment of rMBC. TRIAL REGISTRATION: This clinical trial study was approved by the Ethics Committee of Guizhou Cancer Hospital, and has been registered in the China Clinical Trial Center (December 8, 2014, No. ChiCTR-IPR-14005633).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclobutanos/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ciclobutanos/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Docetaxel/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Projetos Piloto , Análise de Sobrevida
2.
Zhongguo Fei Ai Za Zhi ; 22(2): 90-98, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30827325

RESUMO

BACKGROUND: The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion. METHODS: The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software. RESULTS: A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group. CONCLUSIONS: Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Ciclobutanos/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Derrame Pleural Maligno/tratamento farmacológico , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Ciclobutanos/uso terapêutico , Humanos , Compostos Organoplatínicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Immun Inflamm Dis ; 7(1): 22-40, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30756512

RESUMO

INTRODUCTION: Differences in immune characteristics, including immune gene expression by peripheral blood mononuclear cells (PBMCs), correlating with herpes labialis and good or poor immune control of herpes simplex virus type 1 (HSV-1), and how these characteristics change after dosing with squaric acid dibutyl ester (SADBE), were investigated. METHODS: PBMCs were collected from persons positive for IgG against HSV-1 and having frequent, infrequent, or no herpes labialis outbreaks. The PBMCs were tested for proliferation against HSV-1 and a fungal antigen (Candida) and immune gene expression in the presence of HSV-1 and Candida. On day 1 after blood collection the subjects with frequent outbreaks were dosed topically on the arm once with SADBE, and their PBMCs were collected and tested 8 weeks later. RESULTS: Those with good immune control of their HSV-1 infection (fewer outbreaks) differ from those with poorer immune control in these ways: (1) Greater PBMC proliferation in vitro to HSV-1, HSV-1-infected cell extracts, and Candida considered together (P < 0.01). (2) Higher expression of IFNG and five other immune-related genes (P < 0.05 for each) and lower expression of IL5 and two other immune-related genes (P < 0.05 for each) in PBMCs in vitro stimulated with HSV-1 virus. The subjects with frequent outbreaks were treated once with SADBE, and 56 days later the PBMCs of these subjects differed from PBMCs from the same subjects taken on day 1 before treatment in exactly the same ways listed above as differences between those with good and poor immune control of HSV-1, and at the same levels of significance. CONCLUSIONS: Higher IFNG and lower IL5 expression by PBMCs in the presence of HSV-1 correlate with fewer herpes labialis outbreaks, and a single topical dose of SADBE to the arm of subjects with frequent herpes labialis episodes improves immune response to HSV-1.


Assuntos
Antivirais/uso terapêutico , Candida/imunologia , Ciclobutanos/uso terapêutico , Herpes Labial/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/fisiologia , Leucócitos Mononucleares/fisiologia , Adolescente , Adulto , Feminino , Regulação da Expressão Gênica , Humanos , Interferon gama/metabolismo , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva , Adulto Jovem
4.
Bioorg Med Chem ; 27(5): 865-879, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30728107

RESUMO

Chagas Disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi and affects more than 10 million people. It is a paradigmatic example of a chronic disease without an effective treatment in Latin America where the current therapies, based on Benznidazole and Nifurtimox, are characterised by limited efficacy, toxic side-effects and frequent failures in the treatment. We present a series of new long-chain squaramides, identified based on their 1H and 13C NMR spectra, and their trypanocidal activity and cytotoxicity were tested in vitro through the determination of IC50 values. Compounds 4 and 7 were more active and less toxic than the reference drug Benznidazole, and these results were the basis of promoting in vivo assays, where parasitaemia levels, assignment of cure, reactivation of parasitaemia and others parameters were determined in mice treated in both the acute and chronic phases. Finally, the mechanisms of action were elucidated at metabolic and mitochondrial levels and superoxide dismutase inhibition. The experiments allowed us to select compound 7 as a promising candidate for treating Chagas Disease, where the activity, stability and low cost make long-chain squaramides appropriate molecules for the development of an affordable anti-chagasic agent versus current treatments.


Assuntos
Doença de Chagas/tratamento farmacológico , Ciclobutanos/uso terapêutico , Tripanossomicidas/uso terapêutico , Animais , Chlorocebus aethiops , Ciclobutanos/síntese química , Ciclobutanos/toxicidade , DNA/metabolismo , Feminino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , RNA/metabolismo , Esplenomegalia/tratamento farmacológico , Superóxido Dismutase/metabolismo , Tripanossomicidas/síntese química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/efeitos dos fármacos , Células Vero
5.
Chem Commun (Camb) ; 54(95): 13395-13398, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30426114

RESUMO

We introduce a novel strategy to enhance the fluorescence brightness of organic-molecule-based nanoparticles in the second near-infrared window (NIR-II, 1000-1700 nm) by fabricating J-aggregate nanoparticles SQP-NPs(J). Our prepared J-aggregate nanoparticles SQP-NPs(J) show an emission maximum near 1100 nm, and the emission intensity is 4.8-fold higher than that of H-aggregate SQP-NPs(H). In addition, SQP-NPs(J) can be used for NIR-II imaging guided photothermal therapy on MCF-7 tumor-bearing mice due to the fact that SQP-NPs(J) have highly effective photothermal properties, which are significant for precise tumor diagnostics and treatments.


Assuntos
Ciclobutanos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanopartículas/química , Fenóis/uso terapêutico , Fototerapia , Animais , Ciclobutanos/síntese química , Ciclobutanos/química , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Raios Infravermelhos , Injeções Intravenosas , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Fenóis/síntese química , Fenóis/química
6.
Obes Facts ; 11(4): 335-343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30089303

RESUMO

OBJECTIVE: The aim of the study was to assess the effectiveness and safety of long-term sibutramine therapy in routine clinical practice. METHODS: In total, 98,774 patients (82.3% women, 17.7% men) from 142 cities of the Russian Federation were enrolled in the PRIMAVERA program. The mean age of the patients was 39.39 ± 10.38 years, the mean body weight was 99.1 ± 14.28 kg, and the mean BMI was 35.7 ± 4.41 kg/m2. The duration of the sibutramine therapy was determined by physicians: 59.3% of patients took the drug for 6 months, the treatment course of 37.7% of patients was 12 months, and 3% of patients had treatment for 3 months. RESULTS: The BMI reduction correlated with the treatment duration: 3.4 ± 1.53 kg/m2 after 3 months of therapy, 5.4 ± 2.22 kg/m2 after 6 months, and 7.2 ± 3.07 kg/m2 after 12 months. The body weight reduction after 3, 6 and 12 months of treatment was 9.5%, 15.1%, and 19.7%, respectively. The body weight loss associated with sibutramine treatment was accompanied by a slight decrease in blood pressure and did not lead to any significant increases of the heart rate. CONCLUSIONS: The results of the PRIMAVERA study confirmed the lack of increased risk of using sibutramine in routine clinical practice in patients without underlying cardiovascular disease and low rate of adverse events.


Assuntos
Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Atenção Primária à Saúde , Federação Russa
7.
JAMA Dermatol ; 154(10): 1145-1151, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30073292

RESUMO

Importance: Contact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies. Objective: To summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors. Data Source: A database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric. Study Selection: Clinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded. Data Extraction and Synthesis: The following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies. Main Outcomes and Measures: The main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate. Results: Forty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment. Conclusions and Relevance: Various factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Alopecia em Áreas/terapia , Cabelo/crescimento & desenvolvimento , Imunoterapia/métodos , Adjuvantes Imunológicos/efeitos adversos , Alopecia/tratamento farmacológico , Ciclobutanos/uso terapêutico , Ciclopropanos/uso terapêutico , Humanos , Imunoterapia/efeitos adversos , Recidiva
8.
Fundam Clin Pharmacol ; 32(5): 548-557, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29733466

RESUMO

Lobaplatin is the third-generation platinum drug that has been shown promising antitumor activity in preclinical studies and clinical trials for multiple human cancers except prostate cancer. In this study, we investigated the role of lobaplatin on prostate cancer progression and the underlying molecular mechanism. We treated a variety of prostate cancer cell lines with different doses of lobaplatin and examined cell cycle progression, cell apoptosis, cell proliferation, and cell migration. Moreover, we also assessed the in-vivo antitumor activity of lobaplatin using xenograft mouse model. Importantly, we further dissected the underlying molecular mechanism by examining the expression of AR and ERG, as well as their downstream targets. We found that lobaplatin arrested cell cycle progression in G2/M phase and trigged cell apoptosis. Lobaplatin also dramatically inhibited cell proliferation and migration in vitro. Consistently, lobaplatin significantly suppressed tumor growth in xenograft mouse model. Mechanistically, the expression of AR and ERG, as well as their downstream targets, was markedly decreased upon treatment with lobaplatin in prostate cancer cells. Altogether, our results suggest that lobaplatin displayed favorable antitumor activity on prostate cancer both in vitro and in vivo, providing molecular basis and rational for using lobaplatin to combat human prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Ciclobutanos/farmacologia , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Ciclobutanos/uso terapêutico , Humanos , Masculino , Camundongos , Compostos Organoplatínicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Regulador Transcricional ERG/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Biomed Pharmacother ; 102: 567-574, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29597090

RESUMO

Radiotherapy is one of the common treatments for esophageal squamous cell carcinoma (ESCC). Yet, local recurrence led by radioresistance is still not solved. Lobaplatin (LBP) is known to have powerful clinical anti-tumor activities in various tumors, but its effect in radiotherapy is rarely studied. Here we report that LBP is a promising radiosensitizer for ESCC. We treated ESCC cells with LBP and radiation, both separately and in combination. Untreated cells were set as control groups. We found that LBP inhibited ESCC cell growth and enhanced their radiosensitivity. LBP also impeded the tumor growth in vivo. LBP combined with radiation significantly increased ESCC cell apoptosis. Meanwhile, LBP obviously decreased the expression of cancer stem cells biomarker CD271 both in vitro and in vivo. The molecular mechanism was related to the downregulation of Bcl-2/Bax ratio, PI3K and p-AKT (Ser473) expression. Taken together, our findings indicated that LBP could enhance the radiosensitivity of ESCC cells by increasing radiation-induced apoptosis, attenuating cancer stemness and inhibiting PI3K/AKT pathway. These results provide a foundation for the combined therapy of radiation and LBP for ESCC in clinical practice.


Assuntos
Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/enzimologia , Ciclobutanos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/enzimologia , Células-Tronco Neoplásicas/patologia , Compostos Organoplatínicos/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclobutanos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Proteínas do Tecido Nervoso , Compostos Organoplatínicos/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Receptores de Fator de Crescimento Neural , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
10.
J Med Chem ; 61(3): 1130-1152, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29298069

RESUMO

Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. Our efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, we discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by X-ray crystallographic analysis. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clinical candidate for the treatment of JAK1-mediated autoimmune diseases.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Ciclobutanos/farmacologia , Janus Quinase 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Sulfonamidas/farmacologia , Animais , Artrite Experimental/tratamento farmacológico , Ciclobutanos/química , Ciclobutanos/farmacocinética , Ciclobutanos/uso terapêutico , Cães , Avaliação Pré-Clínica de Medicamentos , Humanos , Concentração Inibidora 50 , Janus Quinase 1/química , Janus Quinase 2/antagonistas & inibidores , Modelos Moleculares , Conformação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/química , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Pirróis/química , Pirróis/farmacocinética , Pirróis/uso terapêutico , Ratos , Especificidade por Substrato , Sulfonamidas/química , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapêutico , Distribuição Tecidual
11.
Future Oncol ; 14(11): 1101-1115, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29359581

RESUMO

A significant number of patients radically treated for prostate cancer (PCa) will develop prostate-specific antigen recurrence (27-53%). Localizing the anatomical site of relapse is critical, in order to achieve the optimal treatment management. To date the diagnostic accuracy of standard imaging is low. Several desirable features have been identified for the amino-acid-based PET agent, fluciclovine (18F) including: long 18F half-life which allows more practical use in centers without a cyclotron onsite; acting as a substrate for amino acid transporters upregulated in PCa or associated with malignant phenotype; lacking of incorporation into protein; and limited urinary excretion. Fluciclovine (18F) is currently approved both in USA and Europe with specific indication in adult men with suspected recurrent PCa based on elevated prostate-specific antigen following prior treatment.


Assuntos
Ácidos Carboxílicos/uso terapêutico , Ciclobutanos/uso terapêutico , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Meios de Contraste/uso terapêutico , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/uso terapêutico
12.
J Immunol Res ; 2018: 9034695, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30648122

RESUMO

Objective: To reduce immune-mediated damage in a rat model of neuromyelitis optica (NMO) by blocking neutrophil migration using SCH527123, a drug that inhibits CXCR2. Background: Neuromyelitis optica is a relapsing autoimmune disease that preferentially targets the optic nerves and spinal cord leading to blindness and paralysis. Part of the immunopathogenesis of this disease is thought to involve neutrophils, which are present within NMO lesions. We tested the effect of blocking neutrophil migration in an NMO rat model. Methods: The Lewis rat model of NMO uses a myelin-reactive experimental autoimmune encephalomyelitis (EAE) background with passive transfer of pooled human antibody from patients with aquaporin-4 (AQP4) seropositive NMO at onset of EAE symptoms. We treated rats early in the course of EAE with CXCR2 inhibitor and assessed the extent of neutrophil infiltration into the spinal cord and the extent of AQP4 depletion. Results: CXCR2 inhibitor decreased neutrophil migration into the spinal cord of AQP4 IgG-treated EAE rats. However, there was no difference in the acute behavioral signs of EAE or the extent and distribution of AQP4 lesions. This suggests that neutrophils are not centrally involved in the immunopathogenesis of the Lewis rat NMO disease model. Conclusions: CXCR2 inhibitor blocks neutrophil migration into the spinal cord during EAE but does not significantly reduce inflammation or AQP4 lesions in the Lewis rat model of NMO.


Assuntos
Benzamidas/uso terapêutico , Ciclobutanos/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Inflamação/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológico , Neutrófilos/imunologia , Animais , Anticorpos/metabolismo , Aquaporina 4/imunologia , Comportamento Animal/efeitos dos fármacos , Benzamidas/farmacologia , Movimento Celular/efeitos dos fármacos , Ciclobutanos/farmacologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/psicologia , Feminino , Humanos , Proteína Básica da Mielina/imunologia , Neuromielite Óptica/psicologia , Neutrófilos/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Receptores de Interleucina-8B/antagonistas & inibidores , Suínos
13.
Prostate Cancer Prostatic Dis ; 21(1): 4-21, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29230009

RESUMO

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising diagnostic imaging platform for prostate cancer. Several radiolabelled tracers have demonstrated efficacy for cancer detection in various clinical settings. In this review, we aim to illustrate the diverse use of PET/CT with different tracers for the detection of prostate cancer. METHODS: We searched MEDLINE using the terms 'prostate cancer', 'PET', 'PET/CT' and 'PET/MR'). The current review was limited to 18F-NaF PET/CT, choline-based PET/CT, fluciclovine PET/CT and PSMA-targeted PET/CT, as these modalities have been the most widely adopted. RESULTS: NaF PET/CT has shown efficacy in detecting bone metastases with high sensitivity, but relatively low specificity. Currently, choline PET/CT has been the most extensively studied modality. Although having superior specificity, choline PET/CT suffers from low sensitivity, especially at low PSA levels. Nevertheless, choline PET/CT was found to significantly improve upon conventional imaging modalities (CIM) in the detection of metastatic lesions at biochemical recurrence (BCR). Newer methods using fluciclovine and PSMA-targeted radiotracers have preliminarily demonstrated great promise in primary and recurrent staging of prostate cancer. However, their superior efficacy awaits confirmation in larger series. CONCLUSIONS: PET/CT has emerged as a promising staging modality for both primary and recurrent prostate cancer. Newer tracers have increased detection accuracies for small, incipient metastatic foci. The clinical implications of these occult PET/CT detected disease foci require organized evaluation. Efforts should be aimed at defining their natural history as well as responsiveness and impact of metastasis-directed therapy.


Assuntos
Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/tendências , Neoplasias da Próstata/diagnóstico por imagem , Ácidos Carboxílicos/uso terapêutico , Colina/uso terapêutico , Ciclobutanos/uso terapêutico , Humanos , Masculino , Imagem Multimodal/tendências , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Traçadores Radioativos
14.
Biomed Pharmacother ; 95: 447-452, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28865364

RESUMO

Esophageal cancer is one of the most aggressive malignancies with poor prognosis. The administration of the first- and second-generation platinum drugs is frequently accompanied by drug resistance and severe toxicity. The aim of present study is to investigate the anti-tumor activity of the third-generation platinum drug Lobaplatin against esophageal squamous cell carcinoma in vitro and in vivo, and clarify the underlying molecular mechanism. The cytotoxicity of Lobaplatin against esophageal squamous cell carcinoma cell lines was determined by the MTT and clonogenic assay. Cell apoptosis was assessed by Annexin V-FITC/PI apoptosis assay using flow cytometry. The expression of proteins was determined by western blot analysis. The in vivo anti-tumor activity was evaluated in nude mice xenograft. Lobaplatin significantly inhibited the growth of KYSE-410 and EC-109 cells in a dose- and time-dependent manner and induced cell apoptosis by increasing expressions of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9 and Bax, decreasing expression of Bcl-2. In vivo study showed that Lobaplatin suppressed tumor growth of EC-109 xenograft. Lobaplatin significantly inhibited the growth of esophageal squamous cell carcinoma by inducing apoptosis through the caspase-dependent pathway. Lobaplatin is an effective anti-cancer agent against esophageal cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/enzimologia , Caspases/metabolismo , Ciclobutanos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/enzimologia , Compostos Organoplatínicos/uso terapêutico , Proteína X Associada a bcl-2/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclobutanos/farmacologia , Carcinoma de Células Escamosas do Esôfago , Humanos , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Organoplatínicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Dermatitis ; 28(5): 308-312, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28885314

RESUMO

BACKGROUND: Contact immunotherapy with squaric acid dibutylester (SADBE) for cutaneous warts has been reported to be effective, although no controlled studies are available so far. OBJECTIVE: The aim of this study was to evaluate the efficacy of SADBE on cutaneous warts by a randomized, double-blind, vehicle-controlled, clinical trial. METHODS: Thirty-six patients were randomly assigned to SADBE (18 cases) or vehicle (18 cases) group. At 8 weeks, subjects were clinically evaluated for number/size reduction rate and for Investigator Global Assessment. Those who showed improvement extended therapy up to 40 weeks, whereas those who showed unresponsiveness were either switched to SADBE application for up to 48 weeks (if in the vehicle group) or withdrawn from the study (if under SADBE). RESULTS: At 8 weeks, a significant reduction in wart number (P = 0.020) and size (P = 0.010) in the SADBE group, with clearing rates of 41.2% versus 12.5% in the SADBE and vehicle groups, respectively, was observed. Nine remaining SADBE responders who underwent treatment extension up to 40 weeks achieved clearing versus 2 patients of the vehicle group who remained unresponsive. Clearing was obtained in 81.8% of patients who underwent previous ineffective vehicle treatment and had been switched to SADBE. CONCLUSIONS: Squaric acid dibutylester is an effective therapeutic option and is significantly more effective than vehicle.


Assuntos
Ciclobutanos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Verrugas/tratamento farmacológico , Administração Cutânea , Adolescente , Adulto , Criança , Ciclobutanos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Imunoterapia , Masculino , Projetos Piloto , Recidiva , Retratamento , Verrugas/terapia , Adulto Jovem
16.
Obes Res Clin Pract ; 11(5): 501-521, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28818558

RESUMO

BACKGROUND: Obesity is a major issue in Australia and globally. Many individuals struggle to maintain weight loss with lifestyle modification, and adjunctive pharmacotherapy may help. Historically, there have been limited pharmacotherapies for managing obesity. In addition, previous treatments such as phentermine-fenfluramine, rimonabant and sibutramine were withdrawn due to safety issues, resulting in lingering safety concerns. METHODS: This is a narrative review of published data examining four new pharmacotherapy options for weight management in Australia. Of four new therapeutic options, three may be approved in Australia shortly and one - liraglutide 3.0mg - was approved in December 2015. Liraglutide is a glucagon-like peptide-1 receptor agonist that appears to act by increasing satiety and reducing food intake. Lorcaserin is a selective agonist of the serotonin2C receptor, which mediates anorectic activity. The naltrexone/bupropion extended release (ER) combination utilises synergistic effects of the two component drugs, mediated via neurons in the hypothalamus, to reduce energy intake. Phentermine/topiramate ER combines the appetite suppressant phentermine with topiramate, an anti-epileptic with appetite-suppressant effects. All can result in meaningful improvements in obesity-related diseases, including diabetes and cardiovascular disorders) in large phase 3 trials, with efficacy demonstrated over 3 years for liraglutide 3.0 mg and 1-2 years for the rest. CONCLUSIONS: The landscape of obesity treatment is changing rapidly. Of the new therapeutic options presented, all options have associated adverse events requiring long-term safety data, but the availability of new options is a welcome development.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Depressores do Apetite/uso terapêutico , Austrália , Benzazepinas/uso terapêutico , Bupropiona/uso terapêutico , Ciclobutanos/uso terapêutico , Dieta , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Liraglutida/uso terapêutico , Naltrexona/uso terapêutico , Fentermina/uso terapêutico , Topiramato , Perda de Peso
17.
Medicine (Baltimore) ; 96(29): e7589, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28723799

RESUMO

To evaluate the safety and efficacy of transarterial arterial chemoembolization (TACE) with gelatin sponge particles (GSPs-TACE) and Huaier granule to treat primary hepatic carcinoma (PHC).A series of 62 patients with PHC were included between June 2009 and December 2011, and randomly assigned to a control (n = 31) or an experimental group (n = 31). The control patients received TACE with 350 to 560 µm GSPs plus lobaplatin chemotherapy. Patients in the experimental group received TACE plus Huaier granule. Treatment safety and mid-to-long-term efficacy were evaluated.Follow-up ranged from 12 to 24 months with a mean of 28.7 months. The 6- and 12-month overall survivals were 100% and 93.5% in the experimental group and 90.3% and 80.6% in control group, respectively. The difference in overall survival at 12 months was significant (χ = 5.213, P < .05), but the difference in median survival in the experimental group (20.6 months) and control group (17.1 months) patients was not significant (χ = 0.745, P > .05). The number of TACE procedures in the experimental group (2.9 ±â€Š8.7) and control group (4.1 ±â€Š7.3) patients was significantly different (χ = 7.262, P < .05). The 6-month (87.1% vs. 73.3%, χ = 5.945) and 12-month (72.4% vs. 64.3%, χ = 6.384) tumor objective response rates in the experimental and control groups were significantly different (P < .05). There were no statistically significant differences in the occurrence of treatment-related adverse reactions in the 2 groups.Transarterial chemoembolization with GSPs and Huaier granule was safe and effective for treating PHC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Misturas Complexas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada/efeitos adversos , Ciclobutanos/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Compostos Organoplatínicos/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
18.
Medicine (Baltimore) ; 96(29): e7601, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28723805

RESUMO

RATIONALE: Drug-induced pancreatitis (DIP) is a rare type of pancreatitis that is not usually observed in the clinical practice. It is generally difficult to distinguish from acute pancreatitis (AP) induced by other causes. PATIENT CONCERNS: Here, we report a 62-year-old Chinese female patient with "small cell lung cancer" as the initial presentation. Because the patient could not bear the surgical treatment, the chemotherapy composed of lobaplatin and etoposide was performed. Three days later, the patient displayed sudden abdominal pain, distension, nausea, and vomiting without obvious inducements. Laboratory tests showed that the levels of serum and urine amylase were enhanced; abdominal computed tomography (CT) result showed the enlargement of the pancreas, peripancreatic effusion, and a rough edge, which suggested the diagnosis of AP. The patient had no history of biliary tract disease, alcoholism, binge overeating, hyperlipidemia, and hereditary pancreatitis. DIAGNOSES: The patient was diagnosed with DIP. INTERVENTIONS: The chemotherapy was stopped at once and we performed fluid resuscitation, pain alleviation, prophylactic antibiotics, and nutritional support, etc on the patient. Later, the patient's clinical symptoms were obviously relieved, and she recovered successfully. OUTCOMES: The chemotherapy was continued, but later, the patient showed abdominal pain, distension, nausea, and vomiting again. The levels of serum amylase and urine amylase were enhanced again. Further imaging examination strongly indicated the recurrence of AP. LESSONS: We should raise awareness of the clinicians regarding DIP, thereby enabling its timely diagnosis and accurate treatment, as well as promoting the rational and safe use of drugs.


Assuntos
Antineoplásicos/efeitos adversos , Ciclobutanos/efeitos adversos , Etoposídeo/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/efeitos adversos , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico , Doença Aguda , Antineoplásicos/uso terapêutico , Ciclobutanos/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
19.
Rev Assoc Med Bras (1992) ; 63(3): 203-206, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28489121

RESUMO

Antiobesity pharmacotherapy remains the main point of disagreement among both scientists and regulators. This is probably due to small sample sizes, high levels of heterogeneity, and low methodological quality. For many years, Brazil was one of the largest consumers of appetite suppressants worldwide, with evidence of irrational use of this drug class. Therefore, the country was the scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa - Agência Nacional de Vigilância Sanitária) and medical societies over the maintenance record of diethylpropion, mazindol and fenproporex. In this context, this commentary presents new arguments to contribute to the discussion, as well as recommendations for future studies.


Assuntos
Depressores do Apetite/uso terapêutico , Dietilpropiona/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Anfetaminas/uso terapêutico , Brasil , Ciclobutanos/uso terapêutico , Aprovação de Drogas , Humanos , Medição de Risco/tendências , Resultado do Tratamento
20.
Medicine (Baltimore) ; 96(16): e6629, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28422858

RESUMO

To retrospectively analyze the safety and efficacy of 350-560 µm gelatin sponge particles combined with single-chemotherapy drug transcatheter arterial chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma without surgical resection.Thirty elderly hepatocellular carcinoma patients without surgical resection, who received Gs-TACE in our hospital, were selected. Slowly injected gelatin sponge particles (350-560 µm)+ 10 mg lobaplatin injection into the regional embolization tumor target vessel. The Response Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response after intervention surgery.Eighty-nine times of intervention TACE were conducted on the 30 patients. The average size of tumor was 8.3 cm. The median survival time was 28 months, and the 1 and 2-year survival rates were 89% and 58%, respectively. The Response Evaluation Criteria for Solid Tumors was used to evaluate the tumor response, and found that the complete response, partial response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after intervention surgery. The patients were divided into groups: 60 to 65 years age group (A), >65 to 75 years age group (B), and >75 years age group (C); the median survival times were 16, 32, and 33 months, respectively, and there was statistical difference between A group, B group, and C group. The analysis of prognosis factors showed that there was statistical significance in age, Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal protein (AFP), and age was the protective factor.Gelatin sponge particles (350-560 µm), combined with transcatheter arterial chemoembolization, provide an alternative method for the treatment of elderly hepatocellular carcinoma without surgical resection.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Ciclobutanos/administração & dosagem , Neoplasias Hepáticas/terapia , Compostos Organoplatínicos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/uso terapêutico , Ciclobutanos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Gelatina , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Tamanho da Partícula , Poríferos/química , Estudos Retrospectivos , Taxa de Sobrevida
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