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1.
Phytochemistry ; 178: 112463, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32888669

RESUMO

Ten undescribed alkaloids, named integerrines A-J, including one racemic heterodimer of carbazole and indole, two racemic, two scalemic, and one enantiomerically enriched biscarbazoles, two aldoximes, and one racemic pyrrolone, were isolated from the dried leaves and stems of Micromelum integerrimum. The racemic or scalemic compounds were resolved using chiral-phase HPLC and their configurations were determined by comparison of experimental and calculated ECD data. Four compounds exhibited moderate to weak cytotoxicities against HepG2, HTC-116, HeLa, and PANC-1 cell lines, with IC50 values of 14.1-67.5 µM.


Assuntos
Alcaloides , Antineoplásicos , Rutaceae , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Folhas de Planta
2.
Medicine (Baltimore) ; 99(35): e21376, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871864

RESUMO

BACKGROUND: COVID-19 is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diseases themselves, as well as the intensity of chemotherapy, lead to significant immunosuppression, leading hematological malignancy patients susceptible to infections. METHODS: This protocol will be performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and reported follow the Cochrane Collaboration Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Electronic databases of PubMed, MEDLINE, Google Scholar, Web of science, Cochrane Library, EMBASE, CNKI, CMB, and Wangfang database from the inception to present will be comprehensively and systematically searched without limitations of language, date, and publication status. Observational, retrospective cohort, prospective case-control, cohort studies, cross-sectional studies, or clinical trials will be included. All assessment of study selection, data extraction, and study quality assessment will be independently performed by 2 reviewers. RevMan V.5.3 program and Stata V.12.0 software will be utilized for the methodological quality assessment and statistical analysis. RESULTS: The result of this systematic review will provide evidence for clinicians on the management of COVID-19 patients with hematological malignancy. CONCLUSION: This systematic review will help raise awareness and guide management of COVID-19 patients with hematological malignancy, as well as to improve outcomes in this population. ETHIC AND DISSEMINATION: The content of this article does not involve moral approval or ethical review because no individual data will be collected. PROSPERO REGISTRATION: CRD42020187493.


Assuntos
Antineoplásicos/farmacologia , Infecções por Coronavirus , Neoplasias Hematológicas , Pandemias , Administração dos Cuidados ao Paciente/métodos , Pneumonia Viral , Betacoronavirus , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
3.
Zhonghua Zhong Liu Za Zhi ; 42(8): 624-628, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867452

RESUMO

Small cell lung cancer (SCLC), a special type of lung cancer, is a highly malignant neuroendocrine tumor with strong invasiveness and rapid progression. SCLC is sensitive to radiotherapy and chemotherapy, so radiotherapy and chemotherapy have been the main first-line treatment of SCLC. However, it is easy to develop drug resistance after treatment. Therefore, the study of anti-angiogenic therapy has attracted more and more attention. At present, anti-angiogenic drugs mainly focus on four categories: monoclonal antibodies (such as bevacizumab), endogenous angiogenesis inhibitors (such as endostar), anti-angiogenic fusion protein (such as aflibercept) and small molecular tyrosine kinase inhibitors (such as anlotinib). There are still some bottlenecks in the research and clinical application of antiangiogenic drugs. It is the right direction to explore better combination therapy and effective dual-field and multi-target drugs.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Medicina de Precisão , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1090-1096, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895173

RESUMO

OBJECTIVE: To investigate the effect of down-regulation of pannexin 2 (Panx-2) channels on cisplatin-induced apoptosis in I-10 cells. METHODS: The expression of Panx-2 protein in testicular cancer cells was detected with Western blotting. The testicular cancer cell line I-10 was transfected with two short hairpin RNA (shRNA1 and shRNA2) via Lipofectamine2000, the empty vector (NC group) or Lipofectamine2000 (blank control group), and the changes in the expression of Panx-2 was detected with Western blotting. The effects of transfection with a Panx-2 inhibitor on surviving fraction of the cells treated with cisplatin (16 µmol/L) for 24 h, 48 h and 72 h was assessed with MTT assay, and the clonogenic capacity of the cells was evaluated with colony-forming assay. At 8 h after incubation with 16 µmol/L cisplatin, AnnexinV/PI double staining was used to detect the early apoptosis of the cells. After 24 h of treatment with 16 µmol/L cisplatin, the cells were examined for expressions of caspase-3, Bcl-2 and Bax using Western blotting. RESULTS: The expression of Panx-2 was significantly increased in cisplatin-resistant I-10/DDP (P < 0.001) cells and Tcam-2/DDP (P < 0.01) cells as compared with I-10 cells and Tcam-2 cells. Transfection of I-10 cells with shRNA1 and shRNA2 resulted in significantly decreased Panx-2 expression (P < 0.05) and significantly reduced cell surviving fraction (P < 0.001). In the presence of cisplatin, the cells in NC group showed a higher clonogenic efficiency than those in shRNA1 and shRNA2 groups (P < 0.001). The early-stage apoptosis rate of the cells in shRNA1 and shRNA2 groups were significantly higher than that in NC group (P < 0.01). Panx-2 knockdown in I-10 cells significantly increased caspase-3 and Bax expressions (P < 0.05) and significantly decreased the expression of Bcl-2 (P < 0.01). CONCLUSIONS: Down-regulation of Panx-2 channel enhances cisplatin-induced apoptosis in cultured testicular cancer cells.


Assuntos
Neoplasias Testiculares , Antineoplásicos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino , Conexinas , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino
5.
Medicine (Baltimore) ; 99(33): e21695, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872042

RESUMO

BACKGROUND AND OBJECTIVES: Chemotherapy does not only affect cancer cells; it also affects, to a greater or lesser degree, all other cells in the body. This toxicity should be assessed according to its severity, frequency, and duration, taking into account objective and subjective dimensions in its assessment. This assessment is a highly relevant aspect when providing care to chemotherapy patients, mainly due to the impact of the treatment on the patient's quality of life, as well as the vital risk it may imply under certain circumstances. For all this, the objective of this study was to assess the relationship between chemotherapy-associated adverse reactions and health-related quality of life in breast cancer patients. MATERIALS AND METHODS: With this purpose, a descriptive cross-sectional study was developed on 110 breast cancer patients who were treated with docetaxel, epirubicin, and cyclophosphamide. RESULTS: It is worth highlighting the negative effect of nausea, dysgeusia, peripheral neuropathy, loss of appetite, myalgia, and peripheral edema on the quality of life. Likewise, it is worth mentioning peripheral neuropathy as the toxicity that affects a greater number of quality-of-life indicators. CONCLUSIONS: To sum up, it would be necessary to make health professionals aware of the importance of chemotherapy-associated adverse reactions.


Assuntos
Atividades Cotidianas/psicologia , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Neoplasias da Mama/psicologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
6.
Medicine (Baltimore) ; 99(33): e21705, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872045

RESUMO

The optimal treatment strategy of newly diagnosed stage I/II, extranodal nasal-type natural killer/T cell lymphoma (NKTCL) remains unclear. This prospective phase II trial was conducted to explore the short-term and the long-term efficacy and safety of upfront concurrent chemoradiotherapy (CCRT) followed by pegaspargase, gemcitabine, dexamethasone, cisplatin (P-GDP) regimen in patients newly diagnosed with early stage NKTCL.Thirty patients newly diagnosed with stage I/II NKTCL were enrolled from January 2013 to December 2016, and treated as the following strategy: upfront CCRT with cisplatin weekly (25 mg/m) for 5 weeks, followed by 3 cycles of P-GDP regimen chemotherapy (pegaspargase 2500IU/m capped at 3750IU, intramuscular on day 4, gemcitabine 850 mg/m intravenous on days 1 and 8; dexamethasone 40 mg/day intravenous on days 1 to 4; and cisplatin 20 mg/m intravenous on days 1-3) 3 weeks after the completion of CCRT. The objective response rate (ORR) and the complete response (CR) rate were the primary endpoints, and the secondary endpoints were the overall survival (OS), progression-free survival (PFS), and the adverse event (AE).The median follow-up period was 51.5 months (range, 5-78months). The ORR was 93.3% (28/30) and all these 28 patients attained CR at the end of the treatment. Two patients suffered from lymphoma associated hemophagocytic syndrome (LAHS) during the period of consolidation chemotherapy and died within 2 months. The 5-year OS was 93.3%, and the 5-year PFS was 89.4%Mucositis was the most common grades 3/4 nonhematologic AEs (10%, 3/30) of CCRT. During the P-GDP chemotherapy, vomiting (6.7%, 2/30), neutropenia (43.3%, 13/30) and thrombocytopenia (23.3%, 7/30) were the major grades 3/4 toxicities during chemotherapy. No treatment-related deaths occurred.The upfront CCRT followed by P-GDP regimen chemotherapy is an effective and well-tolerated first-line treatment strategy for patients diagnosed with early stage NKTCL. Further investigation of larger sample size is warranted.


Assuntos
Antineoplásicos/uso terapêutico , Quimiorradioterapia/métodos , Quimioterapia de Consolidação/métodos , Linfoma Extranodal de Células T-NK/terapia , Neoplasias Nasais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/métodos
7.
Medicine (Baltimore) ; 99(35): e22042, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871961

RESUMO

BACKGROUND: Many cancer patients experience gastrointestinal adverse reaction during chemotherapy. Pharmacological interventions are commonly used to treat chemotherapy-induced gastrointestinal side effects but have various limitations. Clinical trials have indicated that moxibustion may alleviate gastrointestinal dysfunction and improve quality of life (QoL) after chemotherapy. This study aims to assess the efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction through a systematic review and meta-analysis. METHODS: All randomized controlled trials (RCTs) related to moxibution targeting chemotherapy-induced gastrointestinal adverse reaction will be searched in online databases, such as PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP Database) and WanFang Database from their inception to May 1, 2020. The primary outcome is the incidence and severity of chemotherapy-related gastrointestinal toxicities (nausea and vomiting, diarrhea and constipation). The secondary outcomes include the quality of life, biological parameters' alteration, and adverse events. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 researchers. The Cochrane Collaboration's Review Manager (RevMan 5.3) software will be used to conduct the direct meta-analysis. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of chemotherapy-induced gastrointestinal adverse reaction with moxibustion. CONCLUSION: The conclusion of this study will provide evidence to judge whether moxibustion is an effective and safety therapeutic intervention for chemotherapy-induced gastrointestinal adverse reaction. PROSPERO REGISTRATION NUMBER: CRD42020182990.


Assuntos
Gastroenteropatias/terapia , Moxibustão , Antineoplásicos/efeitos adversos , Gastroenteropatias/induzido quimicamente , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
8.
Medicine (Baltimore) ; 99(33): e21559, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872006

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice. METHODS: Pubmed, Embase, the Cochrane Library, and 3 Chinese literature databases were systematically searched. Randomized controlled trials comparing standard regimen (5-hydroxytryptamine-3 receptor antagonist and glucocorticoid) with aprepitant triple regimen (aprepitant plus the standard regimen) for preventing CINV were screened. Literature selection, data extraction, and quality evaluation were performed by 2 reviewers independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the meta-analysis using RevMan 5.3 software. RESULTS: A total of 51 randomized controlled trials were finally included in the systematic review. Compared with the standard regimen, the aprepitant triple regimen significantly improved the complete response in the overall (OR 1.88, 95% CI 1.71-2.07), acute (OR 1.96, 95% CI 1.65-2.32) and delayed (OR 1.96, 95% CI 1.70-2.27) phases, regardless of emetogenic risk of chemotherapy. Aprepitant could also significantly enhance the proportions of patients who have no emesis, nausea, or use of rescue medication respectively in the overall, acute and/or delayed phases. Aprepitant was found to be associated with decreased risk of constipation (OR 0.85, 95% CI 0.74-0.97), but increased the incidence of hiccup (OR 1.26, 95% CI 1.05, 1.51). There were no statistically significant differences between the 2 groups on other safety outcomes. CONCLUSION: The aprepitant triple regimen is effective for the prevention of CINV in patients being treated with moderately or highly emetogenic chemotherapy, and has a significant tendency to reduce the risk of constipation and increase the incidence of hiccup.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Aprepitanto/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Humanos , Náusea/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente
9.
J UOEH ; 42(3): 261-266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879190

RESUMO

Radiation recall pneumonitis is a phenomenon in which a recall-triggering drug induces an acute inflammatory reaction in the lungs, corresponding to a previously irradiated area. Radiation recall reactions have been reported to occur following treatments with various cytotoxic anticancer agents and molecular-targeting drugs; however, only a few reports have described immune checkpoint inhibitor-induced radiation recall pneumonitis. We report a case of radiation recall pneumonitis induced by pembrolizumab in a patient with the postoperative local recurrence of non-small cell lung cancer. This case demonstrated that pembrolizumab might cause severe radiation recall pneumonitis, even after typical radiation pneumonitis has been resolved.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Assintomáticas , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/etiologia , Radioterapia/efeitos adversos , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia
10.
Mar Pollut Bull ; 159: 111493, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32736201

RESUMO

The consumption of anticancer agents has increased in the recent decades, and these substances may be present in sewage. Consequently, they may reach the environment when sanitation infrastructure is ineffective. This study evaluated the toxicity of three anticancer agents-Tamoxifen (TAM), Cisplatin (CisPt), and Cyclophosphamide (CP)-on the development of embryos of the sand-dollar Mellita quinquiesperforata. Adult individuals were collected in sandy beaches, and gametes were obtained. Freshly-fertilized eggs were exposed to increasing sets of concentrations of each compound, and the effective concentrations needed to cause a 50% effect in the organisms (EC50) were calculated. The three compounds were toxic, and their EC50 values were 16.78 ± 2.42 ng·L-1 (TAM), 27.20 ± 38.26 ng·L-1 (CisPt), and 101.82 ± 70.96 ng·L-1 (CP). There is no information on the environmental levels of these compounds in Brazil, but as they were already detected in ng·L-1 levels worldwide, it can be expected that these substances pose environmental risks to the marine biota.


Assuntos
Antineoplásicos , Poluentes Químicos da Água/análise , Animais , Brasil , Ecotoxicologia , Ouriços-do-Mar , Testes de Toxicidade
11.
Lancet Haematol ; 7(9): e649-e659, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758434

RESUMO

BACKGROUND: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. We aimed to examine the safety and preliminary activity of avadomide plus obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma. METHODS: CC-122-NHL-001 was a phase 1b dose escalation and expansion study at eight sites in France, Italy, and the Netherlands. Eligible patients (aged ≥18 years) had histologically confirmed CD20-positive relapsed or refractory non-Hodgkin lymphoma, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had received previous treatment. In the dose expansion phase, only patients with previously treated relapsed or refractory follicular lymphoma (grade 1, 2, or 3a) were included. Avadomide was administered in escalating doses and two formulations: active pharmaceutical ingredient in capsule in 1·0 mg, 2·0 mg, 3·0 mg, and 4·0 mg doses and as formulated capsules in 3·0 mg and 4·0 mg doses orally once daily on days 1-5 followed by 2 days off (5-7-day schedule) every week of each 28-day cycle. Obinutuzumab 1000 mg was administered intravenously on days 2, 8, and 15 of cycle 1 and day 1 of cycles 2-8. Primary objectives were to determine the safety and tolerability, the non-tolerated dose, maximum tolerated dose, and recommended phase 2 dose (RP2D). All patients who received treatment were included in the safety analyses. Efficacy-evaluable patients completed at least one cycle of treatment and had baseline and at least one post-baseline assessment. The study is registered with ClinicalTrials.gov, NCT02417285 and EudraCT 2014-003333-26, and is ongoing. FINDINGS: Between June 24, 2015, and Dec 5, 2018, 73 patients were enrolled and treated; 19 had diffuse large B-cell lymphoma, 53 follicular lymphoma, and one marginal zone lymphoma. Median follow-up was 253 days (IQR 127-448). The median number of previous anticancer regimens was three (IQR 2-4). The maximum tolerated dose and non-tolerated dose were not reached in the dose escalation phase. On the basis of safety and pharmacokinetic-pharmacodynamic data, the avadomide RP2D was established as 3·0 mg as formulated capsules on a 5-7-day schedule in combination with 1000 mg of obinutuzumab. Patients enrolled in the expansion cohort received the established RP2D of avadomide. Across all doses, three patients had dose-limiting toxicities; one patient treated at the RP2D had dose-limiting toxicity (grade 3 sepsis). The most common adverse events of grade 3 and above were neutropenia (41 [56%] of 73) and thrombocytopenia (17 [23%] of 73). 34 (47%) patients had serious adverse events, which were considered to be avadomide-related in 23 (32%) of 73 patients and obinutuzumab-related in 20 (27%) of 73 patients. Two treatment-related deaths occurred, one owing to tumour flare and one from acute myeloid leukaemia after study discontinuation. INTERPRETATION: Avadomide plus obinutuzumab has a manageable toxicity, being a tolerable treatment option for most patients. Although the prespecified threshold for activity was not met in the trial, we believe that the preliminary antitumour activity of cereblon modulators plus next-generation anti-CD20 antibodies in heavily pretreated relapsed or refractory non-Hodgkin lymphoma warrants further investigation as a chemotherapy-free option in this setting. FUNDING: Celgene Corporation.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidonas/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/patologia , Piperidonas/efeitos adversos , Piperidonas/farmacocinética , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Recidiva , Índice de Gravidade de Doença , Trombocitopenia/etiologia , Trombocitopenia/patologia , Resultado do Tratamento
12.
Phytochemistry ; 178: 112479, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768717

RESUMO

Seven undescribed germacranolides, named as scabertopinolide A-G were obtained from whole herbs of Elephantopus scaber L. The determination of their structures was conducted via comprehensive spectroscopic analyses combined with experimental electronic circular dichroism (ECD) spectroscopic data and quantum mechanical ECD calculations. The absolute configuration of scabertopinolide A was determined by X-ray crystallography data analysis. The cytotoxicity of all compounds was evaluated against three human cancer cell lines HepG2, Hep3B (human hepatocellular carcinoma cell lines), and MCF-7 (human breast adenocarcinoma cell line). Scabertopinolide G exhibited the most significant cytotoxic activities against the three cancer cell lines with IC50 values between 7.0 and 10.3 µM. Furthermore, flow cytometry analysis has suggested that scabertopinolide G may cause death of cancer cells through apoptosis induction.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Asteraceae , Neoplasias Hepáticas , Linhagem Celular Tumoral , Humanos , Sesquiterpenos de Germacrano
13.
Medicine (Baltimore) ; 99(34): e21807, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846818

RESUMO

BACKGROUND: Huaier granules, the aqueous product of Huaier (Trametes robiniophila Murr.) extract, are a broad-spectrum anti-tumor drug and have been widely used for the treatment of gastric cancer (GC). The aim of this study is to systematically investigate the efficacy and safety of Huaier granules combined with chemotherapy in the treatment of GC. METHODS: Three English databases and four Chinese databases will be searched from its inception to July 2020. Two methodological trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.2 and stata 14.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Huaier granules combined with chemotherapy is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/9BVJD.


Assuntos
Misturas Complexas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Misturas Complexas/efeitos adversos , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Trametes
14.
Medicine (Baltimore) ; 99(34): e21826, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846826

RESUMO

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment. METHOD: The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS. RESULT: A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028). CONCLUSION: Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/efeitos adversos , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Fumar Cigarros , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Pneumonia/induzido quimicamente , Intervalo Livre de Progressão , Taxa de Sobrevida
15.
Medicine (Baltimore) ; 99(34): e21876, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846844

RESUMO

BACKGROUND: Cancer continues to be a severe global health problem and the leading cause of death worldwide. Chemotherapy as the main treatment has various side effects, of which marrow suppression is the most common one. Acupuncture had shown clinical effects for marrow suppression after chemotherapy in many studies. However, the efficacy and safety of acupuncture therapy for marrow suppression after chemotherapy remains unclear. OBJECTIVE: This protocol aims to evaluate the efficacy and safety of acupuncture for marrow suppression after chemotherapy according to the existing randomized controlled trials. METHODS AND ANALYSIS: The randomized controlled trials on acupuncture therapy for marrow suppression after chemotherapy will be searched in the database of Embase, PubMed and Cochrane Library, Allied and Complementary Medicine Database (AMED), Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), and related registration platforms (WHO ICTRP, Clinical Trials, and Chinese Clinical Trial Register [ChiCTR]), Grey Literature Database from inception to 1 August 2020. The primary outcomes will be assessed using white blood cell (WBC) count, platelet count, hemoglobin count and the number of neutrophils (N). Review Manager V.5.3 software will be applied for statistical analyses. We will measure the risk of bias of the included studies with Cochrane Collaboration Risk of Bias Tool. Finally, Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) will be used to grade the overall quality of evidence. And we will use the intra-group correlation coefficient to assess the consistency of reviewers. RESULT: This systematic review and meta-analysis will put a high-quality synthesis of the efficacy and safety of acupuncture treatment in marrow suppression after chemotherapy. CONCLUSION: The conclusion of this systematic review will provide evidence to assess acupuncture therapy is an efficacy and safe intervention to treat and control marrow suppression after chemotherapy. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020163336.


Assuntos
Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Células da Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Tratamento Farmacológico/métodos , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos/métodos , Masculino , Neoplasias/tratamento farmacológico , Neutrófilos/citologia , Contagem de Plaquetas/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
16.
Science ; 369(6505): 793-799, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32792392

RESUMO

Monoclonal antibodies (mAbs) targeting human antigen CD20 (cluster of differentiation 20) constitute important immunotherapies for the treatment of B cell malignancies and autoimmune diseases. Type I and II therapeutic mAbs differ in B cell binding properties and cytotoxic effects, reflecting differential interaction mechanisms with CD20. Here we present 3.7- to 4.7-angstrom cryo-electron microscopy structures of full-length CD20 in complexes with prototypical type I rituximab and ofatumumab and type II obinutuzumab. The structures and binding thermodynamics demonstrate that upon binding to CD20, type II mAbs form terminal complexes that preclude recruitment of additional mAbs and complement components, whereas type I complexes act as molecular seeds to increase mAb local concentration for efficient complement activation. Among type I mAbs, ofatumumab complexes display optimal geometry for complement recruitment. The uncovered mechanisms should aid rational design of next-generation immunotherapies targeting CD20.


Assuntos
Anticorpos Monoclonais Humanizados/química , Complexo Antígeno-Anticorpo/química , Antígenos CD20/química , Antineoplásicos/química , Imunoterapia , Linfoma de Células B/terapia , Rituximab/química , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo Antígeno-Anticorpo/imunologia , Antígenos CD20/imunologia , Antineoplásicos/imunologia , Linfócitos B/imunologia , Ativação do Complemento , Microscopia Crioeletrônica , Humanos , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/imunologia , Ligação Proteica , Conformação Proteica , Rituximab/imunologia , Rituximab/uso terapêutico
17.
J Med Life ; 13(2): 138-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742504

RESUMO

Treatment with anticancer drugs such as cyclophosphamide can harm the male reproductive system. Vitamin C and zinc are micronutrients with antioxidant activity and are the essential components of semen. Therefore, this study aimed to evaluate whether cyclophosphamide-exposed mice can recover from fertility with vitamin C and zinc therapy. In this experimental study, fifty male mice were divided into five groups. Groups 1-4 received cyclophosphamide (100 mg/kg, once a week for eight weeks). Also, group 2 received zinc (200 mg/kg), group 3 received vitamin C (300 mg/kg), group 4 received zinc and vitamin C (200 mg/kg and 300 mg/kg, respectively), five times per week for eight weeks, and group 5 received normal saline once a week and water five days a week for eight weeks. The data collected were statistically analyzed using SPSS 22. Results showed a significant increase in mount latency and a significant decrease in the number of sperms in the cyclophosphamide group compared to the control group. However, mount latency has been significantly decreased in mice treated with cyclophosphamide plus zinc compared to the cyclophosphamide group. The study also showed that the sperm count in the group that received cyclophosphamide and zinc had been increased compared to the cyclophosphamide group; the other treatments have decreased mount latency and increased the sperm count compared to the group treated with cyclophosphamide but not significantly. The Tubule Differentiation Index showed an increase in the cyclophosphamide-Zinc-Vitamin C group in comparison with the cyclophosphamide group. The current study showed that zinc could improve cyclophosphamide-induced toxicity of the reproductive system in male mice.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Substâncias Protetoras/farmacologia , Reprodução/efeitos dos fármacos , Zinco/farmacologia , Animais , Ácido Ascórbico/administração & dosagem , Ciclofosfamida/efeitos adversos , Hormônios/metabolismo , Humanos , Masculino , Camundongos , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
18.
PLoS Comput Biol ; 16(8): e1008041, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745136

RESUMO

Hypoxia-activated prodrugs (HAPs) present a conceptually elegant approach to not only overcome, but better yet, exploit intra-tumoural hypoxia. Despite being successful in vitro and in vivo, HAPs are yet to achieve successful results in clinical settings. It has been hypothesised that this lack of clinical success can, in part, be explained by the insufficiently stringent clinical screening selection of determining which tumours are suitable for HAP treatments. Taking a mathematical modelling approach, we investigate how tumour properties and HAP-radiation scheduling influence treatment outcomes in simulated tumours. The following key results are demonstrated in silico: (i) HAP and ionising radiation (IR) monotherapies may attack tumours in dissimilar, and complementary, ways. (ii) HAP-IR scheduling may impact treatment efficacy. (iii) HAPs may function as IR treatment intensifiers. (iv) The spatio-temporal intra-tumoural oxygen landscape may impact HAP efficacy. Our in silico framework is based on an on-lattice, hybrid, multiscale cellular automaton spanning three spatial dimensions. The mathematical model for tumour spheroid growth is parameterised by multicellular tumour spheroid (MCTS) data.


Assuntos
Antineoplásicos/farmacologia , Hipóxia Celular/fisiologia , Modelos Biológicos , Pró-Fármacos/farmacologia , Microambiente Tumoral/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Biologia Computacional , Simulação por Computador , Humanos , Radiação Ionizante , Radioterapia , Esferoides Celulares , Células Tumorais Cultivadas
19.
Ther Deliv ; 11(8): 521-534, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32757745

RESUMO

Nanoscale size-dependent properties give nanomaterials unique specifications that are robust in many applications of human medicine. Gold nanoparticles (AuNPs) have recently gained attention because of their unique optical, physical and electrical properties. AuNPs increase the efficacy of biomedical applications in diagnostic treatments for infectious diseases, by targeting or labeling target cells/bioactive compounds. However, it is imperative to develop the regimens for more accurate diagnostic tools, preventive care and effective therapy. Our critical and comprehensive review presents emerging avenues of molecular diagnostics as well as therapeutics translated into clinical approaches. This manuscript critically reviews the rampant future of AuNPs in the diagnosis and treatment of the most important diseases, such as cancer and viruses of respiratory system.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Portadores de Fármacos/química , Humanos , Pneumopatias/diagnóstico , Pneumopatias/terapia , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Pandemias , Fototerapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/virologia
20.
Molecules ; 25(16)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784680

RESUMO

Cardiac glycosides (CGs) have a long history of treating cardiac diseases. However, recent reports have suggested that CGs also possess anticancer and antiviral activities. The primary mechanism of action of these anticancer agents is by suppressing the Na+/k+-ATPase by decreasing the intracellular K+ and increasing the Na+ and Ca2+. Additionally, CGs were known to act as inhibitors of IL8 production, DNA topoisomerase I and II, anoikis prevention and suppression of several target genes responsible for the inhibition of cancer cell proliferation. Moreover, CGs were reported to be effective against several DNA and RNA viral species such as influenza, human cytomegalovirus, herpes simplex virus, coronavirus, tick-borne encephalitis (TBE) virus and Ebola virus. CGs were reported to suppress the HIV-1 gene expression, viral protein translation and alters viral pre-mRNA splicing to inhibit the viral replication. To date, four CGs (Anvirzel, UNBS1450, PBI05204 and digoxin) were in clinical trials for their anticancer activity. This review encapsulates the current knowledge about CGs as anticancer and antiviral drugs in isolation and in combination with some other drugs to enhance their efficiency. Further studies of this class of biomolecules are necessary to determine their possible inhibitory role in cancer and viral diseases.


Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Glicosídeos Cardíacos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Ensaios Clínicos como Assunto , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores Imunológicos/farmacologia , Transdução de Sinais/efeitos dos fármacos
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