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1.
Nat Prod Res ; : 1-5, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38087981

RESUMO

Three new cadinene sesquiterpenoids 1-3, were isolated from the aerial sections of Ageratina adenophora using various chromatographic techniques. Their structures were characterised by comprehensive spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The cytotoxic activity of new compounds 1-3 were evaluated by testing in vitro tumour growth inhibitory rate against five human tumour cell lines, HL-60, A-549, SMMC-7721, MDA-MB-231, and SW480.

2.
Medicine (Baltimore) ; 102(51): e36753, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134099

RESUMO

To summarize the clinical characteristics and explore the risk factors for miscarriage of a viable intrauterine pregnancy following surgical intervention in patients with heterotopic pregnancy (HP). A total of 106 women diagnosed with HP that underwent surgical intervention in the Women's Hospital School of Medicine Zhejiang University between January 2014 and December 2021 were included in this retrospective study. They were divided into a miscarriage group (n = 13) and an ongoing pregnancy group (n = 93) according to the outcomes of the HP within 2 weeks after surgery. Data regarding clinical characteristics, surgical conditions, postoperative recovery, and complications were collected and compared between the groups. Logistic multivariate analysis was performed to explore the risk factors for miscarriage in patients with HP within 2 weeks of surgical intervention. Among the 106 women with HP, 80 had tubal HP, 8 had cornual HP, and 18 had interstitial HP. Eighty-seven (82.1%) patients developed clinical symptoms that manifested primarily as abnormal vaginal bleeding and/or abdominal pain, whereas 19 (17.9%) patients had no clinical symptoms. The mean gestational age on the day of surgery was 7.2 weeks (inter-quartile range, 6.4-8.3). The miscarriage rate within 2 weeks of surgical intervention was 12.3% in patients with HP. Compared to the ongoing pregnancy group, the miscarriage group had a higher body mass index, earlier gestational age at treatment, and higher volume of hemoperitoneum (P < .05 for all). Logistic multivariate analysis indicated that the women with a hemoperitoneum volume > 200 mL had significantly higher risk of miscarriage after adjusting covariates [OR (odds ratio) = 5.285, 95% CI (confidence interval) (1.152-24.238), P < .05]. Hemoperitoneum volume was independently associated with miscarriage of viable intrauterine pregnancies in patients with HP within 2 weeks of surgical intervention.


Assuntos
Aborto Espontâneo , Gravidez Heterotópica , Gravidez , Humanos , Feminino , Recém-Nascido , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Gravidez Heterotópica/epidemiologia , Gravidez Heterotópica/cirurgia , Gravidez Heterotópica/diagnóstico , Estudos Retrospectivos , Hemoperitônio , Fatores de Risco
3.
Nutr Cancer ; 75(5): 1340-1348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36988095

RESUMO

Vitamin D (VD) plays a regulatory role in tumor occurrence and development, although the factors influencing serum 25-hydroxyvitamin D3 (25(OH)D3) levels in patients with cancer have not been studied. Therefore, we aimed to evaluate circulating levels of 25(OH)D3 and factors influencing the VD status in patients with malignant tumors. Adult patients with malignant tumors who had undergone assessments of serum 25(OH)D3 at Beijing Cancer Hospital from January 2019 to July 2022 were included. A multiple logistic regression model was applied to explore the associations of patient characteristics, environment, and disease characteristics with 25(OH)D3 levels. Among the 1,076 included patients, the median 25(OH)D3 serum concentration was 16.25 ng/mL. VD deficiency and the combined VD insufficiency and sufficiency were observed in 811 (75.37%) and 265 (24.63%) patients, respectively. Latitude, season, sex, body mass index, and type of cancer were associated with VD concentration/status in patients with malignant tumors. 25(OH)D3 concentrations were significantly higher in patients with thyroid cancer and significantly lower in patients receiving tumor-related treatment than in untreated patients. Surprisingly, we observed 25(OH)D3 serum concentration was lower in patients receiving nutritional supplementation than in those receiving no nutritional supplements. Patients with malignant tumors are at high risk of VD deficiency.


Assuntos
Neoplasias da Glândula Tireoide , Deficiência de Vitamina D , Adulto , Humanos , Vitamina D , Vitaminas , Calcifediol , Suplementos Nutricionais
4.
J Oncol ; 2023: 9432073, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36793375

RESUMO

Objective: This research intends to investigate the clinical efficacy of radiofrequency ablation and electrocautery in treating grade I or II vaginal intraepithelial neoplasia (VaIN). Methods: This is a single-center retrospective study, which collected the clinical data of 100 patients with VaIN diagnosed by colposcopy and pathological biopsy in the Gynecology and Cervical Center of Xiangzhu Branch of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2020 and June 2021. Patients were divided into the study group (radiofrequency ablation treatment) and the control group (electrocautery) according to differences in treatment approaches. 6- and 12-month follow-ups were performed on all patients. Gynecological examination results, liquid-based thin-layer cytology (TCT), negative conversion of human papillomavirus (HPV), curative effects, and prognosis were recorded. Results: All patients completed regular follow-ups that lasted for 6 and 12 months. The 6- and 12-month cure rates of the study group were 76.0% and 92.0%, respectively, and the data in the control group were 70.0% and 82.0%, respectively. In terms of the 6- and 12-month negative conversion rates of HPV, the data in the study group were 68.0% and 78.0%, versus 60% and 68% in the control group, respectively. The lesion duration rate showed no statistical significance between the study group (8.0%) and the control group (P > 0.05). The analysis of postoperative follow-up complications revealed that the study group had a statistically lower overall incidence of vaginal bleeding, excessive vaginal discharge, vaginal burning sensation, and decreased vaginal elasticity than the control group (8.0% vs. 24.0% P < 0.05). Conclusion: Both radiofrequency ablation and electrocautery have obvious clinical effects in patients with grade I or II VaIN, but the former contributed to fewer operative complications and a good prognosis, which deserves clinical promotion.

5.
World J Clin Cases ; 10(22): 7772-7784, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36158484

RESUMO

BACKGROUND: Non-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumor types. Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years, the prognosis remains poor. Therefore, it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis. AIM: To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients. METHODS: We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas (TCGA) database. We also collected samples from 85 NSCLC patients from the First People's Hospital of Jingzhou City and retrospectively followed the patients. Multivariate Cox regression analysis and survival analysis were performed. RESULTS: Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival: TP53 (P = 0.79), PTEN (P = 0.94), RB1 (P = 0.49), CTNNB1 (P = 0.24), STK11 (P = 0.32), and PIK3CA (P = 0.013). However, the probability of multiple genes (TP53, PTEN, RB1, and STK11) affecting survival was 0.025. Retrospective analysis of clinical data revealed that sex (hazard ratio [HR] = 1.29; [95%CI: 0.64-2.62]), age (HR = 1.05; [95%CI: 1.02-1.07]), smoking status (HR = 2.26; [95%CI: 1.16-4.39]), tumor histology (HR = 0.58; [95%CI: 0.30-1.11]), cancer stage (HR = 16.63; [95%CI: 4.8-57.63]), epidermal growth factor receptor (EGFR) mutation (HR = 1.82; [95%CI: 1.05-3.16]), abundance (HR = 4.95; [95%CI: 0.78-31.36]), and treatment with tyrosine kinase inhibitors (TKIs) (HR = 0.58; [95%CI: 0.43-0.78]) affected patient survival. Co-occurring mutations of TP53, PTEN, RB1, and STK11 did not significantly affect the overall survival of patients receiving chemotherapy (P = 0.96) but significantly affected the overall survival of patients receiving TKIs (P = 0.045). CONCLUSION: Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

6.
J Chemother ; 34(7): 472-482, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34877924

RESUMO

We conducted a meta-analysis to determine if MTHFR polymorphisms are effective biomarkers for non-small cell lung cancer (NSCLC) patient survival and pemetrexed (PEM) treatment toxicity. Because of data heterogeneity, fixed or random effects models were chosen, and pooled HRs and 95% confidence intervals (CIs) were calculated. No correlation between MTHFR 677 C > T polymorphism and progression-free survival (PFS) or overall survival (OS) was detected in NSCLC patients; however, patients with the T allele benefited more than those with the wild-type allele. Two papers reported hematologic toxicity of single-agent PEM treatment in patients with the MTHFR 677 C > T polymorphism. However, data on MTHFR polymorphisms and toxicity could not be combined, even though publication bias and sensitivity analysis results were stable and reliable. We conclude that the MTHFR 677 C > T polymorphism could not predict PEM efficacy in NSCLC patients; however, the T allele may increase the risk of haematological toxicity. A large-scale clinical trial is recommended.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pemetrexede/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética
7.
Bioengineered ; 12(1): 3322-3335, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34224325

RESUMO

Long non-coding RNAs (lncRNAs) are the new regulators and biomarkers for various tumors. However, in cervical cancer (CC), the potential roles of lncRNAs are not well characterized. This research aimed at exploring the roles of MEOX2 antisense RNA 1(MEOX2-AS1) in CC progression and the underlying mechanisms. The examination of MEOX2-AS1 levels in CC specimens and cell lines was conducted by RT-PCR. Loss-of-function experiments were performed for the assays of proliferation, migration, and invasion of CC cells after various treatments. Animal experiments were applied for the determination of the effects of MEOX2-AS1 in vivo. Bioinformatics analysis, together with dual-luciferase reporter assays, was applied to demonstrate the possible relationships among MEOX2-AS1, miR-143-3p and VDAC1. In the paper, we reported that MEOX2-AS1 levels were distinctly upregulated in CC cells and tissues, and higher MEOX2-AS1 expressions indicated a poor clinical outcome. Besides, STAT1 could activate transcriptions of MEOX2-AS1 by binding directly to its promoter region. The silence of MEOX2-AS1 suppressed the metastatic and proliferative ability of CC cells, as revealed by functional assays. Mechanistically, MEOX2-AS1 sponged miR-143-3p to regulate VDAC1 expressions. Furthermore, miR-143-3p inhibitor reversed the anti-proliferation and anti-metastasis effect of MEOX2-AS1 knockdown. Overall, the data indicated that the MEOX2-AS1/miR-143-3p/VDAC1 pathway participated in CC progression, making it a novel therapeutic target for CC cures.


Assuntos
MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT1/genética , Neoplasias do Colo do Útero , Canal de Ânion 1 Dependente de Voltagem/genética , Adulto , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT1/metabolismo , Regulação para Cima/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo
8.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278503

RESUMO

Non­small cell lung cancer (NSCLC), which accounts for ~85% of all lung cancer cases, is commonly diagnosed at an advanced stage and has a high patient mortality rate. Despite the increasing availability of treatment strategies, the prognosis of patients with NSCLC remains poor, with a low 5­year survival rate. This poor prognosis may be associated with the tumor heterogeneity of NSCLC, as well as its acquisition and intrinsic resistance to therapeutic drugs. It has been suggested that combination therapy with telomerase inhibition may be an effective strategy for the treatment of drug­sensitive and drug­resistant types of cancer. Telomerase is the key enzyme for cell survival, and ~90% of human cancers maintain telomeres by activating telomerase, which is driven by the upregulation of telomerase reverse transcriptase (TERT). Several mechanisms of telomerase reactivation have been described in a variety of cancer types, including TERT promoter mutation, epigenetic modifications via a TERT promoter, TERT amplification, and TERT rearrangement. The aim of the present study was to comprehensively review telomerase activity and its association with the clinical characteristics and prognosis of NSCLC, as well as analyze the potential mechanism via which TERT activates telomerase and determine its potential clinical application in NSCLC. More importantly, current treatment strategies targeting TERT in NSCLC have been summarized with the aim to promote discovery of novel strategies for the future treatment of NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Telomerase/genética , Telomerase/metabolismo , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Epigênese Genética , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/enzimologia , Terapia de Alvo Molecular , Mutação , Prognóstico , Taxa de Sobrevida , Telomerase/antagonistas & inibidores
9.
PLoS One ; 15(12): e0241806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33306692

RESUMO

In this study, we investigated the changes in the distribution and regulation of endogenous hormones in Phyllostachys edulis 'Pachyloen' during bamboo shooting. Enzyme-linked immunosorbent assay was used to measure the mass fractions of indole-3-acetic acid (IAA), gibberellic acid (GA), zeatin riboside (ZR), and abscisic acid (ABA) in rhizomes, shoots, and maternal bamboo organs during shoot sprouting, shoot growth, and new-bamboo formation. Measurements were compared among bamboo parts and developmental periods. The overall mass fractions of IAA and ABA were significantly higher than those of ZR and GA, driven by differences among bamboo parts and developmental periods. The abundance of each endogenous hormone varied among bamboo parts and developmental periods. During bamboo shooting, ABA had the highest mass fraction in all bamboo parts sampled, followed by IAA, GA, and ZR. Among bamboo parts, rhizomes had more IAA, ZR, and GA than the other parts, but significantly less ABA. Winter shoots had higher ZR: IAA and GA: IAA ratios than rhizomes and maternal bamboo organs. During shoot growth, ABA was the most abundant hormone in rhizomes and maternal bamboo organs, followed by IAA, ZR, and GA. In contrast, IAA was the most abundant hormone in spring shoots, followed by ABA, ZR, and GA. Maternal bamboo organs had a significantly higher ZR: GA ratio, and significantly lower IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes. Spring shoots had significantly higher IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes and maternal bamboo organs; significantly higher ZR mass fractions, and ZR: GA and ZR: IAA ratios and significantly lower ABA mass fractions than rhizomes; and significantly higher GA: IAA ratio than maternal bamboo organs. During new-bamboo formation, ABA was the most abundant hormone in rhizomes, winter shoots, and maternal bamboo organs, followed by IAA, ZR, and GA. Maternal bamboo organs had significantly lower IAA mass fractions and significantly higher ABA mass fractions than rhizomes and new bamboo tissue. IAA and ABA abundances exhibited an inverse relationship in rhizomes and maternal bamboo organs. GA: ABA and GA: IAA ratios decreased gradually and other hormone ratios exhibited parabolic trends over the bamboo-shooting period, with the highest ratios observed in new bamboo tissues. Overall, the coordination or antagonism among endogenous hormones plays a key regulatory role in bamboo shoot growth. The formation of thick walls in P. edulis 'Pachyloen', one of its major traits, may be partially attributed to the relatively high IAA and ZR and low GA mass fractions.


Assuntos
Reguladores de Crescimento de Plantas/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Poaceae/crescimento & desenvolvimento , Ácido Abscísico/análise , Ácido Abscísico/metabolismo , Giberelinas/análise , Giberelinas/metabolismo , Ácidos Indolacéticos/análise , Ácidos Indolacéticos/metabolismo , Isopenteniladenosina/análogos & derivados , Isopenteniladenosina/análise , Isopenteniladenosina/metabolismo , Reguladores de Crescimento de Plantas/análise , Brotos de Planta/metabolismo , Poaceae/metabolismo , Rizoma/crescimento & desenvolvimento , Rizoma/metabolismo
10.
Cell Death Dis ; 11(11): 982, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191401

RESUMO

Residual disease is the major cause for colorectal cancer (CRC) relapse. Herein, we explore whether and how a natural molecule CADPE killed heterogenic populations in a panel of CRC cell lines with KRAS/BRAF mutations that are natively resistant to EGFR- or VEGFR-targeted therapy, without sparing persistent cells, a reservoir of the disease relapse. Results showed that CADPE killed the tumor bulk and residual cells in the panel of CRC cell lines, rapidly inactivated c-Myc, STAT3, and NF-κB, and then decreased the protein levels of key signaling molecules for CRC, such as ß-catenin, Notch1, and the nodes of mTOR pathways; eukaryotic translation initiation factors (eIF4F); anti-apoptotic proteins (Bcl-xl, Mcl-1, and survivin); and stemness-supporting molecules (CD133, Bim-1, and VEGF). In terms of mechanism of action, concurrent downregulation of Mcl-1, Bcl-xl, and survivin was necessary for CADPE to kill CRC bulk cells, while additional depletion of CD133 and VEGF proteins was required for killing the residual CRC cells. Moreover, the disabled c-Myc, STAT3, NF-κB, and eIF4F were associated with the broadly decreased levels of anti-apoptosis proteins and pro-stemness proteins. Consistently, CADPE suppressed CRC tumor growth associated with robust apoptosis and depleted levels of c-Myc, STAT3, NF-κB, eIF4F, anti-apoptotic proteins, and pro-stemness proteins. Our findings showed the promise of CADPE for treating CRC and suggested a rational polytherapy that disables c-Myc, STAT3, NF-κB, and eIF4F for killing CRC residual disease.


Assuntos
Ácidos Cafeicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , Animais , Ácidos Cafeicos/farmacologia , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução de Sinais
11.
World J Clin Cases ; 8(19): 4380-4387, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083397

RESUMO

BACKGROUND: It is not known whether percutaneous radiofrequency ablation (PRFA) has the same treatment efficacy and fewer complications than laparoscopic resection in patients with small centrally located hepatocellular carcinoma (HCC). AIM: To compare the effectiveness of PRFA with classical laparoscopic resection in patients with small HCC and document the safety parameters. METHODS: In this retrospective study, 85 patients treated with hepatic resection (HR) and 90 PRFA-treated patients were enrolled in our hospital from July 2016 to July 2019. Treatment outcomes, including major complications and survival data, were evaluated. RESULTS: The results showed that minor differences existed in the baseline characteristics between the patients in the two groups. PRFA significantly increased cumulative recurrence-free survival (hazard ratio 1.048, 95%CI: 0.265-3.268) and overall survival (hazard ratio 0.126, 95%CI: 0.025-0.973); PRFA had a lower rate of major complications than HR (7.78% vs 20.0%, P < 0.05), and hospital stay was shorter in the PRFA group than in the HR group (7.8 ± 0.2 d vs 9.5 ± 0.3 d, P < 0.001). CONCLUSION: Based on the data obtained, we conclude that PRFA was superior to HR and may reduce complications and hospital stay in patients with small HCC.

12.
J Pharm Pharmacol ; 72(11): 1528-1535, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32737884

RESUMO

OBJECTIVES: To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs). METHODS: Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated. KEY FINDINGS: In the genotype-toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3-4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes. CONCLUSIONS: The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.


Assuntos
Glucuronosiltransferase/genética , Irinotecano/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Variantes Farmacogenômicos , Inibidores da Topoisomerase I/administração & dosagem , Administração Metronômica , Idoso , Povo Asiático/genética , China/epidemiologia , Feminino , Genótipo , Glucuronosiltransferase/metabolismo , Humanos , Irinotecano/efeitos adversos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/etnologia , Tumores Neuroendócrinos/mortalidade , Farmacogenética , Testes Farmacogenômicos , Fenótipo , Reação em Cadeia da Polimerase , Intervalo Livre de Progressão , Inibidores da Topoisomerase I/efeitos adversos
13.
J Zhejiang Univ Sci B ; 21(1): 64-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31898443

RESUMO

Proteasome inhibitors have shown remarkable success in the treatment of hematologic neoplasm. There has been a lot of attention to applying these drugs for solid tumor treatment. Recent preclinical study has signified the effectiveness on cell proliferation inhibition in lung adenocarcinoma treated by carfilzomib (CFZ), a second generation proteasome inhibitor. However, no insight has been gained regarding the mechanism. In this study, we have systematically investigated the CFZ functions in cell proliferation and growth, cell cycle arrest, and apoptosis in lung adenocarcinoma cells. Flow cytometry experiments showed that CFZ significantly induced G2/M cell cycle arrest and apoptosis in lung adenocarcinoma. MTS and colony formation assays revealed that CFZ substantially inhibited survival of lung adenocarcinoma cells. All results were consistently correlated to the upregulation expression of Gadd45a, which is an important gene in modulating cell cycle arrest and apoptosis in response to physiologic and environmental stresses. Here, upregulation of Gadd45a expression was observed after CFZ treatment. Knocking down Gadd45a expression suppressed G2/M arrest and apoptosis in CFZ-treated cells, and reduced cytotoxicity of this drug. The protein expression analysis has further identified that the AKT/FOXO3a pathway is involved in Gadd45a upregulation after CFZ treatment. These findings unveil a novel mechanism of proteasome inhibitor in anti-solid tumor activity, and shed light on novel preferable therapeutic strategy for lung adenocarcinoma. We believe that Gadd45a expression can be a highly promising candidate predictor in evaluating the efficacy of proteasome inhibitors in solid tumor therapy.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Oligopeptídeos/farmacologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteína Forkhead Box O3/fisiologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Regulação para Cima
14.
Medicine (Baltimore) ; 98(31): e16392, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374006

RESUMO

RATIONALE: Vandetanib is effective for treating symptomatic or progressive medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease, but its toxicity such as photosensitivity reactions should be considered. It is a rare adverse effect of this drug but might cause severe morbidity and even mortality. PATIENT CONCERNS: A 26-year man with MTC developed phototoxic rashes on the sun-exposed areas of his shin after 15 days from the initiation of vandetanib treatment. Grade II skin toxicity was evaluated based on the Common Terminology Criteria for Adverse Events standard. DIAGNOSES: Drug-induced phototoxic rash. INTERVENTIONS: The vandetanib dose was reduced by 30%, and the application of topical steroids and sunscreen was adopted. OUTCOMES: After dose reduction of vandetanib, the symptoms of vandetanib-induced phototoxic rash resolved, although residual pigmentation was observed. LESSONS: Close attention should be paid to the adverse effect of vandetanib, phototoxic rash, and patients should be advised on the prevention and treatment measures.


Assuntos
Dermatite Fototóxica/etiologia , Piperidinas/efeitos adversos , Quinazolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Masculino , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico
15.
Nat Prod Res ; 33(6): 827-834, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29224369

RESUMO

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3-11 was synthesised from 5-hydroxy-3,7,3',4'-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC50 values of 9.51-53.33 µM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4-9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
16.
Cancer Chemother Pharmacol ; 83(1): 71-79, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30357449

RESUMO

PURPOSE: Insufficient serum metabolite concentrations of tamoxifen can compromise treatment efficacy in patients with breast cancer. The purpose of this meta-analysis was to explore correlations between cytochrome P450 (CYP) 2D6*10 gene polymorphisms and serum concentrations of tamoxifen and its active metabolites in patients with breast cancer in Asia. METHODS: The study included a systematic literature search for cohort studies published before March 2018 in English databases (PubMed, Embase, Cochrane Library, and Web of Science) and Chinese databases (Chinese National Knowledge Infrastructure and Wan Fang database). The meta-analysis was performed using RevMan 5.3 software. Pooled means and standard deviations were calculated with 95% confidence intervals. Publication bias and sensitivity analyses were also performed using STATA 14.0. RESULTS: In total, 7 studies and 552 patients were included in the meta-analysis. Serum concentrations of endoxifen were significantly different in each CYP2D6*10 genotype group (p < 0.05). The CC genotype was associated with higher concentrations of 4-OH-TAM than the CT/TT genotype (p < 0.05). However, there were no statistically significant between-group differences in serum concentrations of TAM (p > 0.05). Publication bias and sensitivity analyses confirmed that the meta-analysis results were stable and reliable. CONCLUSIONS: CYP2D6*10 polymorphisms influence the pharmacokinetics of tamoxifen in patients with breast cancer in Asia.


Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Citocromo P-450 CYP2D6/genética , Polimorfismo Genético , Tamoxifeno/farmacocinética , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Ásia/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Tamoxifeno/farmacologia , Distribuição Tecidual , Resultado do Tratamento
17.
Front Pharmacol ; 9: 1007, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356711

RESUMO

Background: Studies have shown that perioperative inflammatory response is one of the important factors that caused postoperative cognitive dysfunction (POCD). Ulinastatin is a broad-spectrum protease inhibitor that inhibits inflammatory. We investigated the effects of ulinastatin on inflammatory response and early postoperative cognitive function in elderly patients undergoing spinal surgery. Methods: This clinical trial was approved by the Xuanwu Hospital Ethical Committee (Registration number: ChiCTR-IPR-16008931). Sixty elderly patients undergoing elective spinal surgery with American Society of Anesthesiologists (ASA) status of I-II were randomized into ulinastatin and control groups; total intravenous anesthesia was performed. The elderly patients in ulinastatin group underwent intravenous infusion of ulinastatin 10,000 units/kg following anesthesia induction and before surgical incision, and 5000 units/kg on post-operative days 1 and 2. Cognitive function was determined with Montreal Cognitive Assessment (MOCA) test preoperatively and on post-operative day 7 by a neurologist. Serum lipopolysaccharide (LPS), interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloprotease-9 (MMP-9) concentration levels were measured at baseline, the end of surgery, and on post-operative days 1 and 3. Results: All elderly patients completed the study. Ulinastatin infusion significantly reduced the incidence of POCD in elderly patients undergoing spine surgery (ulinastatin group 16% vs. control group 43%, χ 2 = 5.079, P = 0.024, P < 0.05). The elderly patients in ulinastatin group exhibited lower serum LPS, IL-6, CRP, and MMP-9 concentrations, as well as a shortened peak value duration, compared with those in the control group following surgery (P < 0.05). Conclusion: Systemic inflammation and translocation of LPS were inhibited by the infusion of ulinastatin in elderly patients undergoing spinal surgery. The anti-inflammation intervention with ulinastatin can significantly improve the elderly patients' postoperative cognitive function.

18.
Comb Chem High Throughput Screen ; 21(10): 801-805, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30605052

RESUMO

BACKGROUND: Esophageal cancer (EC) is a common digestive system tumor, characterized by high invasion, apparent lethality, and poor prognosis. Direct diffusion is the major metastatic mechanism of early EC, whereas advanced EC is spread mainly by lymphatic metastasis, but also can be transferred to the liver, lungs, bones, and so on, by hematogenous metastasis. The incidence of bone metastasis in esophageal cancer is low, and maxillary metastasis of EC is more rare. OBJECTIVE: To explore the differential diagnosis in ECMM, the rare metastasis of EC, and the possible mechanisms and predictors of bone metastasis. METHODS: The clinical materials of a male patient with maxillary metastasis of esophageal cancer (ECMM) were analyzed. Then, the possible mechanism of the ECMM was discussed. CONCLUSION: ECMM may belong to the hematogenous metastasis. The early detection of rare sites of metastasis of EC should be prioritized in tumor marker detection, imaging, pathology, and other diagnostic techniques.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Esofágicas/diagnóstico , Idoso , Neoplasias Ósseas/diagnóstico , Humanos , Masculino
19.
Onco Targets Ther ; 10: 3071-3081, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28790841

RESUMO

PURPOSE: A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type. PATIENTS AND METHODS: Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81). Blood samples for detecting UGT1A1 were collected from each patient after various administration regimens. RESULTS: Colorectal cancer patients with the UGT1A1*6 mutant genotype had a significantly higher risk of severe delayed diarrhea than that of wild-type individuals when administered a CPT-11 dose ≥130 mg/m2 (P=0.042); the same phenomenon was observed when the UGT1A1*6 and UGT1A1*28 mutant genotypes were considered together (P=0.028). However, in lung cancer patients administered a low dose of CPT-11, UGT1A1*6/*28 variants were not significantly associated with severe neutropenia or delayed diarrhea. Furthermore, adult patients with the UGT1A1*6 mutation were more likely to develop severe delayed diarrhea than did wild-type adults (P=0.013); however, the difference was not significant in elderly patients. No significant differences in tumor response were found among the different genotypes (P>0.05). CONCLUSION: Thus, age and tumor type influence our ability to predict adverse reactions based on UGT1A1 gene polymorphisms in cancer patients. Further, UGT1A1 gene polymorphisms are not correlated with the efficacy of CPT-11-based regimens.

20.
Ultrastruct Pathol ; 41(3): 245-251, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28414554

RESUMO

OBJECTIVE: To investigate the antitumour efficacy of pachymic acid (PA), which is a fungal extract component, on nasopharyngeal carcinoma (NPC) cells CNE-1, CNE-2. METHODS: We have chosen NPC cell line CNE-2 for the study, and the cells were treated with PA before the detection. CCK-8 assay was used to detect the proliferative ability, and Annexin V-PI double staining was used for the detection of apoptosis rate; and the nucleus damage was detected by transmission electron microscope, the protein expression of the DNA damage pathway were detected by Western blot. RESULTS: PA can significantly inhibited proliferation of CNE-1, CNE-2 cells. The proportion of apoptotic cells of all cell lines gradually increased in a dose-dependent manner induced by PA, P < 0.05. Meanwhile, the nucleus could be caused morphological changes and the expression of DNA damage-related proteins was upregulated by PA in CNE-2. CONCLUSIONS: PA can significantly inhibit cell proliferation and increase the apoptosis rates and may induce the apoptosis of the human NPC cells.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Nasofaríngeas/patologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma/tratamento farmacológico , Contagem de Células/métodos , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico
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