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2.
J Clin Oncol ; 39(7): 704-712, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492986

RESUMO

PURPOSE: As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% (P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , China , Cromossomos Humanos Par 11 , DNA Viral/genética , Progressão da Doença , Feminino , Herpesvirus Humano 4/genética , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/secundário , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Intervalo Livre de Progressão , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Repressoras/genética , Fatores de Tempo , Carga Viral , Adulto Jovem , Variante 6 da Proteína do Fator de Translocação ETS
3.
Ther Adv Med Oncol ; 12: 1758835920963925, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149768

RESUMO

AIM: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa. METHODS: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A. RESULTS: In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm (p < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm (p < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B). CONCLUSION: The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population.Trial Registration: ClinicalTrials.gov identifier: NCT02763566.

4.
J Clin Oncol ; 38(34): 3987-3998, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32954927

RESUMO

PURPOSE: Many patients with HR+, HER2- early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2- advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. METHODS: This open-label, phase III study included patients with HR+, HER2-, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse-free survival, overall survival, and safety. RESULTS: At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone (P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. CONCLUSION: Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2- node-positive EBC at high risk of early recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto Jovem
5.
Oncologist ; 25(10): e1481-e1491, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32406563

RESUMO

BACKGROUND: Molecular subtyping of triple-negative breast cancers (TNBCs) via gene expression profiling is essential for understanding the molecular essence of this heterogeneous disease and for guiding individualized treatment. We aim to devise a clinically practical method based on immunohistochemistry (IHC) for the molecular subtyping of TNBCs. MATERIALS AND METHODS: By analyzing the RNA sequencing data on TNBCs from Fudan University Shanghai Cancer Center (FUSCC) (n = 360) and The Cancer Genome Atlas data set (n = 158), we determined markers that can identify specific molecular subtypes. We performed immunohistochemical staining on tumor sections of 210 TNBCs from FUSCC, established an IHC-based classifier, and applied it to another two cohorts (n = 183 and 214). RESULTS: We selected androgen receptor (AR), CD8, FOXC1, and DCLK1 as immunohistochemical markers and classified TNBCs into five subtypes based on the staining results: (a) IHC-based luminal androgen receptor (IHC-LAR; AR-positive [+]), (b) IHC-based immunomodulatory (IHC-IM; AR-negative [-], CD8+), (c) IHC-based basal-like immune-suppressed (IHC-BLIS; AR-, CD8-, FOXC1+), (d) IHC-based mesenchymal (IHC-MES; AR-, CD8-, FOXC1-, DCLK1+), and (e) IHC-based unclassifiable (AR-, CD8-, FOXC1-, DCLK1-). The κ statistic indicated substantial agreement between the IHC-based classification and mRNA-based classification. Multivariate survival analysis suggested that our IHC-based classification was an independent prognostic factor for relapse-free survival. Transcriptomic data and pathological observations implied potential treatment strategies for different subtypes. The IHC-LAR subtype showed relative activation of HER2 pathway. The IHC-IM subtype tended to exhibit an immune-inflamed phenotype characterized by the infiltration of CD8+ T cells into tumor parenchyma. The IHC-BLIS subtype showed high expression of a VEGF signature. The IHC-MES subtype displayed activation of JAK/STAT3 signaling pathway. CONCLUSION: We developed an IHC-based approach to classify TNBCs into molecular subtypes. This IHC-based classification can provide additional information for prognostic evaluation. It allows for subgrouping of TNBC patients in clinical trials and evaluating the efficacy of targeted therapies within certain subtypes. IMPLICATIONS FOR PRACTICE: An immunohistochemistry (IHC)-based classification approach was developed for triple-negative breast cancer (TNBC), which exhibited substantial agreement with the mRNA expression-based classification. This IHC-based classification (a) allows for subgrouping of TNBC patients in large clinical trials and evaluating the efficacy of targeted therapies within certain subtypes, (b) will contribute to the practical application of subtype-specific treatment for patients with TNBC, and (c) can provide additional information beyond traditional prognostic factors in relapse prediction.


Assuntos
Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/genética , China , Quinases Semelhantes a Duplacortina , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Recidiva Local de Neoplasia , Prognóstico , Proteínas Serina-Treonina Quinases , Neoplasias de Mama Triplo Negativas/genética
6.
Mitochondrial DNA B Resour ; 5(3): 3170-3171, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-33458099

RESUMO

Symphoricarpos sinensis is an important ornamental plant in China. Due to the lack of efficient molecular markers, although recent studies supported that Symphoricarpos was phylogenetically closely related to Lonicera, Triosteum, Heptacodium, and Leycesteria, relationships among these taxa remained uncertain. To examine the phylogenetic position of Symphoricarpos within Caprifoliaceae, we characterized the complete chloroplast (cp) genome of S. sinensis. The results showed that S. sinensis shared a typical quadripartite structure as with most angiosperms. It was 155,738 bp in length, including two inverted repeat (IR) regions (24,010 bp), a small single-copy (SSC) region (18,942 bp) and a large single-copy (LSC) region (88,776 bp). Phylogenetic analysis demonstrated that Caprifoliaceae and Adoxaceae formed two distinct monophyletic clades, and S. sinensis was closely related to lonicera and Triosteum, albeit with low support. The whole cp genome of S. sinensis will be useful resources for future studies on phylogeny and conservation in Symphoricarpos.

8.
Immunopharmacol Immunotoxicol ; 41(3): 386-393, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30422018

RESUMO

Objective: Recently, immune checkpoints blockers showed higher anti-tumor activity for advanced gastric cancer (GC). The purpose of the study is to find out predictive biomarkers related to anti-cytotoxic lymphocyte antigen 4 (CTLA4) therapy. Materials and methods: Datasets of gene expression omnibus (GEO), the cancer genome atlas (TCGA), and gene set enrichment analysis (GESA) were extracted. Differential expression of CTLA4 between cancer tissues and normal mucosa, enrichment of WT (wild type) vs. CTLA4_KO (knockout) upregulated gene set and clinical significance were analyzed. The expression of CTLA4, CD3, and granzyme A (GZMA) were validated on 30 cases of Chinese GC. Microsatellite instability (MSI) marker MLH1 and Epstein-Barr virus (EBV) marker EBER were examined on 30 cases of Chinese GC by immunohistochemistry and in situ hybridization. Results: CTLA4 was upregulated in GC tissue relative to normal mucosa in datasets of GSE27342 (fold change = 1.586, p < .001) and GSE63089 (fold change = 1.365, p < .001). Increased CTLA4 expression was positively related to CTLA4 activation. EBV-associated GC (EBVaGC) and microsatellite instability GC (MSIGC) disclosed higher CTLA4 levels than other GCs. Genomic stability GC (GSGC) also showed higher enrichment score of CTLA4 activation. CTLA4 activation resulted in shorter overall survival in GC. The expression level of CTLA4 was well correlated to expression levels of GZMA (R = 0.701, p < .001) and CD3 (R = 0.750, p < .001). Conclusions: Based on bioinformatics analysis, GSGC should be worth noticed as a potential GC subtypes responsive to anti-CTLA4 treatment.


Assuntos
Antígeno CTLA-4 , Bases de Dados de Ácidos Nucleicos , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Gástricas , Povo Asiático , Antígeno CTLA-4/biossíntese , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , China , Feminino , Humanos , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
9.
J Glob Oncol ; 3(5): 583-595, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29094098

RESUMO

PURPOSE: The number of cancer cases in China has increased rapidly from 2.1 million in 2000 to 4.3 million in 2015. As a consequence, pain management as an integral part of cancer treatment became an important health care issue. In March 2011, the Good Pain Management (GPM) program was launched to standardize the treatment of cancer pain and improve the quality of life for patients with cancer. With this work, we will describe the GPM program, its implementation experience, and highlight key lessons that can improve pain management for patients with cancer. METHODS: We describe procedures for the selection, implementation, and assessment procedures for model cancer wards. We analyzed published results in areas of staff training and patient education, pain management in practice, analgesic drugs administration, and patient follow-up and satisfaction. RESULTS: Pain management training enabled medical staff to accurately assess the level of pain and to provide effective pain relief through timely dispensation of medication. Patients with good knowledge of treatment of pain were able to overcome their aversion to opioid drugs and cooperate with nursing staff on pain assessment to achieve effective drug dose titration. Consumption of strong opioid drugs increased significantly; however, there was no change for weaker opioids. Higher pain remission rates were achieved for patients with moderate-to-severe pain levels. Proper patient follow-up after discharge enabled improved outcomes to be maintained. CONCLUSION: The GPM program has instituted a consistent and high standard of care for pain management at cancer wards and improved the quality of life for patients with cancer.

10.
Pathol Oncol Res ; 23(1): 47-53, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27342248

RESUMO

We aimed to investigate the influence of radiation on hypoxia-treated breast cancers cells and its underlying mechanism. We mimicked the hypoxic response in MCF-7 cells by the treatment of CoCl2. Meanwhile, hypoxic MCF-7 cells induced by CoCl2 or untreated MCF-7 cells were treated with or without radiation, and then treated with or without hypoxia inducible factors-1α (HIF-1α) inhibitor. Subsequently, glucose update and lactate release rate were determined by commercial kits, as well as the expressions of HIF-1α and the glucose metabolic pathway related genes, including fructose biphoshatase 1 (FBP1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and isocitrate dehydrogenase 2 (IDH20) were detected by western blotting and/or RT-PCR. The results showed that glucose uptake rate and lactate release rate were increased in cells under hypoxia and/or radiation condition compared with untreated cells (p < 0.05), while the addition of HIF-1α inhibitor decreased these rates in hypoxia + radiation treated cells (p < 0.05). In addition, compared with untreated cells, the mRNA and protein levels of HIF-1α were significantly increased under hypoxia and radiation condition (p < 0.05), while which decreased after the addition of HIF-1α inhibitor (p < 0.05). Similar content changing trends (all p < 0.05) were observed in FBP1, IDH2, GLUT1, and LDHA but not HK2. In conclusion, the combination of radiation and hypoxia could promote the glucose metabolism. Furthermore, HIF-1α might inhibit the promoting effect of radiation on glycolysis in hypoxic MCF-7 cells by regulating the glucose metabolic pathway.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Cobalto/fisiologia , Glucose/metabolismo , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Transportador de Glucose Tipo 1/metabolismo , Hexoquinase/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Células MCF-7 , RNA Mensageiro/metabolismo
11.
International Eye Science ; (12): 2170-2173, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-669204

RESUMO

AIM:To investigate the efficacy and visual sensitivity of occlusion therapy combined training for children with ametropic amblyopia.METHODS:Totally 85 children (85 eyes) with anisometropic amblyopia treated in our hospital from January 2013 to January 2015 were selected.All patients were given occlusion therapy combined training.Statistical analysis of clinical efficacy and visual sensitivity changes were taken,and the changes of visual acuity,AULCSF,S Frmax were analyzed.RESULTS:The visual acuity after therapy was significantly better than that before treatment (1.12±0.29 vs0.45±0.25,P<0.01);AULCSF,Smax and Frmax all increased,the difference between the two groups was statistically significant (P< 0.05).The sensitivity of the same spatial frequency was significantly higher than that before treatment,the difference was statistically significant (P < 0.05),and the contrast sensitivity decreased gradually with the increase of spatial frequency.There were statistical differences in the total effective rate of different refractive degrees after treatment (P=0.001).Mild group and moderate group had no significant difference on the total clinical efficiency difference (x2=3.091,P=0.079);between mild group and severe group total effective rate was significantly different (x2 =11.471,P =0.001);the moderate and severe groups total clinical efficiency were no significantly different (x2 =3.359,P=0.067).In addition,the total efficiency rate of wearing glasses under the age of 6 was significantly higher than that after 6 years old (95% vs 77%),statistical difference between the two groups was significant (P<0.05).CONCLUSION:Masking therapy combined with comprehensive training,in the treatment of children with ametropic amblyopia,and wearing a corrective spectacles,is desirable,especially for children under 7 years of age.

12.
Sci Rep ; 6: 34388, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27677242

RESUMO

Neoadjuvant Chemotherapy has been used for the stage III of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, the survival benefits of radiation therapy added in induction regimens remains controversial. We therefore conducted a meta-analysis of the published clinical trials to quantitatively evaluate the benefit of preoperative chemoradiotherapy. After searching the database of Pubmed, CNKI, EMBASE, ESMO, The Cochrane Library databases, The American Society of Clinical Oncology and Clinical Trials.gov. Trials were selected for meta-analysis if they provided an independent assessment of neoadjuvant chemoradiation and neoadjuvant chemotherapy, odds ratio(OR) for tumor downstaging, mediastinal lymph nodes pathological complete response and local control, hazard ratios (HRs) for 5-year survival and progression-free survival were pooled by the stata software version 12.0. Twelve studies involving 2,724 patients were identified, tumor downstaging (p = 0.01), mediastinal lymph nodes pathological complete responses (p = 0.028) and local control (P = 0.002) were achieved, when compared with neoadjuvant chemotherapy. The meta-analysis demonstrated neither 5-year survival nor progression-free-survival benefit in survival from adding radiation. In conclusion, the addition of radiotherapy into chemotherapy was not superior to neoadjuvant chemotherapy. The higher quality of trials need be investigated combining with the histopathological type and genotyping of lung cancer by clinicians.

13.
Mol Med Rep ; 12(1): 119-26, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25738436

RESUMO

Estrogen receptors (ERs) are important for preventing endotoxin-induced myocardial dysfunction. Therefore, plant-derived phytoestrogens, which target ERs may also affect endotoxin-induced toxicity in cardiomyocytes. Our previous study revealed that notoginsenoside-R1 (NG-R1), a predominant phytoestrogen from Panax notoginseng, protects against cardiac dysfunction. However, the effects of NG-R1 on cardiomyocytes and the precise cellular/molecular mechanisms underlying its action remain to be elucidated. In the present study, pretreatment with NG-R1 suppressed the lipopolysaccharide (LPS)-induced degradation of inhibitor of nuclear factor-κB (NF-κB) α, the activation of NF-κB and caspase-3, and the subsequent myocardial inflammatory and apoptotic responses in H9c2 cardiomyocytes. An increase in the mRNA and protein expression of ERα was also observed in the NG-R1-treated cardiomyocytes. However, the expression pattern of ERß remained unaltered. Furthermore, the cardioprotective properties of NG-R1 against LPS-induced apoptosis and the inflammatory response in cardiomyocytes were attenuated by ICI 182780, a non-selective ERα antagonist, and methyl-piperidino-pyrazole, a selective ERα antagonist. These findings suggested that NG-R1 reduced endotoxin-induced cardiomyocyte apoptosis and the inflammatory response via the activation of ERα. Therefore, NG-R1 exerted direct anti-inflammatory and anti-apoptotic effects on the cardiomyocytes, representing a potent agent for the treatment of myocardial inflammation during septic shock.


Assuntos
Receptor alfa de Estrogênio/biossíntese , Ginsenosídeos/administração & dosagem , Inflamação/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Choque Séptico/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Endotoxinas/toxicidade , Receptor alfa de Estrogênio/metabolismo , Regulação da Expressão Gênica , Ginsenosídeos/química , Humanos , Inflamação/induzido quimicamente , Inflamação/complicações , Inflamação/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , NF-kappa B/biossíntese , Panax notoginseng/química , RNA Mensageiro/biossíntese , Ratos , Choque Séptico/complicações , Choque Séptico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa
14.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(4): 486-9, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24812910

RESUMO

OBJECTIVE: To evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats. METHODS: The DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively. RESULTS: The tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05). CONCLUSIONS: Genistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.


Assuntos
Proliferação de Células/efeitos dos fármacos , Genisteína/farmacologia , Neoplasias Mamárias Experimentais/patologia , Nitrilas/farmacologia , Triazóis/farmacologia , 17-Hidroxiesteroide Desidrogenases/metabolismo , Anastrozol , Animais , Linhagem Celular Tumoral , Estradiol/metabolismo , Feminino , Genisteína/administração & dosagem , Neoplasias Mamárias Experimentais/induzido quimicamente , Nitrilas/administração & dosagem , Ovariectomia , Pós-Menopausa , Ratos , Ratos Sprague-Dawley , Triazóis/administração & dosagem
15.
Pathol Oncol Res ; 20(3): 619-24, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24414992

RESUMO

Tumor-associated macrophages (TAMs) have been correlated with increased angiogenesis and poor prognosis in breast cancer. However, the precise role of TAMs in tamoxifen resistance remains unclear. We used immunohistochemical method to examine the expression of epidermal growth factor receptor (EGFR) and CD163+ macrophages in 100 breast cancer tissues. The clinical and biological features of 100 patients were estrogen receptor (ER)-positive and human epidermal growth factor receptor 2(Her-2)-negative tumors. The tamoxifen resistant tissues (n = 48) were the surgical excision samples from patients who developed recurrence or metastasis at the time of adjuvant tamoxifen treatment. The tamoxifen resistant tissues were contrast to tamoxifen sensitive tissues (n = 52). Positive staining for EGFR and CD163+ macrophages were observed in 21 samples (43.8 %) and in 26 samples (54.2 %) respectively in tamoxifen resistance group, which were higher than that of tamoxifen sensitive group (P = 0.001 and P = 0.000279 respectively). Significant positive correlations were found between the expression of EGFR and CD163+ macrophages (r = 0.567, P < 0.01). CD163+ macrophages were positively correlated with tumor size, lymph node metastasis and obesity. Obesity was also related to tamoxifen resistance (P < 0.05). The patients with higher density of CD163+ macrophages infiltration suffered from shorter time to develop recurrence or metastasis (P < 0.05). TAMs may be associated with tamoxifen resistance. Further studies are needed to investigate the potential mechanism between TAMs and tamoxifen resistance.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Macrófagos/patologia , Pós-Menopausa/efeitos dos fármacos , Tamoxifeno/farmacologia , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Receptores ErbB/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
16.
Int J Mol Sci ; 14(9): 18973-88, 2013 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-24065098

RESUMO

Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-ß-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC) and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049). The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007). This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole.


Assuntos
Inibidores da Aromatase/uso terapêutico , Aromatase/genética , Neoplasias da Mama/genética , Nitrilas/uso terapêutico , Triazóis/uso terapêutico , 17-Hidroxiesteroide Desidrogenases/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Anastrozol , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Estudos Retrospectivos , Análise de Sobrevida
17.
Artigo em Chinês | MEDLINE | ID: mdl-24490394

RESUMO

OBJECTIVE: To explore the effect of Pulsatilla chinensis (Bunge) Regel saponins (PRS) against juvenile and adult Schistosoma japonicum and to compare its efficacy with praziquantel (PZQ) in vitro. METHODS: 3 h, 7 d, 14 d schistosomula and 42 d adult schistosomes were incubated with 0, 1, 5, 10, 20 and 30 microg/ml PRS for 4, 24, 48 and 72 hours, then the states of them were observed. The changes of the surface of S. japonicum incubated with 30 microg/ml PRS and PZQ within 4 hours were observed by a scanning electron microscope. RESULTS: The sensitivity of 3 h, 7 d, 14 d schistosomula and adults of S. japonicum to 1, 5, 10, 20, 30 microg/ml PRS displayed a time and dose dependence. All the worms died in 30 microg/ml PRS after 4 hours. The dead worm body appeared a gray-white color accompanied with their altered morphogenesis and opaque body. The tegumental surface of adults with different degrees of damages was observed by the electron microscope within 4 hours affected by PRS in vitro. CONCLUSIONS: The effects of PRS against S. japonicum in different developmental stages in vitro show that PRS may eventually have a therapeutic potential in the treatment or prevention of S. japonicum infection and is expected to become a new anti-schistosome drug.


Assuntos
Anti-Helmínticos/farmacologia , Pulsatilla/química , Saponinas/farmacologia , Schistosoma japonicum/efeitos dos fármacos , Envelhecimento , Animais , Praziquantel/farmacologia
18.
Breast Cancer Res Treat ; 134(1): 307-13, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22527106

RESUMO

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/patologia , Relações Médico-Paciente , Pós-Menopausa , Padrões de Prática Médica , Estudos Prospectivos , Inquéritos e Questionários
19.
Clin Lymphoma Myeloma Leuk ; 11(1): 33-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21454188

RESUMO

BACKGROUND: We analyzed a database from our hospital comprised of 31 cases of primary breast lymphoma (PBL) that included treatment and follow-up information during the past 30 years, and investigated the correlation between microvessel density (MVD) and survival in patients with PBL. PATIENTS AND METHODS: We reviewed all patients diagnosed with primary breast lymphoma from June 1977 to March 2007. Patient demographics such as survival, recurrence, and time to follow-up were recorded, in addition to surgical, radiation, and/or chemotherapy treatment(s). We also assessed microvessel density (MVD) in the pretreatment breast lump of 31 previously untreated patients using α-CD34 immunohistochemical staining. RESULTS: All 31 patients were female ranging in age from 37 years to 75 years. Diffuse large B-cell lymphoma was the most common histologic diagnosis. According to the staging of Wiseman and Liao, 17 patients (55%) were stage IE, and 14 patients (45%) were stage IIE. Treatment that included radiation therapy in stage I patients (node negative) improve the survival rate and lowered the recurrence rates. Treatment that included chemotherapy in stage II patients (node positive) showed benefits in terms of higher survival rate and lower recurrence rate. Increasing microvessel density is a weak but statistically significant predictor of lower survival overall. CONCLUSION: Nodal status predicts the outcome and guides the use of radiation and chemotherapy. There is no statistical difference between the different types of operative methods. Patients with high MVD measured in the microenvironment had worse survival overall than PBL patients with low expression.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linfoma/patologia , Linfoma/terapia , Adulto , Idoso , Neoplasias da Mama/irrigação sanguínea , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Taxa de Sobrevida
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