RESUMO
Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.
Assuntos
Neoplasias da Mama/mortalidade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Estudos Epidemiológicos , Feminino , Humanos , Análise Multivariada , Metástase Neoplásica , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis. METHODS: A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis. RESULTS: Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467-0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325-0.478, P < 0.001). CONCLUSION: This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.
Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Prognóstico , Estudos Retrospectivos , Programa de SEERRESUMO
This study aimed to investigate the effect of inhibiting the Notch signaling pathway on the radiosensitivity of breast cancer cells. Human breast cancer cell lines (MCF-7 and T47D) were selected and treated with radiation of different doses. Cells were treated with Gamma secretase inhibitor (GSI) to analyze the effects of GSI on the Notch signaling, which were detected by Immunofluorescence assay, RT-qPCR, and Western blot analysis. Besides, Transwell assay, Scratch test, colony formation assay, MTT assay, and flow cytometry were conducted to show the effects of GSI on the invasion and migration, survival fraction, cell viability, and apoptosis of MCF-7 and T47D cells after radiation therapy. Moreover, cell transfection with a dominant negative mutant of RBPJ, the key transcription factor of Notch signaling pathway, were also applied to show the inhibition of Notch signaling pathway. Initially, we found that the 4 Gy radiation activated Notch signaling pathway, and enhanced the invasion and migration of MCF-7 and T47D cells. However, GSI inhibited the Notch signaling pathway, and reversed the enhancement of radiation on the migration and invasion, promoted the enhancement of apoptosis and inhibition of proliferation of MCF-7 and T47D cells induced by radiation. Except that, we also determined that GSI and dnRBPJ suppressed the upregulation of Notch signaling after radiation therapy. Our study demonstrated that inhibition of the Notch signaling pathway enhanced the radiosensitivity of breast cancer cells, which may provide evident for a beneficial adjuvant therapy in the breast cancer treatment.
Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Oligopeptídeos/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Receptores Notch/antagonistas & inibidores , Receptores Notch/metabolismo , Análise de Variância , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Neoplasias da Mama/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Células MCF-7 , Mutação , Invasividade Neoplásica , Radiação Ionizante , Receptores Notch/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , TransfecçãoRESUMO
BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mamografia/métodos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , China , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting. CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4 cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3 weeks for 1 year. CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Linfonodos/patologia , Terapia Neoadjuvante/métodos , Receptor ErbB-2/genética , Antineoplásicos Imunológicos/uso terapêutico , Axila , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/terapia , Quimiorradioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfonodos/cirurgia , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/uso terapêuticoRESUMO
The purpose of this study was to conduct a comparative analysis of the perioperative outcomes associated with robot-assisted laparoscopic prostatectomy (RARP) versus open radical prostatectomy (ORP) in the obese population diagnosed with prostate cancer. We performed a comprehensive search in key databases such as PubMed, Embase, Web of Science, and the Cochrane Library, encompassing studies of all languages, with a final search date of April 2024. We also omitted articles that consisted of conference abstracts and content that was not pertinent to our study. The aggregated outcomes were evaluated utilizing the metrics of weighted mean differences (WMDs) and odds ratios (ORs). A sensitivity analysis was also integrated into our assessment. The meta-analysis was facilitated by employing Stata/MP version 18 software. Additionally, the study was duly registered with PROSPERO under the identifier: CRD 42024540216. This meta-analysis, which included five trials, shows that compared to ORP, RARP is associated with a reduced estimated blood loss (EBL) (WMD -445.77, 95%CI -866.08, -25.45; p = 0.038), a decreased transfusion rate (OR 0.17, 95%CI 0.13, 0.21; p < 0.001), and a diminished overall complication rate (OR 0.71, 95%CI 0.58, 0.86; p = 0.001). No statistically significant differences were found in operative time (OT) (WMD 1.88, 95%CI -46.53, 50.28; p = 0.939) or length of stay (LOS) (WMD -0.41, 95%CI -1.07, 0.25; p = 0.221). Among patients with obesity and prostate cancer, RARP demonstrates advantages over ORP by reducing estimated blood loss, transfusion requirements, and the incidence of complications. Notably, there were no significant differences in operative duration and hospital stay between the two surgical approaches. These findings suggest that RARP could be a preferable surgical option for obese individuals with prostate cancer.
Assuntos
Tempo de Internação , Obesidade , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Obesidade/complicações , Neoplasias da Próstata/cirurgia , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Laparoscopia/métodos , Duração da Cirurgia , Transfusão de Sangue/estatística & dados numéricosRESUMO
This study aims to compare the perioperative, oncological, and functional outcomes of perineal hydrodissection (HD) with standard treatment (ST) in patients undergoing robot-assisted radical prostatectomy. We performed an exhaustive search in databases such as PubMed, Embase, Web of Science, and the Cochrane Library, seeking English-language studies relevant to our research question, with a cutoff date of April 2024. The pooled results were assessed using the weighted mean differences (WMDs), standardized mean differences (SMDs), and odds ratios (ORs) metrics. We also performed a sensitivity analysis. The meta-analysis was conducted utilizing Stata/MP version 18 software. The study was registered with PROSPERO (ID: CRD 42024536400). We included a total of five studies (three RCTs and two retrospective studies). According to the data from the Meta-analysis, the HD group showed positive effects in promoting urinary continence (OR 2.64, 95% CI 1.36, 5.12; p = 0.004 < 0.05) and erectile function (SMD 0.92, 95%CI 0.56, 1.27; p < 0.05) within 3 months after surgery. However, no notable disparities were observed in terms of operative time, estimated blood loss, bilateral nerve-sparing rate, or the rate of positive surgical margin. Perineal hydrodissection can be safely applied in robot-assisted radical prostatectomy (RARP), offering a distinct advantage in functional outcomes compared to those who undergo standard robot-assisted prostatectomy alone.
Assuntos
Períneo , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Períneo/cirurgia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento , Incontinência Urinária/etiologia , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: To investigate the changes in sensitivity to anthracycline and taxanes of human breast cancer cells after RABEX-5 downregulated. METHODS: By constructing a lentiviral vector for RNA interference (RNAi) of RABEX-5 gene and transfected into human breast cancer cell line MCF-7 to silence the express of RABEX-5. Real-time PCR and Western blot were used to detect the silencing effect. The changes in sensitivity to chemotherapeutic drugs of MCF-7/RNAi and its negative control cell lines MCF-7/vector were detected by CCK-8 reagent. RESULTS: Compared with MCF-7 cell and MCF-7/vector cell, the expression of RABEX-5 mRNA and protein was downregulated in MCF-7/RNAi cells. The sensitivity to epirubicin was reduced after downregulating the expression of RABEX-5, the 50% inhibition concentration (IC50) of MCF-7/RNAi [(3.590 0 +/- 0.228 69) microg/mL] was higher than that of MCF-7/Vvector [(1.193 3 +/- 0.187 71) microg/mL, P < 0.05]; while the same effect was not found in docetaxel group, the IC50 were (11.162 7 +/- 0.210 26) microg/mL and (10.536 7 +/- 0.430 97) microg/mL, respectively (P > 0.05). CONCLUSION: Downregulation of RABEX-5 can induce chemoresistance to epirubicin in human breast cancer cell MCF-7; while its effect on sensitivity to docetaxel is not significant. This study can provide a theoretical basis for future research RABEX-5 in the individualized treatment of breast cancer.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Antraciclinas/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Vetores Genéticos/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Lentivirus/genética , Interferência de RNA , Taxoides/farmacologia , TransfecçãoRESUMO
Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.
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 QuestionáriosRESUMO
Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers. Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis. Results: A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRage 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung metastasis =0.48, 95% CI: 0.31-0.74). Conclusions: Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.
RESUMO
Extracellular matrix (ECM) is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronic acid (HA) is a component of the ECM, and hyaluronidase (HAase) is a HA-degrading endoglycosidase. Levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1) is the major tumor-derived HAase. In this study, we detected HYAL1 expression levels in breast cancer cells and tissues, and measured the amount HAase activity in breast cancer cells. Compared with nonmalignant breast cell line HBL-100 and normal breast tissues, HYAL1 were overexpressed in breast cancer cell lines MDA-MB-231, MCF-7, invasive duct cancer tissues and metastatic lymph nodes, respectively. Accordingly, the amount HAase activity in MDA-MB-231 and MCF-7 was higher than that in HBL-100. In addition, knockdown of HYAL1 expression in MDA-MB-231 and MCF-7 cells resulted in decreased cell growth, adhesion, invasion and angiogenesis potential. Meantime, the HYAL1 knockdown markedly inhibited breast cancer cell xenograft tumor growth and microvessel density. Further studies showed that the HYAL1, HYAL2 and HA were elevated in breast cancer, and HYAL1 could downregulate HA expression. In conclusion, HYAL1 may be a potential prognostic marker and therapeutic target in breast cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/enzimologia , Carcinoma Ductal de Mama/patologia , Hialuronoglucosaminidase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Western Blotting , Adesão Celular , Movimento Celular , Proliferação de Células , Progressão da Doença , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Endotélio Vascular/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/genética , Técnicas Imunoenzimáticas , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Veias Umbilicais/citologia , Veias Umbilicais/enzimologia , Veias Umbilicais/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. With the emergence of drug-resistant strains of RSV, new antiviral agents are needed urgently. Gentiana rigescens is a kind of Chinese herb, belonging to Gentianaceae, which has long been used as a folk medicine for curing inflammation, bacterial infection, viral infection, and so on. In this research, polysaccharide designated RG4-1 was isolated from G. rigescens by hot water extraction, ethanol precipitation, and macroreticular adsorbing resin column chromatography, and its antiviral activity, cytotoxicity, and possible antiviral mechanisms were assayed by cytopathogenic effect inhibition assay, 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and plaque reduction assay. RG4-1 was a fructose-binding lectin. In host cell cultures, RG4-1 was found to be an effective antiviral component against RSV. It showed good inhibitory effect against RSV when it was added 2 h after virus infection with 50% effective concentration of 12.86 µg/ml. RG4-1 also displayed its direct inactivation, attachment inhibition effect, and penetration inhibition effect against RSV. A time-dependent experiment was set up to confirm that RG4-1 blocked RSV infection at early stages of the infection. But RG4-1 seemed to be ineffective against intracellular virus and viral biosynthesis.
Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Gentiana/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Criança , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Humanos , Lactente , Sais de Tetrazólio/farmacocinética , Tiazóis/farmacocinética , Fatores de Tempo , Células VeroRESUMO
OBJECTIVE: To study the expression and significance of RABEX-5 and RAB5 in human breast cancer. METHODS: In this study the expression of RABEX-5 and RAB5 mRNA and protein was detected by Immunohistochemical techniques, the reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot assay in 60 cases of breast cancer, 15 cases of breast fibroadenomas and 15 cases of normal breast tissue. The relationship of RABEX-5, RAB5 and the clinic pathological features was also analyzed. RESULTS: Expression of RABEX-5 and RAB5 in breast cancer was obviously higher than that in breast fibroadenomas and normal breast tissue (P < 0.05). RABEX-5 and RAB5 expression level in tumor diameter (T) >5 cm group of human breast cancer was obviously higher than that in T < or =2 cm and 2 < T < or =5 cm group (P < 0.05). RABEX-5 and RAB5 expression level in axillary lymph node positive group was obviously higher than that in negative group (P < 0.05). However, there were no significant differences of RABEX-5 and RAB5 levels between HER-2 (+) group and HER-2 (-) group (P > 0.05), ER (-) group and ER (+) group (P > 0.05), PR (-) group and PR (+) group (P> 0.05), and in histological grade I, II and III, there also were no significant differences of RABEX-5 and RAB5 levels. The expression of RABEX-5 is correlated with RAB5 in both mRNA and protein level. CONCLUSION: RABEX-5 and RAB5 may be involved in the development of breast cancer metastasis.
Assuntos
Neoplasias da Mama/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo , Adulto , Idoso , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas rab5 de Ligação ao GTP/genéticaRESUMO
Quorum sensing (QS) plays an essential role in virulence factor production, biofilm formation, and antimicrobial resistance. As a potent QS inhibitor, hordenine can inhibit both QS and biofilm formation in Pseudomonas aeruginosa and Serratia marcescens. In this work, we tested the QS inhibitory potential of 27 hordenine analogs against QS and biofilm formation in P. aeruginosa and S. marcescens. Among the tested analogs, seven (12, 28, 27, 26, 2, 23, and 7) exhibited strong QS inhibitory activity against P. aeruginosa, five of which (12, 28, 27, 26, and 2) showed better inhibitory activity than hordenine. In addition, seven analogs (28, 12, 23, 7, 26, 2, and 27) exhibited better biofilm inhibition against P. aeruginosa than hordenine. Four analogs (7, 28, 2, and 12) showed QS inhibitory activity against S. marcescens, two of which (7 and 28) demonstrated better inhibitory activity than hordenine. Furthermore, analog 7 showed similar biofilm inhibition against S. marcescens as hordenine. Structure-activity relationship (SAR) analysis indicated that the inhibitory activities of the analogs were related to four factors, i.e., carbon chain length, presence or absence of an α,ß-C[bond, double bond]C bond, amino group with/without lipophilic group, such as methyl group, and hydroxyl group in benzene ring.
RESUMO
OBJECTIVE: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. METHODS: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. CONCLUSION: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.
RESUMO
OBJECTIVE: Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal disease (ESRD), and part of SHPT patients need receive parathyroidectomy (PTX). However, as an important postoperative complication of SHPT, thyrotoxicosis has received little attention. Therefore, in this article, we aimed to study the status of transient thyrotoxicosis after PTX for SHPT patients with ESRD and normal thyroid function. METHODS: A total of 24 SHPT patients with preoperative normal thyroid function, normal thyroglobulin (Tg) and normal thyroid antibodies receiving PTX were enrolled from the Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, from January 2017 to January 2019. Tg, high sensitivity thyrotropin stimulating hormone (sTSH), triiodothyronine (T3), free triiodothyronine (fT3), thyroxine (T4) and free thyroxine (fT4) were evaluated the day before PTX and on day 1, 3 and 5 after PTX. Besides, all enrolled patients were evaluated whether there are symptoms associated with thyrotoxicosis. RESULTS: Among the 24 SHPT patients, 1 case (4.2%), 8 cases (33.3%) and 13 cases (54.2%) had suffered thyrotoxicosis at the first, third and fifth day after surgery, respectively. Serum FT4 level increased significantly from pre-operation (0.68 ± 0.15 ng/dl, normal range 0.59-1.25 ng/dl) to the third day after operation (1.91 ± 0.97 ng/dl, p<0.001) and then gradually decline. The frequencies of serum sTSH lower than the normal level gradually increased from the first day (8.3%) to fifth day (66.7%) after surgery. CONCLUSION: Transient thyrotoxicosis is a common postoperative complication of parathyroidectomy for SHPT patients with ESRD and normal thyroid function, and it is necessary for clinicians to evaluate the perioperative thyroid function to make early diagnosis and appropriate prevention and treatment of thyrotoxicosis.
Assuntos
Hiperparatireoidismo Secundário/cirurgia , Falência Renal Crônica/cirurgia , Complicações Pós-Operatórias/cirurgia , Tireotoxicose/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tireoglobulina/metabolismo , Glândula Tireoide/fisiologia , Glândula Tireoide/cirurgiaRESUMO
PURPOSE: Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective and insensitive. This study is to assess the effect of chemotherapy on cognitive function in breast cancer patients stratified by age using objective electrophysiological measure, the P300 component of event-related potentials (ERPs) with a large sample size. METHODS: Totally, 529 primary breast cancer patients, including 178 cases at initial diagnosis stage and before chemotherapy (Group1), 167 cases during chemotherapy (Group2), and 184 cases post chemotherapy and during follow-up period (Group3), were examined with ERPs (P300 component) to assess the effect of chemotherapy on their cognitive function. RESULTS: There were significant differences of P300 latency in Group2 (364.74 ± 15.73 ms) and Group3 (364.02 ± 17.12 ms, mean follow-up period of 2.42 years) compared with Group1 (355.13 ± 19.47 ms, P < 0.001), respectively. With further age stratification: in patients of < 50 years, P300 latency was significantly prolonged in Group2 and Group3 compared with Group1 (P < 0.001), respectively; in patients of 50-59 years, P300 latency was significantly prolonged in Group2 compared with Group1 (P < 0.05), but without difference in Group1 and Group3 (P>0.05); In patients of ≥ 60 years, there were no differences of P300 latency among three the groups (P>0.05). CONCLUSIONS: It is first suggested by our objective detection data that the side effect of chemotherapy on cognitive functions in breast cancer patients may decrease with age. Electrophysiological cognitive impairments mainly occur in younger breast cancer patients undergoing chemotherapy and would last for years after chemotherapy, which highlights the importance of early intervention for those patients, especially in younger patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer/estatística & dados numéricos , Disfunção Cognitiva/patologia , Potenciais Evocados P300/efeitos dos fármacos , Neoplasias da Mama/patologia , Disfunção Cognitiva/induzido quimicamente , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Inflammation-modulating nutrients and inflammatory markers are established cancer risk factors, however, evidence regarding the association between post-diagnosis diet-associated inflammation and breast cancer survival is relatively sparse. We aimed to examine the association between post-diagnosis dietary inflammatory index (DII®) and risks of all-cause and breast cancer-specific mortality. A total of 1064 female breast cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial prospective cohort, were included in this analysis if they had completed the diet history questionnaire (DHQ). Energy-adjusted DII (E-DIITM) scores were calculated based on food and supplement intake. Cox regression and competing risk models were used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by E-DII tertile (T) for all-cause and breast cancer-specific mortality. With median follow-up of 14.6 years, there were 296 (27.8%) deaths from all causes and 100 (9.4%) breast cancer-specific death. The E-DII was associated with all-cause mortality (HR T3 vs T1, 1.34; 95% CI, 1.01-1.81; P trend, 0.049, Table 2) and breast cancer mortality (HR T3 vs T1, 1.47; 95% CI, 0.89-2.43; P trend, 0.13; multivariable-adjusted HR for 1-unit increment: 1.10; 95% CI: 1.00-1.22). Non-linear positive dose-response associations with mortality from all causes were identified for E-DII scores (P non-linearity < 0.05). The post-diagnosis E-DII was statistically significantly associated with mortality risk among breast cancer survivors. Long-term anti-inflammatory diet might be a means of improving survival of breast cancer survivors.
RESUMO
This study aimed to examine the factors related to the ability to obtain nipple aspirate fluids in Chinese women and to evaluate the diagnostic value of carcinoembryonic antigen (CEA) in nipple aspiration fluids. Cross-sectional and case-control studies were used to examine the factors associated with the ability to obtain nipple aspiration fluids. A matched case-control study was used to explore the association of CEA level in nipple aspiration fluids with breast disease. CEA level was log10-transformed to normalize the distribution. Univariate and multivariate logistic regression were adopted to analyze the variables in relation to obtaining fluid and the association of its CEA levels and breast diseases. Receiver operating characteristic curve was used to evaluate the value of CEA levels for the detection of breast disease. The nipple aspiration fluid collection rate was 34.24% (201 of 587). Multivariate logistic regression analysis results showed the following to be significantly associated with a greater ability to obtain nipple aspiration fluids: earlier age at menarche [odds ratio (OR), 2.61; 95% confidence interval (95% CI), 1.15-5.91], lactating>12 months (OR, 2.28; 95% CI, 1.44-3.60), wet-type ear wax (OR, 3.80; 95% CI, 2.39-6.02), and fatty diet (OR, 1.56; 95% CI, 1.02-2.39). CEA levels in nipple aspiration fluids of cancerous breasts were significantly higher than those from breasts with benign disease and healthy controls (ORadj, 5.39; P<0.01). However, the sensitivity of CEAs was 35.42% and the specificity was 85.42% whereas the CEA cutoff value was 307.61 ng/mL. The area under the receiver operating characteristic curve was 0.65. The nipple aspiration fluid collection rate in Chinese native women is lower compared to non-Asian-descendant women. CEA level does not seem to be a useful diagnostic tool for early cancer detection; it can only be used in conjugation with other methods.