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1.
Balkan Med J ; 41(3): 213-221, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700366

RESUMO

Background: The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response. Aims: To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8+-TILs) in patients with HER2-positive BC. Study Design: Retrospective cohort study. Methods: This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8+-TILlow (< 35%) and CD8+-TILhigh (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8+-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility. Results: Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8+-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (p = 0.009, US_ADC vs. US; p < 0.001, US_ADC vs. ADC). Conclusion: US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8+-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.


Assuntos
Neoplasias da Mama , Linfócitos T CD8-Positivos , Imageamento por Ressonância Magnética , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética/métodos , Receptor ErbB-2/análise , Idoso , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricos , Estudos de Coortes , Linfócitos do Interstício Tumoral
3.
Transl Cancer Res ; 11(7): 1970-1976, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35966288

RESUMO

Background: The prognosis of patients with breast cancer (BRCA) is difficult to predict because of the high degree of heterogeneity and complex etiological factors. Ferroptosis, an iron-dependent, new form of cell death, plays an important role in regulation of tumor growth and progression. The aim of this study was to clarify the predictive value of ferroptosis-related genes in the overall survival of patients with BRCA. Methods: The messenger RNA expression profile and clinical information of patients with BRCA were collected from The Cancer Genome Atlas (TCGA) database. The differences between BRCA and adjacent normal tissues were analyzed, and candidates with differentially expressed ferroptosis-related genes were identified. Through Cox and LASSO analyses, the prognostic genetic characteristics of ferroptosis-related genes were established. Lastly, according to the median risk score, the patients were divided into high-risk and low-risk groups, a nomogram was constructed, and the prediction accuracy was tested. Results: It was determined that the four ferroptosis related genes had a significant difference in survival in BRCA (P<0.05); a prognostic model was constructed based on the four ferroptosis related genes, and the overall survival of patients in the high-risk group was significantly worse (P<0.05). The four-gene nomogram can quantify the contribution of each index to survival, and the calibration chart shows high prediction accuracy. Conclusions: This study constructed four ferroptosis related gene characteristics and nomogram, which can effectively predict the prognosis of BRCA patients and provide new insights for future anti-cancer treatments based on ferroptosis targets.

4.
Int J Oncol ; 61(1)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35642668

RESUMO

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing the data from flow cytometry experiments in Figs. 2D, 4D and 5D, and certain of the tumor images featured in Fig. 7A, were strikingly similar to data appearing in different form in other articles by different authors. Furthermore, overlapping data panels were identified within this paper comparing the cell migration assay images between Figs. 2C and 4F. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 54: 315­325, 2019; DOI: 10.3892/ijo.2018.4615].

5.
Anticancer Drugs ; 33(1): e622-e627, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34407046

RESUMO

Brain metastasis is a common cause of death in HER2-positive breast cancer patients. Currently, it is mainly treated by whole-brain radiotherapy. Pyrotinib is an irreversible pan-ErbB inhibitor, which has demonstrated promising tumor-suppressing activity and acceptable tolerance in previous phase trials. In the present study, we evaluated the efficacy of pyrotinib on HER2-positive brain metastatic breast cancer patients treated with whole-brain radiotherapy. A total of 20 such patients were separated into pyrotinib plus capecitabine and capecitabine-only groups in a 1:1 ratio. All patients met either the primary or secondary endpoints. Oral admission of pyrotinib together with radiotherapy can significantly increase the overall response rate, progression-free survival, time to progression and duration of response of HER2+ brain metastatic breast cancer patients, without causing extra adverse events. In addition, pyrotinib can enhance the radiosensitivity of in-vitro cultured HER2+ breast cancer cell lines. The outcome of our study suggests that pyrotinib might be an effective medication to enhance the tumor radiosensitivity of HER2-positive brain metastatic breast cancer patients.


Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Tolerância a Radiação/efeitos dos fármacos , Acrilamidas/administração & dosagem , Acrilamidas/efeitos adversos , Adulto , Idoso , Aminoquinolinas/administração & dosagem , Aminoquinolinas/efeitos adversos , Linhagem Celular Tumoral , Feminino , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Receptor ErbB-2/antagonistas & inibidores
6.
Transl Cancer Res ; 10(7): 3582-3587, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35116661

RESUMO

Primary thyroid lymphoma (PTL) is a rare malignant tumor of the thyroid, the diagnosis, and treatment of which are still controversial. Although the treatment of thyroid lymphoma causing respiratory obstruction is controversial, chemotherapy is considered the most effective treatment. Tracheoesophageal fistula is an extremely rare complication of chemotherapy. Here, we report a case of respiratory obstruction caused by a thyroid tumor. A 66-year-old female patient visited the hospital with a goiter with dyspnea. The patient was diagnosed with diffuse large B-cell lymphoma of the thyroid by core needle biopsy. After chemotherapy with a cyclophosphamide vincristine prednisone (CVP) regimen, the tumor obviously subsided, but the patient began to experience clinical symptoms such as hoarseness and difficulty drinking. Fiberoptic bronchoscopy and neck computed tomography revealed a tracheoesophageal fistula. The phenomenon of tracheoesophageal fistula resulting from chemotherapy for thyroid lymphoma is extremely rare. Standard treatment for thyroid lymphoma that causes respiratory tract obstruction does not exist. Through clinical case sharing, increase awareness and early recognition are particularly important in order to minimize appropriately the effect of the event and through this case report, so as to provide some suggestions for clinicians. Cases of airway obstruction should be fully evaluated before treatment, and temporary airway protection measures, such as tracheotomy, surgical decompression, and tracheal metal.

7.
J Breast Cancer ; 23(4): 373-384, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32908788

RESUMO

PURPOSE: Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied. METHODS: We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes. RESULTS: In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence. CONCLUSION: Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.

8.
Clin Respir J ; 14(10): 891-900, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32510764

RESUMO

OBJECTIVE: Symptoms such as depression and anxiety are common psychiatric symptoms in patients with chronic obstructive pulmonary disease (COPD). Cognitive behavioral therapy (CBT) is still controversial in the treatment of anxiety and depression in patients with COPD. We conducted a meta-analysis and systematic review to evaluate the effect of CBT on anxiety and depression in patients with COPD, with a view to providing some guidance for clinical application. MATERIALS AND METHODS: Computer search Web of Science, EMbase, PubMed, Cochrane Library, search time limit from the establishment of the library to August 2019. Collect the randomized controlled trial (RCT) for this topic. Two investigators independently screened the literature according to inclusion and exclusion criteria, extracted the data and assessed the risk of bias in the included studies. Meta-analysis using RevMan5.3 software. RESULTS: A total of 10 studies were included in a total of 1278 patients. Meta-analysis shows that CBT can improve depression and anxiety in patients with COPD. Subgroup analysis showed that intervention time ≥8 weeks had significant differences in improving anxiety, while intervention time <8weeks had significant differences in improving depression. CONCLUSIONS: Cognitive behavioral therapy may possibly relieve depression in COPD patients in a short period of time, and it takes longer to improve anxiety. Therefore, clinical practice can choose the appropriate intervention time according to the patient's psychological condition.


Assuntos
Terapia Cognitivo-Comportamental , Doença Pulmonar Obstrutiva Crônica , Ansiedade/terapia , Transtornos de Ansiedade , Depressão/terapia , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
J Breast Cancer ; 23(6): 656-664, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33408891

RESUMO

Male breast cancer (MBC) is rare and accounts for approximately 1% of all breast cancer cases worldwide. Previous studies have suggested that several factors significantly increase the risk of MBC. Prolactinoma has the highest incidence rate among patients with functional pituitary tumors. However, whether prolactinoma is involved in the onset and progression of breast cancer remains unclear. To date, there are only five case reports globally on MBC with concurrent prolactinoma. We hereby describe the first case of MBC with prolactinoma in China. We also explored the patient's genetic profile using whole exome sequencing. Our findings may help advance our understanding of the molecular pathogenesis of MBC. Further molecular analyses of such cases are warranted to improve auxiliary molecular diagnostic methods and targeted therapy for MBC.

10.
J Cell Biochem ; 120(9): 15360-15368, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31162714

RESUMO

Breast cancer is the most pervasive cancer tormenting women, with increasing incidence and mortality rates year after year. MicroRNAs (miRNAs) with abnormal expression has various effects in biological processes and progression in diverse tumors. Nevertheless, it is vitally crucial for us to inspect more underlying molecular mechanisms for the therapy of patients with breast cancer. In the paper, we inquired the expression level and potential regulation mechanism of miR-374c-5p in breast cancer. Our research found out that miR-374c-5p was low-level expressed in breast cancer. Upregulation of miR-374c-5p repressed cell proliferation, migration, and also epithelial-mesenchymal transition (EMT), and induced cell apoptosis of breast cancer cells. Further, we concluded that miR-374c-5p interacted with TAF7 and downregulated its expression. Moreover, miR-374c-5p modulated DEP domain containing 1 (DEPDC1) through mediating TAF7. Finally, rescue assays represented that miR-374c-5p suppressed breast cancer development via TAF7-mediated transcriptional regulation of DEPDC1. We uncovered that overexpressed miR-374c-5p inhibited the development of breast cancer via TAF7-regulated transcriptional regulation of DEPDC1, which may be a novel and vital proportion of cancer diagnosis and treatment strategies.


Assuntos
Neoplasias da Mama/genética , Proteínas Ativadoras de GTPase/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos
11.
Int J Oncol ; 54(1): 315-325, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30387841

RESUMO

MicroRNAs (miRNAs/miRs) are widely dysregulated in papillary thyroid cancer (PTC). Dysregulated miRNAs, together with their target genes, comprise a complex network that has been implicated in the regulation of PTC pathogenesis. Further knowledge of the functional roles of aberrantly expressed miRNAs in PTC, and the underlying molecular mechanisms, may assist in the identification of novel therapeutic targets. miR­766 has been well studied in human cancer; however, the expression status, specific roles and regulatory mechanisms of miR­766 in PTC remain unclear. The present study aimed to detect miR­766 expression in PTC tissues and cell lines, to explore the biological roles of miR­766 in the malignant biological behaviors of PTC cells, and to determine the underlying mechanism of action of miR­766 in PTC cells. The results revealed that miR­766 was downregulated in PTC tissues and cell lines, and its downregulation was strongly associated with TNM stage and lymph node metastasis. Overexpression of miR­766 inhibited PTC cell proliferation, colony formation, migration and invasion, promoted cell apoptosis and reduced tumor growth in vivo. Mechanistically, insulin receptor substrate 2 (IRS2) was identified as a direct target of miR­766 in PTC cells. IRS2 was upregulated in PTC tissues, and this was inversely correlated with miR­766 expression. Inhibition of IRS2 simulated the tumor suppressor activity of miR­766 in PTC cells. Restoration of IRS2 expression negated the tumor­suppressing effects of miR­766 overexpression on PTC cells. Notably, miR­766 directly targeted IRS2 to inhibit activation of the phosphoinositide 3­kinase (PI3K)/protein kinase B (Akt) pathway in PTC cells in vitro and in vivo. Overall, these findings indicated that miR­766 may inhibit the malignant biological behaviors of PTC cells by directly targeting IRS2 and regulating the PI3K/Akt pathway, thus suggesting that this miRNA may be a promising therapeutic target for PTC.


Assuntos
Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , MicroRNAs/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
12.
Drug Des Devel Ther ; 12: 3563-3571, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464390

RESUMO

OBJECTIVE: Lobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression. PATIENTS AND METHODS: Clinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression. RESULTS: We found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis. CONCLUSION: Lobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Moléculas de Adesão Celular/deficiência , Moléculas de Adesão Celular/genética , Ciclobutanos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Compostos Organoplatínicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Células MCF-7 , Proteínas de Membrana , Pessoa de Meia-Idade , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase em Tempo Real , Células Tumorais Cultivadas
13.
J Cell Biochem ; 119(5): 4097-4102, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29236327

RESUMO

Thyroid cancer is currently the most common endocrine malignancies, and PI3K/Akt pathway play an important role during its initiation and development. IC87114 is an inhibitor of PI3K/Akt pathway. Little is known about the role of IC87114 in the initiation and progression of thyroid cancer. Here, we demonstrated that IC87114 significantly inhibited both the migration and invasion of thyroid cancer cells, which can be mediated by inhibition of PI3K/Akt pathway. These results suggest that application of IC87114 may prove to be a particularly effective treatment for thyroid cancer.


Assuntos
Adenina/análogos & derivados , Movimento Celular/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/enzimologia , Adenina/farmacologia , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
14.
EXCLI J ; 16: 354-362, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28507479

RESUMO

Long non-coding RNAs (lncRNAs) have been found to show important regulatory roles in various human cancers. Lnc-RNA PANDAR is a novel identified lncRNA that was previously reported to show abnormal expression pattern in various cancers. However, little is known of its expression and biological function in thyroid cancer. Here, we used the quantitative real-time PCR (qRT-PCR) to determine the expression of PANDAR in 64 thyroid cancer tissues. We found that expression of PANDAR was up-regulated in thyroid cancer tissues compared with adjacent non-tumor tissues. Functional assays in vitro demonstrated that knockdown of PANDAR could inhibit proliferation, cell cycle progression, induces the apoptosis, inhibit invasion of thyroid cancer cells. Thus, our study provides evidence that PANDAR may function as a potential target for treatment for patients with thyroid cancer.

15.
Exp Mol Pathol ; 102(3): 500-504, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28506768

RESUMO

The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC.


Assuntos
Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Adulto , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida , Adulto Jovem
16.
Oncol Rep ; 37(6): 3581-3589, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28498478

RESUMO

In breast cancer (BC), silencing of miRNA genes due to miRNA gene promoter methylation are the important mechanisms directly contributing to tumorigenesis and tumor progression. miRNA-495 (miR-495) has been reported to be a tumor suppressor gene in various cancers, but its role and regulation in BC remains unclear. In the present study, the level of miR-495 was inversely correlated with the expression of STAT-3 in BC tissues and cell lines. miR-495 can directly target 3'-UTR of STAT-3 mRNA and thereby decrease the expression of STAT-3 in MCF-7 and HCC1973 cells by Targetscan and Dual-luciferase assay. We further analyzed miR-495 promoter methylation by sodium bisulfite sequencing method (BSP), and found DNA methyltransferase inhibitor, 5-AzaC concomitantly upregulated expression of miR-495 and downregulated its target gene STAT-3 and its downstream target VEGF. Furthermore, we further observed that 5-AzaC treatment, miR-495 mimics and STAT-3 knockdown significantly inhibited cell function in breast cancer by Transwell assay, EdU flow cytometry, Annexin V-FITC/PI combined with flow cytometry and Hoechst staining. Taken together, our data are first to demonstrate that the miR-495 is silenced due to promoter methylation in breast cancer. DNA methyltransferase inhibitor 5-AzaC could reverse miR­495 (suppressor gene) and STAT-3 (oncogene). The anticancer properties of 5-AzaC were preliminarily confirmed in breast cancer.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Fator de Transcrição STAT3/genética , Fator A de Crescimento do Endotélio Vascular/genética , Apoptose/genética , Azacitidina/administração & dosagem , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA/genética , Desmetilação/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Regiões Promotoras Genéticas
17.
Oncotarget ; 8(12): 19923-19933, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28199966

RESUMO

Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer. A total of 11,941 breast cancer patients from 9 trials were included for analysis. Meta-analysis showed that dual HER2 blockade treatment significantly increased the risk of severe diarrhea (OR 2.52, p<0.001) and treatment discontinuation (OR 1.52, p=0.014), but not for severe rash (OR 1.06, p=0.81), liver toxicities (OR 1.16, p=0.28), CHF (OR 1.46, p=0.09), LVEF decline (OR 1.09, p=0.40) and FAEs (OR 0.97, p=0.91). Similar results were observed in sub-group analysis according to anti-HER2 regimens in terms of severe diarrhea and treatment discontinuation. Additionally, trastuzumab plus lapatinib significantly increased the risk of LVEF decline in comparison with lapatinib alone (OR 1.48, p=0.002). Our analysis indicated that dual anti-HER2 blockade treatment significantly increased the risk of developing severe diarrhea and treatment discontinuation in comparison with anti-HER2 monotherapy. These were no evidence of an increased risk of fatal adverse events with dual-HER2 blockade treatment.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Diarreia/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Exantema/induzido quimicamente , Feminino , Humanos , Lapatinib , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico , Resultado do Tratamento , Suspensão de Tratamento
18.
J Gene Med ; 19(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27813254

RESUMO

BACKGROUND: In the present study, we investigated the possible tumor suppressive effect of microRNA-107 (miR-107) in human breast cancer. METHODS: Gene expression of miR-107 in breast cancer cell lines and clinical breast tissues was evaluated by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). MiR-107 was stably overexpressed in MCF-7 and MDA-MB-231 cells via lentiviral transduction. Its role in regulating in vitro cancer proliferation, cell cycle, invasion and in vivo tumor growth was evaluated by MTT, flow cytometry, transwell and in vivo tumorigenicity assays, respectively. Association of miR-107 and its downstream target, brain-derived neurotrophic factor (BDNF), was evaluated by luciferase assay and qRT-PCR. BDNF was further upregulated in miR-107-overexpressed MCF-7 and MDA-MB-231 cells to evaluate its role in regulating breast cancer with respect to in vitro proliferation, cell cycle and invasion. RESULTS: MiR-107 was markedly downregulated in both breast cancer cell lines and breast tumors. MiR-107 overexpression was markedly suppressed with respect to in vitro breast cancer proliferation, cell cycle progression and invasion, as well as with respect to in vivo development of breast cancer xenograft. BDNF was found to be the downstream target of miR-107 in breast cancer. BDNF upregulation functionally facilitated in vitro proliferation, cell cycle progression and invasion in miR-107-overexpressed breast cancer cells. CONCLUSIONS: MiR-107 is downregulated and has a tumor suppressive effect in breast cancer, likely through regulation via its inverted downstream target of BDNF.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Neoplasias da Mama/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Homologia de Sequência do Ácido Nucleico , Transplante Heterólogo
19.
Hum Pathol ; 61: 49-57, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27864123

RESUMO

We explored the relations between PTEN/PI3K/AKT expression and clinicopathological characteristics and prognosis in breast cancer patients with and without axillary lymph node metastasis (LNM). Tissues and follow-up data from 142 patients with (LNM group) and 154 without (non-LNM group) metastases were collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that of PI3K and AKT was increased. Expression of AKT was negatively correlated with PTEN expression but positively correlated with PI3K expression. Apparent correlations were detected between AKT and axillary LNM with a tumor size of 2 cm or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and axillary LNM of histologic grade I or II tumors and non-triple-negative breast cancer (all P<.05). In the LNM group, the 5-year survival rate of patients with PTEN-positive tumors was higher than that of patients with PTEN-negative lesions; whereas in the non-LNM group, the 5-year survival rate of patients with AKT-positive tumors was lower than that of patients with AKT-negative lesions (both P<.05). Cox regression analysis showed that PTEN expression was an independent prognostic factor for patients with LNM; AKT expression, tumor diameter, pathologic grade, and pathologic type were independent prognostic factors for patients without LNM. In conclusion, TEN/PI3K/AKT proteins are related to the clinicopathological features and prognosis of breast cancer with axillary LNM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/enzimologia , Carcinoma/enzimologia , Linfonodos/patologia , PTEN Fosfo-Hidrolase/análise , Fosfatidilinositol 3-Quinase/análise , Proteínas Proto-Oncogênicas c-akt/análise , Adulto , Idoso , Biópsia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma/secundário , Carcinoma/terapia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Carga Tumoral , Adulto Jovem
20.
Cell Physiol Biochem ; 39(6): 2451-2463, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27832644

RESUMO

BACKGROUND: Approximately 10-20 million Americans have been clinically diagnosed with thyroid nodules. Shear wave elastography (SWE) and real-time elastography (RTE) are two primary forms of elastography for identifying the status of thyroid nodules. The aim of this study is to assess the performance of RTE and SWE in identifying malignant thyroid nodules. METHODS: Relevant articles were systematically retrieved from PubMed, Embase and Cochrane Library. In order to evaluate the overall diagnostic accuracy, we have considered pooled sensitivity (SEN), specificity (SPE), area under the curve (AUC) and partial AUC with corresponding 95% confidence intervals (95%CIs). Stratified analyses by ethnicity (Caucasian, Asian), the number of malignant nodules (> 50, < 50), score system (elasticity scores: ES and strain ration: SR) and ES (> 4, < 4) were performed to explore potential sources of heterogeneity. All statistical tests were performed using the R 3.2.1 software package. RESULTS: We analyzed 80 trials from 71 studies with 16,624 subjects (12,348 for SWE, 4,276 for RTE). The pooled results suggested that RTE is more accurate than SWE in diagnosing malignant cases (RTE: SEN= 0.829, 95%CI = 0.799-0.855, SPE = 0.828, 95%CI = 0.789-0.862, AUC = 0.889; SWE: SEN = 0.784, 95%CI = 0.732-0.828, SPE = 0.824, 95%CI = 0.766-0.871, AUC = 0.859). No significant difference was found in the subgroup analyses. CONCLUSION: Our findings revealed that RTE is superior to SWE in differentiating malignant and benign thyroid nodules. Nevertheless, more studies focusing on the diagnostic accuracy of RTE and SWE during different stages of thyroid nodules development should be carried out in the future.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Diagnóstico Diferencial , Etnicidade , Humanos , Viés de Publicação , Curva ROC , Sensibilidade e Especificidade
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