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BACKGROUND: This study aimed to verify the effectiveness, safety, and reliability of the breast biopsy and circumferential excision system. METHODS: It was designed as a multicenter, randomized, open-label, positive control, noninferiority trial. A total of 168 subjects who met the breast lesion screening requirements of the clinical trial protocol were randomly divided into a breast biopsy and circumferential excision dual cutting system test group or Mammotome control group. The main outcome was the successful removal rate of suspected lumps during surgery. Secondary outcomes included the operative times for individual lumps, weight of removed cord tissue, and several indicators of device performance. Safety indicators, including routine blood, blood biochemical and electrocardiogram examinations, were measured at baseline and 24 hours and 48 hours after the operation. Postoperative complications and combined medication use were observed and recorded until 7 days after the operation. RESULTS: The results showed no significant differences in efficacy and safety between the 2 groups (main efficacy, P = .7463; all secondary efficacy indicators, P > .05, except weight of removed cord tissue [P = .0070] and touch sensitivity of the device interface [P = .0275]; all safety indicators, P > .05). The results suggested that the test device is effective and is acceptable safe for use in breast lesion biopsy. CONCLUSION: For patients with a high incidence of breast lesions, the results of this study provide a safe, effective, sensitive and accessible option for the removal of breast mass biopsies at a price much lower than that of imported devices.
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Neoplasias de la Mama , Humanos , Femenino , Reproducibilidad de los Resultados , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Biopsia , Mama/cirugía , Mama/patología , Márgenes de EscisiónRESUMEN
Background: Regional lymph node metastases (LNMs) are very common in papillary thyroid carcinoma (PTC) and associate with locoregional recurrence. The appropriate management of cervical lymph nodes is very important. Therefore, this study evaluated the application of sentinel lymph node biopsy (SLNB) in the lateral neck in PTC patients. Methods: This prospective study was conducted from 1 November 2015 to 31 December 2017 and recruited 78 PTC patients treated with SLNB in the lateral neck and prophylactic lateral neck dissection (compartments II-IV) followed by thyroidectomy or lobectomy and central neck dissection. Results: There were 78 PTC patients enrolled and sentinel lymph nodes (SLNs) were detected among 77 patients. A total of 30 patients were diagnosed with SLN metastases (SLNMs). The remaining 47 patients were pathologically negative of SLN, whereas 4 patients were found with metastases in the non-SLN samples. The detection rate, sensitivity, specificity, and accuracy rate of SLNB in the lateral neck were 98.7%, 87.1%, 98.7%, and 93.6%, respectively. However, the values varied greatly in each specific compartment of the lateral neck, and all of them were no more than 80%. These 34 PTC patients diagnosed with lateral compartment LNM (LLNM) were more likely to be younger (41.38 vs. 48.95 years old, p = 0.002) and exhibit extrathyroidal extension (56.8% vs. 31.7%, p = 0.026) and central compartment LNM (66.7% vs. 12.1%, p < 0.001). Tumors located in the upper third of the thyroid lobe also had a significantly higher probability of LLNM compared with those in middle or inferior location (66.7% vs. 35.3% vs. 34.8%, p = 0.044). At last, age (OR=0.912, p = 0.026), tumor location (upper vs inferior, OR=17.478, p = 0.011), and central compartment LNM (OR=25.364, p < 0.001) were independently predictive of LLNM. Conclusions: SLNB can help surgeons to identify some PTC patients who may benefit from therapeutic lateral neck dissection and protect some patients from prophylactic lateral neck dissection. However, it cannot accurately indicate specific lateral compartment-oriented neck dissection. Meanwhile, LLNM is more likely to occur in PTC patients with younger age or upper pole tumors or central compartment LNM.
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Carcinoma Papilar , Neoplasias de la Tiroides , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Humanos , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Biopsia del Ganglio Linfático Centinela , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugíaRESUMEN
Aberrant methylation has been regarded as a hallmark of cancer. 5-hydroxymethylcytosine (5hmC) is recently identified as the ten-eleven translocase (ten-eleven translocase)-mediated oxidized form of 5-methylcytosine, which plays a substantial role in DNA demethylation. Cell-free DNA has been introduced as a promising tool in the liquid biopsy of cancer. There are increasing evidence indicating that 5hmC in cell-free DNA play an active role during carcinogenesis. However, it remains unclear whether 5hmC could surpass classical markers in cancer detection, treatment, and prognosis. Here, we systematically reviewed the recent advances in the clinic and basic research of DNA 5-hydroxymethylation in cancer, especially in cell-free DNA. We further discuss the mechanisms underlying aberrant 5hmC patterns and carcinogenesis. Synergistically, 5-hydroxymethylation may act as a promising biomarker, unleashing great potential in early cancer detection, prognosis, and therapeutic strategies in precision oncology.
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While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.
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Medicina de Precisión/métodos , Proteómica/métodos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Anciano , Algoritmos , Biomarcadores de Tumor , Quimioterapia Adyuvante/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Checkpoint with FHA and RING finger domains (CHFR) is a G2 phase/mitosis checkpoint. Several studies have reported that CHFR is downregulated in multiple cancer types and serves a tumor suppressor role. However, the biological function of CHFR in breast cancer (BRCA), particularly regarding metastasis, are yet to be elucidated. In the present study, it was revealed that CHFR is upregulated in BRCA compared with normal tissues, according to The Cancer Genome Atlas database. In addition, subgroup analysis of BRCA revealed that CHFR was upregulated in both human epidermal growth factor receptor 2positive and triplenegative BRCA. Meanwhile, patients with high expression levels of CHFR exhibited poorer overall survival rates. Furthermore, the present data revealed that the overexpression of CHFR in SKBR3 cells resulted in enhanced cell migration and invasiveness, and also significantly upregulated mesenchymal markers, such as Ncadherin, vimentin, transcription factor Slug and tight junction protein claudin1. Furthermore, knockdown of CHFR in MDAMB231 cells significantly inhibited cell migration and invasiveness, and also downregulated mesenchymal markers, such as Ncadherin, vimentin and tight junction protein claudin1. In conclusion, the current results indicated that CHFR expression was associated with cell metastasis in BRCA by mediating epithelialtomesenchymal transition.
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Proteínas de Ciclo Celular/metabolismo , Transición Epitelial-Mesenquimal , Proteínas de Neoplasias/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias de la Mama , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Puntos de Control de la Fase M del Ciclo Celular , Mitosis , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Neoplasias de la Mama Triple Negativas , Ubiquitina-Proteína Ligasas/genética , Regulación hacia ArribaRESUMEN
Low-grade adenosquamous carcinoma (LGASC) is a rare invasive tumor that occurs in breast parenchyma. It has previously only been reported in females. Herein, we describe the case of a 52-year-old male who presented with a palpable mass in his right axilla that he reported had been present for 20-years. This is the first report of a male patient with LGASC. Core needle biopsy pathology revealed a benign mass of mammary origin, but its type was initially misdiagnosed. It was only correctly identified via postoperative pathology after local excision, which indicated that the mass exhibited the typical pathological characteristics of LGASC. Immunohistochemical analysis revealed positive expression of estrogen receptor, which was inconsistent with the typical "triple-negative" immunophenotype of LGASC. After resection of the mass the patient was advised to participate in regular outpatient follow-up. In conclusion, LGASC should be considered in male patients with a mass lesion in their breast or axilla, even when core needle biopsy indicates a benign mass of breast origin. One-stage local resection is recommended for the treatment of male patients with LGASC, but it is crucial to ensure that the margins are negative and postoperative adjuvant radiotherapy is not recommended.
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Breast carcinoma retroperitoneal metastasis is rare. The clinical symptoms of this disease are always non-specific. Laboratory tests are not always helpful for diagnosis and evaluation. We reported a case of a 52 year old Chinese patient who was diagnosed with retroperitoneal metastasis from breast invasive ductal carcinoma as the first site of distant metastasis synchronous with brain and mediastinal lymph nodes metastasis 4 years after modified radical mastectomy. Second-line chemotherapy of docetaxel and capecitabine was recommended. The response evaluation every two to three months was good. Unfortunately, the metastasis in the brain advanced. The patient was transferred to a radiotherapy department to receive radiotherapy and died 10 months later. We also review the related literature.
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BACKGROUND: The microRNA plays an important role in tumor progression. MiR-1236-3p acts as a tumor suppressor in various malignancies. OBJECTIVE: The aim of present study was to explore the expression of miR-1236-3p in gastric cancer (GC) and its correlation with clinicopathological features, and evaluate the feasibility of using it as a prognostic biomarker in GC. METHODS: Seventy-six pairs of tissue specimens were collected from GC patients. MiR-1236-3p expression level was detected by using qRT-PCR. The diagnostic value of miR-1236-3p was evaluated by receiver operating characteristic curve, and Kaplan-Meier method was used to analyze the overall survival. Prognosis analysis was performed using multivariate cox proportional hazards regression analysis. RESULTS: The expression of miR-1236-3p was significantly reduced in tumor tissues (P< 0.001). In addition, miR-1236-3p expression was correlated with TNM stage (P= 0.001), lymph node metastasis (P= 0.005) and differentiated degree (P= 0.001). The area under the curve was 0.7016, and its specificity and sensitivity were 60.53% and 73.68%. Kaplan-Meier survival curves showed that patients with high miR-1236-3p expression had better overall survival than those with low expression (P= 0.0190). Multivariate Cox regression analysis showed that the miR-1236-3p expression (P= 0.033) was an independent prognostic factor for overall survival of GC prognosis. CONCLUSIONS: The study showed that miR-1236-3p is downregulated in GC tissues, and low expression of miR-1236-3p is associated with a poor prognosis in GC. It may be a new diagnostic and prognostic biomarker for GC.
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Biomarcadores de Tumor , MicroARNs/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Interferencia de ARN , Curva ROC , Neoplasias Gástricas/mortalidadRESUMEN
BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/mortalidad , Neoplasias de la Mama Masculina/patología , Neutropenia Febril Inducida por Quimioterapia/etiología , Neutropenia Febril Inducida por Quimioterapia/prevención & control , China/epidemiología , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Supervivencia sin Progresión , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Adulto JovenRESUMEN
The Regorafenib is a broad-spectrum kinase inhibitor that has been approved to treat colorectal cancer (CRC). However, evidences have shown that the agent is also implicated in drug interaction with microRNA-21 (miR-21), an oncogenic miRNA which plays a key role in resisting programmed cell death in CRC cells. Here, we supposed that, instead of kinase inhibition, Regorafenib can directly bind to and then stabilize miR-21 pre-element, thus preventing RNase Dicer-meditated cleavage of the pre-element to mature miR-21. In order to verify the notion, an in silico-in vitro integrated investigation of the direct intermolecular interaction between Regorafenib and miR-21 pre-element was performed by using active pocket identification, RNA-ligand docking, molecular dynamics (MD) simulation, binding energetic analysis, and fluorescence-based assay. It was revealed that the Regorafenib can bind at the major groove-like stem region of miR-21 pre-element through three geometrically satisfactory hydrogen bonds (H-bonds) as well as a number of hydrophobic forces and π-π stacking, conferring strong specificity and high stability to the RNA-ligand complex system (Kd=0.73µM). Separate inversion mutation of two base pairs (G6C, C12G) and (A13U, U4A) that are involved in the H-bonding can considerably impair the affinity of Regorafenib to miR-21 pre-element, with Kd increase to 27 and 96µM, respectively. All these supported that Regorafenib can directly bind to miR-21 pre-element at molecular level and the binding mode can be properly modeled by using the proposed integrated strategy. This study would provide a potential, alternative mechanism for anti-colorectal cancer chemotherapy with Regorafenib.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Anisotropía , Antineoplásicos/química , Antineoplásicos/farmacología , Secuencia de Bases , Línea Celular Tumoral , Humanos , Ligandos , Espectroscopía de Resonancia Magnética , MicroARNs/química , MicroARNs/genética , Modelos Moleculares , Simulación de Dinámica Molecular , Mutación/genética , Compuestos de Fenilurea/química , Compuestos de Fenilurea/farmacología , Piridinas/química , Piridinas/farmacología , TermodinámicaRESUMEN
Human epidermal growth factor receptor 2 (HER2) has become a well-established target for the treatment of HER2-positive lung cancer. However, a frequently observed in-frame mutation that inserts amino acid quadruplex Tyr776-Val777-Met778-Ala779 at G776 (G776(YVMA)) in HER2 kinase domain can cause drug resistance and sensitivity, largely limiting the application of reversible tyrosine kinase inhibitors in lung cancer therapy. A systematic investigation of the intermolecular interactions between the HER2(YVMA) mutant and clinical small-molecule inhibitors would help to establish a complete picture of drug response to HER2 G776(YVMA) insertion in lung cancer, and to design new tyrosine kinase inhibitors with high potency and selectivity to target the lung cancer-related HER2(YVMA) mutant. Here, we combined homology modeling, ligand grafting, structure minimization, molecular simulation and binding affinity analysis to profile a number of tyrosine kinase inhibitors against the G776(YVMA) insertion in HER2. It is found that the insertion is far away from HER2 active pocket and thus cannot contact inhibitor ligand directly. However, the insertion is expected to induce marked allosteric effect on some regions around the pocket, including A-loop and hinges connecting between the N- and C-lobes of HER2 kinase domain, which may exert indirect influence to inhibitor binding. Most investigated inhibitors exhibit weak binding strength to both wild-type and mutant HER2, which can be attributed to steric hindrance that impairs ligand compatibility with HER2 active pocket. However, the cognate inhibitor lapatinib and the non-cognate inhibitor bosutinib were predicted to have low affinity for wild-type HER2 but high affinity for HER2(YVMA) mutant, which was confirmed by subsequent kinase assay experiments; the inhibitory potencies of bosutinib against wild-type and mutant HER2 were determined to be IC(50) > 1000 and =27 nM, respectively, suggesting that the bosutinib might be exploited as a selective inhibitor for mutant over wild-type HER2. Structural examination revealed that formation of additional non-bonded interactions such as hydrogen bonds and hydrophobic contacts with HER2 A-loop region due to G776(YVMA) insertion is the primary factor to improve bosutinib affinity upon the mutation.
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Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación/genética , Inhibidores de Proteínas Quinasas/farmacología , Receptor ErbB-2/genética , Bibliotecas de Moléculas Pequeñas/farmacología , Humanos , Neoplasias Pulmonares/genética , Modelos Moleculares , Simulación de Dinámica Molecular , Mutagénesis Insercional , Unión Proteica , Conformación Proteica , Receptor ErbB-2/químicaRESUMEN
Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that have been recently shown to play critical roles in cancer biology. However, little is known about their mechanistic role in breast cancer pathogenesis, especially in triple-negative breast carcinomas (TNBC) that have particular poor outcomes. This study was specifically designed to identify the signatures relevant lncRNAs in breast cancer and characterize lncRNAs that modulate the phenotype. Here we provide detailed methods and analysis of microarray data, which is deposited in the Gene Expression Omnibus (GEO) with the accession number GSE64790. The basic analysis as contained in the manuscript published in Oncotarget with the PMID 26078338. These data can be used to further elucidate the mechanisms of breast cancer.
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BACKGROUND: The sentinel lymph node (SLN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. The aim of this study was to evaluate the clinical application of SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) with occult lymph nodes. METHODS: From April 2006 to October 2012, 212 consecutive PTC patients were treated with SLNB using carbon nanoparticle suspension (CNS). Then, the stained nodes defined as SLN were collected, and prophylactic central compartment neck dissection (CCND) followed by total thyroidectomy or subtotal thyroidectomy were performed. All the samples were sent for pathological examination. RESULTS: There were 78 (36.8%) SLN metastasis (SLNM)-positive cases and 134 (63.2%) SLNM-negative cases. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of SLNB were 78.8%, 100%, 100%, 84.3%, 0%, and 21.2%, respectively. The PTC patients with SLNM were more likely to be male (48.2% vs. 32.7%, p = 0.039) and exhibited multifocality (52.6% vs. 33.3%, p = 0.025) and extrathyroidal extension (56.7% vs. 33.5%, p = 0.015). A greater incidence of non-SLN metastases in the central compartment was found in patients with SLNM (41/78, 52.6%) than in those without SLNM (21/134, 15.7%; p < 0.05). However, the SLNM-negative PTC patients with non-SLN metastases were more likely to be male (37.9% vs. 9.5%, p < 0.05). CONCLUSIONS: The application of SLNB using CNS is technically feasible, safe, and useful, especially for male patients with co-existing multifocality and extrathyroidal extension. However, the sensitivity of SLNB must be improved and its false-negative rate reduced before it can be a routine procedure and replace prophylactic CCND. More attention should be paid to PTC patients (especially males) without SLNM for signs of non-SLN metastases.
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Carcinoma Papilar/patología , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias de la Tiroides/patología , Adulto , Anciano , Carcinoma Papilar/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Disección del Cuello , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto JovenRESUMEN
Triple-negative breast carcinomas (TNBC) are characterized by particularly poor outcomes, and there are no established markers significantly associated with prognosis. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that have been recently shown to play critical roles in cancer biology. However, little is known about their mechanistic role in TNBC pathogenesis. In this report, we investigated the expression patterns of lncRNAs from TNBC tissues and matched normal tissues with Agilent Human lncRNA array. We identified 1,758 lncRNAs and 1,254 mRNAs that were differentially expressed (≥ 2-fold change), indicating that many lncRNAs are significantly upregulated or downregulated in TNBC. Among these, XR_250621.1 and NONHSAT125629 were the most upregulated and downregulated lncRNAs respectively. qRT-PCR was employed to validate the microarray analysis findings, and results were consistent with the data from the microarrays. GO and KEGG pathway analysis were applied to explore the potential lncRNAs functions, some pathways including microtubule motor activity and DNA replication were identified in TNBC pathogenesis. Our study revealed that a set of lncRNAs were differentially expressed in TNBC tissues, suggesting that they may play role in TNBC. These results shed light on lncRNAs' biological functions and provide useful information for exploring potential therapeutic targets for breast cancer.
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Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Neoplasias de la Mama Triple Negativas/genética , Biomarcadores de Tumor , Análisis por Conglomerados , Replicación del ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Pronóstico , Distribución TisularRESUMEN
Autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune endocrine disorders. Interleukin-4 (IL-4), a cytokine secreted by T cells, plays a critical role in antigen-specific Th2 responses. The IL-4 gene is highly polymorphic and it has been reported that the polymorphism at -590 (T/C, rs2243250) in the promoter region of IL-4 may contribute to the development of AITDs. Recently, several case-control studies have examined the association of genetic variants of IL-4 with AITDs. However, the results of these studies remain conflicting. To systematically study the role of IL-4 in the pathogenesis of AITDs, we conducted a meta-analysis including 11 eligible studies (1847 cases and 2068 healthy controls). Fixed-effect or random-effect models were used to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Our results revealed a significant association between the IL-4 genetic variant (-590, T/C, rs2243250) and the risk of developing AITDs (TC + TT versus TT genotype: OR = 1.83, 95% CI = 1.083-3.091, p = 0.024). These findings demonstrate that the IL-4 rs2243250 genetic variant might play a key role in the development of AITDs.
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Predisposición Genética a la Enfermedad , Enfermedad de Graves/genética , Enfermedad de Hashimoto/genética , Interleucina-4/genética , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , Expresión Génica , Frecuencia de los Genes , Enfermedad de Graves/inmunología , Enfermedad de Graves/patología , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/patología , Humanos , Interleucina-4/inmunología , Modelos Genéticos , Oportunidad RelativaRESUMEN
Breast cancer is the leading cause of cancer death in women worldwide, which is closely related to metastasis. Recent studies argue that breast cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the molecular mechanisms underlying this transition are poorly understood. In this study, we found that siRNA-mediated attenuation of B-Myb expression restored E-cadherin expression and cell-cell junction formation in breast cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. In contrast, the forced B-Myb expression decreased the expression of the epithelial marker E-cadherin, but increased the mesenchymal markers in breast cancer cells. We found that B-Myb upregulated expression of the key EMT regulator snail and that it mediated EMT activation and cell invasion by B-Myb.
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Neoplasias de la Mama/patología , Proteínas de Ciclo Celular/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Invasividad Neoplásica/genética , Transactivadores/metabolismo , Factores de Transcripción/biosíntesis , Neoplasias de la Mama/genética , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Immunoblotting , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción de la Familia Snail , Regulación hacia ArribaRESUMEN
B-myb belongs to the myb family of transcription factors that include A-myb and c-myb. While A-myb and c-myb are tissue-specific, B-myb is broadly expressed in rapidly dividing cells of developing adult mammals. Results of our study showed that increased B-myb expression of was associated with the progression of breast cancer and that B-myb protein levels were significantly elevated in matched metastases. High B-myb levels also predict shorter overall survival of breast cancer patients. Moreover, B-myb stimulated transcription of target genes that promoted entry into the S and M-phases of the cell cycle, cell proliferation, migration and invasion in breast cancer. Taken together, our results strongly demonstrated that B-myb had a critical role in both cell cycle progression and tumorigenesis, and might serve as a novel potential target in the diagnosis and/or treatment of human breast cancer.
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Neoplasias de la Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular , Proliferación Celular , Transactivadores/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Femenino , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Ratones Desnudos , Invasividad Neoplásica , Interferencia de ARN , Transducción de Señal , Factores de Tiempo , Transactivadores/genética , Transfección , Carga Tumoral , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ultrasound-guided vacuum-assisted breast biopsy (VABB) is regarded as a feasible, effective, minimally invasive and safe method for the removal of benign breast lesions, without the occurrence of serious complications. The aim of this study was to evaluate the feasibility, efficacy and safety of ultrasound-guided VABB using the Mammotome® biopsy system in the treatment of breast lesions. The clinical outcomes of 3,681 patients with breast lesions were evaluated following excisions by ultrasound-guided VABB in two high-volume teaching hospitals. From January 2008 to December 2012, a total of 4,867 ultrasound-guided VABB procedures were performed in the 3,681 patients, who had a mean age of 37.8 years (range, 16-73 years). The parameters examined in this analysis included lesion size, lesion location in the inner breast, Breast Imaging Reporting and Data System (BI-RADS) ultrasound category and histopathological diagnosis. Ultrasonography follow-up was performed at 3-6 month intervals in order to assess recurrence. The size of the investigated lesions ranged between 6 and 62 mm and a histopathological diagnosis was made in 100% of cases. The results indicated that the majority of specimens (98.89%) were benign. On average, the ultrasound-guided VABB was performed in 10.3 min (range, 7.5-43 min) and the mean number of cores removed in the procedure was 8.1 (range, 3-32). A complete excision was achieved in the majority of cases (99.7%). The presence of a hematoma was the most common complication following the biopsy, and was observed in 27.5% of patients. The mean follow-up period was 25.5 months (range, 1-60 months), during which the rate of recurrence was 4.4%. The results indicated that ultrasound-guided VABB using the Mammotome biopsy system is an effective and safe procedure that is able to rapidly remove the majority of benign breast lesions using a small incision and without the occurrence of scarring or complications.
RESUMEN
BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is the mainstay of management for patients with unresectable hepatocellular carcinoma (HCC). The aim of this study is to evaluate the survival rates of patients with unresectable HCC following TACE performed in a single center. METHODOLOGY: The authors retrospectively assessed the electronic medical records of 512 patients in whom HCC was newly diagnosed from January 2008 to December 2012 at a single tertiary medical center. Patients with decompensated hepatic function were excluded. Hepatic artery infusion chemotherapy was performed using one drug or combinations of oxaliplatin, fluorouracil and doxorubicin. The primary endpoint of the study was overall survival (OS). Survival rates were calculated using Kaplan-Meier method. RESULTS: A total of 512 HCC patients (425 men and 87 women; mean age, 58.9 years; age range, 38.3-86.1 years) were treated with TACE in a single center. The overall survival rates at 1, 2, and 3 years were 62%, 43%, and 37%, respectively. The overall median survival time from the start of TACE treatment was 15 months. CONCLUSIONS: TACE is an effective minimally invasive therapy option for palliative treatment of HCC patients.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Syringocystadenoma papilliferum (SCAP) is an uncommon benign adnexal tumor of the skin. It is frequently seen in association with other benign adnexal lesions, such as nevus sebaceous, apocrine nevus, tubular apocrine adenoma, apocrine hidrocystoma, apocrine cystadenoma, and clear cell syringoma. The unusual reported locations of SCAP include the head and neck, the buttock, the vulva, the scrotum, the pinna, the eyelid, the outer ear canal, the forehead, the back, the scalp, the thigh, the nipple, the axilla, and the postoperative scar. The occurrence of SCAP in the right lower abdomen is distinctly uncommon. Herein, we report an unusual case of a 41-year-old man with SCAP occurring in the right lower abdomen that did not develop malignancy, despite a long disease course and an absence of medical treatment. The clinical and histopathologic features and the differential diagnosis of SCAP are also discussed.