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1.
Surg Innov ; 31(3): 263-273, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38571331

RESUMO

OBJECTIVE: We propose a pedicled perforator flap technique for salvage nipple reconstruction after initial nipple reconstruction fails in breast cancer patients. METHODS: This is a pilot study. A total of 21 female breast cancer patients who underwent nipple reconstruction following initial nipple reconstruction fails were enrolled, and salvage nipple reconstruction based pedicled perforator flap were performed between 2016 and 2020. Operative time, perforator design, postoperative complications, follow-up duration, projection of nipple, as well as patient-reported outcomes measured by the BREAST-Q and visual analogue scale (VAS) were assessed. RESULTS: Sixteen patients underwent fifth lateral intercostal artery perforator reconstruction, while 5 patients underwent fifth anterior intercostal artery perforator flap reconstruction. The surgeries were successful without intraoperative complications, with a mean operative time of 67 minutes. Postoperative complications were absent. The mean follow-up duration was 18 months. The mean nipple projection was 8 mm (range, 6-10 mm) with a shrinkage of 20% at 6 months after surgery. The average scores for psychosocial well-being, satisfaction with breasts, and satisfaction with nipples domains of the BREAST-Q significantly increased (P < .01) at 6 months post-reconstruction. Sexual well-being subdomain showed no statistical difference (P = .9369). The VAS scores for cosmesis and patient satisfaction with surgery were 9 and 9.3, respectively. CONCLUSION: The pedicled perforator flap technique for salvage nipple reconstruction is a safe and effective approach.


Assuntos
Neoplasias da Mama , Mamoplastia , Mamilos , Retalho Perfurante , Humanos , Feminino , Retalho Perfurante/irrigação sanguínea , Projetos Piloto , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Pessoa de Meia-Idade , Mamilos/cirurgia , Adulto , Satisfação do Paciente , Resultado do Tratamento , Idoso , Terapia de Salvação/métodos
2.
Anticancer Res ; 44(2): 593-604, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307587

RESUMO

BACKGROUND/AIM: Protein arginine methyltransferase 5 (PRMT5), a member of the arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical posttranslational modifications (PTMs). Phosphorylated P21-activated kinase 1 (p-PAK1), a serine/threonine protein kinase family member, is a cytoskeletal protein that plays a critical role in metastasis. We examined the expression of PRMT5 and PAK1 in esophageal squamous cell carcinoma (ESCC) and evaluated the correlation between PRMT5/p-PAK1 and both clinicopathological parameters and prognosis of ESCC patients. MATERIALS AND METHODS: 106 tumor tissues collected from ESCC patients were assessed for PRMT5 and PAK1 expression using immunohistochemistry. Pearson's correlation and Kaplan-Meier analysis were used to estimate the correlation with the clinicopathological parameters and effect on patient survival. Western blot analysis was used to determine the PRMT5/p-PAK1 protein expression. The wound healing assay was performed to assess the effect of PRMT5 on the migration of ESCC cells. RESULTS: PRMT5 is upregulated in ESCC and the level of PRMT5 is correlated with metastasis and can serve as an independent prognostic factor for overall survival (OS). PRMT5 knockdown remarkably inhibited ESCC cell migration with concomitantly reduced levels of phosphorylated PAK1 (p-PAK1) but not total PAK1. Kaplan-Meier analysis showed that the OS of the subgroup of patients with PRMT5high/p-PAK1high is remarkably shorter than those of other subgroups (i.e., PRMT5high/p-PAK1low, PRMT5low/p-PAK1low and PRMT5low/p-PAK1high). CONCLUSION: PRMT5-PAK1 signaling participates in ESCC metastasis and can predict patients' outcomes.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo , Biomarcadores Tumorais/metabolismo , Prognóstico , Histonas , Arginina , Estimativa de Kaplan-Meier , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo
3.
Front Immunol ; 14: 1232047, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936713

RESUMO

Background: Protein tyrosine phosphatase non-receptor type 1 (PTPN1), a member of the protein tyrosine phosphatase superfamily, has been identified as an oncogene and therapeutic target in various cancers. However, its precise role in determining the prognosis of human cancer and immunological responses remains elusive. This study investigated the relationship between PTPN1 expression and clinical outcomes, immune infiltration, and drug sensitivity in human cancers, which will improve understanding regarding its prognostic value and immunological role in pan-cancer. Methods: The PTPN1 expression profile was obtained from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases. Kaplan-Meier, univariate Cox regression, and time-dependent receiver operating characteristic curve analyses were utilized to clarify the relationship between PTPN1 expression and the prognosis of pan-cancer patients. The relationships between PTPN1 expression and the presence of tumor-infiltrated immune cells were analyzed using Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data and Tumor Immune Estimation Resource. The cell counting kit-8 (CCK-8) assay was performed to examine the effects of PTPN1 level on the sensitivity of breast cancer cells to paclitaxel. Immunohistochemistry and immunoblotting were used to investigate the relationship between PTPN1 expression, immune cell infiltration, and immune checkpoint gene expression in human breast cancer tissues and a mouse xenograft model. Results: The pan-cancer analysis revealed that PTPN1 was frequently up-regulated in various cancers. High PTPN1 expression was associated with poor prognosis in most cancers. Furthermore, PTPN1 expression correlated highly with the presence of tumor-infiltrating immune cells and the expression of immune checkpoint pathway marker genes in different cancers. Furthermore, PTPN1 significantly predicted the prognosis for patients undergoing immunotherapy. The results of the CCK-8 viability assay revealed that PTPN1 knockdown increased the sensitivity of MDA-MB-231 and MCF-7 cells to paclitaxel. Finally, our results demonstrated that PTPN1 was associated with immune infiltration and immune checkpoint gene expression in breast cancer. Conclusion: PTPN1 was overexpressed in multiple cancer types and correlated with the clinical outcome and tumor immunity, suggesting it could be a valuable potential prognostic and immunological biomarker for pan-cancer.


Assuntos
Neoplasias da Mama , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Prognóstico , Oncogenes , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Proteínas Tirosina Fosfatases , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética
4.
Cancer Lett ; 567: 216283, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37331584

RESUMO

Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase. Notably, epigenetically silenced PTPRO due to promoter hypermethylation is frequently linked to malignancies. In this study, we used cellular and animal models, and patient samples to demonstrate that PTPRO can suppress the metastasis of esophageal squamous cell carcinoma (ESCC). Mechanistically, PTPRO can inhibit MET-mediated metastasis by dephosphorylating Y1234/1235 in the kinase activation loop of MET. Patients with PTPROlow/p-METhigh had significantly poor prognosis, suggesting that PTPROlow/p-METhigh can serve as an independent prognostic factor for patients with ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/genética , Metástase Linfática , Linhagem Celular Tumoral , Monoéster Fosfórico Hidrolases , Prognóstico
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 122912, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37348273

RESUMO

The interfacial and confined water have long been attractive objects due to their crucial roles in biological, geological processes, etc. In this paper, we investigate the hydrogen-bonded structures of water and their low temperature transitions in the subnano channels of AlPO4-11 for the first time on the basis of infrared spectroscopy. The number of the adsorbed water molecules is estimated to be 8.45 per channel in one unit cell by thermogravimetric analysis. It is found that the confined water molecules are involved in saturated and unsaturated coordination with different hydrogen bond strengths at ambient temperature. The former refers to ice-like four-coordinated water and the latter includes liquid-like structures, Al-coordinated and relatively free water molecules. Unique coordination between water molecules and framework Al sites is responsible for the ice-like structures in the channels above the ice melting point. The appearance of liquid-like structures is closely related to the strong channel confinement, which does not allow the formation of extensive tetrahedral hydrogen-bonded configuration. As temperature decreases, a structural transformation of confined water happens in the channels of AlPO4-11. Isolated small water oligomers and two new components with stronger hydrogen bonds, such as low-density amorphous ice-like structures and a kind of low-density liquid-like structures are preferred. Our results provide important insights into the structural organizations and thermal-dynamic behaviors of confined water in extreme narrow channels.

6.
Technol Cancer Res Treat ; 22: 15330338231184990, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37386809

RESUMO

With the improvement of diagnostic techniques, numerous uncommon metastases derived from breast cancer were reported. However, very few studies explored the clinical characteristics and prognostic patterns of these patients. A total of 82 cases of uncommon metastatic breast cancer (MBC) registered at our hospital from January 1, 2010, to July 1, 2022, were selected for this retrospective study. The diagnoses of uncommon metastases were based on pathology, and the potential prognostic indicators (overall survival [OS], uncommon disease-free interval [uDFI], and remaining survival [RS]) were estimated. The uncommon metastases involved distant soft tissue, parotid gland, thyroid, digestive system, urinary system, reproductive system, bone marrow, and pericardium. Stepwise multivariate Cox regression analysis indicates age ≤ 35 is an independent risk factor of poor outcome of OS, uDFI, and RS in uncommon MBC patients. Meanwhile, uncommon metastasis combined with common visceral metastasis is an independent risk factor for poor RS of uncommon MBC patients, with a hazard ratio of 6.625 (95% confidence interval = 1.490-29.455, P = .013). Post hoc pairwise comparisons showed that uncommon MBC patients who developed bone-only metastasis survived longer than those concomitant with common visceral metastasis (P = .029). Although the incidence is low, uncommon MBC may involve multiple metastatic sites. The delayed diagnosis of uncommon metastases could lead to systemic progression of the disease. However, patients who only develop uncommon metastasis have a significantly better prognosis than that of those combined with common visceral metastasis. Even for those complicated by bone-only metastasis, active treatment of bone metastases can still achieve substantially longer survival.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico , Prognóstico , Hospitais , Análise Multivariada
7.
Front Plant Sci ; 14: 1102181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36844094

RESUMO

Peanut is an important oil and food legume crop grown in more than one hundred countries, but the yield and quality are often impaired by different pathogens and diseases, especially aflatoxins jeopardizing human health and causing global concerns. For better management of aflatoxin contamination, we report the cloning and characterization of a novel A. flavus inducible promoter of the O-methyltransferase gene (AhOMT1) from peanut. The AhOMT1 gene was identified as the highest inducible gene by A. flavus infection through genome-wide microarray analysis and verified by qRT-PCR analysis. AhOMT1 gene was studied in detail, and its promoter, fussed with the GUS gene, was introduced into Arabidopsis to generate homozygous transgenic lines. Expression of GUS gene was studied in transgenic plants under the infection of A. flavus. The analysis of AhOMT1 gene characterized by in silico assay, RNAseq, and qRT-PCR revealed minute expression in different organs and tissues with trace or no response to low temperature, drought, hormones, Ca2+, and bacterial stresses, but highly induced by A. flavus infection. It contains four exons encoding 297 aa predicted to transfer the methyl group of S-adenosyl-L-methionine (SAM). The promoter contains different cis-elements responsible for its expression characteristics. Functional characterization of AhOMT1P in transgenic Arabidopsis plants demonstrated highly inducible behavior only under A. flavus infection. The transgenic plants did not show GUS expression in any tissue(s) without inoculation of A. flavus spores. However, GUS activity increased significantly after inoculation of A. flavus and maintained a high level of expression after 48 hours of infection. These results provided a novel way for future management of peanut aflatoxins contamination through driving resistance genes in A. flavus inducible manner.

8.
Acta Pharm ; 73(1): 75-90, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692465

RESUMO

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.


Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Células MDA-MB-231 , Ciclina B1/metabolismo , Ciclina B1/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Proliferação de Células , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral
9.
Technol Cancer Res Treat ; 21: 15330338221132926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36310472

RESUMO

Background: Palbociclib is the most widely used cyclin-dependent kinase 4/6 inhibitor in China, but its early application efficacy on Chinese metastatic breast cancer (MBC) patients was reported deficiently. Methods: Between February 2019 to December 2021, 95 female hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) patients with MBC received palbociclib combined with AI or fulvestrant were retrospectively analyzed in our center. The primary outcome was progression-free survival (PFS). The objective response rate and clinical benefit rate (CBR) were evaluated. Results: The median follow-up period was 15 months (range from 2 to 37). Palbociclib performed superiorly when applicated in first-and-second line therapy than in later lines (P = .002). Palbociclib combined with AI or fulvestrant had a median PFS of 34 months (95% confidence interval [CI] = 6.87-61.13) and 12 months (95%CI = 7.76-16.24), respectively. Univariate subgroup analysis showed that the previous history of salvage chemotherapy (P = .015) and the presence of liver metastases (P < .001) significantly affected the efficacy of palbociclib. Despite the existence of liver metastases and primary endocrine resistance, which are two independent predictors of poor prognosis, early application of palbociclib in advanced stage can bring further benefits to these two groups of patients, rather than choosing salvage chemotherapy in the first place. Conclusion: Palbociclib combined with endocrine therapy has a favorable efficacy and acceptable toxicity in HR+/HER2- Chinese MBC patients. Better performance can be seen when palbociclib was applicated in the early stage.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Humanos , Feminino , Fulvestranto/uso terapêutico , Neoplasias da Mama/patologia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico
10.
Front Immunol ; 13: 947841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003382

RESUMO

Background: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in "immune-cold" breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. Methods: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan-Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. Results: High PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). Conclusion: PTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients.


Assuntos
Neoplasias da Mama , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Linfócitos T CD8-Positivos , Feminino , Humanos , Imunoterapia , Monoéster Fosfórico Hidrolases , Prognóstico , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética , Microambiente Tumoral
11.
Inorg Chem ; 61(7): 3212-3222, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35142209

RESUMO

Ultrasensitive pressure-induced optical materials are of great importance owing to their potential applications in optical pressure sensors. However, the lack of outstanding pressure sensitivity, observable color evolution, and structure reliability limits their further development in both practical applications and luminescence theory. To overcome the above problems, an enlightening methodology is proposed to explore the high sensitivity and phase stability of hafnium silicate K2HfSi2O7 (KHSO) phosphor with a Khibinskite structure. By employing X-ray diffraction (XRD) Rietveld refinement, cryogenic spectroscopy, and ancillary calculations, information on Eu2+ ion occupation is completely obtained at atmospheric pressure. The remarkable pressure sensitivity (dλ/dP = 3.25 nm/GPa-1) and excellent phase stability up to 20 GPa, along with the reproducible color hue variation, exhibit unprecedented superiority when used in optical pressure sensors. These advantages can be assigned to the pressure-induced Eu2+-selective occupation and the unique properties of 5d-4f transition (Stokes shift, nephelauxetic effect, and intense crystal field strength), which are clearly proved by measuring the XRD patterns, Raman spectra, and Gaussian fitting spectra under compression and decompression processes. The excellent luminescence property manifests that KHSO/Eu2+ can be considered as a potential luminescent material for solid-state lighting and optical pressure sensors.

12.
Int J Mol Med ; 45(1): 162-174, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746365

RESUMO

To verify whether amyloid precursor protein (APP) affects the migration and invasion of breast cancer cell lines, and to understand its underlying mechanisms, epithelial­mesenchymal transition (EMT), the mitogen­activated protein kinase (MAPK) signaling pathway and the matrix metalloproteinase (MMP) family were investigated in MDA­MB­231, MCF­7 and BT474 human breast cancer cells. Breast cancer cell lines were transfected with plasmids containing APP coding sequences (pEGFP­n1­APP) and APP short hairpin RNA (pENTR APP shRNA). APP overexpression efficiency, knockout efficiency and the expression levels of related genes were tested using reverse transcription­quantitative PCR (RT­qPCR) and western blot analyses. The effects of APP and mitogen­activated protein kinase kinase (MEK) inhibitor on cell migration and invasion were examined using Transwell assays. The results demonstrated that APP was significantly upregulated in the pEGFP­n1­APP group (P<0.05), and significantly downregulated in the pENTR APP shRNA group (P<0.05), compared with the control group. APP overexpression increased the migratory and invasive ability of human breast cancer cells (P<0.05), whereas APP silencing significantly inhibited cell migration and invasion (P<0.05). RT­qPCR and western blot analysis results suggested that APP overexpression significantly increased the expression of MMP­9, MMP­2, MMP­3, N­cadherin and vimentin (P<0.05). In addition, the enhanced expression of APP markedly affected the phosphorylation of mitogen­activated protein kinase kinase kinase 11 (MLK3), mitogen­activated protein kinase kinase 4 (MEK4) and mitogen­activated protein kinase 10 (JNK3; P<0.05). Additionally, APP overexpression had no effect on the total expression levels of MLK3, MEK4, and JNK3; however, APP overexpression significantly decreased the expression levels of E­cadherin and cytokeratin (P<0.05). Conversely, APP silencing had the opposite effects. When cells were treated with the MEK inhibitor PD0325901, the expression of APP was not altered, nor was the expression levels of MEK and its upstream signaling molecules. Taken together, the present findings suggested that APP could affect the migration and invasion of human breast cancer cells by mediating the activation of the MAPK signaling pathway, thereby promoting the EMT process.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Neoplasias da Mama/metabolismo , Sistema de Sinalização das MAP Quinases , Precursor de Proteína beta-Amiloide/genética , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação , Inibidores de Proteínas Quinases/farmacologia
13.
Eur J Med Chem ; 167: 187-199, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30771605

RESUMO

To get new anti-hepatoma agents with anti-inflammatory activity and hypotoxicity, a series of dissymmetric pyridyl-substituted 3,5-bis(arylidene)-4-piperidones (BAPs, 25-82) were designed and synthesized. Many of them exhibited potential anti-hepatoma properties against human hepatocellular carcinoma cell lines (HepG2, QGY-7703, SMMC-7721) and hypotoxicity for human normal heptical cell line (HHL-5, LO2), and prominently inhibited lipopolysaccharides (LPS) induced IL-6, TNF-α secretion to exert its anti-inflammatory effect. Combining the data of cytotoxicity, cytocompatibility and anti-inflammatory activity, 3-pyridyl and -CF3 substituted 67 may be the potential anti-hepatoma agent. 67 effectively promoted cell apoptosis through up-regulating cleaved caspase-3 and Bax expression and down-regulating Bcl-2 expression. Furthermore, 67 prominently inhibited NF-κB pathway activation by blocking the phosphorylation of IκBα, p65 and the nuclear translocation of NF-κB induced by TNF-α and LPS. In addition, 67 could reasonably bind to the active site of Bcl-2 and NF-κB/p65 protein proved by Molecular docking analyses. Moreover, 67 significantly suppressed the growth and inflammatory response of HepG2 xenografts in nude mice and was relatively nontoxic to mice. These results suggest that 67 may be effective and hypotoxicity anti-hepatoma agent for the clinical treatment of liver cancers.


Assuntos
Antineoplásicos/síntese química , Neoplasias Hepáticas Experimentais/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Piperidonas/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Xenoenxertos , Humanos , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Piperidonas/síntese química , Relação Estrutura-Atividade
14.
Med Sci Monit ; 25: 880-887, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30700694

RESUMO

BACKGROUND The aim of this study was to investigate the role of axillary lymph node dissection on the outcome of patients with tubular carcinoma of the breast. MATERIAL AND METHODS Patients diagnosed with tubular carcinoma of the breast between 2000-2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analysis of the data was undertaken, including analysis of breast cancer-specific survival (BCSS). RESULTS Of the 5,645 patients identified on the SEER database with tubular carcinoma of the breast, 5,032 (89.4%) patients had undergone axillary lymph node dissection, with significantly increased rates after 2002 compared with rates between 2000-2001 (p <0.001), which stabilized between 2002-2013 (p=0.330). Axillary lymph node metastases were present in 6.1% of all patients and in 5.3% of patients with a tumor size ≤2 cm. Lymph node-positive disease was associated with patient age ≤65 years, intermediate-grade or high-grade tumors, and tumor size >2.0 cm. Axillary lymph node dissection was an independent prognostic indicator. The 10-year BCSS was 97.3% and 96.6% in patients with and without axillary lymph node dissection, respectively (p=0.002). The number of removed lymph nodes was not related to breast cancer-specific survival. CONCLUSIONS In patients with tubular carcinoma of the breast, lymph node status was not associated with significant breast cancer-specific survival. However, axillary lymph node dissection may still be considered for patients with for tubular carcinoma of the breast even in patients with a small tumor size.


Assuntos
Adenocarcinoma/patologia , Excisão de Linfonodo/mortalidade , Adenocarcinoma/metabolismo , Adulto , Idoso , Axila/patologia , Mama/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
15.
Phys Chem Chem Phys ; 20(41): 26117-26125, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30306996

RESUMO

The mechanical stability of porous zeolitic materials has long been an important issue due to their advanced applications in many fields. Here, we choose to study the pressure induced structural modifications on the AlPO4-5 (AFI) framework. We find that the Raman characteristics of the confined iodine molecules in the AFI channels, with a low filling density, show discontinuities at around 3 and 10 GPa, which can be attributed to the implications of framework changes. Subsequent theoretical simulations on the AFI framework demonstrate that both a tilting mechanism along the c axis and a rotating mechanism in the ab plane of the tetrahedrons contribute to the structural deformation, and the AFI framework is collapsible at 4 and 10 GPa, which confirms those values found in the Raman studies. In this nanoconfinement system of I@AFI, the host and guest depend on and interact with each other mutually. No supporting effect on the AFI framework is found for the confined individual iodine molecules with such a low filling density, but they can be regarded as molecular probes to reflect the structural collapse of AFI. Thus, we provide a novel way to detect the structural deformation of porous materials under high pressure.

16.
Adv Mater ; 30(22): e1706916, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29658170

RESUMO

As a new category of solids, crystalline materials constructed with amorphous building blocks expand the structure categorization of solids, for which designing such new structures and understanding the corresponding formation mechanisms are fundamentally important. Unlike previous reports, new amorphous carbon clusters constructed ordered carbon phases are found here by compressing C8 H8 /C60 cocrystals, in which the highly energetic cubane (C8 H8 ) exhibits unusual roles as to the structure formation and transformations under pressure. The significant role of C8 H8 is to stabilize the boundary interactions of the highly compressed or collapsed C60 clusters which preserves their long-range ordered arrangement up to 45 GPa. With increasing time at high pressure, the gradual random bonding between C8 H8 and carbon clusters, due to "energy release" of highly compressed cubane, leads to the loss of the ability of C8 H8 to stabilize the carbon cluster arrangement. Thus a transition from short-range disorder to long-range disorder (amorphization) occurs in the formed material. The spontaneous bonding reconstruction most likely results in a 3D network in the material, which can create ring cracks on diamond anvils.

17.
Phys Rev Lett ; 118(24): 245701, 2017 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-28665670

RESUMO

Design and synthesis of new carbon allotropes have always been important topics in condensed matter physics and materials science. Here we report a new carbon allotrope, formed from cold-compressed C_{70} peapods, which most likely can be identified with a fully sp^{3}-bonded monoclinic structure, here named V carbon, predicted from our simulation. The simulated x-ray diffraction pattern, near K-edge spectroscopy, and phonon spectrum agree well with our experimental data. Theoretical calculations reveal that V carbon has a Vickers hardness of 90 GPa and a bulk modulus ∼400 GPa, which well explains the "ring crack" left on the diamond anvils by the transformed phase in our experiments. The V carbon is thermodynamically stable over a wide pressure range up to 100 GPa, suggesting that once V carbon forms, it is stable and can be recovered to ambient conditions. A transition pathway from peapod to V carbon has also been suggested. These findings suggest a new strategy for creating new sp^{3}-hybridized carbon structures by using fullerene@nanotubes carbon precursor containing odd-numbered rings in the structures.

18.
J Chem Phys ; 145(12): 124319, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27782680

RESUMO

We present a joint experimental and theoretical study on the high-pressure behavior of bromine confined in the one-dimensional (1D) nanochannels of zeolite AlPO4-5 (AFI) single crystals. Raman scattering experiments indicate that loading bromine into AFI single crystals can lead to the formation of bromine molecular chains inside the nanochannels of the crystals. High-pressure Raman and X-ray diffraction studies demonstrate that high pressure can increase the length of the confined bromine molecular chains and modify the inter- and intramolecular interactions of the molecules. The confined bromine shows a considerably different high-pressure behavior to that of bulk bromine. The pressure-elongated bromine molecular chains can be preserved when the pressure is reduced to ambient pressure. Theoretical simulations explain the experimental results obtained from the Raman spectroscopy and X-ray diffraction studies. Furthermore, we find that the intermolecular distance between confined bromine molecules gradually becomes comparable to the intramolecular bond length in bromine molecules upon compression. This may result in the dissociation of the bromine molecules and the formation of 1D bromine atomic chains at pressures above 24 GPa. Our study suggests that the unique nanoconfinement has a considerable effect on the high-pressure behavior of bromine, and the confined bromine species concomitantly enhance the structural stability of the host AFI single crystals.

19.
Nanoscale ; 8(3): 1456-61, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26676154

RESUMO

Unlike bulk iodine, iodine molecular chains formed inside one dimensional (1D) nanochannels of AlPO4-5 (AFI) single crystals show unexpected PL behavior. Thanks to its unique 1D structure, the PL exhibits obvious polarization both in excitation and emission, by changing the angle between the c-axis of the channels and the polarization direction of the incident laser. As pressure increases, the PL intensity increases obviously due to the population increase of (I2)n chains upon compression. In contrast, the breaking of the (I2)n chain at high temperature leads to the decrease of PL intensity. Our theoretical calculation further points out that the PL may arise from the intrinsic band structure of (I2)n chains.

20.
J Chem Phys ; 142(3): 034702, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25612720

RESUMO

Raman spectra of onion-like carbon nanospheres (OCNSs) have been studied under pressure up to 48 GPa. A transformation related to a change from sp(2) to sp(3) bonding of carbons in OCNSs was observed at pressures above 20 GPa. The Raman spectra exhibit some vibrational features similar to those of the theoretically proposed Z-carbon phase of cold-compressed graphite, while the transition pressure is obviously higher than that for graphite. In contrast to the transformations in compressed graphite, interlayer bonds are formed on the nanoscale between buckled layers in OCNSs under pressure due to the concentric configuration, and sp(2)-sp(3) conversion is incomplete even up to 48 GPa. This is confirmed by TEM observations on the decompressed samples. Moreover, the onion-like carbon structure is extremely stable and can be recovered even after a compression cycle to 48 GPa. This high stability, beyond that of other sp(2) carbon materials, is related to the unique onion-like configuration and to the interlayer bonding. The transformed material should have excellent mechanical properties so that it can sustain very high pressure.

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