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1.
Aging (Albany NY) ; 12(1): 340-358, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907338

RESUMO

Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells in vitro and causes tumor metastasis in vivo. Furthermore, we find that EBV-miR-BART13-3p directly targets ABI2, known as a tumor suppressor and a cell migration inhibitor, drives epithelial-mesenchymal transition (EMT) by activating c-JUN/SLUG signaling pathway. Silencing ABI2 shows similar effects to overexpression of EBV-miR-BART13-3p, whereas reconstitution of ABI2 resulted in a phenotypic reversion, highlighting the role of ABI2 in EBV-miR-BART13-3p-driven metastasis in NPC. Besides, expression levels of ABI2 in NPC tissue samples correlate with N stages of NPC patients. Taken together, these results suggest a novel mechanism by which ABI2 downregulation by EBV-miR-BART13-3p promotes EMT and metastasis of NPC via upregulating c-JUN/SLUG signaling pathway.

2.
ACS Nano ; 13(11): 12638-12652, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31625721

RESUMO

Photodynamic therapy (PDT) is a clinical cancer treatment modality based on the induction of therapeutic reactive oxygen species (ROS), which can trigger immunogenic cell death (ICD). With the aim of simultaneously improving both PDT-mediated intracellular ROS production and ICD levels, we designed a serum albumin (SA)-coated boehmite ("B"; aluminum hydroxide oxide) organic-inorganic scaffold that could be loaded with chlorin e6 (Ce6), a photosensitizer, and a honey bee venom melittin (MLT) peptide, denoted Ce6/MLT@SAB. Ce6/MLT@SAB was anchored by a boehmite nanorod structure and exhibited particle size of approximately 180 nm. Ce6/MLT@SAB could significantly reduce hemolysis relative to that of free MLT, while providing MLT-enhanced PDT antitumor effects in vitro. Compared with Ce6@SAB, Ce6/MLT@SAB improved Ce6 penetration of cancer cells both in vitro and in vivo, thereby providing enhanced intracellular ROS generation with 660 nm light treatment. Following phototreatment, Ce6/MLT@SAB-treated cells displayed significantly improved levels of ICD and abilities to activate dendritic cells. In the absence of laser irradiation, multidose injection of Ce6/MLT@SAB could delay the growth of subcutaneous murine tumors by more than 60%, compared to controls. When combined with laser irradiation, a single injection and phototreatment with Ce6/MLT@SAB eradicated one-third of subcutaneous tumors in treated mice. The addition of an immune checkpoint blockade to Ce6/MLT@SAB phototreatment further augmented antitumor effects, generating increased numbers of CD4+ and CD8+ T cells in tumors with concomitant reduction of myeloid-derived suppressor cells.

3.
Environ Technol ; : 1-11, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31180796

RESUMO

Tetracycline hydrochloride as an environmental pollutant is biologically toxic and highly difficult to degrade. To solve this problem, an efficient catalyst IO-TiO2-CdS composite with honeycomb-like three-dimensional (3D) inverse opal TiO2 (IO-TiO2) and cadmium sulphide (CdS) was synthesized and applied in the degradation of tetracycline hydrochloride in this paper. More than 99% of the tetracycline hydrochloride (30 mg/L) can be degraded by IO-TiO2-CdS (30 mg) within 20 min under visible light irradiation. Surprisingly, the naphthol rings can be opened and degraded to alkane with a minimum molecular weight of 60, which is the smallest fragment among all publications. The three-dimensional ordered macroporous (3DOM) structure of IO-TiO2 improves the utilization of light via the slow photon effect. Meanwhile, the addition of CdS enhances the degradation efficiency of tetracycline by broadening the range of absorption spectrum and improving the separation of charge carrier on the catalyst. In addition to the degradation of tetracycline hydrochloride, IO-TiO2-CdS also shows a good degradation efficiency of Rhodamine B (RhB). This work provides a promising approach to construct visible light response photocatalysts with non-noble metal for efficient degradation of wastewater pollutants.

4.
J Cardiovasc Pharmacol ; 73(3): 186-194, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30839512

RESUMO

OBJECTIVE: To investigate whether phenylephrine (PE) inhibits sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway. METHODS: A rat model of sepsis was established by cecal ligation and puncture. PE and/or wortmannin (a PI3K inhibitor) were administered to investigate the role of PI3K/Akt signaling in mediating the effects of PE on inhibiting sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury. Hematoxylin-eosin staining, echocardiography, and Langendorff system were used to examine the myocardial injury and function. The concentrations of TNF-α and IL-6 were analyzed by enzyme-linked immunosorbent assay. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, mitochondria-related fusion/fission proteins, and PI3K/Akt signaling pathway-associated proteins were analyzed by Western blotting. RESULTS: PE improved the cardiac function and survival in septic rats. PE decreased TNF-α, IL-6, ICAM-1, VCAM-1, and myeloperoxidase contents in the myocardium of septic rats. Meanwhile, PE increased the fusion-related proteins and decreased the fission-related proteins in the myocardial mitochondria of septic rats. On the other hand, PE activated the PI3K/Akt signaling pathway in the cecal ligation and puncture-treated rats, and all the protective effects of PE were abolished by wortmannin. CONCLUSIONS: PE attenuated sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.

6.
Clinics (Sao Paulo) ; 73: e16536, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30517277

RESUMO

OBJECTIVES: To introduce a new laparoscopic splenectomy (LS) approach. METHODS: Sixteen patients underwent LS with general anaesthesia and carbon dioxide pneumoperitoneum. The details of the surgery are as follows: 1. The omentum was incised along the greater curvature and retracted as much as possible to expose the pancreatic body and tail. 2. The right arteriovenous root in the gastric omentum was ligated to sufficiently expose the pancreatic body and tail. 3. The pancreatic capsula was opened along the inferior margin of the pancreatic tail, elevated and separated until the superior margin of the pancreas was grasped. The entire splenic pedicle was retracted using a string. The branching blood vessels in the splenic hilus were ligated using clamps and separated. The splenogastric and splenophrenic ligaments were transected proximally using an ultrasonic knife, and the thick short gastric blood vessels were clamped. This procedure allows complete exposure of the area above the pancreatic tail where the splenic hilus is located. The splenoportal vasculature was suspended using a 7-0 silk suture to easily manipulate this tissue. The splenic portal vessels were dissected using an ultrasonic knife, and the portal vessels were isolated individually using vascular clamps and transected. The splenogastric and lienorenal ligaments were also transected. The spleen was then placed into a bag, and the surgical port was slightly enlarged. Finally, the spleen was sectioned for removal. RESULTS: Fifteen surgeries were successfully performed from March 2015 to January 2016. One patient underwent laparotomy. No patients developed postoperative intra-abdominal haemorrhage or infection. One patient developed subcutaneous emphysema, and one developed a wound infection. No deaths occurred. CONCLUSIONS: Active exposure of the area dorsal to the pancreatic tail is a safe and simple splenectomy method.


Assuntos
Laparoscopia/métodos , Pâncreas/cirurgia , Esplenectomia/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Reprodutibilidade dos Testes , Fatores de Risco , Esplenectomia/efeitos adversos , Resultado do Tratamento , Adulto Jovem
7.
Int J Cardiol ; 270: 293-301, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29908831

RESUMO

BACKGROUND: Neonatal rat ventricular myocytes (NRVMs) have proven to be an ideal research model for cardiac disease. However, the current methods to purify NRVMs have a limitation to obtain high purity. The purpose of this study was to develop a NRVM purification method by using superparamagnetic iron oxide particles (SIOP). METHODS: NRVMs were purified by using SIOP (SIOP group). The differential attachment with or without bromodeoxyuridine (BrdU) treatment served as control and BrdU groups, respectively. The Percoll gradient (Percoll) and magnetic-activated cell sorting (MACS) methods were performed to compare the purity and viability of NRVMs with SIOP method. RESULTS: The SIOP group enriched NRVMs up to 93.9 ±â€¯2.0% purity determined by flow cytometry (FCM) and 95.6 ±â€¯1.3% by immunofluorescence count (IF). In contrast, the control group gave purities of 71.9 ±â€¯2.9% (by FCM) and 66.8 ±â€¯8.9% (by IF), and the BrdU group obtained 82.0 ±â€¯1.3% (by FCM) and 83.1 ±â€¯2.4% (by IF). The purity of SIOP-isolated NRVMs was not different from that of Percoll and MACS groups. However, the cardiomyocytes separated by these methods, except SIOP protocol, were mixed with intrinsic cardiac adrenergic cells. NRVMs purified by SIOP shaped the similar three-dimensional morphology, with no difference in cell yield, viability and cytosolic Ca2+ homeostasis at 24 h after isolation compared with NRVMs in other groups. Furthermore, SIOP-purified NRVMs retained the responses to phenylephrine and lipopolysaccharide challenge. CONCLUSION: We first reported an efficient and novel method to purify NRVMs using SIOP, which may help accelerate innovative research in the field of cardiomyocyte biology.


Assuntos
Separação Celular/métodos , Compostos Férricos/administração & dosagem , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Nanopartículas de Magnetita/administração & dosagem , Miócitos Cardíacos/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Células Cultivadas , Miócitos Cardíacos/fisiologia , Ratos , Ratos Sprague-Dawley
8.
Transl Oncol ; 11(2): 559-566, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29525633

RESUMO

OBJECTIVE: To investigate the correlation between the expression of PD-L1 and HIF-1α in hepatocellular carcinoma (HCC) tissue and further analyze the association with clinical parameters and the prognostic value of coexpression in HCC patients. METHODS: We assessed the expression of PD-L1 and HIF-1α by immunohistochemistry in tumor tissue from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients. RESULTS: PD-L1 and HIF-1α exhibited in tumor tissue high expression rates of 41.11% (37/90) and 43.33% (43/90), respectively, and their expressions were positively correlated (r = 0.563, P < .01). High expression of PD-L1 was significantly associated with low albumin levels (P < .05); high expression of HIF-1α was significantly correlated with high alpha-fetoprotein (AFP) levels and low albumin levels (P < .05); high expression of both PD-L1 and HIF-1α was also significantly associated with high AFP levels and low albumin levels (P < .05). High expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1 α was respectively significantly associated with worse overall survival (OS) and disease-free survival (DFS) (P < .05). Patients with co-overexpression of PD-L1 and HIF-1α had the worst prognosis compared with other groups. Additionally, multivariate Cox regression models suggested that high expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1α was an independent prognostic factor for OS and DFS (P < .05). Furthermore, the positive correlation and prognostic values of PD-L1 and HIF-1α were validated in an independent data set. CONCLUSION: We demonstrated that HCC patients with co-overexpression of PD-L1 and HIF-1α in tumor tissue had a significantly higher risk of recurrence or metastasis and death compared with others. Therefore, more frequent follow-up is needed for patients with co-overexpression of PD-L1 and HIF-1α. At the same time, a combinational therapy with HIF-1α inhibitors in conjunction with PD-L1 blockade may be beneficial for HCC patients with co-overexpression in the future.

9.
Oncol Lett ; 15(3): 2985-2991, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29435028

RESUMO

Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness-associated marker. However, one stemness-associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness-associated markers is required. Cluster of differentiation 133 (CD133) and α-fetoprotein (AFP) are common stemness-associated markers for HCC that have not yet been employed for HCC subtype classification. In the present study, CD133 expression was assessed by immunohistochemistry in 127 hepatitis B virus-associated HCC tumor specimens. Based on CD133 immunostaining and serum AFP levels, the HCC cases were subclassified into four subtypes, which demonstrated different clinicopathological features and varying prognoses. Among the four subtypes, the number of tumor lesions, histological grade and vascular invasion were significantly different (P=0.002, P=0.018 and P=0.022, respectively). CD133+AFP+ HCC was associated with a relatively poor prognosis, CD133-AFP- HCC was associated with a relatively good prognosis, while CD133+AFP- HCC and CD133-AFP+ HCC were associated with an intermediate prognosis. These prognostic values were confirmed by borderline or statistical significance (between all groups, overall survival, P=0.061; recurrence-free survival, P=0.015). These results define a novel and simple system, based on CD133 and AFP, for classifying HCC into four distinct prognostic subtypes. This classification system may aid the assessment of patients with HCC for personalized therapy.

10.
Clinics ; 73: e16, 2018. graf
Artigo em Inglês | LILACS-Express | ID: biblio-974912

RESUMO

OBJECTIVES: To introduce a new laparoscopic splenectomy (LS) approach. METHODS: Sixteen patients underwent LS with general anaesthesia and carbon dioxide pneumoperitoneum. The details of the surgery are as follows: 1. The omentum was incised along the greater curvature and retracted as much as possible to expose the pancreatic body and tail. 2. The right arteriovenous root in the gastric omentum was ligated to sufficiently expose the pancreatic body and tail. 3. The pancreatic capsula was opened along the inferior margin of the pancreatic tail, elevated and separated until the superior margin of the pancreas was grasped. The entire splenic pedicle was retracted using a string. The branching blood vessels in the splenic hilus were ligated using clamps and separated. The splenogastric and splenophrenic ligaments were transected proximally using an ultrasonic knife, and the thick short gastric blood vessels were clamped. This procedure allows complete exposure of the area above the pancreatic tail where the splenic hilus is located. The splenoportal vasculature was suspended using a 7-0 silk suture to easily manipulate this tissue. The splenic portal vessels were dissected using an ultrasonic knife, and the portal vessels were isolated individually using vascular clamps and transected. The splenogastric and lienorenal ligaments were also transected. The spleen was then placed into a bag, and the surgical port was slightly enlarged. Finally, the spleen was sectioned for removal. RESULTS: Fifteen surgeries were successfully performed from March 2015 to January 2016. One patient underwent laparotomy. No patients developed postoperative intra-abdominal haemorrhage or infection. One patient developed subcutaneous emphysema, and one developed a wound infection. No deaths occurred. CONCLUSIONS: Active exposure of the area dorsal to the pancreatic tail is a safe and simple splenectomy method.

11.
Oncol Lett ; 14(6): 6929-6936, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29151919

RESUMO

Transforming growth factor ß1 (TGF-ß1) has been associated with poor outcomes in patients with breast cancer. However, the functions and underlying molecular mechanisms of TGF-ß1 in breast cancer remain unknown. Therefore, the present study aimed to identify the effects of components of the TGF-ß/microRNA (miR-)21/phosphatase and tensin homolog (PTEN) signaling axis in breast cancer. TGF-ß1 was identified to upregulate the expression of miR-21, and miR-21 was demonstrated to be significantly upregulated in breast cancer tissues compared with benign proliferative breast disease. In addition, the expression of miR-21 was significantly associated with increased TGF-ß1 and clinical characteristics in patients, including tumor grade and lymph node metastasis (all P<0.05). Furthermore, in the breast cancer MCF-7 cell line, TGF-ß1 was revealed to induce the expression of miR-21 in a dose- and time-dependent manner. The results of the present study additionally demonstrated that increased miR-21, in response to TGF-ß1 signaling, was associated with tumor invasion and chemoresistance in vitro. In addition, suppression of PTEN was mediated by TGF-ß1-induced expression of miR-21 in breast cancer cells and using a miR-21 inhibitor revitalized the expression of PTEN. The results of the present study explored the functions of TGF-ß1-stimulated expression of miR-21 to suppress the PTEN axis, which promotes breast cancer progression and chemoresistance.

13.
Cell Death Dis ; 8(8): e2987, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28796263

RESUMO

As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Linhagem Celular , Feminino , Proteínas de Choque Térmico/genética , Humanos , Marcação In Situ das Extremidades Cortadas , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Proteínas de Membrana/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Supressoras de Tumor/genética
14.
ACS Appl Mater Interfaces ; 9(28): 23420-23427, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28636312

RESUMO

We combine the telomerase extension reaction and microRNA (miRNA)-induced rolling circle amplification, followed by graphene oxide (GO) and nicking enzyme-assisted signal amplification as a method to analyze telomerase and miRNA-21 in urine samples with the following merits. First, it is a binary assay and can simultaneously output double signals that correspond to the quantities of telomerase and miRNA, respectively. Second, telomerase activity is enhanced by using a DNA molecular beacon probe to inhibit the formation of G-quadruplex. Third, background noise is decreased significantly via introduction of GO. Fourth, performance tests on about 258 urine samples demonstrate that this binary assay can distinguish between urine from bladder cancer patients, those with cystitis, and normal individuals. Finally, this strategy also shows great potential in distinguishing between muscle-invasive bladder cancers and non-muscle-invasive bladder cancers. The proposed strategy will greatly contribute to clinical decision-making and individualized treatments.


Assuntos
MicroRNAs/análise , Proteínas/análise , Quadruplex G , Grafite , Humanos , Telomerase , Neoplasias da Bexiga Urinária
15.
Dis Markers ; 2017: 8495326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28572700

RESUMO

Accumulating evidence suggests that the tumor microenvironment has a profound influence on tumor initiation and progression, opening a new avenue for studying tumor biology. Nonetheless, the prognostic values of the peritumoral expression of EpCAM and CD13 remain to be elucidated in hepatocellular carcinoma (HCC) patients. In this study, the expression of EpCAM and CD13 was assessed by immunohistochemistry in peritumoral liver hepatocytes from 106 hepatitis B virus- (HBV-) related HCC patients who had undergone curative hepatectomy. The peritumoral EpCAM-positive group had a significantly worse overall survival (OS) (p = 0.003) and recurrence-free survival (RFS) (p = 0.022) compared to the negative group. Peritumoral CD13-positive patients were also associated with poor OS (p = 0.038), while not significantly associated with RFS. The adjusted multivariate COX proportional hazard regression analysis suggested that only the positive expression of peritumoral EpCAM precisely predicted poor OS. Being peritumoral EpCAM positive was also significantly associated with a larger tumor size, liver cirrhosis, and more frequent vascular invasion; however, no statistically significant association was observed between CD13 and any clinicopathological features. Taken together, peritumoral EpCAM and CD13 expression was associated with a poor prognosis, but EpCAM may be a better prognostic marker than CD13 in HBV-related HCC patients. In the future, peritumoral EpCAM could be a good target for adjuvant therapy after curative hepatectomy.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Neoplasias Hepáticas/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Antígenos CD13/genética , Antígenos CD13/metabolismo , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Molécula de Adesão da Célula Epitelial/genética , Feminino , Hepatite B/complicações , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral
16.
Transl Oncol ; 10(4): 511-517, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28558264

RESUMO

BACKGROUND: Recurrence or metastasis of hepatocellular carcinoma (HCC) is mainly intrahepatic after curative resection, demonstrating that the peritumoral environment is important but often neglected. Programmed death ligand 1 (PD-L1) in intratumoral liver tissues is a poor prognosis factor whose impact is removed after curative resection. However, PD-L1 expression remains in the peritumoral liver tissues and its distribution and prognostic value are still not clear. METHODS: We assessed the expression of PD-L1 by immunohistochemistry in peritumoral liver tissues from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients. RESULTS: We found PD-L1 positive expression in 31.11% (28/90) of peritumoral tissues. Peritumoral PD-L1 expression was associated with a significantly worse overall survival (OS) (P=.000) and disease-free survival (DFS) (P=.001) compared to the negative expression group. Additionally, peritumoral PD-L1 positivity significantly correlated with vascular invasion and a lower albumin level (≤35 g/L). Univariate and multivariate Cox regression models both revealed peritumoral PD-L1 as an independent prognostic factor for OS (HR=2.853, P=.002) and DFS (HR=2.362, P=.003). The prognostic value of PD-L1 positivity was validated in the independent data set. CONCLUSIONS: Our data suggest PD-L1 expression in peritumoral hepatocytes is an independent prognostic factor for OS and DFS. This implies that future anti-cancer therapy should target not only residual tumor cells but also the "soil" for promoting tumor growth. Peritumoral PD-L1 could be a good target for adjuvant therapy after hepatectomy.

17.
Transl Oncol ; 10(3): 431-441, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28448959

RESUMO

PURPOSE: Gastric cancer studies indicated a potential correlation between circulating tumor cells (CTCs) in peripheral blood and tumor relapse/metastasis. The prevalence and significance of circulating tumor microemboli (CTM) in gastric cancer remain unknown. We investigated the prevalence and prognostic value of CTCs and CTM for progression-free survival (PFS) and overall survival (OS) in gastric cancer patients. METHODS: Eighty-one gastric cancer patients consented to provide 5ml of peripheral blood before systematic therapy. CTCs and CTM were isolated using isolation by size of epithelial tumor cells and characterized by cytopathologists. For 41 stage IV gastric cancer patients, CTM was investigated as a potential biomarker to predict prognosis. RESULTS: CTCs were detected in 51 patients; the average count was 1.81. In clinical stage I, II, III, and IV patients, the average CTC counts were 1.40, 0.67, 1.24, and 2.71, respectively. CTM were detected in 3 of 33 clinical stage I to IIIb patients, at an average of 0.12 (0-2). CTM were detected in 13 of 53 clinical stage IIIc to IV patients, at an average of 1.26 (0-22). In stage IV patients, CTM positivity correlated with the CA125 level. PFS and OS in CTM-positive patients were significantly lower than in CTM-negative patients (P<.001). CTM positivity was an independent factor for determining the PFS (P=.016) and OS (P=.003) of stage IV patients in multivariate analysis. Using markers of the epithelial-mesenchymal transition, single CTCs were divided into three phenotypes including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs. For CTM, CK-/Vimentin+/CD45- and CK+/Vimentin+/CD45- phenotypes were observed, but the CK+/Vimentin-/CD45- CTM phenotype was not. CA125 was detected in gastric cancer cell lines BGC823 and MGC803. CONCLUSIONS: In stage IV patients, CTM positivity was correlated with serum CA125 level. CTM were an independent predictor of shorter PFS and OS in stage IV patients. Thus, CTM detection may be a useful tool to predict prognosis in stage IV patients.

18.
PLoS One ; 12(3): e0173693, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28296916

RESUMO

PURPOSE: The current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC). METHOD: Electronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model. RESULTS: This meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4-41.5) and 55.6% (95% CI 49.2-61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3-64.9), 70.3% (95% CI 62.6-76.9), and 40.0% (95% CI 30.6-50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1-39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070). CONCLUSIONS: Metronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Humanos , Metástase Neoplásica , Taxa de Sobrevida
19.
Cancer Cell Int ; 17: 6, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28070168

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) detected in peripheral blood (PB) of cancer patients can be identified as isolated CTCs and circulating tumor microemboli (CTM). This study aimed to evaluate the prognostic value of CTM detection and CTC phenotype in advanced colorectal cancer (CRC) patients during chemotherapy. METHODS: A size-based platform for CTC isolation was applied. PB samples (5 ml) from 98 advanced CRC patients during 2-6 cycles chemotherapy were collected for CTC detection, and CTC count was correlated to patient's clinicopathological characteristics and clinical outcome. And CTC phenotype was measured by immunofluorescent staining and evaluate the predictive significance on survival in 32 CTCs-positive patients with advanced CRC. RESULTS: Forty-eight of 98 patients were CTCs-positive, including 18 CTM-positive patients, and CTC detection was positively correlated with lymphatic invasion (P = 0.049), TNM stage (P = 0.023), and serum CEA level (P = 0.014). Moreover, Kaplan-Meier survival and Cox regression analyses revealed that the presence of CTCs was an independent factor for poor PFS and OS (P < 0.05) in advanced CRC patients during chemotherapy, and CTM-positive patients had shooter survival than isolated CTCs-positive patients (P < 0.05). Furthermore, patients with vimentin+ isolated CTCs/CTM had shorter PFS and OS compared with CK+ CTCs (P < 0.05). CONCLUSIONS: This study provided evidence that the presence of CTCs was positively correlated with poor prognosis, and furthermore, CTM and vimentin+ CTCs predicted poorer survival, which indicated that CTM and vimentin+ CTCs detected by a sensitive platform could be used to improve prognostic value of CTCs in advanced CRC patients under treatment.

20.
Wei Sheng Wu Xue Bao ; 55(8): 1018-25, 2015 Aug 04.
Artigo em Chinês | MEDLINE | ID: mdl-26665599

RESUMO

OBJECTIVE: Curdlan is produced by Agrobacterium sp. ATCC 31749 under nitrogen limiting condition. The biosynthesis of crudlan is a typical aerobic bioprocess, and the production of curdlan would be severely restricted under micro-aerobic and anoxic conditions. Proteomic analysis of Agrobacterium sp. was conducted to investigate the effect of dissolved oxygen on the crucial enzymes involved in curdlan biosynthesis. METHODS: Two-dimensional gel electrophoresis was performed to separate and visualize the differential expression of the intracellular proteins extracted from Agrobacterium sp. ATCC 31749 cultured under various dissolved oxygen levels (75%, 50%, 25% and 5%). In addition, a comparative proteomic analysis of the intracellular proteins expression level under various dissolved oxygen levels was done. Significant differently expressed proteins were identified by MALDI-TOF/TOF. RESULTS: Finally, we identified 15 differently expressed proteins involved in polysaccharide synthesis, fatty acid synthesis, amino acid synthesis pathway. Among these proteins, phosphoglucomutase and orotidine 5-phosphate decarboxylase were the key metabolic enzymes directing curdlan biosynthesis. CONCLUSION: Oxygen could affect the expression of the proteins taking charge of curdlan synthesis significantly.


Assuntos
Agrobacterium/metabolismo , Proteínas de Bactérias/química , Oxigênio/metabolismo , beta-Glucanas/metabolismo , Agrobacterium/química , Agrobacterium/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Eletroforese em Gel Bidimensional , Dados de Sequência Molecular , Proteômica
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