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1.
Sci Rep ; 14(1): 10873, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740918

RESUMO

In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model's utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model.


Assuntos
Adenocarcinoma de Pulmão , Anoikis , Antígeno B7-H1 , Imunoterapia , Neoplasias Pulmonares , Receptor de Morte Celular Programada 1 , RNA-Seq , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Anoikis/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Análise de Célula Única , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Biomarcadores Tumorais/genética
2.
J Cancer ; 15(8): 2260-2275, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495502

RESUMO

Background: Hepatocellular carcinoma often results in late-stage diagnosis, leading to decreased treatment success. To improve prognosis, this study integrates cuproptosis with immune risk scoring models for HCC patients. Method: We identified differentially expressed genes connected to cuproptosis and immune responses using Pearson correlation. A risk signature was then constructed via LASSO regression, and its robustness was validated in the International Cancer Genome Consortium dataset. Additionally, qPCR confirmed findings in tumor and normal tissues. Results: Eight genes emerged as key prognostic markers from the 110 differentially expressed genes linked to cuproptosis and immunity. A risk-scoring model was developed using gene expression, effectively categorizing patients into low- or high-risk groups. Validated in the ICGC dataset, high-risk patients had significantly reduced survival times. Multivariate Cox regression affirmed the risk signature's independent predictive capability. A clinical nomogram based on the risk signature was generated. Notably, low-risk patients might benefit more from immune checkpoint inhibitors. qPCR and western blotting results substantiated our bioinformatics findings. Conclusions: The genetic risk signature linked to cuproptosis and immunity holds potential as a vital prognostic biomarker for Hepatocellular carcinoma, providing avenues for tailored therapeutic strategies.

3.
Biochem Biophys Res Commun ; 708: 149808, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38520914

RESUMO

Osteosarcoma is the most common malignant bone tumor. It has a poor prognosis because of a lack of therapeutic targets and strategies. The SET domain-containing lysine-specific methyltransferase, SET7/9, has various functions in different cancer types in tissue-type and signaling context-dependent manners. The role of SET7/9 in osteosarcoma cells is currently controversial and its potential as a therapeutic candidate in osteosarcoma is unknown. In the present study, SET7/9 inhibition or ablation suppressed osteosarcoma cell proliferation by causing G1 arrest. Mechanistically, SET7/9 inhibition disrupted the interaction between cyclin-dependent kinase 4 (CDK4) and cyclin D1, which affected CDK4-cyclin D1 complex function, leading to decreased phosphorylation of retinoblastoma protein. CDK4 was overexpressed in osteosarcoma tissues and was closely related to a poor prognosis in patients with osteosarcoma. We therefore hypothesized that SET7/9 inhibition might increase the sensitivity of osteosarcoma cells to CDK4 inhibitors, potentially decreasing the risk of adverse effects of CDK4 inhibitors. The combination of SET7/9 and CDK4 inhibition enabled dose reductions of both inhibitors and had a synergistic effect against osteosarcoma growth in vivo. Collectively, these findings indicate that SET7/9 plays an oncogenic role in osteosarcoma by regulating CDK4-cyclin D1 complex interaction and function. The combination of SET7/9 and CDK4 inhibition may thus provide a novel effective therapeutic strategy for osteosarcoma with no significant toxicity.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Neoplasias Ósseas/patologia , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Osteossarcoma/patologia , Fosforilação
4.
Medicine (Baltimore) ; 100(3): e24411, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546085

RESUMO

BACKGROUND: Superb microvascular imaging (SMI) is a new ultrasound vascular imaging technology, which uses a new Doppler algorithm, it has the characteristics of high sensitivity and high resolution to detect low velocity blood flow; it is easier to detect microvessels with low-velocity flow compared with color Doppler flow imaging in theory; and it can image the microvessels of the lesion without angiography.[1] Previous studies showed that SMI can detect tumor neovascularization to differentiate benign from malignant focal liver lessions (FLLs). However, the results of these studies have been contradictory with low sample sizes. This meta-analysis tested the hypothesis that SMI is accurate in distinguishing benign and malignant FLLs. METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the November 30, 2020, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis. RESULTS: This systematic review will determine the accuracy of SMI in the differential diagnosis between benign and malignant FLLs. CONCLUSION: Its findings will provide helpful evidence for the accuracy of SMI in the differential diagnosis between benign and malignant FLLs. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020120081.


Assuntos
Protocolos Clínicos , Fígado/anormalidades , Fígado/diagnóstico por imagem , Ultrassonografia/métodos , Ultrassonografia/normas , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
5.
Food Res Int ; 137: 109688, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33233263

RESUMO

In this study, fruit-zone microclimate was modified by three treatments, including inter-row mulch (M), the combination of leaf removal applied at the onset of veraison and inter-row mulch (MLR-BV), and the combination of leaf removal applied at complete veraison and inter-row mulch (MLR-EV), in a semi-arid climate in three consecutive years (2015-2017). M decreased fruit-zone reflected solar radiation from vineyard floor and low temperature (10-20 °C) duration, whereas it increased soil temperature and high temperature (> 30 °C) duration. MLR-BV and MLR-EV increased fruit-zone incident photosynthetically active radiation while decreased the duration of 20-25 °C compared to M. Notably, M significantly decreased grape total norisoprenoid concentrations in 2015-2017, and total terpenoid concentrations in 2015-2016. Applying leaf removal applied at the onset of veraison could compensate the decreases of total norisoprenoids and terpenoids caused by M when two treatments were applied together. Besides, M significantly increased grape total C6/C9 compound concentrations, besides, (Z)-3-hexen-1-ol concentrations were significantly higher in grapes of M than those of MLR-BV in 2015-2017. Light exposure and high temperature duration after veraison had strong positive correlations with total norisoprenoids and terpenoids, besides, low temperature duration was positively correlated with total norisoprenoids. In addition, light exposure after veraison had strong negative correlations with total C6/C9 compounds. With respect to the volatile compounds in wines, M significantly decreased the concentrations of isopentanol and ethyl acetate, and the concentrations of ethyl cinnamate, phenylacetaldehyde, phenylethyl alcohol and 3-methylthio-1-propanol were significantly lower in MLR-BV and MLR-EV than in M. The outcome of this study can assist winegrowers to properly adjust vineyard managements to optimize the concentrations of desired volatile compounds in grapes and wines.


Assuntos
Vitis , Vinho , Fazendas , Frutas/química , Norisoprenoides/análise , Vinho/análise
6.
Ann Palliat Med ; 9(2): 488-492, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32156124

RESUMO

Post-polypectomy syndrome (PPS) results from electrocoagulation injury to the bowel wall that induces a transmural burn and localized peritonitis. It has a good prognosis; however, there are exceptions when complications are observed. We here report a case of a 50-year-old man who developed lumbosacral pain and high fever with chills four days after colonoscopy, during which polypectomy was performed by endoscopic mucosal resection (EMR) and argon plasma coagulation (APC). Both the plain abdominal film and abdominal CT scan showed no free air, and lumbar CT showed no apparent lesions, which satisfied the diagnosis of PPS. However, the patient was in a critical condition as he developed septic shock caused by bacteremia. Following active treatment, the patient's condition rapidly improved. Therefore, we suggest that clinicians should consider the severity of PPS with sepsis and colon transmural burn. Patients with a diagnosis of PPS should be admitted to the hospital for observation and treatment to avoid adverse consequences.


Assuntos
Colo/lesões , Doenças do Colo/etiologia , Colonoscopia/efeitos adversos , Sepse/etiologia , Humanos , Perfuração Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Sepse/terapia , Síndrome
7.
J Anat ; 235(2): 246-255, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31318052

RESUMO

The vomerovaginal canal (VVC) and palatovaginal canal (PVC) are two canals that open forward to the posterior wall of the pterygopalatine fossa (PPF). Although the anatomy and computed tomography (CT) appearances of the PVC have been well studied, the VVC has been rarely reported, especially in endoscopic examinations. Some studies have even failed to distinguish the PVC from the VVC on CT images. The purpose of this study was to demonstrate the anatomy of the VVC on endoscopy and reveal its differences from the PVC, and to analyse the relative positions of the VVC, PVC, and pterygoid canal on CT images. Ten dry skull bases were studied to observe the structures involved in the formation of the VVC. Dissection of four cadaveric heads was performed to demonstrate the anatomy of the VVC on endoscopy. Coronal CT image analysis in 70 patients was conducted to evaluate the distances and relative positions between the VVC, PVC, and pterygoid canal. The PVC and VVC were also compared on axial CT images. The osteological study showed the top wall of the VVC was the antero-inferior wall of the sphenoid sinus. The VVC may be a helpful landmark in endoscopic endonasal transpterygoid approaches. Steps and discrimination in the dissections of the VVC and PVC were described. The interval between the PVC and VVC could be observed on both coronal and axial CT images. The coronal CT images of patients showed differences in the positions and distances among the three canals at both the anterior and posterior apertures of the PVC. The VVC can be easily mistaken for the PVC if its existence is not suspected. The anatomical morphologies and trajectories of the VVC and PVC differed on both nasal endoscopy and CT. The existence of the VVC should be considered during surgery and CT diagnosis within this area.


Assuntos
Cavidade Nasal/anatomia & histologia , Fossa Pterigopalatina/anatomia & histologia , Vômer/anatomia & histologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Cirurgia Endoscópica por Orifício Natural , Fossa Pterigopalatina/diagnóstico por imagem , Fossa Pterigopalatina/cirurgia , Tomografia Computadorizada por Raios X , Vômer/diagnóstico por imagem , Vômer/cirurgia , Adulto Jovem
8.
Med Sci Monit ; 25: 5543-5551, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31347609

RESUMO

BACKGROUND The aim of this study was to elucidate the involvement of cPLA2-AA-COX-2 pathway factors and their potential role in lung cancer early diagnosis and prognosis. MATERIAL AND METHODS We selected 80 lung cancer patients as the cancer group, and 30 normal patients were selected as the normal group. Serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 were measured, and mRNA levels of COX-2, cPLA2, COX-1, and mPGES in serum were determined. Spearman's P-test was used to analyze the correlation between expression of PGI2 and mPGES in serum and the clinical characteristics of these lung cancer patients. The factors affecting the prognosis lung cancer were analyzed by COX regression model. RESULTS The serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 in the cancer patient group were significantly higher (p<0.05) than in the normal group; after treatment, the serum contents of these factors were significantly decreased (p<0.05). However, distant metastasis had a significant effect on serum contents of mPGES and PGI2 (p<0.05), but not on the other factors. The mRNA levels of COX-2, cPLA2, COX-1, and mPGES in cancer patients were significantly higher than in normal patients. In addition, the 5-year survival rate of patients with high expression of mPGES and/or PGI2 was lower than that of the low expression group. Cox regression analysis showed that the expression of mPGES and PGI2 had statistical significance in predicting the prognosis of lung cancer. CONCLUSIONS The cPLA2-AA-COX-2 pathway is closely associated with lung cancer. These findings are important for clinical diagnosis of lung cancer.


Assuntos
Ácido Araquidônico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfolipases A2 Citosólicas/metabolismo , Adulto , Idoso , Ácido Araquidônico/sangue , Ácido Araquidônico/genética , Ciclo-Oxigenase 2/sangue , Ciclo-Oxigenase 2/genética , Citosol/metabolismo , Dinoprostona/metabolismo , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Oxirredutases Intramoleculares/metabolismo , Isoenzimas , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Fosfolipases A2 Citosólicas/sangue , Fosfolipases A2 Citosólicas/genética , Prognóstico , Prostaglandina-E Sintases/genética , Prostaglandina-E Sintases/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/genética
9.
Onco Targets Ther ; 12: 4093-4097, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213830

RESUMO

Background: Carcinoma ex pleomorphic adenoma (CXPA), a very rare malignancy found mostly in the major salivary glands, has no established standardized treatment. Case presentation: This report describes a 67-year-old male with advanced CXPA who was effectively treated by anlotinib. Pleomorphic adenoma of the submandibular gland was first diagnosed in 1976 after a surgical resection of a mass underneath the jaw. The patient underwent re-excision 3 years later due to a recurrent pleomorphic adenoma. CXPA was first diagnosed in 2016 after a surgical removal of the left submandibular mass. A lung nodule was found on a chest CT scan in January 2018. Following a CT-guided lung biopsy that demonstrated findings consistent with pulmonary metastasis, the patient underwent local therapy (microwave ablation and radioactive seed implantation) but suffered a recurrence of disease approximately 6 months later. Anlotinib was administered orally at a dose of 12 mg daily on a 2 weeks on/1 week off schedule. A partial response was observed after two cycles of treatment. The disease remains in continued partial response after completion of his sixth cycle. Conclusion: This is the first report for anlotinib in treating CXPA. Further pre-clinical and clinical studies are needed to validate the efficacy and safety of anlotinib in the treatment of CXPA.

10.
J Cancer Res Ther ; 14(7): 1650-1654, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30589054

RESUMO

PURPOSE: The objective of the study is to explore the etiology, clinical manifestations, imaging features, diagnosis, treatment, and prognosis of cerebral air embolism complicated computed tomography (CT) scan-guided percutaneous liver biopsy. MATERIALS AND METHODS: A case of air embolism was developed in the brain during a CT-guided percutaneous needle biopsy of the liver. In addition, retrospective analysis was performed on the previously reported typical cases of cerebral air embolism secondary to CT-guided percutaneous lung biopsy. RESULTS: Cerebral air embolism has been recognized as a potentially fatal but extremely rare complication following CT-guided percutaneous liver or lung biopsy. It was usually caused by cough, positive pressure ventilation, incorrect puncture position, repeated punctures, cavity or cyst in the target sites, and vascular inflammatory lesions. CONCLUSIONS: Clinicians should focus on timely and correct diagnosis of this complication during their interventional procedures. The current main treatment for this complication has been hyperbaric oxygen therapy.


Assuntos
Embolia Aérea/diagnóstico , Embolia Aérea/etiologia , Biópsia Guiada por Imagem/efeitos adversos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Fígado/patologia , Fígado/cirurgia , Tomografia Computadorizada por Raios X , Biópsia por Agulha/efeitos adversos , Humanos , Aumento da Imagem , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
11.
DNA Cell Biol ; 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30328712

RESUMO

Phospholipase A2-IVA (PLA2G4A) is the most abundant subtype of cytoplasmic phospholipase A2 (cPLA2) and is an important enzyme in tumor development. Our study aimed to explore the role of PLA2G4A in the regulation of lung cancer. The contents of cell-related cytokines (microsomal prostaglandin E synthase-1 [mPGES], PGE2, and prostacyclin [PGI2]) in A549 cells were analyzed by ELISA kits. Cell counting kit-8 (CCK8) was used to detect the effects of inhibitor of cPLA2 (arachidonyl trifluoromethyl ketone [AACOCF3]) on the proliferation of A549 cells. The migration and invasion of A549 cells were tested by cell scratch wound healing assay and transwell assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the effect of inhibitor AACOCF3 on the expression of related mRNA and protein in A549 cells. ELISA result showed that the levels of mPGES, PGE2, and PGI2 in control group were significantly higher than those in the AACOCF3 group. Cell inhibition rate in the control group was significantly lower than that in the AACOCF3 group. The percentage of wound healing in the control group was significantly higher than that in the AACOCF3 group. Meanwhile, the relative invasive number of cells in the control group was significantly higher than those in the AACOCF3 group. The expression levels of related mRNA of PLA2G4A and cyclooxygenase-2 (COX-2) and the expression levels of mPGES, COX-1, and COX-2 protein in the control group were significantly higher than those in the AACOCF3 group. Our research showed that PLA2G4A was involved in migration and invasion of lung cancer cells.

12.
World J Gastroenterol ; 23(30): 5589-5601, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28852318

RESUMO

AIM: To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS: We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME III criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2:1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 °C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS: Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION: Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dispepsia/tratamento farmacológico , Esvaziamento Gástrico/efeitos dos fármacos , Período Pós-Prandial/efeitos dos fármacos , Qualidade de Vida , Adulto , Ansiedade/diagnóstico , Ansiedade/etiologia , Depressão/diagnóstico , Depressão/etiologia , Método Duplo-Cego , Dispepsia/diagnóstico por imagem , Dispepsia/psicologia , Endoscopia Gastrointestinal , Feminino , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
13.
Bioorg Med Chem Lett ; 26(11): 2730-4, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27080177

RESUMO

According to the previous studies, the anticancer activity of flavonoids could be enhanced when they are coordinated with transition metal ions. In this work, kaempferol-zinc(II) complex (kaempferol-Zn) was synthesized and its chemical properties were characterized by UV-VIS, FT-IR, (1)H NMR, elemental analysis, electrospray mass spectrometry (ES-MS) and fluorescence spectroscopy, which showed that the synthesized complex was coordinated with a Zn(II) ion via the 3-OH and 4-oxo groups. The anticancer effects of kaempferol-Zn and free kaempferol on human oesophageal cancer cell line (EC9706) were compared. MTT results demonstrated that the killing effect of kaempferol-Zn was two times higher than that of free kaempferol. Atomic force microscopy (AFM) showed the morphological and ultrastructural changes of cellular membrane induced by kaempferol-Zn at subcellular or nanometer level. Moreover, flow cytometric analysis indicated that kaempferol-Zn could induce apoptosis in EC9706 cells by regulating intracellular calcium ions. Collectively, all the data showed that kaempferol-Zn might be served as a kind of potential anticancer agent.


Assuntos
Antineoplásicos/farmacologia , Quempferóis/farmacologia , Compostos Organometálicos/farmacologia , Zinco/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Quempferóis/química , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Zinco/química
14.
Sci Rep ; 6: 22332, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26923424

RESUMO

Vaccination may be an alternative treatment for infection with multidrug-resistance (MDR) Acinetobacter baumannii. The study reported here evaluated the bactericidal antibody responses following immunization of mice using an inactivated whole-cell vaccine derived from antibiotic-exposed MDR A. baumannii (I-M28-47-114). Mice inoculated with I-M28-47 (non-antibiotic-exposed control) and I-M28-47-114 showed a high IgG antibody response by day 5 post-inoculation. Sera from mice inoculated with I-M28-47-114 collected on day 30 resulted in 80.7 ± 12.0% complement-mediated bacteriolysis in vitro of the test MDR A. baumannii treated with imipenem, which was a higher level of bacteriolysis over sera from mice inoculated with I-M28-47. Macrophage-like U937 cells eliminated 49.3 ± 11.6% of the test MDR A. baumannii treated with imipenem when opsonized with sera from mice inoculated with I-M28-47-114, which was a higher level of elimination than observed for test MDR A. baumannii opsonized with sera from mice inoculated with I-M28-47. These results suggest that vaccination with I-M28-47-114 stimulated antibody responses capable of mounting high bactericidal killing of MDR A. baumannii. Therefore, the inactivated antibiotic-exposed whole-cell vaccine (I-M28-47-114) has potential for development as a candidate vaccine for broad clearance and protection against MDR A. baumannii infections.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/imunologia , Antibacterianos/farmacologia , Vacinas Bacterianas/imunologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/imunologia , Vacinas de Produtos Inativados/imunologia , Infecções por Acinetobacter/microbiologia , Animais , Anticorpos Antibacterianos/imunologia , Linhagem Celular , Proteínas do Sistema Complemento/imunologia , Reações Cruzadas/imunologia , Citotoxicidade Imunológica , Modelos Animais de Doenças , Imunização , Imunoglobulina G/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Fagocitose/imunologia
15.
Scanning ; 38(6): 644-653, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26890985

RESUMO

Kaempferol has been identified as a potential cancer therapeutic agent by an increasing amount of evidences. However, the changes in the topography of cell membrane induced by kaempferol at subcellular- or nanometer-level were still unclear. In this work, the topographical changes of cytomembrane in human cervical cancer cell (SiHa) induced by kaempferol, as well as the role of kaempferol in apoptosis induction and its possible mechanisms, were investigated. At the macro level, MTT assays showed that kaempferol inhibited the proliferation of SiHa cells in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that kaempferol could induce SiHa cell apoptosis, mitochondrial membrane potential disruption, and intracellular free calcium elevation. At the micro level, fluorescence imaging by laser scanning confocal microscopy (LSCM) indicated that kaempferol could also destroy the networks of microtubules. Using high resolution atomic force microscopy (AFM), we determined the precise changes of cellular membrane induced by kaempferol at subcellular or nanometer level. The spindle-shaped SiHa cells shrank after kaempferol treatment, with significantly increased cell surface roughness. These data showed structural characterizations of cellular topography in kaempferol-induced SiHa cell apoptosis and might provide novel integrated information from macro to nano level to assess the impact of kaempferol on cancer cells, which might be important for the understanding of the anti-cancer mechanisms of drugs. SCANNING 38:644-653, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Apoptose/efeitos dos fármacos , Quempferóis/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Cálcio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Feminino , Humanos , Microscopia de Força Atômica , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/ultraestrutura
16.
Future Oncol ; 10(14): 2149-59, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25471030

RESUMO

BACKGROUND: The association of preoperative red blood cell indexes in non-anemic patients undergoing lung resections for non-small-cell lung cancer with recurrence-free survival (RFS) and overall survival (OS) has never been investigated. METHODS: We retrospectively examined the impact of preoperative red blood cell indexes on RFS and OS and the relationships between the indexes and clinicopathological factors in lung cancer. RESULTS: A total of 649 patients were evaluated. The mean corpuscular hemoglobin concentration was showed as an independent prognostic factor in all patients for OS (hazard ratio [HR]: 0.697; 95% CI: 0.502-0.969; p = 0.032) and RFS (HR: 0.688; 95% CI: 0.519-0.914; p = 0.010). The mean corpuscular volume was an independent prognostic factor in all patients for OS (HR: 0.589; 95% CI: 0.380-0.912; p = 0.018), but not for RFS (HR: 0.684; 95% CI: 0.461-1.015; p = 0.059). CONCLUSION: In conclusion, the results of this study suggest that mean corpuscular hemoglobin concentration is an independent prognostic factor for OS and RFS in non-small-cell lung cancer.


Assuntos
Índices de Eritrócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Fatores de Risco , Carga Tumoral , Adulto Jovem
17.
Curr Drug Targets ; 15(7): 674-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24862189

RESUMO

IGF-1R, an important member of the IGF signaling system, is a plasma-membrane-bound receptor composed of two α-subunits and two ß-subunits. IGF-1R has been revealed to play a pivotal role in cancer cell proliferation, differentiation, apoptosis and phenotype transformation, resulting uncontrolled tumor-cell growth. During the last decades, IGF-1R monoclonal antibody combined with chemotherapeutic agents as a novel cancer treatment approach has shown synergistic effect in cancer treatment in some preclinical and clinical trials. Prolonged progression-free survival rate, objective response rate and stable disease were shown in some sorts of cancer patients compared to those implemented traditional standard chemotherapy. However, not all related clinical trials demonstrated expected promising outcomes. Most treatment-related adverse events in those studies are mild and manageable. The most frequently happened side effect is hyperglycemia in majorities of combined cancer therapy studies. Herein, we summarized the recent online and published literatures concerning the safety, tolerability, anti-tumor activity and adverse events of this novel strategy. Besides, this work attempts to provide convincible evidence to warrant further investigation to identify prognostic biomarkers on neoplasm.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Receptor IGF Tipo 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Sinergismo Farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Neoplasias/metabolismo , Neoplasias/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Med Oncol ; 31(2): 809, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24338377

RESUMO

CXC chemokines have been reported to play critical roles in tumor growth, angiogenesis, invasion and metastasis of various human cancers. However, expression of CXC chemokines type 2 (CXCR2) and its association with clinicopathological characters and patients' prognosis in esophageal cancer are scarcely reported. We retrospectively collected clinicopathologic characteristics of 95 esophageal cancer patients undergoing esophagectomies. Immunohistochemistry was used to detect the expression of CXCR2. The survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were then performed to determine the relationship between CXCR2 and the clinical characteristics and to analyze whether CXCR2 expression was a significant independent prognostic factor for esophageal cancer patients. CXCR2 was highly expressed in 57.9 % of the randomly selected specimens. The expression of CXCR2 was significantly related to lymph node metastasis (P = 0.044) and predicted poor overall status in operable esophageal cancer patients (P = 0.012). Cox proportional hazard analysis regression analysis indicated that CXCR2 expression (P = 0.030) and lymphatic metastasis (P < 0.001) may serve as independent prognostic markers for esophageal cancer patients. Our results demonstrate that CXCR2 significantly correlates with lymph node metastasis and is a poor prognostic factor in resected esophageal squamous cell carcinoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Receptores de Interleucina-8B/metabolismo , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Appl Microbiol Biotechnol ; 96(6): 1539-50, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22797600

RESUMO

To develop a high efficiency Candida antarctica lipase B (CALB) yeast display system, we linked two CALB genes fused with Sacchromyces cerevisiae cell wall protein genes, the Sed1 and the 3'-terminal half of Sag1, separately by a 2A peptide of foot-and-mouth disease virus (FMDV) in a single open reading frame. The CALB copy number of recombinant strain KCSe2ACSa that harbored the ORF was identified, and the quantity of CALB displayed on the cell surface and the enzyme activity of the strain were measured. The results showed that the fusion of multiple genes linked by 2A peptide was translated into two independent proteins displayed on the cell surface of stain KCSe2ACSa. Judging from the data of immunolabeling assay, stain KCSe2ACSa displayed 94 % CALB-Sed1p compared with stain KCSe1 that harbored a single copy CALB-Sed1 and 64 % CALB-Sag1p compared with stain KCSa that harbored a single copy CALB-Sag1 on its surface. Besides, strain KCSe2ACSa possessed 170 % hydrolytic activity and 155 % synthetic activity compared with strain KCSe1 as well as 144 % hydrolytic activity and 121 % synthetic activity compared with strain KCSa. Strain KCSe2ACSa even owned 124 % hydrolytic activity compared with strain KCSe2 that harbored two copies CALB-Sed1. The heterogeneous glycosylphosphatidylinositol-anchored proteins co-displaying yeast system mediated by FMDV 2A peptide was shown to be an effective method for improving the efficiency of enzyme-displaying yeast biocatalysts.


Assuntos
Vírus da Febre Aftosa/genética , Proteínas Fúngicas/genética , Lipase/genética , Peptídeos/genética , Pichia/genética , Engenharia de Proteínas/métodos , Candida/enzimologia , Candida/genética , Vírus da Febre Aftosa/metabolismo , Proteínas Fúngicas/metabolismo , Expressão Gênica , Lipase/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Peptídeos/metabolismo , Pichia/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
20.
Analyst ; 135(3): 570-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20174712

RESUMO

Here we describe the biocatalytic growth of high-density gold agglomerates on a gold electrode surface to form a carrier for aptamer probe immobilization. The present approach provides a simple strategy to promote the seed-mediated deposition of Au from AuCl(4)(-) onto surface-attached 12 nm diameter Au nanoparticles (AuNPs) in the presence of reductive coenzyme and surfactant. The growth process was studied by electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). This nanostructured platform is effective and prospective toward the aptamer probe immobilization. For the nice performance of enhanced substrate, the aptamer-sensing interface showed excellent applicability under the investigations such as alternating current voltammetry (ACV) and surface-enhanced Resonance Raman scattering (SERRS) spectra.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Ouro/química , Nanopartículas Metálicas/química , Adenosina/urina , Biocatálise , Coenzimas/química , Coenzimas/metabolismo , Eletrodos , Humanos , Microscopia Eletrônica de Varredura , Análise Espectral Raman , Tensoativos/química
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