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1.
Proc Natl Acad Sci U S A ; 121(39): e2402162121, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39292741

RESUMO

Liquid-like protein condensates have recently attracted much attention due to their critical roles in biological phenomena. They typically show high fluidity and reversibility for exhibiting biological functions, while occasionally serving as sites for the formation of amyloid fibrils. To comprehend the properties of protein condensates that underlie biological function and pathogenesis, it is crucial to study them at the single-condensate level; however, this is currently challenging due to a lack of applicable methods. Here, we demonstrate that optical trapping is capable of inducing the formation of a single liquid-like condensate of α-synuclein in a spatiotemporally controlled manner. The irradiation of tightly focused near-infrared laser at an air/solution interface formed a condensate under conditions coexisting with polyethylene glycol. The fluorescent dye-labeled imaging showed that the optically induced condensate has a gradient of protein concentration from the center to the edge, suggesting that it is fabricated through optical pumping-up of the α-synuclein clusters and the expansion along the interface. Furthermore, Raman spectroscopy and thioflavin T fluorescence analysis revealed that continuous laser irradiation induces structural transition of protein molecules inside the condensate to ß-sheet rich structure, ultimately leading to the condensate deformation and furthermore, the formation of amyloid fibrils. These observations indicate that optical trapping is a powerful technique for examining the microscopic mechanisms of condensate appearance and growth, and furthermore, subsequent aging leading to amyloid fibril formation.


Assuntos
Amiloide , Pinças Ópticas , alfa-Sinucleína , alfa-Sinucleína/metabolismo , alfa-Sinucleína/química , Amiloide/química , Amiloide/metabolismo , Humanos , Análise Espectral Raman/métodos
2.
BMC Cancer ; 24(1): 195, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347468

RESUMO

BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.


Assuntos
Neoplasias da Mama , Furanos , Cetonas , Policetídeos de Poliéter , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neutrófilos , Estudos Retrospectivos , Linfócitos , Contagem de Linfócitos
3.
Chemotherapy ; 68(1): 23-34, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36108618

RESUMO

BACKGROUND: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. METHODS: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. RESULTS: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). CONCLUSIONS: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.


Assuntos
Neoplasias da Mama , Neutropenia , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Resultado do Tratamento , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Furanos/efeitos adversos
4.
Cancer Sci ; 112(10): 4234-4245, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34382727

RESUMO

Development of acquired resistance to lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor, severely limits the duration of clinical response in advanced HER2-driven breast cancer patients. Although the compensatory activation of the PI3K/Akt survival signal has been proposed to cause acquired lapatinib resistance, comprehensive molecular mechanisms remain required to develop more efficient strategies to circumvent this therapeutic difficulty. In this study, we found that suppression of HER2 by lapatinib still led to Akt inactivation and elevation of FOX3a protein levels, but failed to induce the expression of their downstream pro-apoptotic effector p27kip1 , a cyclin-dependent kinase inhibitor. Elevation of miR-221 was found to contribute to the development of acquired lapatinib resistance by targeting p27kip1 expression. Furthermore, upregulation of miR-221 was mediated by the lapatinib-induced Src family tyrosine kinase and subsequent NF-κB activation. The reversal of miR-221 upregulation and p27kip1 downregulation by a Src inhibitor, dasatinib, can overcome lapatinib resistance. Our study not only identified miRNA-221 as a pivotal factor conferring the acquired resistance of HER2-positive breast cancer cells to lapatinib through negatively regulating p27kip1 expression, but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Lapatinib/farmacologia , MicroRNAs/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Animais , Neoplasias da Mama/química , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p27/efeitos dos fármacos , Dasatinibe/farmacologia , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Proteína Forkhead Box O3/metabolismo , Fator 3-gama Nuclear de Hepatócito/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/efeitos dos fármacos , Análise em Microsséries , Subunidade p50 de NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/efeitos dos fármacos , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo
5.
Opt Express ; 28(19): 27727-27735, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32988060

RESUMO

Laser trapping at an interface is a unique platform for aligning and assembling nanomaterials outside the focal spot. In our previous studies, Au nanoparticles form a dynamically evolved assembly outside the focus, leading to the formation of an antenna-like structure with their fluctuating swarms. Herein, we unravel the role of surface plasmon resonance on the swarming phenomena by tuning the trapping laser wavelength concerning the dipole mode for Au nanoparticles of different sizes. We clearly show that the swarm is formed when the laser wavelength is near to the resonance peak of the dipole mode together with an increase in the swarming area. The interpretation is well supported by the scattering spectra and the spatial light scattering profiles from single nanoparticle simulations. These findings indicate that whether the first trapped particle is resonant with trapping laser or not essentially determines the evolution of the swarming.

6.
Transgenic Res ; 29(5-6): 511-527, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32776308

RESUMO

The ß-glucosidase, which hydrolyzes the ß(1-4) glucosidic linkage of disaccharides, oligosaccharides and glucose-substituted molecules, has been used in many biotechnological applications. The current commercial source of ß-glucosidase is mainly microbial fermentation. Plants have been developed as bioreactors to produce various kinds of proteins including ß-glucosidase because of the potential low cost. Sulfolobus solfataricus is a thermoacidophilic archaeon that can grow optimally at high temperature, around 80 °C, and pH 2-4. We overexpressed the ß-glucosidase gene from S. solfataricus in transgenic tobacco via Agrobacteria-mediated transformation. Three transgenic tobacco lines with ß-glucosidase gene expression driven by the rbcS promoter were obtained, and the recombinant proteins were accumulated in chloroplasts, endoplasmic reticulum and vacuoles up to 1%, 0.6% and 0.3% of total soluble protein, respectively. By stacking the transgenes via crossing distinct transgenic events, the level of ß-glucosidase in plants could further increase. The plant-expressed ß-glucosidase had optimal activity at 80 °C and pH 5-6. In addition, the plant-expressed ß-glucosidase showed high thermostability; on heat pre-treatment at 80 °C for 2 h, approximately 70% residual activity remained. Furthermore, wind-dried leaf tissues of transgenic plants showed good stability in short-term storage at room temperature, with ß-glucosidase activity of about 80% still remaining after 1 week of storage as compared with fresh leaf. Furthermore, we demonstrated the possibility of using the archaebacterial ß-glucosidase gene as a reporter in plants based on alternative ß-galactosidase activity.


Assuntos
Nicotiana/genética , Plantas Geneticamente Modificadas/genética , Proteínas Recombinantes/metabolismo , Sulfolobus solfataricus/genética , beta-Glucosidase/genética , Proteínas Arqueais/genética , Proteínas Arqueais/metabolismo , Celobiose/metabolismo , Clonagem Molecular , Estabilidade Enzimática , Genes Reporter , Vetores Genéticos , Glucose/metabolismo , Concentração de Íons de Hidrogênio , Regiões Promotoras Genéticas , Proteínas Recombinantes/genética , Sulfolobus solfataricus/enzimologia , Temperatura , Nicotiana/metabolismo , beta-Glucosidase/metabolismo
7.
BMC Public Health ; 13: 975, 2013 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-24138825

RESUMO

BACKGROUND: To assess the prevalence of obesity and major physical examination items including dental caries, myopia, pinworm, hematuria, and proteinuria among school children in Hualien, Taiwan. In addition, the health status differences between gender, grader, levels of residence urbanization, and body mass index (BMI) were examined. METHODS: Cross-sectional studies with a total of 11,080 students (age, 7-14 years) in grades 1, 4, and 7 were evaluated for weight, height, routine physical examination, and urine analysis during the 2010 Student Health Examination in Hualien. Frequencies, Chi-square test, and logistic regression were conducted using SPSS. RESULTS: Of the 11,080 students evaluated, 1357 (12.2%) were overweight, and 1421 (12.8%) were obese. There were significant differences in overweight/obese prevalence by gender, by grader, and by levels of residence urbanization. Dental caries, myopia, and obesity were the most prevalent health problems among these students (75.6%, 33.0%, and 12.8%, respectively). In crude and adjusted analyses, research results showed that there were significant differences in the prevalence of major physical examination items between different gender, grader, levels of residence urbanization, and BMI groups. Girls had a higher prevalence of dental caries, myopia, and hematuria than boys (all p < 0.01), whereas boys had a higher prevalence of pinworm than girls (p = 0.02). Students in higher grades had significantly higher prevalence of myopia, hematuria, and proteinuria (all p < 0.01), whereas students in lower grades had higher prevalence of dental caries and pinworm (p < 0.01). Students with abnormal BMI had lower prevalence of pinworm (p < 0.01). Students residing in suburban and rural areas had higher prevalence of dental caries, pinworm, and hematuria (all p < 0.01), and lower prevalence of myopia than students residing in urban areas (all p < 0.01). CONCLUSION: Routine health examination provides an important way to detect students' health problems. Our study elucidated major health problems among school children in Hualien, Taiwan. In addition, the results also indicated that the prevalence of health problems had a significant relationship with gender, grader, levels of residence urbanization, and BMI. It is suggested that school health interventions should consider students' health profiles along with their risk factors status in planning.


Assuntos
Índice de Massa Corporal , Nível de Saúde , Exame Físico/estatística & dados numéricos , Adolescente , Fatores Etários , Peso Corporal , Criança , Estudos Transversais , Cárie Dentária/epidemiologia , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Prevalência , Serviços de Saúde Escolar/estatística & dados numéricos , Fatores Sexuais , Estudantes/estatística & dados numéricos , Taiwan/epidemiologia , Urbanização
8.
ACS Nano ; 17(4): 3797-3808, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36800201

RESUMO

Mapping of the spatial and temporal motion of particles inside an optical field is critical for understanding and further improvement of the 3D spatio-temporal control over their optical trapping dynamics. However, it is not trivial to capture the 3D motion, and most imaging systems only capture a 2D projection of the 3D motion, in which the information about the axial movement is not directly available. In this work, we resolve the 3D incorporation trajectories of 200 nm fluorescent polystyrene particles in an optical trapping site under different optical experimental conditions using a recently developed widefield multiplane microscope (imaging volume of 50 × 50 × 4 µm3). The particles are gathered at the focus following some preferential 3D channels that show a shallow cone distribution. We demonstrate that the radial and the axial flow speed components depend on the axial distance from the focus, which is directly related to the scattering/gradient optical forces. While particle velocities and trajectories are mainly determined by the trapping laser profile, they cannot be completely explained without considering collective effects resulting from hydrodynamic forces.

9.
Plants (Basel) ; 11(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36365313

RESUMO

At least two sets of RNA polymerase (RNAP), nucleus (NEP)- and plastid (PEP)-encoded polymerases, recognizing distinct promoters exist in the plastids of land plants. Most plastid genes are regulated by multiple promoters with different strengths in their response to developmental stages and environmental cues. Recently, we applied chloroplast-targeted transcription activator-like effector nuclease (cpTALEN) technology to site-specifically cause double-strand DNA breaks in the rpoB gene of tobacco, which encodes the ß-subunit of PEP. The repair of damaged chloroplast DNA (cpDNA) through microhomology-mediated recombination caused the functional loss of the rpoB operon and resulted in the heterotrophic growth of an albino plant. We conducted a genome-wide analysis of the steady state of gene expression in the leaf tissue of PEP-deficient tobacco by RNA-Seq and compared it with that of wild-type plants. The expression of NEP genes was up-regulated in PEP-deficient tobacco; in particular, the level of RpoT3 transcripts encoding the specifically plastid-targeted NEP was significantly increased. Alongside most housekeeping genes, NEP also plays an important role in the regulation of gene expression involved in photosynthesis. In contrast, alongside the photosynthesis-related genes, PEP also plays an important role in the regulation of gene expression involved in some housekeeping functions. Furthermore, the mitochondrial DNA copy number and the level of most mitochondrial protein-coding transcripts were slightly increased in PEP-deficient tobacco. The disruption of PEP function not only affected plastid gene expression, but also nuclear and mitochondrial gene expression. This study demonstrated the intercompartmental retrograde signaling in the regulation of gene expression.

10.
Nat Commun ; 13(1): 5325, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088393

RESUMO

Optical binding has recently gained considerable attention because it enables the light-induced assembly of many-body systems; however, this phenomenon has only been described between directly irradiated particles. Here, we demonstrate that optical binding can occur outside the focal spot of a single tightly focused laser beam. By trapping at an interface, we assemble up to three gold nanoparticles with a linear arrangement which fully-occupies the laser focus. The trapping laser is efficiently scattered by this linear alignment and interacts with particles outside the focus area, generating several discrete arc-shape potential wells with a half-wavelength periodicity. Those external nanoparticles inside the arcs show a correlated motion not only with the linear aligned particles, but also between themselves even both are not directly illuminated. We propose that the particles are optically bound outside the focal spot by the back-scattered light and multi-channel light scattering, forming a dynamic optical binding network.

11.
Cancers (Basel) ; 14(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35406559

RESUMO

Genetic aberrations involving DNA damage repair (DDR) remain underexplored in gastrointestinal stromal tumors (GISTs). We characterized DDR abnormalities using targeted next-generation sequencing and multiplex ligation-dependent probe amplification, and performed immunofluorescence (IF) and immunohistochemistry (IHC) analyses of γH2AX and 53BP1. Consistent with IF-validated nuclear co-localization, γH2AX and 53BP1 showed robust correlations in expression levels, as did both biomarkers between IF and IHC. Without recurrent pathogenic single-nucleotide variants, heterozygous deletions (HetDels) frequently targeted DNA damage-sensing genes, with CHEK2-HetDel being the most prevalent. Despite their chromosomal proximity, BRCA2 and RB1 were occasionally hit by HetDels and were seldom co-deleted. HetDels of CHEK2 and BRCA2 showed a preference for older age groups, while RB1-HetDel predominated in the non-gastric, high-risk, and 53BP1-overexpressing GISTs. Higher risk levels were consistently related to γ-H2AX or 53BP1 overexpression (all p < 0.01) in two validation cohorts, while only 53BP1 overexpression was associated with the deletion of KIT exon 11 (KITex11-del) among genotyped GISTs. Low expressers of dual biomarkers were shown by univariate analysis to have longer disease-free survival (p = 0.031). However, higher risk levels, epithelioid histology, and KITex11-del retained prognostic independence. Conclusively, IHC is a useful surrogate of laborious IF in the combined assessment of 53BP1 and γ-H2AX to identify potential DDR-defective GISTs, which were frequently aberrated by HetDels and a harbinger of progression.

12.
Data Policy ; 32021.
Artigo em Inglês | MEDLINE | ID: mdl-35083434

RESUMO

The quality of service in healthcare is constantly challenged by outlier events such as pandemics (i.e., Covid-19) and natural disasters (such as hurricanes and earthquakes). In most cases, such events lead to critical uncertainties in decision-making, as well as in multiple medical and economic aspects at a hospital. External (geographic) or internal factors (medical and managerial) lead to shifts in planning and budgeting, but most importantly, reduce confidence in conventional processes. In some cases, support from other hospitals proves necessary, which exacerbates the planning aspect. This paper presents three data-driven methods that provide data-driven indicators to help healthcare managers organize their economics and identify the most optimum plan for resources allocation and sharing. Conventional decision-making methods fall short in recommending validated policies for managers. Using reinforcement learning, genetic algorithms, traveling salesman, and clustering, we experimented with different healthcare variables and presented tools and outcomes that could be applied at health institutes. Experiments are performed; the results are recorded, evaluated, and presented.

13.
Plant Sci ; 313: 111028, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763881

RESUMO

Transcription activator-like effector nuclease (TALEN) technology has been widely used to edit nuclear genomes in plants but rarely for editing organellar genomes. In addition, ciprofloxacin, commonly used to cause the double-strand break of organellar DNA for studying the repair mechanism in plants, confers no organellar selectivity and site-specificity. To demonstrate the feasibility of TALEN-mediated chloroplast DNA editing and to use it for studying the repair mechanism in plastids, we developed a TALEN-mediated editing technology fused with chloroplast transit peptide (cpTALEN) to site-specifically edit the rpoB gene via Agrobacteria-mediated transformation of tobacco leaf. Transgenic plants showed various degrees of chlorotic phenotype. Repairing damaged plastid DNA resulted in point mutation, large deletion and small inversion surrounding the rpoB gene by homologous recombination and/or microhomology-mediated recombination. In an albino line, microhomology-mediated recombination via a pair of 12-bp direct repeats between rpoC2 and ycf2 genes generated the chimeric ycf2-rpoC2 subgenome, with the level about 3- to 5-fold higher for subgenomic DNA than ycf2. Additionally, the expression of chimeric ycf2-rpoC2 transcripts versus ycf2 mRNA agreed well with the level of corresponding DNA. The ycf2-rpoC2 subgenomic DNA might independently and preferentially replicate in plastids.


Assuntos
Reparo do DNA , DNA de Cloroplastos , Edição de Genes/métodos , Nicotiana/genética , Melhoramento Vegetal/métodos , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Recombinação Homóloga , Fenótipo , Plantas Geneticamente Modificadas/genética
14.
Front Pharmacol ; 12: 614673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267653

RESUMO

The proviral integration site for moloney murine leukemia virus 1 (Pim1) is a serine/threonine kinase and able to promote cell proliferation, survival and drug resistance. Overexpression of Pim1 has been observed in many cancer types and is associated with the poor prognosis of breast cancer. However, it remains unclear whether Pim1 kinase is a potential therapeutic target for breast cancer patients. In this study, we found that Pim1 expression was strongly associated with HER2 expression and that HER2-overexpressing breast cancer cells were more sensitive to Pim1 inhibitor-induced inhibitions of cell viability and metastatic ability. Mechanistically, Pim1 inhibitor suppressed the expression of HER2 at least in part through transcriptional level. More importantly, Pim1 inhibitor overcame the resistance of breast cancer cells to HER2 tyrosine kinase inhibitor lapatinib. In summary, downregulation of HER2 by targeting Pim1 may be a promising and effective therapeutic approach not only for anti-cancer growth but also for circumventing lapatinib resistance in HER2-positive breast cancer patients.

15.
Mol Ther Nucleic Acids ; 25: 536-553, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34589276

RESUMO

Mutant p53 (mutp53) commonly loses its DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced long intergenic noncoding RNA-p21 (lincRNA-p21) expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity. However, estrogen receptor alpha (ERα) suppressed mutp53-mediated lincRNA-p21 expression by hijacking mutp53 to upregulate damaged DNA binding protein 2 (DDB2) transcription for subsequent DNA repair and chemoresistance. Levels of lincRNA-p21 positively correlated with the clinical responses of breast cancer patients to neoadjuvant chemotherapy and had an inverse correlation with the ER status and DDB2 level. In contrast, the carboplatin-induced DDB2 expression was higher in ER-positive breast tumor tissues. These results demonstrated that ER status determines the oncogenic function of mutp53 in chemoresistance by switching its target gene preference from lincRNA-p21 to DDB2 and suggest that induction of lincRNA-p21 and targeting DDB2 would be effective strategies to increase the chemosensitivity of mutp53 breast cancer patients.

16.
Stem Cells ; 27(3): 724-32, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19259939

RESUMO

Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extracellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.


Assuntos
Cardiomioplastia/métodos , Matriz Extracelular/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Animais , Células Cultivadas , Ecocardiografia , Masculino , Células-Tronco Mesenquimais/citologia , Ratos , Ratos Endogâmicos Lew , Células Estromais/transplante , Função Ventricular Esquerda
17.
J Gastroenterol Hepatol ; 25(9): 1578-86, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20796158

RESUMO

BACKGROUND AND AIM: Thrombocytopenia due to hypersplenism is usually a serious condition in cirrhotic patients who have undergone invasive procedures. We designed a new treatment method using a high-frequency alternating electromagnetic force to treat the disease condition in a rat model. METHODS: Sprague-Dawley rats were given thioacetamide in drinking water and injected with methylcellulose intraperitoneally to create a cirrhotic hypersplenism model. Spleen volume was determined using the Carlson method. The Control Group consisted of 14 rats, 15 weeks old, that were used to determine the normal platelet count and normal spleen size. Experimental Group I, consisting of 15 rats, received electromagnetic thermoablation of their spleens, after which the spleen was returned to the abdomen. Group II consisted of 13 rats, receiving the same electromagnetic thermoablation as Group I, but the ablated portion was removed. Group III consisted of 14 rats receiving total splenectomies. RESULTS: Cirrhotic hypersplenism was confirmed during laparotomy and pathological examination. Spleen volume enlarged from 1513 +/- 375 mm(3) (Control Group) to 7943 +/- 2822 mm(3) (experimental groups). Platelet counts increased from 0.35 +/- 0.21 x 10(6)/mm(3) to 0.87 +/- 0.24 x 10(6)/mm(3) for Group I, from 0.52 +/- 0.23 x 10(6)/mm(3) to 1.10 +/- 0.20 x 10(6)/mm(3) for Group II, and from 0.47 +/- 0.23 x 10(6)/mm(3) to 1.18 +/- 0.26 x 10(6)/mm(3) for Group III. No rats died due to the treatment in any of the experimental groups. CONCLUSIONS: Our animal model performed successfully and our proposed electromagnetic thermotherapy effectively treated thrombocytopenia due to cirrhotic hypersplenism.


Assuntos
Ablação por Cateter/métodos , Fenômenos Eletromagnéticos , Hiperesplenismo/cirurgia , Cirrose Hepática Experimental/complicações , Esplenectomia , Trombocitopenia/cirurgia , Animais , Hiperesplenismo/induzido quimicamente , Hiperesplenismo/complicações , Hiperesplenismo/patologia , Cirrose Hepática Experimental/induzido quimicamente , Masculino , Metilcelulose , Contagem de Plaquetas , Ratos , Ratos Sprague-Dawley , Tioacetamida , Trombocitopenia/sangue , Trombocitopenia/etiologia , Fatores de Tempo
18.
Int J Hyperthermia ; 26(6): 604-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20707654

RESUMO

PURPOSE: Electromagnetic thermal surgery is a new technique. It applies an electrical current through coils to generate a high frequency magnetic field to heat up magnetic materials in the targeted area. Using this technique, we aim to perform liver resection without bleeding in rats and rabbits. MATERIALS AND METHODS: The electromagnetic machine can produce a high frequency magnetic field, with an input of 220 V-55 A-60 Hz, an output frequency of 62.1 kHz, and a power of 2.2 kW. The magnetic materials used in this study were fine needles made of stainless steel. For ex vivo experiments, we used porcine liver explants; in the animal model, sixteen Sprague-Dawley rats and seven New Zealand White rabbits were used. We inserted one needle array along the attempted resection lines and then used the magnetic coils to heat up the needles for three min. After heating, we resected the designated liver portions using surgical scalpels. RESULTS: In the ex vivo test, the fine needles were heated up effectively to achieve tissue coagulation (more than 90 degrees C). In the animal model the liver resection was performed without bleeding and no bile peritonitis was observed after the surgery. All animals were alive after the surgery until the end of the experiment (30 days). CONCLUSIONS: The experiments showed that our thermal surgery system is very effective in performing bloodless liver resection without further ligation or embolisation needed. Our technique is new and the system has great potential to develop into clinical practice.


Assuntos
Ablação por Cateter/métodos , Fenômenos Eletromagnéticos , Fígado/cirurgia , Animais , Perda Sanguínea Cirúrgica , Eletrocoagulação , Hepatectomia/instrumentação , Hepatectomia/métodos , Masculino , Modelos Animais , Coelhos , Ratos , Ratos Sprague-Dawley , Suínos
19.
Chem Commun (Camb) ; (47): 6369-71, 2008 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-19048158

RESUMO

Unprotected arylbiuret units were smoothly introduced onto pi-conjugated structures to afford new supramolecular materials leading to interpenetrated networks.

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