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1.
Sci Rep ; 9(1): 12591, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467297

RESUMO

This paper reports the long term observation of particle-associated polycyclic aromatic hydrocarbons (PAHs) at Cape Hedo Atmosphere and Aerosol Monitoring Station, a remote site in the Western Pacific Ocean, from 2008 to 2015. This is the first long-term study that evaluated the contribution of long-range transport of PAHs in East Asia. No obvious trend (P > 0.05) was found in a particular season over the years. However, there are seasonal variations of PAH concentrations with higher in spring and winter. The higher PAH are attributed to air masses from the area including part of China. Source apportionment using three different approaches, i.e., PAH compositional pattern analysis, PAH diagnostic ratio analysis and positive matrix factorization modeling, showed the combined high contribution of biomass burning (18%, 14%) and coal combustion (33%, 24%) in spring and winter. In addition, the contribution of ship emissions (35%) was relatively high in spring, whereas that of vehicle emissions (36%) was relatively high in winter. The contribution of coal combustion to PAH has decreased throughout the years, likely due to changes in energy structure in China. The contribution of biomass burning to PAH has showed no trend, being stable, and that of vehicular emissions has increased.

2.
Contrast Media Mol Imaging ; 2018: 4617493, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30046295

RESUMO

Novel probe development for positron emission tomography (PET) is leading to expanding the scope of molecular imaging. To begin responding to challenges, several biomaterials such as natural products and small molecules, peptides, engineered proteins including affibodies, and antibodies have been used in the development of targeted molecular imaging probes. To prepare radiotracers, a few bioactive materials are unique challenges to radiolabelling because of their complex structure, poor stability, poor solubility in aqueous or chemical organic solutions, and sensitivity to temperature and nonphysiological pH. To overcome these challenges, we developed a new radiolabelling strategy based on photoactivated 1,3-dipolar cycloaddition between alkene dipolarophile and tetrazole moiety containing compounds. Herein, we describe a light-triggered radiochemical synthesis via photoactivated click reaction to prepare 18F-radiolabelled PET tracers using small molecular and RGD peptide.


Assuntos
Química Click/métodos , Marcação por Isótopo/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/síntese química , Alcenos/química , Animais , Linhagem Celular Tumoral , Reação de Cicloadição , Radioisótopos de Flúor/química , Xenoenxertos , Humanos , Luz , Sondas Moleculares/síntese química , Ratos , Tetrazóis/química
3.
Cancer Biother Radiopharm ; 33(2): 52-59, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29498544

RESUMO

Histone deacetylases (HDACs) are an important regulator of expression and activity of numerous proteins in terms of epigenetic aberrations. This makes HDACs attractive for antitumor therapy and imaging in certain cancers. The authors report the radiochemical synthesis of 2-[18F]fluoroethyltriazolesuberohydroxamine acid ([18F]FETSAHA) as a HDAC-targeted radiolabel probe for positron imaging tomography/computed tomography. The authors also evaluated the in vivo tumor targeting in subcutaneously implanted RR1022 rats. [18F]FETSAHA was produced in less than 2 h with 31.2% ± 4.6% (n = 6) decay-corrected yields and specific activity of 21.4 ± 9.1 GBq/µmol (n = 6) at end of synthesis. [18F]FETSAHA showed significant radioactivity accumulation in tumors with rapid blood clearance and both gastrointestinal track and renal excretion. Tumor-to-blood and tumor-to-muscle uptake ratios in the RR1022 tumor bearing rat model were 1.21 and 1.83 and 2.75 and 2.76 at 30 and 60 min, respectively. An inhibition study of [18F]FETSAHA in the presence of excess amount of suberanilohydroximic acid (SAHA) revealed receptor specific activity accumulation. [18F]FETSAHA has favorable in vivo tumor imaging properties and may be useful for noninvasive evaluation of the correlation between cancer and HDACs.


Assuntos
Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/síntese química , Tomografia por Emissão de Pósitrons/métodos , Radioquímica/métodos , Animais , Linhagem Celular Tumoral , Química Click , Humanos , Ácidos Hidroxâmicos/química , Camundongos
4.
Photochem Photobiol ; 94(3): 583-588, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29349780

RESUMO

Previous studies have reported that 450 nm blue light emitting diode (BLED) induces apoptosis through a mitochondria-mediated pathway in cancer cells and reduces the early stage tumor growth. This study was performed to determine the effects of BLED-irradiated cell metabolites on cell injury. Our results showed that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM) inhibited apoptosis and increased cell survival. Cell protection-related proteins were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF analysis. Treatment with LCM inhibited apoptotic cell death and increased the live cell population. The cellular protective effect of LCM was associated with keratin and collagen type VI secretion from cells after low dose of BLED irradiation. Interestingly, expression of endoplasmic reticulum stress proteins was dose dependently increased after 4 h BLED irradiation. Only levels of BiP, CHOP and ERO1-Lα were decreased significantly after 24 h incubation, indicating their anti-apoptotic property in these cells. These results indicated that cell metabolites stimulated by low-dose BLED irradiation have a cytoprotective effect on cell injury via increasing transient intracellular ER stress. Further studies remain to provide the molecular mechanisms of LCM for cytoprotective activity.


Assuntos
Luz , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Relação Dose-Resposta à Radiação , Eletroforese em Gel Bidimensional , Estresse do Retículo Endoplasmático/efeitos da radiação , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
5.
Environ Sci Pollut Res Int ; 23(17): 16946-54, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27151242

RESUMO

A potential source contribution function (PSCF) can indicate the source areas of high air pollutant concentrations using backward trajectories. However, the conventional two-dimensional PSCF (2D-PSCF) cannot consider the emission and transport height of air pollutants. That missing information might be critical because injection height varies depending on the source type, such as with biomass burning. We developed a simple algorithm to account for the height of trajectories with high concentrations and combined it with the conventional PSCF to devise 3D-PSCF. We demonstrate the applicability of the 3D-PSCF by applying it to particulate PAH data collected from September 2006 to August 2007 in Seoul. We found variation in the results from 3D-PSCF with threshold heights from 3,000 to 1,500 m. Applying 2,000 m as the threshold height in the PSCF calculation most clearly determined the possible source areas of air pollutants from biomass fuel burning that were affecting the air quality in Seoul.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Biomassa , Monitoramento Ambiental/métodos , Seul
6.
J Pediatr Adolesc Gynecol ; 29(1): 74-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26026220

RESUMO

BACKGROUND: Although paratubal cysts are common, borderline paratubal cysts are extremely rare. We describe the case of a large borderline paratubal cyst in a 17-year-old adolescent female treated with laparo-endoscopic single-site surgery (LESS), and review the literature. CASE: A 17-year-old female was referred due to a large right adnexal cyst on pelvic sonogram. A CT scan showed a 19-cm cystic lesion with enhancing papillary projection along the wall. Laparo-endoscopic single-site surgery confirmed a large cystic mass that originated from the right salpinx. Right salpingectomy and right ovarian wedge resection were performed, and intraoperative frozen section analysis was conducted. The result of the frozen section analysis and final pathologic review indicated that the cyst was a serous papillary-type borderline tumor in a paratubal cyst. SUMMARY AND CONCLUSION: To the best of our knowledge, this is the first case report of a BPC treated with LESS. We suggest that minimally invasive, fertility-preserving surgery should be considered as a standard treatment of borderline paratubal cysts if patients desire future fertility.


Assuntos
Cistadenoma Seroso/cirurgia , Endoscopia/métodos , Neoplasias Ovarianas/cirurgia , Cisto Parovariano/cirurgia , Adolescente , Cistadenoma Seroso/patologia , Feminino , Preservação da Fertilidade , Humanos , Neoplasias Ovarianas/patologia , Ovário/cirurgia , Cisto Parovariano/diagnóstico , Pelve/diagnóstico por imagem , Salpingectomia , Tomografia Computadorizada por Raios X , Ultrassonografia
7.
Chem Commun (Camb) ; 50(55): 7273-6, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-24869786

RESUMO

We developed a multiplexed fluorophore system on a DNA scaffold (MFD) that produced new and diverse fluorescence properties depending on the mixing pattern and sequence that could not be obtained from each monomer fluorophore. Our approach for producing new fluorescence properties is relatively facile: simply mixing fluorophores on a DNA scaffold provides large variations in the color and intensity using only one excitation wavelength with high "Stokes shifts" (~190 nm). Furthermore these special fluorescence properties could be controlled by the hybridization pattern and were therefore dependent on the structural changes in DNA.


Assuntos
DNA/química , Corantes Fluorescentes/química , Hibridização de Ácido Nucleico , Espectrometria de Fluorescência
8.
Diagn Cytopathol ; 42(12): 1058-62, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24825374

RESUMO

The purpose of this study was to evaluate the clinical significance of Human papillomavirus (HPV) DNA cotesting in Korean women with abnormal Papanicolaou (Pap) smear results based on colposcopic pathology. A total of 1012 women underwent liquid-based Pap smears and hybrid capture II HPV DNA tests followed by colposcopy at the Korea University Hospital from January 2007 to May 2012. Of these women, 832 women were included in this retrospective study. The mean patient age was 45.4 ± 13.7 years (range:15-80). The distribution of Pap smear results was normal (4.7%), atypical squamous cells of uncertain significance (ASCUS) (42.1%), low-grade squamous intraepithelial lesion (26.8%), ASC-H (7.0%), and high-grade squamous intraepithelial lesion (HSIL) (19.5%). In women with ASCUS, none of the 87 HPV-negative had ≥cervical intraepithelial neoplasia (CIN2) (P < 0.001). In women with ASC-H, only one out of 17 HPV-negative vs. 14 out of 41 HPV-positive had ≥CIN2 (P = 0.025). In patients with HSIL, 54.5% of HPV-negative had ≥CIN2, as compared to 80.8% of HPV-positive with ≥CIN2 (P = 0.039). Patients were further analyzed by age groups: <30 and ≥30 years. In HPV-negative women, there was a significant difference in the ratio of ≥CIN2 (30.8% <30 vs. 4.5% ≥30, P = 0.005). When the HPV DNA test was negative in women ≥30, the risk of ≥CIN2 was significantly lower (P < 0.001). HPV DNA cotesting in women with ASCUS and ASC-H furnish healthcare providers with informative data. There is a lower proportion of ≥CIN2 in HPV-negative women and a higher proportion of ≥CIN2 in HPV-positive. When HPV data were further evaluated by age group, the risk of ≥CIN2 was lower in HPV-negative women, especially in women ≥30.


Assuntos
DNA Viral/genética , Testes de DNA para Papilomavírus Humano , Papillomaviridae/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Testes de DNA para Papilomavírus Humano/métodos , Humanos , Pessoa de Meia-Idade , Gravidez , República da Coreia , Estudos Retrospectivos , Sensibilidade e Especificidade , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Adulto Jovem
9.
Bioorg Med Chem Lett ; 24(6): 1589-91, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24513043

RESUMO

We developed a probing system to detect the intramolecular G-quadruplex of telomeric repeat-containing RNA (TERRA 1). We used a fluorescent adenosine derivative rA(py) as a fluorophore and incorporated it into the dangling position of the parallel-type G-quadruplex sequence of TERRA 1. The rA(py)-modified G-quadruplex structure exhibited a strong fluorescence emission signal, while the emission signals of the single-strand and duplex structures were much lower.


Assuntos
Corantes Fluorescentes/química , Quadruplex G , RNA/análise , Dicroísmo Circular , Hibridização de Ácido Nucleico , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , RNA/química , Espectrometria de Fluorescência , Temperatura
10.
Oncol Lett ; 6(5): 1319-1322, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24179516

RESUMO

Acute myeloid leukemia presenting as leukemia cutis (LC) with hepatocellular carcinoma is extremely rare. The current study presents a case of a 53-year-old male with generalized cutaneous nodules on the face and anterior chest wall. Laboratory tests, including bone marrow biopsy revealed acute myelomonocytic leukemia (AML-M4) with skin and tonsilar involvement. Liver magnetic resonance imaging (MRI) revealed a 6-cm mass in hepatic segments 4 and 8, and a liver biopsy demonstrated that hepatocellular carcinoma cells and immature blast cells coexisted. Although LC has been reported in Korea, a case of LC associated with acute myelomonocytic leukemia was diagnosed simultaneously with hepatocellular carcinoma and tonsillar involvement. The present study describes this case with a review of the literature.

11.
Int Surg ; 98(4): 315-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24229016

RESUMO

Isolated colonic schwannomas are rare gastrointestinal mesenchymal tumors. Only a small number of cases have been reported. Occurrence of these tumors is more common in the stomach than in the large intestine. These spindle cell lesions are distinct from leiomyoma, leiomyosarcoma, and gastrointestinal stromal tumors because the tumor cells have a distinct immunophenotype, with strong diffuse positivity for S-100 and vimentin, as well as corroborative negative staining of CD117 and smooth muscle markers. We present a case of colonic schwannoma in a 70-year-old woman who had no specific symptoms. The patient was diagnosed with a submucosal tumor in the ascending colon on colonoscopy and abdominal computed tomography. Laparoscopic-assisted wedge resection of colon was performed. The very rare pathologic diagnosis of ascending schwannoma was made postoperatively. This case is interesting because schwannomas of the colon and rectum are extremely rare and are treated by laparoscopic-assisted wedge resection.


Assuntos
Colo Ascendente , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Idoso , Colonoscopia , Feminino , Humanos , Tomografia Computadorizada por Raios X
12.
Am J Infect Control ; 41(10): e97-e100, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23769832

RESUMO

BACKGROUND: We evaluated the current vaccination rate and immunity in the Korean adolescent population and analyzed their parents' attitudes toward hepatitis A virus (HAV) vaccination. METHODS: Between March and April 2011, sera were collected for immunoglobulin (Ig) G anti-HAV testing from students in their first year of high school from 12 different high schools located in southwestern Seoul. Simultaneously, questionnaires were given to the parents of the students to evaluate factors related to HAV vaccination, including demographics, HAV vaccination status, reason for getting the vaccination, and awareness regarding HAV. RESULTS: Sera from 2,879 subjects and questionnaires from their parents were collected. The HAV vaccination rate among adolescents aged between 14 and 17 years was 18.9%, and the seroprevalence was 15.4%. Among subjects who reported receiving the HAV vaccination, the IgG anti-HAV seropositivity rate was only 42.2%. For subjects who were not vaccinated, the IgG anti-HAV seropositivity rate was 9.1%. The most significant reason for receiving the vaccination was recommendation from health care providers; the most important source of information regarding the vaccination was public health organizations. CONCLUSION: HAV vaccination rate and anti-HAV seroprevalence in Korean adolescents was low; the seropositivity rate in the vaccinated group was lower than expected. Actively recommending HAV vaccination in this group is required, and routine, nationwide, government-sponsored vaccination of adolescents against HAV should be considered.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vacinas contra Hepatite A/administração & dosagem , Hepatite A/prevenção & controle , Vacinação , Adolescente , Feminino , Humanos , Imunoensaio , Imunoglobulina G/sangue , Masculino , República da Coreia , Instituições Acadêmicas , Estudantes , Inquéritos e Questionários
13.
Oncol Lett ; 5(2): 598-600, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23420814

RESUMO

Mayer-Rokitansty-Küster-Hauser (MRKH) syndrome is a Müllerian anomaly that presents with varying degrees of uterovaginal aplasia and is secondarily associated with cervicothoracic, auditory and skeletal anomalies. However, MRKH syndrome patients have normal and functional ovaries. A supernumerary ovary is an extremely rare form of an ectopic ovary and there are no reported cases of MRKH syndrome with cancer of the supernumerary ovary in the current literature. A 31-year-old female with a history of MRKH syndrome that was diagnosed 4 years previously presented with abdominal pain and a suspected malignant pelvic mass was identified. During the staging surgery, both ovaries were separated from the main mass, observed and removed. A third ovary was discovered in the pelvic mass and the diagnosis of primary ovarian cancer from the third ovary was confirmed by immunohistochemistry. We report the first known case of cancer of the supernumerary ovary in a patient with MRKH syndrome. Although both ovaries were confirmed to be normal in the patient with MRKH syndrome, we propose that an ovarian neoplasm should be considered in the diagnosis of a pelvic mass.

14.
Indian J Surg ; 75(Suppl 1): 331-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24426608

RESUMO

BACKGROUND: Primary hepatic lymphoma (PHL) is a very rare malignancy, and constitutes about 0.016 % of all cases of non-Hodgkin's lymphoma and is often misdiagnosed. The optimal therapy is still unclear and the outcomes are uncertain. Among PHLs, a primary hepatic low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is extremely rare. METHODS: We present a case of primary hepatic lymphoma (MALT lymphoma) treated with surgical resection and adjuvant chemotherapy. A 38-year-old Korean man, who was diagnosed with chronic hepatitis B 20 years ago, was admitted for liver biopsy after liver lesions were detected on follow-up computed tomography scan (CT). Liver biopsy revealed the diagnosis of marginal zone B-cell malignant lymphoma (MALT lymphoma). The preoperative clinical staging was IE, given that no additional foci of lymphoma were found anywhere else in the body. The patient underwent left hemihepatectomy. Subsequently, the patient received two cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) regimen. RESULTS: After 15 months of follow-up, the patient is alive and well without any evidence of disease recurrence. CONCLUSION: Although the prognosis is variable, good response to early surgery combined with postoperative chemotherapy can be achieved in strictly selected patients.

15.
Korean J Pathol ; 46(5): 436-42, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23136570

RESUMO

BACKGROUND: Understanding the biologic behavior of a tumor is a prerequisite for tumor registration code assignment. The aim of this report was to propose appropriate behavior codes of the International Classification of Disease Oncology 3 (ICD-O3) to rare, yet pathologically interesting hematopoietic and soft tissue tumors. METHODS: The Study Group for Hematopathology, the Bone and Soft Tissue Pathology Study Group, and the Cancer Registration Committee prepared the questionnaire containing provisional behavior codes of selected diseases. RESULTS: In situ lesions of mantle cell and follicular lymphomas, dendritic cell tumors, and neoplasms with perivascular epithelioid cell differentiation (PEComa), not otherwise specified were classified as malignant (-/3). The fibromatosis group, with the exception of lipofibromatosis, was proposed as benign (-/0). Lipofibromatosis and several diseases that belong to the PEComa group were proposed as uncertain malignant potential (-/1). For the hematologic and soft tissue tumors, 274 and 288 members of the Korean Society of Pathologists, respectively, provided opinions through questionnaire, and most responders showed agreement with the provisional behavior code proposed. CONCLUSIONS: The determination of behavior codes for the rare diseases described in this study, especially those of the PEComa group or malignant lymphoma, could be viewed as impractical and premature, but this study provides the basis for future research on this topic.

16.
Korean J Pathol ; 46(2): 142-50, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23109994

RESUMO

BACKGROUND: It has generally been proven that histone acetylation and deacetylation are involved in the malignant transformation. To date, however, this has rarely been studied in cases of malignant lymphoma. METHODS: We studied nine cases of reactive lymphoid hyperplasia, 78 cases of diffuse large B-cell lymphoma (DLBCL), 13 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 cases of extranodal NK/T-cell lymphoma, nasal type (NKTCL). Thus, we attempted to elucidate the associations of the degree of the expression of histone acetyltransferase 1 (HAT1), histone deacetylase (HDAC) 1, HDAC2, and HDAC3 with the clinical behaviors of above malignant lymphomas using the immunohistochemistry and a western blot analysis. RESULTS: The degree of the expression of HAT1 was higher in cases of DLBCL, PTCL-NOS or NKTCL as compared with reactive lymphoid hyperplasia (p<0.05). The degree of the expression of HAT1 was correlated with that of HDAC1 in cases of DLBCL or NKTCL (p<0.05). The degree of the expression of HAT1 and HDAC1 was correlated with a poor survival in cases of DLBCL or PTCL-NOS (p>0.05). CONCLUSIONS: HAT1, HDAC1, and HDAC2 play a critical role in the development of malignant lymphomas. Both HAT1 and HDAC1 might be indicators for a poor prognosis in cases of DLBCL as cooperating factors.

17.
Korean J Hematol ; 47(2): 150-3, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22783364

RESUMO

Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the basis of immunohistochemical findings of a biopsy specimen of the inferior nasal concha. Immunohistochemical staining showed a positive reaction for CD68, leukocyte common antigen, and S-100 protein, but a negative reaction for CD34, CD1a, and CD21. Imaging studies showed cervical and axillary lymphadenopathies, subcutaneous nodules, and a soft tissue lesion in the nasal cavity. Treatment with the ABVD regimen resulted in complete remission after 8 cycles of chemotherapy.

18.
Int J Pharm ; 422(1-2): 374-80, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22079718

RESUMO

Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu)(2)Et](3) (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD(50) value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.


Assuntos
Antineoplásicos/farmacologia , Portadores de Fármacos , Peptídeos/química , Polietilenoglicóis/química , Taxoides/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Química Farmacêutica , Docetaxel , Composição de Medicamentos , Estabilidade de Medicamentos , Feminino , Humanos , Injeções Intravenosas , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Micelas , Fotólise , Ratos , Ratos Sprague-Dawley , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Taxoides/química , Taxoides/farmacocinética , Taxoides/toxicidade , Tecnologia Farmacêutica/métodos , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Nanosci Nanotechnol ; 11(2): 1803-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21456296

RESUMO

Anionic nanoclays, so-called layered double hydroxide (LDH) nanoparticles, have been extensively applied as drug delivery systems, since they efficiently enter cells via endocytosis pathway and possess controlled release property. However, the stability of LDHs varies, depending on the type of interlayer anions, which can also affect their toxicity. In this study, we investigated the effects of two different forms of LDH, carbonate form (MgAl-LDH-CO3) and chloride form (MgAl-LDH-Cl), on cytotoxicity in human lung epithelial cells. The result showed that MgAl-LDH-Cl was more easily dissolved into metal ions under simulated lysosomal (pH 4.5) and body fluid (pH 7.4) conditions than did MgAl-LDH-CO3. According to cytotoxicity evaluation, MgAl-LDH-CO3 exhibited high toxicity compared with MgAl-LDH-Cl in terms of induction of oxidative stress, apoptosis and membrane damage. These results suggest that easily dissoluble MgAl-LDH-Cl has low cytotoxicity, while high stability of MgAl-LDH-CO3 is correlated to elevated cytotoxicity.


Assuntos
Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Ânions , Apoptose/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Humanos , L-Lactato Desidrogenase/metabolismo , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Nanotecnologia , Estresse Oxidativo/efeitos dos fármacos
20.
J Control Release ; 147(1): 144-50, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20654662

RESUMO

A hydrophobic and water-insoluble platinum(II) compound, cis-(cha)(2)Pt(NO(3))(2) was encapsulated by macromolecular micelles self-assembled from an amphiphilic cyclotriphosphazene [NP(MPEG750)(GlyPheLeu)(2)Et](3) (CP750). The micelle-encapsulated platinum(II) compound exhibited outstanding pharmacokinetics in rats by showing long blood circulation and much larger systemic exposure (AUC=43.5 µgh/ml) compared with the free carboplatin (AUC=4.32 µgh/ml). Biodistribution study of the micellar platinum(II) compound using male Sprague-Dawley rats has shown excellent tumor to tissue ratios of 4.03 at 2h post injection and 4.67 at 24h post injection. Furthermore, the micellar platinum(II) compound exhibited more than 6 times higher cellular uptake in human cervical (HeLa) and lung (A549) tumor cells compared with the free platinum compound. Also it is surprising that the micellar platinum(II) compound displayed specifically high cytotoxicity against the stomach tumor cells (SNU638), which are one of the least responsive to chemotherapeutic agents currently in clinical use. The acute toxicity study has shown that the LD(50) values of free and the micellar cis-(cha)(2)Pt(NO(3))(2) are approximately 70 mg/kg and 90 mg/kg, respectively. Thus the platinum compound encapsulated by cyclotriphosphazene micelles is a promising candidate for preclinical studies.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Compostos Organoplatínicos/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Disponibilidade Biológica , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Dose Letal Mediana , Masculino , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/toxicidade , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
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