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1.
Cancer Lett ; 597: 217070, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880227

RESUMO

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

2.
Asian J Androl ; 25(6): 695-698, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37488835

RESUMO

This study aimed to investigate the incidence of patent processus vaginalis (PPV) in pediatric patients with a unilateral nonpalpable testis and explore the associated factors. From May 2014 to April 2017, 152 boys who were diagnosed with a unilateral nonpalpable testis and underwent laparoscopy in Shanghai Children's Hospital (Shanghai, China) were included in this study. The data were collected and reviewed, and the results were analyzed regarding the age at operation, side, development, and position of the nonpalpable testis. The mean age of the patients was 2.6 (standard deviation: 2.3) years. The testis was absent in 14 cases, nonviable in 81 cases, and viable in 57 cases. The incidence of PPV was 37.5% (57 of 152) on the ipsilateral side and 16.4% (25 of 152) on the contralateral side. The ipsilateral PPV was more prevalent when the nonpalpable testis occurred on the right side ( P < 0.01). Besides, patients with a viable testis had a greater incidence of ipsilateral PPV than those with a nonviable or absent testis ( P < 0.01). Moreover, this rate was the highest when the testis was in the abdominal cavity and the lowest when the testis was in the scrotum (both P < 0.01). However, the incidence of contralateral PPV was independent of all the factors. In conclusion, in children with a nonpalpable testis, the incidence of an ipsilateral PPV was significantly related to the side, development, and position of the testis, while it was independent of these factors on the contralateral side.


Assuntos
Criptorquidismo , Hérnia Inguinal , Laparoscopia , Hidrocele Testicular , Masculino , Criança , Humanos , Lactente , Pré-Escolar , Testículo , China , Hidrocele Testicular/cirurgia , Escroto , Hérnia Inguinal/cirurgia , Criptorquidismo/cirurgia
3.
Jpn J Radiol ; 41(1): 83-91, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35976561

RESUMO

PURPOSE: To investigate the differences in clinicopathological and imaging features according to KRAS mutation status in left- and right-sided colorectal cancer. METHOD: A total of 157 patients with pathologically proven colorectal cancer and preoperative contrast-enhanced multidetector CT examinations were enrolled. According to the tumor location and KRAS status, they were divided into two groups: the left-sided colorectal cancer (LCC) group (wild type, mutant type) and the right-sided colorectal cancer (RCC) group (wild type, mutant type). Clinicopathological and imaging features were recorded in each group. The imaging observation indicators included short axis diameter (SAD), longitudinal tumor length (LTL), tumor shape, pericolic fat stranding, bowel stenosis, intratumoral low-density range, enhancement pattern, and bowel obstruction. Univariate and multivariate logistic regression analyses were performed to compare the difference in KRAS mutation status between groups. RESULTS: In the LCC group, SAD, tumor shape, degree of pericolic fat stranding, and bowel obstruction were significant indicators for predicting KRAS status (P < 0.05). In the RCC group, CA19-9, SAD, and intratumoral low-density range were significant indicators for predicting KRAS status (P < 0.05.). The area under the curve (AUC) of the combination image indicators in the LCC group was 0.802 [cutoff point 0.372, 95% confidence interval (CI) 0.718-0.888, sensitivity 85.4%, specificity 72.0%]. The AUC in the RCC group was 0.828 (cutoff point 0.647, 95% CI 0.726-0.931, sensitivity 79.5%, specificity 75.0%). CONCLUSION: The CT imaging features associated with KRAS mutation status in the LCC and RCC groups were different. The combination of tumor location and imaging features can help to further improve the predictive value of KRAS status.


Assuntos
Carcinoma de Células Renais , Neoplasias Colorretais , Neoplasias Renais , Humanos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Mutação , Tomografia Computadorizada Multidetectores , Prognóstico
4.
Nanoscale ; 14(27): 9736-9742, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35765938

RESUMO

Peaking carbon emissions and achieving carbon neutrality have become the consensus goal of the international community to solve the environmental problems threatening mankind caused by accumulative greenhouse gases like CO2. Herein we proposed vacancy engineering of two-dimensional (2D) topological W2N3 for efficient CO2 hydrogenation into high value-added chemicals and fuels. Spherical aberration corrected scanning transmission electron microscopy (Cs-corrected STEM) confirmed a large amount of N vacancies on the catalyst surface, which significantly reduced the energy barrier for the formation of the essential intermediates of *CO and *CHO as revealed by density functional theory (DFT) calculations. Consequently, the highly stable catalyst exhibited efficient CO2 hydrogenation superior to many previous reports with a maximum CO2 conversion rate of 24% and a high selectivity of 23% for C2+ hydrocarbons. This work provided not only insight into the vacancy-controlled CO2 hydrogenation mechanism, but also fresh ammunition to bring the remaining potential of 2D topological transition metal nitrides in the field of catalysis.

5.
Nano Lett ; 21(23): 10047-10053, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34807619

RESUMO

Design of biosensors capable of imaging ATP and glutathione (GSH) in mitochondria remains a challenge, despite their importance in elucidating their correlated pathophysiological events. Here, we report a new strategy that uses redox-activatable aptamer sensor design combined with nanoparticle-based targeting capability to achieve spatially controlled, AND-gated imaging of ATP and GSH in mitochondria. The DNA nanodevice was designed by the controlled assembly of the redox-responsive ATP aptamer probe on the nanoparticles and further decorated with mitochondria-targeting signals. We demonstrate that the system allows for mitochondria-specific, correlated imaging of ATP and GSH in living cells and in vivo. Furthermore, because the system can be lighted up only when meeting the "dual keys" (overexpressed ATP and GSH in mitochondria) simultaneously, the DNA nanodevice enables specific imaging of tumors in vivo with improved tumor-to-normal tissue ratio. This work illustrates the potential of the DNA nanodevices in the imaging of mitochondrial multivariate targets.


Assuntos
DNA , Glutationa , Trifosfato de Adenosina/metabolismo , DNA/metabolismo , Glutationa/metabolismo , Mitocôndrias/metabolismo , Oxirredução
6.
Front Med (Lausanne) ; 8: 726103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660636

RESUMO

Objective: The health-related quality of life (HRQoL) of donors deserves attention and must be considered for a long time. Many of the published studies had small sample sizes, and research from mainland China, in particular, is scant. Thus, this study aimed to investigate the HRQoL of living liver donors and identify the influencing factors of the HRQoL in mainland China. Methods: This is a cross-sectional study. The data were collected from the liver transplantation center, the Tianjin First Center Hospital, China. Living liver donors older than 18 years and at a minimum of 1-month, post-donation was included. The HRQoL was evaluated using the Medical Outcome Study Short form 36 (SF-36). Sociodemographic and clinical-related variables, HRQoL status, and its potential impact factors were analyzed. Results: A total of 382 living liver donors completed the survey. The median number of months post-donation was 25, and parental donors (99.2%) were the most frequent relationship. The majority of the participants (372, 97.4%) donated their left lateral lobes. Thirty-two (8.4%) donors suffered complications, and of them, 7 suffered from biliary leakage (1.8%), which was the most common one in this study. The physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), social functioning (SF), role-emotional (RE), and mental health (MH) scores among the living liver donors were significantly better than those of the Chinese norms. Short-time post-donation [odds ratio (OR): 0.008; p < 0.001] and male recipients (OR:0.195; p = 0.024) were associated with the likelihood of a poor physical related quality of life. Conclusions: Despite, in general, good HRQoL outcomes, we also believed that liver donation has an obvious influence on the physical functions of liver donors. More attention and long-term follow-ups are necessary for donors at higher risk based on identified influencing factors and correlates.

7.
Nuklearmedizin ; 60(3): 240-248, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33759146

RESUMO

AIM: To observe the effect of pHLIP(Var7)-P1AP on the proliferation of MDA-MB-231 triple-negative breast cancer cells and the small-animal single-photon-emission computed tomography (SPECT) imaging of breast cancer-bearing mice carrying MDA-MB-231 cells. METHODS: Peptide pHLIP(Var7)-P1AP was synthesized by solid-phase peptide synthesis. The binding of fluorescently labeled pHLIP(Var7)-P1AP to MDA-MB-231 cells under various pH conditions and its effect on MDA-MB-231 cell proliferation were analyzed. pHLIP(Var7)-P1AP was labeled with 125I, and the biological distribution of 125I-pHLIP(Var7)-P1AP in the breast cancer mouse model carrying MDA-MB-231 cells as well as the outcome of small-animal SPECT imaging were evaluated. RESULTS: pHLIP(Var7)-P1AP was successfully synthesized. Under pH 6.0, fluorescently labeled pHLIP(Var7)-P1AP had a higher binding ability to MDA-MB-231 cells and significantly inhibited the proliferation of MDA-MB-231 cells. The labeling efficiency of pHLIP(Var7)-P1AP with 125I was 33.1 ±â€Š2.7 %, and the radiochemical purity was 98.5 ±â€Š1.8 %. 125I-pHLIP(Var7)-P1AP showed a high concentration in tumors. Small-animal SPECT imaging showed clearly visible tumors at 4 h after injection. CONCLUSIONS: In the acidic environment, pHLIP(Var7)-P1AP can efficiently target MDA-MB-231 cells and inhibit their growth. Small-animal SPECT of 125I-pHLIP(Var7)-P1AP can clearly image tumors.


Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Radioisótopos do Iodo , Camundongos , Camundongos Nus , Tomografia Computadorizada de Emissão de Fóton Único
8.
Front Pharmacol ; 11: 578887, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192520

RESUMO

BACKGROUND: Immunosuppressant non-adherence is a widespread problem among solid organ recipients. With the newly published clinical trials, the randomized controlled trials (RCTs) based systematic review of adherence-enhancing interventions on immunosuppressant adherence in solid organ recipients has not been completed. In this systematic review and meta-analysis, we compared the efficacy of adherence-enhancing interventions versus routine intervention, as performed with RCTs, on immunosuppressant adherence in solid organ transplantation recipients. METHODS: PubMed, Embase, Cochrane Library, CINAHL full text, and PsycINFO were searched from database inception to December 2019. This review was conducted following the PRISMA's reporting guidelines and according to the principles recommended by Cochrane Handbook for Systematic Review. RESULTS: The search yielded 10,479 articles. A total of 27 articles (26 studies) with 715 participants were included in our analysis. Results from the meta-analysis revealed that as compared with that of the routine intervention group, the rates of overall adherence, dosing adherence, and timing adherence were significantly increased within the adherence-enhancing intervention group, with the pooled risk ratio (RR) of overall adherence = 1.17, [95% confidence interval (CI): 1.07 to 1.28; p = 0.0006]; RR of dosing adherence = 1.21 (95% CI: 1.08 to 1.36, p = 0.001); RR of timing adherence = 1.16 (95% CI: 1.03 to 1.29, p = 0.01). There was a significantly increased adherence score in the adherence-enhancing intervention group; however, no statistical significance on the immunosuppressant blood concentration was found between the two study groups. Results obtained from a subgroup analysis shown interventions led by a multidisciplinary team, both the assessment time at 6 months and 12 months demonstrated a significantly increased adherence rate in the intervention group compared with the control group. CONCLUSIONS: The findings of this report indicate that clinicians (doctors and nurses) should maintain a long-term intervention protocol to ensure immunosuppressant adherence within solid organ transplant recipients. To accomplish this goal, we recommend a multidisciplinary team-led, comprehensive intervention approach combined with mobile health monitoring for the administration of an effective immunosuppressive therapy regimen.

10.
Medicine (Baltimore) ; 95(48): e5462, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27902598

RESUMO

The aim of the study was to investigate the correlation of glucose transporter-1 (Glut-1) and glucose transporter-3 (Glut-3) expression with F-18 FDG uptake in pulmonary inflammatory lesions.Twenty-two patients with pulmonary inflammatory lesions underwent positron emission tomography/computed tomography (PET/CT) examination preoperatively, and Glut-1 and Glut-3 expression were detected by immunohistochemistry in these lesions. Correlations of Glut-1 and Glut-3 with F-FDG uptake were assessed using Spearman's rank correlation test.The maximum standardized uptake value (SUVmax) of pulmonary inflammatory lesions in 22 patients was 0.50 to 7.50, with a mean value of 3.66 ±â€Š1.62. Immunohistochemical staining scores of Glut-1 and Glut-3 were 2.18 ±â€Š0.96 and 2.82 ±â€Š1.37, respectively. The expression of Glut-1 and Glut-3 was positively correlated with F-18 FDG uptake. Glut-3 expression was evidently higher than Glut-1 expression in 22 patients.Glut-1 and Glut-3 expressions are high in pulmonary inflammatory lesions, and Glut-3 plays a more important role in F-18 FDG uptake in pulmonary inflammatory lesions.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Pneumopatias/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 939-42, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30048086

RESUMO

To achieve the object of NIF ignition , it is required to prepare high density fuel targets . For DD layer, IR-layering can be used to improve its surface roughness. In this paper, glow discharge polymer (GDP) flat films and capsules were synthesized. The IR absorptive properties of GDP were thoroughly studied by using infrared spectrometer and microscopy while the extinction coefficients of GDP flat film at specific wavelengths were obtained. By comparing absorption properties of flat films and capsules, it is found that thermal treatments can lower the OH content of GDP and thus improve IR layering of DD ice. Finally, the needed IR power of integration sphere were estimated by using data obtained for future DD layering experiments in this paper. The results have laid a solid foundation for the implementation of DD IR layering.

13.
Acta Pharmacol Sin ; 36(12): 1528-36, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26592518

RESUMO

AIM: TPN729MA is a novel selective PDE5 inhibitor currently under clinical development in China for the treatment of erectile dysfunction. In this study we characterized its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. METHODS: The preclinical PK of TPN729MA was studied in rats and dogs. Human clearance (CL) values for TPN729MA were predicted from various allometric methods and from intrinsic CL determined in human liver microsomes. Human PK and plasma concentration versus time profiles of TPN729MA were predicted by using a PBPK model in GastroPlus. Considering the uncertainties in the prediction, a preliminary human study was conducted in 3 healthy male volunteers with an oral dose of 25 mg. RESULTS: After a single intravenous administration of TPN729MA at a dose of 1 mg/kg in rats and 3 mg/kg in dogs, the plasma CL was 69.7 mL·min(-1)·kg(-1) in rats and 26.3 mL·min(-1)·kg(-1) in dogs, and the steady-state volumes of distribution (V(ss)) were 7.35 L/kg in rats and 6.48 L/kg in dogs. The oral bioavailability of TPN729MA was 10% in rats and above 34% in dogs. Profiles of predicted plasma concentration versus time were similar to those observed in humans at 25 mg, and the predicted T(max), C(max) and AUC values were within 2-fold of the observed values. CONCLUSION: TPN729MA demonstrates good preclinical PK. This compound is a valuable candidate for further clinical development. This study shows the benefits of using a PBPK model to predict PK in humans.


Assuntos
Inibidores da Fosfodiesterase 5/farmacocinética , Animais , Proteínas Sanguíneas/metabolismo , Células CACO-2 , Cães , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Microssomos Hepáticos/metabolismo , Modelos Biológicos , Inibidores da Fosfodiesterase 5/sangue , Inibidores da Fosfodiesterase 5/metabolismo , Ratos
14.
Bioresour Technol ; 175: 51-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25459803

RESUMO

This work studied the feasibility of co-gasification of biosolids with biomass as a means of disposal with energy recovery. The kinetics study at 800°C showed that biomass, such as switchgrass, could catalyze the reactions because switchgrass ash contained a high proportion of potassium, an excellent catalyst for gasification. However, biosolids could also inhibit gasification due to interaction between biomass alkali/alkaline earth metals and biosolids clay minerals. In the pilot scale experiments, increasing the proportion of biosolids in the feedstock affected gasification performance negatively. Syngas yield and char conversion decreased from 1.38 to 0.47m(3)/kg and 82-36% respectively as the biosolids proportion in the fuel increased from 0% to 100%. Over the same range, the tar content increased from 10.3 to 200g/m(3), while the ammonia concentration increased from 1660 to 19,200ppmv. No more than 25% biosolids in the fuel feed is recommended to maintain a reasonable gasification.


Assuntos
Biomassa , Reatores Biológicos , Panicum/química , Eliminação de Resíduos/métodos , Catálise , Gases , Cinética , Projetos Piloto
15.
PLoS One ; 9(5): e97113, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24820970

RESUMO

BACKGROUND: Apolipoprotein A-I (apoA-I), the major protein for high density lipoprotein, is essential for reverse cholesterol transport. Decreased serum levels of apoA-I have been reported to correlate with subcortical infarction and dementia, both of which are highly related to white matter lesions (WMLs). However, the association between apoA-I and WMLs has never been investigated. In this study, we sought to investigate the association between apoA-I and the presence of WMLs in middle-aged and elderly subjects. METHODS: Consecutive patients aged 50 years and older of our department were prospectively enrolled in this study (n = 1282, 606 men and 676 women, 65.9 ± 9.4 years). All participants underwent MRI scans to assess the presence and severity of WMLs. Multivariate logistic regression analyses were performed to examine the association of apoA-I with WMLs. RESULTS: Patients with WMLs were older and showed significantly higher proportion of male sex, hypertension, diabetes mellitus, previous stroke, and coronary heart disease whereas levels of total cholesterol, high density lipoprotein cholesterol, and apoA-I were lower. After adjustment for potential confounders, the lowest apoA-I quartile was independently associated with an increased risk of WMLs (odds ratio: 1.87, 95% confidence interval: 1.29-2.72). In sex-specific analyses, this relationship was observed only in women. CONCLUSIONS: Our findings demonstrated that apoA-I was inversely associated with the presence of WMLs in middle-aged and elderly subjects. This results suggest that therapies which increase apoA-I concentration may be beneficial to reduce the risk of WMLs, dementia and stroke.


Assuntos
Apolipoproteína A-I/metabolismo , Leucoaraiose/epidemiologia , Leucoaraiose/metabolismo , Idoso , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Risco
16.
Zhongguo Zhong Yao Za Zhi ; 39(20): 3969-73, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25751948

RESUMO

Sixteen compounds including daphnoretin (1), isofraxidin (2), scopoletin (3), kaempferol (4), quercetin (5), guaijaverin (6), astragalin (7), quercetin-3-O-ß-D-glucopyranoside (8), naringenin-7-O-ß-D-glucopyranoside (9), 5-O-methylapi- genin-7-O-ß-D-glucopyranoside (10), methyl gallate (11), prionitiside A (12), (2S)-2,3-dihydroxypropyl-1,6,8-trihydroxy-3- methyl-9,10- dioxoanthracene-2-carboxylate (13), 3,3'-di-O-methyl ellagic acid (14), 3'-O-methyl-3,4-O,O-metheneellagic acid-4'-O-ß-D- glucopyranoside (15) and 3,4-methylenedioxy-3'-O-methylellagic acid (16), were isolated from the 70% acetone extract of Euphorbia dracunculoides Lam. Among them, compounds 1-3, 6-9, 11, and 14 were isolated from E. dracunculoides for the first time, and compounds 10, 12, 13, 15, and 16 were firstly obtained from the genus Euphorbia. Their structures were elucidated by spectroscopic analysis, including 1H-NMR, 13C-NMR, and ESI-MS.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Euphorbia/química , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química , Espectrometria de Massas por Ionização por Electrospray
17.
Yao Xue Xue Bao ; 49(12): 1684-8, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25920197

RESUMO

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.


Assuntos
Antineoplásicos/farmacocinética , Indóis/farmacocinética , Pirróis/farmacocinética , Receptores Proteína Tirosina Quinases/farmacocinética , Animais , Haplorrinos , Humanos , Modelos Biológicos , Ratos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Distribuição Tecidual
18.
J Pharm Biomed Anal ; 85: 21-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23872212

RESUMO

Controlling and minimizing the adverse effects of drugs are the key issues in ensuring the safety of drug therapy. Carboxymethyl chitosan has been widely used as an anti-adhesion material. However, recently in China there have been several reported instances of conjunctival hyperemia associated with the use of carboxymethyl chitosan containing products. Through MS, FTIR, and GC analysis, an impurity, diglycolic acid, was discovered in carboxylmethyl chitosan products. Pharmacological tests further indicated diglycolic acid has antithrombogenicity properties and induces vasodilation, both of which can cause conjunctival hyperemia. Thus, through these tests it was ascertained that diglycolic acid was the culprit responsible for the adverse clinical effects. Next, emphasis shifted to trying to discover the mechanism responsible for generating the diglycolic acid. Under strong basic conditions, chloroacetic acid can generate glycolic acid, which, upon etherification, can become diglycolic acid. In order to avoid future adverse effects, we have established an HPLC method to detect and determine diglycolic acid in carboxymethyl chitosan products. This method is specific, accurate, and precise, and can be easily implemented into routine monitoring practice. Concurrently, a refined method has also been established in order to eliminate diglycolic acid from carboxymethyl chitosan.


Assuntos
Quitosana/análogos & derivados , Contaminação de Medicamentos , Glicolatos/análise , Animais , Quitosana/efeitos adversos , Quitosana/análise , Cromatografia Líquida de Alta Pressão , Coelhos , Espectrometria de Massas por Ionização por Electrospray
19.
Chin Med J (Engl) ; 126(3): 471-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23422109

RESUMO

BACKGROUND: Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na(131)I labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis. METHODS: The 10-mer cyclic peptide contained the LyP-1 sequence (YCGNKRTRGC) was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na(131)I using the chloramine-T method. The [(131)I] LyP-1 peptide and a [(131)I] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. Biodistribution and imaging results in vivo were obtained. RESULTS: The labeling efficiencies of LyP-1 peptide reached 80% ± 5% (n = 5). The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37°C. In the biodistribution studies, the [(131)I] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [(131)I] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts. CONCLUSIONS: The LyP-1 peptide could be effectively labeled with Na(131)I and the labeled compound is stable in human serum at 37°C for 24 hours. The high specificity of [(131)I] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.


Assuntos
Peptídeos Cíclicos/química , Animais , Neoplasias da Mama/diagnóstico , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Tomografia Computadorizada de Emissão de Fóton Único
20.
Chin J Cancer Res ; 24(1): 52-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23359762

RESUMO

OBJECTIVE: To explore a tumor peptide imaging agent Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg- Leu-Gly-Gly-Cys, tripeptide RRL [tRRL]) that targeted to tumor cells and tumor-derived endothelial cells (TDECs) and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 (VEGFR-2). METHODS: The tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs. Tyrosine was conjugated to the amino terminal of RRL (Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys) for labeling with radionuclide iodine-131 ((131)I-tRRL). The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro. Whether VEGFR-2 is the binging site of tRRL was investigated. Biodistribution and single-photon emission computed tomography (SPECT) imaging of (131)I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice. RESULTS: In vitro cellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells. VEGFR-2, which is highly expressed on TDECs, was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium. (131)I-tRRL mainly accumulated in tumors in vivo, not other organs at 24 h after injection. SPECT imaging with (131)I-tRRL clearly visualized tumors in nude mice, especially at 24 h. CONCLUSION: Radioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors targeted to neovascularization, and may be a promising candidate for tumor radioimmunotherapeutic carrier.

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