RESUMEN
Water lily is an important ornamental flower plant which is capable of viviparous plantlet development. But no study has been reported on the molecular basis of viviparity in water lily. Hence, we performed a comparative transcriptome study between viviparous water lily Nymphaea micrantha and a nonviviparous species Nymphaea colorata at four developmental stages. The higher expression of highly conserved AUX/IAA, ARF, GH3, and SAUR gene families in N. micrantha compared to N. colorata is predicted to have a major impact on the development and evolution of viviparity in water lily. Likewise, differential regulation of hormone signaling, brassinosteroid, photosynthesis, and energy-related pathways in the two species provide clues of their involvement in viviparity phenomenon. This study revealed the complex mechanism of viviparity trait in water lily. The transcriptomic signatures identified are important basis for future breeding and research of viviparity in water lily and other plant species.
Asunto(s)
Nymphaea , Flores/genética , Flores/metabolismo , Fitomejoramiento , Transcriptoma/genéticaRESUMEN
OBJECTIVE: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a d-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. METHODS: This novel contrast agent was specifically studied because of its ability to "target" metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2 mmol Gd/kg over a 120 min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. RESULTS: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15 min after injection of Gd-DTPA-DG (p<0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. CONCLUSION: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI.
Asunto(s)
Adenocarcinoma/metabolismo , Medios de Contraste/síntesis química , Gadolinio DTPA/síntesis química , Glucosamina/química , Neoplasias Pulmonares/metabolismo , Imagen por Resonancia Magnética/métodos , Neoplasias Experimentales/metabolismo , Análisis de Varianza , Animales , Medios de Contraste/farmacocinética , Gadolinio DTPA/farmacocinética , Glucosamina/farmacocinética , Humanos , Ratones , Ratones Desnudos , Trasplante HeterólogoRESUMEN
OBJECTIVE: We aimed to synthesize diethylenetriamine pentaacetic acid-deoxyglucose (DTPA-DG) radiolabeled with (188)Re and to evaluate its biologic characteristics using mammary tumor-bearing mice. MATERIALS AND METHODS: The biodistribution of the radiolabeled compound was determined by tissue counting at 3, 12, and 24 hours after injection in experimental animals. Scintigraphic examinations of nude mice bearing breast cancer (MCF-7 cells) were performed after (188)Re-DTPA-DG (18.5 MBq) was injected in the tail vein. For the tumor inhibitory portion of this work, tumor volumes were measured and recorded every 3 days until the 21st day after injection. RESULTS: The radiochemical purity of (188)Re-DTPA-DG was 95.0%. Based on biodistribution measurements, (188)Re-DTPA-DG was taken up at high levels by the tumor. The mean tumoral percent injected dosages per gram (% ID/g) were 1.98 +/- 0.29 (SD), 2.89 +/- 0.43, and 0.42 +/- 0.06 % ID/g at 3, 12, and 24 hours, respectively, after injection. In the (188)Re-DTPA-DG scintigraphic examinations, the tumors were clearly delineated on the images recorded 2, 4, 8, 12, and 24 hours after injection. In the tumor inhibitory evaluations, the tumor volume of the (188)Re-DTPA-DG-treated group increased more slowly than that of the control groups, which were treated with (188)Re-perrhenate or saline (p < 0.01). Rhenium-188-DTPA-DG showed excellent tumor targeting and tumor growth suppression properties on MCF-7 tumor cells. CONCLUSION: Rhenium-188-DTPA-DG may be a potential agent for the diagnosis and radiotherapy of tumors.
Asunto(s)
Desoxiglucosa/análogos & derivados , Neoplasias Mamarias Animales/diagnóstico por imagen , Ácido Pentético/análogos & derivados , Radiofármacos , Animales , Desoxiglucosa/química , Desoxiglucosa/farmacocinética , Femenino , Ratones , Ratones Desnudos , Ácido Pentético/química , Ácido Pentético/farmacocinética , Cintigrafía , Radiofármacos/química , Radiofármacos/farmacocinética , Distribución TisularRESUMEN
OBJECTIVE: To evaluate apoptosis induced by rehenium-188-labeled diethylenetriamine pentaacetic acid-glucosamine (188Re-DTPA-DG) in MCF-7 breast carcinoma cells and A549 pulmonary carcinoma cells. METHODS: Through the use of flow cytometry (FCM) with CBA software to detect apoptosis, cells of both the MCF-7 and A549 cell lines were divided into groups exposed to 188Re-DTPA-DG, 188Re-perrhenate (188ReO4-), and saline, respectively. The first two groups were further divided into subgroups on the basis of their exposure to radioactivity at 37, 55.5, or 74 kBq/mL, with the saline-exposed group divided into three corresponding subgroups. Each subgroup was introduced into 5 replicate wells of a culture plate, and the morphology of the cells in each well was determined by flow cytometry at 6-hour intervals for 18 hours. In order to determine the affinity of 188Re-DTPA-DG for tumor tissue, the biodistribution of the radiolabeled agent was assessed in breast tumor-bearing nude mice. RESULTS: Change in morphology of the cell nucleus was more evident in the 188Re-DTPA-DG-treated than in the 188ReO4--treated group, and no change in nuclear morphology was seen in the saline-exposed group. The study data suggested that there was a greater ratio of apoptotic to nonapoptotic cells among the 188Re-DTPA-DG-treated than among the 188ReO4--treated or saline-exposed cells (p<0.01), and a greater change in cell-nuclear morphology in the 188Re-DTPA-DG-treated than in the 188ReO4--treated cells. Furthermore, 188Re-DTPA-DG had a more significant apoptosis-inducing effect on both MCF-7 and A549 cells than did 188ReO4-. The biodistribution study in tumor-bearing nude mice showed that the concentration of 188Re-DTPA-DG in tumor tissue was much higher than in normal tissue, that 188Re-DTPA-DG was rapidly cleared from the blood, and that the main route of its clearance was via the kidneys. CONCLUSIONS: 188Re-DTPA-DG has a significant apoptotic effect on carcinoma cells. 188Re-DTPA-DG is an effective radiopharmaceutical for intratumoral radiation therapy.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Neoplasias Pulmonares/patología , Compuestos Organometálicos/toxicidad , Animales , Línea Celular Tumoral , Humanos , Ratones , Ratones Desnudos , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacocinética , Compuestos Organometálicos/farmacología , Radiofármacos/química , Radiofármacos/farmacocinética , Radiofármacos/farmacología , Radiofármacos/toxicidadRESUMEN
This study describes the radiolabeling and preliminary biologic testing of diethylenetriaminepentaacetic acid (DTPA)-deoxyglucose (DG) labeled with (99m)Tc. A one-step [(99m)Tc]-DTPA-DG kit was prepared using the stannous chloride reduction method. When (99m)TcO(4)(-) was added to the DTPA-DG kit at room temperature the radiochemical purity 30 min later was 99.2%, and it remained >98.6% for 6 h. Rapid blood clearance of [(99m)Tc]-DTPA-DG was observed in in vivo biodistribution, the main route of clearance was via the kidneys. No significant accumulation in any other organs was seen. The tumor-to-brain and tumor-to-muscle concentration ratios for [(99m)Tc]-DTPA-DG uptake were higher than those for fluorine-18-flurodeoxyglucose ((18)F-FDG). Scintigraphic results demonstrated the feasibility of [(99m)Tc]-DTPA-DG imaging tumors. The [(99m)Tc]-DTPA-DG complex is a potential imaging agent due to the ideal physical characteristics of the radionuclide, ease of preparation, low cost, early accumulation and the preference for the renal route of excretion.