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Nowotwory kości : nowe możliwości terapeutyczne

Wyszkowska Roksana, Drzeżdżon Joanna, Musiał Claudia, Górska-Ponikowska Magdalena

Wiadomości Chemiczne

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2019

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[Z] 73, 11-12

701--713

EN

Among bone tumours, Osteosarcoma (OS), Chondrosarcoma (CS) and Fibrosarcoma (FS) are highly metastatic with poor prognostic for survival. Standard procedures as surgery resection, radiotherapy and chemotherapy do not lead to full recovery or they do not affect metastasis [1-4]. Nowadays new molecular targets to cure cancer are during clinical trials. Clinical trials for OS are focused on using monoclonal antibody (dinutuximab) [5], immunotherapy (as using GM-CSF with influence on white blood cells) [6] or compounds acting as VEGFR inhibitor or PDGFR inhibitor - to reduce metastasis [7-9]. Clinical trials for CS are targeting the hedgehog pathway, focused on its inhibition [10], inhibition of IDH1/2 (common mutation in CS leading to hypermethylation) [11] or, as in OS treatment, inhibition of metastasis by acting on VEGFR [12]. Beyond new chemotherapy and chemotherapy correlated with radiotherapy [13] clinical trials for FS are targeting gene fusion NTRK acting through inhibition of tropomyosin kinase receptor [14]. This approach to treatment is a novelty on the global scale [15]. Nitric oxide (NO) has many biological functions, e.g.: acting as neurotransmitter, reduced aggregation of platelets, acting as EDRF or reducing the oxidative stress in tumours [16-18]. Due to the dual nature of NO [19] anti-proliferative, pro-apoptotic and cell cycle arrest effect of NO were observed [20-25]. It could be a new area to find novel anti-cancer compound. One of the molecular targets under the scientists consideration is the activation of nitric oxide synthase (NOS). Górska-Ponikowska et al. [26-28] focused on experiments on OS 143B cells with 2-methoxyestradiol (2-ME) treatment, potentially novel compound playing the role of n-NOS activator. The researchers reported influence of 2-ME on down-regulation of mitochondrial biogenesis via direct influence on n-NOS level in OS 143B cells. What is more, L-lactate was indicated as potential molecular marker of anticancer therapy of tumours with metastasis.

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Preparation and evaluation of a [66Ga]gallium chitosan complex in fibrosarcoma bearing animal models

Pourjavadi A., Akhlaghi M., Jalilian A. R.

Nukleonika

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2011

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Vol. 56, No. 1

35-40

EN

[66Ga]gallium chitosan complex was prepared with a high radiochemical purity (greater than 99%) in dilute acetic acid solution. The radiochemical purity of [66Ga]gallium chitosan complex was checked by using paper chromatography technique. The prepared complex solution was injected intratumoral to fibrosarcoma-bearing mice and the leakage of radioactivity from injection site was investigated. Approximately, 85.4% of the injected dose was retained in the injection site 54 h after injection and most of the leaked radioactivity was accumulated in the blood, liver (0.5%) and lung (6.5%).

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Preparation, quality control and biodistribution studies of [61Cu]-oxinate for PET tumor imaging

Jalilian A. R., Zolghadri S., Faghihi R., Yousefnia H., Garousi J., Shafaii K., Bolourinovin F.

Nukleonika

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2009

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Vol. 54, No. 3

175-179

EN

Targeting apoptosis is an interesting issue in molecular imaging and various modalities have been presented. However, recent experiences in nuclear pharmacy demonstrated the application of small tracer molecules is more desired. This work was conducted for production of a radiolabeled copper complex, i.e. 61Cu-oxinate as a potential PET tracer for apoptosis imaging in oncology. Cu-61 was prepared by natural zinc target irradiation with 22 MeV protons (150 miA) via the natZn(p, xn)61Cu nuclear reaction with a yield of 3.33 mCi/miAh. In order to obtain the best labeling method, optimization reactions were performed for pH, temperature and concentration followed by solid phase extraction. Biodistribution of the tracer was studied in wild-type and fibrosarcoma bearing mice. Under the optimized conditions, radio-thin-layer chromatography (RTLC) and HPLC showed radiochemical purities of 99.99% and 97% respectively (with a minimum specific activity of 16 Ci/mM). Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated a significant tumor uptake after 3 h. Tumor:blood and tumor:muscle ratios were 2.0 and 6.0 after 3 h, respectively.

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Preparation and biological evaluation of [61Cu]bleomycin complex as a possible PET radiopharmaceutical in normal and fibrosarcoma-bearing animals

Jalilian A. R., Zandi H., Sardari D., Akhlaghi M., Kamali-Dehghan M., Shafaei K., Majdabadi A.

Nukleonika

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2009

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Vol. 54, No. 2

135-141

EN

[61Cu]bleomycin ([61Cu]BLM) was prepared using [61Cu]CuCl2 produced via natZn(p,x)61Cu. [61Cu]BLM was prepared under optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 92.5–370 MBq 61CuCl2) with radiochemical purity over 98% shown by HPLC and RTLC. [61Cu]BLM was administered into normal and tumor bearing rodents up to 210 min followed by biodistribution and co-incidence imaging studies. A significant tumor/non tumor accumulation was observed either by animal sacrification or an imaging method. [61Cu]BLM can be a potential PET radiotracer for tumor imaging.

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Biologiczne aspekty terapii fotodynamicznej chlorinem E6 w mięsaku włóknistym

Bronowicz A., Bednarkiewicz A., Symonowicz K., Stręk W., Ziółkowski P., Koszubieev A.

Acta Bio-Optica et Informatica Medica. Inżynieria Biomedyczna

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2001

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Vol. 7, nr 3-4

179-184

PL

W przedstawionej pracy zastosowano naturalny związek fotouczulający chlorin e6 (Ce6), otrzymany w wyniku ekstrakcji z chlorofilu a. Związek ten charakteryzuje się dobrymi właściwościami cytotoksycznymi i cytofototoksy-cznymi in vitro oraz znikomą toksycznością in vivo, szybkim gromadzeniem się w nowotworze i także szybkim wydalaniem z organizmu. Nowym aspektem jest zastosowanie lasera półprzewodnikowego do uaktywniania Ce6 w terapii fotodynamicznej mięsaka włóknistego BFS1, zaszczepionego myszom BALB/c. W terapii fotodynamicz-nej z zastosowanien Ce6 uzyskano blisko trzykrotne wydłużenie czasu przeżycia w stosunku do grup kontrolnych. W grupie zwierząt naświetlanych dawką 90 J/cm2 średni czas przeżycia wyniósł 82,4 dni, a w grupie naświetlanych dawką 135 J/cm2 - 85,7 dni. W grupach kontrolnych nie przekroczył on 30,6 dni.

EN

In the presented paper the natural photosensitising compound chlorin e6 (Ce6), obtained by extraction from chlorophyll a, was used. The compound has high cytotoxic and cytophototoxic properties in vitro, neglectible in vivo toxicity, fast accumulation in the neoplasm tissue and fast expelling from the organism. The new aspect of this work is the application of semiconductor laser diode for photoactivation of the Ce6 in the PDT of fibrosarcoma BFS1, implanted into the BALB/c mice. The results of photodynamic therapy with the use of Ce6 were very good, which means almost threefold extending of the lifetime of the mice comparing to control groups. In the group of animals treated with 90 J/cm2 dose of light, average lifetime was 82.4 days, in the group of animals treated with 135 J/cm2 dose of light - 85.7 days, whereas in the control groups did not exceed 30.6 days.