| 1. |
- Wiegell, S. R., et al.
(author)
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A randomized, multicentre study of directed daylight exposure times of 11/2 vs. 21/2 h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp
- 2011
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 164:5, s. 1083-1090
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Journal article (peer-reviewed)abstract
- Background Vascular endothelial growth factor (VEGF)-A, placenta growth factor (PlGF) and their corresponding membrane receptors are involved in autocrine and paracrine regulation of melanoma growth and metastasis. Besides the membrane receptors, a soluble form of the VEGF receptor (VEGFR)-1 (sVEGFR-1) has been identified, that behaves both as a decoy receptor, sequestering VEGF-A and PlGF, and as an extracellular matrix (ECM) molecule, promoting endothelial cell adhesion and migration through the interaction with alpha 5 beta 1 integrin. Objectives To analyse whether sVEGFR-1 plays a role during melanoma progression. Methods sVEGFR-1 expression was evaluated in a panel of 36 melanoma cell lines and 11 primary human melanocyte cultures by quantitative real-time polymerase chain reaction analysis and in specimens of primary or metastatic melanoma lesions from 23 patients by immunohistochemical analysis. Results sVEGFR-1 expression was highly upregulated in melanoma cell lines with respect to human melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed a significant reduction of sVEGFR-1 expression, as compared with cell lines derived from primary tumours. These results were confirmed by immunohistochemical analysis of sections from primary skin melanomas and the corresponding cutaneous metastases, suggesting that modulation of sVEGFR-1 expression influences ECM invasion by melanoma cells and metastasis localization. Moreover, we provide evidence that adhesion of melanoma cells to sVEGFR-1 is favoured by the activation of a VEGF-A/VEGFR-2 autocrine loop. Conclusions Our data strongly suggest that sVEGFR-1 plays a role in melanoma progression and that low sVEGFR-1/VEGF-A and sVEGFR-1/transmembrane VEGFR-1 ratios might predict a poor outcome in patients with melanoma.
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| 2. |
- Wiegell, S. R., et al.
(author)
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Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp : a randomized multicentre study
- 2012
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 166:6, s. 1327-1332
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Journal article (peer-reviewed)abstract
- Background Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. Objectives In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. Methods One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1 1/2 or 2 1/2 h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. Results No difference in lesion response was found between the 1 1/2 and 2 1/2 h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75.9%) than in grade II (61.2%) and grade III (49.1%) lesions (P < 0.0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3.5 J cm(-2). Conclusions Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.
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| 3. |
- Marco, M., et al.
(author)
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Pterocarpans and isoflavones from the root bark of Millettia micans and of Millettia dura
- 2017
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In: Phytochemistry Letters. - : Elsevier BV. - 1874-3900. ; 21, s. 216-220
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Journal article (peer-reviewed)abstract
- From the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia micans, a new pterocarpan, (6aR, 11aR)-3-hydroxy- 7,8,9-trimethoxypterocarpan (1), named micanspterocarpan, was isolated. Similar investigation of the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia dura gave a further new pterocarpan, (6aR, 11aR)-8,9-methylenedioxy-3-prenyloxypterocarpan (2), named 3-O-prenylmaackiain, along with six known isoflavones (38) and a chalcone (9). All purified compounds were identified by NMR and MS, whereas the absolute configurations of the new pterocarpans were established by chriptical data analyses including quantum chemical ECD calculation. Among the isolated constituents, calopogonium isoflavone B (3) and isoerythrin A-4'-(3-methylbut-2-enyl) ether (4) showed marginal activities against the 3D7 and the Dd2 strains of Plasmodium falciparum (70-90% inhibition at 40 mu M). Maximaisoflavone B (5) and 7,2'-dimethoxy-4', 5'-methylenedioxyisoflavone (7) were weakly cytotoxic (IC50 153.5 and 174.1 mu M, respectively) against the MDA-MB-231 human breast cancer cell line. None of the tested compounds showed in-vitro translation inhibitory activity or toxicity against the HEK-293 human embryonic kidney cell line at 40 mu M.
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| 4. |
- Atilaw, Yoseph, et al.
(author)
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Prenylated Flavonoids from the Roots of Tephrosia rhodesica
- 2020
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In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 83:8, s. 2390-2398
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Journal article (peer-reviewed)abstract
- Five new compounds-rhodimer (1), rhodiflavan A (2), rhodiflavan B (3), rhodiflavan C (4), and rhodacarpin (5)-along with 16 known secondary metabolites, were isolated from the CH2Cl2-CH3OH (1:1) extract of the roots of Tephrosia rhodesica. They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2-5, 9, 15, and 21 showed activity (100% at 10 mu g and IC50 = 5-15 mu M) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
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| 5. |
- Atilaw, Y., et al.
(author)
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Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata
- 2017
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In: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 22:2
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Journal article (peer-reviewed)abstract
- In our search for new antiplasmodial agents, the CH2Cl2/CH3OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4-ethoxy-3-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
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| 6. |
- de Vera, Jean Paul, et al.
(author)
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EUROX (Europa Explorer): An astrobiology mission concept to the Jovian icy moon Europa.
- 2008
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In: Geophysical Research Abstracts. ; 10, EGU2008-A-01483, 2008
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Conference paper (other academic/artistic)abstract
- The discovery of so-called extremophiles indicates how robust life is. That microbial life can resist extreme and harsh environmental conditions as e.g. very high and cold temperatures, desiccation, acidity, salinity and wide ranges of radiation spectra including UV and X-rays, suggests that micro organisms are capable of surviving and maintaining essential living functions, or often thriving, in conditions previously thought impossible. Recently it seems that only liquid water and an energy source are the core prerequisites for the development of life, greatly expanding the range of potential habitats for life both on Earth and in the solar system. In light of these discoveries, the definition of the “Habitable Zone” as the region where liquid water can exist at a planetary surface may need revision. Energy in the form of heat may be found on several volcanic worlds in our solar system, and subsurface liquid water may exist there, too. One likely candidate for such a reserve of water is the jovian icy moon Europa. Imaged by the Voyager and Galileo probes, this icy body appears to have a geologically young outer surface. Spectroscopic studies from Earth have confirmed that the European crust is composed of water ice. Long cracks across its surface may be suggestive of huge ice blocks rafting upon an underlying liquid layer. Darker non ice material also covers much of the surface and is spatially associated with the cracks. Recent modeling suggests that tidal forces imparted upon the moon by Jupiter may cause heating in the depth – raising the possibility of a liquid water ocean beneath Europa’s icy crust. Further on it is supposed that a weak induced magnetic field is present on the moon. This classifies Europa as an object of great scientific interest, warranting investigation for habitability and even the presence of life within the supposed ocean of the moon. The Europa Explorer (EUROX) mission complements other proposed missions to study Europa. EUROX will characterize the habitability potential of Europa, with the aim of understanding whether life could exist there or not. The mission will address the following key questions: (i) existence or non- existence of a liquid ocean beneath the surface, (ii) the nature of the non icy material visible upon the surface cracks, (iii) the physical characteristics of the ice crust, (iv) effects by local radiation on the surface chemistry, (v) the depth of radiation penetration in the ice and probably shielding effects by a magnetic field and (vi) the presence of organic compounds on or in the Europan ice crust. Our proposed mission will operate as a fully European and further on international mission, with the aim of providing the initial information required for later, larger missions to visit Europa. EUROX will involve both remote-sensing and in-situ research. Its mission architecture sees a single space craft deployed to Europa, launched by an Ariane 5. This vehicle will use conventional propulsion and a Venus-Earth-Earth flight path to travel to the jovian system in six years. Upon arrival at Europa, the space craft will commence remote observations of the icy moon, to determine the physical nature of the ice crust, and to investigate the presence of a subsurface liquid ocean. The orbiter will carry two independent vehicles (two penetrators) that will then separate, de-orbit, and penetrate the crust nearby or in the cracks to a depth of several meters. A suite of compact instruments will address the physical and chemical properties of the crust, as well as seeking organic compounds and pre-biotic material in the ice. The use of a laser communication system removes the need for a relay spacecraft in orbit around Jupiter, decreasing overall mission cost. Expected orbiter mission duration is on the order of two months, with each penetrator functioning for approximately 24 hours.
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| 7. |
- Deyou, Tsegaye, et al.
(author)
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Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp teitensis
- 2017
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In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:7, s. 2060-2066
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Journal article (peer-reviewed)abstract
- A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A-D (2-5), along with nine known compounds (6-14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 mu M, respectively.
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| 8. |
- Deyou, Tsegaye, et al.
(author)
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Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis
- 2015
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In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025 .- 0974-5211. ; 78:12, s. 2932-2939
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Journal article (peer-reviewed)abstract
- Five new compounds, 4-O-geranylisoliquiritigenin (1), 12-dihydrousararotenoid B (2), 12-dihydrousararotenoid C (3), 4'-O-geranyl-7-hydroxyflavanone (4), and 4'O-geranyl-7-hydroxydihydroflavanol (5), along with 12 known natural products (6-17) were isolated from the CH2Cl2/MeOH (1:1) extract of the root bark of Millettia usaramensis ssp. usaramensis by chromatographic separation. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas their absolute configurations were established on the basis of chiroptical data and in some cases also by X-ray crystallography. The crude extract was moderately active (IC50 = 11.63 mu g/mL) against the ER-negative MDB-MB-231 human breast cancer cell line, and accordingly compounds 6, 8, 9, 10, 12, and 16 also showed moderate to low cytotoxic activities (IC50 25.7-207.2 mu M). The new natural product 1 exhibited antiplasmodial activity with IC50 values of 3.7 and 5.3 mu M against the chloroquine-sensitive 3D7 and the chloroquine-resistant Dd2 Plasmodium falciparum strains, respectively, and was also cytotoxic to the HEK293 cell line.
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| 9. |
- Chepkirui, Carolyne, et al.
(author)
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Antiplasmodial and antileishmanial flavonoids from Mundulea sericea
- 2021
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In: Fitoterapia (Milano). - : Elsevier BV. - 0367-326X .- 1873-6971. ; 149
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Journal article (peer-reviewed)abstract
- Five known compounds (1–5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6–8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC50 of 2.0 μM against chloroquine-resistant W2, and 6.6 μM against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC50 values of 9.0 and 5.0 μM, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 μM) and HePG2 (IC50 10.8 μM) human cell lines. All the other compounds showed low cytotoxicity (IC50 > 30 μM) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2)
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| 10. |
- Irungu, Beatrice N., et al.
(author)
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Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica
- 2015
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In: Journal of Ethnopharmacology. - : Elsevier Ireland Ltd. - 0378-8741 .- 1872-7573. ; 174, s. 419-425
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Journal article (peer-reviewed)abstract
- Ethnopharmacological relevance: Turraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities. Materials and methods: From the stem bark of T. robusta six compounds, and from various parts of T. nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-3H, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2). Results: The extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50<10 μg/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4±0.03 μM and 1.1±0.01 μM against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4-40.5 μM. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0±0.03 and 8.4 ±0.01 μM against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity. Conclusion: From the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices. © 2015 The Authors. Published by Elsevier Ireland Ltd.
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