Estramustine and its Derivatives in Potentiating Radiotherapy of Prostate Cancer

The purpose of this study was to deepen our knowledge of the combined use of estramustine and radiotherapy in the treatment of prostate cancer. Prostate cancer is a common disease, with a high variability between subjects in its malignant potential. In many cases, the disease is an incidental finding with little or no clinical significance. In other cases, however, prostate cancer may be an aggressive malignant disease, which, if the initial treatment fails, lacks an effective cure and may lead to severe symptoms, metastasis, and death despite all treatment. In many cases, the methods of treatment available at the moment provide cure or significant regression of symptoms, but often at the cost of considerable side effects. Estramustine, a cytostatic drug used for treating advanced cancer of the prostate, has been shown to inhibit prostate cancer progression and also to increase the sensitivity of cancer cells to radiotherapy. The goals of this study were, first, to find out whether it is possible to use either estramustine or an antibody against estramustine binding protein as carrier molecules for bringing therapeutic radioisotopes into prostate cancer cells, and, secondly, to gain more understanding of the mechanisms behind the known radiosensitising effect of estramustine. Estramustine and estramustine binding protein antibody were labelled with iodine-125 to study the biodistribution of these substances in mice. In the first experiment, both of the substances accumulated in the prostate, but radioiodinated estramustine also showed affinity to the liver and the lungs. Since the radiolabelled antibody was found out to accumulate more selectively to the prostate, we studied its biodistribution in nude mice with DU-145 human prostate cancer implants. In this experiment, the prostate and the tumour accumulated more radioactivity than other organs, but we concluded that the difference in the dose of radiation compared to other organs was not sufficient for the radioiodinated antibody to be advocated as a carrier molecule for treating prostate cancer. Mice with similar DU-145 prostate cancer implants were then treated with estramustine and external beam irradiation, with and without neoadjuvant estramustine treatment. The tumours responded to the treatment as expected, showing the radiation potentiating effect of estramustine. In the third experiment, this effect was found without an increase in the amount of apoptosis in the tumour cells, despite previous suggestions to the contrary. In the fourth experiment, we gave a similar treatment to the mice with DU-145 tumours. A reduction in proliferation was found in the groups treated with radiotherapy, and an increased amount of tumour hypoxia and tumour necrosis in the group treated with both neoadjuvant estramustine and radiation. This finding is contradictory to the suggestion that the radiation sensitising effect of estramustine could be attributed to its angiogenic activity.

Effect of phenoxy acids and their derivatives on lipid metabolism in groundnut (Arachis hypogaea) leaves

The effect of four phenoxy compounds [2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid, 4-chlorophenoxyacetic acid 2-(dimethylamino)ethyl ester (centrophenoxine), and 4-chlorophenoxy ethyl 2-(dimethylamino) ethyl ether (neophenoxine)] on lipid metabolism in groundnut (Arachis hypogaea) leaves was investigated under nonphotosynthetic conditions. In experiments with leaf disks, the uptake of [1-14C]acetate, [32P]orthophosphate, [35S]sulfate and [methyl-14C]choline was substantially inhibited by all the phenoxy compounds except neophenoxine. When the incorporation of these precursors into lipids was measured and expressed as percentage of total uptake, there was significant inhibition of incorporation of [1-14C]acetate and [32P]orthophosphate into lipids by all the compounds except neophenoxine. The incorporation of [methyl-14C]choline was unaffected by all except centrophenoxine which showed stastically significant stimulation. [35S]Sulfate incorporation into lipids was markedly inhibited only by centrophenoxine. The fatty acid synthetase of isolated chloroplasts assayed in the absence of light was inhibited 20–50% by the phenoxy compounds at 0.5 mM concentration. This inhibition showed a dependence on time of preincubation with the herbicide suggesting an interaction with the enzyme. It was, however, reversible and excess substrate did not prevent the inhibition, suggesting that the herbicide interaction may not be at the active site. sn-Glycerol-3-phosphate acyltransferase in the chloroplast and microsomal fractions was inhibited by 2,4-D while the phosphatidic acid phosphatase was insensitive to all the phenoxy compounds. It is concluded that phenoxy compounds affect precursor uptake, their incorporation into lipids, and the chloroplast fatty acid synthetase. The free acids were the most potent compounds while the ester (centrophenoxine) was less effective and the ether (neophenoxine) was completely ineffective in their influence on lipid metabolism.

The link between foreign aid, public investment and economic growth

Länsimaat ovat rahoittaneet kehitysyhteistyöhankkeita jo lähes kuuden vuosikymmenen ajan, mutta kehitysavun tehokkuudesta ei olla edelleenkään päästy yksimielisyyteen. Yksi avunantajamaiden tapa vaikuttaa kehitysavun tehokkuuteen, eli avun vaikutukseen vastaanottajamaan taloudellisen kasvun kiihdyttäjänä, on sitoa ne julkisen sektorin infrastruktuurihankkeisiin. Joissain tapauksissa tämä vaikuttaa avun vastaanottajan käytökseen ja asenteisiin kehitysapua kohtaan. Tutkielmassa käsitellään kehitysavun tehokkuutta tilanteessa, jossa se on sidottu julkisen sektorin investointeihin kehitysmaassa. Tutkimus pohjaa Kalaitzidakisin ja Kalyvitisin (2008) malliin, jossa osa kehitysmaan julkisen talouden investoinneista rahoitetaan kehitysavulla. Seuraavaksi tarkastellaan ylijäämää tavoittelevan käyttäytymisen (rent- seeking) vaikutusta kehitysavun tehokkuuteen pohjaten Economidesin, Kalyvitisin ja Philippopoulosin (2008) malliin. Tutkielmassa referoidaan lisäksi tutkimuskysymystä sivuavia empiirisiä tutkimuksia, esitellään aluksi tavallisimmat kehitysyhteistyön muodot, sekä esitellään talousteoreettisia näkökulmia kehitysyhteistyön tehokkuuden määrittelylle. Tutkielma perustuu puhtaasti teoreettisiin malleihin ja niissä sovelletut menetelmät ovat matemaattisia. Tutkielmassa käsitellään ensin tapaus, jossa kehitysyhteistyöllä rahoitetaan julkisen sektorin investointihankkeita. Jossain tapauksissa kehitysavun kasvu lasku siirtää vastaanottajamaan kulutusta julkisista investoinneista kulutukseen, jolloin kehitysyhteistyövaroin osittain rahoitettujen hankkeiden koko pienenee, ja suhteellinen tehokkuus laskee. Seuraavaksi tarkastellaan tilannetta, jossa kehitysyhteistyövaroista vain osa päätyy hankkeen rahoittamiseen, ja todetaan, että kehitysavun tehokkuus ja vaikutus maan kansantulon kasvuun vähenee talouden toimijoiden ylijäämää tavoittelevan käyttäytymisen (mukaan lukien korruptio) myötä entisestään. Tämän tutkimuksen perusteella voidaan todeta, että kehitysapu vaikuttaa kehittyvän maan talouden kasvuun tapauksessa, jossa julkisia infrastruktuurihankkeita rahoitetaan osittain maan omin verovaroin ja osittain kehitysyhteistyövaroin. Ylijäämää tavoitteleva käyttäytyminen vaikuttaa kehitysavun tehokkuuteen negatiivistesti vähentäen kehitysavun positiivisia kasvuvaikutuksia.

Synthesis of both enantiomers of 1-phenylethane-1,2-diol via chirality transfer from bile acid derivatives

Both enantiomers of 1-phenylethane-1,2-diol were synthesized with good to excellent enantioselectivities via selective reduction of the phenylglyoxalates derived from bile acids, followed by reductive cleavage. (C) 2000 Elsevier Science Ltd. All rights reserved.

Preparation and characterization of hydrazinium derivatives

A number of simple and complex hydrazinium derivatives have been prepared by the reaction of hydrazine hydrate with ammonium salts. The products were characterized by chemical analysis and infrared spectra.

Rearrangement of homobrendane derivatives. Total syntheses of racemic copacamphor, ylangocamphor, and their homologs

Rearrangement of a homobrendane derivative 8a to perhydro-1,4-methanoindenesy stem 9a could be brought about either by p-toluenesulfonic acid or boron trifluoride etherate. Similarly, rearrangement of 8b-d led to the formation of perhydro-1,4-methanoindened erivatives 9b-d. On the basis of the location of substituents in the starting material and the product, a probable mechanistic pathway has been suggested. The appropriate modification of the peripheral functionalities in 9 led to efficient total syntheses of (f)-copacamphor (15a),(f)-ylangocamphor (16a), and their homologues 15b and 16b.

cis-trans Enantiomerism in the Diels-Alder cycloadducts of 6-arylfulvenes with maleic anhydride: resolution of the exo adducts via the N-((1S)-1-(naphth-1-yl)ethyl)imide derivatives: assignment of the absolute configurations based on the crystal structure of an imide diastereomer

A new case of the uncommon cis-trans enantiomerism is presented. The titled anhydride adducts were prepared in good yields by the known reaction of three 6-arylfulvenes with maleic anhydride (aryl = phenyl, p-tolyl and p-anisyl). The exo adducts were converted to the corresponding imides by reaction with (1S)-1-(naphth-1-yl)ethylamine in similar to 80% yields, and the resulting diastereomeric imides separated by silica gel column chromatography. They were hydrolysed and recyclised to the chiral anhydrides, in `one-pot' with 10% NaOH-EtOH, followed by treatment with 2 M HCl, in similar to 40% yields. The titled anhydrides were thus obtained in homochiral form, in enantiomeric purities (generally) of similar to 90% as indicated by chiral HPLC. The chiral anhydrides were also converted to the corresponding imides (presumably stereospecifically), by treatment with ammonia solution in excellent yields. The crystal structure of one of the above diastereomeric imides (derived from 6-phenylfulvene) was determined, and based on the known (S)-configuration of the naphthylethylamine moiety, the `configurations' of the original anhydride adducts were assigned. (c) 2005 Elsevier Ltd. All rights reserved.

Why Don't Students Talk? Causes of Foreign Language Communication Apprehension in English Classes: A Comparison of High Apprehensive and Low Apprehensive Upper Secondary Students.

OBJECTIVES. Oral foreign language skills are an integral part of one's social, academic and professional competence. This can be problematic for those suffering from foreign language communication apprehension (CA), or a fear of speaking a foreign language. CA manifests itself, for example, through feelings of anxiety and tension, physical arousal and avoidance of foreign language communication situations. According to scholars, foreign language CA may impede the language learning process significantly and have detrimental effects on one's language learning, academic achievement and career prospects. Drawing on upper secondary students' subjective experiences of communication situations in English as a foreign language, this study seeks, first, to describe, analyze and interpret why upper secondary students experience English language communication apprehension in English as a foreign language (EFL) classes. Second, this study seeks to analyse what the most anxiety-arousing oral production tasks in EFL classes are, and which features of different oral production tasks arouse English language communication apprehension and why. The ultimate objectives of the present study are to raise teachers' awareness of foreign language CA and its features, manifestations and impacts in foreign language classes as well as to suggest possible ways to minimize the anxiety-arousing features in foreign language classes. METHODS. The data was collected in two phases by means of six-part Likert-type questionnaires and theme interviews, and analysed using both quantitative and qualitative methods. The questionnaire data was collected in spring 2008. The respondents were 122 first-year upper secondary students, 68 % of whom were girls and 31 % of whom were boys. The data was analysed by statistical methods using SPSS software. The theme interviews were conducted in spring 2009. The interviewees were 11 second-year upper secondary students aged 17 to 19, who were chosen by purposeful selection on the basis of their English language CA level measured in the questionnaires. Six interviewees were classified as high apprehensives and five as low apprehensives according to their score in the foreign language CA scale in the questionnaires. The interview data was coded and thematized using the technique of content analysis. The analysis and interpretation of the data drew on a comparison of the self-reports of the highly apprehensive and low apprehensive upper secondary students. RESULTS. The causes of English language CA in EFL classes as reported by the students were both internal and external in nature. The most notable causes were a low self-assessed English proficiency, a concern over errors, a concern over evaluation, and a concern over the impression made on others. Other causes related to a high English language CA were a lack of authentic oral practise in EFL classes, discouraging teachers and negative experiences of learning English, unrealistic internal demands for oral English performance, high external demands and expectations for oral English performance, the conversation partner's higher English proficiency, and the audience's large size and unfamiliarity. The most anxiety-arousing oral production tasks in EFL classes were presentations or speeches with or without notes in front of the class, acting in front of the class, pair debates with the class as audience, expressing thoughts and ideas to the class, presentations or speeches without notes while seated, group debates with the class as audience, and answering to the teacher's questions involuntarily. The main features affecting the anxiety-arousing potential of an oral production task were a high degree of attention, a large audience, a high degree of evaluation, little time for preparation, little linguistic support, and a long duration.

Development of foreign direct investment in Finland

During 1990 to 2009, Foreign Direct Investment (FDI henceforth) in Finland has fluctuated greatly. This paper focused on analyzing the overall development and basic characteristics of Foreign Direct Investment in Finland, covering the period from 1990 to present. By comparing FDI in Finland with FDI in other countries, the picture of Finland’s FDI position in the world market is clearer. A lot of statistical data, tables and figures are used to describe the trend of Foreign Direct Investment in Finland. All the data used in this study were obtained from Statistics Finland, UNCTAD, OECD, World Bank and International Labor Office, Investment map website and etc. It is also found that there is a big, long-lasting and increasing imbalance of the inward FDI and outward FDI in Finland, the performance of outward FDI is stronger than the inward FDI in Finland. Finland’s position of FDI in the world is rather modest. And based on existing theories, I tried to analyze the factors that might determine the size of the inflows of FDI in Finland. The econometric model of my thesis is based on time series data ranging from 1990 to 2007. A Log linear regression model is adopted to analyze the impact of each variable. The regression results showed that Labor Cost and Investment in Education have a negative influence on the FDI inflows into Finland. Too high labor cost is the main impediment of FDI in Finland, explaining the relative small size of FDI inflows into Finland. GDP and Economy openness have a significant positive impact on the inflows of FDI into Finland; other variables do not emerge as significant factor in affecting the size of FDI inflows in Finland as expected. Meanwhile, the impacts of the most recent financial and economic crisis on FDI in the world and in Finland are discussed as well. FDI inflows worldwide and in Finland have suffered from a big setback from the 2008 global crisis. The economic crisis has undoubtedly significant negative influence on the FDI flows in the world and in Finland. Nevertheless, apart from the negative impact, the crisis itself also brings in chances for policymakers to implement more efficient policies in order to create a pro-business and pro-investment climate for the recovery of FDI inflows. . The correspondent policies and measures aiming to accelerate the recovery of the falling FDI were discussed correspondently.

Directing role of functional groups in selective generation of C-H center dot center dot center dot pi interactions: In situ cryo-crystallographic studies on benzyl derivatives

The in situ cryo-crystallization study of benzyl derivatives reveals that the molecular packing in these compounds is either through methylene (sp(3)) C-H center dot center dot center dot pi or aromatic (sp(2)) C-H center dot center dot center dot pi interactions depending on the level of acidity of the benzyl proton. These studies of low melting compounds bring out the subtle features of such weak interactions and point to the directional preferences depending on the nature (electron withdrawing, polarizability) of the neighbouring functional group.

Novel rhodanine derivatives induce growth inhibition followed by apoptosis

We have designed and synthesized three novel compounds, 5-isopropylidiene derivatives of 3-dimethyl-2-thio-hydantoin (ITH-1), 3-ethyl-2-thio-2,4-oxazolidinedione (ITO-1), and 5-benzilidene-3-ethyl rhodanine (BTR-1), and have tested their chemotherapeutic properties. Our results showed that all three compounds induced cytotoxicity in a time-and concentration-dependent manner on leukemic cell line, CEM. Among the compounds tested, BTR-1 was 5- to 7-fold more potent than ITH-1 and ITO-1 when compared by trypan blue and MTT assays. IC50 value of BTR-1 was estimated to be <10 mu M. Both cell cycle analysis and tritiated thymidine assays revealed that BTR-1 affects DNA replication by inducing a block at S phase. BTR-1 treatment led to increased level of ROS production and DNA strand breaks suggesting activation of apoptosis for induction of cell death. (C) 2010 Elsevier Ltd. All rights reserved.

Crystallographic characterization of the conformation of the 1-aminocyclohexane-1-carboxylic acid residue in simple derivatives and peptides

The crystal structures of 1-aminocyclohexane-1-carboxylic acid (H-Acc6-OH) and six derivatives (including dipeptides) have been determined. The derivatives are Boc-Acc6-OH, Boc-(Acc6)2-OH, Boc-L-Met-Acc6-OMe, ClCH2CO-Acc6-OH, p-BrC6H4CO-Acc6-OH oxazolone, and the symmetrical anhydride from Z-Acc6-OH, [(Z-Acc6)2O]. The cyclohexane rings in all the structures adopt an almost perfect chair conformation. The amino group occupies the axial position in six structures; the free amino acid is the only example where the carbonyl group occupies an axial position. The values determined for the torsion angles about the N–Cα(φ) and Cα–CO (ψ) bonds correspond to folded, potentially helical conformations for the Acc6 residue.

Analysis of Cl center dot center dot center dot Cl and C-H center dot center dot center dot Cl intermolecular interactions involving chlorine in substituted 2-chloroquinoline derivatives

Six crystal structures of substituted 2-chloroquinoline derivatives have been analysed to evaluate the role of Cl atom as a self recognizing unit resulting in the formation of Cl center dot center dot center dot Cl and C-H center dot center dot center dot Cl interactions to generate supramolecular assembly in the solid state. The features of Type I and Type II geometries associated with Cl center dot center dot center dot Cl interactions have been analysed to show directional preferences leading to differences in the packing motifs in these crystal structures. C-H center dot center dot center dot Cl interactions are generated exclusively in structures depicting Type II Cl center dot center dot center dot Cl interaction have been observed in these structures.