This work is concerned with the design and synthesis of the cheap, late first row transition metal complexes of Schiff base ligand systems. The prepared complexes readily afford systematic variation in order to probe potency and understand the role of metal, chelating ligands and anionic ligands when carrying out their cytotoxic effect. This study has lead to a better understanding of the action of these classes of complex and will be used to direct the design of new anti-cancer metallopharmaceuticals going forward. This thesis details the synthesis of a library of Schiff base macroacyclic ligands and their novel late first row transition metal complexes with varying anionic counterparts. The creation of a library with several degrees of variability provides a wide array of parameters to afford subtle variation in structure and chemistry e.g. denticity, co-ordination mode, chelate hole size, metal centred redox potentials, hydrolysis rates, co-ordinative saturation, lipophilicity, solubility and more. Complexation of the ligands was carried out by the free ligand and a novel macroacyclic metal template approach using the cheap late first row transition metal salts of Cobalt (II), Nickel (II), Copper (II) and Zinc (II) plus one Ru (III) complex. Structural studies of the 80 generated complexes was carried out by vibrational spectroscopy, elemental analysis, mass spectrometry, magnetic susceptibility and NMR. Single crystal X-ray structures have been determined with 20 reported in this thesis. All ligands act as tridentate ligands in all except one case to form monomeric distorted trigonal-bipyramidal, square-pyramidal or octahedral structures. In the case of zinc nitrate, the ligand L2PhMe acts as a tetradentate ligand to give a distorted octahedral structure. Paramagnetic NMR and solution magnetic susceptibility of paramagnetic complexes was achieved by the Evans NMR method and analysis of the solution NMR showed that L2R and L3R ligands display 2-fold symmetry and are likely either tetradentate in solution or a fast exchange between imine N-donar sites is occurring even down to -65°C. The majority of the resulting complexes of L1R were screened against a panel of three cancer cell lines. Several categories of complex were able to afford structure activity relationships. It was discovered that the ligand is indeed essential for activity of the metal salts against the panel of cell lines and it was largely discovered that the variation in ¿tail group¿ and anionic coordinating ligands played little role in providing a dramatic variation in activity of the metal salt. In general all L1R complexes displayed moderate cytotoxicity showing a trend in activity with respect to the metal in the order RuIII¿CoII>CuII¿ZnII>NiII, over a 6 day exposure to the three cell panel RuIII was shown to be the most potent metal of the L1R series providing IC50 values of 4.6 (0.7) and 7.5 (1.2) ¿M against the DLD-1 and H460 cell lines respectively, which is Ca. 4.6 and 15 iii times less potent than cisplatin to the same cell panel respectively. RuIII was also discovered to be the only metal to provide an IC50 value from a 1 hour exposure to the DLD-1 cell panel. The value of 20.4 (3.5) ¿M is a moderate figure but again Ca. 10 fold less potent than cisplatin for the same test. The L2R and L3R complexes could not be screened by the same comprehension due to their low solubilities. However the lone screen that was possible from the very sparingly soluble complex [CuCl2(L3Bui)] gave the most exciting result and most potent complex of this thesis. After a 6 day exposure, [CuCl2(L3Bui)] gave IC50 values of 4.3 (0.1) and 2.9 (0.1) ¿M against the DLD-1 and H460 cell lines respectively. These values are merely 4 and 6 fold more than Cisplatin to the same cell lines respectively and demonstrates the potential of this class of complex as cytostatic agents. Further studies utilising a semi-quantitative DNA damaging assay, demonstrated that all first row complexes can damage DNA when in the presence of hydrogen peroxide, with the exception of ZnII complexes. CoII appeared to afford the greatest DNA damage with the most intsense bands for double strand breaks and the CuII complex of the ligand L3Bui also demonstrated a greater DNA damage as opposed to its L1Bui analogue.

Minimizing anti-cancer drug toxicity is a major challenge for the pharmaceutical industry. Toxicity is most frequently due to either the direct interaction of the drug on previously unidentified targets or its conversion to metabolites by drug metabolizing enzymes (e.g. CYP450 enzymes) that cause cellular, tissue or organ damage. Pharmacoproteomics is beginning to take a central role in studying changes in protein expression corresponding to drug administration, the results of which, inform about the mode of action, toxicity, and resistance in pre-clinical and clinical stages of drug development. The main aim of this research is to apply comparative proteomics studies on livers from male and female mice xenograft models treated with major anti-cancer drugs (5-flourouracil, paclitaxel, cisplatin, and doxorubicin) and CYP inducer, TCPOBOP, to investigate their effect on protein expression profiles (proteome). Within this thesis, an attention is paid to optimise a highly validated proteomics workflow for biomarker identification. Proteins were extracted from liver microsomes of mice treated in two separate sets; Set A – male (5-fluoruracil, doxorubicin, cisplatin and untreated) or Set B – female (5-fluoruracil, paclitaxel, TCPOBOP and untreated) using cryo-pulverization and sonication method. The extracts were digested with trypsin ii and the resulting peptides labelled with 4-plex iTRAQ reagents. The labelled peptides were subjected for separation in two-dimensions by iso-electric focusing (IEF) and RP-HPLC techniques before analysis by mass spectrometry and database searching for protein identification. Set A and Set B resulted in identification and quantification of 1146 and 1743 proteins, respectively. Moreover, Set A and Set B recovered 26 and 34 cytochrome P450 isoforms, respectively. The microsomal changes after drug treatments were quite similar. However, more changes were observed in the male set. Up-regulation of MUPs showed the greatest distinction in the protein expression patterns in the treated samples comparing to the untreated controls. In Set A, 5-fluoruracil and cisplatin increased the expression of three isoforms (MUP1, 2, and 6), whereas doxorubicin has increased the expression of four isoforms (MUP1, 2, 3, and 6). On the other side, only TCPOBOP in Set B has increased the expression of two isoforms (MUP1 and 6). Our findings showed that the expression of MUP, normally involved in binding and excretion of pheromones, have drug- and sex-specific differences. The mechanism and significance of MUP up-regulation are ambiguous. Therefore, the impact of each therapeutic agent on MUP and xenobiotic enzymes will be discussed.

No description available.

No description available.

The statin family of hydroxymethylglutaryl coenzyme A reductase (HMGCR) inhibitors, used to control hypercholesterolemia, triggers apoptosis of various human tumour cells. HMGCR is the rate-limiting enzyme of the mevalonate (MVA) pathway, a fundamental metabolic pathway required for the generation of a number of biochemical end-products including cholesterol and isoprenoids, but the contribution of the MVA pathway to human cancer remains largely unexplored. Furthermore, as only a subset of tumour cells has been shown to be highly responsive to statins, the identification of appropriate subsets of patients will be required to successfully advance these agents as anticancer therapeutics. To this end, there were two major aims to this work: 1) Elucidate a molecular rationale for the observed therapeutic index of statin-induced apoptosis in normal and tumour cells; 2) Identify molecular determinants of sensitivity for statin-induced apoptosis in human tumour cells. To address the first aim we demonstrated that dysregulation of the MVA pathway, achieved by ectopic expression of either full length HMGCR (HMGCR-FL) or its novel splice variant lacking exon 13 (HMGCR-D13), increases transformation. Ectopic HMGCR promotes growth of transformed and non-transformed cells under anchorage-independent conditions or as xenografts in immunocompromised mice. We also show that high mRNA levels of HMGCR and four out of five other MVA pathway genes correlate with poor prognosis in primary breast cancer, suggesting the MVA pathway may play a role in the etiology of human cancers. To address the second aim, we show that dysregulation of the MVA pathway is a key determinant of sensitivity to statin-induced apoptosis in multiple myeloma. In a panel of 17 distinct myeloma cell lines, half were sensitive to statin-induced apoptosis and the remainder were insensitive. Interestingly, in sensitive cells, the classic feedback response to statin exposure is lost, a feature we demonstrated could distinguish a subset of statin-sensitive primary myeloma cells. We further illustrated that statins are highly effective and well tolerated in an orthotopic model of myeloma using cells harboring a dysregulated MVA pathway. Taken together, this work provides a molecular rationale and determinants of sensitivity for statin-induced apoptosis of human tumour cells.

This diploma thesis brings new data about design, synthesis, physico-chemical characterisation and biological efficacy of the novel star-like HPMA-based conjugates intended for treatment of solid tumors. Recently, many different water-soluble drug delivery systems based on N-(2- hydroxypropyl)methacrylamide (HPMA) copolymers have been described. Here, we report synthesis and physico-chemical characterisation of high molecular weight star-like HPMA- based polymer carriers with low polydispersity prepared by controlled grafting of HPMA copolymers onto PAMAM dendrimer core. With the aim to keep the polydispersity of drug delivery system as low as possible, reversible Addition-Fragmentation Chain Transfer (RAFT) polymerisation was used for HPMA-based polymer precursor preparation. The end groups of the polymer presursors was afterwards used for grafting using carbodidimide condensation reaction or copper free click chemistry on polyamidoamine (PAMAM) dendrimers resulting in a formation of star-like high-molecular-weight (HMW) drug carriers. Described synthetic procedure provided preparation of star-like HMW drug carriers with Mw between 1.105 - 3.105 g/mol and narrow distribution of Mw. The model drug, doxorubicin (Dox), was attached to the hydrazide group containing polymer cariers by pH- sensitive...

Doctor of Philosophy / Department of Chemistry / Duy H. Hua / Our research work is divided into three chapters. In the first chapter, synthesis of substituted phenolic compounds including halogenated di- and trihydroxybenzenes, aminophenols, and substituted di-tert-butylphenols, their redox potential, laccase oxidation, and mosquito anti-larval activities are discussed. The synthesized substituted phenols were found to be the substrates but not the inhibitors of laccase. An inverse correlation between the oxidation potential and the laccase oxidation efficiency of halogenated hydroxybenzenes and aminophenols was established. However, substituted di-tert-butylphenols were found to have anti-larval activities in mosquitoes resulting in the death of the larvae just before reaching pupation. Among the di-tert-butyl phenols studied, water insoluble, 2,4-di-tert-butyl-6-(3-methyl-2-butenyl)phenol (16), 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-methylpropanal oxime (14), and 6,8-di-tert-butyl-2,2-dimethyl-3,4-dihydro-2H-chromene (17) caused the mortility of 98%, 93%, and 92% of Anopheles gambiae larvae in the concentration of 182 nM, 3.4 µM, and 3.7 µM, respectively. In particular, compound 16 had similar anti-larval activities as compared to MON-0585, an anti-larval agent reported by Monsanto in the 70’s. In the second chapter, inhibition of protein kinase C (PKC) phosphorylation by substituted quinolines (PQs) is inverstigated. PQ compounds such as N-(3-aminopropyl)-6-methoxy-4-methyl-5-(3-(trifluormethyl)phenoxy)quinolin-8-amine (PQ1), N-(furan-2-ylmethyl)-6-methoxy-4-methyl)-5-(3-(trifluoromethyl)phenoxy)quinolin-8-amine (PQ11), and 6-methoxy-4-methyl-N-(quinolin-4-ylmethyl)-5-(3-(trifluoromethyl)phenoxy)quinolin-8-amine (PQ15) were found to inhibit PKC phosphorylation with IC50 values of 35 nM, 42.3 nM, and 216.3 nM respectively, among which PQ1 and PQ11 were found to be potent PKC inhibitors as comparable to that of staurosporine (IC50 = 33 nM). In chapter three, the tissue distribution of PQ1 and PQ11 in normal C57BL/6J mice and the effect of PQ1 on the normal tissues of mice were investigated. Substituted quinolines, PQ1 and PQ11 were distributed in the tissues in concentrations that were more than 40 folds of their effective dose. PQ1 and PQ11 were also found to penetrate the blood brain barrier and collect in the tissue in significant amounts. The administration of PQ1 and PQ11 had no effect in the normal behavior of the animals indicating no short term adverse effects. PQ1 was found to increase the expression of survivin, an anti-apoptotic factor and decrease the expression of cleaved caspase-3 and caspase-8, pro-apoptotic proteins. These studies suggests that PQ1 might have anti-apoptotic activities in normal cells, in contrast to the role of PQ1 in cancer cells where it has demonstrated to induce apoptosis. The study also indicated that PQ11 was better metabolized from the tissues over time as compared to PQ1.

Este trabalho teve como foco a preparação de compostos orgânicos de selênio, fundamentado em plataformas estruturais de moléculas pequenas que pudessem ter suas preparações viabilizadas em reduzido número de etapas, a partir de matérias primas comerciais ou de fácil preparação e economicamente viáveis. O trabalho ficou dividido em 3 partes, sendo que na primeira, optou-se por preparar compostos fundamentados em estruturas derivadas dos ácidos acético, propiônico e butírico. As estratégias de preparação ficaram centradas na geração de HSeNa ou Se2Na2, por reação de selênio e borohidreto de sódio em água ou etanol. As espécies nucleofílicas foram então submetidas a reação com cloro-acetato de sódio ou de etila, levando aos correspondentes diorgano-selenetos ou disselenetos. Também foram preparados derivados de ácido propiônico, α-hidroxilados. Para isso duas abordagens foram empregadas, sendo que em uma mantivemos a estratégia de substituição nucleofílica de um haleto terminal por reação com MeSeLi, levando ao β-metilseleno-α-hidroxipropóide. Na outra, optamos por fazer reacão de abertura de um epóxido glicídico. Neste caso observamos mistura de regioisômeros quando MeSeLi foi empregado. Quando o Grignard correspondente foi usado na reação de abertura do epoxido além de mistura de regioisômeros, também se observou como produto majoritário, o monoseleneto dimérico (provavelmente oriundo de uma de-metilação). Por fim, empregou-se também abertura da γ-butirolactona com disselenolato de sódio, levando ao disselenodi-ácido correspondente. Esses compostos foram submetidos a ensaios preliminares de atividade antioxidante. Destes, o seleno-diacetato de etila apresentou alta seletividade para reação com HOCl, mesmo frente a outras espécies oxidantes e em experimento in vitro com células Hela-60. Além disso foi preparado um seleno-diglicosídeo, também empregando hidrogenoselenolato de sódio, gerado in situ à partir de selênio elementar e borohidreto de sódio. Esse composto foi submetido a ensaios de atividade anticâncer, em associação com β-glucana, levando a ótimos resultados para os experimentos envolvendo câncer de mama e pulmão. Cabe mencionar que nesse caso foram feitos experimentos in vivo com ratos, acrescendo o derivado seleno-açucar e glucana, à dieta dos animais. Por último, foram investigadas estratégias de preparação de sais de Bunte (tiossulfatos orgânicos) de diferentes padrões de substituição. Nessa parte do estudo, tivemos como propósito investigar alguns fatores de reatividade desses compostos frente a espécies nucleofílicas e eletrofílicas de selênio e telúrio, a fim de preparar seleno- e telurosulfetos. Esses por sua vez devem ser submetidos a ensaios biológicos variados. Das estratégias investigadas observamos uma serie de subprodutos das reações envolvendo os sais de Bunte com espécies nucleofílicas de selênio, sendo o que o produto principal foi formado apenas em baixo rendimento e alguns derivados se mostraram bastante instáveis. Em contrapartida, reação bastante seletiva e bons rendimentos foram observados para os casos em que o sal de Bunte agiu como nucleófilo em reações com cátions de selênio e telúrio, gerados por clivagem do dicalcogeneto por persufato de amônio em solvente protônico. Alguns exemplos dos dicalcogenetos puderam ser preparados e caracterizados. / This work was devoted to the preparation of organic selenides, based on structural platforms of small molecules taking in account scalable synthetic procedures in a small steps numbers, from commercial raw materials or from easily prepared and economically viable starting materials. The work was divided into 3 parts, and in the first, it was decided to prepare compounds based on structures derived from acetic, propionic and butyric acids. The preparation strategies were centered on the generation of HSeNa or Na2Se2, by reaction of elemental selenium and sodium borohydride in water or ethanol. The nucleophylic species were then subjected to reaction with sodium chloroacetate, leading to the corresponding diorgano-selenides or disselenides. They were also prepared from α-hydroxylated propionic acid derivatives. For this purpose, two approaches were employed, and in one we maintained the nucleophylic substitution strategy of a terminal halide by reaction with MeSeLi, leading to β-methylseleno-α- hydroxy-propoide. In the other, we chose to perform an epoxi-glycidic opening reaction. In this case, we observed a mixture of regioisomers when MeSeLi was employed. When the corresponding seleno-Grignard was used in the epoxide opening reaction besides a mixture of regioisomers, it was also observed as a major product, the symmetric monoselenide (probably originated from a de-methylation reaction). Finally, it was also used the γ-butyrolactone opening reaction with sodium disselenolate, leading to the corresponding disseleno-diacid. These compounds were submitted to preliminary assays of antioxidant activity. The ethyl Seleno-diacetate showed high selectivity for reaction with HOCl, even in the presence of other oxidant species and in an in vitro experiment with Hela-60 cells. In addition, a Selene-diglycoside was prepared, also employing sodium hydrogen selenide, generated, in situ from elemental selenium and sodium borohydride. It was subjected to anticancer activity assays, in association with β-glucan, leading to great results for experiments involving breast and lung cancer. It is worth mentioning that inthis case experiments were made in vivo with rats, adding our seleno-sugar/glucan system to the diet of the animals. Finally, strategies for the preparation of Bunte salts (organic thiosulphates) of different substitution patterns were investigated. In this part of the study, we intend to investigate some factors of reactivity of these compounds through nucleophilic and electrophilic selenium and tellurium species, in order to prepare seleno- and telluro-sulfides. Opportunely, these compounds should be submitted to biological assays. Under the investigated reaction conditions, we observed a series of by-products of reactions involving the Bunte salts with nucleophilic selenium species, and the main product was formed only in low yield and some derivatives showed to be quite unstable. On the other hand, a fairly selective reaction and good yields were observed for cases in which the Bunte salt was used as the nucleophile in reactions with selenium and tellurium cations, generated by the cleavage of the dichalcogenide by ammonium peroxysulphate in protonic solvent. Some examples of dichalcogenides were prepared and characterized.

<p>Pancreatic ductal adenocarcinoma (PDAC) is an incredibly lethal disease with a 5-year survival rate of less than 8 percent in the United States due to a lack of viable treatment options. The failures of chemo- and radiotherapies have been linked to the heterogeneous nature of the tumor microenvironment which forms a hypovascular, immunosuppressive and high coagulation activity tissue. Indeed, PDAC patients have one of the highest rates of thrombosis complications among all cancer types. The expression of two key coagulation factors, Tissue Factor (TF) and Protease Activated Receptor 1 (PAR-1), have been associated with poor patient prognosis and aggressive cancer progression. However, the molecular roles/mechanisms of TF and PAR-1 in PDAC progression are not known. To establish how clotting factors (PAR-1, TF) influence PDAC tumor progression, I utilized a genetically modified mouse model (KPC) where <i>KRas^G12D</i> and <i>TRP53^R172H</i> mutations were specifically introduced into mouse pancreas acinar cells to initiate PDAC progression. Multiple primary mouse PDAC cell lines were generated and characterized. TF and PAR-1 were highly expressed in primary KPC pancreatic lesions, in PDAC tumors, and in KPC-derived cell lines, an expression profile that is also observed in PDAC patient biopsies. In allograft studies, tumor growth and metastatic potential were significantly diminished by shRNA reduction of TF or PAR-1 in cancer cells or by genetic or pharmacological reduction of the coagulation zymogen prothrombin in mice. Notably, PAR-1 deleted KPC cells (KPC-Par-1^KO) failed to generate sizable tumors; a phenotype completely rescued by restoration of PAR-1 expression. To test the significance of targeting PAR-1 in a clinical setting, PAR-1 expression was withdrawn from established tumors to mimic a potential inhibitory effect of PAR-1 on solid PDAC tumors. Removal of PAR-1 from tumors (11 days post injection) yielded a diverse effect on tumor growth which can be categorized into (i) a decline in tumor growth; (ii) continued tumor growth; and (iii) stagnant tumor growth. Immunohistochemistry analysis of KPC2 shCon vs. shPar-1 subcutaneous allograft tumor samples revealed a massive immune cell infiltration in KPC2 shPAR-1 tumors when compared to KPC2 shCon control tumors. Accordingly, KPC-Par-1^KO cells failed to form tumors in immune-competent mice but displayed robust tumor growth in immune-compromised <i>NSG</i> mice, providing the first evidence of a PAR-1 mediated tumor immune evasion pathway operating in PDAC. </p> <p>Together, these results demonstrate that PDAC disease is driven by activation of the coagulation system through tumor cell-derived TF, circulating prothrombin, and tumor cell-derived PAR-1. These studies also highlight a novel mechanism by which thrombin/PAR-1-mediated tumor growth involves suppression of anti-tumor immunity in the tumor microenvironment. <b></b></p>

The first aim of the research was to determine the applicability of certain variables from the Health Belief Model (HBM), the Theory of Reasoned Action (TRA), the risk dimensions from the Psychometric Paradigm, the Common-Sense Model of Illness Representations and the Locus of Control to Italian women’s beliefs and behaviours in relation to screening mammography. These models have predominantly been derived and evaluated with English-speaking persons. The study used quantitative and qualitative methods to enable explanation of research-driven and participant-driven issues. The second aim was to include Italian women in health behaviour research and to contrast the Italian sample with the Anglo-Australian sample to determine if differences exist in relation to their beliefs. In Australia many studies in health behaviour research do not include women whose first language is not English. The third aim was to evaluate the Anti-Cancer Council of Victoria’s (ACCV) Community Language Program (CLP) by: (a) identifying the strengths and weaknesses of the program as seen by the participants; and (b) assessing the impact of the program on women’s knowledge and beliefs about breast cancer, early detection of breast cancer, self-reported and intended breast screening behaviours. The CLP is an information service that uses women’s first language to convey information to women whose first language is not English. The CLP was designed to increase knowledge about breast and cervical cancer. The research used a pre-test-intervention-post-test design with 174 Italian-born and 138 Anglo-Australian women aged 40 years and over. Interviews for the Italian sample were conducted in Italian. The intervention was an information session that related to breast health and screening mammography. Demographic variables were collected in the Pre-Test only. Qualitative open-ended questions that related specifically to the information session were collected in the Post-Test phase of the study. Direct logistic regression was used with the participants’ beliefs and behaviours to identify the relevant variables for language (Italian speaking and English-speaking), attendance to an information session, mammography screening and breast self-examination (BSE) behaviour. Pre- and Post-Test comparisons were conducted using chi-square tests for the non-parametric data and paired sample t-tests for the parametric data. Differences were found between the Italian and Anglo-Australian women in relation to their beliefs about breast cancer screening. The Italian women were: (1) more likely to state that medical experts understood the causes of breast cancer; (2) more likely to feel that they had less control over their personal risk of getting breast cancer; (3) more likely to be upset and frightened by thinking about breast cancer; (4) less likely to perceive breast cancer as serious; (4) more likely to only do what their doctor told them to do; and (5) less likely to agree that there were times when a person has cancer and they don’t know it. A pattern emerged for the Italian and Anglo-Australian women from the logistic regression analyses. The Italian women were much more likely to comply with medical authority and advice. The Anglo-Australian women were more likely to feel that they had some control over their health. Specifically, the risk variable ‘dread’ was more applicable to the Italian women’s behaviour and internal locus of control variable was more relevant to the Anglo-Australian women. The qualitative responses also differed for the two samples. The Italian women’s comments were more general, less specific, and more limited than that of the Anglo-Australian women. The Italian women talked about learning how to do BSE whereas the Anglo-Australian women said that attending the session had reminded them to do BSE more regularly. The key findings and contributions of the present research were numerous. The focus on one cultural group ensured comprehensive analyses, as did the inclusion of an adequate sample size to enable the use of multivariate statistics. Separating the Italian and Anglo-Australian samples in the analyses provided theoretical implications that would have been overlooked if the two groups were combined. The use of both qualitative and quantitative data capitalised on the strengths of both techniques. The inclusion of an Anglo-Australian group highlighted key theoretical findings, differences between the two groups and unique contributions made by both samples during the collection of the qualitative data. The use of a pre-test-intervention-post-test design emphasised the reticence of the Italian sample to participate and talk about breast cancer and confirmed and validated the consistency of the responses across the two interviews for both samples. The inclusion of non-cued responses allowed the researcher to identify the key salient issues relevant to the two groups. The limitations of the present research were the lack of many women who were not screening and reliance on self-report responses, although few differences were observed between the Pre- and Post-Test comparisons. The theoretical contribution of the HBM and the TRA variables was minimal in relation to screening mammography or attendance at the CLP. The applicability of these health behaviour theories may be less relevant for women today as they clearly knew the benefits of and the seriousness of breast cancer screening. The present research identified the applicability of the risk variables to the Italian women and the relevance of the locus of control variables to the Anglo-Australian women. Thus, clear cultural differences occurred between the two groups. The inclusion of the illness representations was advantageous as the responses highlighted ideas and personal theories salient to the women not identified by the HBM. The use of the illness representations and the qualitative responses further confirmed the relevance of the risk variables to the Italian women and the locus of control variables to the Anglo-Australian women. Attendance at the CLP did not influence the women to attend for mammography screening. Behavioural changes did not occur between the Pre- and Post-Test interviews. Small incremental changes as defined by the TTM and the stages of change may have occurred. Key practical implications for the CLP were identified. Improving the recruitment methods to gain a higher proportion of women who do not screen is imperative for the CLP promoters. The majority of the Italian and Anglo-Australian women who attended the information sessions were women who screen. The fact that Italian women do not like talking or thinking about cancer presents a challenge to promoters of the CLP. The key theoretical finding that Italian women dread breast cancer but comply with their doctor provides clear strategies to improve attendance at mammography screening. In addition, the inclusion of lay health advisors may be one way of increasing attendance to the CLP by including Italian women already attending screening and likely to have attended a CLP session. The present research identified the key finding that improving Anglo-Australian attendance at an information session is related to debunking the myth surrounding familial risk of breast cancer and encouraging the Anglo-Australian women to take more control of their health. Improving attendance for Italian women is related to reducing the fear and dread of breast cancer and building on the compliance pattern with medical authority. Therefore, providing an information session in the target language is insufficient to attract non-screeners to the session and then to screen for breast cancer. Suggestions for future research in relation to screening mammography were to include variables from more than one theory or model, namely the risk, locus of control and illness representations. The inclusion of non-cued responses to identify salient beliefs is advantageous. In addition, it is imperative to describe the profile of the cultural sample in detail, include detailed descriptions of the translation process and be aware of the tendency of Italian women to acquiesce with medical authority.