Links between gender norms and the intergenerational transmission of health information in parents carrying BRCA1/2 pathogenic variants.

Understanding how gender norms affect parents' communication of genetic and cancer risk information to their children can enable healthcare professionals to better facilitate cascade genetic testing. We conducted a qualitative study with semi-structured interviews to determine social factors associated with parents carrying the BRCA1/2 pathogenic variants who communicated cancer prevention practices to their children. Thirty adult carriers (23 women, 7 men) participated in the interviews. All had at least one child aged over 8 years old. Interview topics included their discovery of the variants, their relationship to their body and to the risk of cancer, as well as disclosure to and subsequent communication with their children after testing positive for BRCA1/2. The interviews were analyzed qualitatively, and the major themes identified were identified and compared. We described the roles played by the BRCA1/2 carriers and their partners in communicating cancer prevention practices to their children, from how they managed their own risk of cancer after testing positive, to how they disclosed the risks linked to these pathogenic variants to their children. We also described their involvement in the process of their children going for professional genetic consultation. Gender norms lead women to be more attentive than men to their own health and that of their loved ones. In the context of the transmission of genetic information to children, gender differences in behavior are reinforced by perceptions of the risks of BRCA1/2 variants and women's related health management practices. Cancer prevention is shaped by complex links between gender norms and health management practices.

In vitro biocompatibility assessment of Ti40Cu38Zr10Pd12 bulk metallic glass.

The use of biocompatible materials has attained an increasing importance for tissue regeneration and transplantation. The excellent mechanical and corrosion properties of Ti40Cu38Zr10Pd12 bulk metallic glass (BMG) turn it into a potential candidate for its use in orthopaedic implants. Before being considered as a biomaterial, some biological parameters must be taken into account. In this study,mouse preosteoblasts were cultured in the presence or absence of the alloy at different times (24 h, 7 and 21 days) and no differences in cell viability were detected.Moreover, cells were able to adhere to the alloy surface by establishing focal contacts, and displayed a flattened polygonal morphology. After 14 days in culture, differentiation into osteoblasts was observed. Besides, the amount of Cu ions released and their potential toxic effects were analyzed, showing that the amount of Cu released did not increase cell death. Finally, the low levels of inflammatory cytokines secreted by THP-1 differentiated macrophages exposed to the alloy suggest the absence of an immunogenic response to the alloy. In conclusion, in vitro studies indicate that the Ti40Cu38Zr10Pd12 BMG could be considered as a biomaterial to be used in orthopaedic implants.

Short-term psychological impact of the BRCA1/2 test result in women with breast cancer according to their perceived probability of genetic predisposition to cancer.

BACKGROUND: The effect of BRCA1/2 gene test result on anxiety, depression, cancer-related thought intrusion or avoidance and perceived control over cancer risk was assessed in breast cancer (BC) patients, according to their perceived probability of genetic predisposition to cancer. METHODS: Two hundred and forty-three (89% response rate) women with BC completed questionnaires after an initial genetic counselling visit (T1), of which 180 (66%) completed questionnaires again after receiving the BRCA1/2 results (T2). The discrepancy between women's perceived probability of cancer genetic predisposition at T1 and the geneticist's computed estimates was assessed. RESULTS: In all, 74% of women received a negative uninformative (NU), 11% a positive BRCA1/2 and 15% an unclassified variant (UV) result. On hierarchical regression analysis, in women with a positive BRCA1/2 result (vs NU or UV), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted lower levels of anxiety at T2 (ß=-0.28; P<0.01), whereas in women receiving a UV result (vs NU or positive BRCA1/2), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted higher levels of anxiety (ß=0.20; P<0.01), depression (ß=0.19; P<0.05) and intrusion (ß=0.18; P<0.05) at T2. CONCLUSION: The type of BRCA1/2 test result differently affects distress according to women's perceived probability of genetic predisposition before testing.

Lack of referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes: a nationwide study based on 240,134 consultations and 134,652 genetic tests.

Based on nationwide data from the French national cancer institute (INCa), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR genes mutation. Genetic testing and consultations for familial high-risk individuals are exclusively funded and monitored by the INCa in France. All nationwide cancer genetics centers reported annually standardized parameters of activity from 2003 to 2011. The analysis included a total of 240,134 consultations and 134,652 genetic tests enabling to identify 32,494 mutation carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698) consultations, respectively. From 2003 to 2011, we found a dramatic and steady increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P < 0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall percentage of deleterious mutations identified in the probands tested was 13.8 and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2 and Lynch syndrome tests showed an inverse relationship between the percentage of mutation detected and the absolute number of tests performed over the time (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or MMR identified mutations, there was an average number of 2.94 and 3.28 relatives performing targeted tests, respectively. This nationwide study shows a lack of referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third of relatives of a proband with a predisposing mutation performed a targeted test. Enhanced information about benefit of genetic testing should be given to clinicians and patients for Lynch syndrome and relatives of a proband carrying an identified predisposing mutation.

Rare germline large rearrangements in the BRCA1/2 genes and eight candidate genes in 472 patients with breast cancer predisposition.

Hereditary breast cancers account for up to 5-10 % of breast cancers and a majority are related to the BRCA1 and BRCA2 genes. However, many families with breast cancer predisposition do not carry any known mutations for BRCA1 and BRCA2 genes. We explored the incidence of rare large rearrangements in the coding, noncoding and flanking regions of BRCA1/2 and in eight other candidate genes--CHEK2, BARD1, ATM, RAD50, RAD51, BRIP1, RAP80 and PALB2. A dedicated zoom-in CGH-array was applied to screen for rearrangements in 472 unrelated French individuals from breast-ovarian cancer families that were being followed in eight French oncogenetic laboratories. No new rearrangement was found neither in the genomic regions of BRCA1/2 nor in candidate genes, except for the CHEK2 and BARD1 genes. Three heterozygous deletions were detected in the 5' and 3' flanking regions of BRCA1. One large deletion introducing a frameshift was identified in the CHEK2 gene in two families and one heterozygous deletion was detected within an intron of BARD1. The study demonstrates the usefulness of CGH-array in routine genetic analysis and, aside from the CHEK2 rearrangements, indicates there is a very low incidence of large rearrangements in BRCA1/2 and in the other eight candidate genes in families already explored for BRCA1/2 mutations. Finally, next-generation sequencing should bring new information about point mutations in intronic and flanking regions and also medium size rearrangements.

Chemical functionalization of polysilicon microparticles for single-cell studies.

In this work, two types of polycrystalline silicon (polysilicon) microparticles were modified with specific ligands in order to be selectively attached to chemical residues located at the plasma membrane and thus to be applied to study individual cells in culture. Two different functionalization approaches based on adsorption and covalent attachment were assayed. A comparative study of the efficiency of the ligand immobilization and stability of the modified particle in the culture medium was carried out using the selected ligands labeled with a fluorophore. Cylindrical microparticles (nonencoded microparticles) and shape-encoded microparticles (bar codes) were used with the aim of demonstrating the nondependence of the particle size and shape on the efficiency of the immobilization protocol. Fluorescence imaging and statistical analysis of the recorded fluorescence intensity showed that the covalent attachment of the ligand to the surface of the microparticle, previously modified with an aldehyde-terminated silane, gave the best results. As a proof of concept, Vero cells in culture were labeled with the covalently modified bar codes and successfully tracked for up to 1 week without observing any alteration in the viability of the cells. Bar code numbers could be easily read by eye using a bright-field optical microscope. It is anticipated that such modified microparticles could be feasible platforms for the introduction of other analytical functions of interest in single-cell monitoring and cell sorting in automatic analysis systems.

Focus ion beam micromachined glass pipettes for cell microinjection.

Cell handling is currently hindered by rudimentary-manufactured manipulators. Restrictive designs of glass pipettes and other micromanipulators limit functionality and often damage cells, ultimately resulting in lysis. We present a novel technique to design and mill conventional glass pipettes at specifically chosen angles and geometries. Focus ion beam milling by Ga+ ions yields extremely polished edges. Results from mouse embryo piercing correlate increased penetration rates with decreased pipette angle. Milled pipettes maintain structural integrity after repeated piercing. For the first time, the effects of unintentionally implanted Ga+ on embryo development are addressed. Optimum embryo development up to blastocyst stage after manipulation reveal little impact of residual implanted Ga+, suggesting biocompatibility and paving the way to introducing ion milling techniques in the biomedical device arena. The milling technique can be adequately tailored to specific applications and allows for mass production, presenting a promising avenue for future, increasingly demanding, cell handling.

Allogeneic Mesenchymal Stromal Cells (MSCs) are of Comparable Efficacy to Syngeneic MSCs for Therapeutic Revascularization in C57BKSdb/db Mice Despite the Induction of Alloantibody.

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKSdb/db mice. Phosphate-buffered saline (control group), and MSCs (1 × 106) from B6 (allogeneic group) or C57BKSdb/db (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKSdb/db mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.

The contribution of germline rearrangements to the spectrum of BRCA2 mutations.

BACKGROUND: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. OBJECTIVE: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.

Cell Death Mechanisms in Tumoral and Non-Tumoral Human Cell Lines Triggered by Photodynamic Treatments: Apoptosis, Necrosis and Parthanatos.

Cell death triggered by photodynamic therapy can occur through different mechanisms: apoptosis, necrosis or autophagy. However, recent studies have demonstrated the existence of other mechanisms with characteristics of both necrosis and apoptosis. These new cell death pathways, collectively termed regulated necrosis, include a variety of processes triggered by different stimuli. In this study, we evaluated the cell death mechanism induced by photodynamic treatments with two photosensitizers, meso-tetrakis (4-carboxyphenyl) porphyrin sodium salt (Na-H2TCPP) and its zinc derivative Na-ZnTCPP, in two human breast epithelial cell lines, a non-tumoral (MCF-10A) and a tumoral one (SKBR-3). Viability assays showed that photodynamic treatments with both photosensitizers induced a reduction in cell viability in a concentration-dependent manner and no dark toxicity was observed. The cell death mechanisms triggered were evaluated by several assays and cell line-dependent results were found. Most SKBR-3 cells died by either necrosis or apoptosis. By contrast, in MCF-10A cells, necrotic cells and another cell population with characteristics of both necrosis and apoptosis were predominant. In this latter population, cell death was PARP-dependent and translocation of AIF to the nucleus was observed in some cells. These characteristics are related with parthanatos, being the first evidence of this type of regulated necrosis in the field of photodynamic therapy.

Sequence dependence of charge transport properties of DNA.

The electrical conduction through three short oligomers (26 base pairs, 8 nm long) with differing numbers of GC base pairs was measured. One strand is poly(A)-poly(T), which is entirely devoid of GC base pairs. Of the two additional strands, one contains 8 and the other 14 GC base pairs. The oligomers were adsorbed on a gold substrate on one side and to a gold nanoparticle on the other side. Conducting atomic force microscope was used for obtaining the current versus voltage curves. We found that in all cases the DNA behaves as a wide band-gap semiconductor, with width depending on the number of GC base pairs. As this number increases, the band-gap narrows. For applied voltages exceeding the band-gap, the current density rises dramatically. The rise becomes sharper with increasing number of GC base pairs, reaching more than 1 nA/nm2 for the oligomer containing 14 GC pairs.

Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer.

A family history of breast and/or ovarian cancer is the main criterion used in screening BRCA1 gene carriers. However, ascertaining a patient's family history is a difficult task, which significantly restricts the use of this parameter in clinical practice. Alternative individual criteria that can be used to identity BRCA1 gene carriers would, therefore, be of great value. In this context, it was recently established that BRCA1-associated breast cancers (BRCA1-BCs) show a specific morphoclinical pattern. In multivariate analyses, the two most discriminant morphoclinical parameters available for establishing the BRCA1 status, in addition to an early age at onset, are estrogen receptor negativity (ER-) and poor tumor differentiation (TD3). Here we tested the efficacy of these two morphological parameters as BRCA1 mutation indicators and investigated their economic impact, in a population-based survey on a series of women who developed invasive breast cancer by the age of 35 years, regardless of their family history. A high rate of 28.6% of BRCA1 mutations was found to have occurred in the group of tumors with both ER- and TD3 versus only 3.6% in tumors with other profiles (P = 0.007; odds ratio, 10.8). When the sole criterion used was early onset by the age of 35 years, the mutation rate was found to be 8.6%. The resulting cost of testing only women with ER- and TD3 tumors worked out at 30% that of testing the whole population of women with cancer by the age of 35 years, and the sensitivity was found to be of 66%. Lastly, the family history of ER- and TD3 cases with a BRCA1 mutation was investigated retrospectively, and none of these cases was found to have a particularly extensive family history of breast and/or ovarian cancer. The use of these morphological features of BRCA1-BCs that are currently typed in clinical practice, therefore, provides a helpful and cost-effective tool for those making decisions about genetic screening. This strategy makes it possible to identify gene carriers who would be overlooked using current criteria.

Overexpression of BRCA2 gene in sporadic breast tumours.

The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript that encodes a 3418-amino acid protein involved in the response to DNA damage. To obtain better a molecular characterization of BRCA2 expression in sporadic breast cancer, we quantified BRCA2 mRNA by means of RT - PCR in a large series of human primary breast tumours. BRCA2 expression showed wide variations in tumour tissues, being underexpressed in 14/127 (11%) and overexpressed in 25/127 (20%). BRCA2 overexpression (but not underexpression) correlated significantly with Scarff, Bloom and Richardson (SBR) histopathological grade III (P=0.007) and was mainly attributed to nuclear polymorphism (P=0.005) and mitotic index (P=0.048), suggesting that the BRCA2 gene contributes to the proliferation rate in breast tumours. BRCA2 status (under and/or overexpression versus normal expression) was not associated with subsequent relapse and with significantly shorter disease-free survival. The observed disruption of BRCA2 expression is not due to allelic loss, because the latter did not correlate with altered BRCA2 mRNA expression in our tumour series. Taken together, these data suggest the involvement, especially by overexpression, of the BRCA2 gene in sporadic breast tumours, and the existence of another important tumour-suppressor gene in breast cancer, in the 13q12-q13 region.

The CGA gene as new predictor of the response to endocrine therapy in ER alpha-positive postmenopausal breast cancer patients.

We recently identified CGA (coding for the alpha subunit of glycoprotein hormones) as a new estrogen receptor alpha (ER alpha)-responsive gene in human breast tumors. Here, we assessed the relationship between CGA status (as determined by real-time quantitative RT-PCR) and the response to tamoxifen therapy in a well-defined cohort of 125 ER alpha-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. CGA overexpression, observed in 37.6% of patients, was associated with good relapse-free survival (P=0.037; univariate analysis). CGA status, combined with ERBB2 status (a marker of poor outcome), was an independent predictor of the response to tamoxifen (P=0.020; multivariate analysis). CGA status, especially when combined with ERBB2 status, may thus provide useful predictive information on tamoxifen responsiveness in breast cancer.

Quantitation of hTERT gene expression in sporadic breast tumors with a real-time reverse transcription-polymerase chain reaction assay.

Recent observations support the notion that telomerase expression is essential for the formation of human tumor cells [W-C. Hahn et al., Nature (Lond.), 400: 464-468, 1999]. The expression pattern of hTERT, the human telomerase catalytic subunit gene, is a rate-limiting determinant of the enzymatic activity of human telomerase. We have developed a real-time quantitative RT-PCR assay based on Taq-Man fluorescence methodology to quantify the full range of hTERT mRNA copy numbers. We validated the method on a series of 134 unilateral invasive primary breast cancer patients with known long-term outcome. Three-quarters of the breast tumors (75.4%; 101 of 134) were hTERT positive, i.e., contained detectable and quantifiable hTERT mRNA. hTERT-positive patients had significantly shorter relapse-free survival (P = 0.017) after surgery compared with hTERT-negative patients. The prognostic significance of hTERT status persisted in Cox multivariate regression analysis. When we subdivided hTERT-positive patients (n = 101) into three equal groups (tumors showing small, intermediate, or high increase in hTERT mRNA content), we observed statistical (or a trend toward) links between high hTERT mRNA levels and Scarff-Bloom-Richardson histopathological grade III (P = 0.066), and negative estrogen (P = 0.002) and progesterone (P = 0.048) receptor status, and therefore with higher aggressiveness of breast tumors. High hTERT mRNA levels were also linked to MYC gene overexpression (P = 0.007). These findings show that the quantitative evaluation of hTERT mRNA can have important prognostic significance in human breast cancer. In addition, our simple, rapid, and semiautomated assay method is suitable for routine hTERT mRNA detection and quantification and will be a powerful tool in large, randomized, prospective, cooperative group trials and in the hTERT-based therapy project.

Prognostic value of chorionic gonadotropin beta gene transcripts in human breast carcinoma.

The beta subunit of human chorionic gonadotropin is potentially encoded by six genes, which can be categorized into two types based on a sequence change at codon 117: GCC for the type I and GAC for the type II genes. We previously showed that, whereas type I genes were exclusively expressed in normal breast tissues, expression of type II genes was associated with malignant transformation (Bellet, D., et al. Cancer Res., 57: 516-523, 1997). We designed a simple and robust test (the CG117 assay) that measures the percentage of type II over both types of chorionic gonadotropin beta mRNAs. Normal breast tissues consistently had a negative CG117 index, whereas cancer breast tissues showed indexes ranging from 0 to 100%. The prognostic significance of the CG117 index was investigated in a series of 99 unilateral invasive primary breast cancer patients with known long-term outcome (median follow-up, 9 years). The CG117 index was positive in 48 (48.5%) of the 99 tumor mRNA samples. The index was not significantly associated with standard prognostic parameters, including clinical and macroscopic tumor size, histopathological grade, and lymph node status or steroid receptor status. Patients with a positive CG117 index in primary tumor mRNA had significantly shorter metastasis-free survival (P = 0.014) and overall survival (P = 0.038) after surgery, compared to patients with a negative index. The prognostic significance of the CG117 index persisted in Cox multivariate regression analysis, both for metastasis-free survival (P = 0.008) and overall survival (P = 0.016), together with lymph node status (P = 0.027 and P = 0.009, respectively). These findings indicate that the CG117 index may contribute to the identification of high-risk breast cancer patients.

Silicon-nanowire based attachment of silicon chips for mouse embryo labelling.

The adhesion of small silicon chips to cells has many potential applications as direct interconnection of the cells to the external world can be accomplished. Hence, although some typical applications of silicon nanowires integrated into microsystems are focused on achieving a cell-on-a-chip strategy, we are interested in obtaining chip-on-a-cell systems. This paper reports the design, technological development and characterization of polysilicon barcodes featuring silicon nanowires as nanoscale attachment to identify and track living mouse embryos during their in vitro development. The chips are attached to the outer surface of the Zona Pellucida, the cover that surrounds oocytes and embryos, to avoid the direct contact between the chip and the embryo cell membrane. Two attachment methodologies, rolling and pushpin, which allow two entirely different levels of applied forces to attach the chips to living embryos, are evaluated. The former consists of rolling the mouse embryos over one barcode with the silicon nanowires facing upwards, while in the latter, the barcode is pushed against the embryo with a micropipette. The effect on in vitro embryo development and the retention rate related to the calculated applied forces are stated. Field emission scanning electron microscopy inspection, which allowed high-resolution imaging, also confirms the physical attachment of the nanowires with some of them piercing or wrapped by the Zona Pellucida and revealed extraordinary bent silicon nanowires.

Controlling colloidal stability of silica nanoparticles during bioconjugation reactions with proteins and improving their longer-term stability, handling and storage.

Despite the potential of antibody-coated nanoparticles (Ab-NPs) in many biological applications, there are very few successful, commercially available examples in which the carefully engineered nanomaterial has made it beyond the laboratory bench. Herein we explore the robustness and cost of protein-nanoparticle conjugation. Using multivalent polyamidoamine (PAMAM) dendrimers and dextran as crosslinkers, it was possible to retain colloidal stability during (i) NP-linker binding and (ii) the subsequent conjugation reaction between linker-coated NPs and proteins to generate monodisperse Ab-NPs. This was attributed to the physicochemical properties of the linkers, which were inherited by the NPs and thus benefited colloidal stability. Attaching negatively charged, EDC/sulfo-NHS-activated PAMAM to the NPs contributed to overall negative charge of particles, and in turn led to high electrostatic attraction between the protein and PAMAM-coated NPs during the reaction conditions. In contrast, using an uncharged, EDC/NHS-activated PAMAM dendrimer led to NP aggregation and lower protein binding efficiency. Dextran as a cost-effective, uncharged macromolecule allowed for steric repulsions between neighbouring particles during protein binding, thus inducing NP stability in solution, and also produced monodisperse Ab-NPs. By freeze-drying Ab-NPs from a 1% BSA solution it is possible to reconstitute the solid-form colloid back to a stable state by adding solvent and simply shaking the sample vial by hand. The consequences of the different surface chemistries and freeze-drying stabilizers on the colloidal stability of the NPs were probed by dynamic light scattering. The performance of Ab-NPs was compared in a simple fluorescence linked immunoassay in whole serum. Interestingly, the signal-to-noise ratios were similar for Ab-NPs using PAMAM and dextran, despite dextran binding fewer Abs per NP. We believe this work provides researchers with the tools and strategies for reliably generating Ab-NPs that can be used for a variety of biological applications.

Nanostructured Ti-Zr-Pd-Si-(Nb) bulk metallic composites: Novel biocompatible materials with superior mechanical strength and elastic recovery.

The microstructure, mechanical behaviour, and biocompatibility (cell culture, morphology, and cell adhesion) of nanostructured Ti45 Zr15 Pd35- x Si5 Nbx with x = 0, 5 (at. %) alloys, synthesized by arc melting and subsequent Cu mould suction casting, in the form of rods with 3 mm in diameter, are investigated. Both Ti-Zr-Pd-Si-(Nb) materials show a multi-phase (composite-like) microstructure. The main phase is cubic ß-Ti phase (Im3m) but hexagonal α-Ti (P63/mmc), cubic TiPd (Pm3m), cubic PdZr (Fm3m), and hexagonal (Ti, Zr)5 Si3 (P63/mmc) phases are also present. Nanoindentation experiments show that the Ti45 Zr15 Pd30 Si5 Nb5 sample exhibits lower Young's modulus than Ti45 Zr15 Pd35 Si5 . Conversely, Ti45 Zr15 Pd35 Si5 is mechanically harder. Actually, both alloys exhibit larger values of hardness when compared with commercial Ti-40Nb, (HTi-Zr-Pd-Si ≈ 14 GPa, HTi-Zr-Pd-Si-Nb ≈ 10 GPa and HTi-40Nb ≈ 2.7 GPa). Concerning the biological behaviour, preliminary results of cell viability performed on several Ti-Zr-Pd-Si-(Nb) discs indicate that the number of live cells is superior to 94% in both cases. The studied Ti-Zr-Pd-Si-(Nb) bulk metallic system is thus interesting for biomedical applications because of the outstanding mechanical properties (relatively low Young's modulus combined with large hardness), together with the excellent biocompatibility.

Cancer genetic clinics: why do women who already have cancer attend?

Cancer patients attend oncogenetic clinics so that the existence of a genetic risk can be checked and the relatives informed. The aim of this study was to describe the expectations of cancer patients about genetic counselling and their beliefs about the aetiology of their disease. A survey based on self-administered questionnaires before and after the consultation was carried out on 115 women with breast/ovarian cancer who attended one of the six French participating clinics. In 59 cases (51%), the consultees' expectations focused on the preventive options available and in 86 cases (75%) on their offspring; 87 (76%) found the consultation informative. On average, the women rated heredity and diet as lower risk factors (P < 0.05) after the consultation than before. Heredity, stress and the environment were thought to be more decisive than diet, smoking and alcohol. 34 patients who seemed unlikely to have a genetic risk in the consultant's opinion thought heredity to be less relevant (P < 0.05) after the consultation than before. At the time of the survey, cancer patients accounted for at least half of the consultees attending oncogenetic clinics in France. They need to have the clinical specificities of their disease and its medical management explained. They attend mainly for their offspring's sake, whereas healthy clients attend for their own sake.