Daniela Barsotti Santos

Imagem corporal de mulheres com câncer de mama: uma revisão sistemática da literatura

Women experience a major process of reshaping their body image when they deal with breast cancer. This article seeks to understand the relationship that breast cancer and its treatment have in the process of (re)construction of a womans body image. The ultimate objective is to promote knowledge to train health professionals to become more aware of a womans quality of life. A systematic review of the literature of scientific articles published between 2004 and 2009 available in three scientific databases was conducted and a total of 56 articles were reviewed and grouped into four thematic categories. There is a pressing need for further studies on the socio-cultural characteristics of women with breast cancer, the differences of (re)construction of body image of young and older women, and Brazilian publications about the personal experience and socio-cultural context of women with breast cancer.

Sexualidade e normas de gênero em revistas para adolescentes brasileiros

Abstract The change in the relation of space and time causedby new technologies and by the media expansion, inthe globalization that has derived from the late mo-dernity, has modified the identity and reflexivity ofthe “self”. The security foundations that constitutethe identity are dynamically altered as the social re-lations are modified. Today the identity cannot be re-garded as immutable. Thus, it becomes increasinglyconvenient to support it by means of recipes of lifes-tyles, produced by various social sectors that createand disseminate, through the media, manuals on howto develop a self-identity. Our objective was to analyzethe ideals of femininity in articles published in twomagazines for Brazilian teens, considering aspectsof sexuality, sexual health and relationships betweengenders. We performed a qualitative study based on agender perspective. The research corpus was compo-sed of articles extracted from 22 issues of the maga-zines Capricho and Todateen. Three groups were iden-tified in the following themes: Kiss and squeeze, Be-ginning of sexual life, and Sexual Practices. Both ma-gazines approach ideals of relations between gendersthat perpetuate traditional dichotomic standards. Thearticles prescribe feminine attitudes and behaviors,which despite seeming different and advanced, aredesigned to maintain a gender standard in which thefeminine initiative involves the “jeitinho feminino”:indirect actions of manipulation that can give the boythe impression that he was the one who had the ideathat was put into practice. These data seem particu-larly important when we think of health programstargeted at this segment of the population.Keywords: Femininity Ideals; Sexuality; Sexual Health;Adolescence; Gender and Media.

Breast cancer and sexuality: the impacts of breast cancer treatment on the sex lives of women in Brazil.

This paper presents findings from a qualitative study of the impact on women’s sexual lives after diagnosis and treatment for breast cancer in Ribeirao Preto, São Paulo. The study involved 36 women, 15 of whom were interviewed and the remainder of whom participated in focus and body-image group discussions. Data collection was undertaken between 2008 and 2010. Findings focus on women’s experience of breast cancer as a life-threatening condition and document reappraisals of their lives in general, seeking to situate these women’s sexual lives within the context of wider ideals about femininity and sexual cultures in Brazil. Women expressed anxiety concerning the effects of treatment for breast cancer, particularly concerns about body image. We draw together implications of the prior findings for the sexual scripts played out in women’s sexual relationships and lives. Three main sexual scripts – ‘traditional gender roles’, ‘ageing’ and ‘egalitarian pleasure-oriented’ – are identified and discussed in relation to both the life-changing impact of diagnosis of cancer and wider changes in gender dimensions of Brazilian sexual culture.

Experience of sexuality after breast cancer: a qualitative study with women in rehabilitation

Objective to comprehend the psychosocial and cultural repercussions of breast cancer and its treatment on the sexuality of women. Method this is a qualitative study grounded in the Sexual Scripts Theory with the participation of 23 women who were interviewed and participated in focus groups discussion. Results each category was related to a level of the sexual scripts. At the cultural scenario level a discourse on sexuality that includes definitions of sexual attractiveness and sexuality was highlighted. The interpersonal scripts level focused on the communication regarding sexuality established with the partner and with healthcare professionals category; and at the subjectivity scripts level the reports of improvement, deterioration and no change in the sexual life after cancer were analyzed. Conclusion the experience of cancer involves cultural, relational, and subjective aspects that affect the sexual life, therefore, healthcare professionals should be aware of them to improve integral healthcare.

The sexual life of women with breast cancer: meanings attributed to the diagnosis and its impact on sexuality

O câncer de mama e a principal neoplasia que acomete as mulheres. Por afetar um simbolo corporeo da feminilidade, produz alteracoes emocionais, que se somam as fisicas e sociais. Este estudo teve por objetivo investigar a vida sexual da mulher com câncer de mama no primeiro ano apos o procedimento cirurgico, buscando-se demarcar os significados atribuidos ao diagnostico e suas repercussoes na sexualidade. Foram entrevistadas dez mulheres que participavam de um servico de reabilitacao. Alem da entrevista individual realizou-se analise de prontuarios. Da analise tematica emergiram duas categorias, evidenciando o impacto tanto negativo como positivo do câncer na vida sexual. Essa variedade de significados encontrados mostra que nao existe um padrao unico de vivencia sexual apos o câncer. A maneira como cada mulher ressignifica o adoecimento contribui para que vivencie singularmente sua sexualidade. Conclui-se que e preciso incorporar questoes de sexualidade nas intervencoes oferecidas no contexto do cuidado a essas mulheres.

Sexualidade e câncer de mama: uma revisão sistemática da literatura

O objetivo deste estudo foi compreender como o câncer de mama e seus tratamentos afetam a vivencia da sexualidade da mulher acometida. Foi realizada uma revisao sistematica qualitativa de artigos cientificos, publicados entre 2000 e 2010, disponiveis nas bases de dados PubMed, Web of Science, LILACS e SciELO. Foram obtidos 50 artigos cujos textos foram categorizados segundo analise de conteudo tematica. Foram identificadas seis categorias tematicas: a cirurgia mamaria e os demais tratamentos para o câncer de mama; a experiencia da mulher acometida; o relacionamento afetivo-sexual; estudos sobre relacao entre sexualidade e caracteristicas especificas do câncer; os profissionais de saude e a atencao a sexualidade; e propostas para amenizar as consequencias negativas dos tratamentos na sexualidade. Ha necessidade de novos estudos a respeito dos aspectos culturais da sexualidade, diversidade sexual, relacionamento com o parceiro, formacao do profissional de saude e intervencoes em sexualidade no contexto do câncer de mama.

Validação do Body Image Relationship Scale para mulheres com câncer de mama

PURPOSE To validate the instrument Body Image Relationship Scale (BIRS) for Brazilian women with breast cancer. METHODS The instrument was administered by trained interviewers to 139 women who used the Brazilian Unified Health System (SUS). All of them had been submitted to cancer treatments between 2006 and 2010. The instrument was validated considering internal consistency and reliability. In order to compare the techniques, the same factorial analysis as used in the original paper was carried out. RESULTS The Spearman-Brown correlation value was 0.8, indicating high internal reliability. The Cronbachs alpha found was 0.9, indicating a high level of internal consistency. Factorial analysis showed that four items had low factorial load and no discriminatory power, and another five items were relocated to other factors. When the instrument was applied, it showed variability to that of the original instrument. CONCLUSION The Brazilian version of the Body Image Relationship Scale (BIRS), named Escala de Relacionamento e Imagem Corporal (ERIC), showed evidence of adequate reliability and internal consistency, making this instrument suitable to be recommended for application to Brazilian women with breast cancer, despite some limitations.

Vivencia de la sexualidad después del cáncer de mama: estudio cualitativo con mujeres en rehabilitación

Objective to comprehend the psychosocial and cultural repercussions of breast cancer and its treatment on the sexuality of women. Method this is a qualitative study grounded in the Sexual Scripts Theory with the participation of 23 women who were interviewed and participated in focus groups discussion. Results each category was related to a level of the sexual scripts. At the cultural scenario level a discourse on sexuality that includes definitions of sexual attractiveness and sexuality was highlighted. The interpersonal scripts level focused on the communication regarding sexuality established with the partner and with healthcare professionals category; and at the subjectivity scripts level the reports of improvement, deterioration and no change in the sexual life after cancer were analyzed. Conclusion the experience of cancer involves cultural, relational, and subjective aspects that affect the sexual life, therefore, healthcare professionals should be aware of them to improve integral healthcare.

Vivência da sexualidade após o câncer de mama: estudo qualitativo com mulheres em reabilitação

Objective to comprehend the psychosocial and cultural repercussions of breast cancer and its treatment on the sexuality of women. Method this is a qualitative study grounded in the Sexual Scripts Theory with the participation of 23 women who were interviewed and participated in focus groups discussion. Results each category was related to a level of the sexual scripts. At the cultural scenario level a discourse on sexuality that includes definitions of sexual attractiveness and sexuality was highlighted. The interpersonal scripts level focused on the communication regarding sexuality established with the partner and with healthcare professionals category; and at the subjectivity scripts level the reports of improvement, deterioration and no change in the sexual life after cancer were analyzed. Conclusion the experience of cancer involves cultural, relational, and subjective aspects that affect the sexual life, therefore, healthcare professionals should be aware of them to improve integral healthcare.

Sexuality of Brazilian women in the context of breast cancer: A mixed methods analysis

T lecture will address the function of the translation initiation factor eIF2 in stressed-induced tumorigenesis as well as in anti-tumor treatments with chemotherapeutic drugs. eIF2 is a master regulator of stress through its ability to control protein synthesis in response to various forms of stress including DNA damage, oxidative stress, oncogenic stress as well as stress in the tumor microenvironment. Cells respond to stress by inducing the phosphorylation of the alpha (α) subunit of eIF2 at serine 51 (S51) (herein referred to as eIF2αP), a modification that leads to the inhibition of global protein synthesis. eIF2αP is mediated by four kinases, namely HRI, PKR, PERK/PEK and GCN2 each of which becomes activated to distinct form of stress. Despite the general inhibition of protein synthesis, specific mRNAs can bypass the blockade, and in fact, be efficiently translated under stress. Such mRNAs encode for proteins that facilitate cell adaptation to stress as shown for transcription factors ATF4 and ATF5 in mammalian cells or GCN4 in yeast. Our work focuses on eIF2αP function as a cell fate decision maker through its ability to induce either cell survival or death in stressed tumor cells. We investigate how the dual but opposing function of eIF2αP relates to the activation of the MAPK and Akt/PKB-mTORC1 pathways in stressed cells. Our work suggests that inhibition of eIF2αP is a powerful approach to disarm cell survival and induce death in tumor cells treated with pro-oxidant drugs or drugs targeting the PI3K-Akt/PKB-mTORC1 pathway.Patients and methods: the study was performed at al Bairouni university hospital and Kenj Cytogenetic Lab in Damascus (SYRIA). Blood samples were obtained from 100 chemonaive metastatic breast cancer patients. Samples were cultured in (DMEM) media, and after certain passages we obtained breast cancer stem cells CD44/CD24 confirmed through passage in flowcytometer and PCR of protein product of CD44 surface protein. Then, obtained cells were subjected to immunohistochemistry for ER/PR/Her-2 after they were embedded in paraffin by means of Liquid based cytology.W there any many varied treatments for cancer, one emerging non-medical approach is the use of cryosurgery. Cryosurgery involves the freezing of tissues in order to cause their subsequent death. A standard protocol is complicated by the nature of cellular injury which is governed by complex biological mechanisms. For instance, tissue which is frozen very quickly results in intracellular ice formation and the subsequent damage to cellular membranes. Alternatively, for cases with slow freezing, the water is able to pass out of the cells and freezes in the extracellular spaces, thereby resulting in cell injury by dehydration. Regardless of the mechanism of cellular injury, for clinical settings it is essential that the treating physician is able to visualize the size, shape and position of the targeted area. When cryo-surgical probes are used in the treatment, their number, placement, temperature setting, and treatment duration are factors which determine the treated region. Here, we use advanced numerical simulation along with patient-specific kidney geometries. In the computational model, the tumors can be placed arbitrarily to match those of the patient. The software allows the treating physician to experiment with various techniques and to perfect the ultimate procedure in a virtual environment prior to real-life treatment. In this way, it is possible to more accurately target the tumor to ensure it is completely enclosed in the treatment zone meanwhile minimize the damage to nearby healthy tissue. The simulations can be carried out in less than four minutes so that their employment is not onerous to the physician.A resistance through genetic mutations is a major obstacle in targeted cancer therapy, but the underlying mechanisms are poorly understood. Using chronic myeloid leukemia (CML) as a disease model, we studied mechanisms of CML acquired resistance to tyrosine kinase inhibitors. By examining genome-wide gene expression and Exome sequencing of CML cells before and after developing genetic resistance, we identified key changes in cellular differentiation status when CML cell acquired genetic resistance. Forced differentiation overcame CML acquired resistance by altering CD38 expression and cellular NAD metabolism, which led to inhibition of SIRT1 functions and error-prone DNA damage repair in CML cells and blocking mutation acquisition. Our study sheds novel insight of cancer acquired resistance and has clinical implication of using differentiation agents to overcome drug resistance to tyrosine kinase inhibitors.Results: In the quantitative component, 67 women answered the Female Sexual Function Index (FSFI) among the total of 139 participants. By the FSFI score it was obtained 6 clusters in which half of them presented sexual dysfunction or suggestion of some sexual problems. Three sexual scripts were identified: the script of sexuality based on traditional gender roles, the script of sexuality related to aging, and the script of sexuality based on wellbeing. The alteration of sexual function was not decisive for some women consider worsening of their sexual life after cancer. There were some reports of improvement of sexual life and some women reported that sex life remained the same as before.M of the mitochondria in tumors have been presented in the literature, as most cancer cells have to support metabolic transformation in order to promote their proliferation and survival. One of the hallmark alterations of tumor cell metabolism is known as the Warburg Effect, which tumor cells prefer deriving energy through glycolysis, opposed to the more efficient process of oxidative phosphorylation. Defective oxidative phosphorylation will lead to production of reactive oxygen species (ROS), which may enhance cell transformation and ultimately lead to tumor initiation, promotion, and progression. The high metabolic rate of cancer cells drives their intracellular ROS up to an intermediate level, resulting in a shift in redox balance. The peroxisome proliferator-activated receptorcoactivator1 (PGC-1) family members are main regulators of several mitochondrial genes. PGC-1α e β have been considered as main regulators of energy homeostasis of the cell and it has been demonstrated that variations of PGC-1s expression occur in tumor cells in order to promote cell survival. Thus, it is known that breast cancer cells display several mechanisms to promote their survival involving redox-signaling pathways and modifying their metabolism. The mechanisms by which PGC-1s act to control tumor cells proliferations are not completely understood. During this lecture, it will be discussed recent findings regarding redox and metabolic changes in distinct breast cancer subtypes with a special focus in PGC-1s family members.W present first report on novel and previously reported chromosomal mosaicism and genetic copy number variation in histopathologically characterized medulloblastoma (MB) in North Indian cases using array based comparative genomic hybridization (CNV-targeted; CytoScan 750K Array). In first case, the results revealed gain mosaic (CN state=2.91)/gains (CN=3.00) at Ch: 1q and Loss Mosaic (CN=1.22) at Ch: 1p, Ch: 2 q37.1-37.3 (CN=1.50), Ch: 4 q28.1-35.2 (CN=1.18) and Ch: 8 q22.3-24.13 (CN=1.73). Importantly, Loss of HHIP gene at 4q31.21, suggests it to be SHH Type of MB. In second case, gain mosaic of 17 q (CN=3.00), 16p (CN=2.23) 12 (CN=2.48; Gain at 3 regions) 2p (CN=2.91)7 (CN=3.00) and 1q (CN=2.91) and loss mosaic of 17 p (CN=1.61), 16q (CN=1.27) 13 (CN=1.61) 11 (CN=1.56), 10 (CN=1.27 and Loss at 10q), 8 (CN=1.67), 2q (CN=1.62) was observed. Additionally, amplification at MYCN at 2p24.3, CDK6 at 7q21.2, GLI1 at 12q13.3, Loss of MYC at 8q24.2, IRS2 at 13q34, Tp53 in 17p31.1, SUFU at 10q24.32, PAX6 at 11p13, SFRP1 at 8p11.21 classify this case into SHH group of MB. Gain of 17q, 7 and 1q and Loss of 17p, 16q, 11p, 10q and 8 have been previously reported, however gains in Ch: 16p, 12, 7, 2p, 1q and X, as well as losses of Ch: 20, 13q, 11, 10, 8, 4q and 2q were the novelty. The results validate the previously reported as well as novel alterations in oncoand tumor-suppressor genes and classify both the samples as SHH type of MB............................................................................... 3The identification of biomarkers in the presence of Barretts esophagus (BE) and esophageal adenocarcinoma( EAC) has the potential to improve patient outcomes through earlier diagnosis and treatment. AIM Evaluate the esophageal tissue expression of glutathione S-transferaseP1 (GSTP1) and matrix metalloproteinase-9 (MMP-9) in patients with reflux esophagitis, BE and EAC. Tissue expression of both GSTP1 and MMP-9 were analyzed in 120 paraffin-embedded esophageal samples by immune histochemistry obtained from 60 Egyptian patients; gastro-esophageal reflux disease(GERD)(n= 15), BE (n= 15), EAC (n= 15) in addition to a control group with normal gross and histologic esophageal tissue (n= 15). Immunostaining was determined semi-qualitatively in all groups. Normal esophageal mucosa demonstrated the lowest MMP-9 and highest GSTP1 tissue expression compared to all other groups; p<0.001. In contrast, the tissue expression of MMP-9 was significantly higher and GSTP1 was significantly lower in EAC and dysplastic BE than other groups; p value <0.001. Dysplastic BE demonstrated a significant higher MMP-9; p<0.04 and lower GSTP1 tissue expression; p<0.003 compared to patients with non-dysplastic BE and GERD, however, no major changes were observed between non-dysplastic BE and GERD. The significant down-regulation of MMP-9 was coupled by up-regulation of GSTP1 expression along the whole spectrum of the disease, p value <0.001. The imbalance between tissue GSTP1 and MMP-9 in BE and EAC could be considered as potential markers that might be useful to identify patients at higher risk for progression to cancer.C is a surface marker of tumor-initiating cells (TICs); high tumor levels correlate with metastasis and recurrence, as well as poor outcomes of patients. Monoclonal antibodies against CD44s might eliminate TICs with minimal toxicity. This strategy is unclear for treatment of pancreatic cancer, and little is known about how anti-CD44s affect pancreatic cancer initiation or recurrence after radiotherapy. We measured CD44s levels in tissue samples and pancreatic cancer cell lines by immunohistochemistry, real-time PCR and immunoblot; levels were correlated with patient survival times. We studied the effects of anti-CD44s in mice with human pancreatic tumor xenografts, and used flow cytometry to determine effects on TICs. Changes in CD44s signaling were examined by real-time PCR, immunoblot, reporter assay, and in vitro tumorsphere formation assays. The levels of CD44s were significantly higher in pancreatic cancer than adjacent non-tumor tissues. Patients whose tumors expressed high levels of CD44s had a median survival of 10 months, compared to 43 months for those with low levels. Anti-CD44s reduced growth, metastasis, and post-radiation recurrence of pancreatic xenograft tumors in mice. The antibody reduced the number of TICs in cultured pancreatic cancer cells and in xenograft tumors, as well as their tumorigenicity. In cultured pancreatic cancer cell lines, anti-CD44s downregulated the stem cell self-renewal genes Nanog, Sox-2, and Rex-1 and inhibited STAT3-mediated cell proliferation and survival signaling. The TIC marker CD44s is upregulated in human pancreatic tumors and associated with patient survival time. CD44s is required for initiation, growth, metastasis, and post-radiation recurrence of xenograft tumors in mice. Anti-CD44s eliminated bulk tumor cells as well as TICs from the tumors. Strategies to target CD44s might be developed to block pancreatic tumor formation and post-radiotherapy recurrence in patients.A major clinical challenge in prostate cancer is the elucidation of pathways of tumor progression, recurrence and metastasis, which could lead to the design of better diagnostic and therapeutic strategies against the disease. This lecture will address the role of novel microRNA (miRNA) genes located at frequently deleted genomic region in prostate cancer epithelial-to mesenchymal transition (EMT), recurrence and metastasis. The most frequent alteration in the prostate oncogenome is the loss of chromosome (chr) 8p21 that has been traditionally associated with the loss of homeodomain protein, NKX3.1, that plays important roles in prostate carcinogenesis. Genomic deletions of this region increase significantly with tumor grade and are associated with poor prognosis in prostate cancer suggesting the critical involvement of this region in prostate cancer progression. Recent genomic studies suggest that this region harbors alternative tumor suppressor genes apart from NKX3.1. However, the identity of these tumor suppressors has largely remained elusive. Our studies support a novel, paradigm shifting hypothesis that this frequently deleted locus is associated with a cluster of miRNA genes that are lost in prostate cancer and play an important mechanistic role in prostate cancer progression and metastasis by regulating Epithelial-mesenchymal transition (EMT). Also, these miRNA genes regulate prostate cancer tumor-initiating cells, implicating a role in prostate cancer recurrence. These studies have high transformative potential in the field of prostate cancer and will potentially identify new agents for diagnosis, prognosis and therapy of advanced prostate cancer.T epithelial-mesenchymal transition (EMT) constitutes a relevant process during the progression of carcinomas, as it mediates the conversion of stationary, epithelial tumor cells into mesenchymal-like, invasive cancer cells. We recently identified the T-box transcription factor brachyury, a molecule predominantly expressed in human tumors but only rarely expressed in normal adult tissues, as a novel driver of the EMT process in human carcinoma cells. Brachyury was demonstrated to induce the expression of molecules associated with the mesenchymal phenotype, human tumor cell motility and invasiveness in vitro, as well as metastatic propensity in xenograft models. Analysis of expression in multiple human tumor tissues demonstrated a preferential expression of Brachyury in higher stage lung tumors, suggestive of a role of Brachyury in human lung cancer progression. Analysis of breast cancer tissues also revealed expression of Brachyury in primary breast tumor samples as well as in 100% of breast cancer metastatic lesions analyzed by immunohistochemistry. We have now shown a positive correlation between Brachyury expression in epithelial tumor cells and features of tumor stemness, including resistance in response to treatment with various chemotherapeutic agents or radiation. In search for an approach to target tumor cells with high levels of brachyury, we have characterized its immunogenicity and developed brachyury-based cancer vaccine platforms, one of which is currently undergoing Phase I clinical testing. We hypothesize that the eradication of brachyury-expressing tumor cells via immunotherapeutic approaches could be efficient at eliminating tumor cells with invasive/metastatic potential as well as tumor resistance to conventional therapies.T Notch1 receptor and signaling pathway is upregulated in HCC. The present study was conducted to evaluate the effect of mesenchymal stem cells (MSCs) and a novel curcumin derivative (NCD) on hepatocellular carcinoma (HCC) in hepatoma induced rats, and to investigate their effect on Notch1 signaling pathway target genes. One hundred rats were divided equally into: control group, control group received MSCs, control group received a NCD, HCC group, HCC group received MSCs only, HCC group received a NCD only, HCC group received MSCs and a NCD simultaneously, HCC group received MSCs followed by a NCD 2 weeks later, HCC group received MSCs pretreated with a NCD and HCC group received MSCs conditioned medium (CM). Histopathological examination, gene expression of Notch1 signaling target genes by RT-PCR in rat liver tissue were assessed and serum levels of alpha fetoprotein, ALT and albumin were assesed in all groups. Administration of MSCs or a NCD after induction of HCC improved the histopathological picture while administration of MSCs and a NCD or MSCs pretreated with a NCD showed restoration of liver parenchyma. Notch1 and its target genes were downregulated in all treated groups. Liver function was ameliorated in all treated groups. These data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD may be considered as a therapeutic target in HCC.W have demonstrated that Notch1 is required for trastuzumab resistance in ErbB2 positive breast cancer. This indicates that ErbB2 suppresses Notch1 in breast cancer and therapeutic intervention targeting ErbB2 might have an unintended consequence which is aberrant up regulation of Notch1 which is a breast oncogene.However, the mechanism of action by which ErbB2 restricts Notch1 activation is unknown. In this current study, we investigated the role of cisand trans-activation of Notch signaling by Notch ligands which are developmentally conversed to tightly regulate Notch activation. To address this hypothesis, we performed co-culture studies using fibroblasts expressing no Notch ligands or over-expressing human Jagged1 or Deltalike1 and ErbB2 positive breast cancer cells. We performed flow cytometry to isolate breast cancer cells after co-culture and extracted RNA to measure expression of Notch gene targets as a measure of Notch activity. The results showed that trastuzumab, Lapatinib, or ErbB2 knockdown increased overall Notch activation. Similarly, Co-culture with Jagged1expressing fibroblasts increased overall Notch activation. However, Knocked down of Jagged1 in the breast cancer cells had little effect on ligand-induced Notch activation relieving the possibility of cis-inhibition. In contrast, Jagged1 knocked down abrogated trastuzumab-induced Notch activation in the breast cancer cells. These results suggest that ErbB2 might restrict Notch activation by preventing Jagged1-mediated trans activation of Notch and not by promoting cis-inhibition. Confocal immunofluorescence showed that Jagged1 is localized with Notch1 when ErbB2 is hyperactive but is trafficked to the cell surface in response to trastuzumab. K44ADynamin abrogated Jagged1 expression on the cell surface as measured by IF and surface biotinylation studies. Furthermore, K44ADynamin expression abrogated trastuzumab-induced Notch1 activation. Importantly, we measured growth consequences of Jagged1-mediated Notch activation in response to trastuzumab and found that Jagged1 is necessary for survival of ErbB2 positive breast cancer cells and trastuzumab resistance as measured by cell cycle analysis and Annexin V staining. These results taken together indicate that ErbB2 restricts Notch by limiting Jagged1-mediated trans-activation.Cross-cultural end-of-life health care is described in the literature as a dynamic new direction for research and treatment (Field, Maher, & Webb, 2002; Searight & Gafford, 2005). A recent review of the Canadian literature suggests that there are distinct cultural differences with respect to Aboriginal families (Kelly & Minty, 2007). Over the last 7 years, culturally appropriate end-of-life care with Aboriginal families in the Canadian province of Saskatchewan has been the focus of our research team at the University of Regina. We have learned a great deal about ways in which Aboriginal families are poorly served at end of life by the health-care system and ways in which they could be better served. Our interdisciplinary team is composed of both Aboriginal and nonAboriginal academic researchers, Aboriginal guiding Elders, and healthcare providers who direct palliative services in our health region and/or services offered at a freestanding bereavement centre in our region. Together we have been able to create space for Aboriginal Elders and community members to speak about culturally appropriate end-of-life care for Aboriginal families.