Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR-) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer.

Effects of Calophyllum inophyllum fruit extract on the proliferation and morphological characteristics of human breast cancer cells MCF-7

Objective: To evaluate the antiproliferative activity of Calophyllum inophyllum (C. inophyllum) fruit extract against human breast cancer cells MCF-7.

Methods: The cytotoxic effect of C. inophyllum fruit extract against MCF-7 cancer cells was evaluated through MTT and CyQuant assays for 24 h and the morphological investigation of treated MCF-7 cells was observed under optical microscope using Giemsa staining.

Results: The cytotoxic effect of C. inophyllum fruit extract against MCF-7 cancer cells was evaluated through MTT and CyQuant assays simultaneously for 24 h after treatment, which demonstrated the inhibition of cell viability with the IC50 values of 19.63 μg/mL and 27.54 μg/mL, respectively. The preliminary time-based morphological investigation of MCF-7 cells treated with the IC50 value (23.59 μg/mL) of C. inophyllum fruit extract was observed under an optical microscopy via Giemsa staining, which exhibited prominent histological characteristics of apoptosis.

Conclusions: This study clearly proved that the proliferation of human breast cancer cell MCF-7 was inhibited by C. inophyllum fruit extract resulted from the induction of apoptosis in MCF-7 cells.

Characteristics of patients with haematological and breast cancer (1996-2009) who died of heart failure-related causes after cancer therapy

Aims To describe the characteristics and time to death of patients with breast or haematological cancer who died of heart failure (HF) after cancer therapy. Patients with an index admission for HF who died of HF-related causes (IAHF) and those with no index admission for HF who died of HF-related causes (NIAHF) were compared.

Methods and results We performed a linked data analysis of cancer registry, death registry, and hospital administration records (n = 15 987). Index HF admission must have occurred after cancer diagnosis. Of the 4894 patients who were deceased (30.6% of cohort), 734 died of HF-related causes (50.1% female) of which 279 (38.0%) had at least one IAHF (41.9% female) post-cancer diagnosis. Median age was 71 years [interquartile range (IQR) 62–78] for IAHF and 66 years (IQR 56–74) for NIAHF. There were fewer chemotherapy separations for IAHF patients (median = 4, IQR 2–9) compared with NIAHF patients (median = 6, IQR 2–12). Of the IAHF patients, 71% had died within 1 year of the index HF admission. There was no significant difference in HF-related mortality in IAHF patients compared with NIAHF (HR, 1.10, 95% CI, 0.94–1.29, P = 0.225).

Conclusions The profile of IAHF patients who died of HF-related causes after cancer treatment matched the current profile of HF in the general population (over half were aged ≥70 years). However, NIAHF were younger (62% were aged ≤69 years), female patients with breast cancer that died of HF-related causes before hospital admission for HF-related causes—a group that may have been undiagnosed or undertreated until death.

Effects of message framing on breast-cancer-related beliefs and behaviours: the role of mediating factors

The effects of gain-loss message framing on breast-cancer-related cognitions and behaviors were assessed among 539 women aged 30 to 70 years. The design involved a prebrochure telephone interview, followed by a brochure mailout, and a postbrochure telephone interview. The brochures contained information about breast cancer and the risk of family history. Recommended behaviors were framed to emphasize gains, losses, or were neutral; and statistical risk information was presented either positively or negatively. Measures included demographics, family history, breast self-examination (BSE) performance, BSE intention, self-efficacy in performing BSE, perceived early detection risk of breast cancer, perceived susceptibility to breast cancer, and anxiety about breast cancer. A loss-framed message led to greater positive change in BSE behavior. Interactions between framing effects and variables of issue involvement, perceived early detection risk, and self-efficacy indicated effects on behavior, but not beliefs.

Women's perceptions of familial aspects of breast cancer

Women’s understanding of familial aspects of breast cancer was examined using both focus groups and interviews. The studies covered issues related to perceptions of breast cancer risk factors, perceived breast cancer risk, understanding of risk information, and family history of breast cancer as a risk factor. Study 1 consisted of four focus group discussions with women from the general community. Study 2 comprised ten face-to-face interviews with women who had a family history of breast cancer. The results in combination indicate a fairly high level of awareness of family history as a risk factor for breast cancer. However, the definition of a familial history of breast cancer differed between the groups, with those without a family history being more inclusive than those with such a history. The paper concludes with suggestions for use by those developing resources materials for those with a familial history of breast cancer.

Experiences of men with breast cancer: a qualitative study

Background
Recent reports indicate that male breast cancer rates are increasing in North America. While there have been numerous large-scale studies examining women's experiences with breast cancer, to date there have been no North American studies examining what a man experiences with a breast cancer diagnosis. The objective of this qualitative study was to describe the experiences of a sample of Canadian men diagnosed with breast cancer.

Methods
After written informed consent, unstructured audio-taped interviews were conducted with 20 men. Since little is known about a man's experience with breast cancer, an exploratory qualitative approach was utilized.

Results
Participants experienced concerns related to the lack of awareness of male breast cancer within both public and health professional groups. Many men suffered stress related to the cancer diagnosis, body image concerns and role strain. The lack of male-specific breast cancer information was identified as a major concern. All denied interest in traditional support groups. In retrospect, a number of men felt the breast cancer experience vastly improved their lives.

Conclusions
Needs identified by participants include increased public and health professional awareness of male breast cancer, written information specific for men, and male participation in breast cancer research. Further study is also necessary to identify supports considered helpful by men with breast cancer and other malignancies.

Kernel-based naive bayes classifier for breast cancer prediction

The classification of breast cancer patients is of great importance in cancer diagnosis. Most classical cancer classification methods are clinical-based and have limited diagnostic ability. The recent advances in machine learning technique has made a great impact in cancer diagnosis. In this research, we develop a new algorithm: Kernel-Based Naive Bayes (KBNB) to classify breast cancer tumor based on memography data. The performance of the proposed algorithm is compared with that of classical navie bayes algorithm and kernel-based decision tree algorithm C4.5. The proposed algorithm is found to outperform in the both cases. We recommend the proposed algorithm could be used as a tool to classify the breast patient for early cancer diagnosis.

Metallothionein 2A expression is associated with cell proliferation in breast cancer

Metallothioneins (MTs) belong to a family of cysteine-rich, metal-binding intracellular proteins, which have been linked with cell proliferation. In this study, expression levels of the 8 known MT-1 and MT-2 functional isoforms in human invasive ductal breast cancer specimens were determined by RT–PCR. The expression profiles of the MT protein and MT-2A mRNA were further evaluated in 79 cases of human invasive ductal breast carcinoma by immunohistochemistry and in situ hybridization, and correlated with cancer cell proliferation (determined by Ki-67 nuclear antigen immunolabeling). MT-1A, MT-1E, MT-1F, MT-1G, MT-1H, MT-1X and MT-2A but not MT-1B, were detected in breast cancer tissue samples. The MT-2A mRNA transcript was the highest among all the isoforms detected. A positive correlation was observed between MT-2A mRNA and MT protein expression with Ki-67 labeling (P = 0.0003 and P < 0.0001, respectively) but not with apoptosis (P = 0.1244 and P = 0.8189, respectively). Co-localization of the MT protein and Ki-67 nuclear antigen in breast cancer cells was demonstrated by double immunofluorescence staining. There was also significantly higher MT protein and MT-2A mRNA expression in histological grade 3 tumors than in histological grade 1 and 2 tumors. The finding that MT 2A appears to be the main isoform associated with cell proliferation in invasive ductal breast cancer tissues, may have therapeutic implications.

External breast prosthesis use: experiences and views of women with breast cancer, breast care nurses, and prosthesis fitters

After mastectomy, the provision of an appropriate breast prosthesis can help to improve body image and quality of life and reduce associated emotional distress. Although up to 90% of women use an external breast prosthesis after mastectomy, little is known about their experiences and satisfaction with breast prosthesis use. Focus groups were conducted with women who had been fitted with an external breast prosthesis, breast care nurses, and prosthesis fitters to explore women's experiences of prosthesis use. Qualitative thematic content analysis of focus group transcripts indicated that whereas women's initial reaction to the prosthesis generally was negative, this improved over time. Provision of adequate information and support, characteristics of the fitter and the fitting experience, and relationships with breast care nurses and prosthesis fitters were important to women's acceptance and satisfaction with their prosthesis. The study results highlighted the key role that breast care nurses play and the underestimation of the prosthesis fitter's role. Common themes concerning the impact of prosthesis use included body image, appearance, and feminine identity. These findings have important implications for professionals involved in the delivery of breast prostheses services.

The breast cancer related burden of morbidity and mortality in six European coutries

Background: The burden of breast cancer expressed in Disability Adjusted Life Years (DALYs) was compared for six European countries and its sensitivity to different sources of variation examined. Methods: DALYs were calculated using country-specific epidemiological data and European Disability Weights. Epidemiological data for 1996 were obtained for Denmark, England and Wales, France, the Netherlands, Spain and Sweden. Disability weights were empirically derived. Results:  Denmark and the Netherlands lost the largest number of DALYs (approximately 1100 DALYs per 100,000 women). They were followed by England (87% of the Danish burden), France (72%), Sweden (68%) and Spain (67%). 70 to 80% of the burden was caused by mortality. Cross-national variation in disease epidemiology was the largest source of variation in the burden of breast cancer. Variation in disability weights and uncertainty in epidemiological data had smaller effects. Conclusion: To compare the burden of breast cancer and most other types of cancer mortality rates provide sufficient information.

Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc

Human telomerase reverse transcriptase (hTERT) underlies cancer cell immortalization, and the expression of hTERT is regulated strictly at the gene transcription. Here, we report that transcription factor Ets2 is required for hTERT gene expression and breast cancer cell proliferation. Silencing Ets2 induces a decrease of hTERT gene expression and increase in human breast cancer cell death. Reconstitution with recombinant hTERT rescues the apoptosis induced by Ets2 depression. In vitro and in vivo analyses show that Ets2 binds to the EtsA and EtsB DNA motifs on the hTERT gene promoter. Mutation of either Ets2 binding site reduces the hTERT promoter transcriptional activity. Moreover, Ets2 forms a complex with c-Myc as demonstrated by co-immunoprecipitation and glutathione S-transferase pulldown assays. Immunological depletion of Ets2, or mutation of the EtsA DNA motif, disables c-Myc binding to the E-box, whereas removal of c-Myc or mutation of the E-box also compromises Ets2 binding to EtsA. Thus, hTERT gene expression is maintained by a mechanism involving Ets2 interactions with the c-Myc transcription factor and the hTERT gene promoter, a protein-DNA complex critical for hTERT gene expression and breast cancer cell proliferation.

Dietary patterns across the life course, mammographic density and implications for breast cancer : results from a British prospective cohort

Background : Previous epidemiological studies have investigated the relationship between individual nutrients such as vitamin D and vitamin B12 and mammographic density, a strong marker of breast cancer risk [1], with varied results. There has been limited research on overall dietary patterns and most studies have focused on adult dietary patterns [2]. We examine prospective data to determine whether dietary patterns from childhood to adult life affect mammographic density.

Methods : The Medical Research Council National Survey of Health and Development is a national representative sample of 2,815 men and 2,547 women followed since their birth in March 1946 [3]. A wealth of medical and social data has been collected in over 25 follow-ups by home visits, medical examinations and postal questionnaires. Dietary intakes at age 4 years were determined by 24-hour recalls and in adulthood (ages 36, 43 years) by 5-day food records. Copies of the mammograms (two views for each breast) taken when the women were closest to age 50 years were obtained from the relevant NHS centres. A total of 1,319 women were followed up since birth in 1946 for whom a mammogram at age 50 years was retrieved, and the percentage mammographic density was measured using the computer-assisted threshold method for all 1,161 women. Breast cancer incidence for the whole cohort is being ascertained through the National Health Service Central Register.

Statistical analysis : Reduced rank regression analysis, a relatively new approach to dietary pattern analysis, is being used to identify dietary patterns associated with mammographic density [4]. This approach identifies patterns in food intake that are predictive of an intermediate outcome of the disease process, such as mammographic density, and subsequently examines the relationship between the identified dietary patterns and breast cancer risk.

Results : Preliminary analyses so far suggest that variations in dietary patterns in adulthood might explain more than 10% of the variation in percentage mammographic density at age 50 years (age 36 years: 13%; age 43 years: 14%), with variations in patterns in childhood explaining slightly less. Further work is being carried out on the characteristics of these dietary patterns and their effects on percentage mammographic density and its two components (that is, absolute areas of dense and nondense tissues) and on breast cancer risk, after adjusting for socioeconomic status, anthropometric variables and reproductive factors.

Conclusion : The present study will provide for the first time information on the relationship between dietary patterns across the life course and mammographic density, and will help to clarify the pathways through which diet may affect breast cancer risk.