Analysis of breast cancer by small angle X-ray scattering (SAXS)

Small angle X-ray scattering (SAXS) images of normal breast tissue and benign and malignant breast tumour tissues, fixed in formalin, were measured at the momentum transfer range of 0.063 nm(-1) <= q (=4 pi sin(theta/2)/lambda) <= 2.720 nm(-1). Four intrinsic parameters were extracted from the scattering profiles (1D SAXS image reduced) and, from the combination of these parameters, another three parameters were also created. All parameters, intrinsic and derived, were subject to discriminant analysis, and it was verified that parameters such as the area of diffuse scatter at the momentum transfer range 0.50 <= q <= 0.56 nm(-1), the ratio between areas of fifth-order axial and third-order lateral peaks and third-order axial spacing provide the most significant information for diagnosis (p < 0.001). Thus, in this work it was verified that by combining these three parameters it was possible to classify human breast tissues as normal, benign lesion or malignant lesion with a sensitivity of 83% and a specificity of 100%.

Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model

Background: Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-alpha and IL-10 expression and to evaluate antitumour activity. Methods: For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF-cells. Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-alpha in the BCG-treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group. Conclusion: These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-alpha and IL-10 cytokine productions may have therapeutic value.

Adherence to cervical and breast cancer programs is crucial to improving screening performance

Introduction: Cervical and breast cancer are the most common malignancies among women worldwide. Effective screening can facilitate early detection and dramatically reduce mortality rates. The interface between those screening patients and patients most needing screening is complex, and women in remote areas of rural counties face additional barriers that limit the effectiveness of cancer prevention programs. This study compared various methods to improve compliance with mass screening for breast and cervical cancer among women in a remote, rural region of Brazil. Methods: In 2003, a mobile unit was used to perform 10 156 mammograms and Papanicolaou smear tests for women living in the Barretos County region of Sao Paulo state, Brazil (consisting of 19 neighbouring cities). To reach the women, the following community outreach strategies were used: distribution of flyers and pamphlets; media broadcasts (via radio and car loudspeakers); and community healthcare agents (CHCAs) making home visits. Results: The most useful intervention appeared to be the home visits by healthcare agents or CHCAs. These agents of the Family Health Programme of the Brazilian Ministry of Health reached an average of 45.6% of those screened, with radio advertisements reaching a further 11.9%. The great majority of the screened women were illiterate or had elementary level schooling (80.9%) and were of 'poor' or 'very poor' socioeconomic class (67.2%). Conclusions: Use of a mobile screening unit is a useful strategy in developing countries where local health systems have inadequate facilities for cancer screening in underserved populations. A multimodal approach to community outreach strategies, especially using CHCAs and radio advertisements, can improve the uptake of mass screening in low-income, low-educational background female populations.

Variability in Estrogen-Metabolizing Genes and Their Association with Genomic Instability in Untreated Breast Cancer Patients and Healthy Women

In the present study, we investigated the relationship between polymorphisms in the estrogen-metabolizing genes CYP17, CYP1B1, CYP1A1, and COMT and genomic instability in the peripheral blood lymphocytes of 62 BC patients and 62 controls considering that increased or prolonged exposure to estrogen can damage the DNA molecule and increase the genomic instability process in breast tissue. Our data demonstrated increased genomic instability in BC patients and that individuals with higher frequencies of MN exhibited higher risk to BC when belonging Val/Met genotype of the COMT gene. We also observed that CYP17 and CYP1A1 polymorphisms can modify the risk to BC depending on the menopause status. We can conclude that the genetic background in estrogen metabolism pathway can modulate chromosome damage in healthy controls and patients and thereby influence the risk to BC. These findings suggest the importance to ally biomarkers of susceptibility and effects to estimate risk groups.

Sexuality and quality of life of breast cancer patients post mastectomy

Aim: To evaluate the sexual functioning of breast cancer patients post mastectomy and its association with their quality of life, the personal characteristics of women and their partners, breast reconstruction, cancer staging and adjuvant therapies. Methods: A cross-sectional study was carried out in a University hospital located in the SouthEast of Brazil. A total of 100 women were included in the study. The parameters evaluated were sexual functioning, which was assessed based on the Sexual Quotient Female Version (SQ-F), quality of life (QoL), evaluated by the Medical Outcomes Study 36-item Short Form (SF-36), cancer staging, breast reconstruction, adjuvant therapies and the personal characteristics of patients (age, years of study and years of marriage) and their partners (age, years of study). Results: The majority (40.48%) of women had an unfavorable to regular SQ-F score. A significant positive correlation (p < 0.05) was found between the SQ-F score and years of education (p = 0.03), and the following SF-36 domains: functional capacity (p = 0.03), vitality (p = 0.06), emotional limitations (p = 0.00) and mental health (p = 0.03). A significant negative correlation was found between SQ-F score and the age of the partners (p = 0.03). SQ-F mean value was significantly higher (p = 0.04) among women who underwent breast reconstruction. Conclusions: Women with low educational level, who have older partners, and who did not have a breast reconstruction should receive special attention with respect to their sexuality, and the effects of mastectomy on the sexuality of patients should be assessed. Oncology nurses are best qualified to recognize issues related to sexuality and quality of life, and can offer specific and meaningful support for breast cancer patients. (C) 2010 Elsevier Ltd. All rights reserved.

Psychosocial perspectives of the partners of breast cancer patients treated with a mastectomy

The family members of cancer patients play a central role as caregivers. This study reports on the perspectives of men whose wives underwent a mastectomy because of breast cancer. This qualitative research used a narrative analysis method, and 17 men were interviewed. Five main themes emerged from the analysis of the narratives: initial reactions to the diagnosis, involvement in caregiving, support received, influence of breast cancer on the couples` relationships, and evaluation of care provided by the institution. The findings indicated the existence of substantive evidence that the spouses attended to and followed the recommendations of healthcare providers on ways to care for their wives, including their emotional demands and care needs. In this sense, the healthcare professionals should interact with a. patient`s primary caregiver, take the family dynamics and the caregiver`s personal characteristics into account, and systematically consider and include the needs of the patients` caregivers in the entire healthcare process.

Analysis of plasma and erythrocyte zinc levels in premenopausal women with breast cancer

Introduction: Zinc deficiency has been associated with damage and oxidative changes in DNA that may increase an individual`s risk of cancer. Furthermore, zinc metabolism may be affected in cancer patients, leading to alterations in its distribution that would favor carcinogenesis. Plasma and erythrocyte zinc levels in women with breast cancer were evaluated in this cross-sectional, controlled study. Material and methods: Fifty-five premenopausal women of 25 to 49 years of age with and without breast cancer were divided into two groups: Group A, composed of women without breast cancer (controls, n = 26) and Group B, composed of women with breast cancer (cases, n = 29). Plasma and erythrocyte zinc levels were measured by flame atomic absorption spectrophotometry at gamma = 213.9 nm. Diet was assessed using the 3-day diet recall method and analyzed using the NutWin software program, version 1.5. Student`s t-test was used to compare means and significance was established at p <0.05. Results: Mean plasma zinc levels were 69.69 +/- 9.00 g/dt, in the breast cancer patients and 65.93 +/- 12.44 g/dt. in the controls (p = 0.201). Mean erythrocyte zinc level was 41.86 +/- 8.28 mu gZn/gHb in the cases and 47.93 +/- 7.00 mu gZn/gHb in the controls (p < 0.05). In both groups, dietary zinc levels were above the estimated average requirement. Conclusions: The present results suggest that zinc levels are lower in the erythrocyte compartment of premenopausal women with breast cancer.

The anti-cancer agent nemorosone is a new potent protonophoric mitochondrial uncoupler

Nemorosone, a natural-occurring polycyclic polyprenylated acylphloroglucinol, has received increasing attention due to its strong in vitro anti-cancer action. Here, we have demonstrated the toxic effect of nemorosone (1-25 mu M) on HepG2 cells by means of the MTT assay, as well as early mitochondrial membrane potential dissipation and ATP depletion in this cancer cell line. In mitochondria isolated from rat liver, nemorosone (50-500 nM) displayed a protonophoric uncoupling activity, showing potency comparable to the classic protonophore, carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Nemorosone enhanced the succinate-supported state 4 respiration rate, dissipated mitochondrial membrane potential, released Ca(2+) from Ca(2+)-loaded mitochondria, decreased Ca(2+) uptake and depleted ATP. The protonophoric property of nemorosone was attested by the induction of mitochondrial swelling in hyposmotic K(+)-acetate medium in the presence of valinomycin. In addition, uncoupling concentrations of nemorosone in the presence of Ca(2+) plus ruthenium red induced the mitochondrial permeability transition process. Therefore, nemorosone is a new potent protonophoric mitochondrial uncoupler and this property is potentially involved in its toxicity on cancer cells. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

In vitro cultivation of Wolbachia pipientis in an Aedes albopictus cell line

A continuous cell line, Aa23, was established from eggs of a strain of the Asian tiger mosquito, Aedes albopictus, naturally infected with the intracellular symbiont Wolbachia pipientis. The resulting cell line was shown to be persistently infected with the bacterial endosymbiont. Treatment with antibiotics cured the cells of the infection. In the course of establishing this cell line it was noticed that RFLPs in the PCR products of two Wolbachia genes from the parental mosquitoes were fixed in the infected cell line. This indicates that the mosquito host was naturally superinfected with different Wolbachia strains, whereas the infected cell line derived from these mosquitoes only contained one of the original Wolbachia strains. The development of anin vitroculture system for this fastidious microorganism should facilitate molecular analysis of the reproduction distorting phenotypes it induces in natural arthropod hosts.

The effect of mammographic screening on invasive breast cancer in Western Australia

Objective: To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. Design: Population-based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. Setting: Western Australia (population 1.8 million), Active recruitment of women aged 50-69 years for mammographic screening began in 1989. Main outcome measures: Size and stage of invasive breast cancers at diagnosis. Results: From 1989 to 1994, the age-standardised incidence rose from 109 to 123 per 100 000 woman-years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of impalpable tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumours that were negative on assays for oestrogen and progesterone receptors. Conclusions: A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.

Early diagnosis of lymphedema in postsurgery breast cancer patients

Lymphedema is an accumulation of lymph fluid in the limb resulting from an insufficiency of the lymphatic system. It is commonly associated with surgical or radiotherapy treatment for breast cancer. As with many progressively debilitating disorders, the effectiveness of treatment is significantly improved by earlier intervention. Multiple frequency bioelectrical impedance analysis (MFBIA) previously was shown to provide accurate relative measures of lymphedema in the upper limb in patients after treatment for breast cancer, This presentation reports progress to date on a three-year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in breast cancer patients following treatment. Bioelectrical impedance measurements of each upper limb were recorded in a group of healthy control subjects (n = 50) to determine the ratio of extracellular limb-fluid volumes. From this population, the expected normal range of asymmetry (99.7% confidence) between the limbs was determined, Patients undergoing surgery to treat breast cancer were recruited into the study, and MFBIA measurements were recorded presurgery, at one month and three months after surgery, and then at two-month intervals for up to 24 months postsurgery, When patients had an MFBIA measure outside the 99.7% range of the control group, they were referred to their physician for clinical assessment. Results to date: Over 100 patients were recruited into the study over the past two years; at present, 19 have developed lymphedema and, of these, 12 are receiving treatment. In each of these 19 cases, MFBIA predicted the onset of the condition up to four months before it could be clinically diagnosed. The false-negative rate currently is zero, The study will continue to monitor patients over the remaining year to accurately ascertain estimates of specificity and sensitivity of the procedure.

Absolute risk of breast cancer for Australian women with a family history

Background: The purpose of the present paper was to estimate the absolute risk of breast cancer over the remainder of a lifetime in Australian women with different categories of family history. Methods: Age-specific breast cancer incidence rates were adjusted for screening effects, and rates in those with no family history were estimated using the attributable fraction (AF). Relative risks from a published meta-analysis were applied to obtain incidence rates for different categories of family history, and age-specific incidence was converted to cumulative risk of breast cancer. The risk estimates were based upon Australian population statistics and published relative risks. Breast cancer incidence was from New South Wales women for 1996. The AF was calculated using prevalence of a family history of breast cancer from data on Queensland women. The cumulative absolute risk of breast cancer was calculated from decade and mid-decade ages to age 79 years, not adjusted for competing causes of death. Results: Lifetime risk is approximately 8.6% (1 in 12) for the general population and 7.8% (1 in 13) for those without a family history. Women with one relative affected have lifetime risks of 1 in 6-8 and those with two relatives affected have lifetime risks of 1 in 4-6. The cumulative residual lifetime risk decreases with advancing age; by age 60 years all groups with only one relative affected have well above a 90% probability of not developing breast cancer to age 79 years. Conclusions: These Australian risk statistics are useful for public information and in the clinical setting. Risks given here apply to women with average breast cancer risk from other risk factors.

Estradiol-regulated expression of the immunophilins cyclophilin 40 and FKBP52 in MCF-7 breast cancer cells

The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with the unactivated estrogen receptor in mutually exclusive heterocomplexes and may differentially modulate receptor activity, We have recently shown that CyP40 and FKBP52 mRNA's are differentially elevated in breast carcinomas compared with normal breast tissue. Other studies suggest that such alterations ill the ratio of immunophilins might potentially influence steroid receptor function. Studies were therefore initiated to investigate the influence of estradiol on CyP40 and FKBP52 expression in MCF-7 breast cancer cells. Over a 24-h-treatment period with estradiol, CyP40 and FKBP52 mRNA expression was increased approximately five- and 14-fold, respectively. The corresponding protein levels were also elevated in comparison to controls. The antiestrogen, ICI 182,780, was an antagonist for CyP40 and FKBP52 mRNA induction. Cycloheximide treatment did not inhibit this increased immunophilin expression, suggesting that estradiol-mediated activation is independent off de novo protein synthesis. Treatment of MCF-7 cells with estradiol resulted in an increased half-life of both CyP40 and FKBP52 mRNA, as determined by actinomycin D studies. These results suggest that estradiol regulates CyP40 and FKBP52 mRNA expression through both transcriptional and posttranscriptional mechanisms. (C) 2001 Academic Press.