Palladium(II) Complexes with Thiosemicarbazones. Syntheses, Characterization and Cytotoxicity against Breast Cancer Cells and Anti-Mycobacterium tuberculosis Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer

To evaluate the relationship between carotenoid concentrations in serum and breast tissue, we measured serum carotenoid concentrations and endogenous carotenoid levels in breast adipose tissue of women with benign breast tumor (n = 46) or breast cancer (n = 44). Before extraction, serum was digested with lipase and cholesterol esterase, and breast adipose tissue was saponified. Serum and tissue carotenoids were extracted with ether/hexane and measured by using HPLC with a C30 column. Serum retinoic acid was extracted with chloroform/methanol and measured using HPLC with a C18 column. There were no significant differences in serum carotenoids [lutein, zeaxanthin, cryptoxanthin (both α- and β-), α-carotene, all-trans β-carotene, 13-cis β-carotene and lycopene], retinoids (retinol, all-trans and 13-cis retinoic acids), and α- and -γ- tocopherol concentrations between benign breast tumor patients and breast cancer patients. A substantial amount of 9-cis β- carotene was present in adipose tissue and was the only carotenoid that had a significantly lower level in benign breast tumor patients than in breast cancer patients. Correlations between carotenoid concentrations in serum and in breast adipose tissue were determined by combining the data of the two groups. Concentrations of the major serum carotenoids except cryptoxanthin showed significant correlations with breast adipose tissue carotenoid levels. When the concentrations of serum carotenoids were adjusted for serum triglycerides or LDL, correlations between serum carotenoid concentrations and breast adipose tissue carotenoid levels markedly increased, including that of cryptoxanthin (P <0.001). The strong correlation between serum carotenoid concentrations and endogenous breast adipose tissue carotenoid levels indicate that dietary intake influences adipose tissue carotenoid levels as well as serum concentrations, and that adipose tissue is a dynamic reservoir of fat-soluble nutrients.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Infertility represents one of the main long-term consequences of combination chemotherapy used for the treatment of breast cancer. Approximately 60%-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ tumors with respect to recurrence-free survival and overall survival, Presentation of the hypothesis: It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. Testing the hypothesis: Assessment of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen. The recurrence-free survival and overall survival should be analysed. Implications of the hypothesis: The major implication will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

A Pilot Study Addressing the Impact of Religious Practice on Quality of Life of Breast Cancer Patients During Chemotherapy

The aim of this preliminary study was to investigate whether religious practice can modify quality of life (QoL) in BC patients during chemotherapy. QoL and religion practice questionnaire (RPQ) scores were evaluated in a sample of BC patients in different moments. Before chemotherapy initiation, women with lower physical and social functional scores displayed higher RPQ scores. On the other hand, low RPQ patients worsened some QoL scores over time. Body image acceptance was positively correlated with religious practice and specifically praying activity. This preliminary study suggests the importance of religion in coping with cancer chemotherapy. © 2011 Springer Science+Business Media, LLC.

New ruthenium(II)/phosphines/diimines complexes: Promising antitumor (human breast cancer) and Mycobacterium tuberculosis fighting agents

The synthesis and characterization of ruthenium compounds of the type [RuCl2(P)2(N-N)] [(P)2 = (PPh3) 2, dppb = 1,4-bis(diphenylphosphino)butano; dppp = 1,3-bis(diphenylphosphino)propane; N-N = 5,5′-dimethyl-2,2′dipyridyl (5,5′-mebipy) or 4,4′-dimethyl-2,2′dipyridyl (4,4′-mebipy)] are described. The complexes were characterized using elemental analysis, UV-Vis and infrared spectroscopies, cyclic voltammetry, and X-ray crystallography. In vitro evaluation of the complexes, using the MTT methodology, revealed their cytotoxic activities in a range of 5.4-15.7 μM against the MDA-MB-231 breast tumor cells and showed that, in this case, they are more active than the reference metallodrug cisplatin. The in vitro antimycobacterial activities of the complexes had their Minimum Inhibitory Concentration (MIC) for MTB cell growth measured, by the REMA method. The MICs for these complexes were found to be between 12.5 and 25.0 μg/mL. The results are comparable with the second line drug cycloserine (MIC = 12.5-50.0 μg/mL), commonly used in the treatment of TB. © 2013 Elsevier Ltd. All rights reserved.

Risk of metabolic syndrome in postmenopausal breast cancer survivors

The aim of this study was to assess the risk of metabolic syndrome (MetS) in postmenopausal breast cancer survivors as compared with postmenopausal women without breast cancer. METHODS: In this cross-sectional study, 104 postmenopausal breast cancer survivors were compared with 208 postmenopausal women (controls) attending a university hospital. Eligibility criteria included the following: amenorrhea longer than 12 months and aged 45 years or older, treated for breast cancer, and metastasis-free for at least 5 years. The control group consisted of women with amenorrhea longer than 12 months and aged 45 years or older and without breast cancer, matched by age and menopause status (in a proportion of 1:2 as sample calculation). Clinical and anthropometric data were collected. Biochemical parameters, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and C-reactive protein, were measured. Women showing three or more diagnostic criteria were diagnosed as having MetS: waist circumference of 88 cm or larger, blood pressure of 130/85 mm Hg or higher, triglycerides level of 150 mg/dL or higher, high-density lipoprotein cholesterol level lower than 50 mg/dL, and glucose level of 100 mg/dL or higher. For statistical analysis, Student's t test, χ2 test, and logistic regression (odds ratio [OR]) were used. RESULTS: The mean (SD) age of breast cancer survivors was 60.6 (8.6) years, with a mean (SD) follow-up of 9.4 (4.4) years. A higher percentage of breast cancer survivors (46.2%) were obese as compared with controls (32.7%; P < 0.05), and a smaller percentage showed optimal values for low-density lipoprotein cholesterol, glucose, and C-reactive protein versus controls (P < 0.05). MetS was diagnosed in 50% of breast cancer survivors and in 37.5% of control group women (P < 0.05). Among the MetS diagnostic criteria, the most prevalent was abdominal obesity (waist circumference >88 cm), affecting 62.5% and 67.8% of the participants, respectively. In the control group, breast cancer survivors had a higher risk for MetS (OR, 1.66; 95% CI, 1.04-2.68), dysglycemia (OR, 1.05; 95% CI, 1.09-3.03), and hypertension (OR, 1.71; 95% CI, 1.02-2.89). CONCLUSIONS: Postmenopausal breast cancer survivors present a higher risk of developing MetS as compared with women without breast cancer. © 2012 by The North American Menopause Society.

Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an 'establishment' phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. © 2013 Spandidos Publications Ltd. All rights reserved.

Clinicopathological significance of ERCC1 expression in breast cancer

The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in different types of cancer. The aim of the present study was to evaluate the clinicopathological significance of ERCC1 expression in breast cancer patients. We analyzed the immunohistochemical expression of ERCC1 in a tissue microarray from 135 primary breast carcinomas and correlated the immunohistochemical findings with clinicopathological factors and outcome data. ERCC1 expression analysis was available for 109 cases. In this group, 58 (53.2%) were positive for ERCC1. ERCC1-positive expression was correlated with smaller tumor size (P=0.007) and with positivity for estrogen receptor (P=0.040), but no correlation was found with other clinicopathological features. Although not statistically significant, triple negative breast cancers were more frequently negative for ERCC1 (61.5% of the cases) compared to the non-triple negative breast cancer cases (41.5%). In conclusion, ERCC1 expression correlated significantly with favorable prognostic factors, such as smaller tumor size and ER-positivity, suggesting a possible role for ERCC1 as a predictive and/or prognostic marker in breast cancer. © 2013 Elsevier GmbH.

Role of Ca, Fe, Cu and Zn in breast cancer: Study by X-ray fluorescence techniques and immunohistochemical analysis

In recent years, several studies have shown that concentrations of trace elements are altered in neoplastic breast tissues. However, the microenvironment and metabolic changes caused by tumors are complex and still not completely understood. Under this aspect, the combination of different techniques to investigate the role of trace elements in promoting and/or maintaining a tumor is interesting once the combination of information obtained by analytical techniques and immunohistochemical assays, associated with clinicopathological data, may allow a better metabolic understanding of trace elements in breast cancer. In this work, the role of the trace elements Ca, Fe, Cu and Zn in neoplastic breast tissues was investigated by X-ray fluorescence (XRF) techniques and immunohistochemical assays. We determined concentrations of Ca, Fe, Cu and Zn in normal and neoplastic breast tissues using energy dispersive XRF, and these values were used to set the positive or negative expression of elements in normal and neoplastic tissues. These expressions were correlated with the spatial distributions of trace elements (evaluated by micro-XRF) and with immunoexpression of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs and vascular endothelial growth factor. The results revealed that the expression of the trace elements Fe, Cu and vascular endothelial growth factor are related, indicating that higher levels of these elements can be associated with the angiogenic process in breast cancer. Also, associations between Ca, Zn and MMPs expression have been observed, possibly because of the fact that both metals are present in these proteins. © 2013 John Wiley & Sons, Ltd.

Glutathione and glutathione peroxidase expression in breast cancer: An immunohistochemical and molecular study

The use of prognostic markers for breast cancer allows therapeutic strategies to be defined more efficiently. The expression of glutathione (GSH) and glutathione peroxidase (GPX) in tumor cells has been evaluated as a predictor of prognosis and response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results showed that high GSH expression was associated with tumors negative for the estrogen receptor (ER) (P<0.05), and GPX expression was associated with tumors negative for the progesterone receptor (PR) and patient mortality. Focusing on the 37 patients who received adjuvant chemotherapy/radiotherapy (Group I), high expression of GPX was associated with a high rate of patient mortality (P<0.05). The 19 patients who received only adjuvant chemotherapy (Group II) showed high expression of GSH in relation to metastasis (P<0.05). In addition, high levels of GPX expression were significantly associated with a shorter overall survival (P<0.05). To confirm this, the expression of precursor genes of GSH [glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS)] and the GPX gene was analyzed using quantitative PCR in cultured neoplastic mammary cells treated with doxorubicin. Doxorubicin treatment was able to eliminate tumor cells without alterations in the gene expression of GSS, but led to underexpression of the GCLC and GPX genes. Our results suggest that high levels of GPX may be related to the development of resistance to chemotherapy in these tumors, response to treatment and the clinical course of the breast cancer patients.

Development and characterization of a new bio-nanocomposite (bio-NCP) for diagnosis and treatment of breast cancer

Breast cancer is a public health problem throughout the world. Moreover, breast cancer cells have a great affinity for hydroxyapatite, leading to a high occurrence of bone metastasis. In this work we developed a bio-nanocomposite (bio-NCP) in order to use such affinity in the diagnosis and treatment of breast cancer. The bio-NCP consists of magnetic nanoparticles of Mn and Zn ferrite inside a polymeric coating (chitosan) modified with nanocrystals of apatite. The materials were characterized with synchrotron X-ray Powder Diffraction (XPD), Time-of-Flight Neutron Powder Diffraction (NPD), Fourier Transformed Infra-red Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and magnetic measurement with a Physical Property Measurement System (PPMS). We obtained ferrite nanoparticles with a high inversion degree of the spinel structure regarding the Fe and Mn, but with all the Zn in the A site. The coating of such nanoparticles with chitosan had no notable effects to the ferrite microstructure. In addition, the polymeric surface can be easily modified with apatite nanocrystals since the hydration of the bio-NCP during synthesis can be controlled. The resulting bio-NCP presents a spherical shape with a narrow size distribution and high magnetic response at room temperature and is a very promising material for early diagnosis of breast cancer and its treatment. © 2013 Elsevier B.V.