Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis.

BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells. METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples. RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS. CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.

Comparison of methods for the isolation of human breast epithelial and myoepithelial cells.

Two lineages, epithelial, and myoepithelial cells are the main cell populations in the normal mammary gland and in breast cancer. Traditionally, cancer research has been performed using commercial cell lines, but primary cell cultures obtained from fresh breast tissue are a powerful tool to study more reliably new aspects of mammary gland biology, including normal and pathological conditions. Nevertheless, the methods described to date have some technical problems in terms of cell viability and yield, which hamper work with primary mammary cells. Therefore, there is a need to optimize technology for the proper isolation of epithelial and myoepithelial cells. For this reason, we compared four methods in an effort to improve the isolation and primary cell culture of different cell populations of human mammary epithelium. The samples were obtained from healthy tissue of patients who had undergone mammoplasty or mastectomy surgery. We based our approaches on previously described methods, and incorporated additional steps to ameliorate technical efficiency and increase cell survival. We determined cell growth and viability by phase-contrast images, growth curve analysis and cell yield, and identified cell-lineage specific markers by flow cytometry and immunofluorescence in 3D cell cultures. These techniques allowed us to better evaluate the functional capabilities of these two main mammary lineages, using CD227/K19 (epithelial cells) and CD10/K14 (myoepithelial cells) antigens. Our results show that slow digestion at low enzymatic concentration combined with the differential centrifugation technique is the method that best fits the main goal of the present study: protocol efficiency and cell survival yield. In summary, we propose some guidelines to establish primary mammary epithelial cell lines more efficiently and to provide us with a strong research instrument to better understand the role of different epithelial cell types in the origin of breast cancer.

Role of oncogenic pathways and KRAS/BRAF mutations in the behavior of colon adenocarcinoma in renal transplant patients.

BACKGROUND: The behavior and mechanisms of colorectal carcinoma in solid organ transplantation have not been well characterized. Our aim was to determine the clinical and molecular phenotypes of colorectal carcinoma in kidney transplant recipients and compare with those in the nonimmunosuppressed population. For the first time, we analyzed the impact of KRAS and BRAF mutations in kidney transplantation. METHODS: Kidney transplant recipients with colorectal carcinoma were diagnosed and followed up from 1992 to 2007. Twelve patients fulfilled inclusion criteria and were matched with the general population with colorectal cancer. To assess the possible mechanisms involved in the clinical behavior of colorectal carcinoma, we compared the tumoral expression by immunohistochemical analysis of molecule markers of mammalian target of rapamycin (mTOR) pathway, angiogenesis and proliferation, and the role of activating mutations in KRAS and BRAF genes. RESULTS: Colorectal carcinoma was more prevalent and exhibited a trend for worse prognosis in transplant patients. Although the mTOR pathway was activated in both populations, activation was lower in transplant patients because of relatively higher phosphatase and tensin homolog expression in the former. Angiogenesis was activated in colorectal carcinoma in both groups. KRAS mutations were found in transplant recipients treated with calcineurin inhibitors and with high expression of phosphatase and tensin homolog. CONCLUSION: The activation of oncogenic pathways could be responsible for the clinical behavior of posttransplant colorectal carcinoma. The mutation status of the KRAS gene is likely involved in mTOR pathway and to be a prognosis marker for colorectal cancer in kidney transplantation.

Gangrena gaseosa espontánea diagnosticada en autopsia. A propósito de un caso y revisión de la literatura / Spontaneous gas gangrene diagnosed on autopsy. A case report and review of the literature

La gangrena gaseosa espontánea es una entidad rara, deevolución fatal y diagnóstico difícil. Está producida porclostridios, se asocia a enfermedades malignas en un altoporcentaje de casos y la puerta de entrada es presumiblementela región ileocecal. Existen muy pocos casos descritosen la literatura. Presentamos un nuevo caso de gangrenagaseosa no traumática, diagnosticada en autopsia(AU)

Spontaneous gas gangrene is a rare and fatal conditionwhich is difficult to diagnose. It is caused by Clostridiumand the majority of cases are associated with malignancy.The portal of entry is thought to be the ileocaecal region.Very few cases have been reported in literature. We describea new case of spontaneous gas gangrene diagnosed onautopsy(AU)

18F-FDG PET/CT for early prediction of response to neoadjuvant chemotherapy in breast cancer.

PURPOSE: The aim of this study was to prospectively evaluate 18F-FDG PET/CT in predicting response to neoadjuvant chemotherapy in large primary breast cancer. METHODS: Fifty consecutive patients underwent PET/CT at baseline and after the second cycle. Baseline MRI was performed to establish tumour size. All findings were confirmed by histopathological analysis. Changes in maximum standardized uptake value (SUV(max)) between baseline study and after two cycles of neoadjuvant chemotherapy (epirubicin + cyclophosphamide + taxanes) were compared using response evaluation criteria in solid tumours (RECIST) criteria and the Miller and Payne (M&P) scale. RESULTS: The mean tumour size was 4.3 +/- 1.4 cm. Forty patients were considered responders and ten as non-responders. SUV(max) changes in patients with good prognosis (M&P grades 4-5) were higher than in patients with bad prognosis (M&P grades 1-3) (p = 0.025). SUV(max) changes between responders and non-responders following RECIST criteria were also statistically significant (p = 0.0028). A cut-off DeltaSUV value of 40% differentiates both groups, with a sensitivity of 77% and a specificity of 80%. CONCLUSION: 18F-FDG PET/CT can predict response to neoadjuvant chemotherapy at an early stage.