Genes up- and down-regulated by dermcidin in breast cancer: a microarray analysis

Dermcidin (DCD) is a human gene mapped to chromosome 12q13 region, which is co-amplified with multiple oncogenes with a well-established role in the growth, survival and progression of breast cancers. Here, we present a summary of a DNA microarray-based study that identified the genes that are up- and down-regulated in a human MDA-361 pLKO control clone and three clones expressing short hairpin RNA against three different regions of DCD mRNA. A list of 235 genes was differentially expressed among independent clones (> 3-fold change and P < 0.005). The gene expression of 208 was reduced and of 27 was increased in the three DCD-RNAi clones compared to pLKO control clone. The expression of 77 genes (37%) encoding for enzymes involved in amino acid metabolism, glucose metabolism and oxidoreductase activity and several genes required for cell survival and DNA repair were decreased. The expression of EGFR/ErbB-1 gene, an important predictor of outcome in breast cancer, was reduced together with the genes for betacellulin and amphiregulin, two known ligands of EGFR/ErbB receptors. Many of the 27 genes up-regulated by DCD-RNAi expression have not yet been fully characterized; among those with known function, we identified the calcium-calmodulin-dependent protein kinase-II delta and calcineurin A alpha. We compared 132 up-regulated and 12 down-regulated genes in our dataset with those genes up- and down-regulated by inhibitors targeting various signaling pathway components. The analysis showed that the genes in the DCD pathway are aligned with those functionally influenced by the drugs sirolimus, LY-294002 and wortmannin. Therefore, DCD may exert its function by activating the PI3K/AKT/mTOR signaling pathway. Together, these bioinformatic approaches suggest the involvement of DCD in the regulation of genes for breast cancer cell metabolism, proliferation and survival.

Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3K/Akt and p38MAPK signaling pathways

Glypican-3 (GPC3) is a proteoglycan involved in proliferation and cell survival. Several reports demonstrated that GPC3 is downregulated in some tumors, such as breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their invasive and metastatic capacities, associated with a decrease of their motility and an increase of their cell death. We demonstrated that GPC3 inhibits canonical Wnt signaling, as well as it activates non canonical pathway. Now, we identified signaling pathways responsible for the pro-apoptotic role of GPC3 in LM3 cells. We found for the first time that GPC3 inhibits the PI3K/Akt anti-apoptotic pathway while it stimulates the p38MAPK stress-activated one. We report a concomitant modulation of CDK inhibitors as well as of pro- and anti-apoptotic molecules. Our results provide new clues regarding the mechanism involved in the modulation induced by GPC3 of mammary tumor cell growth and survival.

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.

Discriminant analysis of trace elements in normal, benign and malignant breast tissues measured by total reflection X-ray fluorescence

In this work total reflection X-ray fluorescence spectrometry has been employed to determine trace element concentrations in different human breast tissues (normal, normal adjacent, benign and malignant). A multivariate discriminant analysis of observed levels was performed in order to build a predictive model and perform tissue-type classifications. A total of 83 breast tissue samples were studied. Results showed the presence of Ca, Ti, Fe, Cu and Zn in all analyzed samples. All trace elements, except Ti, were found in higher concentrations in both malignant and benign tissues, when compared to normal tissues and normal adjacent tissues. In addition, the concentration of Fe was higher in malignant tissues than in benign neoplastic tissues. An opposite behavior was observed for Ca, Cu and Zn. Results have shown that discriminant analysis was able to successfully identify differences between trace element distributions from normal and malignant tissues with an overall accuracy of 80% and 65% for independent and paired breast samples respectively, and of 87% for benign and malignant tissues. (C) 2009 Elsevier B.V. All rights reserved.

The Ruthenium Complex cis-(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines

The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

Photodynamic therapy with aluminum-chloro-phtalocyanine induces necrosis and vascular damage in mice tongue tumors

In this paper we describe the efficacy of the liposomal-AlClPc (aluminum-chloro-phthalocyanine) formulation in PDT study against Ehrlich tumor cells proliferation in immunocompetent swiss mice tongue. Experiments were conduced in sixteen tumor induced mice that were divided in three control groups: (1) tumor without treatment; (2) tumor with 100 J/cm(2) laser (670 nm) irradiation; and (3) tumor with AlClPc peritumoral injection; and a PDT experimental group when tumors received AlClPc injection followed by tumor irradiation. Control groups present similar macroscopically and histological patterns after treatments, while PDT treatment induced 90% of Ehrlich tumor necrosis after 24 h of one single showing the efficacy of liposome-AlClPc (aluminum-chloro-phthalocyanine) mediated PDT application, on the treatment of oral cancer. (C) 2008 Elsevier B.V. All rights reserved.

Preliminary study of human breast tissue using synchrotron radiation combining WAXS and SAXS techniques

Using synchrotron radiation, we combined simultaneously wide angle X-ray scattering (WAXS) and small angle X-ray scattering (SAXS) techniques to obtain the scattering profiles of normal and neoplastic breast tissu-es samples at the momentum transfer range 6.28 nm(-1) <= Q(=4 pi.sin(theta/2)lambda) <= 50.26 nm(-1) and 0.15 nm(-1) <= Q <= 1.90 nm(-1), respectively. The results obtained show considerable differences between the scattering profiles of these tissues. We verified that the combination of some parameters (ratio between glandular and adipose peak intensity and third-order axial peak intensity) extracted from scattering profiles can be used for identifying breast cancer. (c) 2009 Elsevier Ltd. All rights reserved.

Management of brachial plexus region tumours and tumour-like conditions: relevant diagnostic and surgical features in a consecutive series of eighteen patients

Tumours of the brachial plexus region are rare and most publications are case reports or studies with a small series of patients. The aim of this study is to present our experience in managing these lesions. We review 18 patients with tumours in the brachial plexus region submitted to surgical treatment in a 6 year period, including their clinical presentation, neuro-imaging data, surgical findings and outcome. The tumours comprised a heterogeneous group of lesions, including schwannomas, neurofibromas, malignant peripheral nerve sheath tumour (MPNST), sarcomas, metastases, desmoids and an aneurysmal bone cyst. The most common presentation was an expanding lump (83.33%). Eleven tumours were benign and 7 were malignant. Neurofibromatosis was present in only 2 patients (11.11%). Gross total resection was achieved in 14 patients and sub-total resection in the others. Only 3 patients presented with new post-operative motor deficits. The incidence of complications was low (16.5 %). The majority of tumours were benign and most of them could be excised with a low incidence of additional deficits. Some of the malignant tumours could be controlled by surgery plus adjuvant therapy, but this category is still associated with high morbidity and mortality rates.

Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis

Purpose: To identify papillary thyroid carcinoma (PTC)-associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue. Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. The BRAF(V600E) mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling. Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAF(V600E) mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway. Conclusion: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for FTC therapy.

Management of Neuroendocrine Tumors: A Meeting of Experts from Latin America

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors ( NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs. Copyright (C) 2008 S. Karger AG, Basel

Immediate Locally Advanced Breast Cancer and Chest Wall Reconstruction: Surgical Planning and Reconstruction Strategies with Extended V-Y Latissimus Dorsi Myocutaneous Flap

Background: Surgical resection in locally advanced breast cancer produces large defects that may not be suitable for primary closure. Immediate reconstruction is controversial and presents a complicated scenario for breast surgeons and plastic surgeons. Methods: In this study, a different design was planned for the latissimus dorsi musculocutaneous flap with primary closure in V-Y for the correction of major lesions in the anterior chest wall. Twenty-five patients underwent immediate locally advanced breast cancer reconstruction with a V-Y latissimus dorsi musculocutaneous flap. This flap was raised from adjacent tissue located on the lateral and posterior thoracic region and presented a triangular shape whose base was the lateral aspect of the mastectomy wound. The technique was indicated in patients with large thoracic wounds. Results: Mean follow-up time was 16 months. Closure was obtained in the donor and recipient sites without the use of skin grafts or other more major procedures. Complications occurred in nine patients (36 percent), including dorsal wound dehiscence in five patients and seroma in three. All cases except one were treated by a conservative approach with a good result. No total flap loss was reported. All patients achieved a satisfactory thoracic reconstruction and adequate wound care. Conclusions: The V-Y latissimus dorsi musculocutaneous flap is a reliable technique for immediate locally advanced breast cancer reconstruction. The technique is advantageous because the V-Y design allows primary closure of the chest wound and donor defect. Success depends on patient selection, coordinated planning with the breast cancer surgeon, and careful intraoperative management. (Plast. Reconstr. Surg. 127: 2186, 2011.)

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation

Purpose: Hepatectomy remains a complex operation even in experienced hands. The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results. Methods: The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan. Surgery was performed by surgeons competent in liver transplantation. As in liver living donor operation, vascular anomalies were investigated. The main arterial anomalies found were the right hepatic artery emerging from the superior mesenteric artery and left hepatic artery from left gastric artery. Hilar structures were dissected very close to liver parenchyma. The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe. During dissection of the suprahepatic veins, the venous infusion was decreased to reduce central venous pressure and potential bleeding from hepatic veins and the vena cava. Results: Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable. There were 31 cases of hepatoblastoma, with a 9.6% mortality rate. Ten children presented with other malignant tumors-3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma. These cases had a 50% mortality rate. Six children had benign tumors-4 mesenchymal hamartoma, 1 focal nodular hyperplasia, and a mucinous cystadenoma. All of these children had a favorable outcome. Hepatic resections included 22 right lobectomies, 9 right trisegmentectomies, 8 left lobectomies, 5 left trisegmentectomies, 2 left segmentectomies, and 1 case of monosegment (segment IV) resection. The overall mortality rate was 14.9%, and all deaths were related to recurrence of malignant disease. The mortality rate of hepatoblastoma patients was less than other malignant tumors (P = .04). Conclusion: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate. (C) 2009 Elsevier Inc. All rights reserved.

Aesthetic Quality of the Nipple-Areola Complex in Breast Reconstruction with a New Local Graft Technique

Reconstruction of the nipple-areola complex (NAC) is the last stage of breast reconstruction and represents the search for symmetry in regard to the contralateral breast. The objective of this study was to present an areola reconstruction technique with local skin graft to improve the texture and aspect of the reconstructed areola, searching for a natural look. This technique was performed on 122 patients who in the period from January 2000 to December 2005 were submitted to nipple and areola reconstruction. Once the position of the new nipple was determined, markings were made for the reconstruction of the areola. Then the external limit of the new areola was incised and the skin was centripetally deepidermized up to 85% of its diameter. After this procedure the detached skin was repositioned in its bed as a graft and sutured with 4.0 mononylon thread. Incisions with an 11-blade scalpel were then made in V and C forms associated with the detachment of this skin of the receptor area along the local graft so that at the end of the healing process they would determine alterations in the areolar texture mimicking the texture of a normal areola. All patients underwent tattooing 3 months after reconstruction of the NAC taking into account the different shades of the contralateral areola and nipple colors. The use of a local skin graft associated with C and V incisions allowed alteration in the texture of the reconstructed areola. The use of different ink shades for tattooing helped to give a tridimensional aspect to this areola. These factors determined a good aesthetic result in these patients. This areola reconstruction using a local skin graft allows change in the areola texture and a tridimensional aspect similar to that of a normal areola without the inconvenience of grafting from a distance.