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News Article | May 16, 2017

A study published now on Nature Communications* shows that breast cancer cells undergo a stiffening state prior to acquiring malignant features and becoming invasive. The discovery made by a research team led by Florence Janody, from Instituto Gulbenkian de Ciencia (IGC; Portugal), identifies a new signal in tumor cells that can be further explored when designing cancer-targeting therapies. The progression of breast cancer disease takes several stages, from a benign lesion to an invasive carcinoma, possibly with metastasis. But actually, only 20 to 50% of benign tumors end up as invasive cancer. Predicting what lesions are within this group could result in a better use of therapeutics accordingly to the severity of the disease. Florence Janody's group has been looking for signals inside the cells that could help predicting benign tumors that will progress to invasive carcinoma. Their attention focus on the cell skeleton - the cytoskeleton --, an intricate network of fibers that can either exert or resist forces, and that may have an impact on tumor invasion and malignancy. These fibers can be organized into distinct architectures to confer cells a more rigid or soft structure. "Previously, it had been shown that cancer cell invasion requires cell softening. What we observed now is that prior to becoming invasive cells undergo a transient stiffening state caused by the accumulation of cytoskeleton fibers ", explains Sandra Tavares, first author of this study. The research team discovered that cell stiffening induces the activity of proteins that promote cell proliferation, driving the growth of benign tumors. Most importantly, this cell rigidity state also triggers the subsequent progression into invasive cancer. The proteins involved in this mechanism were identified by studies on a human breast cell line, which recapitulates the multistep development of breast cancer, and biopsies of breast cancers. The importance of these proteins for the formation of tumors was further confirmed in the fruit fly. Florence Janody says: "Our work adds an important piece to the intricate puzzle of breast tumor progression. Knowing what happens inside the cell before a cell becomes pre-invasive and acquires malignant features may help us predict, in the future, which tumors may result in metastasis. Also, it may help designing therapeutics better tailored for each type of lesion." This study was conducted at the IGC in collaboration with the Instituto de Investigacao e Inovacao em Saude (i3S), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Faculty of Medicine of the University of Porto (Portugal), Biotechnology Center from the Technische Universitat Dresden (Germany), and Ophiomics - Precision Medicine (Portugal). Fundacao para a Ciencia e a Tecnologia, Liga Portuguesa contra o Cancro/Pfizer and Laco Grant in Breast Cancer 2015 funded this research. *Tavares, S., Vieira, A.F., Taubenberger, A.V., Araujo, M., Martins, N.P.S., Bras-Pereira, C., Polonia, A., Herbig, M., Barreto, C., Otto, O., Cardoso, J., Pereira-Leal, J.B., Guck, J., Paredes, J., Janody, F. (2017) Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells. Nature Communications. DOI: 10.1038/NCOMMS15237

Martinez-Mier G.,Corporativo San Gabriel Alacio Perez 928 | Canas-Acar J.,Cirugia Pediatrica | Gomez-Dorantes S.,Pediatria Oncologica | Santos-Aguilar U.,Cirugia | And 2 more authors.
Cirugia y Cirujanos | Year: 2012

Background: mesenchymal hamartoma of the liver is a rare benign liver tumor in children, usually arising from the right liver lobe and represents about 5 to 6% of all primary hepatic tumors. Complete surgical resection of the tumor is curative. Clinical case: a 30 months old male presented with epigastrium abdominal pain and a palpable mass over a period of two days with no other symptom. The mass was excised completely. Postoperatively the patient recovered with an uneventful course and was discharge 13 days following surgery. All microscopic findings were consistent with the diagnosis of mesenchymal hamartoma of the liver. Conclusions: approximately 75% of mesenchymal hamartoma of the liver occur in the right lobe of the liver. Several diagnostic considerations should be elucidated to differentiate these type of tumors in the left lobe from other benign liver tumors. Sometimes a multidisciplinary approach is necessary to complete a successful complete surgical excision. Our case exemplifies a rare entity in a rare location, an adequate treatment in a third level reference hospital setting.

PubMed | Medicina Interna, Gastroenterologia, Radiologia e Imagen and Patologia
Type: | Journal: Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva | Year: 2017

Schwannomas (or neurilemmomas) are slow-growing mesenchymal neoplasms of the peripheral nerve sheath that may arise at almost any anatomical site. Mesentery schwannoma is extremely rare, with less than ten previously described cases. We present the case of a 38-year-old woman with arterial hypertension and chronic kidney disease with an abdominal painless mass of two years duration and an inconclusive pre-operative clinical diagnosis; she was successfully treated by complete surgical resection of the mass. The aim of this report is to recognize the possibility of schwannomas in the differential diagnosis of abdominal slowly growing tumors.

Herkenhoff M.E.,Ciencia Animal Genetica | Gaulke R.,Biomedicina | De Souza J.G.,Biologia | Thome N.S.,Farmaceutica | And 2 more authors.
Jornal Brasileiro de Patologia e Medicina Laboratorial | Year: 2012

Introduction: Prothrombin (factor II) is a blood protein synthesized in the liver in the presence of vitamin K. It is a thrombin precursor, which induces fbrin formation. Prothrombin G20210A mutation and high prothrombin levels have been closely associated with thrombophilia. This allelic variant is a single mutation, also denominated single nucleotide polymorphism (SNP), in which guanine is replaced with adenine in the messenger ribonucleic acid (mRNA) cleavage of nucleotide 20210. The replacement is characterized by the presence of allele A and the absence of mutation in allele G. Objective: To quantify the number of individuals homozygous for allele G, allele A and heterozygotes. The samples were collected in Paraná and Santa Catarina from January 1 st, 2009 to October 10th, 2010 and were sent to Genolab Análises Genéticas. Methods: Analysis of single mutation by polymerase chain reaction in real time (RT-PCR). Results: From 243 individuals, 51.03% were from Paraná and 48.97% were from Santa Catarina. 88.89% individuals were homozygous for G genotype, none of them were homozygous for A. Only 11.11% were heterozygotes. Santa Catarina presented a higher frequency in heterozygous genotype in comparison with Paraná. Conclusion: This study showed that patients with suspected thrombophilia should undergo genotype identifcation in both states.

Cruz-Benitez L.,Servicio de Cirugia Oncologica | Cortes-Cardenas S.A.,Servicio de Cirugia Oncologica | Farias-Alarcon M.A.,Servicios Modulares | Tenorio-Torres J.A.,CMN | And 2 more authors.
Gaceta Mexicana de Oncologia | Year: 2011

Introduction: Myxoid fibrosarcoma or Evans' tumor is an aggressive sarcoma of fibroblastic origin. Histologically, it contains a myxoid matrix. Objective: To report a case of a low-grade myxoid fibrosarcoma and to perform a bibliographic review of the condition. Case Description: A 36 year-old male patient, whose disease started 20 years ago with enlargement of the right lumbosacral region and increased pain with active motion. Computed tomography (CT) showed a 10 x 15 cm right lumbosacral tumor. The patient underwent surgery at some other facility, where wide resection of the tumor was performed and fibromyxoid sarcoma diagnosis was made. The patient was sent to assessment for adjuvant radiotherapy and a 66 Gy total dose radiation therapy was scheduled; however, he did not attend the appointment and was subsequently assessed on November 11 2010 when a 35 x 40 cm, lobulated, exophytic tumor fixed to the lumbar spine was detected in the lumbosacral region. In November 2010, the patient underwent surgery consisting of wide resection of the tumor, facet denervation, and flaps rotation. The pathology report was fibromyxoid sarcoma with surgical margins infiltrated by the tumor. The immunohistochemical report stated the tumor was positive both to vimentin and muscle-specific action. Discussion: Fibromyxoid sarcoma is a rare malignant neoplasm, with less than 150 cases reported worldwide. Hence, the purpose of reviewing this condition as its unusual presentation may lead to diagnostic confusion with other soft tissue sarcomas.

Moreira L.F.,Patologia | Moreira L.F.,Pontifical Catholic University of Minas Gerais | Carvalho M.R.N.V.,Veterinaria | Carvalho M.R.N.V.,Federal University of Minas Gerais | And 3 more authors.
Jornal Brasileiro de Patologia e Medicina Laboratorial | Year: 2010

Introduction; Ghrelin is a 28 amino acid peptide secreted mainly by endocrine cells present in the gastric mucosa and acknowledged as an endogenous releaser of growth hormone. The immunohistochemical expression of ghrelin has been described in neuroendocrine tumors, and it is believed that may exert modulating action related to the growth of these tumors. Objective; To study the presence of ghrelin and preproghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis. Methods; Endoscopic biopsies from 15 patients with neuroendocrine tumor of the gastric mucosa associated with atrophic body gastritis were performed for immunohistochemistry, and specifc chromogranin, ghrelin and preproghrelin antibodies were applied. The immunohistochemical expression was assessed in tumor cells and endocrine micronodular hyperplasia present in mucosa adjacent to the tumor, and it was classifed in relation to the number of stained cells. Results; Chromogranin was positive in 14 out of 15 tumors. Ghrelin and preproghrelin immunoreactive cells were detected in 11 (73%) and 13 (87%) tumors, respectively. There was a signifcant correlation between the immunohistochemical results of both antigen expressions (kappa = 81%). Ghrelin and preproghrelin expression was detected in hyperplastic nodules present in the mucosa adjacent to the tumor in seven and eight cases, respectively. There was no correlation between these results and those observed in neoplastic cells. Conclusion: Ghrelin and preproghrelin immunoreactive cells may be found in variable number in Type I neuroendocrine gastric tumors and in hyperplastic nodules associated with these tumors. However, it remains unclear what role these peptides play on the development of these tumors.

The World Health Organization released the 4th edition of the Classification of Breast Tumors in July 2012. This review summarizes the principal changes that were introduced in the new classification with emphasis on diagnostic and therapeutic implications. The major changes were: (i) the new edition is entirely dedicated to breast tumors; (ii) the epithelial tumors were sorted differently, recognizing nine special types and variants, and eleven rare types of breast tumors apart from invasive ductal carcinoma of no special type. New codes were included for the lobular, medullary, and metaplastic subtypes; (iii) new scores were suggested for the immunohistochemical evaluation of hormone receptor (> 1% positive cells) and human epidermal growth factor receptor 2 (HER2) (> 30% highly positive cells surrounding the whole membrane); (iv) a new approach to molecular and genomic classification of breast cancer was presented including predictive and prognostic tests using gene expression profile; (v) the traditional terminology of intraductal proliferative lesions was maintained and the terminology ductal intraepithelial neoplasia was not recommended; (vi) the prognostic importance of distinguishing atypical lobular hyperplasia and lobular carcinoma in situ (LCIS) within the spectrum of lobular neoplasia was acknowledged; (vii) the columnar cell lesions (columnar cell change and columnar cell hyperplasia without atypia) were excluded from the fiat epithelial atypia group, whose biological behavior is still unknown. It is expected that the widespread use of the new classification by pathologists and oncologists will benefit patients by improving diagnostic and therapeutic decisions.

Siqueira G.G.,Patologia | De Araujo L.C.,University of Brasilia | Rezende G.C.,Cirurgiao Toracico | De Lima N.F.,Hospital Universitario | Marinho L.C.,University of Brasilia
Jornal Brasileiro de Patologia e Medicina Laboratorial | Year: 2012

We present a rare case of thymoma in a 36-year old woman, who was initially diagnosed with severe myasthenia gravis and subsequently undergone surgical resection. During surgery tumor was found at the anterior mediastinum, tightly attached to the phrenic nerve, pleura and pericardium. Histological assessment showed large areas of sclerosis and fibrous collagenous tissue as well as islands of epithelial and lymphoid cells. Sclerosing thymoma, which is a rare subtype of thymoma (< 1%), was diagnosed, thus confirming the first report in Brazil. The patient showed partial improvement of symptoms associated with myasthenia gravis.

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