The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells.

Cancer stem cells (CSCs) are proposed to drive tumor initiation and progression. Yet, our understanding of the cellular and molecular mechanisms that underlie CSC properties is limited. Here we show that the activity of TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in breast CSCs. TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors and have prognostic value. Gain of TAZ endows self-renewal capacity to non-CSCs. In epithelial cells, TAZ forms a complex with the cell-polarity determinant Scribble, and loss of Scribble--or induction of the epithelial-mesenchymal transition (EMT)--disrupts the inhibitory association of TAZ with the core Hippo kinases MST and LATS. This study links the CSC concept to the Hippo pathway in breast cancer and reveals a mechanistic basis of the control of Hippo kinases by cell polarity.

Colitis cystica profunda of the rectum: report of a case and review of the literature.

Colitis cystica profunda is a rare intestinal lesion. Because of its clinical expression (rectorrhagia, mucorrhea and abdominal pain) and the way it appears to current imaging techniques this disease presents features which can be associated with colon neoplasm. Its diagnosis has to be confirmed histologically, and its etiology remains unclear. The following is a case report of colitis cystica profunda recurring 20 years after a first episode in a white woman, who had had an anterior resection of the sigmoid colon and upper rectum to deal with a colitis cystica profunda-induced stenosis of the sigmoid colon and at 41 underwent the transanal removal of a polypoid lesion. A review of 20 cases in the literature showed that colitis cystica profunda has a predilection for the male and generally affects the medial and lower rectum and the sigmoid colon. The literature also confirmed the association with ulcerative rectocolitis, Crohn's disease and rectal prolapse. The type of treatment varies from surgical, medical, and endoscopic to no treatment at all.

Molecular and morphometric description of adipose tissue during weight changes: a quantitative tool for assessment of tissue texture.

The aim of this study was to evaluate the morphometric changes of adipose tissue of lean and obese rats as assessed by computerized image analysis (IA) system in experimental conditions, with different degrees of adiposity. Moreover, to validate measures obtained by image analysis by correlation with direct measures of adiposity (body weight, epididimal fat, mean fat cell size and serum leptin). Finally to correlate these changes to expression of genes involved in lipid deposition and mobilization in adipose tissue. Lean (Fa/?) and genetically obese (fa/fa) Zucker rats were studied. Obese rats were food-restricted or treated with retinoic acid (ATRA) in order to reduce body weight and fat content. Moreover, gene expression of two key enzymes involved in fat metabolism (HSL and DGAT) were assessed in adipose tissue by RT-PCR. Our results show that HSL expression in adipose tissue was lower in obese compared to lean rats (1.47+/-0.02 vs 0.35+/-0.03, p<0.005) and was upregulated during food restriction in obese rats. DGAT expression was similar in lean and obese rats and was reduced by treatment with ATRA in obese rats. Tissue texture assessed by IA was significantly higher in lean compared to obese rats (23.2+/-0.6 vs 11.6+/-2.4%; p=0.01). Tissue structure highly correlated with adiposity in obese rats with different amount of body fat (area fraction vs epididimal fat depot: p=0.001). Distribution of measures for each sample, an index of spread of adipose tissue texture, as expressed by the standard deviation, correlated with adiposity (standard deviation vs epididimal fat depot: p=0.002) thus suggesting that adipose tissue texture increases its heterogeneity when adiposity is lower. This observation is in agreement with the hypothesis that the process of lipid mobilization from adipose tissue is not uniform, but a subpopulation of slimming adipocytes undergoes a complete release of their fat content while the rest of the tissue is much less affected. Moreover, image analysis system seems a reliable quantitative tool for assessment of adipose tissue texture.

Uncommon metastatic site of renal adenocarcinoma: the oral tongue.

Primary tumours metastasizing to the tongue are very unusual and only anecdotal cases have been reported. An exhaustive literature review covering the period from 1970 onwards disclosed only 22 cases of renal adenocarcinoma metastasizing to the tongue. We report the case of an 87-year-old female patient with oral tongue, lung, liver, thyroid gland, pancreas and renal adenocarcinoma metastases. She had undergone contralateral nephrectomy for clear cell carcinoma 10 years before diagnosis of the metastases. The tongue lesion was surgically removed under local anaesthesia. Tongue metastasis of renal adenocarcinoma is usually a manifestation of widespread disease. The prognosis for patients with lingual metastasis of renal adenocarcinoma is poor, the mean interval from diagnosis of tongue metastasis to death being 5.8 months. In our patient, metastatic involvement of the tongue was detected approximately 5 months before death. Treatment of renal adenocarcinoma metastasis to the tongue is usually palliative and aims to provide patient comfort by means of pain relief and prevention of bleeding and infection. Surgical excision is recommended as the primary treatment, with emphasis on preservation of tongue structure and function. Recent data regarding immunotherapy or immunochemotherapy for metastatic renal adenocarcinoma are encouraging.

MALT-type lymphoma and Warthin's tumour presenting in the same parotid gland.

Non-disseminated malignant lymphomas of salivary glands occurring in association with Warthin's tumour have rarely been reported. We describe the first case of association of an extranodal mucosa-associated lymphoid tissue (MALT)-type non-Hodgkin's lymphoma with Warthin's tumour of the parotid gland. Total parotidectomy with preservation of the facial nerve was performed. Surgical and pathological evidence confirmed that the parotid MALT lymphoma did not arise in the lymphoid stroma of the Warthin's tumour. Immunostaining of the MALT lymphoma cells proved negative for Epstein-Barr virus and Helicobacter pylori antibodies and polymerase chain reaction assays did not identify human herpesvirus 8. The patient has been followed up for 11 months, without evidence of recurrent disease. It cannot be ruled out that long-term immunological stimulation by the Warthin's tumour may have caused lymphoid accumulation, chronic stimulation of B cells and extranodal parotid MALT lymphomagenesis.

Medullary thyroid cancer secreting carbohydrate antigen 19-9 (Ca 19-9): a fatal case report.

BACKGROUND: During follow-up for patients with medullary thyroid cancer (MTC), the levels of serum calcitonin and carcinoembryonic antigen are important, and the doubling time of these biomarkers significantly correlates with disease progression. Other antigens are present in tumor tissue and the sera of patients with MTC, but there are scarce published data on the serum levels of carbohydrate antigen 19-9 (Ca 19-9), a tumor marker primarily used for the diagnosis and follow-up of pancreatic and gastrointestinal neoplasias. Recently, the case of a 56-year-old woman with multiple endocrine neoplasia type 2B with high serum levels of Ca 19-9 was reported; this patient experienced rapid disease progression that led to her death. CASE PRESENTATION: A 28-year-old man was referred to the Department of Endocrinology of the University Hospital of Pisa with suspected MTC with laterocervical lymph node metastasis, a single liver lesion (10 mm), several bone metastases, and bilateral pheochromocytomas. RET genetic testing revealed a germline Cys634Arg mutation. During the hospitalization, the carcinoembryonic antigen and Ca 19-9 levels increased while the calcitonin concentration remained stable; despite the apparent stability of the lesions, the condition of the patient worsened rapidly and resulted in death. CONCLUSIONS: High levels of serum Ca 19-9 could be considered a marker of the dedifferentiation of MTC and disease aggressiveness, but additional data on the association between Ca 19-9 and advanced MTC are required to confirm this hypothesis.