Src kinase phosphorylates Caspase-8 on Tyr380: a novel mechanism of apoptosis suppression.

We identified Caspase-8 as a new substrate for Src kinase. Phosphorylation occurs on Tyr380, situated in the linker region between the large and the small subunits of human Procaspase-8, and results in downregulation of Caspase-8 proapoptotic function. Src activation triggers Caspase-8 phosphorylation on Tyr380 and impairs Fas-induced apoptosis. Accordingly, Src failed to protect Caspase-8-defective human cells in which a Caspase-8-Y380F mutant is expressed from Fas-induced cell death. Remarkably, Src activation upon EGF-receptor stimulation triggers endogenous Caspase-8 phosphorylation and prevents Fas-induced apoptosis. Tyr380 is phosphorylated also in human colon cancers where Src is aberrantly activated. These data provide the first evidence for a direct role of tyrosine phosphorylation in the control of caspases and reveal a new mechanism through which tyrosine kinases inhibit apoptosis and participate in tumor progression.

Bilateral synchronous parathyroid carcinoma in a patient on long-term hemodialysis: presentation of a rare clinical case and review literature.

Synchronous bilateral carcinoma of the parathyroid in subjects undergoing prolonged hemodialysis is an extremely rare pathology. After observing a clinical case, we reviewed the literature on parathyroid carcinoma. We describe the clinical case of a 61-year-old man with synchronous bilateral carcinoma of the parathyroid. He had a long history of terminal renal insufficiency and had been undergoing hemodialysis for about 18 years before being referred to us with a diagnosis of secondary hyperparathyroidism. The patient underwent total parathyroidectomy and total thyroidectomy. The interoperative parathormone assay displayed a 68% decrease in parathyroid hormone (PTH) compared with baseline value, and the histologic examination of the two inferior parathyroid glands revealed the presence of invasive parathyroid carcinoma. After reviewing the case, we hypothesized that in the presence of chronic parathyroid stimulation, the hyperplasia of the gland may subsequently be transformed into carcinoma. In patients undergoing hemodialysis, the predominance of females in cases of carcinoma of the parathyroid might be accounted for by a hormonal mechanism or by statistical artifacts attributable to the small number of case histories available. Further analysis was made of the apparently favorable prognosis of this type of patient compared with sporadic parathyroid carcinomas; the mean follow-up period reported in the literature was 42.2 months, with a relapse rate of 15.8%.

Epithelioid haemangioendothelioma of the parotid salivary gland: a case report.

Haemangioendothelioma is a vascular tumour characterised by the proliferation of endothelial cells with an epithelioid appearance. The behaviour of this neoplasm is intermediate between haemangioma and angiosarcoma. It may be localised in a wide range of sites, with a preference for soft and bone tissue. It is only rarely localised in the head and neck and even more rarely in the salivary glands. We describe a case of haemangioendothelioma in a 28-year-old man that originated in the retroneural region of the parotid gland, compressing the gland tissue and posteriorly infiltrating the muscular plane. A total parotidectomy surgical operation including the removal of lymph nodes in the region was performed followed by radiotherapy. An immunohistochemical investigation, carried out using the oxidase-antiperoxidase method, indicated that the neoplastic elements of the marker of the endothelial cells CD34 were positive for vimentine and for muscle-specific actin, showing a moderate proliferative action of the cellular elements with MIB-1 positivity estimated at around 6%. The peculiarity of the case we describe resides in the rarity of the haemangioendothelioma localisation in the parotid gland.

Expression of the proto-oncogene c-KIT in normal and tumor tissues from colorectal carcinoma patients.

BACKGROUND AND AIMS: The proto-oncogene c-KIT encodes a tyrosine kinase receptor essential during embryonic development and postnatal life. Although deregulated expression of c-KIT has been reported, its role in colorectal carcinoma remains controversial: some authors have described a correlation between c-KIT expression and colorectal cancer (CRC), while others have failed to detect the receptor in the majority of neoplasia examined. To address this question, we designed a prospective study to analyze the expression of c-KIT in normal and neoplastic colonic mucosa of the same patient. PATIENTS AND METHODS: We analyzed the tissues of 20 patients undergoing surgical resection for colorectal carcinoma by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry, whose results were correlated with histopathological parameters. RESULTS: Most patients (90%) showed c-KIT expression in normal tissue both at RNA and protein level, while in neoplastic tissue it was observed in 30% of patients at RNA level and in 10% at protein level. By immunohistochemistry the localization of c-KIT protein in the normal colon was restricted to interstitial cells scattered in the stroma, whereas the non-neoplastic epithelium was always negative. The mucinous carcinomas were all c-KIT negative, whereas the only case in which c-KIT was displayed in the neoplastic epithelium was a G3 adenocarcinoma. CONCLUSION: Most colorectal carcinomas do not express c-KIT. We suggest that c-KIT expression is rarely present in this neoplasia; thus, the use of receptor inhibitors should be conducted in selected sub-groups of colon carcinoma patients, subsequent to the clear demonstration of c-KIT overexpression in the neoplastic cells.