No abstract

Purpose: Colon cancer is one of the most common human malignancies, yet studies have only begun to identify the multiple mechanisms that underlie the development of this tumor. In this study, we have identified a novel mechanism, dysregulation of endocytic sorting, which promotes colon cancer development. Experimental Design: Immunohistochemical and microarray analyses were done on human colon cancer tissue specimens to determine the levels of one endocytic protein, sorting nexin 1 (SNX1). SW480 cells, a human colon cancer cell line that retains a relatively high level of SNX1 expression, were used to assess the effects of down-regulating this protein by small hairpin RNA. Activation of signal transduction cascades was evaluated in these cells using Western blotting, and multiple functional assays were done. Results: We determined by immunohistochemistry that the level of SNX1 was significantly down-regulated in 75% of human colon cancers. In corroborative studies using microarray analysis, SNX1 message was significantly decreased (log 2 ratio less than À1) for 8 of 19 colon carcinomas. Cell lines with reduced SNX1 levels showed increased proliferation, decreased apoptosis, and decreased susceptibility to anoikis. They also showed increased activation of epidermal growth factor receptor and extracellular signal-regulated kinase 1/2 in response to epidermal growth factor. This increased activation was abolished by inhibition of endocytosis. Conclusions: These data suggest that loss of SNX1 may play a significant role in the development and aggressiveness of human colon cancer, at least partially through the mechanism of increased signaling from endosomes. Further, these findings suggest that dysregulation of endocytic proteins may represent a new paradigm in the process of carcinogenesis.

Biliary duct hamartomas are benign intrahepatic bile duct lesions. Despite being primarily incidental findings on imaging, these lesions can provide a diagnostic conundrum due to their shared characteristics with malignant tumors. The goal of this systematic review is to offer a thorough clinical profile of biliary duct hamartomas. There were 139 cases of biliary duct hamartomas identified in a structured systematic review of the literature. Patient demographics, clinical presentation, significant laboratory and imaging data, diagnostic modalities, treatment choices, and outcomes were all studied and reported. Biliary duct hamartomas present with mild symptoms and laboratory abnormalities, and while being visible on imaging, the results are non-specific and may require biopsy in case of red flag signs such as weight loss and a progressive increase in the size of the lesion. Furthermore, there are currently no published guidelines for the treatment of biliary duct hamartomas, and many people have had surgery despite the clinically benign nature of these abnormalities. As per the findings of the study, individuals who exhibit signs of malignancy should be investigated further. Eyeballing for red flag symptoms, followed by a specialized imaging scan and invasive treatment, is the three-step approach to biliary duct hamartomas. Since our recommendations include a shift in strategy and do not contradict existing rules, there are likely to be few roadblocks to improvement; the key barriers being technological equipment and image quality. In this study, we intended to pave the way for future research in the field. In our opinion, the next decade will bring a better understanding of the characteristics of biliary hamartomas, disease symptoms, and better recognition of any suspicious features. These indications will aid in reducing the number of unneeded surgical or invasive operations. Finally, the findings of these future studies will allow the medical community to improve and provide the best care possible.

No abstract