18F-Fluorodeoxyglucose PET/CT in a Patient with Esophageal and Genital Leiomyomatosis

Diffuse esophageal leiomyomatosis is a rare benign tumor, which can be associated with leiomyoma in female genital tracts involving the uterus, vagina, and vulva. Alport syndrome, an inherited disorder that includes the kidneys, eyes, and sensorineural hearing loss, is also rarely associated with these multiple leiomyomatosis. In our case, 18F-fluoroseoxyglucose positron emission tomography/computed tomography was used to distinguish esophageal and genital leiomyomatosis from malignant masses

Cleavage of ST6Gal I by Radiation-Induced BACE1 Inhibits Golgi-Anchored ST6Gal I-Mediated Sialylation of Integrin β1 and Migration in Colon Cancer Cells

<p>Abstract</p> <p>Background</p> <p>Previously, we found that β-galactoside α2,6-sialyltransferase (ST6Gal I), an enzyme that adds sialic acids to N-linked oligosaccharides of glycoproteins and is frequently overexpressed in cancer cells, is up-regulated by ionizing radiation (IR) and cleaved to a form possessing catalytic activity comparable to that of the Golgi-localized enzyme. Moreover, this soluble form is secreted into the culture media. Induction of ST6Gal I significantly increased the migration of colon cancer cells via sialylation of integrin β1. Here, we further investigated the mechanisms underlying ST6Gal I cleavage, solubilization and release from cells, and addressed its functions, focusing primarily on cancer cell migration.</p> <p>Methods</p> <p>We performed immunoblotting and lectin affinity assay to analyze the expression of ST6 Gal I and level of sialylated integrin β1. After ionizing radiation, migration of cells was measured by in vitro migration assay. α2, 6 sialylation level of cell surface was analyzed by flow cytometry. Cell culture media were concentrated and then analyzed for soluble ST6Gal I levels using an α2, 6 sialyltransferase sandwich ELISA.</p> <p>Result</p> <p>We found that ST6Gal I was cleaved by BACE1 (β-site amyloid precursor protein-cleaving enzyme), which was specifically overexpressed in response to IR. The soluble form of ST6Gal I, which also has sialyltransferase enzymatic activity, was cleaved from the Golgi membrane and then released into the culture media. Both non-cleaved and cleaved forms of ST6Gal I significantly increased colon cancer cell migration in a sialylation-dependent manner. The pro-migratory effect of the non-cleaved form of ST6Gal I was dependent on integrin β1 sialylation, whereas that of the cleaved form of ST6Gal I was not, suggesting that other intracellular sialylated molecules apart from cell surface molecules such as integrin β1 might be involved in mediating the pro-migratory effects of the soluble form of ST6Gal I. Moreover, production of soluble form ST6Gal I by BACE 1 inhibited integrin β1 sialylation and migration by Golgi-anchored form of ST6Gal I.</p> <p>Conclusions</p> <p>Our results suggest that soluble ST6Gal I, possibly in cooperation with the Golgi-bound form, may participate in cancer progression and metastasis prior to being secreted from cancer cells.</p

Increased IKKα Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors

Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKKα expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKKα in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKKα transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-α6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKKα-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKKα in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-α6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKKα skin tumors

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Childhood blindness in India.

To date there are no published studies on blindness in children or on its incidence. Recently information on the causes of blindness in children identified by community based rehabilitation programmes in two states of India has provided very useful population based data. Prevalence and magnitude of blindness in children in India, avoidable causes and control of blindness in children at the primary, secondary and tertiary levels of health care are discussed in this article along with probable areas of research

Determination of optimal CT exposure factors for lung lesions using an anthropomorphic chest phantom for SPECT-CT

PURPOSE: SPECT‐CT is a valuable modality for diagnosis and staging of primary and secondary malignant disease and also diagnosing benign conditions. CT incurs a significant radiation burden; consequently CT acquisition parameters require optimisation to conform to the ALARP principle. METHOD: An anthropomorphic chest phantom was scanned on the Toshiba Aquilion 16‐ slice MDCT at 135kV, 1mmx16 detector configuration (reconstructed at 3mm slices and 3mm intervals), 320mm FOV with variation of mA (10‐25) and pitch (0.94 and 1.44). Simulated lesions (5, 8 and 10mm at 100HU) were placed in clinically relevant positions within the phantom. 5 image readers of varying CT experience completed the study; data was analysed via Jackknife Free‐Response Receiver Operating Characteristic (JAFROC) and Dorfman‐Berbaum‐Metz Multi‐ Reader Multi‐Case (DBM‐MRMC) analysis. Signal to noise ratio (SNR) was also measured for all simulated lesions. RESULTS: JAFROC method revealed no significant difference between acquisition options (variation of mA and pitch) or image readers (ANOVA). Image readers with experience in producing reports on investigations made a greater number of non‐lesion localisations (NL) (false positives) compared to those who had no reporting responsibility or experience. Reader performance was generally better at lower pitch protocols for the same mA. Increased partial voluming could account for this. CONCLUSION: Results suggest equal performance for acquisition parameters in terms of the localisation information provided. This suggests no significant deterioration in image quality at lower resolutions. Despite this it is thought that low pitch (0.94) techniques should be favoured due to general improved reader performance at this level. No correlation was seen between SNR and JAFROC confidence ratings. Further study would attempt to investigate an even lower mA range for further dose saving potential