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Trufant J Kurz W Frankel A Muthusamy V McKinnon W Greenblatt M Lazar A Cook D Bosenberg M 《Journal of cutaneous pathology》2012,39(4):440-443
Pilomatrixomas are benign follicular tumors that occur most commonly in children. Rare multiple or familial pilomatrixomas have been associated with myotonic dystrophy and other disorders. Although sporadic pilomatrixomas and hybrid cutaneous cysts with pilomatrixoma-like features have been observed in some kindreds with Gardner syndrome, an autosomal dominant form of familial adenomatous polyposis, no definitive association has been made with multiple or familial pilomatrixomas. Here we describe two siblings with multiple pilomatrixomas who were also found to have a family history of colonic adenocarcinoma. Genetic testing revealed a mutation in the 5' portion of the adenomatous polyposis coli (APC) gene, in a region associated with an attenuated APC phenotype. These findings show that multiple pilomatrixomas may be the presenting symptom of patients with APC gene mutations. 相似文献
334.
Selvaraman Nagamani Karthikeyan Muthusamy Palani Kirubakaran Kh Dhanachandra Singh Gopinath Krishnasamy 《Medicinal chemistry research》2012,21(9):2169-2180
Biotin carboxylase (AccC) protein plays an essential role in cell wall biosynthesis in majority of bacterial genera. Inhibition of cell wall biosynthesis might be an ideal way to control the bacterial multiplication in the host system. AccC is one of the promising targets for the antibacterial drugs production. The benzimidazole derivatives are hopeful biotin carboxylase inhibitors, which sensitizes to the Escherichia coli (E. coli) and many other bacterial species too. In steam of developing better benzimidazole derivatives, we describe a quantitative pharmacophore model of benzimidazole derivatives using Phase module of Schr?dinger LLC. This model suggested that the following features are essential for ligand binding, i.e., two aromatic rings, two hydrogen bond donors, one hydrogen bond acceptor, and one hydrophobic group. Further, atom-based 3D-QSAR model was constructed using training set of 37 inhibitors. The constructed QSAR model has cross validated co-efficient value of (Q 2) 0.736 and regression co-efficient value of (R 2) 0.937. The external validation indicated that our QSAR model possessed high predicted powers with $ r_{o}^{2} $ value of 0.933, $ r_{\text m}^{2} $ value of 0.876. The best active and least active compounds were docked into the active site of receptor using Glide and hotspots of the active site were analyzed. The QSAR elucidated here for benzimidazole derivatives combined with their binding information will provide an opportunity to explore the chemical space to promote the potency of AccC inhibitors. 相似文献
335.
Greenblatt DY Kunnimalaiyaan M Chen H 《American journal of surgery》2007,193(3):331-5; discussion 335
BACKGROUND: Gastrointestinal carcinoid tumors are highly metastatic. Activation of the Raf-1 signaling pathway in carcinoid cells results in morphologic changes. These Raf-1-induced structural changes may affect cellular adhesion, thereby altering metastatic potential. METHODS: An estrogen-inducible Raf-1 cell line (BON-raf) was used to study the effects of Raf-1 on cellular adhesion. Cell adhesion was measured before and after Raf-1 induction. Western blot analysis was used to confirm Raf-1 activation and measure levels of an essential adhesion regulator, beta-catenin. RESULTS: Estrogen treatment of BON-raf cells resulted in Raf-1 activation and a marked decrease (68%) in cell adhesion. In the absence of Raf-1 induction, carcinoid cells expressed high levels of beta-catenin. Raf-1 activation led to decreased expression of beta-catenin. CONCLUSIONS: Raf-1 induction in carcinoid cells results in a significant decrease in adhesion. Furthermore, the important adhesion regulator, beta-catenin, is decreased in activated BON-raf cells. These Raf-1-related changes in adhesion may alter the metastatic phenotype of carcinoid cells. 相似文献
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Yang D Thangaraju M Greeneltch K Browning DD Schoenlein PV Tamura T Ozato K Ganapathy V Abrams SI Liu K 《Cancer research》2007,67(7):3301-3309
Apoptotic resistance is often associated with metastatic phenotype in tumor cells and is considered a hallmark of tumor progression. In this study, IFN regulatory factor 8 (IRF8) expression was found to be inversely correlated with an apoptotic-resistant and metastatic phenotype in human colon carcinoma cell lines in vitro. This inverse correlation was further extended to spontaneously arising primary mammary carcinoma and lung metastases in a mouse tumor model in vivo. Exogenous expression of IRF8 in the metastatic tumor cell line restored, at least partially, the sensitivity of the tumor cells to Fas-mediated apoptosis, and disruption of IRF8 function conferred the poorly metastatic tumors with enhanced apoptotic resistance and metastatic capability. DNA demethylation restored IRF8 expression and sensitized the metastatic tumor cells to Fas-mediated apoptosis. Analysis of genomic DNA isolated from both primary and metastatic tumor cells with methylation-sensitive PCR revealed hypermethylation of the IRF8 promoter in metastatic tumor cells but not in primary tumor cells. Taken together, our data suggest that IRF8 is both an essential regulator in Fas-mediated apoptosis pathway and a metastasis suppressor in solid tumors and that metastatic tumor cells use DNA hypermethylation to repress IRF8 expression to evade apoptotic cell death and to acquire a metastatic phenotype. 相似文献
338.
Arya Mariam Roy MD Vasanthan Muthusamy Kumarasamy MBBS Ajay Dhakal MBBS Ruth O’Regan MD Shipra Gandhi MD 《Cancer》2023,129(18):2773-2788
The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)-status to HER2-low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2-low expression has emerged as a targetable biomarker, and anti-HER2 antibody-drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2-low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor–positive and triple-negative BC needs to be reconsidered, as approximately half of these BCs are HER2-low. Although there are different therapeutic agents for hormone receptor–positive and hormone receptor–negative HER2-low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2-low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed. 相似文献
339.
Anil Kumar Patil Karthik Muthusamy Sanjith Aaron Mathew Alexander Nanda Kachare Sunithi Mani Sudhakar Sniya 《Annals of Indian Academy of Neurology》2015,18(3):338-341
Erdheim Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, commonly involving the musculoskeletal system. Other tissue can also be involved, including the central nervous system with wide spectrum of clinical features, at times being nonspecific. This can cause diagnostic dilemmas with delay in diagnosis and initiation of therapy. Here we describe a 63-year-old man who had presented with ataxia and behavioral changes, bony pains, weight loss, and fatigue. His computed tomography (CT), 99Tc scintigraphy and histopathological features on bone biopsy were consistent with ECD. Thus, ECD should be considered as a differential diagnosis in patients presenting with bony pain and nonspecific features of multiorgan involvement. 相似文献
340.