Primary hepatic gastrointestinal stromal tumor showing remarkable myxoid change and hemangiopericytoma-like pattern

Gastrointestinal stromal tumors (GISTs) in the liver are exceedingly rare. We report a case of hepatic GIST with myxoid changes and hemangiopericytoma-like patterns. A 69-year-old woman presented with epigastric discomfort, and underwent laparotomy for an extruded tumor in the liver. Five years later, recurrent tumor was excised. The primary tumor contained extensive necrotic and myxoid areas. Spindle and epithelioid cells plus a few giant cells with abundant myxoid matrix surrounded the necrotic areas. Immunohistochemically, the spindle cells were distinctly positive for KIT as well as vimentin and smooth muscle actin, leading to a diagnosis of hepatic GIST. The second excised tumor showed increased cellularity and nuclear atypia of epithelioid cells with hemangiopericytoma-like patterns. Although rare, we should consider GIST as a differential diagnosis for a hepatic mesenchymal tumor

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

Background: Hypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited.Methods: Venturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas.Results: The first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P 0.5, P Conclusion: We newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients.</p

TRIM44 Is a Poor Prognostic Factor for Breast Cancer Patients as a Modulator of NF-κB Signaling

Many of the tripartite motif (TRIM) proteins function as E3 ubiquitin ligases and are assumed to be involved in various events, including oncogenesis. In regard to tripartite motif-containing 44 (TRIM44), which is an atypical TRIM family protein lacking the RING finger domain, its pathophysiological significance in breast cancer remains unknown. We performed an immunohistochemical study of TRIM44 protein in clinical breast cancer tissues from 129 patients. The pathophysiological role of TRIM44 in breast cancer was assessed by modulating TRIM44 expression in MCF-7 and MDA-MB-231 breast cancer cells. TRIM44 strong immunoreactivity was significantly associated with nuclear grade (p = 0.033), distant disease-free survival (p = 0.031) and overall survival (p = 0.027). Multivariate analysis revealed that the TRIM44 status was an independent prognostic factor for distant disease-free survival (p = 0.005) and overall survival (p = 0.002) of patients. siRNA-mediated TRIM44 knockdown significantly decreased the proliferation of MCF-7 and MDA-MB-231 cells and inhibited the migration of MDA-MB-231 cells. Microarray analysis and qRT–PCR showed that TRIM44 knockdown upregulated CDK19 and downregulated MMP1 in MDA-MB-231 cells. Notably, TRIM44 knockdown impaired nuclear factor-kappa B (NF-κB)-mediated transcriptional activity stimulated by tumor necrosis factor α (TNFα). Moreover, TRIM44 knockdown substantially attenuated the TNFα-dependent phosphorylation of the p65 subunit of NF-κB and IκBα in both MCF-7 and MDA-MB-231 cells. TRIM44 would play a role in the progression of breast cancer by promoting cell proliferation and migration, as well as by enhancing NF-κB signaling

Primary hepatic gastrointestinal stromal tumor showing remarkable myxoid change and hemangiopericytoma-like pattern

Gastrointestinal stromal tumors (GISTs) in the liver are exceedingly rare. We report a case of hepatic GIST with myxoid changes and hemangiopericytoma-like patterns. A 69-year-old woman presented with epigastric discomfort, and underwent laparotomy for an extruded tumor in the liver. Five years later, recurrent tumor was excised. The primary tumor contained extensive necrotic and myxoid areas. Spindle and epithelioid cells plus a few giant cells with abundant myxoid matrix surrounded the necrotic areas. Immunohistochemically, the spindle cells were distinctly positive for KIT as well as vimentin and smooth muscle actin, leading to a diagnosis of hepatic GIST. The second excised tumor showed increased cellularity and nuclear atypia of epithelioid cells with hemangiopericytoma-like patterns. Although rare, we should consider GIST as a differential diagnosis for a hepatic mesenchymal tumor