IHC is a reliable screening tool for identification of ALK rearrangement in NSCLC and is antibody dependent. D5F3 (Cell Signaling) and 5A4 (Novocastra) can be used with FISH for identification of IHC-positive cases to reduce screening costs.
Connexin proteins form gap junctions, which permit direct exchange of cytoplasmic contents between neighboring cells. Evidence indicates that gap junctional intercellular communication (GJIC) is important for maintaining homeostasis and preventing cell transformation. Furthermore, connexins may have independent functions including tumor growth suppression. Most tumors express less connexins, have reduced GJIC and have increased growth rates compared with non-tumorigenic cells. The purpose of this study was to determine whether common flavonoids, genistein and quercetin, increase connexin43 (Cx43) levels, improve GJIC and suppress growth of a metastatic human breast tumor cell line (MDA-MB-231). Quercetin (2.5, 5 microg/ml) and genistein (0.5, 2.5, 15 microg/ml) upregulated Cx43 but failed to increase GJIC. Cx43 localized to the plasma membrane following genistein treatment (2.5, 15 mug/ml). In contrast, Cx43 aggregated in the perinuclear region following quercetin treatment (0.5, 2.5, 5, 15 microg/ml). Both genistein (15 microg/ml) and quercetin (2.5, 5, 15 microg/ml) significantly reduced MDA-MB-231 cell proliferation. In summary, genistein and quercetin increase Cx43 and suppress MDA-MB-231 cell proliferation at physiologically relevant concentrations. These results demonstrate that genistein and quercetin are potential anti-breast cancer agents.
The five main subtypes of ovarian surface epithelial carcinoma (high-grade serous, low-grade serous, endometrioid, clear cell and mucinous) are different diseases, with differences in genetic and environmental risk factors, precursor lesions, molecular events during oncogenesis, patterns of spread and response to treatment. With recent advances in surgical pathology, it is possible to reproducibly diagnose these subtypes in routine surgical pathology practice. This review examines these subtypes of ovarian carcinoma, focusing on differential diagnosis, molecular features and current treatment strategies. The increasing understanding of the molecular abnormalities associated with each subtype is leading to exploration and introduction of more subtype-specific treatment of ovarian carcinoma.
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