Purpose-To study the histopathologic features of CT screen-detected Stage IA adenocarcinomas to determine whether survival differed by the proportion of bronchioloalveolar component (BAC) or by the presence of multiple lesions in node-negative patients.Methods-Five pathologists with expertise in pulmonary pathology examined 279 resected cases of adenocarcinomas, 30 mm or less in length diagnosed by CT screening for lung cancer. The panel determined the consensus diagnosis for each case, identified additional cancers, and classified each case as solitary or non-solitary. The presence and proportion of BAC was also documented.Results-Of the cases of adenocarcinoma, 20 (7%) were BAC subtype, 246 (88%) mixed subtype and 13 (5%) adenocarcinoma-OTHER. BAC cases manifested as non-solid and part solid nodules, mixed as solid and part-solid, and other as solid only. Kaplan-Meier 10-year survival rates were 100% for BAC and adeno-MIXED with 90-99% BAC cases, 95% for mixed with 1-90% BAC, 90% for those without a BAC component, and 75% for other cases. Conflicts of interestThe authors other than Claudia I. Henschke and David F. Yankelevitz indicated no potential conflicts of interest. The potential conflicts of Claudia I. Henschke and David F. Yankelevitz are not related to pathology, but could be interpreted as being related to screening. carcinomas and 44 of these were node negative; the non-solitary node-negative cases had the same excellent prognosis as solitary node-negative cases. NIH Public AccessAuthor Manuscript Lung Cancer. Author manuscript; available in PMC 2010 April 5.Conclusions-The proportion of BAC component was a positive prognostic factor and correlated with CT consistency. Contrary to staging predictions, cases of non-solitary node-negative adenocarcinoma had the same excellent prognosis as solitary node-negative cases, suggesting that most of the small, node-negative multiple carcinomas probably represent multiple primaries rather than intrapulmonary metastasis.

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The elongation of long-chain fatty acids family member 6 (Elovl6) is a key enzyme in lipogenesis that catalyzes the elongation of saturated and monounsaturated fatty acids. Insulin resistance involves upregulation of Elovl6, which has been linked to obesity-related malignancies, including hepatocellular carcinoma (HCC). However, the role of Elovl6 in cancer progression remains unknown. In this study, we analyzed the expression of Elovl6 in 61 clinical HCC specimens. Patients with Elovl6 high-expressing tumors were associated with shorter disease-free survival and overall survival compared to those with Elovl6 low-expressing tumors. Knockdown of Elovl6 in HCC cells reduced cell proliferation and Akt activation, as well as sensitivity to fatty acids. Inhibition of Elovl6 reduced tumor growth and prolonged survival in mice bearing tumors. Taken together, our results indicate that Elovl6 enhances oncogenic activity in liver cancer and is associated with poor prognosis in patients with HCC. Elovl6 may be a therapeutic target for HCC; thus, further studies to confirm this strategy are warranted.

Purpose: Hepatocellular cancer (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-related death worldwide. Cellular immunotherapy against glypican 3 (GPC3) has recently been used in the treatment of HCC, following the success of chimeric antigen receptor (CAR)-T therapy in treatment of B cell malignancy. However, CART cells are not "off-the-shelf" and always cause cytokine release syndrome, which can be eliminated by using natural killer (NK) cells as effector cells. Since a costimulatory signal is necessary for the activation, persistence, or cytotoxicity of CART cells, we speculated that the costimulatory signal is also required for CAR-NK cells in HCC treatment. Methods: Five anti-GPC3 CAR plasmids containing different costimulatory domains were constructed. They included Z (only the CD3ζ domain, no costimulatory domain), CD28.Z (T-cell costimulatory domain CD28), DNAM1/2B4.Z (NK-cell-associated costimulatory domain DNAM1 or 2B4), and DNAM1.2B4.Z (both NK-cell-associated costimulatory domains). Respective CAR-NK-92 cells were generated. The MTT viability assay was performed to evaluate the effect of the different costimulatory domains on CAR-NK-cell proliferation. The effect on persistence was analyzed using an apoptosis assay and flow cytometry. Special cytotoxicity against normal hepatocellular cells and GPC3 + malignant cells was investigated in vitro. The concentration of cytokines (TNF-α and IFN-γ) released by CAR-NK-92 cells was also measured by ELISA. Results: NK-cell-associated costimulatory signal was necessary for CAR-NK-92 cells. CAR-NK-92 cells with DNAM1 and/or 2B4 expanded more quickly and persisted with a lower apoptotic ratio, compared to the presence of CD28 or no costimulatory signal. All CAR-NK-92 cells showed special cellular cytotoxicity in vitro. CAR-NK-92 cells with NK-cell-associated costimulatory domains exhibited higher cytotoxic ability compared with those without any costimulatory domain or with T-cell costimulatory domain. CAR-NK-92 cells with both DNAM1 and 2B4 displayed the highest cytotoxicity. The cytokine release assay results were consistent with those of the cytotoxicity assay. Conclusion: We provided the first evidence supporting a strategy using DNAM1 and 2B4 costimulatory domains to generate anti-GPC3 CAR-NK-92 cells, which exhibits enhanced cytotoxicity against hepatocellular cancer cells in vitro.