RT as primary therapy resulted in good outcome in early-stage disease, and the addition of CT to RT was not accompanied by an improvement in survival.

Mitochondrial dysfunction has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through poorly defined mechanisms. Melatonin supplementation has been found to protect liver function in diabetes and obesity. Here, we intensively explored the role and mechanism of melatonin in the development of NAFLD. We demonstrated that the onset of diet-induced NAFLD greatly caused K E Y W O R D SDNA-PKcs, melatonin, mitochondrial fission, mitophagy, NAFLD, NR4A1, p53

Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and lamellipodium formation, resulting into the impairment of lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis.

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Purpose: To determine the clinical characteristics, prognosis, and treatment outcome for patients with nasal natural killer (NK)/T-cell lymphoma (N-NKTL) and Waldeyer ring NK/T-cell lymphoma (WR-NKTL). Experimental Design: A total of 145 patients with N-NKTL and 95 patients with WR-NKTL were compared. Results: Compared with N-NKTL, WR-NKTL exhibited distinct differences in clinical features with a propensity for nodal involvement, more advanced stages, low elevated lactate dehydrogenase, intermediate chemosensitivity, and a favorable prognosis. Compared with patients with WR-NKTL, patients with N-NKTL were associated with a lower overall response (54% versus 89%) and higher persistent or progressive disease after initial chemotherapy (46% versus 11%; P = 0.000). The 5-year overall survival and progression-free survival rates were 67% and 56% for N-NKTL and 65% and 47% for WR-NKTL, respectively. Patients with stage II WR-NKTL showed favorable prognosis compared with those with stage II N-NKTL. Compared with radiotherapy alone, patients with early-stage WR-NKTL that received radiotherapy and chemotherapy showed a superior progression-free survival and improved overall survival. In contrast, the addition of chemotherapy to radiotherapy did not provide any survival benefit for patients with early-stage N-NKTL. Conclusions: N-NKTL and WR-NKTL represent heterogeneous groups with variable clinical features, responses, prognosis, and treatment options.