Medical Oncology

Multiple myeloma (MM) is the second most common hematopoietic malignancy characterized by plasma cell proliferative disorder. In this study, we disclosed that expression of BUB1B significantly increased in high-risk myeloma patients especially in the most aggressive myeloma genetic subgroups of proliferation. Increased BUB1B expression promotes MM cell proliferation. Mechanism study showed that BUB1B expression was highly correlated to CDC20 and CCNB1/2 expression in MM cells, leading to increased MM cell proliferation. Therefore, BUB1B may be a potential target for MM treatment especially for high-risk MM patients.

CC chemokine receptor-9 (CCR9) is highly expressed in non-small cell lung cancer (NSCLC) tissues and cell lines. However, the biological functions and the signals elicited by the interaction between CCR9 and its natural ligand CCL25 in NSCLC are unknown. Here, we selectively depleted CCR9 and inhibited CCR9–CCL25 interaction in NSCLC cells using small recombinant lentivirus-mediated miRNA, and investigated the tumorigenic effects in vitro and in vivo. Compromised CCR9–CCL25 interaction promoted apoptosis in NSCLC cells by activating phosphoinositide 3-kinase (PI3K)/Akt in vitro. In addition, we showed that CCR9–CCL25 interaction mediated the activation of the PI3K/Akt pathway in NSCLC cells, resulting in the up-regulation of anti-apoptotic proteins, as well as the down-regulation of apoptotic proteins in a PI3K-/Akt-dependent manner. These CCR9–CCL25-mediated effects were abrogated in the presence of a PI3K inhibitor (wortmannin 10 nM) or by inhibiting the CCR9–CCL25 interaction through CCR9 silencing, which also suggested that the biological function of CCR9–CCL25 was mainly regulated by PI3K. In vivo studies also demonstrated a significantly lower tumor burden in mice receiving CCR9-silence cells than those in mice receiving control cells. Together, these data suggested that CCR9–CCL25 interaction induced tumorigenesis of NSCLC cells and that this induction might be accomplished through the activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of CCR9–CCL25 interaction and provide clues for identifying novel therapeutic and preventive molecular markers for NSCLC.

The enhancer of zeste homolog 2 (EZH2) is encoded by the Enhancer of zeste 2 polycomb repressive complex 2 subunit gene. EZH2 is involved in the cell cycle, DNA damage repair, cell differentiation, autophagy, apoptosis, and immunological modulation. The main function of EZH2 is to catalyze the methylation of H3 histone of H3K27Me3, which inhibits the transcription of target genes, such as tumor suppressor genes. EZH2 also forms complexes with transcriptions factors or directly binds to the promoters of target genes, leading to regulate gene transcriptions. EZH2 has been as a prominent target for cancer therapy and a growing number of potential targeting medicines have been developed. This review summarized the mechanisms that EZH2 regulates gene transcription and the interactions between EZH2 and important intracellular signaling molecules (Wnt, Notch, MEK, Akt) and as well the clinical applications of EZH2-targeted drugs.

Currently there is no predictor for survival after adjuvant sorafenib in patients with hepatocellular carcinoma (HCC) who have undergone curative resection. Thirty-eight patients who underwent curative resection of HCC received adjuvant sorafenib therapy between August 2009 and March 2012. Clinicopathological parameters including patient factors, tumor factors, liver background, and inflammatory factors (before surgery and dynamic changes after sorafenib therapy) were evaluated to identify predictors for overall survival (OS) and recurrence-free survival (RFS). The recurrence rate, mortality rate, and clinicopathological data were also compared. Increased NLR after sorafenib (HR = 3.199, 95 % CI 1.365–7.545, P = 0.008), increased GGT after sorafenib (HR = 3.204, 95 % CI 1.333–7.700, P = 0.009), and the presence of portal vein thrombosis (HR = 2.381, 95 % CI 1.064–5.328, P = 0.035) were risk factors related to RFS. By contrast, increased NLR after sorafenib was the only independent risk factor related to OS (HR = 4.647, 95 % CI 1.266–17.053, P = 0.021). Patients with increased NLR or increased GGT after sorafenib had a higher incidence of recurrence and death. Patients who had increased NLR tended to have higher preoperative levels of NLR and GGT. There were no differences in clinicopathological factors in patients with increased GGT and decreased GGT. In conclusion, increased NLR predicted a worse OS and RFS in patients with HCC who underwent curative resection with adjuvant sorafenib therapy. Increased GGT predicted a worse OS. NLR and GGT can be monitored dynamically before and after sorafenib therapy.