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Wu Yi,1 Tianxin Yang,2 Sisi Lin,1 Rui Hao,1 Jin Yu,1 Ying Wang,1,3 Xiangming Tong2,4 1Phase I Clinical Research Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Hematology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 4The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of ChinaCorrespondence: Xiangming TongThe Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13758183497, Email tongxiangmin@163.comAbstract: Extranodal NK/T cell lymphoma (ENKL) is a rare subtype of lymphoma that shows a poor clinical outcome. The most common sites are the nasal cavity, nasopharynx, paranasal sinuses, tonsils and larynx. Because of P-glycoprotein expression on ENKL cells, ENKL is resistant to anthracycline-based chemotherapy. L-asparaginase-based chemotherapy with or without radiotherapy shows promising outcomes for advanced ENKL, but has limited efficacy in relapsed/refractory ENKL. immune-checkpoint inhibitors, histone deacetylase inhibitors, and monoclonal antibodies are being investigated. In this review, we summarize the new treatments for ENKL.Keywords: extranodal NK/T cell lymphoma, pathway, PD-1, immunotherapy

Objective To examine whether a combinative treatment with curcumin enhances the effects of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib on cell proliferation, clonogenic capacity and apoptosis in the drug-resistant lung cancer cell line NCI-H1975, and further investigate the molecular mechanisms involved. Methods NCI-H1975 cells were treated with curcumin and gefitinib alone or in combination, and cell proliferation, clonogenic capacity and apoptosis were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clone forming experiments, and flow cytometry, respectively, while p38, extracellular regulated protein kinase (ERK)1/2, and protein kinase B (AKT) phosphorylation were examined using Western blotting. Results Compared with the effects of either agent alone, the combination of curcumin and gefitinib had a stronger suppressive effect on proliferation and the clonogenic capacity ( P P P Conclusion Co-treatment of curcumin and gefitinib significantly improves the ability of gefitinib to inhibit cell proliferation, suppress the clonogenic capacity and enhance apoptosis in NCI-H1975 cells, and these effects are possibly mediated via a decrease in phosphorylation of proteins in downstream pathways of the epidermal growth factor receptor.

Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL-60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase-3 activation, and cleavage of poly(ADP-ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT-induced cell death, whereas the expression of bcl-2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia.