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Tumor protein 53 (TP53) mutation predicts an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL), but the molecular basis for this association remains unclear. In several malignancies, the cytidine deaminase apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) has been reported to be associated with the TP53 G/C-to-A/T mutation. Here, we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) than in non-R/R DLBCL, which was positively associated with the APOBEC3B expression level. APOBEC3B overexpression induced the TP53 G/C-to-A/T mutation in vitro, resulting in a phenotype similar to that of DLBCL specimens. Additionally, APOBEC3B-induced p53 mutants promoted the growth of DLBCL cells and enhanced drug resistance. These results suggest that APOBEC3B is a critical factor in mutant p53-driven R/R DLBCL and is therefore a potential therapeutic target.

The fluctuations of fruit market price are mainly related to the fruit output quantity that may be influenced by climate, pest, and many other natural disasters. In this paper, in order to precisely forecast the coming trend of fruit market, image clustering-based deep learning framework is proposed. Initially, a series of data points indicating fruit prices are transformed into a series of fixed-length two-dimensional curve images at intervals, and each image is segmented into the input curve and the output curve. Furthermore, to make training set, K class labels are obtained on the output curves using the Kmeans clustering. Finally, the training set are employed for training convolutional neural network, long short-term memory and the hybrid of convolutional neural network and long short-term memory. The comparative study shows that the convolutional neural network has more advanced capability in predicting the fruit market than the other two, while the prediction accuracy of these trained models may not be sufficiently high.

Hepatoma-derived growth factor (HDGF) is related to tumorigenesis and the development of cancer; it is an independent factor associated with the prognosis of liver cancer, non-small cell lung cancer and pancreatic cancer. However, the molecular mechanism by which HDGF participates in gastric carcinogenesis and development as well as its functional regulation during the development of gastric precancerous lesions needs to be further analyzed. In the present study, we analyzed the effect of HDGF transfection on the proliferation and on the changes of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-κB (NF-κB) pathways in gastric cancer AGS cells. HDGF transfection significantly activated Erk1/2 in AGS cells and promoted anchorage-independent growth. Further studies showed that HDGF expression gradually increased in the gastric carcinogenesis process and HDGF showed a high expression in poorly differentiated adenocarcinoma prone to lymphoid metastasis; these findings suggest that HDGF is involved in the gastric carcinogenesis process and promotes proliferation and metastasis via Erk1/2 activation. (Cancer Sci 2008; 99: 2120–2127)

Protein microarrays for parallel detection of multiple viral antigens and antibodies have not yet been described in the field of human hepatitis virus infections. Here, we describe a simple, rapid and sensitive integrated protein microarray with three different reaction models. The integrated protein microarray could simultaneously determine in human sera two viral antigens (HBsAg, HBeAg) and seven viral antibodies (HBsAb, HBcAb, HBeAb, HCVAb, HDVAb, HEVAb, HGVAb) of human hepatitis viruses within 20 min. The results of the protein microarray were assessed directly by the naked eye but can also be analyzed by a quantitative detector. The detection limit of this protein microarray was 0.1 ng/ml for HBsAg. Overall, >85% concordance was observed between the integrated protein microarrays and an enzyme-linked immunosorbent assay for above hepatitis viral antigen and antibody detections in human sera. This integrated protein microarray can be easily optimized for clinical use and epidemiological screening for multiple hepatitis virus infections.

Human DNA polymerases kappa, eta, iota, and zeta are responsible for the translesion DNA synthesis. Numerous in vitro studies indicated that these enzymes may contribute to DNA lesion-triggered and spontaneous mutation. We measured the transcripts of these 4 enzymes in 131 self-paired cancerous and non-tumor samples, including 23 lung cancers, 49 stomach cancers, and 59 colorectal cancers. Our results indicated that, except pol eta in colorectal cancers, these enzymes are all significantly down-regulated in human lung, stomach, and colorectal cancers, suggesting that these enzymes are probably not closely associated with the elevated mutations in human cancer.

Bcr-Abl tyrosine kinase inhibitors (TKIs) have been a remarkable success for the treatment of Ph+ chronic myeloid leukemia (CML). However, a significant proportion of patients treated with TKIs develop resistance because of leukemia stem cells (LSCs) and T315I mutant Bcr-Abl. Here we describe the unknown activity of the natural product berbamine that efficiently eradicates LSCs and T315I mutant Bcr-Abl clones. Unexpectedly, we identify CaMKII γ as a specific and critical target of berbamine for its antileukemia activity. Berbamine specifically binds to the ATP-binding pocket of CaMKII γ, inhibits its phosphorylation and triggers apoptosis of leukemia cells. More importantly, CaMKII γ is highly activated in LSCs but not in normal hematopoietic stem cells and coactivates LSC-related β-catenin and Stat3 signaling networks. The identification of CaMKII γ as a specific target of berbamine and as a critical molecular switch regulating multiple LSC-related signaling pathways can explain the unique antileukemia activity of berbamine. These findings also suggest that berbamine may be the first ATP-competitive inhibitor of CaMKII γ, and potentially, can serve as a new type of molecular targeted agent through inhibition of the CaMKII γ activity for treatment of leukemia.

Linalool, a natural small molecule monoterpene, has been shown to have anti-tumor activity against several human tumor cell lines in vitro; however, the anti-leukemia spectrum and molecular mechanisms inhibiting tumor cell growth are not fully understood. In the present study, we demonstrated that linalool preferentially induced growth arrest and apoptosis of a variety of human leukemia cells, but spared normal hematopoietic cells. Treatment of leukemia cells by linalool for 12h led to strong activation of p53, cyclin-dependent kinase inhibitors (CDKIs), GADD45alpha, c-jun and phosphorylated-JNK, suggesting that linalool-induced apoptosis might be associated with activation of p53 and CDKIs. The findings here warrant further investigation of this class of natural product as lead compound for developing novel therapeutic agents for leukemia.

In our previous study, we demonstrated that azurin could selectively trigger apoptosis in human osteosarcoma cell line U2OS cells. However, the rate of apoptosis (35.8 ± 3.2%) is not very high, and azurin is too expensive to obtain readily. To solve these problems, we constructed a eukaryotic expression plasmid containing the azurin gene with an influenza virus haemagglutinin 9 peptide HA epitope tag, and transfected the recombinant plasmid pcDNA3.1(+)/azurin into U2OS cells. RT-PCR and Western blot analysis validated the successful transfection and the expression of the azurin-HA protein. Conspicuous apoptosis of the transfected cells was detected by flow cytometry (FCM) and the DNA ladder test. The apoptosis rate reached 64.3 ± 13.1%. The transcriptional levels of the Bax and p53 genes increased significantly in U2OS cells transfected with pcDNA3.1(+)/azurin, but the Bcl-2 mRNA level decreased. There was no difference in the levels of Bcl-xl mRNA and Survivin mRNA. We propose that the transfection of the recombinant plasmid pcDNA3.1(+)/azurin can significantly induce apoptosis in U2OS cells. This is closely associated with the up-regulation of the transcriptional level of the Bax and p53 genes, and the down-regulation of that of the Bcl-2 gene.

Human DNA polymerases kappa, eta, iota, and zeta are responsible for the translesion DNA synthesis. Numerous in vitro studies indicated that these enzymes may contribute to DNA lesion-triggered and spontaneous mutation. We measured the transcripts of these 4 enzymes in 131 self-paired cancerous and non-tumor samples, including 23 lung cancers, 49 stomach cancers, and 59 colorectal cancers. Our results indicated that, except pol eta in colorectal cancers, these enzymes are all significantly down-regulated in human lung, stomach, and colorectal cancers, suggesting that these enzymes are probably not closely associated with the elevated mutations in human cancer.