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Three-dimensional (3D) printing is a novel promising technology based on 3D imaging and layer-by-layer additive fabrication. It has a profound influence on all aspects of our lives and is playing an increasing important role in many areas including engineering, manufacturing, art, education and medicine. "3D bioprinting" has been put forward with the technical progress in 3D printing and might be a possible way to solve the serious problem of human organ shortage in tissue engineering and regenerative medicine. Many research groups flung them into this area, and have already made some gratifying achievements. However, it is a long way to fabricate a live organ. There are many elements leads to the limitation of 3D bioprinting. This review introduces the background and development history of 3D bioprinting, compares different approaches of 3D bioprinting, and illustrates the key factors of the printing process. Meanwhile, this review also points out existing challenges of 3D bioprinting and has a great prospect. Some points proposed in this review might be served as reference for the research of this field.

Background: Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. Methods: The expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression.Results: We found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3'UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Conclusion: ANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer.

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Liver tumorigenesis Lung metastasis p53 mut/+ Highlights Tsc1 deficiency facilitates p53 (haplo)insufficiency-mediated activation of the PTEN/Akt/mTOR axis to drive HCC tumorigenesis and metastasis. Inhibiting mTOR activation is a potential therapeutic strategy for p53 insufficiency and Tsc1 insufficiency-driven hepatocarcinogenesis. The oncogenic activity of the Akt/mTOR axis relies on Abcc4, which labels an aggressive subtype of human HCC.

Lung cancer treatment remains a challenge for clinical practice and new therapeutic approaches are urgently needed. Loss of functional WEE1 kinase causes DNA replication stress, DNA damage and unscheduled mitotic entry due to elevated CDK activity. The selective WEE1 inhibitor MK-1775 synergize with DNA-damaging agent to inhibit cancer cell growth. Here we report that inhibition of Sirt1 deacetylase through small interfering RNA or selective inhibitor Ex527 greatly enhances MK-1775-induced growth inhibition and apoptosis in human lung cancer cells. We further demonstrate that Sirt1 interacts and deacetylates homologous recombination (HR) repair machinery proteins, including NBS1 and Rad51. Inhibition of Sirt1 impairs HR repair activity, which causes unrepairable damage when combining MK-1775 and Ex527. Meanwhile, combination of MK-1775 and Ex527 induces cooperative antitumor activity in lung cancer xenograft model in vivo. Thus, our study provides a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with very poor prognosis. Therefore, it is important to fully understand the molecular mechanism underlying its occurrence and development. Pumilio RNA-binding family member 1 (PUM1) has been reported to function as an oncogene in ovarian cancer and nonsmall cell lung cancer. However, its role and mechanism in PDAC have not been fully illuminated. Here, we found that the PUM1 protein levels were higher in PDAC tissues than in adjacent tissues and that PUM1 levels were significantly associated with TNM stage and overall survival time, indicating a correlation between high PUM1 expression and poor prognosis in patients with PDAC. In vitro and in vivo assays showed that PUM1 knockdown inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), and promoted apoptosis in MIA PaCa-2 and PANC-1 cells. Through cDNA microarrays and ingenuity pathway analysis, we found that the activation of the eIF2 signaling pathway significantly correlated with PUM1 knockdown. These results were further confirmed by the increased levels of key components of the eIF2 signaling pathway, p-PERK, p-EIF2A, and ATF4 in PUM1 knockdown cells. We also found that PUM1 levels have a significant negative correlation with p-PERK levels in PDAC tissues and that PERK overexpression inhibited cell proliferation, migration, invasion, and EMT, and promoted apoptosis in vitro. Moreover, a PERK inhibitor alleviated the effects of PUM1 knockdown on cell proliferation, apoptosis, migration, invasion, and EMT. Taken together, our results revealed that PUM1 knockdown suppressed cell growth, invasion, and metastasis, and promoted apoptosis by activating the PERK/eIF2/ATF4 signaling pathway in PDAC cells. PUM1 could be a potential target to develop pharmaceuticals and novel therapeutic strategies for the treatment of PDAC.