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[This corrects the article DOI: 10.3389/fonc.2021.640863.].
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Pancreatic cancer has an extremely low prognosis, which is attributable to its high aggressiveness, invasiveness, late diagnosis, and lack of effective therapies. Among all the drugs joining the fight against this type of cancer, microtubule-targeting agents are considered to be the most promising. They inhibit cancer cells although through different mechanisms such as blocking cell division, apoptosis induction, etc. Hereby, we review the functions of microtubule cytoskeletal proteins in tumor cells and comprehensively examine the effects of microtubule-targeting agents on pancreatic carcinoma.
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Bone-related malignancies, such as osteosarcoma, Ewing's sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing's sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing's sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients' chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing's sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing's sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing's sarcoma.
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Background and Aims: The best treatment modalities for elderly patients with stage I-II HCC (hepatocellular carcinoma) remain controversial in an era of a shortage of liver donors. Methods: From the SEER database (Surveillance, Epidemiology, and End Results program), 2,371 elderly patients were sampled as Cohort 1. OS (Overall Survival) and CSS (Cancer-Specific Survival) were compared between the Non-surgery and Surgery groups. A stratification analysis in a CSS Cox model was also conducted among sub-groups, and propensity score matching was performed to generate Cohort 2 (746 pairs), reducing the influences of confounders. Results: For Cohort 1, the median follow-up times of the Non-surgery and Surgery groups were 11 months (95% CI, confidence interval: 9.74-12.26) vs. 49 months (44.80-53.21) in OS, and 14 months (12.33-15.67) vs. 74 months (64.74-83.26) in CSS, respectively. In the stratification analysis, for the elderly patients (age >= 70 years), Larger Resection was associated with a higher HR (hazard ratio) than Segmental Resection: 0.30 (95% CI, confidence interval: 0.22-0.41) vs. 0.29 (0.21-0.38) in 70-74 year-olds; 0.26 (0.18-0.38) vs. 0.23 (0.16-0.32) in 75-79 year-olds; 0.32 (0.21-0.49) vs. 0.21 (0.13-0.32) in those 80+ years old. For Cohort 2, a similar result could be seen in the CSS Cox forest plot. The HRs of Larger Resection and Segmental Resection were 0.27 (0.21-0.33) and 0.25 (0.20-0.31), respectively. Conclusions: It is cautiously recommended that, when liver transplantation is not available, segmental or wedge liver resection is the better treatment choice for elderly patients with stage I-II HCC (AJCC edition 6), especially those over 70 years old, compared with other surgeries, based on the SEER data.
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Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease and has the worst prognosis and survival rate. TUBA1C is a microtubule component implicated in multiple cancers, however, the clinical significance and biological functions of TUBA1C in the progression of PDAC remain unexplored. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) data were employed to detect the TUBA1C mRNA expression and the relation between TUBA1C expression and overall survival (OS) in PDAC. Then, bioinformatic analysis was employed to determine the potential pathway and genes related to TUBA1C. Human pancreatic cancer tissue and adjacent non-tumor tissues samples were detected by immunochemistry (IHC) staining, and the correlation between TUBA1C expression and the clinicopathological features were investigated. Meanwhile, TUBA1C expression in PDAC cell lines was evaluated by western blotting. Furthermore, functional assays including cell viability, apoptosis, cell cycle, transwell assay, wound healing assay, and a xenograft tumor model were performed to determine the oncogenic role of TUBA1C in PDAC, respectively. Results: TUBA1C was overexpressed in the PDAC tissues and cells. IHC analysis showed that the TUBA1C overexpression was associated with short OS. Bioinformatic analysis indicated that TUBA1C overexpression was mainly associated with cell cycle regulation. The downregulation of TUBA1C significantly suppressed cell proliferation, induced cell apoptosis and cycle arrest, and inhibited invasion and migration in PDAC cells. Furthermore, TUBA1C downregulation also inhibited tumor growth in vivo. Conclusion: These findings suggested that TUBA1C downregulation suppressed PDAC aggressiveness via cell cycle pathway and that TUBA1C may serve as a potential prognostic marker for PDAC therapy.
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Pancreatic cancer is a common malignancy that has a poor prognosis and limited therapeutic options. Enhancer of zeste homolog 2 (EZH2) serves a key role in the progression of different types of cancers. The effect of GSK343 (a competitive inhibitor of EZH2) on pancreatic cancer cells was assessed in the present study. Cell viability was evaluated using MTT and cell counting kit-8 assays in AsPC-1 and PANC-1 cells. Flow cytometry and an EdU assay were also performed to assess the effects of GSK343 on cell proliferation, apoptosis and the cell cycle. The induction of autophagy and associated molecular mechanisms were studied using fluorescence microscopy and western blot analysis. The results demonstrated that GSK343 inhibited cell viability in a dose- and time-dependent manner. Furthermore, GSK343 suppressed cell proliferation, promoted apoptosis and blocked cell cycle progression at the G1-phase. Furthermore, GSK343 induced autophagy in pancreatic cancer via the AKT/mTOR signaling pathway. In conclusion, GSK343 exhibited an anti-cancer effect on pancreatic cancer cells, downregulating the AKT/mTOR signaling pathway.
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Objective To evaluate the hemolysis and fatigue resistance self suspension ventricular assist device (NIVAD) in vitro.Methods Resettled NIVAD which is filled with 2 500 ml fresh anticoagulant blood from pig in vitro loop system.The speed of blood pump was adjusted to 8 000 rpm.The afterload and the flow of pump were set as 100 mmHg and 3.5 L/min respectively.Keep the temperature at around 37 degree centigrade which is equal to average internal temperature in pig.Then harvest and measure the free hemoglobin(FHB) of blood samples at different time points before and after working.Then calculated the normalized index of hemoylsis(NIH) by comparing to control group, the unused pig blood at the same period.In fatigue test, conditions remained unchanged, except the blood was replaced by pure water.The blood pump had operated for 90 d continuously and recorded its performance.Results The FHB of experimental blood is higher than that of the control.The normal index of hemolysis NIVAD is(0.0052 ±0.0019)mg/L.Fatigue test , the blood pump operated smoothly, and every parameters was stable.Conclusion The blood pump of NIVAD does a certain degree of destruction to blood, but the NIH is in criterion range of hemolysis, it has certain advantages compared to similar products in china and aboard.At the same time it has good resistance and stable property to fatigue.
