Oncotarget
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Gastric cancer is the third leading cause of cancer-related mortality worldwide. Chemotherapy is frequently used for gastric cancer treatment. Most patients with advanced gastric cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. ⋯ Disruption of ABCG2 function, through ectopic expression of an ABCG2 dominant negative construct or a specific ABCG2 inhibitor, increased drug sensitivity of cancer cells both in culture and in mice. The relevance of our studies to gastric cancer patient care is reflected by our discovery that high ABCG2 expression was associated with poor survival in the gastric cancer patients who underwent chemotherapy. Taken together, we have identified a molecular mechanism by which gastric cancer cells gain chemotherapy resistance.
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Randomized Controlled Trial
Randomized clinical trial comparing the effects of sevoflurane and propofol on carbon dioxide embolism during pneumoperitoneum in laparoscopic hepatectomy.
Laparoscopic hepatectomy carries a high risk of gas embolism due to the extensive hepatic transection plane and large hepatic vena cava. Here, we compared the influence of inhaled and intravenous anesthetics on gas embolism during laparoscopic hepatectomy. Fifty patients undergoing laparoscopic hepatectomy were divided into two groups to receive sevoflurane anesthesia (group S, n = 25) or intravenous propofol anesthesia (group p, n = 25). ⋯ At the point of the most severe gas embolism, the PTCO2 was higher in group S than group p (44.00±4.47 vs. 41.36±2.77 mmHg, p < 0.05), while the PO2/FiO2 (450.52±54.08 vs. 503.80±63.18, p < 0.05) and pH values (7.35±0.05 vs. 7.38±0.02, p < 0.05) were lower in group S than group P. Patients with a history of abdominal surgery or liver cirrhosis had higher gas embolism grades. Thus volatile anesthetics may lengthen the duration of embolism episodes and worsen hemodynamics and pulmonary blood gas exchange during surgery.
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The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM). ⋯ Treatment decisions driven by tumor genomic analysis can lead to significant clinical benefit in a minority of patients. The success of genomically driven therapy depends both on access to drugs and robustness of bioinformatics analysis. While novel clinical trial designs are increasing the utility of genomic testing, robust data sharing of outcomes is needed to optimize clinical benefit for all patients.
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Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung. ⋯ Cytokine profiling showed that the levels of CXCL16, a chemokine with effects on T cell populations and NKT cells, were significantly lower in lungs of Mcpt4/Mcpt6/Cpa3-deficient animals vs. controls, suggesting that multiple mast cell protease deficiency might affect T cell or NKT cell populations. In line with this, we found that the Mcpt4/Mcpt6/Cpa3-deficiency was associated with a reduction in cells expressing CD1d, a MHC class 1-like molecule that is crucial for presenting antigen to invariant NKT (iNKT) cells. Together, these findings indicate a protective role of mast cell-specific proteases in melanoma dissemination, and suggest that this effect involves a CXCL16/CD1d/NKT cell axis.
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Alpha-fetoprotein-producing gastric cancer (AFPGC) accounts for 1.5%-7.1% of all gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor prognosis. To improve understanding of AFPGC we reviewed a consecutive series of 82 AFPGC patients and investigated the prognostic factors. ⋯ Age, American Joint Committee on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and surgery were prognostic factors for overall survival; however, TNM stage was the only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare, unique, and heterogeneous entity, and its proper identification and treatment remain a challenge. More attention should be paid to AFPGC to improve patient care and the dismal prognosis.