Cut here to cure: Doxorubicin attached to pH‐sensitive mesoporous silica nanoparticles (MSN‐hydrazone‐Dox) shows potential in the chemotherapeutic treatment of liver cancer. Hydrolysis of the pH‐sensitive hydrazone bond in the acidic environment of endosomes/lysosomes (see picture) releases Dox intracellularly from the MSN nanochannels, resulting in highly efficient apoptotic cell death.

This matched case-control study demonstrated that TaTME is safe and feasible. Compared with LapTME, TaTME not only achieves identical circumferential margin status without compromising other operative and quality parameters but also benefits patients by achieving a longer distal margin. Thus, TaTME has the potential to become an option in managing irradiated rectal cancer.

Multidrug resistance (MDR) is the major clinical obstacle in the management of cancer by chemotherapy. Overexpression of ATP-dependent efflux transporter P-glycoprotein (PGP) is a key factor contributing to multidrug resistance of cancer cells. The purpose of the present study was to use the endosomal pH-sensitive MSN (mesoporous silica nanoparticles; MSN-Hydrazone-Dox) for controlled release of doxorubicin (Dox) in an attempt to overcome the PGP-mediated MDR. In vitro cell culture studies indicate that uptake of MSNHydrazone-Dox by the human uterine sarcoma MES-SA/Dox-resistant tumor (MES-SA/Dx-5) cell occurs through endocytosis, thus bypassing the efflux pump resistance. This improves the efficacy of the drug and leads to significant cytotoxicity and DNA fragmentation evidenced by terminal deoxynucleotidyl transferasemediated dUTP nick end labeling and DNA laddering assays. In vivo studies show that the intratumor injection of MSN-Hydrazone-Dox induces significant apoptosis of MES-SA/Dox-resistant cancer cells. This is validated by active caspase-3 immunohistochemical analysis. However, MSN-Hydrazone, without doxorubicin conjugation, cannot induce apoptosis in vitro and in vivo. In conclusion, both in vitro and in vivo studies show that MSN could serve as an efficient nanocarrier entering cell avidly via endocytosis, thus bypassing the PGP efflux pump to compromise the PGP-mediated MDR. MSN-Hydrazone-Dox could further respond to endosomal acidic pH to release doxorubicin in a sustained manner. Besides the cell study, this is the first report that successfully shows the therapeutic efficacy of using MSN against MDR cancer in vivo. Mol Cancer Ther; 10(5); 761-9. Ó2011 AACR.

Rohr frei zur Krebsbekämpfung: Mit Doxorubicin bestückte pH‐empfindliche mesoporöse Siliciumdioxidnanopartikel (MSN‐Hydrazon‐Dox) eignen sich möglicherweise für die Chemotherapie von Leberkrebs. Nach der Hydrolyse der pH‐empfindlichen Hydrazon‐Verbindung im sauren Milieu von Endosomen/Lysosomen (siehe Bild) wird Dox aus den Nanokanälen der MSNs ins Zellinnere freigesetzt, wo es hoch wirksam eine Apoptose induzieren kann.

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Hybrid NOTES for rectal cancer is safe and feasible. Rapid experience-building accelerates its evolution, as reflected here by the high stapling rate and the idea of a two-team approach. It has the potential to become an option of treating rectal cancers.

Background: Elevated plasma C-terminal fibroblast growth factor-23 (cFGF-23) levels are associated with higher mortality in patients with chronic kidney disease (CKD) and acute kidney injury (AKI). Our study explored the outcome forecasting accuracy of cFGF-23 in critically ill patients with CKD superimposed with AKI (ACKD). Methods: Urine and plasma biomarkers from 149 CKD patients superimposed with AKI before dialysis were checked in this multicenter prospective observational cohort study. Endpoints were 90-day mortality and 90 days free from dialysis after hospital discharge. Associations with study endpoints were assessed using hierarchical clustering analysis, the generalized additive model, the Cox proportional hazard model, competing risk analysis, and discrimination evaluation. Results: Over a median follow up of 40 days, 67 (45.0%) patients died before the 90th day after hospital discharge and 39 (26.2%) progressed to kidney failure with replacement therapy (KFRT). Hierarchical clustering analysis demonstrated that cFGF-23 levels had better predictive ability for 90-day mortality than did other biomarkers. Higher serum cFGF-23 levels were independently associated with greater risk for 90-day mortality [hazard ratio (HR): 2.5; 95% confidence interval (CI) 1.5–4.1; p < 0.001]. Moreover, adding plasma cFGF-23 to the Demirjian AKI risk score model substantially improved risk prediction for 90-day mortality than the Demirjian model alone (integrated discrimination improvement: 0.06; p < 0.05; 95% CI 0.02–0.10). The low plasma cFGF-23 group was predicted having more weaning from dialysis in surviving patients (HR = 0.53, 95% CI, 0.29–0.95, p = 0.05). Conclusions: In patients with ACKD, plasma cFGF-23 levels are an independent risk factor to forecast 90-day mortality and 90-day progression to KFRT. In combination with the clinical risk score, plasma cFGF-23 levels could substantially improve mortality risk prediction.

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