Role of autophagy in acute myeloid leukemia therapy

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Phase Ⅰ clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis

T lymphopenia,occurring in the early phase of sepsis in response to systemic inflammation,is commonly associated with morbidity and mortality of septic infections.We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors(TLRs)mediated hyperinflammation.However,the underlying mechanisms remains unsolved.Herein,we unveil that CD4^(+)T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling.

Effect of increased intra-abdominal pressure and decompressive laparotomy on aerated lung volume distribution

Increased intra-abdominal pressure(IAP) is common in intensive care patients,affecting aerated lung volume distribution.The current study deals with the effect of increased IAP and decompressive laparotomy on aerated lung volume distribution.The serial whole-lung computed tomography scans of 16 patients with increased IAP were retrospectively analyzed between July 2006 and July 2008 and compared to controls.The IAP increased from(12.1±2.3) mmHg on admission to(25.2±3.6) mmHg(P<0.01) before decompressive laparotomy and decreased to(14.7±2.8) mmHg after decompressive laparotomy.Mean time from admission to decompressive laparotomy and length of intensive-care unit(ICU) stay were 26 h and 16.2 d,respectively.The percentage of normally aerated lung volume on admission was significantly lower than that of controls(P<0.01).Prior to decompressive laparotomy,the total lung volume and percentage of normally aerated lung were significantly less in patients compared to controls(P<0.01),and the absolute volume of non-aerated lung and percentage of non-aerated lung were significantly higher in patients(P<0.01).Peak inspiratory pressure,partial pressure of carbon dioxide in arterial blood,and central venous pressure were higher in patients,while the ratio of partial pressure of arterial O2 to the fraction of inspired O2(PaO2/FIO2) was decreased relative to controls prior to laparotomy.An approximately 1.8 cm greater cranial displacement of the diaphragm in patients versus controls was observed before laparotomy.The sagittal diameter of the lung at the T6 level was significantly increased compared to controls on admission(P<0.01).After laparotomy,the volume and percentage of non-aerated lung decreased significantly while the percentage of normally aerated lung volume increased significantly(P<0.01).In conclusion,increased IAP decreases total lung volume while increasing non-aerated lung volume.Decompressive laparotomy is associated with resolution of these effects on lung volumes.

Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with L-serine ligand on septic pigs

A novel adsorber,polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser),was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfusion.Endotoxin adsorption efficiency (EAE) of the adsorber was firstly measured in vitro.The biocompatibility and hemodynamic changes during extracorporeal circulation were then evaluated.One half of 16 pigs receiving lipopolysaccharide (Escherichia coli O111:B4,5 μg/kg) intravenously in 1 h were consecutively treated by hemoperfusion with the new adsorber for 2 h.The changes of circulating endotoxin and certain cytokines and respiratory function were analyzed.The 72 h-survival rate was assessed eventually.EAE reached 46.3% (100 EU/ml in 80 ml calf serum) after 2 hcirculation.No deleterious effect was observed within the process.The plasma endotoxin,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) levels were decreased during the hemoperfusion.Arterial oxygenation was also improved during and after the process.Furthermore,the survival time was significantly extended (>72 h vs.47.5 h for median survival time).The novel product PVDF-Ser could adsorb endotoxin with high safety and efficacy.Early use of extracorporeal hemoperfusion with the new adsorber could reduce the levels of circulating endotoxin,IL-6,and TNF-α,besides improve respiratory function and consequent 72 h-survival rate of the septic pigs.Endotoxin removal strategy with blood purification using the new adsorber renders a potential promising future in sepsis therapy.

Aortoduodenal fistula following aortic reconstruction of a pseudoaneurysm caused by stab wound 12 years ago

Gastrointestinal bleeding due to aortoenteric fistula is extremely rare.Aortoenteric fistula is difficult to be diagnosed timely and entails a significant morbidity and mortality.Herein,we present an uncommon case of gastrointestinal bleeding caused by aortoduodenal fistula,which was a complication of a successful aortic reconstruction 4 months ago for an aortic pseudoaneurysm resulted from a stab wound 12 years ago.An urgent laparotomy confirmed an aortoduodenal fistula and repaired the defects in aorta and duodenum,but a prolonged shock led to the patient's death.In summary,early diagnosis and surgical intervention for aortoenteric fistula are vital for survival.