Effect of dietary arginine supplementation on reproductive performance of mice with porcine circovirus type 2 infection

The objective of this study was to investigate whether supplemental dietary arginine increases reproductive performance in mice infected with porcine circovirus type2 (PCV2). A total of 50KM female mice were allotted randomly to the arginine group (0.6% arginine + gestation diet) and control group (1.22% alanine + gestation diet). All the mice began to mate after 14 days of treatment with our prepared feed and challenged with PCV2 at the dose of 100 TCID50 (50% tissue culture infection dose, TCID50) after 7 days of pregnancy. Abortion rate, litter number, litter birth weight, the daily weight gain in the first 7 days and survival rate in the first 2 weeks of the neonates were calculated. The serum progesterone, estrogen, nitric oxide and superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) on the 14th day of pregnancy were measured. Arginine supplementation decreased the abortion rate of pregnant mice and mortality of neonates caused by PCV2 infection. Further, litter number, litter birth weight and the daily weight gain of neonates increased in the arginine group compared to the control group. Arginine supplementation increased significantly the serum progesterone (P < 0.01) and nitric oxide levels (P < 0.05), but had little effect on the serum estrogen level. SOD activity and T-AOC in the arginine group were significantly higher (P < 0.01) than the control group. In conclusion, arginine supplementation partially reversed the reproductive failure in mice caused by PCV2 infection

Risk Factors and Medico-Economic Effect of Pancreatic Fistula after Pancreaticoduodenectomy

The study aimed to uncover the risk factors for the new defined pancreatic fistula (PF) and clinical related PF (CR-PF) after pancreaticoduodenectomy (PD) surgery and to evaluate the medico-economic effect of patients. A total of 412 patients were classified into two groups according to different criteria, PF and NOPF according to PF occurrence: CR-PF (grades B and C) and NOCR-PF (grade A) based on PF severity. A total of 28 factors were evaluated by univariate and multivariate logistic regression test. Hospital charges and stays of these patients were assessed. The results showed that more hospital stages and charges are needed for patients in PF and CR-PF groups than in NOPF and NOCR-PF groups (P<0.05). The excessive drinking, soft remnant pancreas, preoperative albumin, and intraoperative blood transfusion are risk factors affecting both PF and CR-PF incidence. More professional surgeons can effectively reduce the PF and CR-PF incidence. Patients with PF and CR-PF need more hospital costs and stages than that in NOPF and NOCR-PF groups. It is critical that surgeons know the risk factors related to PF and CR-PF so as to take corresponding therapeutic regimens for each patient

Integrated analysis of breast cancer cell lines reveals unique signaling pathways

Mapping of sub-networks in the EGFR-MAPK pathway in different breast cancer cell lines reveals that PAK1 may be a marker for sensitivity to MEK inhibitors

An integrative genomic and proteomic analysis of PIK3CA, PTEN and AKT mutations in breast cancer

Phosphatidylinositol-3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT and PTEN mutations, and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in-vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor positive (33.8%) and HER2-positive (24.6%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor-positive cancers with PTEN protein levels also being significantly lower in hormone receptor-positive cancers. Unlike AKT1 mutations, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant impact on outcome in 166 hormone receptor-positive breast cancer patients after adjuvant tamoxifen. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and indeed inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines, and PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss but not PIK3CA mutations rendered cells sensitive to growth inhibition by the PI3K inhibitor LY294002. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer

Basal-Subtype and MEK-Pl3K Feedback Signaling Determine Susceptibility of Breast Cancer Cells to MEK Inhibition

Specific inhibitors of MEK have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We employed a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understand molecular mechanisms conferring resistance to such compounds. Basal-type breast cancer cells were found to be particularly susceptible to growth-inhibition by small-molecule MEK inhibitors. Activation of the PI3 kinase pathway in response to MEK inhibition through a negative MEK-EGFR-PI3 kinase feedback loop was found to limit efficacy. Interruption of this feedback mechanism by targeting MEK and PI3 kinase produced synergistic effects, including induction of apoptosis and, in some cell lines, cell cycle arrest and protection from apoptosis induced by proapoptotic agents. These findings enhance our understanding of the interconnectivity of oncogenic signal transduction circuits and have implications for the design of future clinical trials of MEK inhibitors in breast cancer by guiding patient selection and suggesting rational combination therapies

Clonality and cycling status of leukemic progenitors from patients with acute myeloid leukemia (AML)

We have detected a high concentration of cytogenetically normal long term culture-initiating cells (LTC-IC) in the peripheral blood (PB) of 12 patients with newly-diagnosed AML. To determine if these progenitors originated from normal polyclonal hematopoiesis the PCR-based human androgen receptor allele (HUMARA) assay was used to study PB cells from 5 female patients with cytogenetically abnormal AML. In 4/5 samples cytogenetics and clonality data from LTC indicate that a substantial number of normal polyclonal hematopoietic progenitors often persist in AML PB at diagnosis. However, the fifth AML sample contrasted with the others since the HUMARA assay demonstrated that LTC-derived colonies were predominantly clonal although the majority of the progenitors were cytogenetically normal. Thus, it appears that the abnormality detected on routine cytogenetics is not a reliable marker of the leukemic clone in this case. The second goal of this thesis was to characterize cycling status of different leukemic progenitors. An overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in CFC, LTC-IC and NOD/SCID mouse leukemia initiating cell (NOD/SL-IC) assays from the peripheral blood of 15 patients with newly-diagnosed AML. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC from the 15 samples as well as cytogenetically normal LTC-IC detected were actively cycling. However, the same assay has demonstrated that some AML LTC-IC and most NOD/SL-IC were largely quiescent. The growth factor responsiveness of quiescent AML cells was then studied and their functional properties compared to those of AML cells in active cell cycle. Hoechst 33342/Pyronin Y staining and FACS sorting were used to isolate Go cells in from the G1 and S/G2+M subpopulations of peripheral blood cells from 4 newly diagnosed AML patients. Go AML cells from these patients exhibited a strong tendency to enter active cell cycle when cultured even in the absence of supportive growth factors. LTC-ICs were easily detected among cycling AML cells that had been cultured for 72 hours. In contrast, the exit from Go dramatically reduced the ability of AML progenitors to engraft in mouse bone marrow.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat