CHROMOSOME 3 MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

Glioblastoma multiforme (GBM), the most malignant type of glioma, is the most common primary brainneoplasm. Although comprehensive therapeutic measures are applied, the prognosis of GBM remains dismal with a median post-treatment survival of less than one year.Modern molecular genetics has demonstrated thatabnormal alterations of tumor suppressor genes (TSGs) and oncogenes are the major mechanisms responsible for the initiation and progression of this malignant tumor.Identifying of related…     

Enriched feeding formula and immune responses and outcome after Listeria monocytogenes challenge in mice.

Immunocompromised malnourished patients are at high risk of developing serious opportunistic infection. This study examined the effect of feeding a special nutrient-enriched formula (Immun-Aid) on immune responses and mortality in mice challenged with Listeria monocytogenes. Two protocols were followed. In the first protocol, the animals were challenged with microorganisms when the experimental formula was introduced as the sole source of their nutrition. There was no significant effect on total T-lymphocyte number, but the proportion of helper T cells increased by day 7, resulting in a higher helper/suppressor (H/S) T lymphocyte ratio as well. Response to the mitogen phytohemagglutinin (PHA) was slightly higher on day 3 but came down and was comparable with that of control animals by day 7. Natural killer cell activity was slightly higher on day 7. Other immunologic parameters were unchanged. There was no significant difference in mortality between the two groups. In the second protocol, the animals were fed the experimental diet for 7 days before the infectious challenge. There was a slight increase in the total number of T lymphocytes on day 7. The numbers of helper and suppressor T lymphocytes were unchanged, but H/S was slightly higher on day 3 in the experimental group. Response to PHA was again higher on day 3 but plateaued on day 7. Natural killer cell activity was not altered. Mortality after infectious challenge was slightly but significantly decreased in the group of animals fed the enriched special formula. These results indicate a slight enhancement of selected parameters of immunity in mice fed the specially enriched formula and show that prior feeding with this formula for several days may partly protect against infectious challenge, resulting in reduced mortality.     

High-dose intravenous immunoglobulin downregulates the activated levels of inflammatory indices except erythrocyte sedimentation rate in acute stage of Kawasaki Disease

We evaluated the effects of high-dose intravenous immunoglobulin (IVIG) administration on various protein parameters, including inflammatory profiles, in children with Kawasaki disease (KD). Sixty-three children with KD were treated with IVIG at 2 g/kg over 12 h. Serial examinations of laboratory indices were performed three times: before IVIG treatment, 24 h after IVIG treatment, and 7 days after IVIG treatment. The white blood cell and neutrophil counts showed significant decreases 24 h and 7 days after IVIG administration. The erythrocyte sedimentation rate (ESR) increased significantly 24 h after IVIG, and the elevated level was sustained for 7 days. The levels of hemoglobin, albumin and inflammation-associated proteins, including C-reactive protein, decreased 24 h after IVIG treatment. Inflammation-associated proteins, except transferrin, decreased further to near normal levels after 7 days. On the other hand, IgM and IgA were not affected after 24 h, rather increased significantly after 7 days. High-dose IVIG causes immediate changes in the levels of various proteins, except IgA and IgM, and downregulates the activated levels of inflammatory indices, except ESR, in the acute stage of KD.     

Infant immune response to human rotavirus serotype G1 vaccine candidate reassortant WI79-9: different dose response patterns to virus surface proteins VP7 and VP4

BACKGROUND: Rotavirus is the leading cause of morbidity from gastroenteritis in the developed world and the leading cause of mortality from viral gastroenteritis (estimated 600000 deaths) worldwide. G1 is the most prevalent human serotype. Reassortant rotavirus between simian rotavirus RRV or bovine rotavirus WC3 and human strain rotaviruses have been extensively tested as candidate vaccines. Rotavirus (RV) reassortant strain WI79-9 consists of a human (strain WI79) G1 serotype VP7 surface protein on a bovine (strain WC3) background. It is a key component of a pentavalent (G1, G2, G3, G4 and P1) WC3 reassortant vaccine candidate, RotaTeq, now being tested in Phase III clinical trials. METHODS: We studied 84 infants between the ages of 2 and 8 months who received 3 oral doses of WI79-9. Serum neutralizing antibody was measured to the human (WI79 serotype P1 G1) and bovine (WC3 serotype P7 G6) parent RV after each dose. A significant response was defined as a > or =3-fold rise in antibody titer between the predose and postdose sera. RESULTS: In two separate cohorts of vaccinees given three doses of WI79-9 reassortant rotavirus, 68 to 75% of infants demonstrated a significant response to WC3 (VP4, P7) after Dose 1, fewer (24 to 39%) responses were detected after Dose 2 and rare (0 to 4%) additional responses occurred after Dose 3. The cumulative response rate to WC3 after three doses was 95% in both trials. In contrast 23 to 37% had a significant response to WI79 (VP7, G1) after Dose 1, and 57 to 61% had a significant response after Dose 2. Additional significant responses after Dose 3 led to a cumulative response of 70 to 84%. CONCLUSION: Two doses of G1 reassortant WI79 were necessary to induce significant antibody responses to human G1 (VP7) antigen in >50% of infants. Three doses were required to achieve significant antibody responses to VP7 in >70% of infants.     

Fibronectin induces colon cancer MMP-2 activation through a Src- and NfκB-dependent mechanism

Background. MMP-2 is a matrix metalloproteinase implicated in colon cancer invasion. MMP-2 is secreted in latent form (72 kDa) then cleaved into the active form (69 kDa) by membrane-bound type MMP (MT1-MMP). The signals regulating MMP-2 activation are poorly understood. Fibronectin is a major extracellular matrix component of cancer-associated stroma. Because integrin-mediated interactions with fibronectin are implicated to modulate cancer cell invasion, here we tested the hypothesis that fibronectin regulates MMP-2 activation through a Src- and NFκB-dependent signal. Methods. We tested three human colon cancer cell lines, SW480, HCT116, and HT29. Cells were seeded onto noncoated and fibronectin- or laminin-coated plates. MMP-2 activation was assessed by zymography and Western blotting. MT1-MMP expression, Src activation, and NFκB activation were assayed using Western blotting, immunoprecipitation, and EMSA, respectively. We treated cells with anti-integrin blocking antibody, PP2, or PDTC to inhibit cell attachment to fibronectin, Src, or NFκB, respectively. Results. Minimal NFκB activation was detected under baseline conditions in each of the three cell lines. Fibronectin, but not laminin, induced MT1-MMP, Src phosphorylation, and NFκB activation at 6 h in all three cell lines, with concomitant induction of active form of MMP-2. Anti-α4β1, but not α5β1 integrin blocking antibody (2.5 μg/ml) suppressed MT-MMP1 expression (by 84, 80, and 82% for SW480, HCT116, and HT29 respectively, P < 0.05). PP2 (20 μM), and PDTC (100 μM) suppressed Src activation (by 93, 91, and 88% for each cell line, P < 0.05) and NFκB activation (by 95, 92, and 88% for each cell line, P < 0.05), respectively, and they each abolished fibronectin-induced MT1-MMP expression as well as MMP-2 activation. Conclusion. These findings suggested that fibronectin induces MMP-2 activation by MT1-MMP through a α4β1 integrin, -Src-, and NFκB-dependent signal in colon cancer cells. This signaling pathway may represent a therapeutic target for strategies designed to inhibit colon cancer progression.