VIRAL AND CELLULAR SURFACE ANTIGENS OF MURINE LEUKEMIAS AND MYELOMAS : SEROLOGICAL ANALYSIS BY IMMUNOELECTRON MICROSCOPY

Immunoelectron microscopy (IEM) of mouse cells which were productively infected with murine leukemia virus (MuLV) yielded the following conclusions: See PDF for Structure With two exceptions, the alloantigens H-2, θ, Ly-A, and Ly-B were not present on complete or incomplete virions produced by cells bearing these antigens.The exceptions were H-2k (but not H-2b) and θ both appeared on only a minority of virions and never on more than a small part of the circumference. The incidental discovery of an additional envelope antigen on virions produced by a BALB/c mouse myeloma but lacking from passage A Gross virions distinguishes these two viruses as MuLV subtypes; it also illustrates that IEM can be applied as a primary tool for antigenic analysis, as well as for its usual purpose of finding out where antigens are situated

Tendências em informática para processamento de informações no Centro de Pesquisa e Desenvolvimento da Telebrás

O Centro de Pesquisa e Desenvolvimento da Telebrás tem dedicado considerável esforço à organização de uma infraestrutura em informática, que viabiliza, entre outras metas, a automatização, em considerável grau, de tarefas de tratamento de informações. Este trabalho descreve sucintamente as diretrizes traçadas, as atividades já desenvolvidas e as perspectivas da área no CPqD

Interleukin-1α enhances the aggressive behavior of pancreatic cancer cells by regulating the α(6)β(1)-integrin and urokinase plasminogen activator receptor expression

BACKGROUND: In human pancreatic cancer progression, the α(6)β(1)-integrin is expressed on cancer cell surface during invasion and metastasis formation. In this study, we investigated whether interleukin (IL)-1α induces the alterations of integrin subunits and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) expression in pancreatic cancer cells. We hypothesize that the alterations of integrin subunits and uPA/uPAR expression make an important role in signaling pathways responsible for biological behavior of pancreatic cancer cells. RESULTS: IL-1α upregulated the expression of α(6 )and β(1 )integrins without any alterations of α(5 )and α(v )integrins expression. IL-1α also induced enhancement in the expression of uPA/uPAR in pancreatic cancer cells. IL-1α enhanced the proliferation, adhesion, and migration in pancreatic cancer cells, and IL-1α-induced alterations of uPA/uPAR expression correlated with the increased the migration of pancreatic cancer cells. Upregulation of α(6 )integrin subunit and uPA/uPAR correlated with the activation of Ras and downstream extracellular signal-regulated kinase (ERK) pathways. IL-1α-induced activation of Ras and downstream ERK can be inhibited by using inhibitory antibodies against α(6 )and β(1 )integrin and uPAR, consistent with the inhibition of proliferation, adhesion and migration of pancreatic cancer cells. Immunohistochemical analysis demonstrated a significant association between strong expressions of α(6 )integrin with uPAR in pancreatic cancer specimens. Furthermore, the strong expression of α(6 )integrin and uPAR was found to be independent prognosticator in pancreatic cancer patients. CONCLUSION: Based on these findings, we conclude that IL-1α can induce selective upregulation of α(6)β(1)-integrin and uPA/uPAR in pancreatic cancer cells and these changes may modulate the aggressive functions of pancreatic cancer

Immunoregulatory effects triggered by immunobiotic Lactobacillus jensenii TL2937 strain involve efficient phagocytosis in porcine antigen presenting cells

Background: Immunobiotic Lactobacillus jensenii TL2937 modulates porcine mononuclear phagocytes from Peyer?s patches (PPMPs) and induces a differential production of pro- and anti-inflammatory cytokines in response to Toll-like receptor (TLR)-4 activation. Objective: In view of the important role played by phagocytosis in the activation of antigen presenting cells (APCs), the aim of the present work was to examine the interaction of TL2937 with porcine PPMPs focusing on phagocytosis. In addition, this study aimed to investigate whether the effects of L. jensenii TL2937 in porcine blood monocyte-derived dendritic cells (MoDCs) are similar to those found in PPMPs considering that MoDCs do not recapitulate all functions of mucosal APCs. Results: studies showed a high ability of porcine CD172a+ PPMPs to phagocytose L. jensenii TL2937. Interestingly, our results also revealed a reduced capacity of the non-immunomodulatory L. plantarum TL2766 to be phagocytosed by those immune cells. Phagocytosis of L. jensenii TL2937 by porcine PPMPs was partially dependent on TLR2. In addition, we demonstrated that TL2937 strain was able to improve the expression of IL-1, IL-12 and IL-10 in immature MoDCs resembling the effect of this immunobiotic bacterium on PPMPs. Moreover, similarly to PPMPs those immunomodulatory effects were related to the higher capacity of TL2937 to be phagocytosed by immature MoDCs. Conclusions: Microbial recognition in APCs could be effectively mediated through ligand-receptor interactions that then mediate phagocytosis and signaling. For the immunobiotic strain TL2937, TLR2 has a partial role for its interaction with porcine APCs and it is necessary to investigate the role of other receptors. A challenge for future research will be advance in the full understanding of the molecular interactions of immunobiotic L. jensenii TL2937 with porcine APCs that will be crucial for the successful development of functional feeds for the porcine host. This study is a step in that direction.Fil: Tsukida, Kohichiro. Tohoku University; JapónFil: Takahashi, Takuya. Tohoku University; JapónFil: Iida, Hikaru. Tohoku University; JapónFil: Kanmani, Paulraj. Tohoku University; JapónFil: Suda, Yoshihito. Miyagi University; JapónFil: Nochi, Tomonori. Tohoku University; JapónFil: Ohwada, Shuichi. Tohoku University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Ohkawara, Sou. Meiji Seika Pharma Co., Ltd. Agricultural & Veterinary Division; JapónFil: Makino, Seiya. Meiji Co., Ltd. Division of Research and Development; JapónFil: Kano, Hiroshi. Meiji Co., Ltd. Division of Research and Development; JapónFil: Saito, Tadao. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kitazawa, Haruki. Tohoku University; Japó

Inhibition of motility and invasiveness of renal cell carcinoma induced by short interfering RNA transfection of β1,4GalNAc transferase

AbstractHuman renal cell carcinoma (RCC) has been characterized by remarkable changes in ganglioside composition. TOS1 cells, typical of metastatic RCC, are characterized by predominance of GM2 as monosialoganglioside, and β1,4GalNAc disialyl-Lc4 (RM2 antigen) as disialoganglioside [J. Biol. Chem. 276 (2001) 16695]. In order to observe the functional role of gangliosides in RCC malignancy, TOS1 cells were transfected with short interfering RNA (siRNA) based on open reading frame sequence of β1,4GalNAc transferase (β1,4GalNAc-T), and its disordered sequence of siRNA (dsiRNA) as control. In siRNA transfectant, β1,4GalNAc-T mRNA level and GM2 expression were greatly reduced, whereby GM3 expression appeared. In contrast, RM2 antigen level was unchanged, even though it has the same β1,4GalNAc epitope at the terminus. dsiRNA transfectant showed no change of β1,4GalNAc-T mRNA and did not express GM3. Concomitant with reduction of GM2 and appearance of GM3, siRNA transfectant showed greatly reduced motility and invasiveness, although growth rate was unaltered. Both transfectants with siRNA and dsiRNA expressed the same level of tetraspanin CD9. Since CD9/GM3 complex is known to reduce integrin-dependent motility and invasiveness [Biochemistry 40 (2001) 6414], it is plausible that motility and invasiveness of siRNA transfectant of TOS1 cells may be reduced by enhanced formation of such complex

The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells

BACKGROUND: The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RESULTS: RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 μM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 μM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers