- Email: [email protected]
P-050 Loco-regional chemokine treatment inhibits tumor growth in anorthotopic model of lung cancer
Posters/Basic science~Celt and molecular biology estimated. However, a number of other works have shown that the theoretic analysis and results of cellular automaton model are in agreement with data from the ideal differeotlal equation logistic tumor growth (R. Hu, & X. Ruan. 2003). Methods: In multlvanable logistic regression analysis, longer time since smoking exposure remained a significant predictor of adenocaJ'~nomas (p < 0 02), but history of asbestos ev,posure did not predict tumor histology ON. L. Burton. C. W. John, et. al.. '1998). Tango and Toshiro (1994) also described a Poisson regression model for time trends of mortality to detect the Iong4erm effects of common laveis of aJr pollution on lung cancer The conclusions of Burton (1998) and Tango (1994) had been used to calculate the regression we~ghtlngs for the g e o ~ c and behavioral determinants. Other data for celibratlon and validation of the models are mainly from MSKCC (Memorial Sloan Kettenng Cancer Center. http://wwwski.mskcc.org/) and Guangdong province of China. Results: Here in this study focusing on the logistic lung tumor growth model, we proposed a statistical modei for the estimation of lung tumor growth doubling time. which combines the genetic and behavioral determinants. We defined the lavels of the environmental ev,posure nsk classification by using the regression welghtings Conclusions: The statistical models for the estimation of lung tumor growth doub4ing time are well in agreement with data from what we had Keywords: lung cancer, tumor growth, environmental exposure, statistical modeling [~7]
Growt~ inhibition and apoptosis induction of protopenaxtnol on human lung cancer cells
J. He. H Gou, Z Wang, K Liu Shangdeng Engineering Research Center
for Natural Drugs, Yantal, ChJna Background: Panax ginseng has been proved to posess various important pharmacological effects. Pretopanaxadiol sabonins possesses a distinct effect and induces apoptosis and tumor regression of human lung cancer. This study intended to analy?e the effects of protopanaxtnol (PPT) on a lung cancer cell line Methods: The human lung cancer cell line. A549 were used for the study Cell viability was tested by M I ~ assay, and cell death rate was measured by lactate dehydrogenase (LDH) release Apoptosis was estimated by flow cytometnc analys~s and nuclear staJning. The ability of cells to move through Matngel~':rOated filters was measured in a ~,oydan chamber supplemented with 10% fetal calf serum. Results: The half inhibition concentration (IC50) of PPT on the proliferation of A549 lung cancer cells is 28.3 p.g/ml sn wtro. 30 p.g]ml PPT significantly induced A54g apoptosis (apoptosis rate-46 2%) characterized by flow cytometric analysis and typical morphological changes, such as nuclear shnnkage, chromatln condensation and nuclear fragmantalJon, aboptosis body were observed by fluorescence microscope after Izeatmeot for 48 h. 10 p.g/ml PPT had no effects on the viability of A54g, but inhibited the migration ofA549 cells obviously (inhibition rate 76 3%) Conclusions: All results indicated that PPT could decrease the viability and induces the apoptosis of lung cancer cells And PPT could inhibit the migration of lung cancer cells Further studies will be needed to investigate the mechanisms of protopanaxthors effects
$127
of pnmary non small cell lung cancers (NSCLC). DAF was expressed as a 55-65 kDa PNA4~inding protein in non-tumor regions, while it was expressed as a 65-75 kDa protein v,qth no PNAJ~inding act]wty in tumor lesions. The treaITnant with neuraminidase resulted In decrease of the molecular mass to 55 kDa both in the tumor and normal regions, indicating that the difference in molecular weight is mainly due to the amount of sialic acid in the sugar moiety In addition, two novel splicing variants of DAF were increased in tumor lesions, which have longer senne, threonine and pmlin~nch domaJns serving as an Olinked glycosylatlon sites Conclusions: These results suggest that DAF is structurally processed to more stable and more functional form to protect the tumor cells from autologous complement attack. Systemic chemokine CCL19 adminisb'ation reduces tumor burden in a late stage model of spontaneous lung cancer S Hillinoer 1 S yang2, M Huang 2, R Ratra2, R Stheter ~, W Weder 1, S Dubinett ~, S Sharma2 lUruversity Hospital ZLtrich, Thoracic Surgery,
7udch, Switzerland, ~University of California Los Angeles, Pu/menary Medlctne, Los Angeles, CalJforma, USA Background: It has bean demonstrated that local administTalJon of chemokines as stimulators of the immune response is beoefic~al as potent anti-cancer strategy Epstein Ban" virus-induced molecule 1 ligand chemokine (FI C/CCL19) is a CC chemokine that chemoattracts both dendntic cells (DC) and T lymphocytes In this study we evaluated the anti-tumor efficacy of systemic CCLlg administration in a late stage spontaneous bronchogeoic carQnoma model of transgenic mice in which the SV 40 large T antigen is ev,pressed under control of the munne Clara cell specific promoter, CC 10 Mice ev,pressing the transgane davelop diffuse bilateral bronchoalveolar carcinoma and have an average life span of 4 months Methods: Three months old CC 10 mice have been treated with recombinant CCL19 three times a week for one month either intraperitoneal or in the a~llar lymph node region. Lungs from 4 months old treated mice and corresponding controls have been assessed for tumor burden, cytokine profiles by ELISA and T cell subsets. Results: Histological avaluation of tumor sections from mice treated at three months of age w ~ recombinant C0~19 (0.5 ~.gJdose) by intrapentoneal or intranodal (aX]llar lymph node region) injection three times per week for 4 weeks revealed exteos[ve lymphocytic infiltration with a marked reducl]on in tumor burden compared to diluent treated controls Row cytometdc analysis showed a significant increase in both CD4 and CD6 subsets as well as deodntlc cells. However. there was a decrease in CD4+CD25+ T regulatory ceils in the lungs of CCLIO treated mice Lung tissue cytokine profiles showed a shift towards immunostimulatory molecules Conclusions: Systemic administration of ELC/CCLlg e4ther infrapentoneal or intranodal leads to co localization of both DC and • lymphocytes as well as reduction of CD4+CD25+ regulatory T cells at the tumor site and a generation of systemic anti tumor responses in a late stage model of spontaneous lung cancer This study provides a strong rationale for further evaluation of this potent substance in the regulation of tumor immun~y and its use in immunotharapy for lung cancer Control
CCL19~reated for 4 weeks. 3x/week InVapentoneel Irtranodal
Identification of decay-accelerating factor (DAF, CD55) as a peanut aggutinin (PNA)-binding protein and its sl]'uctural modification in non-small cell lung cancers (NSCLC) M Hl~luchi1. Y Endo 2, H SUZUki I , F Osuka I . J OsugJ 1, Y Shio I , R Kanno 1, A Ohishi 3. T Fujita~. M Gotoh I ~Fukustuma Medical University, Department
of Surgery 1st Fukushima, Japan, 2Fukushima Medical University, Department of B~ocherntstry, Fukushtma, Japan, 3Fukushtma Red Cross HospitaJ, Depar~nent of Thorac/c Surgery, Fukush/ma, Japan Lungs of 4 months old CC10 tTansgeoic mice Background: Peanut agglutinin (PNA) is a plant leotln which recognizes protein bound galactose~.l 3N acetylgalactosamine. This carbohydrates structure is called tumor-associated carbohydrate or Thomseo-Fdedanreich antlgeo (Tantlgeo) The relal3onships between ev,.pression of PNA recognizing carbohydrates and dinlcepathological factors have been reported in several cancers such as coloreotal cancer, breast cancer, lung cancer and malignant melanoma The expression frequency and localization pattern of PNA4~inding carbohydrates in human carcinomas correlates with the aggressiveness of some carcinomas. In this study, we ideotlfied a PNA4~inding protein with the broad molecular masses of 55 65 kDa, which is speolficelly expressing in human lung Methods and Results: Enzymatic t]ealmants suggest that this protein is a glycosyl phosphatidylinositol (GPI) anchored membrane protein carrying O-linked carbohydrates Using immunopreo~pitation and affinity chromatography, we found that the core protein is decay accelerating factor (DAF. CD55). one of complement regulatory proteins. The total amount of DAF estimated by PNA leo~n blots and Western blots significantly decreased in tumor lesions
•P•T
Loco-rogional chemokine b'eatment inhibits tumor growth in an orthotopic model of lung cencer
S. Hillingerl: S Yang2, M Cardell 1, S Korom 1, D Lardinois 1, S Dubinetl 2, S. Sharma~, W. Weder 1. 1Ur~versity Hospttal Zurich, Thoractc Surgery, ZUrich, Swttzerland, 2Un/verssty of Callforma Los Angeles, Pulmonary
Medicine, Los Angeles, California, USA Background: Effective anti-tumor responses require both antigen presenting cells and lymphocyte effeotors Although lung cancers ~v,.press tumor antigens, they are ineffective as antigen presenting ceils because tumor ceils often have lim~ed expression of MHC Ags and lack co-stimulatory molecules It has been demonstrated that local and systemic administration of chemoklnes as stimulators of the immune response Is beneficial as potent anticancer strategy Epstein Ban" virus induced molecule 1 Iigand chemokine
Growt~ inhibition and apoptosis induction of protopenaxtnol on human lung cancer cells
J. He. H Gou, Z Wang, K Liu Shangdeng Engineering Research Center
for Natural Drugs, Yantal, ChJna Background: Panax ginseng has been proved to posess various important pharmacological effects. Pretopanaxadiol sabonins possesses a distinct effect and induces apoptosis and tumor regression of human lung cancer. This study intended to analy?e the effects of protopanaxtnol (PPT) on a lung cancer cell line Methods: The human lung cancer cell line. A549 were used for the study Cell viability was tested by M I ~ assay, and cell death rate was measured by lactate dehydrogenase (LDH) release Apoptosis was estimated by flow cytometnc analys~s and nuclear staJning. The ability of cells to move through Matngel~':rOated filters was measured in a ~,oydan chamber supplemented with 10% fetal calf serum. Results: The half inhibition concentration (IC50) of PPT on the proliferation of A549 lung cancer cells is 28.3 p.g/ml sn wtro. 30 p.g]ml PPT significantly induced A54g apoptosis (apoptosis rate-46 2%) characterized by flow cytometric analysis and typical morphological changes, such as nuclear shnnkage, chromatln condensation and nuclear fragmantalJon, aboptosis body were observed by fluorescence microscope after Izeatmeot for 48 h. 10 p.g/ml PPT had no effects on the viability of A54g, but inhibited the migration ofA549 cells obviously (inhibition rate 76 3%) Conclusions: All results indicated that PPT could decrease the viability and induces the apoptosis of lung cancer cells And PPT could inhibit the migration of lung cancer cells Further studies will be needed to investigate the mechanisms of protopanaxthors effects
$127
of pnmary non small cell lung cancers (NSCLC). DAF was expressed as a 55-65 kDa PNA4~inding protein in non-tumor regions, while it was expressed as a 65-75 kDa protein v,qth no PNAJ~inding act]wty in tumor lesions. The treaITnant with neuraminidase resulted In decrease of the molecular mass to 55 kDa both in the tumor and normal regions, indicating that the difference in molecular weight is mainly due to the amount of sialic acid in the sugar moiety In addition, two novel splicing variants of DAF were increased in tumor lesions, which have longer senne, threonine and pmlin~nch domaJns serving as an Olinked glycosylatlon sites Conclusions: These results suggest that DAF is structurally processed to more stable and more functional form to protect the tumor cells from autologous complement attack. Systemic chemokine CCL19 adminisb'ation reduces tumor burden in a late stage model of spontaneous lung cancer S Hillinoer 1 S yang2, M Huang 2, R Ratra2, R Stheter ~, W Weder 1, S Dubinett ~, S Sharma2 lUruversity Hospital ZLtrich, Thoracic Surgery,
7udch, Switzerland, ~University of California Los Angeles, Pu/menary Medlctne, Los Angeles, CalJforma, USA Background: It has bean demonstrated that local administTalJon of chemokines as stimulators of the immune response is beoefic~al as potent anti-cancer strategy Epstein Ban" virus-induced molecule 1 ligand chemokine (FI C/CCL19) is a CC chemokine that chemoattracts both dendntic cells (DC) and T lymphocytes In this study we evaluated the anti-tumor efficacy of systemic CCLlg administration in a late stage spontaneous bronchogeoic carQnoma model of transgenic mice in which the SV 40 large T antigen is ev,pressed under control of the munne Clara cell specific promoter, CC 10 Mice ev,pressing the transgane davelop diffuse bilateral bronchoalveolar carcinoma and have an average life span of 4 months Methods: Three months old CC 10 mice have been treated with recombinant CCL19 three times a week for one month either intraperitoneal or in the a~llar lymph node region. Lungs from 4 months old treated mice and corresponding controls have been assessed for tumor burden, cytokine profiles by ELISA and T cell subsets. Results: Histological avaluation of tumor sections from mice treated at three months of age w ~ recombinant C0~19 (0.5 ~.gJdose) by intrapentoneal or intranodal (aX]llar lymph node region) injection three times per week for 4 weeks revealed exteos[ve lymphocytic infiltration with a marked reducl]on in tumor burden compared to diluent treated controls Row cytometdc analysis showed a significant increase in both CD4 and CD6 subsets as well as deodntlc cells. However. there was a decrease in CD4+CD25+ T regulatory ceils in the lungs of CCLIO treated mice Lung tissue cytokine profiles showed a shift towards immunostimulatory molecules Conclusions: Systemic administration of ELC/CCLlg e4ther infrapentoneal or intranodal leads to co localization of both DC and • lymphocytes as well as reduction of CD4+CD25+ regulatory T cells at the tumor site and a generation of systemic anti tumor responses in a late stage model of spontaneous lung cancer This study provides a strong rationale for further evaluation of this potent substance in the regulation of tumor immun~y and its use in immunotharapy for lung cancer Control
CCL19~reated for 4 weeks. 3x/week InVapentoneel Irtranodal
Identification of decay-accelerating factor (DAF, CD55) as a peanut aggutinin (PNA)-binding protein and its sl]'uctural modification in non-small cell lung cancers (NSCLC) M Hl~luchi1. Y Endo 2, H SUZUki I , F Osuka I . J OsugJ 1, Y Shio I , R Kanno 1, A Ohishi 3. T Fujita~. M Gotoh I ~Fukustuma Medical University, Department
of Surgery 1st Fukushima, Japan, 2Fukushima Medical University, Department of B~ocherntstry, Fukushtma, Japan, 3Fukushtma Red Cross HospitaJ, Depar~nent of Thorac/c Surgery, Fukush/ma, Japan Lungs of 4 months old CC10 tTansgeoic mice Background: Peanut agglutinin (PNA) is a plant leotln which recognizes protein bound galactose~.l 3N acetylgalactosamine. This carbohydrates structure is called tumor-associated carbohydrate or Thomseo-Fdedanreich antlgeo (Tantlgeo) The relal3onships between ev,.pression of PNA recognizing carbohydrates and dinlcepathological factors have been reported in several cancers such as coloreotal cancer, breast cancer, lung cancer and malignant melanoma The expression frequency and localization pattern of PNA4~inding carbohydrates in human carcinomas correlates with the aggressiveness of some carcinomas. In this study, we ideotlfied a PNA4~inding protein with the broad molecular masses of 55 65 kDa, which is speolficelly expressing in human lung Methods and Results: Enzymatic t]ealmants suggest that this protein is a glycosyl phosphatidylinositol (GPI) anchored membrane protein carrying O-linked carbohydrates Using immunopreo~pitation and affinity chromatography, we found that the core protein is decay accelerating factor (DAF. CD55). one of complement regulatory proteins. The total amount of DAF estimated by PNA leo~n blots and Western blots significantly decreased in tumor lesions
•P•T
Loco-rogional chemokine b'eatment inhibits tumor growth in an orthotopic model of lung cencer
S. Hillingerl: S Yang2, M Cardell 1, S Korom 1, D Lardinois 1, S Dubinetl 2, S. Sharma~, W. Weder 1. 1Ur~versity Hospttal Zurich, Thoractc Surgery, ZUrich, Swttzerland, 2Un/verssty of Callforma Los Angeles, Pulmonary
Medicine, Los Angeles, California, USA Background: Effective anti-tumor responses require both antigen presenting cells and lymphocyte effeotors Although lung cancers ~v,.press tumor antigens, they are ineffective as antigen presenting ceils because tumor ceils often have lim~ed expression of MHC Ags and lack co-stimulatory molecules It has been demonstrated that local and systemic administration of chemoklnes as stimulators of the immune response Is beneficial as potent anticancer strategy Epstein Ban" virus induced molecule 1 Iigand chemokine