The Experts below are selected from a list of 4287 Experts worldwide ranked by ideXlab platform

Shengteng Huang - One of the best experts on this subject based on the ideXlab platform.

  • anti tumor and anti angiogenic effects of phyllanthus urinaria in mice bearing Lewis Lung Carcinoma
    International Immunopharmacology, 2006
    Co-Authors: Shengteng Huang, Rongchi Yang, Suhui Yang, Shuenkuei Liao, Tzuya Chen, Jonghwei S Pang
    Abstract:

    Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its anti-tumor effect in vivo for the first time. The anti-tumor activity in P. urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice with implantation of Lewis Lung Carcinoma cells. The oral administration of P. urinaria to mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. Neither the total body weight of mouse nor the weights of organs including heart, Lung, liver, spleen and kidney revealed any difference between two groups, suggesting limited in vivo cytotoxic effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis in tumor sections prepared from P. urinaria-treated mice compared with control mice. It is worth of note that the neovascularization in tumor was inhibited in P. urinaria-treated mice, which implicated the potential anti-angiogenic effect of P. urinaria. Further study using an in vitro matrix-induced tube formation of HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria exerted no inhibitory effect on the growth of HUVECs, however, the migration of HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria in a dose-dependent manner. All together, the present study indicated that P. urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used safely in animals.

  • phyllanthus urinaria triggers the apoptosis and bcl 2 down regulation in Lewis Lung Carcinoma cells
    Life Sciences, 2003
    Co-Authors: Shengteng Huang, Rongchi Yang, Lijiun Yang, Peinir Lee, Jonghwei S Pang
    Abstract:

    Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect in its water extract for the first time. The water extract of P. urinaria significantly decreased the number of Lewis Lung Carcinoma cells in a dose-and time-dependent manner as determined by MTT assay. However, the water extract of P. urinaria did not exert any cytotoxic effect on normal cells such as endothelial cells and liver cells. Result from flow cytometry revealed a dose-dependent increase of dead cells 24 hours after treating Lewis Lung Carcinoma cells with P. urinaria extract. The anticancer activity of P. urinaria extract was due to the apoptosis induced in Lewis Lung Carcinoma cells, which was demonstrated by DNA fragmentation analysis and increased caspase-3 activity. The apoptosis triggered by P. urinaria extract in Lewis Lung Carcinoma cells was associated with the down-regulation of Bcl-2 gene expression, but not with p53, p21 and Bax. Furthermore, the partial inhibition of P. urinaria-induced apoptosis in Lewis Lung Carcinoma cells by pretreatment with cyclosporin A, a mitochondria permeability transition pore inhibitor, suggesting that P. urinaria extract induced the apoptosis of Lewis Lung Carcinoma cells, at least in part, through a mitochondria-associated intrinsic pathway.

  • phyllanthus urinaria triggers the apoptosis and bcl 2 down regulation in Lewis Lung Carcinoma cells
    Life Sciences, 2003
    Co-Authors: Shengteng Huang, Rongchi Yang, Lijiun Yang, Jonghwei S Pang
    Abstract:

    Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect in its water extract for the first time. The water extract of P. urinaria significantly decreased the number of Lewis Lung Carcinoma cells in a dose-and time-dependent manner as determined by MTT assay. However, the water extract of P. urinaria did not exert any cytotoxic effect on normal cells such as endothelial cells and liver cells. Result from flow cytometry revealed a dose-dependent increase of dead cells 24 hours after treating Lewis Lung Carcinoma cells with P. urinaria extract. The anticancer activity of P. urinaria extract was due to the apoptosis induced in Lewis Lung Carcinoma cells, which was demonstrated by DNA fragmentation analysis and increased caspase-3 activity. The apoptosis triggered by P. urinaria extract in Lewis Lung Carcinoma cells was associated with the downregulation of Bcl-2 gene expression, but not with p53, p21 and Bax. Furthermore, the partial inhibition of P. urinaria-induced apoptosis in Lewis Lung Carcinoma cells by pretreatment with cyclosporin A, a mitochondria permeability transition pore inhibitor, suggesting that P. urinaria extract induced the apoptosis of Lewis Lung Carcinoma cells, at least in part, through a mitochondria-associated intrinsic pathway. D 2002 Elsevier Science Inc. All rights reserved.

Jonghwei S Pang - One of the best experts on this subject based on the ideXlab platform.

  • anti tumor and anti angiogenic effects of phyllanthus urinaria in mice bearing Lewis Lung Carcinoma
    International Immunopharmacology, 2006
    Co-Authors: Shengteng Huang, Rongchi Yang, Suhui Yang, Shuenkuei Liao, Tzuya Chen, Jonghwei S Pang
    Abstract:

    Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its anti-tumor effect in vivo for the first time. The anti-tumor activity in P. urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice with implantation of Lewis Lung Carcinoma cells. The oral administration of P. urinaria to mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. Neither the total body weight of mouse nor the weights of organs including heart, Lung, liver, spleen and kidney revealed any difference between two groups, suggesting limited in vivo cytotoxic effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis in tumor sections prepared from P. urinaria-treated mice compared with control mice. It is worth of note that the neovascularization in tumor was inhibited in P. urinaria-treated mice, which implicated the potential anti-angiogenic effect of P. urinaria. Further study using an in vitro matrix-induced tube formation of HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria exerted no inhibitory effect on the growth of HUVECs, however, the migration of HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria in a dose-dependent manner. All together, the present study indicated that P. urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used safely in animals.

  • phyllanthus urinaria triggers the apoptosis and bcl 2 down regulation in Lewis Lung Carcinoma cells
    Life Sciences, 2003
    Co-Authors: Shengteng Huang, Rongchi Yang, Lijiun Yang, Peinir Lee, Jonghwei S Pang
    Abstract:

    Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect in its water extract for the first time. The water extract of P. urinaria significantly decreased the number of Lewis Lung Carcinoma cells in a dose-and time-dependent manner as determined by MTT assay. However, the water extract of P. urinaria did not exert any cytotoxic effect on normal cells such as endothelial cells and liver cells. Result from flow cytometry revealed a dose-dependent increase of dead cells 24 hours after treating Lewis Lung Carcinoma cells with P. urinaria extract. The anticancer activity of P. urinaria extract was due to the apoptosis induced in Lewis Lung Carcinoma cells, which was demonstrated by DNA fragmentation analysis and increased caspase-3 activity. The apoptosis triggered by P. urinaria extract in Lewis Lung Carcinoma cells was associated with the down-regulation of Bcl-2 gene expression, but not with p53, p21 and Bax. Furthermore, the partial inhibition of P. urinaria-induced apoptosis in Lewis Lung Carcinoma cells by pretreatment with cyclosporin A, a mitochondria permeability transition pore inhibitor, suggesting that P. urinaria extract induced the apoptosis of Lewis Lung Carcinoma cells, at least in part, through a mitochondria-associated intrinsic pathway.

  • phyllanthus urinaria triggers the apoptosis and bcl 2 down regulation in Lewis Lung Carcinoma cells
    Life Sciences, 2003
    Co-Authors: Shengteng Huang, Rongchi Yang, Lijiun Yang, Jonghwei S Pang
    Abstract:

    Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect in its water extract for the first time. The water extract of P. urinaria significantly decreased the number of Lewis Lung Carcinoma cells in a dose-and time-dependent manner as determined by MTT assay. However, the water extract of P. urinaria did not exert any cytotoxic effect on normal cells such as endothelial cells and liver cells. Result from flow cytometry revealed a dose-dependent increase of dead cells 24 hours after treating Lewis Lung Carcinoma cells with P. urinaria extract. The anticancer activity of P. urinaria extract was due to the apoptosis induced in Lewis Lung Carcinoma cells, which was demonstrated by DNA fragmentation analysis and increased caspase-3 activity. The apoptosis triggered by P. urinaria extract in Lewis Lung Carcinoma cells was associated with the downregulation of Bcl-2 gene expression, but not with p53, p21 and Bax. Furthermore, the partial inhibition of P. urinaria-induced apoptosis in Lewis Lung Carcinoma cells by pretreatment with cyclosporin A, a mitochondria permeability transition pore inhibitor, suggesting that P. urinaria extract induced the apoptosis of Lewis Lung Carcinoma cells, at least in part, through a mitochondria-associated intrinsic pathway. D 2002 Elsevier Science Inc. All rights reserved.

Robert M Hoffman - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the selective targeting efficacy of salmonella typhimurium a1 r and vnp20009 on the Lewis Lung Carcinoma in nude mice
    Oncotarget, 2015
    Co-Authors: Yong Zhang, Nan Zhang, Ming Zhao, Robert M Hoffman
    Abstract:

    Salmonella typhimurium A1-R is auxotrophic for arg and leu, which attenuates growth in normal tissue but allows high tumor targeting and virulence. A1-R is effective against metastatic human prostate, breast, and pancreatic cancer as well as osteosarcoma, fibrosarcoma, and glioma in clinically-relevant mouse models. VNP20009 is also a genetically-modified strain of Salmonella typhimurium that has been tested in Phase I clinical trials, but is more attenuated than S. typhimurium A1-R and in addition of multiple amino-acid auxotrophs, is purine auxotropic with the purI mutation. In the present study, mouse Lewis Lung Carcinoma-bearing nude mouse models were treated with S. typhimurium A1-R or VNP20009. S. typhimurium A1-R and VNP20009 were both eliminated from the liver and spleen approximately 3-5 days after administration via the tail vein. However, A1-R showed higher tumor targeting and inhibited the Lewis Lung Carcinoma to a greater extent than VNP20009, with less body weight loss. The mice tolerated S. typhimurium A1-R to at a least 2-fold higher dose than VNP20009 when the bacteria were administered iv. The results of the present study suggest that S. typhimurium A1-R has greater clinical potential than VNP20009.

  • abstract 704 comparison of salmonella typhimurium a1 r and vnp20009 on the Lewis Lung Carcinoma
    Cancer Research, 2014
    Co-Authors: Yong Zhang, Robert M Hoffman, Nan Zhang, Ming Zhao
    Abstract:

    Salmonella typhimurium A1-R (A1-R) is auxotrophic for arg and leu, which attenuates growth in normal tissue but allows high tumor virulence. A1-R is effective against metastatic human prostate, breast, and pancreatic cancer as well as osteosarcoma, fibrosarcoma, and glioma in clinically-relevant mouse models. VNP20009 is also a genetically-modified strain of Salmonella typhimurium that has been tested in a Phase I clinical trial, but has more attenuation mutations than A1-R. Lewis-Lung mouse Lung cancer-bearing mice were treated with A1-R and VNP20009 in nude mice. A1-R and VNP20009 were both eliminated from the liver and spleen approximately 3-5 days after administration via tail vein, however A1-R showed higher tumor targeting and increased mouse survival than VNP20009 with less body weight loss. The mice tolerated A1-R at least 2-fold higher than NVP20009 when bacteria were administered iv. The results of the present study suggest that A1-R has greater clinical potential than VNP20009. Citation Format: Yong Zhang, Nan Zhang, Robert M. Hoffman, Ming Zhao. Comparison of Salmonella typhimurium A1-R and VNP20009 on the Lewis Lung Carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 704. doi:10.1158/1538-7445.AM2014-704

  • syngeneic lymph node targeting model of green fluorescent protein expressing Lewis Lung Carcinoma
    Clinical & Experimental Metastasis, 2005
    Co-Authors: Vladimir Bobek, Katarina Kolostova, Daniela Pinterov, Michael Boubelik, Ping Jiang, Meng Yang, Robert M Hoffman
    Abstract:

    The Lewis Lung tumor has been extensively studied in both syngeneic and allogeneic mouse models. However, its metastatic potential and mechanism are poorly understood. The aim of the present study was to develop a highly metastatic lymph-node targeting, imageable model of the Lewis Lung Carcinoma in a syngeneic host. We report here a syngeneic model of the Lewis Lung Carcinoma in which the Carcinoma cells are labeled with green fluorescent protein (GFP). The tumor cells were transplanted in the dorsal side of the ear of C57-B16 mice in order to give the tumor cells access to the lymphatic system. This model of the Lewis Lung Carcinoma extensively metastasized to numerous lymph nodes throughout the body of the animal as well as visceral organs, as visualized by fluorescence microscopy using the bright GFP signal. Twenty-one different metastatic sites, including lymph nodes throughout the body, were identified among the cohort of transplanted animals. The data demonstrate a predilection of the Lewis Lung Carcinoma for lymphatic pathways for metastasis throughout the animal body. The concomitant macrometastases to the visceral organs observed in this model may be remetastasis from the lymph nodes. This model of the Lewis Lung Carcinoma should be very useful in defining cellular trafficking and targeting mechanisms of metastasis, in particular those involving lymphatic pathways.

  • A highly metastatic Lewis Lung Carcinoma orthotopic green fluorescent protein model
    Clinical & Experimental Metastasis, 2000
    Co-Authors: Babak Rashidi, Ping Jiang, Meng Yang, Eugene Baranov, Xiaoen Wang, A.r. Moossa, Robert M Hoffman
    Abstract:

    The Lewis Lung Carcinoma has been widely used for many important studies. However, the subcutaneous transplant or orthotopic cell-suspension injection models have not allowed the expression of its full metastatic potential. A powerful new highly metastatic model of the widely-used Lewis Lung Carcinoma is reported here using surgical orthotopic implantation (SOI) of tumor fragments and enhanced green fluorescent protein (GFP) transduction of the tumor cells. To achieve this goal, we first developed in vitro a stable high-expression GFP transductant of the Lewis Lung Carcinoma with the pLEIN retroviral expression vector containing the enhanced Aequorea victoria GFP gene. Stable high-level expression of GFP was found maintained in vivo in subcutaneously-growing Lewis Lung tumors. The in vivo GFP-expressing tumors were harvested and implanted as tissue fragments by SOI in the right Lung of additional nude mice. This model resulted in rapid orthotopic growth and extensive metastasis visualized by GFP-expression. 100% of the animals had metastases on the ipsilateral diaphragmatic surface, contralateral diaphragmatic surface, contralateral Lung parenchima, and in mediastinal lymph nodes. Heart metastases were visualized in 40%, and brain metastases were visualized in 30% of the SOI animals. Mice developed signs of respiratory distress between 10–15 days post-tumor implantation and were sacrificed. The use of GFP-transduced Lewis Lung Carcinoma transplanted by SOI reveals for the first time the high malignancy of this tumor and provides an important useful model for metastasis, angiogenesis and therapeutic studies.

Lin Yan - One of the best experts on this subject based on the ideXlab platform.

  • data_sheet_1_Lipidomic Impacts of an Obesogenic Diet Upon Lewis Lung Carcinoma in Mice.xlsx
    2018
    Co-Authors: Sneha Sundaram, Michael R Bukowski, Aaron Mehus, Petr Zacek, Lin Yan, Matthew J. Picklo
    Abstract:

    Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Consumption of a high-fat obesogenic diet enhances spontaneous metastasis using a Lewis Lung Carcinoma (LLC) model. In order to gain further insights into the mechanisms by which dietary fats impact cancer progression, we conducted a lipidomic analysis of primary tumors originated from LLC from mice fed with a standard AIN93G diet or a soybean oil-based high-fat diet (HFD). Hierarchical clustering heatmap analysis of phosphatidylcholine (PC) lipids and phosphatidylethanolamine (PE) lipids demonstrated an increase in polyunsaturated fatty acids (PUFA)-containing phospholipids and a decrease in monounsaturated fatty acids (MUFA)-containing lipids in tumors from mice fed the HFD. The quantities of 51 PC and 24 PE lipids differed in primary tumors of LLC from mice fed the control diet and the HFD. Analysis of triacylglycerol (TAG) lipids identified differences in 32 TAG (by brutto structure) between the two groups; TAG analysis by neutral loss identified 46 PUFA-containing TAG species that were higher in mice fed with the HFD than in the controls. Intake of the HFD did not alter the expression of the de novo lipogenesis enzymes (fatty acid synthase, acetyl-CoA carboxylase-1, and stearoyl-CoA desaturase-1). Our results demonstrate that the dietary fatty acid composition of the HFD is reflected in the higher order lipidomic composition of primary tumors. Subsequent studies are needed to investigate how these lipidomic changes may be used for targeted dietary intervention to reduce tumor growth and malignant progression.

  • abstract c33 effects of monocyte chemotactic protein 1 deficiency on spontaneous metastasis of Lewis Lung Carcinoma in mice fed a high fat diet
    Cancer Research, 2016
    Co-Authors: Lin Yan, Sneha Sundaram
    Abstract:

    Obesity is a risk factor for cancer. Adipose tissue is considered an endocrine organ that produces pro-inflammatory adipokines, e.g. monocyte chemotactic protein-1 (MCP-1), that may contribute to obesity-related malignant progression. This study investigated effects of MCP-1 deficiency on pulmonary metastasis of Lewis Lung Carcinoma (LLC) in male C57BL/6 mice using a spontaneous metastasis model. The high-fat diet (45% of energy from fat) significantly increased the number and size (cross-sectional area and volume) of Lung metastases compared to the AIN93G control diet (16% of energy from fat). Deficiency of MCP-1 reduced the number of Lung metastases by 37% (p Citation Format: Lin Yan, Sneha Sundaram. Effects of monocyte chemotactic protein-1 deficiency on spontaneous metastasis of Lewis Lung Carcinoma in mice fed a high-fat diet. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C33.

  • abstract 4325 high fat diet enhances and monocyte chemoattractant protein 1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis Lung Carcinoma
    Cancer Research, 2016
    Co-Authors: Sneha Sundaram, Lin Yan
    Abstract:

    Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesity-related diseases. This study (2×2 factorial design) investigated the effects of a high-fat diet (45% of energy from corn oil) and MCP-1 deficiency on bone micro-structural changes, analyzed by micro-computed tomography, in male C57BL/6 mice bearing Lung metastases of Lewis Lung Carcinoma (LLC). Subcutaneous injection of LLC cells resulted in Lung metastasis which was significantly enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Micro-computed tomographic measurement showed significant reductions in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in right femurs and vertebrae of LLC-bearing mice compared to non-tumor-bearing controls. In LLC-bearing mice, compared to the low-fat diet (16% of energy from corn oil), the high-fat diet significantly reduced BV/TV, Tb.N and BMD in femurs but not in vertebrae. Furthermore, compared to wild-type mice, MCP-1 deficiency significantly increased BV/TV and Tb.N in both femurs and vertebrae and BMD in vertebrae in LLC-bearing mice. These results demonstrate that metastasis causes bone loss which is enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Overall, it indicates that the high-fat diet and MCP-1 contribute positively to metastasis-associated bone deterioration. Citation Format: Sneha Sundaram, Lin Yan. High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis Lung Carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4325.

  • dietary supplementation with methylseleninic acid but not selenomethionine reduces spontaneous metastasis of Lewis Lung Carcinoma in mice
    International Journal of Cancer, 2012
    Co-Authors: Lin Yan, Lana C S Demars
    Abstract:

    The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA), in comparison with selenomethionine (SeMet), on spontaneous metastasis of Lewis Lung Carcinoma (LLC) in male C57BL/6 mice using intramuscular and subcutaneous injection models. Mice were fed AIN93G control diet or that diet supplemented with MSeA or SeMet at 2.5 mg selenium/kg for 4 weeks at which time they were injected intramuscularly or subcutaneously with 2.5 × 105 viable LLC cells. Experiments were terminated 2 weeks later for mice injected intramuscularly or 2 weeks after surgical removal of primary tumors from mice subcutaneously injected with cancer cells. Dietary supplementation with MSeA significantly reduced pulmonary metastatic yield when compared with the controls (p < 0.05) in both models; however, SeMet did not have such an effect. Supplementation with MSeA significantly decreased plasma concentrations of urokinase-type plasminogen activator (p < 0.05) and plasminogen activator inhibitor-1 (p < 0.05). Furthermore, MSeA significantly reduced plasma concentrations of vascular endothelial growth factor (p < 0.05), fibroblast growth factor basic (p < 0.05) and platelet-derived growth factor-BB (p < 0.05) when compared with the controls. Selenomethionine did not affect any of the aforementioned measurements. These results demonstrate that MSeA reduces spontaneous metastasis of LLC in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis.

Sneha Sundaram - One of the best experts on this subject based on the ideXlab platform.

  • lipidomic impacts of an obesogenic diet upon Lewis Lung Carcinoma in mice
    Frontiers in Oncology, 2018
    Co-Authors: Sneha Sundaram, Michael R Bukowski, Aaron Mehus, Matthew J. Picklo, Petr Zacek
    Abstract:

    Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Consumption of a high-fat obesogenic diet enhances spontaneous metastasis using a Lewis Lung Carcinoma (LLC) model. In order to gain further insight into the mechanisms by which dietary fats impact cancer progression, we conducted a lipidomic analysis of primary tumors originated from LLC from mice fed a standard AIN93G diet or a soybean oil-based high-fat diet (HFD). Hierarchical clustering heatmap analysis of phosphatidylcholine (PC) lipids and phosphatidylethanolamine (PE) lipids demonstrated an increase in polyunsaturated fatty acids (PUFA)-containing phospholipids and a decrease in mono-unsaturated fatty acids (MUFA)-containing lipids in tumors from mice fed the HFD. The quantities of 51 PC and 24 PE lipids differed in LLC tumors derived from mice fed the control diet and the HFD. Analysis of triacylglycerol (TAG) lipids identified differences in 32 TAG (by brutto structure) between the two groups; TAG analysis by neutral loss identified 46 PUFA-containing TAG species that were higher in mice fed the HFD than in the controls. Intake of the HFD did not alter the expression of the de novo lipogenesis enzymes (fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1). Our results demonstrate that the dietary fatty acid composition of a HFD is reflected in the higher order lipidomic composition of primary tumors. Subsequent data are needed to investigate how these lipidomic changes may be used for targeted dietary intervention to reduce tumor growth and malignant progression.

  • data_sheet_1_Lipidomic Impacts of an Obesogenic Diet Upon Lewis Lung Carcinoma in Mice.xlsx
    2018
    Co-Authors: Sneha Sundaram, Michael R Bukowski, Aaron Mehus, Petr Zacek, Lin Yan, Matthew J. Picklo
    Abstract:

    Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Consumption of a high-fat obesogenic diet enhances spontaneous metastasis using a Lewis Lung Carcinoma (LLC) model. In order to gain further insights into the mechanisms by which dietary fats impact cancer progression, we conducted a lipidomic analysis of primary tumors originated from LLC from mice fed with a standard AIN93G diet or a soybean oil-based high-fat diet (HFD). Hierarchical clustering heatmap analysis of phosphatidylcholine (PC) lipids and phosphatidylethanolamine (PE) lipids demonstrated an increase in polyunsaturated fatty acids (PUFA)-containing phospholipids and a decrease in monounsaturated fatty acids (MUFA)-containing lipids in tumors from mice fed the HFD. The quantities of 51 PC and 24 PE lipids differed in primary tumors of LLC from mice fed the control diet and the HFD. Analysis of triacylglycerol (TAG) lipids identified differences in 32 TAG (by brutto structure) between the two groups; TAG analysis by neutral loss identified 46 PUFA-containing TAG species that were higher in mice fed with the HFD than in the controls. Intake of the HFD did not alter the expression of the de novo lipogenesis enzymes (fatty acid synthase, acetyl-CoA carboxylase-1, and stearoyl-CoA desaturase-1). Our results demonstrate that the dietary fatty acid composition of the HFD is reflected in the higher order lipidomic composition of primary tumors. Subsequent studies are needed to investigate how these lipidomic changes may be used for targeted dietary intervention to reduce tumor growth and malignant progression.

  • abstract c33 effects of monocyte chemotactic protein 1 deficiency on spontaneous metastasis of Lewis Lung Carcinoma in mice fed a high fat diet
    Cancer Research, 2016
    Co-Authors: Lin Yan, Sneha Sundaram
    Abstract:

    Obesity is a risk factor for cancer. Adipose tissue is considered an endocrine organ that produces pro-inflammatory adipokines, e.g. monocyte chemotactic protein-1 (MCP-1), that may contribute to obesity-related malignant progression. This study investigated effects of MCP-1 deficiency on pulmonary metastasis of Lewis Lung Carcinoma (LLC) in male C57BL/6 mice using a spontaneous metastasis model. The high-fat diet (45% of energy from fat) significantly increased the number and size (cross-sectional area and volume) of Lung metastases compared to the AIN93G control diet (16% of energy from fat). Deficiency of MCP-1 reduced the number of Lung metastases by 37% (p Citation Format: Lin Yan, Sneha Sundaram. Effects of monocyte chemotactic protein-1 deficiency on spontaneous metastasis of Lewis Lung Carcinoma in mice fed a high-fat diet. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C33.

  • abstract 4325 high fat diet enhances and monocyte chemoattractant protein 1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis Lung Carcinoma
    Cancer Research, 2016
    Co-Authors: Sneha Sundaram, Lin Yan
    Abstract:

    Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesity-related diseases. This study (2×2 factorial design) investigated the effects of a high-fat diet (45% of energy from corn oil) and MCP-1 deficiency on bone micro-structural changes, analyzed by micro-computed tomography, in male C57BL/6 mice bearing Lung metastases of Lewis Lung Carcinoma (LLC). Subcutaneous injection of LLC cells resulted in Lung metastasis which was significantly enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Micro-computed tomographic measurement showed significant reductions in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in right femurs and vertebrae of LLC-bearing mice compared to non-tumor-bearing controls. In LLC-bearing mice, compared to the low-fat diet (16% of energy from corn oil), the high-fat diet significantly reduced BV/TV, Tb.N and BMD in femurs but not in vertebrae. Furthermore, compared to wild-type mice, MCP-1 deficiency significantly increased BV/TV and Tb.N in both femurs and vertebrae and BMD in vertebrae in LLC-bearing mice. These results demonstrate that metastasis causes bone loss which is enhanced by the high-fat diet and attenuated by MCP-1 deficiency. Overall, it indicates that the high-fat diet and MCP-1 contribute positively to metastasis-associated bone deterioration. Citation Format: Sneha Sundaram, Lin Yan. High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis Lung Carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4325.