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Rakesh K. Jain - One of the best experts on this subject based on the ideXlab platform.

  • effect of Antiangiogenic Therapy on tumor associated macrophages in recurrent glioblastoma
    Journal of Clinical Oncology, 2012
    Co-Authors: Christine Luemerson, Dan G Duda, Tracy T Batchelor, Matija Snuderl, Nathaniel D Kirkpatrick, Christian Davidson, Yuhui Huang, Marek Ancukiewicz, Anat Stemmerrachamimov, Rakesh K. Jain
    Abstract:

    2010 Background: Antiangiogenic Therapy is associated with increased radiographic responses in glioblastoma (GBM), but tumors invariably recur. Tumor associated macrophages (TAMs) have been proposed as a mechanism of resistance to anti-angiogenic Therapy in preclinical models. To examine the role of TAMs in recurrent GBM, we analyzed autopsy specimens from patients with or without history of Antiangiogenic Therapy. Methods: We compared autopsy brain specimens from 17 recurrent GBM patients who received anti-angiogenic treatment and chemoradiation (AAT+) to 7 patients who received chemoTherapy and/or radioTherapy without anti-angiogenic Therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically identified with flow cytometry and immunohistochemistry (IHC) with CD68, CD11b, CD14, and CD163 markers. All specimens were obtained from the Department of Pathology at Massachusetts General Hospital and clinical information gained through review of the patients’ records. Results: Using flow cytom...

  • biomarkers of response and resistance to Antiangiogenic Therapy
    Nature Reviews Clinical Oncology, 2009
    Co-Authors: Rakesh K. Jain, Dan G Duda, Christopher G Willett, Dushyant V Sahani, Jay S Loeffler, Tracy T Batchelor, Gregory A Sorensen
    Abstract:

    No validated biomarkers currently exist for appropriately selecting cancer patients for Antiangiogenic Therapy. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged as suitable candidate biomarkers, but all require prospective validation. The authors discuss the current challenges in establishing biomarkers, the advantages and disadvantages of systemic, circulating, tissue and imaging biomarkers, and the future opportunities for validating biomarkers of Antiangiogenic Therapy.

  • effect of vascular normalization by Antiangiogenic Therapy on interstitial hypertension peritumor edema and lymphatic metastasis insights from a mathematical model
    Cancer Research, 2007
    Co-Authors: Rakesh K. Jain, Ricky T. Tong, Lance L. Munn
    Abstract:

    Preclinical and clinical evidence shows that Antiangiogenic agents can decrease tumor vessel permeability and interstitial fluid pressure (IFP) in a process of vessel “normalization.” The resulting normalized vasculature has more efficient perfusion, but little is known about how tumor IFP and interstitial fluid velocity (IFV) are affected by changes in transport properties of the vessels and interstitium that are associated with Antiangiogenic Therapy. By using a mathematical model to simulate IFP and IFV profiles in tumors, we show here that Antiangiogenic Therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels. Within a certain window of Antiangiogenic effects, interstitial convection within the tumor can increase dramatically, whereas fluid convection out of the tumor margin decreases . This would result in increased drug convection within the tumor and decreased convection of drugs, growth factors, or metastatic cancer cells from the tumor margin into the peritumor fluid or tissue. Decreased convection of growth factors, such as vascular endothelial growth factor-C (VEGF-C), would limit peritumor hyperplasia, and decreased VEGF-A would limit angiogenesis in sentinel lymph nodes. Both of these effects would reduce the probability of lymphatic metastasis. Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies. [Cancer Res 2007;67(6):2729–35]

  • Effect of vascular normalization by Antiangiogenic Therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: Insights from a mathematical model
    Cancer Research, 2007
    Co-Authors: Rakesh K. Jain, Ricky T. Tong, Lance L. Munn
    Abstract:

    Preclinical and clinical evidence shows that Antiangiogenic agents can decrease tumor vessel permeability and interstitial fluid pressure (IFP) in a process of vessel "normalization." The resulting normalized vasculature has more efficient perfusion, but little is known about how tumor IFP and interstitial fluid velocity (IFV) are affected by changes in transport properties of the vessels and interstitium that are associated with Antiangiogenic Therapy. By using a mathematical model to simulate IFP and IFV profiles in tumors, we show here that Antiangiogenic Therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels. Within a certain window of Antiangiogenic effects, interstitial convection within the tumor can increase dramatically, whereas fluid convection out of the tumor margin decreases. This would result in increased drug convection within the tumor and decreased convection of drugs, growth factors, or metastatic cancer cells from the tumor margin into the peritumor fluid or tissue. Decreased convection of growth factors, such as vascular endothelial growth factor-C (VEGF-C), would limit peritumor hyperplasia, and decreased VEGF-A would limit angiogenesis in sentinel lymph nodes. Both of these effects would reduce the probability of lymphatic metastasis. Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies.

  • Antiangiogenic Therapy for cancer current and emerging concepts
    Oncology, 2005
    Co-Authors: Rakesh K. Jain
    Abstract:

    Angiogenesis is an essential step in the growth and spread of solid tumors-the cause of more than 85% of cancer mortality. Inhibiting angiogenesis would therefore seem to be a reasonable approach to prevent or treat cancer. However, tumor angiogenesis differs from normal angiogenesis in that the resulting vessels are tortuous, irregularly shaped, and hyperpermeable. These abnormalities result in irregular blood flow and high interstitial fluid pressure within the tumor, which can impair the delivery of oxygen (a known radiation sensitizer) and drugs to the tumor. Emerging evidence suggests that Antiangiogenic Therapy can prune some tumor vessels and normalize the structure and function of the rest, thereby improving drug delivery and normalizing the tumor microenvironment. This normalization effect may underlie the therapeutic benefit of combined Antiangiogenic and cytotoxic therapies. This paper reviews current and emerging concepts of the mechanism of action of Antiangiogenic therapies and discusses the implications of these mechanisms for their optimal clinical use.

Lance L. Munn - One of the best experts on this subject based on the ideXlab platform.

  • effect of vascular normalization by Antiangiogenic Therapy on interstitial hypertension peritumor edema and lymphatic metastasis insights from a mathematical model
    Cancer Research, 2007
    Co-Authors: Rakesh K. Jain, Ricky T. Tong, Lance L. Munn
    Abstract:

    Preclinical and clinical evidence shows that Antiangiogenic agents can decrease tumor vessel permeability and interstitial fluid pressure (IFP) in a process of vessel “normalization.” The resulting normalized vasculature has more efficient perfusion, but little is known about how tumor IFP and interstitial fluid velocity (IFV) are affected by changes in transport properties of the vessels and interstitium that are associated with Antiangiogenic Therapy. By using a mathematical model to simulate IFP and IFV profiles in tumors, we show here that Antiangiogenic Therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels. Within a certain window of Antiangiogenic effects, interstitial convection within the tumor can increase dramatically, whereas fluid convection out of the tumor margin decreases . This would result in increased drug convection within the tumor and decreased convection of drugs, growth factors, or metastatic cancer cells from the tumor margin into the peritumor fluid or tissue. Decreased convection of growth factors, such as vascular endothelial growth factor-C (VEGF-C), would limit peritumor hyperplasia, and decreased VEGF-A would limit angiogenesis in sentinel lymph nodes. Both of these effects would reduce the probability of lymphatic metastasis. Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies. [Cancer Res 2007;67(6):2729–35]

  • Effect of vascular normalization by Antiangiogenic Therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: Insights from a mathematical model
    Cancer Research, 2007
    Co-Authors: Rakesh K. Jain, Ricky T. Tong, Lance L. Munn
    Abstract:

    Preclinical and clinical evidence shows that Antiangiogenic agents can decrease tumor vessel permeability and interstitial fluid pressure (IFP) in a process of vessel "normalization." The resulting normalized vasculature has more efficient perfusion, but little is known about how tumor IFP and interstitial fluid velocity (IFV) are affected by changes in transport properties of the vessels and interstitium that are associated with Antiangiogenic Therapy. By using a mathematical model to simulate IFP and IFV profiles in tumors, we show here that Antiangiogenic Therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels. Within a certain window of Antiangiogenic effects, interstitial convection within the tumor can increase dramatically, whereas fluid convection out of the tumor margin decreases. This would result in increased drug convection within the tumor and decreased convection of drugs, growth factors, or metastatic cancer cells from the tumor margin into the peritumor fluid or tissue. Decreased convection of growth factors, such as vascular endothelial growth factor-C (VEGF-C), would limit peritumor hyperplasia, and decreased VEGF-A would limit angiogenesis in sentinel lymph nodes. Both of these effects would reduce the probability of lymphatic metastasis. Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies.

  • a mathematical model of the contribution of endothelial progenitor cells to angiogenesis in tumors implications for Antiangiogenic Therapy
    Blood, 2003
    Co-Authors: Brian R Stoll, Lance L. Munn, Cristiano Migliorini, Ananth Kadambi, Rakesh K. Jain
    Abstract:

    The traditional view of angiogenesis emphasizes proliferation and migration of vessel wall-associated endothelial cells. However, circulating endothelial progenitor cells have recently been shown to contribute to tumor angiogenesis. Here we quantify the relative contributions of endothelial and endothelial progenitor cells to angiogenesis using a mathematical model. The model predicts that during the early stages of tumor growth, endothelial progenitors have a significant impact on tumor growth and angiogenesis, mediated primarily by their localization in the tumor, not by their proliferation. The model also shows that, as the tumor grows, endothelial progenitors adhere preferentially near the tumor periphery, coincident with the location of highest vascular density, supporting their potential utility as vectors for targeted delivery of therapeutics. Model simulations of various Antiangiogenic strategies show that those therapies that effectively target both endothelial and endothelial progenitor cells, either by restoring the balance between angiogenic stimulators and inhibitors or by targeting both types of cells directly, are most effective at delaying tumor growth. The combination of continuous low-dose chemoTherapy and Antiangiogenic Therapy is predicted to have the most significant effect on therapeutic outcome. The model offers new insight into tumor angiogenesis with implications for the rational design of Antiangiogenic Therapy. (Blood. 2003;102:2555-2561)

Marek Ancukiewicz - One of the best experts on this subject based on the ideXlab platform.

  • increase in tumor associated macrophages after Antiangiogenic Therapy is associated with poor survival among patients with recurrent glioblastoma
    Neuro-oncology, 2013
    Co-Authors: Christine Luemerson, Dan G Duda, Matija Snuderl, Nathaniel D Kirkpatrick, Jermaine Goveia, Christian Davidson, Yuhui Huang, Lars Riedemann, Jennie Taylor, Marek Ancukiewicz
    Abstract:

    Antiangiogenic Therapy is associated with increased radiographic responses in glioblastomas, but tumors invariably recur. Because tumor-associated macrophages have been shown to mediate escape from Antiangiogenic Therapy in preclinical models, we examined the role of macrophages in patients with recurrent glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent glioblastoma who received Antiangiogenic treatment and chemoradiation with 8 patients who received chemoTherapy and/or radioTherapy without Antiangiogenic Therapy or no treatment. Tumor-associated macrophages were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in macrophages in the Antiangiogenic-treated patients. Immunohistochemical analysis demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and infiltrative areas (P = .02) in Antiangiogenic-treated patients. We also observed an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ macrophages in infiltrative tumor (P = .02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) correlated with poor overall survival among patients who first received Antiangiogenic Therapy at recurrence. In summary, recurrent glioblastomas showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after Antiangiogenic Therapy. Higher numbers of CD11b+ cells correlated with poor survival among these patients. These data suggest that tumor-associated macrophages may participate in escape from Antiangiogenic Therapy and may represent a potential biomarker of resistance and a potential therapeutic target in recurrent glioblastoma.

  • abstract lb 339 increase in tumor associated macrophages tams after Antiangiogenic Therapy is associated with poor survival in recurrent glioblastoma gbm patients
    Cancer Research, 2013
    Co-Authors: Christine Luemerson, Dan G Duda, Matija Snuderl, Nathaniel D Kirkpatrick, Jermaine Goveia, Christian Davidson, Yuhui Huang, Lars Riedemann, Jennie Taylor, Marek Ancukiewicz
    Abstract:

    Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Antiangiogenic Therapy is associated with increased radiographic responses in glioblastomas (GBMs), but tumors invariably recur. Because tumor-associated macrophages (TAMs) have been shown to mediate escape from Antiangiogenic Therapy in preclinical models, we examined the role of TAMs in recurrent glioblastoma (rGBM) patients. We compared autopsy brain specimens from 20 rGBM patients who received Antiangiogenic treatment and chemoradiation (AAT+) to 8 patients who received chemoTherapy and/or radioTherapy without Antiangiogenic Therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry (IHC) for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in TAMs in the AAT+ patients. IHC analysis demonstrated an increase in CD68+ TAMs in the tumor bulk (p<0.01) and infiltrative areas (p=0.02) in AAT+ patients. We also observed an increase in CD11b+ cells in the tumor bulk (p<0.01) and an increase in CD163+ TAMs in infiltrative tumor (p=0.02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumor (p=0.05 and p=0.05, respectively) correlated with poor overall survival in patients who first received Antiangiogenic Therapy at recurrence. In summary, rGBMs showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after Antiangiogenic Therapy. Higher numbers of CD11b+ cells correlated with poor survival in rGBM patients. These data suggest that TAMs may participate in escape from Antiangiogenic Therapy and may represent a potential biomarker of resistance and a potential therapeutic target in rGBM. Citation Format: Christine Lu-Emerson, Matija Snuderl, Nathaniel D. Kirkpatrick, Jermaine Goveia, Jennie Taylor, Christian Davidson, Yuhui Huang, Lars Riedemann, S. Percy Ivy, G. Dan Duda, Marek Ancukiewicz3, Scott R. Plotkin, Andrew Chi, Elizabeth R. Gerstner, April F. Eichler, Jorg Dietrich, Anat O. Stemmer-Rachamimov, Tracy T. Batchelor, Rakesh K. Jain. Increase in tumor-associated macrophages (TAMs) after Antiangiogenic Therapy is associated with poor survival in recurrent glioblastoma (GBM) patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-339. doi:10.1158/1538-7445.AM2013-LB-339

  • effect of Antiangiogenic Therapy on tumor associated macrophages in recurrent glioblastoma
    Journal of Clinical Oncology, 2012
    Co-Authors: Christine Luemerson, Dan G Duda, Tracy T Batchelor, Matija Snuderl, Nathaniel D Kirkpatrick, Christian Davidson, Yuhui Huang, Marek Ancukiewicz, Anat Stemmerrachamimov, Rakesh K. Jain
    Abstract:

    2010 Background: Antiangiogenic Therapy is associated with increased radiographic responses in glioblastoma (GBM), but tumors invariably recur. Tumor associated macrophages (TAMs) have been proposed as a mechanism of resistance to anti-angiogenic Therapy in preclinical models. To examine the role of TAMs in recurrent GBM, we analyzed autopsy specimens from patients with or without history of Antiangiogenic Therapy. Methods: We compared autopsy brain specimens from 17 recurrent GBM patients who received anti-angiogenic treatment and chemoradiation (AAT+) to 7 patients who received chemoTherapy and/or radioTherapy without anti-angiogenic Therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically identified with flow cytometry and immunohistochemistry (IHC) with CD68, CD11b, CD14, and CD163 markers. All specimens were obtained from the Department of Pathology at Massachusetts General Hospital and clinical information gained through review of the patients’ records. Results: Using flow cytom...

Ronald M Bukowski - One of the best experts on this subject based on the ideXlab platform.

  • antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior Antiangiogenic Therapy
    The Journal of Urology, 2008
    Co-Authors: Ila Tamaskar, Jorge A Garcia, Paul Elson, Laura S Wood, Tarek Mekhail, Robert Dreicer, Brian I Rini, Ronald M Bukowski
    Abstract:

    Purpose: Antiangiogenic Therapy with sunitinib and sorafenib has become the standard of care for patients with advanced renal cell carcinoma. However, the clinical benefit of these agents after prior Antiangiogenic Therapy has not been defined. Currently, several agents with a putative Antiangiogenic mechanism exist and they are often being used in sequence with little to no data regarding activity in a second line or later setting.Materials and Methods: Patients with advanced renal cell carcinoma currently being treated with either sunitinib or sorafenib after receiving 1 or more prior Antiangiogenic agent(s) were investigated in a retrospective analysis. Time to progression and the overall response rate by Response Evaluation Criteria in Solid Tumors were evaluated.Results: Thirty patients receiving current sunitinib (16 patients) or sorafenib (14 patients) were identified. Patients received 1 or more prior Antiangiogenic therapies: thalidomide, lenalidomide, bevacizumab, volociximab, AG13736, sorafenib...

Christine Luemerson - One of the best experts on this subject based on the ideXlab platform.

  • increase in tumor associated macrophages after Antiangiogenic Therapy is associated with poor survival among patients with recurrent glioblastoma
    Neuro-oncology, 2013
    Co-Authors: Christine Luemerson, Dan G Duda, Matija Snuderl, Nathaniel D Kirkpatrick, Jermaine Goveia, Christian Davidson, Yuhui Huang, Lars Riedemann, Jennie Taylor, Marek Ancukiewicz
    Abstract:

    Antiangiogenic Therapy is associated with increased radiographic responses in glioblastomas, but tumors invariably recur. Because tumor-associated macrophages have been shown to mediate escape from Antiangiogenic Therapy in preclinical models, we examined the role of macrophages in patients with recurrent glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent glioblastoma who received Antiangiogenic treatment and chemoradiation with 8 patients who received chemoTherapy and/or radioTherapy without Antiangiogenic Therapy or no treatment. Tumor-associated macrophages were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in macrophages in the Antiangiogenic-treated patients. Immunohistochemical analysis demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and infiltrative areas (P = .02) in Antiangiogenic-treated patients. We also observed an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ macrophages in infiltrative tumor (P = .02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) correlated with poor overall survival among patients who first received Antiangiogenic Therapy at recurrence. In summary, recurrent glioblastomas showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after Antiangiogenic Therapy. Higher numbers of CD11b+ cells correlated with poor survival among these patients. These data suggest that tumor-associated macrophages may participate in escape from Antiangiogenic Therapy and may represent a potential biomarker of resistance and a potential therapeutic target in recurrent glioblastoma.

  • abstract lb 339 increase in tumor associated macrophages tams after Antiangiogenic Therapy is associated with poor survival in recurrent glioblastoma gbm patients
    Cancer Research, 2013
    Co-Authors: Christine Luemerson, Dan G Duda, Matija Snuderl, Nathaniel D Kirkpatrick, Jermaine Goveia, Christian Davidson, Yuhui Huang, Lars Riedemann, Jennie Taylor, Marek Ancukiewicz
    Abstract:

    Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Antiangiogenic Therapy is associated with increased radiographic responses in glioblastomas (GBMs), but tumors invariably recur. Because tumor-associated macrophages (TAMs) have been shown to mediate escape from Antiangiogenic Therapy in preclinical models, we examined the role of TAMs in recurrent glioblastoma (rGBM) patients. We compared autopsy brain specimens from 20 rGBM patients who received Antiangiogenic treatment and chemoradiation (AAT+) to 8 patients who received chemoTherapy and/or radioTherapy without Antiangiogenic Therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry (IHC) for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in TAMs in the AAT+ patients. IHC analysis demonstrated an increase in CD68+ TAMs in the tumor bulk (p<0.01) and infiltrative areas (p=0.02) in AAT+ patients. We also observed an increase in CD11b+ cells in the tumor bulk (p<0.01) and an increase in CD163+ TAMs in infiltrative tumor (p=0.02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumor (p=0.05 and p=0.05, respectively) correlated with poor overall survival in patients who first received Antiangiogenic Therapy at recurrence. In summary, rGBMs showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after Antiangiogenic Therapy. Higher numbers of CD11b+ cells correlated with poor survival in rGBM patients. These data suggest that TAMs may participate in escape from Antiangiogenic Therapy and may represent a potential biomarker of resistance and a potential therapeutic target in rGBM. Citation Format: Christine Lu-Emerson, Matija Snuderl, Nathaniel D. Kirkpatrick, Jermaine Goveia, Jennie Taylor, Christian Davidson, Yuhui Huang, Lars Riedemann, S. Percy Ivy, G. Dan Duda, Marek Ancukiewicz3, Scott R. Plotkin, Andrew Chi, Elizabeth R. Gerstner, April F. Eichler, Jorg Dietrich, Anat O. Stemmer-Rachamimov, Tracy T. Batchelor, Rakesh K. Jain. Increase in tumor-associated macrophages (TAMs) after Antiangiogenic Therapy is associated with poor survival in recurrent glioblastoma (GBM) patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-339. doi:10.1158/1538-7445.AM2013-LB-339

  • effect of Antiangiogenic Therapy on tumor associated macrophages in recurrent glioblastoma
    Journal of Clinical Oncology, 2012
    Co-Authors: Christine Luemerson, Dan G Duda, Tracy T Batchelor, Matija Snuderl, Nathaniel D Kirkpatrick, Christian Davidson, Yuhui Huang, Marek Ancukiewicz, Anat Stemmerrachamimov, Rakesh K. Jain
    Abstract:

    2010 Background: Antiangiogenic Therapy is associated with increased radiographic responses in glioblastoma (GBM), but tumors invariably recur. Tumor associated macrophages (TAMs) have been proposed as a mechanism of resistance to anti-angiogenic Therapy in preclinical models. To examine the role of TAMs in recurrent GBM, we analyzed autopsy specimens from patients with or without history of Antiangiogenic Therapy. Methods: We compared autopsy brain specimens from 17 recurrent GBM patients who received anti-angiogenic treatment and chemoradiation (AAT+) to 7 patients who received chemoTherapy and/or radioTherapy without anti-angiogenic Therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically identified with flow cytometry and immunohistochemistry (IHC) with CD68, CD11b, CD14, and CD163 markers. All specimens were obtained from the Department of Pathology at Massachusetts General Hospital and clinical information gained through review of the patients’ records. Results: Using flow cytom...