Wake Forest Comprehensive Cancer Center

Wake Forest, NC, United States

Wake Forest Comprehensive Cancer Center

Wake Forest, NC, United States

Time filter

Source Type

Palmer N.R.A.,San Francisco General Hospital | Weaver K.E.,Social Science and Health Policy | Hauser S.P.,Wake Forest Comprehensive Cancer Center | Lawrence J.A.,Wake Forest Comprehensive Cancer Center | Geiger A.M.,U.S. National Cancer Institute
Supportive Care in Cancer | Year: 2015

Purpose: Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors. Methods: We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009–2011, 6–24 months post-treatment (N = 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates. Results: Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %, p = 0.01), other health care costs (21.3 vs. 45.2 %, p = 0.01), anxiety/worry (29.4 vs. 51.6 %, p = 0.02), and transportation (4.4 vs. 16.1 %, p = 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1–10.1). Conclusions: Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors. © 2015, Springer-Verlag Berlin Heidelberg.


Barlow K.D.,Medical Center Boulevard | Sanders A.M.,Medical Center Boulevard | Soker S.,Wake Forest Comprehensive Cancer Center | Soker S.,Wake Forest Institute for Regenerative Medicine | And 3 more authors.
Cancer Microenvironment | Year: 2013

The induction of tumor vasculature, known as the 'angiogenic switch', is a rate-limiting step in tumor progression. Normal blood vessels are composed of two distinct cell types: endothelial cells which form the channel through which blood flows, and mural cells, the pericytes and smooth muscle cells which serve to support and stabilize the endothelium. Most functional studies have focused on the responses of endothelial cells to pro-angiogenic stimuli; however, there is mounting evidence that the supporting mural cells, particularly pericytes, may play key regulatory roles in both promoting vessel growth as well as terminating vessel growth to generate a mature, quiescent vasculature. Tumor vessels are characterized by numerous structural and functional abnormalities, including altered association between endothelial cells and pericytes. These dysfunctional, unstable vessels contribute to hypoxia, interstitial fluid pressure, and enhanced susceptibility to metastatic invasion. Increasing evidence points to the pericyte as a critical regulator of endothelial activation and subsequent vessel development, stability, and function. Here we discuss both the stimulatory and inhibitory effects of pericytes on the vasculature and the possible utilization of vessel normalization as a therapeutic strategy to combat cancer. © 2012 Springer Science+Business Media B.V.


PubMed | San Francisco General Hospital, Social Science and Health Policy, U.S. National Cancer Institute and Wake Forest Comprehensive Cancer Center
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2015

Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors.We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009-2011, 6-24 months post-treatment (N = 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates.Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %, p = 0.01), other health care costs (21.3 vs. 45.2 %, p = 0.01), anxiety/worry (29.4 vs. 51.6 %, p = 0.02), and transportation (4.4 vs. 16.1 %, p = 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1-10.1).Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors.


Bussard K.M.,Wake Forest Comprehensive Cancer Center | Bussard K.M.,Thomas Jefferson University | Mutkus L.,Wake forest University | Stumpf K.,Wake forest University | And 3 more authors.
Breast Cancer Research | Year: 2016

The tumor microenvironment is a heterogeneous population of cells consisting of the tumor bulk plus supporting cells. It is becoming increasingly evident that these supporting cells are recruited by cancer cells from nearby endogenous host stroma and promote events such as tumor angiogenesis, proliferation, invasion, and metastasis, as well as mediate mechanisms of therapeutic resistance. In addition, recruited stromal cells range in type and include vascular endothelial cells, pericytes, adipocytes, fibroblasts, and bone-marrow mesenchymal stromal cells. During normal wound healing and inflammatory processes, local stromal cells change their phenotype to become that of reactive stroma. Under certain conditions, however, tumor cells can co-opt these reactive stromal cells and further transition them into tumor-associated stromal cells (TASCs). These TASCs express higher levels of proteins, including alpha-smooth muscle actin, fibroblast activating protein, and matrix metalloproteinases, compared with their normal, non-reactive counterparts. TASCs are also known to secrete many pro-tumorigenic factors, including IL-6, IL-8, stromal-derived factor-1 alpha, vascular endothelial growth factor, tenascin-C, and matrix metalloproteinases, among others, which recruit additional tumor and pro-tumorigenic cells to the developing microenvironment. Here, we review the current literature pertaining to the origins of recruited host stroma, contributions toward tumor progression, tumor-associated stromal cells, and mechanisms of crosstalk between endogenous host stroma and tumor cells. © 2016 The Author(s).


Burger K.L.,Wake Forest Comprehensive Cancer Center | Learman B.S.,Wake Forest Comprehensive Cancer Center | Boucherle A.K.,Wake Forest Comprehensive Cancer Center | Sirintrapun S.J.,Wake Forest Comprehensive Cancer Center | And 4 more authors.
Prostate | Year: 2014

BACKGROUND The Src tyrosine kinase substrate and adaptor protein Tks5 had previously been implicated in the invasive phenotype of normal and transformed cell types via regulation of cytoskeletal structures called podosomes/ invadopodia. The role of Src-Tks5 signaling in invasive prostate cancer, however, had not been previously evaluated. METHODS We measured the relative expression of Tks5 in normal (n = 20) and cancerous (n = 184, from 92 patients) prostate tissue specimens by immunohistochemistry using a commercially available tumor microarray. We also manipulated the expression and activity of wild-type and mutant Src and Tks5 constructs in the LNCaP and PC-3 prostate cancer cell lines in order to ascertain the role of Src-Tks5 signaling in invadopodia development, matrix-remodeling activity, motility, and invasion. RESULTS Our studies demonstrated that Src was activated and Tks5 upregulated in high Gleason score prostate tumor specimens and in invasive prostate cancer cell lines. Remarkably, overexpression of Tks5 in LNCaP cells was sufficient to induce invadopodia formation and associated matrix degradation. This Tks5-dependent increase in invasive behavior further depended on Src tyrosine kinase activity and the phosphorylation of Tks5 at tyrosine residues 557 and 619. In PC-3 cells we demonstrated that Tks5 phosphorylation at these sites was necessary and sufficient for invadopodia-associated matrix degradation and invasion. CONCLUSIONS Our results suggest a general role for Src-Tks5 signaling in prostate tumor progression and the utility of Tks5 as a marker protein for the staging of this disease. Prostate 74:134-148, 2014. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.


Burger K.L.,Wake Forest Comprehensive Cancer Center | Davis A.L.,Wake Forest Comprehensive Cancer Center | Isom S.,Wake Forest Comprehensive Cancer Center | Mishra N.,Wake Forest Comprehensive Cancer Center | Seals D.F.,Wake Forest Comprehensive Cancer Center
Cytoskeleton | Year: 2011

Tks5 is a Src substrate and adaptor protein previously recognized for its regulation of cancer cell invasion through modulation of specialized adhesion structures called podosomes/invadopodia. Here we show for the first time that Tks5 localizes to the podosomes of primary macrophages, and that Tks5 protein levels increase concurrently with podosome deposition during the differentiation of monocytes into macrophages. Similar results are reported for model THP-1 cells, which differentiate into macrophages and form proteolytically active podosomes in response to a PKC signaling agonist (PMA) and with sensitivity to a PKC inhibitor (bisindolylmaleimide). Genetic manipulation of Tks5 expression (silencing and overexpression) in stable THP-1 cell lines does not independently alter this macrophage differentiation process. Nor do these cells lose the ability to focalize F-actin and its accessory proteins into podosome-like structures following PMA treatment. However, Tks5 directly controls podosome-associated gelatin degradation and invasion through collective changes in adhesion, chemotaxis, and the expression/proteolytic activity of MMP9. The Src family kinase-dependent phosphorylation of Tks5 is also implicated in the regulation of THP-1 macrophage invasive behavior. These results therefore define a previously unappreciated function of Tks5 signaling specific to the functional attributes of the macrophage podosome in adhesion, motility, and extracellular matrix-remodeling. © 2011 Wiley Periodicals, Inc.


Colonna S.V.,George E Whalen Veterans Affairs Hospital | Higgins A.K.,Wake Forest Comprehensive Cancer Center | Alvarez J.,Vanderbilt University | Saville B.R.,Vanderbilt University | And 2 more authors.
Clinical Breast Cancer | Year: 2015

Introduction: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with higher recurrence rates than other breast cancer subtypes. Increasing numbers of women are being diagnosed with early-stage breast cancer because of improvements in screening mammography. TNBC is known to be highly sensitive to chemotherapy; however, the benefit of adjuvant chemotherapy among women with ≤ 1-cm, lymph node-negative TNBC is unknown. Materials and Methods: We evaluated the recurrence rates and recurrence-free survival of 437 women diagnosed with stage T1a-T1bN0 breast cancer from 1997 to 2009 at 2 institutions, with a median follow-up time of 6.2 years. Furthermore, we examined the treatment regimens of these women and evaluated the association of adjuvant chemotherapy with recurrence-free survival. Results: Chemotherapy was administered more often to younger women and to women with high-grade, human epidermal growth factor receptor 2-positive or TNBC. Recurrence-free survival did not differ significantly between TNBC and estrogen receptor-positive breast cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.04; P = .058). After appropriate adjustments, no significant differences were detected in recurrence-free survival between the women who had received chemotherapy and those who had not among the women with TNBC (P = .132) or within any of the breast cancer subtypes (HR, 0.6; 95% CI, 0.2-1.9; P = .392). Conclusion: Prospective trials of this subcentimeter node-negative breast cancer population are warranted to guide adjuvant chemotherapy decisions. © 2015.


PubMed | Wake Forest Comprehensive Cancer Center
Type: Journal Article | Journal: The Prostate | Year: 2013

The Src tyrosine kinase substrate and adaptor protein Tks5 had previously been implicated in the invasive phenotype of normal and transformed cell types via regulation of cytoskeletal structures called podosomes/invadopodia. The role of Src-Tks5 signaling in invasive prostate cancer, however, had not been previously evaluated.We measured the relative expression of Tks5 in normal (n = 20) and cancerous (n = 184, from 92 patients) prostate tissue specimens by immunohistochemistry using a commercially available tumor microarray. We also manipulated the expression and activity of wild-type and mutant Src and Tks5 constructs in the LNCaP and PC-3 prostate cancer cell lines in order to ascertain the role of Src-Tks5 signaling in invadopodia development, matrix-remodeling activity, motility, and invasion.Our studies demonstrated that Src was activated and Tks5 upregulated in high Gleason score prostate tumor specimens and in invasive prostate cancer cell lines. Remarkably, overexpression of Tks5 in LNCaP cells was sufficient to induce invadopodia formation and associated matrix degradation. This Tks5-dependent increase in invasive behavior further depended on Src tyrosine kinase activity and the phosphorylation of Tks5 at tyrosine residues 557 and 619. In PC-3 cells we demonstrated that Tks5 phosphorylation at these sites was necessary and sufficient for invadopodia-associated matrix degradation and invasion.Our results suggest a general role for Src-Tks5 signaling in prostate tumor progression and the utility of Tks5 as a marker protein for the staging of this disease.


PubMed | Wake forest University, University of Houston and Wake Forest Comprehensive Cancer Center
Type: Journal Article | Journal: Breast cancer research : BCR | Year: 2016

The tumor microenvironment is a heterogeneous population of cells consisting of the tumor bulk plus supporting cells. It is becoming increasingly evident that these supporting cells are recruited by cancer cells from nearby endogenous host stroma and promote events such as tumor angiogenesis, proliferation, invasion, and metastasis, as well as mediate mechanisms of therapeutic resistance. In addition, recruited stromal cells range in type and include vascular endothelial cells, pericytes, adipocytes, fibroblasts, and bone-marrow mesenchymal stromal cells. During normal wound healing and inflammatory processes, local stromal cells change their phenotype to become that of reactive stroma. Under certain conditions, however, tumor cells can co-opt these reactive stromal cells and further transition them into tumor-associated stromal cells (TASCs). These TASCs express higher levels of proteins, including alpha-smooth muscle actin, fibroblast activating protein, and matrix metalloproteinases, compared with their normal, non-reactive counterparts. TASCs are also known to secrete many pro-tumorigenic factors, including IL-6, IL-8, stromal-derived factor-1 alpha, vascular endothelial growth factor, tenascin-C, and matrix metalloproteinases, among others, which recruit additional tumor and pro-tumorigenic cells to the developing microenvironment. Here, we review the current literature pertaining to the origins of recruited host stroma, contributions toward tumor progression, tumor-associated stromal cells, and mechanisms of crosstalk between endogenous host stroma and tumor cells.


PubMed | Vanderbilt Ingram Cancer Center, Vanderbilt University, George E Whalen Veterans Affairs Hospital and Wake Forest Comprehensive Cancer Center
Type: Journal Article | Journal: Clinical breast cancer | Year: 2016

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with higher recurrence rates than other breast cancer subtypes. Increasing numbers of women are being diagnosed with early-stage breast cancer because of improvements in screening mammography. TNBC is known to be highly sensitive to chemotherapy; however, the benefit of adjuvant chemotherapy among women with 1-cm, lymph node-negative TNBC is unknown.We evaluated the recurrence rates and recurrence-free survival of 437 women diagnosed with stage T1a-T1bN0 breast cancer from 1997 to 2009 at 2 institutions, with a median follow-up time of 6.2 years. Furthermore, we examined the treatment regimens of these women and evaluated the association of adjuvant chemotherapy with recurrence-free survival.Chemotherapy was administered more often to younger women and to women with high-grade, human epidermal growth factor receptor 2-positive or TNBC. Recurrence-free survival did not differ significantly between TNBC and estrogen receptor-positive breast cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.04; P= .058). After appropriate adjustments, no significant differences were detected in recurrence-free survival between the women who had received chemotherapy and those who had not among the women with TNBC (P= .132) or within any of the breast cancer subtypes (HR, 0.6; 95% CI, 0.2-1.9; P= .392).Prospective trials of this subcentimeter node-negative breast cancer population are warranted to guide adjuvant chemotherapy decisions.

Loading Wake Forest Comprehensive Cancer Center collaborators
Loading Wake Forest Comprehensive Cancer Center collaborators