[simplecontent lang="" source="answers" backup="answer"]stage 1 Breast cancer treatment[/simplecontent]
FREE VIDEO – Stage 1 Breast Cancer Info From Dr. Harness
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Angiotensin-(1-7): A novel small molecule for the targeted treatment of triple negative breast cancer. $49.99 Triple negative breast cancer (TNBC), an aggressive breast tumor that disproportionately affects young and minority women, is associated with a poor survival rate regardless of stage at diagnosis due to development of distant metastases. Tumors from women with TNBC lack estrogen receptors and progesterone receptors and have basal expression of the human epidermal growth factor receptor 2 (HER2), severely limiting therapeutic strategies. The purpose of this study was to determine whether angiotensin-(1-7) [Ang-(1-7)], an endogenous peptide hormone that activates the AT(1-7) receptor mas , inhibits the growth of triple negative breast cancer cells and tumors and identify the molecular mechanisms for the inhibition of cancer cell growth. Injection of MDA-MB-231 cells into the mammary fat pad of athymic mice resulted in triple negative breast tumors that were treated for 28 days with either saline or Ang-(1-7). The average tumor volume from mice treated with the heptapeptide was approximately 3-fold less than the size of tumors from control animals (170.8 +/- 21.4 mm3 vs. 546.7 +/- 87.9 mm3; n = 5, p < 0.05) and tumor weight was reduced from 1.0 +/- 0.2 g in the saline-treated mice to 0.5 +/- 0.1 g in Ang-(1-7)-treated mice (n = 5, p < 0.05). The reduced size of Ang-(1-7)-treated tumors was associated with low immunoreactivity to Ki67, a proliferation marker (84.2 +/- 8.2 compared to 41 +/- 7.6), suggesting that Ang-(1-7) attenuates cell growth. Activity of the MAP kinases ERK1 and ERK2 was reduced in tumors of Ang-(1-7)-treated mice which was associated with a receptor-mediated increase in the MAP kinase phosphatase DUSP1 (1.01 +/- 0.1 relative gene expression in tumors from saline-treated mice compared to 1.78 +/- 0.13 in tumors from Ang-(1-7)-treated mice). The decrease in tumor growth of Ang-(1-7)-treated mice was also associated with a reduction in the endothelial cell marker CD34 (a decrease in vessel density from 87.8 +/- 6.4 in tumors from saline-treated |
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Angiotensin-(1-7): A novel small molecule for the targeted treatment of triple negative breast cancer. $49.99 Triple negative breast cancer (TNBC), an aggressive breast tumor that disproportionately affects young and minority women, is associated with a poor survival rate regardless of stage at diagnosis due to development of distant metastases. Tumors from women with TNBC lack estrogen receptors and progesterone receptors and have basal expression of the human epidermal growth factor receptor 2 (HER2), severely limiting therapeutic strategies. The purpose of this study was to determine whether angiotensin-(1-7) [Ang-(1-7)], an endogenous peptide hormone that activates the AT(1-7) receptor mas , inhibits the growth of triple negative breast cancer cells and tumors and identify the molecular mechanisms for the inhibition of cancer cell growth. Injection of MDA-MB-231 cells into the mammary fat pad of athymic mice resulted in triple negative breast tumors that were treated for 28 days with either saline or Ang-(1-7). The average tumor volume from mice treated with the heptapeptide was approximately 3-fold less than the size of tumors from control animals (170.8 +/- 21.4 mm3 vs. 546.7 +/- 87.9 mm3; n = 5, p < 0.05) and tumor weight was reduced from 1.0 +/- 0.2 g in the saline-treated mice to 0.5 +/- 0.1 g in Ang-(1-7)-treated mice (n = 5, p < 0.05). The reduced size of Ang-(1-7)-treated tumors was associated with low immunoreactivity to Ki67, a proliferation marker (84.2 +/- 8.2 compared to 41 +/- 7.6), suggesting that Ang-(1-7) attenuates cell growth. Activity of the MAP kinases ERK1 and ERK2 was reduced in tumors of Ang-(1-7)-treated mice which was associated with a receptor-mediated increase in the MAP kinase phosphatase DUSP1 (1.01 +/- 0.1 relative gene expression in tumors from saline-treated mice compared to 1.78 +/- 0.13 in tumors from Ang-(1-7)-treated mice). The decrease in tumor growth of Ang-(1-7)-treated mice was also associated with a reduction in the endothelial cell marker CD34 (a decrease in vessel density from 87.8 +/- 6.4 in tumors from saline-treated |
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Disparities in the treatment of early breast cancer. $49.99 The aims of this dissertation were to: (1) determine the frequency of use of adjuvant systemic treatment for early breast cancer among women 65 years of age and older, (2) examine whether differences exist in receipt of standard treatment for early breast cancer between black and white women, and (3) examine whether differences exist in delays in initiation of treatment for early breast cancer between black and white women.;Aim 1 utilized data from the population-based New Jersey Cancer Registry (NJSCR) to ascertain the frequency of use of adjuvant systemic treatment among 200 women (100 fatal cases and 100 non-fatal cases) who were ≥ 65 years of age and diagnosed with early stage breast cancer during 1987-1998. For Aims 2 and 3 of this dissertation, a retrospective cohort study was designed using a linked NJSCR and New Jersey Medicaid dataset for the years 1997 through 2001. Participants in these studies were women 20-64 years of age who were diagnosed with early-stage breast cancer (SEER Summary Stage ‘localized’ and ‘regional spread to lymph nodes’) between January 1997 and December 2001.;Results. Aim 1 of this dissertation showed that 28% of elderly New Jersey women with early breast cancer received chemotherapy alone or in combination with hormonal therapy whereas 42% received hormonal therapy alone. Only 40% of the women with ER negative tumors received chemotherapy alone or in combination with hormonal treatment and 30% of patients did not receive any adjuvant therapy. Examination of racial differences in receipt of standard treatment (Aim 2) revealed no differences in receipt of surgical, radiation, or adjuvant systemic treatment. Breast cancer specific mortality (Hazard ratio=1.37; 95% confidence interval = 0.94–1.98) and all-cause mortality (Hazard Ratio=1.43; 95% confidence interval=1.08-1.89) were higher among blacks than whites. Although no racial differences were noted in receipt of standard treatment, Aim 3 showed that blacks as compared to |
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Disparities in the treatment of early breast cancer. $49.99 The aims of this dissertation were to: (1) determine the frequency of use of adjuvant systemic treatment for early breast cancer among women 65 years of age and older, (2) examine whether differences exist in receipt of standard treatment for early breast cancer between black and white women, and (3) examine whether differences exist in delays in initiation of treatment for early breast cancer between black and white women.;Aim 1 utilized data from the population-based New Jersey Cancer Registry (NJSCR) to ascertain the frequency of use of adjuvant systemic treatment among 200 women (100 fatal cases and 100 non-fatal cases) who were ≥ 65 years of age and diagnosed with early stage breast cancer during 1987-1998. For Aims 2 and 3 of this dissertation, a retrospective cohort study was designed using a linked NJSCR and New Jersey Medicaid dataset for the years 1997 through 2001. Participants in these studies were women 20-64 years of age who were diagnosed with early-stage breast cancer (SEER Summary Stage ‘localized’ and ‘regional spread to lymph nodes’) between January 1997 and December 2001.;Results. Aim 1 of this dissertation showed that 28% of elderly New Jersey women with early breast cancer received chemotherapy alone or in combination with hormonal therapy whereas 42% received hormonal therapy alone. Only 40% of the women with ER negative tumors received chemotherapy alone or in combination with hormonal treatment and 30% of patients did not receive any adjuvant therapy. Examination of racial differences in receipt of standard treatment (Aim 2) revealed no differences in receipt of surgical, radiation, or adjuvant systemic treatment. Breast cancer specific mortality (Hazard ratio=1.37; 95% confidence interval = 0.94–1.98) and all-cause mortality (Hazard Ratio=1.43; 95% confidence interval=1.08-1.89) were higher among blacks than whites. Although no racial differences were noted in receipt of standard treatment, Aim 3 showed that blacks as compared to |
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HEYL, a novel negative regulator of TGF-beta pathway in breast cancer. $49.99 Through serial analysis of gene expression of endothelial cells isolated from breast carcinoma and normal breast tissue, we found that HEYL (hairy/enhancer-of-split related with YRPW motif-like), a basic helix-loop-helix transcription repressor, was consistently overexpressed in tumor endothelial cells. Functional assays showed that overexpression of HEYL in human umbilical vein endothelial cells (HUVEC) increased cell proliferation and conferred strong anti-apoptosis ability, suggesting that HEYL may promote tumor angiogenesis. However, wild-type and HEYL knockout mice supported the growth of xenografts of a syngeneic melanoma cell line equally well, challenging the role of HEYL in neoangiogenesis. Gene expression data provided evidence that HEYL was also overexpressed in the epithelial component of breast cancers. Immunohistochemical analysis on clinical samples showed that HEYL was frequently overexpressed in breast carcinomas. Elevated mRNA expression was also observed at the same frequency in breast carcinomas. DNA amplification of the HEYL gene was not seen, thereby discounting this mechanism for the overexpression of HEYL mRNA and protein. Rather, our work suggested that activation of the Notch pathway may lead to induction of HEYL expression in breast cancer. For the first time, we showed a direct interaction of HEYL with Smad3. This interaction inhibited the TGF-beta signaling, repressing the effects of TGF-beta on reporter gene luciferase assays. Further, the upregulations of both PAI-1 and p15 mRNA induced by TGF-beta were repressed in HEYL-overexpressing cells, and the reduction of HEYL expression in MDA-MB-231 breast cancer cells caused the partial cell growth inhibition upon TGF-beta treatment. Taken together, the data demonstrated that HEYL was a novel negative regulator of the TGF-beta pathway. Acquired resistance to TGF-beta is a key step in the early-stage tumorigenesis. Little is known about the development of this resistance in breast cancer. On |
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HEYL, a novel negative regulator of TGF-beta pathway in breast cancer. $49.99 Through serial analysis of gene expression of endothelial cells isolated from breast carcinoma and normal breast tissue, we found that HEYL (hairy/enhancer-of-split related with YRPW motif-like), a basic helix-loop-helix transcription repressor, was consistently overexpressed in tumor endothelial cells. Functional assays showed that overexpression of HEYL in human umbilical vein endothelial cells (HUVEC) increased cell proliferation and conferred strong anti-apoptosis ability, suggesting that HEYL may promote tumor angiogenesis. However, wild-type and HEYL knockout mice supported the growth of xenografts of a syngeneic melanoma cell line equally well, challenging the role of HEYL in neoangiogenesis. Gene expression data provided evidence that HEYL was also overexpressed in the epithelial component of breast cancers. Immunohistochemical analysis on clinical samples showed that HEYL was frequently overexpressed in breast carcinomas. Elevated mRNA expression was also observed at the same frequency in breast carcinomas. DNA amplification of the HEYL gene was not seen, thereby discounting this mechanism for the overexpression of HEYL mRNA and protein. Rather, our work suggested that activation of the Notch pathway may lead to induction of HEYL expression in breast cancer. For the first time, we showed a direct interaction of HEYL with Smad3. This interaction inhibited the TGF-beta signaling, repressing the effects of TGF-beta on reporter gene luciferase assays. Further, the upregulations of both PAI-1 and p15 mRNA induced by TGF-beta were repressed in HEYL-overexpressing cells, and the reduction of HEYL expression in MDA-MB-231 breast cancer cells caused the partial cell growth inhibition upon TGF-beta treatment. Taken together, the data demonstrated that HEYL was a novel negative regulator of the TGF-beta pathway. Acquired resistance to TGF-beta is a key step in the early-stage tumorigenesis. Little is known about the development of this resistance in breast cancer. On |