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Larry Tait - One of the best experts on this subject based on the ideXlab platform.
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Comedo dcis is a precursor lesion for basal like breast carcinoma identification of a novel p63 her2 neu expressing subgroup
Oncotarget, 2013Co-Authors: Malathy P V Shekhar, Pratima Nangiamakker, Ikuko Kato, Larry TaitAbstract:// Malathy P.V. Shekhar 1,2 , Ikuko Kato 1,2 , Pratima Nangia-Makker 1,2 , and Larry Tait 2 1 Department of Oncology, Wayne State University, Detroit, MI, U.S.A. 2 Karmanos Cancer Institute, Detroit, MI, U.S.A. Correspondence: Malathy P.V. Shekhar, email: // Keywords : breast cancer, p63, Her2/neu, cytokeratin, EGFR Received : January 11, 2013 Accepted : February 22, 2013 Published : February 24, 2013 Abstract Basal breast cancer comprises ~15% of invasive ductal breast cancers, and presents as high-grade lesions with aggressive clinical behavior. Basal breast carcinomas express p63 and cytokeratin 5 (CK5) antigens characteristic of the myoepithelial lineage, and typically lack Her2/neu and hormone receptor expression. However, there is limited data about the precursor lesions from which they emerge. Here we wished to determine whether Comedo-ductal carcinoma in situ (Comedo-DCIS), a high-risk in situ breast lesion, serve as precursors for basal-like breast cancer. To determine this link, p63, CK5, Her2/neu, epidermal growth factor receptor (EGFR), estrogen receptor (ER) and progesterone receptor (PgR) expression were analyzed by immunohistochemistry in 17 clinical Comedo- and 12 nonComedo-DCIS cases, and in tumors derived from unfractionated and CK5-overexpressing subpopulation (MCF10DCIS.com-CK5 high ) of MCF10DCIS.com cells, a model representative of clinical Comedo-DCIS. p63 and Her2/neu coexpression was analyzed by immunofluorescence double labeling. A novel p63/CK5/Her2/neu expressing subpopulation of cells that are ER - /PgR - /EGFR - were identified in the myoepithelial and luminal areas of clinical Comedo-DCIS and tumors derived from unfractionated MCF10DCIS.com and MCF10DCIS.com-CK5 high cells. These data suggest that p63 and Her2/neu expressors may share a common precursor intermediate. P63, but not Her2/neu, expression was significantly associated ( P = 0.038) with microinvasion/recurrence of clinical Comedo-DCIS, and simultaneous expression of p63 and Her2/neu was marginally associated ( P = 0.067) with Comedo-DCIS. These data suggest that p63/Her2/neu expressing precursor intermediate in Comedo-DCIS may provide a cellular basis for emergence of p63+/Her2/neu- or p63+/Her2/neu+ basal-like breast cancer, and that p63/Her2/neu coexpression may serve as biomarkers for identification of this subgroup of basal-like breast cancers.
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ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases
Cancer Biology & Therapy, 2013Co-Authors: Pratima Nangiamakker, Tirza Raz, Larry Tait, Malathy P V Shekhar, Vitaly Balan, Hemanckur Makker, Rafael Fridman, Krishnarao Maddipati, Avraham RazAbstract:Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast Comedo-ductal carcinoma in situ (Comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide ...
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Comedo ductal carcinoma in situ a paradoxical role for programmed cell death
Cancer Biology & Therapy, 2008Co-Authors: Malathy P V Shekhar, Pratima Nangiamakker, Larry Tait, Robert J Pauley, Steven J Santner, Varun Shekhar, Hind Nassar, Daniel W Visscher, Gloria H Heppner, Fred R MillerAbstract:Comedo-DCIS is a histologic subtype of preinvasive breast neoplasia that is characterized by prominent apoptotic cell death and has greater malignant potential than other DCIS subtypes. We investigated the mechanisms of apoptosis in Comedo-DCIS and its role in conversion of Comedo-DCIS to invasive cancer. Clinical Comedo-DCIS excisions and the MCF10DCIS.com human breast cancer model which produces lesions resembling Comedo-DCIS were analyzed. Apoptotic luminal and myoepithelial cells were identified by TUNEL and reactivity to cleaved PARP antibody and cell death assessed by Western blotting, Mitocapture and immunohistochemical assays. MCF10DCIS.com cells undergo spontaneous apoptosis in vitro, both in monolayers and multicellular spheroids; it is associated with increased mitochondrial membrane permeability, increase in Bax/Bcl-2 ratio and occurs via caspase-9-dependent p53-independent pathway. This suggests that apoptosis is stromal-independent and that the cells are programmed to undergo apoptosis. Immunostaining with cleaved PARP antibody showed that myoepithelial apoptosis occurs before lesions progress to Comedo-DCIS in both clinical Comedo-DCIS and in vivo MCF10DCIS.com lesions. Intense staining for MMP-2, MMP-3, MMP-9 and MMP-11 was observed in the stroma and epithelia of solid DCIS lesions prior to conversion to Comedo-DCIS in clinical and MCF10DCIS.com lesions. Gelatin zymography showed higher MMP-2 levels in lysates and conditioned media of MCF10DCIS. com cells undergoing apoptosis. These data suggest that signals arising from the outside (microenvironmental) and inside (internal genetic alterations) of the duct act in concert to trigger apoptosis of myoepithelial and luminal epithelial cells. Our findings implicate spontaneous apoptosis in both the etiology and progression of Comedo-DCIS. It is possible that spontaneous apoptosis facilitates elimination of cells thus permitting expansion and malignant transformation of cancer cells that are resistant to spontaneous apoptosis.
Malathy P V Shekhar - One of the best experts on this subject based on the ideXlab platform.
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Comedo dcis is a precursor lesion for basal like breast carcinoma identification of a novel p63 her2 neu expressing subgroup
Oncotarget, 2013Co-Authors: Malathy P V Shekhar, Pratima Nangiamakker, Ikuko Kato, Larry TaitAbstract:// Malathy P.V. Shekhar 1,2 , Ikuko Kato 1,2 , Pratima Nangia-Makker 1,2 , and Larry Tait 2 1 Department of Oncology, Wayne State University, Detroit, MI, U.S.A. 2 Karmanos Cancer Institute, Detroit, MI, U.S.A. Correspondence: Malathy P.V. Shekhar, email: // Keywords : breast cancer, p63, Her2/neu, cytokeratin, EGFR Received : January 11, 2013 Accepted : February 22, 2013 Published : February 24, 2013 Abstract Basal breast cancer comprises ~15% of invasive ductal breast cancers, and presents as high-grade lesions with aggressive clinical behavior. Basal breast carcinomas express p63 and cytokeratin 5 (CK5) antigens characteristic of the myoepithelial lineage, and typically lack Her2/neu and hormone receptor expression. However, there is limited data about the precursor lesions from which they emerge. Here we wished to determine whether Comedo-ductal carcinoma in situ (Comedo-DCIS), a high-risk in situ breast lesion, serve as precursors for basal-like breast cancer. To determine this link, p63, CK5, Her2/neu, epidermal growth factor receptor (EGFR), estrogen receptor (ER) and progesterone receptor (PgR) expression were analyzed by immunohistochemistry in 17 clinical Comedo- and 12 nonComedo-DCIS cases, and in tumors derived from unfractionated and CK5-overexpressing subpopulation (MCF10DCIS.com-CK5 high ) of MCF10DCIS.com cells, a model representative of clinical Comedo-DCIS. p63 and Her2/neu coexpression was analyzed by immunofluorescence double labeling. A novel p63/CK5/Her2/neu expressing subpopulation of cells that are ER - /PgR - /EGFR - were identified in the myoepithelial and luminal areas of clinical Comedo-DCIS and tumors derived from unfractionated MCF10DCIS.com and MCF10DCIS.com-CK5 high cells. These data suggest that p63 and Her2/neu expressors may share a common precursor intermediate. P63, but not Her2/neu, expression was significantly associated ( P = 0.038) with microinvasion/recurrence of clinical Comedo-DCIS, and simultaneous expression of p63 and Her2/neu was marginally associated ( P = 0.067) with Comedo-DCIS. These data suggest that p63/Her2/neu expressing precursor intermediate in Comedo-DCIS may provide a cellular basis for emergence of p63+/Her2/neu- or p63+/Her2/neu+ basal-like breast cancer, and that p63/Her2/neu coexpression may serve as biomarkers for identification of this subgroup of basal-like breast cancers.
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ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases
Cancer Biology & Therapy, 2013Co-Authors: Pratima Nangiamakker, Tirza Raz, Larry Tait, Malathy P V Shekhar, Vitaly Balan, Hemanckur Makker, Rafael Fridman, Krishnarao Maddipati, Avraham RazAbstract:Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast Comedo-ductal carcinoma in situ (Comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide ...
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Comedo ductal carcinoma in situ a paradoxical role for programmed cell death
Cancer Biology & Therapy, 2008Co-Authors: Malathy P V Shekhar, Pratima Nangiamakker, Larry Tait, Robert J Pauley, Steven J Santner, Varun Shekhar, Hind Nassar, Daniel W Visscher, Gloria H Heppner, Fred R MillerAbstract:Comedo-DCIS is a histologic subtype of preinvasive breast neoplasia that is characterized by prominent apoptotic cell death and has greater malignant potential than other DCIS subtypes. We investigated the mechanisms of apoptosis in Comedo-DCIS and its role in conversion of Comedo-DCIS to invasive cancer. Clinical Comedo-DCIS excisions and the MCF10DCIS.com human breast cancer model which produces lesions resembling Comedo-DCIS were analyzed. Apoptotic luminal and myoepithelial cells were identified by TUNEL and reactivity to cleaved PARP antibody and cell death assessed by Western blotting, Mitocapture and immunohistochemical assays. MCF10DCIS.com cells undergo spontaneous apoptosis in vitro, both in monolayers and multicellular spheroids; it is associated with increased mitochondrial membrane permeability, increase in Bax/Bcl-2 ratio and occurs via caspase-9-dependent p53-independent pathway. This suggests that apoptosis is stromal-independent and that the cells are programmed to undergo apoptosis. Immunostaining with cleaved PARP antibody showed that myoepithelial apoptosis occurs before lesions progress to Comedo-DCIS in both clinical Comedo-DCIS and in vivo MCF10DCIS.com lesions. Intense staining for MMP-2, MMP-3, MMP-9 and MMP-11 was observed in the stroma and epithelia of solid DCIS lesions prior to conversion to Comedo-DCIS in clinical and MCF10DCIS.com lesions. Gelatin zymography showed higher MMP-2 levels in lysates and conditioned media of MCF10DCIS. com cells undergoing apoptosis. These data suggest that signals arising from the outside (microenvironmental) and inside (internal genetic alterations) of the duct act in concert to trigger apoptosis of myoepithelial and luminal epithelial cells. Our findings implicate spontaneous apoptosis in both the etiology and progression of Comedo-DCIS. It is possible that spontaneous apoptosis facilitates elimination of cells thus permitting expansion and malignant transformation of cancer cells that are resistant to spontaneous apoptosis.
Pratima Nangiamakker - One of the best experts on this subject based on the ideXlab platform.
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Comedo dcis is a precursor lesion for basal like breast carcinoma identification of a novel p63 her2 neu expressing subgroup
Oncotarget, 2013Co-Authors: Malathy P V Shekhar, Pratima Nangiamakker, Ikuko Kato, Larry TaitAbstract:// Malathy P.V. Shekhar 1,2 , Ikuko Kato 1,2 , Pratima Nangia-Makker 1,2 , and Larry Tait 2 1 Department of Oncology, Wayne State University, Detroit, MI, U.S.A. 2 Karmanos Cancer Institute, Detroit, MI, U.S.A. Correspondence: Malathy P.V. Shekhar, email: // Keywords : breast cancer, p63, Her2/neu, cytokeratin, EGFR Received : January 11, 2013 Accepted : February 22, 2013 Published : February 24, 2013 Abstract Basal breast cancer comprises ~15% of invasive ductal breast cancers, and presents as high-grade lesions with aggressive clinical behavior. Basal breast carcinomas express p63 and cytokeratin 5 (CK5) antigens characteristic of the myoepithelial lineage, and typically lack Her2/neu and hormone receptor expression. However, there is limited data about the precursor lesions from which they emerge. Here we wished to determine whether Comedo-ductal carcinoma in situ (Comedo-DCIS), a high-risk in situ breast lesion, serve as precursors for basal-like breast cancer. To determine this link, p63, CK5, Her2/neu, epidermal growth factor receptor (EGFR), estrogen receptor (ER) and progesterone receptor (PgR) expression were analyzed by immunohistochemistry in 17 clinical Comedo- and 12 nonComedo-DCIS cases, and in tumors derived from unfractionated and CK5-overexpressing subpopulation (MCF10DCIS.com-CK5 high ) of MCF10DCIS.com cells, a model representative of clinical Comedo-DCIS. p63 and Her2/neu coexpression was analyzed by immunofluorescence double labeling. A novel p63/CK5/Her2/neu expressing subpopulation of cells that are ER - /PgR - /EGFR - were identified in the myoepithelial and luminal areas of clinical Comedo-DCIS and tumors derived from unfractionated MCF10DCIS.com and MCF10DCIS.com-CK5 high cells. These data suggest that p63 and Her2/neu expressors may share a common precursor intermediate. P63, but not Her2/neu, expression was significantly associated ( P = 0.038) with microinvasion/recurrence of clinical Comedo-DCIS, and simultaneous expression of p63 and Her2/neu was marginally associated ( P = 0.067) with Comedo-DCIS. These data suggest that p63/Her2/neu expressing precursor intermediate in Comedo-DCIS may provide a cellular basis for emergence of p63+/Her2/neu- or p63+/Her2/neu+ basal-like breast cancer, and that p63/Her2/neu coexpression may serve as biomarkers for identification of this subgroup of basal-like breast cancers.
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ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases
Cancer Biology & Therapy, 2013Co-Authors: Pratima Nangiamakker, Tirza Raz, Larry Tait, Malathy P V Shekhar, Vitaly Balan, Hemanckur Makker, Rafael Fridman, Krishnarao Maddipati, Avraham RazAbstract:Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast Comedo-ductal carcinoma in situ (Comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide ...
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Comedo ductal carcinoma in situ a paradoxical role for programmed cell death
Cancer Biology & Therapy, 2008Co-Authors: Malathy P V Shekhar, Pratima Nangiamakker, Larry Tait, Robert J Pauley, Steven J Santner, Varun Shekhar, Hind Nassar, Daniel W Visscher, Gloria H Heppner, Fred R MillerAbstract:Comedo-DCIS is a histologic subtype of preinvasive breast neoplasia that is characterized by prominent apoptotic cell death and has greater malignant potential than other DCIS subtypes. We investigated the mechanisms of apoptosis in Comedo-DCIS and its role in conversion of Comedo-DCIS to invasive cancer. Clinical Comedo-DCIS excisions and the MCF10DCIS.com human breast cancer model which produces lesions resembling Comedo-DCIS were analyzed. Apoptotic luminal and myoepithelial cells were identified by TUNEL and reactivity to cleaved PARP antibody and cell death assessed by Western blotting, Mitocapture and immunohistochemical assays. MCF10DCIS.com cells undergo spontaneous apoptosis in vitro, both in monolayers and multicellular spheroids; it is associated with increased mitochondrial membrane permeability, increase in Bax/Bcl-2 ratio and occurs via caspase-9-dependent p53-independent pathway. This suggests that apoptosis is stromal-independent and that the cells are programmed to undergo apoptosis. Immunostaining with cleaved PARP antibody showed that myoepithelial apoptosis occurs before lesions progress to Comedo-DCIS in both clinical Comedo-DCIS and in vivo MCF10DCIS.com lesions. Intense staining for MMP-2, MMP-3, MMP-9 and MMP-11 was observed in the stroma and epithelia of solid DCIS lesions prior to conversion to Comedo-DCIS in clinical and MCF10DCIS.com lesions. Gelatin zymography showed higher MMP-2 levels in lysates and conditioned media of MCF10DCIS. com cells undergoing apoptosis. These data suggest that signals arising from the outside (microenvironmental) and inside (internal genetic alterations) of the duct act in concert to trigger apoptosis of myoepithelial and luminal epithelial cells. Our findings implicate spontaneous apoptosis in both the etiology and progression of Comedo-DCIS. It is possible that spontaneous apoptosis facilitates elimination of cells thus permitting expansion and malignant transformation of cancer cells that are resistant to spontaneous apoptosis.
Hironobu Sasano - One of the best experts on this subject based on the ideXlab platform.
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Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and Comedo necrosis.
Cancer Science, 2017Co-Authors: Mayuko Chishiki, Akiko Ebata, Yukiko Shibahara, Yasuhiro Miki, Mika Watanabe, Takanori Ishida, Ai Sato, Yuta Yamamoto, Kiyoshi Takagi, Hironobu SasanoAbstract:: It is well known that Comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of Comedo DCIS based on microarray data and identified CYC1 as a gene associated with Comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC1 has not yet been examined in DCIS. We therefore immunolocalized CYC1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC1 status was significantly associated with tumor size, nuclear grade, Comedo necrosis, van Nuys classification, and Ki-67 labeling index. Subsequent in vitro studies indicated that CYC1 was significantly associated with mitochondrial membrane potential in MCF10DCIS.com DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of MCF10DCIS.com cells and the cells transfected with CYC1 siRNA decreased pro-apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC1 plays important roles in cell proliferation and Comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS.
Hassan Khan - One of the best experts on this subject based on the ideXlab platform.
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Infiltrating ductal carcinoma breast with central necrosis closely
2016Co-Authors: Shahid Pervez, Hassan KhanAbstract:mimicking ductal carcinoma in situ (Comedo type): a case serie
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infiltrating ductal carcinoma breast with central necrosis closely mimicking ductal carcinoma in situ Comedo type a case series
Journal of Medical Case Reports, 2007Co-Authors: Shahid Pervez, Hassan KhanAbstract:Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis) so closely mimicking 'DCIS with central Comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, Comedo). However on further histological work up and by using immunohistochemistry (IHC) for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial lining is very useful to differentiate DCIS Comedo from invasive carcinoma with central necrosis.