BACKGROUND Breast cancer (BC) is one of the leading causes of cancer mortality in women. Glutathi... more BACKGROUND Breast cancer (BC) is one of the leading causes of cancer mortality in women. Glutathione S-transferase (GSTT1) is involved in activation of detoxification reactions and catalysis of chemicals conjugation with glutathione. GSTT1 genotype is a limiting factor for some environmental diseases. Epigenetic changes have an essential role in BC through inappropriate interaction between genomic and environmental risk factors. AIM This study was directed to explore the association of BC risk with GSTT1 genetic variations and its methylation status in Egyptian women. DESIGN AND METHODS This study included 100 healthy women as control group and 100 patients, clinically and histologically diagnosed as breast cancer. All blood samples were used for genomic DNA extraction. GSTT1 genotyping was accomplished by multiplex polymerase chain reaction (PCR) and methylation-specific PCR was used to analyze the GSTT1 promoter methylation status. RESULTS Breast cancer patients showed significant incidence of null GSTT1in relation to controls (p = 0.004). GSTT1 gene promoter methylation status showed significant difference between hypermethylated and unmethylated patients when compared with healthy subjects (p = 0.005). GSTT1promoter methylation status was not significantly associated with null genotype. There was no significant association between GSTT1-null genotypes and BC stage in cases with or without family history, but for promotor methylation, there was significant association with stage III and IV breast cancer disease. CONCLUSION GSTT1 null genetic variant and promoter hypermethylation in the GSTT region of the gene may be considered as critical risk factors for BC in Egyptian women. This article is protected by copyright. All rights reserved.
Cost and power consumption are substantial challenges<br> for multiple-input-multiple-outpu... more Cost and power consumption are substantial challenges<br> for multiple-input-multiple-output (MIMO) wireless communication<br> systems when the number of antennas and the<br> operating carrier frequency increase. We present a low cost<br> and low power consumption receive spatial modulation (RSM)<br> architecture based on a simple receiver design. We propose<br> a time-division-duplex (TDD) transmission protocol aimed to<br> reduce the training overhead where the channel knowledge is<br> required only at the base station. Simulation results presented<br> show that the power consumption and the energy efficiency<br> of the proposed RSM architecture outperform the hybrid and<br> conventional MIMO systems.
Recently, a receive spatial modulation (RSM) for<br> massive multiple-input-multiple-output... more Recently, a receive spatial modulation (RSM) for<br> massive multiple-input-multiple-output operating in millimeter<br> wave (mmWave) was introduced with the purpose of simplifying<br> user terminal circuit by employing only one radio-frequency<br> chain and attaining high spectral efficiency by exploiting the<br> receive spatial dimension. However, when RSM is applied in<br> a mmWave channel, it demands a challenging receive antenna<br> selection (RAS) procedure. On the other hand, the power<br> consumption at the transmitter side is high when a full digital<br> (FD) precoder is envisioned. We consider the joint problem<br> of RAS and precoder designs based low complexity hybrid<br> architecture. For the sake of simplicity, we divide this problem<br> into two subproblems. First, we design the RAS assuming FD<br> precoder, and then, we design the hybrid precoder. We propose<br> two novel and efficien...
Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary glan... more Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal mammary gland development but still developed mammary tumors with a slightly longer latency than the WAP-Int3 mice. Thus, Notch-induced mammary tumor development is Rbpj-independent. Here, we show that Int3 activates NF-κB in HC11 cells in absence of Rbpj through an association with the IKK signalosome. Int3 induced the canonical NF-κB activity and P50 phosphorylation in HC11 cells without altering the NF-κB2 pathway. The minimal domain within the Int3 protein required to activate NF-κB consists of the CDC10/Ankyrin (ANK) repeats domain. Treatment of WAP-Int3 tumor bearing mice with an IKK...
Experimental biology and medicine (Maywood, N.J.), Jan 21, 2016
Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the... more Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment. In addition, these mice do not develop mammary tumors. We investigated the mechanism for Gleevec regulation of Notch signaling and found that Gleevec treatment results in a loss of Int3 protein but not of Int3 mRNA in HC11 mouse mammary epithelial cells expressing Int3. The addition of MG-132, a proteasome inh...
The accumulation of mutations is a contributing factor in the initiation of premalignant mammary ... more The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent le...
BACKGROUND Breast cancer (BC) is one of the leading causes of cancer mortality in women. Glutathi... more BACKGROUND Breast cancer (BC) is one of the leading causes of cancer mortality in women. Glutathione S-transferase (GSTT1) is involved in activation of detoxification reactions and catalysis of chemicals conjugation with glutathione. GSTT1 genotype is a limiting factor for some environmental diseases. Epigenetic changes have an essential role in BC through inappropriate interaction between genomic and environmental risk factors. AIM This study was directed to explore the association of BC risk with GSTT1 genetic variations and its methylation status in Egyptian women. DESIGN AND METHODS This study included 100 healthy women as control group and 100 patients, clinically and histologically diagnosed as breast cancer. All blood samples were used for genomic DNA extraction. GSTT1 genotyping was accomplished by multiplex polymerase chain reaction (PCR) and methylation-specific PCR was used to analyze the GSTT1 promoter methylation status. RESULTS Breast cancer patients showed significant incidence of null GSTT1in relation to controls (p = 0.004). GSTT1 gene promoter methylation status showed significant difference between hypermethylated and unmethylated patients when compared with healthy subjects (p = 0.005). GSTT1promoter methylation status was not significantly associated with null genotype. There was no significant association between GSTT1-null genotypes and BC stage in cases with or without family history, but for promotor methylation, there was significant association with stage III and IV breast cancer disease. CONCLUSION GSTT1 null genetic variant and promoter hypermethylation in the GSTT region of the gene may be considered as critical risk factors for BC in Egyptian women. This article is protected by copyright. All rights reserved.
Cost and power consumption are substantial challenges<br> for multiple-input-multiple-outpu... more Cost and power consumption are substantial challenges<br> for multiple-input-multiple-output (MIMO) wireless communication<br> systems when the number of antennas and the<br> operating carrier frequency increase. We present a low cost<br> and low power consumption receive spatial modulation (RSM)<br> architecture based on a simple receiver design. We propose<br> a time-division-duplex (TDD) transmission protocol aimed to<br> reduce the training overhead where the channel knowledge is<br> required only at the base station. Simulation results presented<br> show that the power consumption and the energy efficiency<br> of the proposed RSM architecture outperform the hybrid and<br> conventional MIMO systems.
Recently, a receive spatial modulation (RSM) for<br> massive multiple-input-multiple-output... more Recently, a receive spatial modulation (RSM) for<br> massive multiple-input-multiple-output operating in millimeter<br> wave (mmWave) was introduced with the purpose of simplifying<br> user terminal circuit by employing only one radio-frequency<br> chain and attaining high spectral efficiency by exploiting the<br> receive spatial dimension. However, when RSM is applied in<br> a mmWave channel, it demands a challenging receive antenna<br> selection (RAS) procedure. On the other hand, the power<br> consumption at the transmitter side is high when a full digital<br> (FD) precoder is envisioned. We consider the joint problem<br> of RAS and precoder designs based low complexity hybrid<br> architecture. For the sake of simplicity, we divide this problem<br> into two subproblems. First, we design the RAS assuming FD<br> precoder, and then, we design the hybrid precoder. We propose<br> two novel and efficien...
Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary glan... more Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal mammary gland development but still developed mammary tumors with a slightly longer latency than the WAP-Int3 mice. Thus, Notch-induced mammary tumor development is Rbpj-independent. Here, we show that Int3 activates NF-κB in HC11 cells in absence of Rbpj through an association with the IKK signalosome. Int3 induced the canonical NF-κB activity and P50 phosphorylation in HC11 cells without altering the NF-κB2 pathway. The minimal domain within the Int3 protein required to activate NF-κB consists of the CDC10/Ankyrin (ANK) repeats domain. Treatment of WAP-Int3 tumor bearing mice with an IKK...
Experimental biology and medicine (Maywood, N.J.), Jan 21, 2016
Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the... more Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment. In addition, these mice do not develop mammary tumors. We investigated the mechanism for Gleevec regulation of Notch signaling and found that Gleevec treatment results in a loss of Int3 protein but not of Int3 mRNA in HC11 mouse mammary epithelial cells expressing Int3. The addition of MG-132, a proteasome inh...
The accumulation of mutations is a contributing factor in the initiation of premalignant mammary ... more The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent le...
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