qanastek/HoC · Datasets at Hugging Face

document_id stringlengths 9 11	text stringlengths 6 739	label list
22668016_2	Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment ( 18 weeks ) .	[ 7 ]
22668016_3	At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis .	[ 7 ]
22668016_4	In treated animals ( simvastatin 180 mg/kg ) , significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation .	[ 7 ]
22668016_5	Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells .	[ 4 ]
22668016_6	In high grade control carcinoma cells , the expression of Ki67 increased by 37% ( non-significantly ) in comparison with control low grade carcinomas .	[ 7 ]
22668016_7	A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment .	[ 7 ]
22668016_8	The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment .	[ 4 ]
22083956_0	Estrogen receptor ( ER ) and NF-κB are transcription factors with profound effects on breast cancer cell proliferation and survival .	[ 7 ]
22083956_1	While many studies demonstrate that ER and NF-κB can repress each other , we previously identified a gene signature that is synergistically upregulated by these two factors in more aggressive luminal B breast tumors .	[ 7 ]
22083956_2	Herein , we examine a novel mechanism of cross talk between ER and NF-κB that results in the upregulation of the antiapoptotic gene BIRC3 ( also known as cIAP2 ) .	[ 7 ]
22083956_3	We demonstrate that NF-κB , acting through two response elements , is required for ER recruitment to an adjacent estrogen response element ( ERE ) in the BIRC3 promoter .	[ 7 ]
22083956_4	This effect is accompanied by a major increase in NF-κB-dependent histone acetylation around the ERE .	[ 7 ]
22083956_5	Interestingly , CBP , a histone acetyltransferase previously implicated in repressive interactions between ER and NF-κB , plays a permissive role by promoting histone acetylation and ER recruitment , as well as enhanced expression of BIRC3 .	[ 7 ]
22083956_6	These findings suggest a new gene regulatory mechanism by which inflammation and NF-κB activation can influence ER recruitment to inherently inactive ER binding sites .	[ 9, 1 ]
22083956_7	This fine-tuning mechanism may explain how two factors that generally repress each other's activity may work together on certain genes to promote breast cancer cell survival and tumor progression .	[ 7 ]
12370496_0	We investigated the mode of cell death induced by the anthracyclines , aclarubicin , doxorubicin and daunorubicin in the human leukemia cell lines , HL60 and Jurkat .	[ 7 ]
12370496_1	The cells were incubated with drug concentrations up to 500 nM for periods between 3 and 24 hours , followed by morphological and biochemical analyses .	[ 7 ]
12370496_2	All three substances induced DNA fragmentation , evident as DNA laddering and appearance of cells with hypodiploid DNA content , externalization of phosphatidyl serine , activation of caspases and degradation of the apoptosis-specific endonuclease inhibitor DFF45 .	[ 4 ]
12370496_3	However , concentrations and times necessary for these effects to occur were different , aclarubicin being the quickest acting drug with a lag phase of 3 h , followed by daunorubicin with 6 h and doxorubicin with 24 h .	[ 7 ]
12370496_4	More importantly , aclarubicin induced these effects while the cell membrane was intact , whereas doxorubicin and daunorubicin led to immediate loss of membrane integrity .	[ 7 ]
12370496_5	Programmed cell death is characterised by preservation of membrane integrity in order to allow removal of apoptotic bodies , whereas cell rupture is an early event in necrosis .	[ 4 ]
12370496_6	We therefore suggest that , in our experimental settings , doxorubicin- and daunorubicin-induced cell death occurs by necrosis , while aclarubicin induces programmed cell death .	[ 4 ]
12508658_0	BACKGROUND & OBJECTIVE Usually pituitary adenomas are histological benign and grow slowly , but a proportion of them will become locally aggressive , and develop into invasive pituitary adenomas .	[ 7 ]
12508658_1	The reasons for these differences in tumor behavior are poorly understood .	[ 7 ]
12508658_2	Pituitary adenomas are abounding blood vessels .	[ 7 ]
12508658_3	Angiogenesis and tumor invasion both require degradation of the extracellular matrix components to allow cell migration .	[ 7 ]
12508658_4	The matrix metalloproteinases ( MMPs ) and their nature inhibitors-the tissue inhibitors of metalloproteinases ( TIMPs ) may play a central role in these processes .	[ 7 ]
12508658_5	The aggressive mechanism of pituitary adenomas was studied through investigating the expression of MMP-9 , MMP-2 , TIMP-1 , and TIMP-2 in both invasive and non-invasive adenomas .	[ 7 ]
12508658_6	METHODS Sixty-one surgical removed pituitary adenomas ( forty-nine cases invasive and twelve non-invasive adenomas ) were investigated .	[ 7 ]
12508658_7	Immunohistochemistry staining ( SP method ) was used to detect the expression of MMP-9 , MMP-2 , TIMP-1 , and TIMP-2 in two groups .	[ 7 ]
12508658_8	The results were treated with semi-quantitative method and analyzed by using non-parameter rank sum test .	[ 7 ]
12508658_9	RESULTS Immunohistochemical staining of tumor cells for MMP-9 , TIMP-1 , MMP-2 , and TIMP-2 were noted 95.9% ( 47/49 ) , 57.1% ( 28/49 ) , 75.5% ( 37/49 ) and 89.8% ( 44/49 ) in invasive adenomas , and 100% ( 12/12 ) , 91.7% ( 11/12 ) , 66.7% ( 8/12 ) , and 91.7% ( 11/12 ) in non-invasive adenomas , respectively .	[ 5 ]
12508658_10	Invasive tumors were significantly less expressing TIMP-1 and TIMP-2 ( P < 0.05 ) .	[ 5 ]
12508658_11	There was no significant difference for MMP-9 or MMP-2 between invasive and non-invasive groups ( P > 0.05 ) .	[ 5 ]
12508658_12	CONCLUSIONS TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior .	[ 5 ]
20661828_0	The biological activities of tocotrienols are receiving increasing attention .	[ 7 ]
20661828_1	Herein , we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate ( TRAMP ) mouse model .	[ 7 ]
20661828_2	Male TRAMP mice , 8 wk old , were fed 0.1% , 0.3% , or 1% mixed tocotrienols in AIN-76A diet up to 24 wk old .	[ 7 ]
20661828_3	Likewise , a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old .	[ 7 ]
20661828_4	Our results show that mixed-tocotrienol-fed groups had a lower incidence of tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus .	[ 7 ]
20661828_5	Furthermore , mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls .	[ 7 ]
20661828_6	This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic proteins BAD ( Bcl(2) antagonist of cell death ) and cleaved caspase-3 and cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27 .	[ 0, 4 ]
20661828_7	In contrast , the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups .	[ 9 ]
20661828_8	Taken together , our results show that by modulating cell cycle regulatory proteins and increasing expression of proapoptotic proteins , mixed tocotrienols suppress prostate tumorigenesis in the TRAMP mice .	[ 0, 9 ]
23209410_0	Many viruses subvert the host cell's ability to mount and complete various DNA damage responses ( DDRs ) after infection .	[ 7 ]
23209410_1	HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication , but the DDRs remain uncompleted without arrest or apoptosis .	[ 7 ]
23209410_2	We believe this was in part due to partitioning of the damage response and double strand break repair components .	[ 7 ]
23209410_3	After extraction of soluble proteins , the localization of these components fell into three groups : specifically associated with the viral replication centers ( RCs ) , diffused throughout the nucleoplasm and excluded from the RCs .	[ 7 ]
23209410_4	Others have shown that cells are incapable of processing exogenously introduced damage after infection .	[ 7 ]
23209410_5	We hypothesized that the inability of the cells to process damage might be due to the differential association of repair components within the RCs and , in turn , potentially preferential repair of the viral genome and compromised repair of the host genome .	[ 7 ]
23209410_6	To test this hypothesis we used multiple strategies to examine repair of UV-induced DNA damage in mock and virus-infected fibroblasts .	[ 7 ]
23209410_7	Comet assays indicated that repair was initiated , but was not completed in infected cells .	[ 6 ]
23209410_8	Quantitative analysis of immunofluorescent localization of cyclobutane pyrimidine dimers ( CPDs ) revealed that after 24 h of repair , CPDs were significantly reduced in viral DNA , but not significantly changed in the infected host DNA .	[ 6 ]
23209410_9	To further quantitate CPD repair , we developed a novel dual-color Southern protocol allowing visualization of host and viral DNA simultaneously .	[ 7 ]
23209410_10	Combining this Southern methodology with a CPD-specific T4 endonuclease V alkaline agarose assay to quantitate repair of adducts , we found efficient repair of CPDs from the viral DNA but not host cellular DNA .	[ 6 ]
23209410_11	Our data confirm that NER functions in HCMV-infected cells and almost exclusively repairs the viral genome to the detriment of the host's genome .	[ 6 ]
22694344_0	Airway mucin secretion and MC ( mast cell ) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively .	[ 7 ]
22694344_1	We found the exocytic protein Munc18b to be highly expressed in mouse airway epithelial cells and MCs , and localized to the apical pole of airway secretory cells .	[ 7 ]
22694344_2	To address its functions , we created a mouse with a severely hypomorphic Munc18b allele such that protein expression in heterozygotes was reduced by Homozygous mutant mice were not viable , but heterozygotes showed a reduction in stimulated release of mucin from epithelial cells and granule contents from MCs .	[ 7 ]
22694344_3	The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion .	[ 7 ]
22694344_4	The severity of passive cutaneous anaphylaxis was also reduced by showing that reduction of Munc18b expression results in an attenuation of physiological responses dependent on MC degranulation .	[ 7 ]
22694344_5	The Munc18b promoter is controlled by INR ( initiator ) , Sp1 ( specificity protein 1 ) , Ets , CRE ( cAMP-response element ) , GRE ( glucocorticoid-response element ) , GATA and E-box elements in airway epithelial cells ; however , protein levels did not change during mucous metaplasia induced by allergic inflammation .	[ 7 ]
22694344_6	Taken together , the results of the present study identify Munc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs .	[ 7 ]
19895865_0	Chromated copper arsenate , which is used worldwide as a wood preservative , can adversely affect human health .	[ 7 ]
19895865_1	Accumulating evidence suggests that chromium ( Cr ) and arsenic ( As ) can potentially disrupt the redox balance and cause respiratory diseases and cancer in humans .	[ 7 ]
19895865_2	The present study was designed to determine the combined toxic effects of these metals in the lungs and to clarify the specific molecules that are stimulated by combined exposure to both metals .	[ 7 ]
19895865_3	Male C57BL/6J mice were intratracheally instilled with arsenate [ As(V) ] , hexavalent chromium [ Cr(VI) ] , or a combination of both metals .	[ 7 ]
19895865_4	Mice were sacrificed 2 days after treatment to collect bronchoalveolar lavage fluid and lung tissue samples .	[ 7 ]
19895865_5	Inflammation , cytotoxicity , apoptosis , and oxidative stress markers were measured .	[ 7 ]
19895865_6	Our results indicated that administration of Cr(VI) alone or in combination with As(V) induced neutrophil-dominant inflammation as well as phosphorylation of mitogen-activated protein kinases ; effects of treatment with As(V) alone were comparatively less potent .	[ 1 ]
19895865_7	By analyzing the production of interleukin-6 and activity of lactate dehydrogenase and caspase , we confirmed that co-treatment intensified pulmonary injury and that it was accompanied by oxidative stress , as confirmed by marked increases in the production of reactive oxygen species , reduced glutathione content , and thioredoxin reductase ( TRXRD ) activity .	[ 1 ]
19895865_8	Expressed mRNA levels of heme oxygenase-1 , glutamylcysteine ligase , glutathione peroxidase 2 , thioredoxin ( TRX ) 1 , and TRXRD1 were also enhanced by co-treatment , whereas treatment with As(V) alone reduced the mRNA expression level of TRX2 .	[ 1 ]
19895865_9	Our data suggest that co-treatment with As(V) exacerbated Cr(VI)-induced pulmonary injury and that this effect may be exerted through a disruption in the balance among several antioxidant genes .	[ 7 ]
21120602_0	The role of estrogen receptor beta ( ERβ ) in breast cancer is unclear .	[ 7 ]
21120602_1	ERβ is considered to have a protective role in breast cancer development based on findings demonstrating that ERβ expression inhibits ERα-mediated proliferation of breast cancer cells .	[ 7 ]
21120602_2	We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells .	[ 7 ]
21120602_3	To study the mechanisms of the ERβ-mediated G2 cell cycle arrest , we investigated its effects on the regulatory pathways responsible for the G2/M phase transition .	[ 7 ]
21120602_4	We found that ERβ inhibits CDK1 activity , which is the critical determinant of the G2/M progression .	[ 9 ]
21120602_5	CDK1 activity is modulated by both stimulatory and inhibitory factors .	[ 7 ]
21120602_6	Cyclin B1 is the major activator of CDK1 .	[ 9 ]
21120602_7	ERβ inhibited the cell cycle-dependent stimulation of cyclin B1 mRNA and protein .	[ 9 ]
21120602_8	GADD45A and BTG2 are two major inhibitors of CDK1 , which have been implicated in breast tumor formation .	[ 7 ]
21120602_9	Based on these findings , we explored if the expression pattern of GADD45A and BTG2 is affected by ERβ .	[ 7 ]
21120602_10	We found that ERβ stimulates GADD45A and BTG2 mRNA levels .	[ 7 ]
21120602_11	The induction of these two genes is caused by ERβ binding directly to these genes and recruiting c-jun and NCOA2 .	[ 7 ]
21120602_12	Our findings demonstrated that unliganded ERβ causes a G2 cell cycle arrest by inactivating CDK1 through the repression of cyclin B1 and stimulation of GADD45A and BTG2 expression .	[ 9 ]
21120602_13	These results provide evidence that drugs that stimulate the production of unliganded ERβ may be effective new therapies to prevent breast cancer .	[ 7 ]
22443054_0	OBJECTIVE To investigate the effects of CdTe QDs ( cadmium telluride quantum dots ) on oxidative stress and DNA damage of liver cells in mice .	[ 7 ]
22443054_1	METHODS Thirty ICR male mice were randomly divided into 5 groups : one negative control ( normal saline ) group .	[ 7 ]
22443054_2	Three CdTe QDs groups ( exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 3.75 , 37.5 and 375 nmol/ml respectively ) for electron paramagnetic resonance ( EPR ) test , and another positive control group ( exposed by intravenous injection of 0.2 ml of cyclophosphamide 20 mg/ml ) for single cell gel electrophoresis ( SCGE ) test .	[ 7 ]
22443054_3	All mice were decapitated 24h after the injection , free radicals and DNA damage of liver cells were detected by EPR and SCGE .	[ 7 ]
22443054_4	RESULTS The levels of oxygen free radicals detected by EPR were increased with the increase of CdTe QDs .	[ 1 ]
22443054_5	The tail length , olive tail moment , tail DNA ( % ) and the ratio of tail/head examined by SCGE were also increased with the increase of the dosage of CdTe QDs ( P < 0.01 ) .	[ 6 ]
22443054_6	CONCLUSION CdTe QDs could induce oxidative stress and DNA damage of liver cells in mice with a dose-effect relationship .	[ 6, 1 ]
22851646_0	Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity .	[ 7 ]
22851646_1	Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled .	[ 7 ]
22851646_2	Inbred Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors that have tumor gene expression profiles closely resembling mature human mammary luminal cell signatures .	[ 7 ]
22851646_3	We genomically characterized mammary adenocarcinomas from these mice to identify cancer-causing genomic events that overlap common alterations in human breast cancer .	[ 7 ]
22851646_4	Chaos3 tumors underwent recurrent copy number alterations ( CNAs ) , particularly deletion of the RAS inhibitor Neurofibromin 1 ( Nf1 ) in nearly all cases .	[ 7 ]
22851646_5	These overlap with human CNAs including NF1 , which is deleted or mutated in 27.7% of all breast carcinomas .	[ 6 ]

22668016_2

Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment ( 18 weeks ) .

[ 7 ]

22668016_3

At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis .

[ 7 ]

22668016_4

In treated animals ( simvastatin 180 mg/kg ) , significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation .

[ 7 ]

22668016_5

Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells .

[ 4 ]

22668016_6

In high grade control carcinoma cells , the expression of Ki67 increased by 37% ( non-significantly ) in comparison with control low grade carcinomas .

[ 7 ]

22668016_7

A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment .

[ 7 ]

22668016_8

The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment .

[ 4 ]

22083956_0

Estrogen receptor ( ER ) and NF-κB are transcription factors with profound effects on breast cancer cell proliferation and survival .

[ 7 ]

22083956_1

While many studies demonstrate that ER and NF-κB can repress each other , we previously identified a gene signature that is synergistically upregulated by these two factors in more aggressive luminal B breast tumors .

[ 7 ]

22083956_2

Herein , we examine a novel mechanism of cross talk between ER and NF-κB that results in the upregulation of the antiapoptotic gene BIRC3 ( also known as cIAP2 ) .

[ 7 ]

22083956_3

We demonstrate that NF-κB , acting through two response elements , is required for ER recruitment to an adjacent estrogen response element ( ERE ) in the BIRC3 promoter .

[ 7 ]

22083956_4

This effect is accompanied by a major increase in NF-κB-dependent histone acetylation around the ERE .

[ 7 ]

22083956_5

Interestingly , CBP , a histone acetyltransferase previously implicated in repressive interactions between ER and NF-κB , plays a permissive role by promoting histone acetylation and ER recruitment , as well as enhanced expression of BIRC3 .

[ 7 ]

22083956_6

These findings suggest a new gene regulatory mechanism by which inflammation and NF-κB activation can influence ER recruitment to inherently inactive ER binding sites .

[ 9, 1 ]

22083956_7

This fine-tuning mechanism may explain how two factors that generally repress each other's activity may work together on certain genes to promote breast cancer cell survival and tumor progression .

[ 7 ]

12370496_0

We investigated the mode of cell death induced by the anthracyclines , aclarubicin , doxorubicin and daunorubicin in the human leukemia cell lines , HL60 and Jurkat .

[ 7 ]

12370496_1

The cells were incubated with drug concentrations up to 500 nM for periods between 3 and 24 hours , followed by morphological and biochemical analyses .

[ 7 ]

12370496_2

All three substances induced DNA fragmentation , evident as DNA laddering and appearance of cells with hypodiploid DNA content , externalization of phosphatidyl serine , activation of caspases and degradation of the apoptosis-specific endonuclease inhibitor DFF45 .

[ 4 ]

12370496_3

However , concentrations and times necessary for these effects to occur were different , aclarubicin being the quickest acting drug with a lag phase of 3 h , followed by daunorubicin with 6 h and doxorubicin with 24 h .

[ 7 ]

12370496_4

More importantly , aclarubicin induced these effects while the cell membrane was intact , whereas doxorubicin and daunorubicin led to immediate loss of membrane integrity .

[ 7 ]

12370496_5

Programmed cell death is characterised by preservation of membrane integrity in order to allow removal of apoptotic bodies , whereas cell rupture is an early event in necrosis .

[ 4 ]

12370496_6

We therefore suggest that , in our experimental settings , doxorubicin- and daunorubicin-induced cell death occurs by necrosis , while aclarubicin induces programmed cell death .

[ 4 ]

12508658_0

BACKGROUND & OBJECTIVE Usually pituitary adenomas are histological benign and grow slowly , but a proportion of them will become locally aggressive , and develop into invasive pituitary adenomas .

[ 7 ]

12508658_1

The reasons for these differences in tumor behavior are poorly understood .

[ 7 ]

12508658_2

Pituitary adenomas are abounding blood vessels .

[ 7 ]

12508658_3

Angiogenesis and tumor invasion both require degradation of the extracellular matrix components to allow cell migration .

[ 7 ]

12508658_4

The matrix metalloproteinases ( MMPs ) and their nature inhibitors-the tissue inhibitors of metalloproteinases ( TIMPs ) may play a central role in these processes .

[ 7 ]

12508658_5

The aggressive mechanism of pituitary adenomas was studied through investigating the expression of MMP-9 , MMP-2 , TIMP-1 , and TIMP-2 in both invasive and non-invasive adenomas .

[ 7 ]

12508658_6

METHODS Sixty-one surgical removed pituitary adenomas ( forty-nine cases invasive and twelve non-invasive adenomas ) were investigated .

[ 7 ]

12508658_7

Immunohistochemistry staining ( SP method ) was used to detect the expression of MMP-9 , MMP-2 , TIMP-1 , and TIMP-2 in two groups .

[ 7 ]

12508658_8

The results were treated with semi-quantitative method and analyzed by using non-parameter rank sum test .

[ 7 ]

12508658_9

RESULTS Immunohistochemical staining of tumor cells for MMP-9 , TIMP-1 , MMP-2 , and TIMP-2 were noted 95.9% ( 47/49 ) , 57.1% ( 28/49 ) , 75.5% ( 37/49 ) and 89.8% ( 44/49 ) in invasive adenomas , and 100% ( 12/12 ) , 91.7% ( 11/12 ) , 66.7% ( 8/12 ) , and 91.7% ( 11/12 ) in non-invasive adenomas , respectively .

[ 5 ]

12508658_10

Invasive tumors were significantly less expressing TIMP-1 and TIMP-2 ( P < 0.05 ) .

[ 5 ]

12508658_11

There was no significant difference for MMP-9 or MMP-2 between invasive and non-invasive groups ( P > 0.05 ) .

[ 5 ]

12508658_12

CONCLUSIONS TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior .

[ 5 ]

20661828_0

The biological activities of tocotrienols are receiving increasing attention .

[ 7 ]

20661828_1

Herein , we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate ( TRAMP ) mouse model .

[ 7 ]

20661828_2

Male TRAMP mice , 8 wk old , were fed 0.1% , 0.3% , or 1% mixed tocotrienols in AIN-76A diet up to 24 wk old .

[ 7 ]

20661828_3

Likewise , a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old .

[ 7 ]

20661828_4

Our results show that mixed-tocotrienol-fed groups had a lower incidence of tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus .

[ 7 ]

20661828_5

Furthermore , mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls .

[ 7 ]

20661828_6

This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic proteins BAD ( Bcl(2) antagonist of cell death ) and cleaved caspase-3 and cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27 .

[ 0, 4 ]

20661828_7

In contrast , the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups .

[ 9 ]

20661828_8

Taken together , our results show that by modulating cell cycle regulatory proteins and increasing expression of proapoptotic proteins , mixed tocotrienols suppress prostate tumorigenesis in the TRAMP mice .

[ 0, 9 ]

23209410_0

Many viruses subvert the host cell's ability to mount and complete various DNA damage responses ( DDRs ) after infection .

[ 7 ]

23209410_1

HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication , but the DDRs remain uncompleted without arrest or apoptosis .

[ 7 ]

23209410_2

We believe this was in part due to partitioning of the damage response and double strand break repair components .

[ 7 ]

23209410_3

After extraction of soluble proteins , the localization of these components fell into three groups : specifically associated with the viral replication centers ( RCs ) , diffused throughout the nucleoplasm and excluded from the RCs .

[ 7 ]

23209410_4

Others have shown that cells are incapable of processing exogenously introduced damage after infection .

[ 7 ]

23209410_5

We hypothesized that the inability of the cells to process damage might be due to the differential association of repair components within the RCs and , in turn , potentially preferential repair of the viral genome and compromised repair of the host genome .

[ 7 ]

23209410_6

To test this hypothesis we used multiple strategies to examine repair of UV-induced DNA damage in mock and virus-infected fibroblasts .

[ 7 ]

23209410_7

Comet assays indicated that repair was initiated , but was not completed in infected cells .

[ 6 ]

23209410_8

Quantitative analysis of immunofluorescent localization of cyclobutane pyrimidine dimers ( CPDs ) revealed that after 24 h of repair , CPDs were significantly reduced in viral DNA , but not significantly changed in the infected host DNA .

[ 6 ]

23209410_9

To further quantitate CPD repair , we developed a novel dual-color Southern protocol allowing visualization of host and viral DNA simultaneously .

[ 7 ]

23209410_10

Combining this Southern methodology with a CPD-specific T4 endonuclease V alkaline agarose assay to quantitate repair of adducts , we found efficient repair of CPDs from the viral DNA but not host cellular DNA .

[ 6 ]

23209410_11

Our data confirm that NER functions in HCMV-infected cells and almost exclusively repairs the viral genome to the detriment of the host's genome .

[ 6 ]

22694344_0

Airway mucin secretion and MC ( mast cell ) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively .

[ 7 ]

22694344_1

We found the exocytic protein Munc18b to be highly expressed in mouse airway epithelial cells and MCs , and localized to the apical pole of airway secretory cells .

[ 7 ]

22694344_2

To address its functions , we created a mouse with a severely hypomorphic Munc18b allele such that protein expression in heterozygotes was reduced by Homozygous mutant mice were not viable , but heterozygotes showed a reduction in stimulated release of mucin from epithelial cells and granule contents from MCs .

[ 7 ]

22694344_3

The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion .

[ 7 ]

22694344_4

The severity of passive cutaneous anaphylaxis was also reduced by showing that reduction of Munc18b expression results in an attenuation of physiological responses dependent on MC degranulation .

[ 7 ]

22694344_5

The Munc18b promoter is controlled by INR ( initiator ) , Sp1 ( specificity protein 1 ) , Ets , CRE ( cAMP-response element ) , GRE ( glucocorticoid-response element ) , GATA and E-box elements in airway epithelial cells ; however , protein levels did not change during mucous metaplasia induced by allergic inflammation .

[ 7 ]

22694344_6

Taken together , the results of the present study identify Munc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs .

[ 7 ]

19895865_0

Chromated copper arsenate , which is used worldwide as a wood preservative , can adversely affect human health .

[ 7 ]

19895865_1

Accumulating evidence suggests that chromium ( Cr ) and arsenic ( As ) can potentially disrupt the redox balance and cause respiratory diseases and cancer in humans .

[ 7 ]

19895865_2

The present study was designed to determine the combined toxic effects of these metals in the lungs and to clarify the specific molecules that are stimulated by combined exposure to both metals .

[ 7 ]

19895865_3

Male C57BL/6J mice were intratracheally instilled with arsenate [ As(V) ] , hexavalent chromium [ Cr(VI) ] , or a combination of both metals .

[ 7 ]

19895865_4

Mice were sacrificed 2 days after treatment to collect bronchoalveolar lavage fluid and lung tissue samples .

[ 7 ]

19895865_5

Inflammation , cytotoxicity , apoptosis , and oxidative stress markers were measured .

[ 7 ]

19895865_6

Our results indicated that administration of Cr(VI) alone or in combination with As(V) induced neutrophil-dominant inflammation as well as phosphorylation of mitogen-activated protein kinases ; effects of treatment with As(V) alone were comparatively less potent .

[ 1 ]

19895865_7

By analyzing the production of interleukin-6 and activity of lactate dehydrogenase and caspase , we confirmed that co-treatment intensified pulmonary injury and that it was accompanied by oxidative stress , as confirmed by marked increases in the production of reactive oxygen species , reduced glutathione content , and thioredoxin reductase ( TRXRD ) activity .

[ 1 ]

19895865_8

Expressed mRNA levels of heme oxygenase-1 , glutamylcysteine ligase , glutathione peroxidase 2 , thioredoxin ( TRX ) 1 , and TRXRD1 were also enhanced by co-treatment , whereas treatment with As(V) alone reduced the mRNA expression level of TRX2 .

[ 1 ]

19895865_9

Our data suggest that co-treatment with As(V) exacerbated Cr(VI)-induced pulmonary injury and that this effect may be exerted through a disruption in the balance among several antioxidant genes .

[ 7 ]

21120602_0

The role of estrogen receptor beta ( ERβ ) in breast cancer is unclear .

[ 7 ]

21120602_1

ERβ is considered to have a protective role in breast cancer development based on findings demonstrating that ERβ expression inhibits ERα-mediated proliferation of breast cancer cells .

[ 7 ]

21120602_2

We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells .

[ 7 ]

21120602_3

To study the mechanisms of the ERβ-mediated G2 cell cycle arrest , we investigated its effects on the regulatory pathways responsible for the G2/M phase transition .

[ 7 ]

21120602_4

We found that ERβ inhibits CDK1 activity , which is the critical determinant of the G2/M progression .

[ 9 ]

21120602_5

CDK1 activity is modulated by both stimulatory and inhibitory factors .

[ 7 ]

21120602_6

Cyclin B1 is the major activator of CDK1 .

[ 9 ]

21120602_7

ERβ inhibited the cell cycle-dependent stimulation of cyclin B1 mRNA and protein .

[ 9 ]

21120602_8

GADD45A and BTG2 are two major inhibitors of CDK1 , which have been implicated in breast tumor formation .

[ 7 ]

21120602_9

Based on these findings , we explored if the expression pattern of GADD45A and BTG2 is affected by ERβ .

[ 7 ]

21120602_10

We found that ERβ stimulates GADD45A and BTG2 mRNA levels .

[ 7 ]

21120602_11

The induction of these two genes is caused by ERβ binding directly to these genes and recruiting c-jun and NCOA2 .

[ 7 ]

21120602_12

Our findings demonstrated that unliganded ERβ causes a G2 cell cycle arrest by inactivating CDK1 through the repression of cyclin B1 and stimulation of GADD45A and BTG2 expression .

[ 9 ]

21120602_13

These results provide evidence that drugs that stimulate the production of unliganded ERβ may be effective new therapies to prevent breast cancer .

[ 7 ]

22443054_0

OBJECTIVE To investigate the effects of CdTe QDs ( cadmium telluride quantum dots ) on oxidative stress and DNA damage of liver cells in mice .

[ 7 ]

22443054_1

METHODS Thirty ICR male mice were randomly divided into 5 groups : one negative control ( normal saline ) group .

[ 7 ]

22443054_2

Three CdTe QDs groups ( exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 3.75 , 37.5 and 375 nmol/ml respectively ) for electron paramagnetic resonance ( EPR ) test , and another positive control group ( exposed by intravenous injection of 0.2 ml of cyclophosphamide 20 mg/ml ) for single cell gel electrophoresis ( SCGE ) test .

[ 7 ]

22443054_3

All mice were decapitated 24h after the injection , free radicals and DNA damage of liver cells were detected by EPR and SCGE .

[ 7 ]

22443054_4

RESULTS The levels of oxygen free radicals detected by EPR were increased with the increase of CdTe QDs .

[ 1 ]

22443054_5

The tail length , olive tail moment , tail DNA ( % ) and the ratio of tail/head examined by SCGE were also increased with the increase of the dosage of CdTe QDs ( P < 0.01 ) .

[ 6 ]

22443054_6

CONCLUSION CdTe QDs could induce oxidative stress and DNA damage of liver cells in mice with a dose-effect relationship .

[ 6, 1 ]

22851646_0

Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity .

[ 7 ]

22851646_1

Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled .

[ 7 ]

22851646_2

Inbred Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors that have tumor gene expression profiles closely resembling mature human mammary luminal cell signatures .

[ 7 ]

22851646_3

We genomically characterized mammary adenocarcinomas from these mice to identify cancer-causing genomic events that overlap common alterations in human breast cancer .

[ 7 ]

22851646_4

Chaos3 tumors underwent recurrent copy number alterations ( CNAs ) , particularly deletion of the RAS inhibitor Neurofibromin 1 ( Nf1 ) in nearly all cases .

[ 7 ]

22851646_5

These overlap with human CNAs including NF1 , which is deleted or mutated in 27.7% of all breast carcinomas .

[ 6 ]