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401
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 ) .
[ "none" ]
402
22668016_3
At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis .
[ "none" ]
403
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 .
[ "none" ]
404
22668016_5
Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells .
[ "resisting cell death" ]
405
22668016_6
In high grade control carcinoma cells , the expression of Ki67 increased by 37% ( non-significantly ) in comparison with control low grade carcinomas .
[ "none" ]
406
22668016_7
A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment .
[ "none" ]
407
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 .
[ "resisting cell death" ]
408
22083956_0
Estrogen receptor ( ER ) and NF-κB are transcription factors with profound effects on breast cancer cell proliferation and survival .
[ "none" ]
409
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 .
[ "none" ]
410
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 ) .
[ "none" ]
411
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 .
[ "none" ]
412
22083956_4
This effect is accompanied by a major increase in NF-κB-dependent histone acetylation around the ERE .
[ "none" ]
413
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 .
[ "none" ]
414
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 .
[ "sustaining proliferative signaling", "tumor promoting inflammation" ]
415
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 .
[ "none" ]
416
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 .
[ "none" ]
417
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 .
[ "none" ]
418
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 .
[ "resisting cell death" ]
419
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 .
[ "none" ]
420
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 .
[ "none" ]
421
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 .
[ "resisting cell death" ]
422
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 .
[ "resisting cell death" ]
423
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 .
[ "none" ]
424
12508658_1
The reasons for these differences in tumor behavior are poorly understood .
[ "none" ]
425
12508658_2
Pituitary adenomas are abounding blood vessels .
[ "none" ]
426
12508658_3
Angiogenesis and tumor invasion both require degradation of the extracellular matrix components to allow cell migration .
[ "none" ]
427
12508658_4
The matrix metalloproteinases ( MMPs ) and their nature inhibitors-the tissue inhibitors of metalloproteinases ( TIMPs ) may play a central role in these processes .
[ "none" ]
428
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 .
[ "none" ]
429
12508658_6
METHODS Sixty-one surgical removed pituitary adenomas ( forty-nine cases invasive and twelve non-invasive adenomas ) were investigated .
[ "none" ]
430
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 .
[ "none" ]
431
12508658_8
The results were treated with semi-quantitative method and analyzed by using non-parameter rank sum test .
[ "none" ]
432
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 .
[ "activating invasion and metastasis" ]
433
12508658_10
Invasive tumors were significantly less expressing TIMP-1 and TIMP-2 ( P < 0.05 ) .
[ "activating invasion and metastasis" ]
434
12508658_11
There was no significant difference for MMP-9 or MMP-2 between invasive and non-invasive groups ( P > 0.05 ) .
[ "activating invasion and metastasis" ]
435
12508658_12
CONCLUSIONS TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior .
[ "activating invasion and metastasis" ]
436
20661828_0
The biological activities of tocotrienols are receiving increasing attention .
[ "none" ]
437
20661828_1
Herein , we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate ( TRAMP ) mouse model .
[ "none" ]
438
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 .
[ "none" ]
439
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 .
[ "none" ]
440
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 .
[ "none" ]
441
20661828_5
Furthermore , mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls .
[ "none" ]
442
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 .
[ "resisting cell death", "evading growth suppressors" ]
443
20661828_7
In contrast , the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups .
[ "sustaining proliferative signaling" ]
444
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 .
[ "sustaining proliferative signaling", "evading growth suppressors" ]
445
23209410_0
Many viruses subvert the host cell's ability to mount and complete various DNA damage responses ( DDRs ) after infection .
[ "none" ]
446
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 .
[ "none" ]
447
23209410_2
We believe this was in part due to partitioning of the damage response and double strand break repair components .
[ "none" ]
448
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 .
[ "none" ]
449
23209410_4
Others have shown that cells are incapable of processing exogenously introduced damage after infection .
[ "none" ]
450
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 .
[ "none" ]
451
23209410_6
To test this hypothesis we used multiple strategies to examine repair of UV-induced DNA damage in mock and virus-infected fibroblasts .
[ "none" ]
452
23209410_7
Comet assays indicated that repair was initiated , but was not completed in infected cells .
[ "genomic instability and mutation" ]
453
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 .
[ "genomic instability and mutation" ]
454
23209410_9
To further quantitate CPD repair , we developed a novel dual-color Southern protocol allowing visualization of host and viral DNA simultaneously .
[ "none" ]
455
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 .
[ "genomic instability and mutation" ]
456
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 .
[ "genomic instability and mutation" ]
457
22694344_0
Airway mucin secretion and MC ( mast cell ) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively .
[ "none" ]
458
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 .
[ "none" ]
459
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 .
[ "none" ]
460
22694344_3
The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion .
[ "none" ]
461
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 .
[ "none" ]
462
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 .
[ "none" ]
463
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 .
[ "none" ]
464
19895865_0
Chromated copper arsenate , which is used worldwide as a wood preservative , can adversely affect human health .
[ "none" ]
465
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 .
[ "none" ]
466
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 .
[ "none" ]
467
19895865_3
Male C57BL/6J mice were intratracheally instilled with arsenate [ As(V) ] , hexavalent chromium [ Cr(VI) ] , or a combination of both metals .
[ "none" ]
468
19895865_4
Mice were sacrificed 2 days after treatment to collect bronchoalveolar lavage fluid and lung tissue samples .
[ "none" ]
469
19895865_5
Inflammation , cytotoxicity , apoptosis , and oxidative stress markers were measured .
[ "none" ]
470
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 .
[ "tumor promoting inflammation" ]
471
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 .
[ "tumor promoting inflammation" ]
472
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 .
[ "tumor promoting inflammation" ]
473
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 .
[ "none" ]
474
21120602_0
The role of estrogen receptor beta ( ERβ ) in breast cancer is unclear .
[ "none" ]
475
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 .
[ "none" ]
476
21120602_2
We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells .
[ "none" ]
477
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 .
[ "none" ]
478
21120602_4
We found that ERβ inhibits CDK1 activity , which is the critical determinant of the G2/M progression .
[ "sustaining proliferative signaling" ]
479
21120602_5
CDK1 activity is modulated by both stimulatory and inhibitory factors .
[ "none" ]
480
21120602_6
Cyclin B1 is the major activator of CDK1 .
[ "sustaining proliferative signaling" ]
481
21120602_7
ERβ inhibited the cell cycle-dependent stimulation of cyclin B1 mRNA and protein .
[ "sustaining proliferative signaling" ]
482
21120602_8
GADD45A and BTG2 are two major inhibitors of CDK1 , which have been implicated in breast tumor formation .
[ "none" ]
483
21120602_9
Based on these findings , we explored if the expression pattern of GADD45A and BTG2 is affected by ERβ .
[ "none" ]
484
21120602_10
We found that ERβ stimulates GADD45A and BTG2 mRNA levels .
[ "none" ]
485
21120602_11
The induction of these two genes is caused by ERβ binding directly to these genes and recruiting c-jun and NCOA2 .
[ "none" ]
486
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 .
[ "sustaining proliferative signaling" ]
487
21120602_13
These results provide evidence that drugs that stimulate the production of unliganded ERβ may be effective new therapies to prevent breast cancer .
[ "none" ]
488
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 .
[ "none" ]
489
22443054_1
METHODS Thirty ICR male mice were randomly divided into 5 groups : one negative control ( normal saline ) group .
[ "none" ]
490
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 .
[ "none" ]
491
22443054_3
All mice were decapitated 24h after the injection , free radicals and DNA damage of liver cells were detected by EPR and SCGE .
[ "none" ]
492
22443054_4
RESULTS The levels of oxygen free radicals detected by EPR were increased with the increase of CdTe QDs .
[ "tumor promoting inflammation" ]
493
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 ) .
[ "genomic instability and mutation" ]
494
22443054_6
CONCLUSION CdTe QDs could induce oxidative stress and DNA damage of liver cells in mice with a dose-effect relationship .
[ "genomic instability and mutation", "tumor promoting inflammation" ]
495
22851646_0
Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity .
[ "none" ]
496
22851646_1
Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled .
[ "none" ]
497
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 .
[ "none" ]
498
22851646_3
We genomically characterized mammary adenocarcinomas from these mice to identify cancer-causing genomic events that overlap common alterations in human breast cancer .
[ "none" ]
499
22851646_4
Chaos3 tumors underwent recurrent copy number alterations ( CNAs ) , particularly deletion of the RAS inhibitor Neurofibromin 1 ( Nf1 ) in nearly all cases .
[ "none" ]
500
22851646_5
These overlap with human CNAs including NF1 , which is deleted or mutated in 27.7% of all breast carcinomas .
[ "genomic instability and mutation" ]