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hallmarks_of_cancer

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12001

19003298_4

Rat tumor cell line U41 is derived from tumors in the subcutaneous implantation of PEU films .

12002

19003298_5

The GJIC and the expression of Cx43 were suppressed in U41 .

12003

19003298_6

The restoration of normal phenotype , such as reduction of growth rate , recovery of contact inhibition and loss of colony formation ability in soft agar , was achieved by Cx43 transfection .

12004

19003298_7

These results strongly suggest that suppression of Cx43 expression plays an important role in the development of rat malignant fibrous histiocytoma ( MFHC ) caused by PEUs and that Cx43 transfection is effective for prevention of tumorigenesis induced by PEUs .

12005

22465023_0

The homodimeric bc(1) complexes are membrane proteins essential in respiration and photosynthesis .

12006

22465023_1

The distance between the two b(L)-hemes of the dimer opens the possibility of electron transfer between them , but contradictory reports make such inter-monomer electron transfer controversial .

12007

22465023_2

We have constructed in Rhodobacter sphaeroides a heterodimeric expression system similar to those used before , in which the bc(1) complex can be mutated differentially in the two copies of cyt b to test for inter-monomer electron transfer , but found that genetic recombination by cross-over then occurs to produce wild-type homodimer .

12008

22465023_3

Selection pressure under photosynthetic growth always favored the homodimer over heterodimeric variants enforcing inter-monomer electron transfer , showing that the latter are not competitive .

12009

22465023_4

These results , together with kinetic analysis of myxothiazol titrations , demonstrate that inter-monomer electron transfer does not occur at rates competitive with monomeric turnover .

12010

22465023_5

We examine the results from other groups interpreted as demonstrating rapid inter-monomer electron transfer , conclude that similar mechanisms are likely to be in play , and suggest that such claims might need to be re-examined .

12011

1312701_0

The oncogenic potential of a human papillomavirus type 16 ( HPV16 ) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes .

12012

1312701_1

The HPV16 variant was able to extend the lifespan of , but failed to immortalize , human keratinocytes .

12013

1312701_2

It could however cooperate with an activated ras oncogene to transform primary rodent cells .

12014

1312701_3

Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein .

12015

1312701_4

DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional , but a deletion in the viral E2 open reading frame was detected .

12016

1312701_5

This truncated E2 only weakly stimulated transcription of the viral regulatory region .

12017

1312701_6

Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency .

12018

1312701_7

These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer .

12019

1459429_0

We studied the effects of double-strand breaks on intramolecular extrachromosomal homologous recombination in mammalian cells .

12020

1459429_1

Pairs of defective herpes thymidine kinase ( tk ) sequences were introduced into mouse Ltk- cells on a DNA molecule that also contained a neo gene under control of the SV40 early promoter/enhancer .

12021

1459429_2

With the majority of the constructs used , gene conversions or double crossovers , but not single crossovers , were recoverable .

12022

1459429_3

DNA was linearized with various restriction enzymes prior to transfection .

12023

1459429_4

Recombination events producing a functional tk gene were monitored by selecting for tk-positive colonies .

12024

1459429_5

For double-strand breaks placed outside of the region of homology , maximal recombination frequencies were measured when a break placed the two tk sequences downstream from the SV40 early promoter/enhancer .

12025

1459429_6

We observed no relationship between recombination frequency and either the distance between a break and the tk sequences or the distance between the tk sequences .

12026

1459429_7

The quantitative effects of the breaks appeared to depend on the degree of homology between the tk sequences .

12027

1459429_8

We also observed that inverted repeats recombined as efficiently as direct repeats .

12028

1459429_9

The data indicated that the breaks influenced recombination indirectly , perhaps by affecting the binding of a factor(s) to the SV40 promoter region which in turn stimulated or inhibited recombination of the tk sequences .

12029

1459429_10

Taken together , we believe that our results provide strong evidence for the existence of a pathway for extrachromosomal homologous recombination in mammalian cells that is distinct from single-strand annealing .

12030

1459429_11

We discuss the possibility that intrachromosomal and extrachromosomal recombination have mechanisms in common .

12031

23227181_0

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians .

12032

23227181_1

The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival .

12033

23227181_2

This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread .

12034

23227181_3

In this study , we used one- and two-dimensional gel electrophoresis , mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas .

12035

23227181_4

Using a refinement for classifying oral carcinomas in regard to prognosis , we analyzed small but lymph node metastasis-positive versus large , lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination .

12036

23227181_5

Specific protein patterns favoring metastasis were observed in the " more-aggressive " group defined by the present study .

12037

23227181_6

This group displayed upregulation of proteins involved in migration , adhesion , angiogenesis , cell cycle regulation , anti-apoptosis and epithelial to mesenchymal transition , whereas the " less-aggressive " group was engaged in keratinocyte differentiation , epidermis development , inflammation and immune response .

12038

23227181_7

Besides the identification of several proteins not yet described as deregulated in oral carcinomas , the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas .

12039

11849319_0

Interferon-gamma ( IFN-gamma ) has pleiotropic activities other than its antivirus action , including cell growth inhibition , natural killer ( NK ) cell and cytotoxic T lymphocyte ( CTL ) activation , and angiogenesis inhibitory activity , and these activities are supposed to be involved in its antitumour activity .

12040

11849319_1

However , it has not been completely elucidated which activity is mainly involved in the tumour suppression in vivo .

12041

11849319_2

In this study , we analysed inhibitory mechanisms of endogenous IFN-gamma against B16 melanoma experimental metastasis .

12042

11849319_3

After intravenous injection of tumour cells , tumour deposits in the lungs and liver were increased and life span was shorter in IFN-gamma(-/-) mice , indicating important roles for IFN-gamma in antitumour mechanisms .

12043

11849319_4

Interestingly , tumour deposits were not increased in IFN-gamma receptor ( R)(-/- ) mice .

12044

11849319_5

Furthermore , only low levels of cell-mediated immunity against the tumour and activation of NK cells were observed , indicating that antimetastatic effects of IFN-gamma is not mediated by host cells .

12045

11849319_6

The survival period of B16 melanoma-bearing IFN-gamma R(-/-) mice was , however , shorter than wild-type mice .

12046

11849319_7

These observations suggest that IFN-gamma prevents B16 melanoma experimental metastasis by directly inhibiting the cell growth , although antitumour host functions may also be involved in a later phase .

12047

20080488_0

RAD51 is a key enzyme of homologous recombination and repair of DNA double-strand breaks .

12048

20080488_1

RAD51 mRNA expression levels are significantly increased in laser-microdissected mammary simple carcinomas and their lymph node metastases when compared to adenomas or nonneoplastic mammary gland of the same dog .

12049

20080488_2

Here , RAD51 protein expression was analyzed by immunohistochemistry in paraffin-embedded mammary carcinomas and their lymph node metastases of 40 dogs , adenomas of 48 dogs , and nonneoplastic mammary gland of 88 dogs .

12050

20080488_3

Number of cells with nuclear RAD51 expression was significantly ( P < or = .05 ) increased in carcinomas when compared to adenomas and metastases .

12051

20080488_4

In contrast , no significant differences in the number of RAD51-expressing cells were detected when metastases were compared with adenomas and nonneoplastic gland .

12052

20080488_5

RAD51 expression in carcinomas was correlated with expression in metastases but not with histologic grade .

12053

20080488_6

In conclusion , the increased number of RAD51-expressing cells in carcinomas might indicate genomic instability in these cells .

12054

20080488_7

Nevertheless , the increased RAD51 mRNA expression in metastases could not be confirmed by immunohistochemistry .

12055

22677908_0

Despite recent population data , the influence of dietary folate supplementation on colon cancer risk remains controversial .

12056

22677908_1

This study examines the effects of folate deficiency , in combination with choline , methionine , and vitamin B12 depletion , on intestinal tumorigenesis in Apc(Min/+) mice .

12057

22677908_2

Methyl donor sufficient ( MDS ) and deficient ( MDD ) diets were started at five or 10 weeks of age and tumors evaluated at 16 weeks .

12058

22677908_3

MDD suppressed intestinal tumor formation in Apc(Min/+) mice ( when started at five weeks of age .

12059

22677908_4

The protective effect was lost when MDD was initiated at 10 weeks of age , indicating an important time dependency on cancer suppression .

12060

22677908_5

Concomitant with cancer protection , MDD restricted body weight gain .

12061

22677908_6

Therefore , a second study was conducted in which MDS was given ad libitum or pair-fed with MDD .

12062

22677908_7

Although small intestinal tumors were reduced 54% in pair-fed MDS mice , MDD caused a further reduction ( 96% ) .

12063

22677908_8

In colon , although MDD did not affect tumor numbers , tumor size was reduced .

12064

22677908_9

Gene expression profiling of normal-appearing colonic mucosa after 11 weeks on MDD identified a total of 493 significantly downregulated genes relative to the MDS group .

12065

22677908_10

Pathway analysis placed many of these genes within general categories of inflammatory signaling and cell-cycle regulation , consistent with recently published human data obtained during folate depletion .

12066

22677908_11

Further studies are warranted to investigate the complex interplay of methyl donor status and cancer protection in high-risk populations .

12067

20099325_0

The purpose of this study was to combine a three-dimensional NMR-compatible bioreactor with hyperpolarized ( 13)C NMR spectroscopy in order to probe cellular metabolism in real time .

12068

20099325_1

JM1 ( immortalized rat hepatoma ) cells were cultured in a three-dimensional NMR-compatible fluidized bioreactor .

12069

20099325_2

( 31)P spectra were acquired before and after each injection of hyperpolarized [ 1-(13)C ] pyruvate and subsequent ( 13)C spectroscopy at 11.7 T .

12070

20099325_3

( 1)H and two-dimensional ( 1)H-(1)H-total correlation spectroscopy spectra were acquired from extracts of cells grown in uniformly labeled ( 13)C-glucose , on a 16.4 T , to determine ( 13)C fractional enrichment and distribution of ( 13)C label .

12071

20099325_4

JM1 cells were found to have a high rate of aerobic glycolysis in both two-dimensional culture and in the bioreactor , with 85% of the ( 13)C label from uniformly labeled ( 13)C-glucose being present as either lactate or alanine after 23 h .

12072

20099325_5

Flux measurements of pyruvate through lactate dehydrogenase and alanine aminotransferase in the bioreactor system were 12.18 +/- 0.49 nmols/sec/10(8) cells and 2.39 +/- 0.30 nmols/sec/10(8) cells , respectively , were reproducible in the same bioreactor , and were not significantly different over the course of 2 days .

12073

20099325_6

Although this preliminary study involved immortalized cells , this combination of technologies can be extended to the real-time metabolic exploration of primary benign and cancerous cells and tissues prior to and after therapy .

12074

23029264_0

Forkhead box protein O1 ( FOXO1 ) , a key member of the FOXO family of transcription factors , acts as a tumor suppressor and has been associated with various key cellular functions , including cell growth , differentiation , apoptosis and angiogenesis .

12075

23029264_1

Therefore , it is puzzling why FOXO protein expression is downregulated in cancer cells .

12076

23029264_2

MicroRNAs , non-coding 20 nucleotide single-stranded RNAs , result in translational repression or degradation and gene silencing of their target genes , and significantly contribute to the regulation of gene expression .

12077

23029264_3

In the current study , we report that miR-370 expression was significantly upregulated in five prostate cancer cell lines , compared to normal prostatic epithelial ( PrEC ) cells .

12078

23029264_4

Ectopic expression of miR-370 induced proliferation and increased the anchorage-independent growth and colony formation ability of DU145 and LNCaP prostate cancer cells , while inhibition of miR-370 reduced proliferation , anchorage-independent growth and colony formation ability .

12079

23029264_5

Furthermore , upregulation of miR-370 promoted the entry of DU145 and LNCaP prostate cancer cells into the G1/S cell cycle transition , which was associated with downregulation of the cyclin-dependent kinase ( CDK ) inhibitors , p27(Kip1) and p21(Cip1) , and upregulation of the cell-cycle regulator cyclin D1 mRNA .

12080

23029264_6

Additionally , we demonstrated that miR-370 can downregulate expression of FOXO1 by directly targeting the FOXO1 3'-untranslated region .

12081

23029264_7

Taken together , our results suggest that miR-370 plays an important role in the proliferation of human prostate cancer cells , by directly suppressing the tumor suppressor FOXO1 .

12082

22883142_0

Signals of archaic admixture have been identified through comparisons of the draft Neanderthal and Denisova genomes with those of living humans .

12083

22883142_1

Studies of individual loci contributing to these genome-wide average signals are required for characterization of the introgression process and investigation of whether archaic variants conferred an adaptive advantage to the ancestors of contemporary human populations .

12084

22883142_2

However , no definitive case of adaptive introgression has yet been described .

12085

22883142_3

Here we provide a DNA sequence analysis of the innate immune gene STAT2 and show that a haplotype carried by many Eurasians ( but not sub-Saharan Africans ) has a sequence that closely matches that of the Neanderthal STAT2 .

12086

22883142_4

This haplotype , referred to as N , was discovered through a resequencing survey of the entire coding region of STAT2 in a global sample of 90 individuals .

12087

22883142_5

Analyses of publicly available complete genome sequence data show that haplotype N shares a recent common ancestor with the Neanderthal sequence ( thousand years ago ) and is found throughout Eurasia at an average frequency of Interestingly , N is found in Melanesian populations at higher frequency ( than in Eurasian populations .

12088

22883142_6

A neutrality test that controls for demography rejects the hypothesis that a variant of N rose to high frequency in Melanesia by genetic drift alone .

12089

22883142_7

Although we are not able to pinpoint the precise target of positive selection , we identify nonsynonymous mutations in ERBB3 , ESYT1 , and STAT2-all of which are part of the same 250 kb introgressive haplotype-as good candidates .

12090

23089335_0

BACKGROUND : It is unclear whether distinct weight-related trajectory classes , differing in course , demographics , and health characteristics , exist in the elderly population .

12091

23089335_1

METHODS : Data came from the 10-year ( 1986-1996 ) Duke Established Populations for Epidemiologic Studies of the Elderly study of 3,861 black ( 54% ) and white ( 46% ) participants aged 65-105 years .

12092

23089335_2

Latent-class trajectories of body mass index ( BMI : kg/m(2) ) based on self-reported weight and height at baseline , 3 , 6 , and 10 years later were determined using generalized mixture models .

12093

23089335_3

Polytomous logistic regression was used to identify baseline demographic and health characteristics that distinguished the trajectories , and 10-year postbaseline data to confirm the findings .

12094

23089335_4

RESULTS : We identified three trajectories : normal weight ( BMI 27.6% of the sample ) , overweight ( BMI 65.1% ) , and obese ( BMI 7.3% ) .

12095

23089335_5

Demographic characteristics distinguished the three trajectories : highest odds of blacks , women , and less education in the obese trajectory , lowest in the normal-weight trajectory .

12096

23089335_6

Obese and overweight differed adversely from normal-weight trajectories , but not significantly from each other on cognitive impairment , hypertension , and diabetes .

12097

23089335_7

Depressive symptomatology was more prevalent in the obese ; they were also younger .

12098

23089335_8

There was no association with cancer or heart disease .

12099

23089335_9

CONCLUSION : Distinct trajectories and course of BMI were present in this older population .

12100

23089335_10

Weight loss increased with increase in BMI class .