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hallmarks_of_cancer

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11901

1354348_4

To test whether overexpression of normal human HER-2 can transform cells independently of the EGF receptor , we have introduced multiple copies of HER-2 into the EGF receptor-negative cell line , NR6 , and have performed assays for both transformation and tumorigenicity .

11902

1354348_5

Engineered NR6 cells that overexpress the HER-2 gene product display a highly transformed and tumorigenic phenotype as compared with control cells .

11903

1354348_6

Additionally , a monoclonal antibody to the extracellular domain of the HER-2 receptor is able to inhibit the proliferation of the overexpressing cells in vitro as well as tumor growth in vivo .

11904

1354348_7

This study provides clear evidence that HER-2-mediated transformation can be achieved independently of the EGF receptor .

11905

20422883_0

BACKGROUND/AIMS The use of chemotherapy in hepatocellular carcinoma is still controversial .

11906

20422883_1

The aim of this study was to investigate whether the combined use of epirubicin and progesterone has a synergistic effect on cell proliferation and apoptosis in HepG2 cells .

11907

20422883_2

METHODOLOGY Different concentrations of epirubicin ( 0.1 microg/ml , 0.25 microg/ml and 0.5microg/ml ) or progesterone ( 12.5 microM , 25 microM and 50 microM ) were added to HepG2 cells either alone or in combinations consisting of different concentrations of the two .

11908

20422883_3

Their effects on HepG2 cells were studied by ( 1 ) XTT assay for analysis of cell proliferation , ( 2 ) 3H-Thymidine incorporation for DNA synthesis , ( 3 ) annexin V-FITC/ propidium iodide ( PI ) flowcytometery for cell apoptosis , ( 4 ) flowcytometry for cell cycle distributions , and ( 5 ) reverse transcription-polymerase chain reaction for expression of cell cycle modulator , cyclin D1 .

11909

20422883_4

RESULTS 50 microM progesterone increased both the cytotoxic and apoptotic effects of 0.1 microg/ml epirubicin on HepG2 cells at 48 hr culture due to 50 microM progesterone accumulated cells in S phase of the cell cycle and subsequently reduced cyclin D1 expression .

11910

20422883_5

These effects on HepG2 cells induced by this combination were comparable to those induced by 0.5 microg/ml epirubicin alone .

11911

20422883_6

CONCLUSIONS In vitro , progesterone can increase the cytotoxicity and apoptosis induced by epirubicin on HepG2 cells .

11912

22653530_0

Semiconductor nanoparticles ( NPs ) became important and wide-used tool for cell imaging because of their unique remarkable properties .

11913

22653530_1

Nevertheless , all previous investigations in this area were done on proliferating cells .

11914

22653530_2

For the first time , this work demonstrates strong influence of cell active proliferation/contact inhibition of proliferation on uptake of NPs .

11915

22653530_3

In addition , we show that cell division plays key-role in penetration of silicon carbide based NPs ( SiC NPs ) inside the cell nucleus .

11916

22653530_4

This may very likely concern other types of NPs able to reach the cell nuclei .

11917

22653530_5

In particular , observed effect of cell division gives perspectives for future selective cancer treatment with NPs .

11918

22934133_0

We show that sufficient concentrations of gold nanoparticles produced by an original synthesis method in EMT-6 and CT-26 cancer cells make it possible to detect the presence , necrosis and proliferation of such cells after inoculation in live mice .

11919

22934133_1

We first demonstrated that the nanoparticles do not interfere with the proliferation process .

11920

22934133_2

Then , we observed significant differences in the tumor evolution and the angiogenesis process after shallow and deep inoculation .

11921

22934133_3

A direct comparison with pathology optical images illustrates the effectiveness of this approach .

11922

20953816_0

The multi-kinase inhibitor dasatinib induced a variable but significant decrease of viability in both p53(wild-type) ( EHEB , JVM-2 , JVM-3 ) and p53(mutated) ( MEC-1 , MEC-2 , BJAB ) prolymphocytic B leukemic cells , due to a combination of cell cycle block in G1 and apoptosis .

11923

20953816_1

Antibody phospho-kinase array analysis revealed that dasatinib inhibited the phosphorylation of various kinases , including ERK1/2 and p38/MAPK as well as of STAT3 transcription factors , in both p53(wild-type) and p53(mutated) cells .

11924

20953816_2

Therefore , dasatinib might offer a novel therapeutic strategy not only for p53(wild-type) , but also for p53(mutated) B malignancies that have the worst prognosis and urgently need innovative therapeutic approaches .

11925

21947232_0

Plasminogen activator inhibitor type 1 ( PAI-1 ) is a serpin protein , a natural inhibitor of urokinase ( uPA ) and tissue plasminogen activators ( tPA ) .

11926

21947232_1

By inhibiting uPA it can block growth of the cancer tumors by suppressing angiogenesis , while when acting on tPA in the blood it can avert conversion of plasminogen to plasmin preventing lysis of the clot .

11927

21947232_2

Furthermore , blocking PAI-1 activity can protect against thrombosis .

11928

21947232_3

Thus PAI-1 makes great impact on human homeostasis and is desirable for clinical application .

11929

21947232_4

Wild-type PAI-1 ( wt-PAI-1 ) has a short span of activity with a t1/2 of h , being spontaneously converted into a latent form .

11930

21947232_5

An enormous effort has been made to create a more stable molecule with >600 PAI-1 variants constructed to study its structure-function relationship .

11931

21947232_6

In the present study , we evaluate the structure of the active recombinant VLHL-PAI-1 ( very long half life , active >700 h ) which is glycosylated similarly to wt-PAI-1 at N232 and N288 , with the extended reactive center loop , intact engineered -S-S-bridge ( Q174C , G323C ) that precludes latency without affecting structure , and can be controlled by a reducing agent to terminate activity at will .

11932

21947232_7

We have already proven its usefulness to control cancer in human cancer cells , as well as preventing clot lysis in human whole blood and plasma and in a mouse model .

11933

21947232_8

Our results demonstrate the potential therapeutic applications ( topical or systemic ) of this protein in the treatment of cancer , for the trauma patients to ward off an excessive blood loss , or for people with the PAI-1 deficiency , especially during surgery .

11934

22252523_0

Breast cancer is the most common malignancy in women , and many breast cancer patients fail conventional treatment strategies of chemotherapy , radiation , and antiestrogen therapy .

11935

22252523_1

Research into the molecular pathways and biomarkers involved in the development of breast cancer should yield information that will guide therapeutic decisions .

11936

22252523_2

Epidermal growth factor receptor ( EGFR ) and cyclooxygenase-2 ( COX-2 ) are involved in the carcinogenesis of breast cancer and exist tight crosstalk with estrogen receptor ( ER ) pathway .

11937

22252523_3

Combination of EGFR and COX-2 inhibitors , therefore , could be an effective strategy for reducing cell growth in estrogen-dependent breast cancer .

11938

22252523_4

In order to verify the effects of EGFR and COX-2 inhibitors , breast cancer cells MCF-7 and SKBR-3 were characterized for receptors status and then treated with respective inhibitors ( nimotuzumab and celecoxib ) alone and in combination .

11939

22252523_5

Both cell lines were sensitive to celecoxib , but not to nimotuzumab .

11940

22252523_6

However , combination of two drugs demonstrated synergistic effects on cell killing .

11941

22252523_7

Moreover , association of two drugs resulted in SKBR-3 cells , a further G0/G1 phase arrest than one drug alone .

11942

22252523_8

Downregulation of p-EGFR , p-Akt , p-mTOR , and amplified in breast cancer 1 ( AIB1 ) were observed in both cell lines , and upregulation of E-cadherin was only found in MCF-7 , after treatment with single agent or in combination .

11943

22252523_9

These studies suggest that nimotuzumab and celecoxib exert synergistic antiproliferation effects in breast cancer , which partly correlates with ER status .

11944

22252523_10

Due to Akt/mTOR , EMT and AIB1 pathways participate in this process , therefore , E-cadherin and AIB1 may be considered as possible biomarkers to predict response in ER-positive breast cancer cells treated with EGFR and COX-2 inhibitors .

11945

23147699_0

DNA damage induced by benzene and its metabolites is thought of as an important mechanism underlying benzene genotoxicity in chronic benzene poisoning ( CBP ) .

11946

23147699_1

Therefore , genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population .

11947

23147699_2

Since benzene-induced DNA damages include DNA adducts , we hypothesized that the polymorphisms of ERCC1 ( Excision repair cross complementation group 1 ) and ERCC2/XPD ( Excision repair cross complementation group 2/xeroderma pigmentosum group D ) are associated with the risk of CBP .

11948

23147699_3

A case-control study involving 102 benzene-poisoned patients and 204 none-benzene-poisoned controls occupationally exposed to benzene was carried out in the Northeast region of China .

11949

23147699_4

The polymorphisms of codon 118 ( rs11615 ) and C8092A ( rs3212986 ) of ERCC1 , codon 751 ( rs13181 ) , 312 ( rs1799793 ) and 156 ( rs238406 ) of ERCC2/XPD were genotyped by TaqMan(®) Real-time PCR .

11950

23147699_5

The results showed that individuals carrying the ERCC1 codon 118 TT genotype had an increased risk of CBP ( OR(adj)=3.390 ; 95%CI : 1.393-8.253 ; P=0.007 ) comparing with its CC genotype .

11951

23147699_6

After stratified by smoking , gender and exposure duration we found that the increased risk of CBP associated with the ERCC1 codon 118 TT genotype confined to nonsmokers ( OR=3.214 ; 95% CI : 1.359-7.601 ; P=0.006 ) , female ( OR=3.049 ; 95% CI : 1.235-7.529 ; P=0.013 ) and exposure duration> 12 years ( OR=3.750 ; 95% CI : 1.041-13.513 ; P=0.035 ) .

11952

23147699_7

Since ERCC1 and ERCC2/XPD are both located on chromosome 19q13.3 , haplotype analysis of all 5 SNPs was also conducted .

11953

23147699_8

However no correlations between the risks of CBP and other genotypes or haplotypes were found .

11954

23147699_9

Therefore , our findings suggest an important role of ERCC1 codon 118 polymorphisms for a biomarker to CBP in the Chinese occupational population .

11955

12444953_0

The ultraviolet ( UV ) radiation present in sunlight is immune-suppressive .

11956

12444953_1

Recently we showed that solar-simulated UV radiation ( UVA + UVB ; 295-400 nm ) , applied after immunization , suppressed immunological memory and the elicitation of delayed-type hypersensitivity to the common opportunistic pathogen , Candida albicans .

11957

12444953_2

Further , we found that wavelengths in the UVA region of the solar spectrum ( 320-400 nm ) , devoid of UVB , were equally effective in activating immune suppression as UVA + UVB radiation .

11958

12444953_3

Here we report on the mechanisms involved .

11959

12444953_4

No immune suppression was found in UV-irradiated mice injected with monoclonal anti-interleukin ( IL)-10 antibody , or mice exposed to solar-simulated UV radiation and injected with recombinant IL-12 .

11960

12444953_5

Antigen-specific suppressor T cells were found in the spleens of mice exposed to UVA + UVB radiation .

11961

12444953_6

Applying liposomes containing bacteriophage T4N5 to the skin of mice exposed to solar-simulated UVA + UVB radiation or mice exposed to UVA radiation blocked immune suppression , demonstrating an essential role for UV-induced DNA damage in the suppression of established immune reactions .

11962

12444953_7

These findings indicate that UV radiation activates similar immunological pathways to suppress the induction , or the elicitation , of the immune response .

11963

22778799_0

We demonstrate that reactive oxygen species ( ROS ) plays an important role in the process of apoptosis in human peripheral blood mononuclear cell ( PBMC ) which is induced by the radiation of 900 MHz radiofrequency electromagnetic field ( RFEMF ) at a specific absorption rate ( SAR ) of W/kg when the exposure lasts longer than two hours .

11964

22778799_1

The apoptosis is induced through the mitochondrial pathway and mediated by activating ROS and caspase-3 , and decreasing the mitochondrial potential .

11965

22778799_2

The activation of ROS is triggered by the conformation disturbance of lipids , protein , and DNA induced by the exposure of GSM RFEMF .

11966

22778799_3

Although human PBMC was found to have a self-protection mechanism of releasing carotenoid in response to oxidative stress to lessen the further increase of ROS , the imbalance between the antioxidant defenses and ROS formation still results in an increase of cell death with the exposure time and can cause about 37% human PBMC death in eight hours .

11967

21129360_0

Tobacco-induced oxidative stress leads to chronic inflammation and is implicated in the development of many human epithelial cancers , including head and neck cancer .

11968

21129360_1

Cigarette smoke exposure was shown to induce the expression of the ΔNp63α and nitric oxide synthase ( NOS)-2 in head and neck squamous cell carcinoma cells and immortalized oral keratinocytes .

11969

21129360_2

The NOS2 promoter was found to contain various cognate sequences for several transcription factors including interferon regulatory factor ( IRF)-6 and p63 , which were shown in vivo binding to the NOS2 promoter in response to smoke exposure .

11970

21129360_3

Small interfering ( si)-RNAs against both ΔNp63α and IRF6 decreased the induction of NOS2 promoter-driven reporter luciferase activity and were shown to inhibit NOS2 activity .

11971

21129360_4

Furthermore , both mainstream ( MSE ) and sidestream ( SSE ) smoking extracts induced changes in expression of autophagic marker , LC3B , while siRNA against ΔNp63α , IRF6 and NOS2 modulated these autophagic changes .

11972

21129360_5

Overall , these data support the notion that ΔNp63α/IRF6 interplay regulates NOS2 transcription , thereby underlying the autophagic-related cancer cell response to tobacco exposure .

11973

20525350_0

BACKGROUND The immune system plays an important role in the multifactorial biologic system during the development of neoplasias .

11974

20525350_1

However , the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial , and the cell subsets and the mechanisms involved are poorly investigated .

11975

20525350_2

The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas .

11976

20525350_3

METHODS Fifty-one animals with mammary carcinomas , classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis ( tumor size ; presence of lymph node and pulmonary metastasis ; clinical stage ; histological grade ; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity ) and survival rates .

11977

20525350_4

Twenty-four animals ( MC-BMT = 16 and MC = 8 ) were elected to the immunophenotypic study performed by flow cytometry .

11978

20525350_5

RESULTS Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC .

11979

20525350_6

Univariate analysis demonstrated that the intensity of inflammation ( moderate/intense ) and the proportion of CD4+ ( > or = 66.7% ) or CD8+ T-cells ( <33.3% ) were not associated with worse survival rate .

11980

20525350_7

Multivariate analysis demonstrated that only lymphocytic infiltrate intensity > or = 600 ( P = 0.02 ) remained as independent prognostic factor .

11981

20525350_8

Despite the clinical manifestation , the lymphocytes represented the predominant cell type in the tumor infiltrate .

11982

20525350_9

The percentage of T-cells was higher in animals with MC-BMT without metastasis , while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT ( P < 0.05 ) .

11983

20525350_10

The relative percentage of CD4+ T-cells was significantly greater in metastasized tumors ( both MC-BMT and MC ) , ( P < 0.05 ) while the proportion of CD8+ T-cells was higher in MC-BMT without metastasis .

11984

20525350_11

Consequently , the CD4+/CD8+ ratio was significantly increased in both groups with metastasis .

11985

20525350_12

Regardless of the tumor type , the animals with high proportions of CD4+ and low CD8+ T-cells had decreased survival rates .

11986

20525350_13

CONCLUSION The intensity of lymphocytic infiltrate and probably the relative abundance of the CD4+ and CD8+ T-lymphocytes may represent important survival prognostic biomarkers for canine mammary carcinomas .

11987

23201449_0

Phyllanthus urinaria is widely used as anti-inflammatory , antiviral , antibacterial , and anti-hepatotoxic medicines in almost every tropical country .

11988

23201449_1

However , scientific evidence supporting its use in cancer metastasis is limited , particularly osteosarcoma .

11989

23201449_2

We investigated the effect of P. urinaria extract ( PUE ) on cell viability , invasion , and migration in the human osteosarcoma Saos-2 cell line , and looked at the impact of PUE on several relevant proteases and signaling pathways .

11990

23201449_3

This study demonstrates that PUE , at a range of concentrations ( from 0 to 100 μg/ml ) , concentration-dependently inhibited the migration/invasion capacities of Saos-2 without cytotoxic effects .

11991

23201449_4

Zymographic and western blot analyses revealed that PUE inhibited the urokinase-type plasminogen activator ( u-PA ) and matrix metalloproteinase-2 ( MMP-2 ) enzyme activity , as well as protein expression .

11992

23201449_5

Western blot analysis also showed that PUE inhibits phosphorylation of ERK1/2 and Akt .

11993

23201449_6

Testing of mRNA level , quantitative real-time PCR , and promoter assays evaluated the inhibitory effects of PUE on u-PA expression in Saos-2 cells .

11994

23201449_7

The chromatin immunoprecipitation ( ChIP ) assay was reactive to the transcription protein SP-1 , which was inhibited by PUE .

11995

23201449_8

In conclusion , PUE suppresses human osteosarcoma Saos-2 cell invasion and migration by transcriptionally inhibiting u-PA via ERK and Akt signaling pathways .

11996

23201449_9

Therefore , PUE produces anti-metastatic activity in Saos-2 cells .

11997

19003298_0

Biomaterials such as polyetherurethans ( PEUs ) are the scaffolding , which is indispensable for the development of the bio-artificial organs .

11998

19003298_1

However , PEUs can induce tumors in subcutaneous implantation sites in rat .

11999

19003298_2

We have shown that the different inhibitory potential of gap junctional intercellular communication ( GJIC ) on the surface of the biomaterials , including PEUs , is a key step in determining the tumorigenic potential .

12000

19003298_3

Here we show that suppression of a gap junctional protein connexin 43 ( Cx43 ) plays an important role in in vivo tumorigenesis induced by PEUs for the first time and that Cx43 transfection may be an effective strategy for preventing tumorigenesis induced by biomaterials .