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The me

Vero László

1Institut

2Crysta

3South-

4Depar

5Depar

 

Corres E-mail

Articl

Accep Availa Keywo skin ca malign produ melan

   

 

e effec lanoma

nika Wolh ó Szabó2, A

te of Public He al International -Transdanubia rtment of Occ rtment of Dent

sponding au address: wo

le Info

pted on 28 Ju able online 18

ords:

ancer, melan num, antioxid ucts, preventi

noma cells.

   

The

t of fla a transp

her1,*, Kata Andor Seb

ealth, Medical l Kft., Eger

n Regional He cupational Hea

tal Public Heal

thor. Tel.:+36 olher.veronika

une 2012 8 June 2012

noma dant ion, B16

Journ

Internationa

Jo

avonoid planted

lin Gombo estyén3, A

School, Pécs U ealth Care Insu

alth, Medical S lth, Medical Sc

72 536 394 a@gmail.com

Abstrac Melanom mortality malignum malignum to full re life age also pla surveys.

also risk substanc In recen product mice m chemop organs investiga flavonoid carcinog

nal of P

al Journal o and

urnal home

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os1, Krisztin ndrás Husz

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nopause o , 9, 10, 11) revention

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)

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oducts are administra

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ration decre es of tum

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g cells essels mful.

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and or a

roduct of g and stered ble to ultiple mune efence ghted on on eases mours, ations, eases s. (12,

(3)

Hidvegi and coworkers investigated the effect of a benzokinone-containing product on transplanted B16 melanoma growth and metastasis supplementing certain groups with vitamin-C.

Administered orally the product itself and in combination with vitamin-C significantly inhibited metastasis, vitamin-C alone did not exert this effect. In contrast, the administration of vitamin-C one hour after the benzokinone-containing product lead to reduced anti-metastatic effect.

(17).

Many scientist tend to believe that antioxidant supplementation may negatively modify the effect of certain anticancer treatments and able to worsen the prognosis of certain tumours. Heinen and coworkers investigated the association between antioxidant nutrient intake (vitamin C, E, A, other supplements) and the risk ofbasal cell (BCC) and squamous cell carcinomas (SCC) of the skin. According to their results, there is no

obvious and significant connection between antioxidant supplementation, and skin cancer development (18).

The importance of miRNAs, as molecular epidemiological biomarkers of primary tumour prevention is improved in the past few years.

miRNAs are short RNA segments which does not translate to proteins.

The expression patterns of miRNA of malignant melanoma were characterised recently from tissue as well as from blood samples.

There is unambiguous evidence to prove the role of miRNAs as unique biomarkers in melanoma malignant prevention and treatment. A group of concerned miRNAs that are in connection with malignant skin tumours are shown in Table 1.

(19).

Table 1. miRNAs in connection with malignant skin tumours B16 is a transplantable murine melanoma cell

line, which is well known for evaluating the effect of potential anti-tumor and chemopreventive compounds.

Kyoko and Nomeli transplanted C57BL/6J mice with B16 melanoma cell line and lung metastasis were investigated. The mice received ethanol.

Ethanol supplementation inhibited lung metastasis and this inhibition has also affected body weight, insulin and leptin secretion. The expression of Il6, Nf b, Snai1 were decreased,

and the expression level of E-Cadherin, Kiss1, Nm23-m1 and Nm23-m2 were elevated.

Kyoko and Nomeli concluded, that in cell cultures and in animal models ethanol is able to decrease the metastatic ability of B16 cells. (20).

Materials and method

6 week old C57BL/6N male mice (20 g overall bodyweight) were transplanted with B16 melanoma cell line. Each mouse was subcutan injected with 105 B16 cells in the dorsal region of

Epigenetic element Publication year Possible biomarker use Sample Target/pathway

Epigenetic  melanoma  expression

Function

miR‐29c 2011 Progression, prognosis Tissue DNMT3 Down Tumor suppressor

miR‐214 2011 Diagnosis, progression Cell, tissue TFAP2C Up Oncogene

miR‐205 2011 Detection, progression Cell, tissue E2F1, E2F5 Down Tumor suppressor

miR‐30b/miR‐30d 2011 Progression, prognosis Cell, tissue GALNT7 Up Oncogene

miR‐34b 2011 Progression Cell, tissue Cell adhesion, 

migration, motility Down Tumor suppressor miR‐506/miR‐514  2011 Detection, progression Cell, tissue Growth, apoptosis, 

invasion Up Oncogene

miR‐21/miR‐155 2011 Detection, prognosis Tissue Proliferation, 

metastasis Up Oncogene

miR‐221 2011 Progression Serum

P27Kip1/CDKN1B  and C‐Kit (from a 

prior  study18417445)

Up Oncogene

miR‐375 2011 Detection, progression Cell, tissue Proliferation, 

invasion, migration Down Tumor suppressor DNA Methylation 

LINE‐1  2011 Prognosis Cell

Surrogate for  hypomethylated 

TSGs

Up Marker for inactive  tumor suppressor DNA Histone 

Modifier EZH2 2011 Detection, progression Cell Proliferation Up Oncogene

(4)

the n contr receiv libitum antiox Witho mice kidne anim miRN cDNA miRN cDNA μl tr buffe deoxy trans prime PCR PCR Mast Resu Surviv Meie

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V. Wolhe 5-15 male ups.The c nd standa

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(5)

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Figure 3.

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. miRNA expr

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(6)

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Figur

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re 5. miRNA e

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(7)

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an.

(8)

V. Wolher / Journal of Proactive Medicine 1 (2012)13-20 References

1. Burton C. Malignant melanoma in the year 2000. CA Cancer J Clin 2000; 50:209-213.

2. Marks R. The changing incidence and mortality of melanoma in Australia. Rec Res Cancer Res 2002; 160:113- 121.

3. Ember I, Kiss I. B rdaganatok. Daganatok és daganatmegel z állapotok molekuláris epidemiológiája 2005;

217-232. (Article in Hungarian)

4. Diepgen T, Mahler V. The epidemiology of skin cancer. Br J Dermatol 2002; 146. 61:1-6.

5.

http://portal.ksh.hu/portal/page?_pageid=37,115776&_dad=po rtal&_schema=PORTAL

6. Ottó Sz, Kásler M. Rákmortalitás és incidencia hazánkban, az európai adatoktükrében. Magyar Onkológia 2002; 46:111- 118. (Article in Hungarian)

7. Rigel D, Carucci J. Malignant melanoma. Prevention, early detection and treatment in the 21 century. Ca Cancer J Clin 2000; 50:215-223a.

8. Schottenfeld D, Fraumeni J, Joseph F. Cancer Epidemiology and Prevention. New York Oxford University Press. 2006; 101–138.

9. Tompa A. A daganatos betegségek el fordulása a hazai és a nemzetközi helyzet ismertetése. Magyar Tudományos Akadémia folyóirata 2011; 172 éf. 11:1333-1346. (Article in Hungarian)

10. Proctor JW, Auclair BG, Stokowski L. Endocrine factors and the growth and spread of B16 melanoma. J Natl Cancer Inst 1976; 57: 1197–8.

11. Ladányi A, Tímár J, Bocsi J et al. Sex-dependent liver metastasis of human melanoma lines in SCID mice.

Melanoma Res. 1995; 5(2):83-6.

12. Dennert G, Zwahlen M, Brinkman M et al. Selenium for preventing cancer. Sao Paulo Medical Journal 2012; 130: 67- 67.

13. Perchellet JP, Perchellet EM. Antioxidants and multistage carcinogenesis in mouse skin. Free Radic Biol Med 1989;

7(4):377-408.

14. Ozten-Kanda N, Bosland MC. Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence. J Carcinog 2011; 10:27.

15. Rodek E. Táplálkozásunk és a rák. Új Diéta 1999; 1:15-16.

16. Ember I, Kiss I. Táplálkozás és a rák. Új Diéta 2001; 1:4-8.

17. Hidvegi M, Lapis K, Paku S et al. Effect of Avemar and Avemar + vitamin C on tumor growth and metastasis in experimental animals. Anticancer Research Journal 1998;

18(4A):2353-8.

18. Heinen MM, Hughes MC, Ibiebele TI et al. Intake of antioxidant nutrients and the risk of skin cancer. Eur J Cancer 2007; 43(18):2707-16.

19. Greenberg ES, Chong KK, Huynh KT, Tanaka R, Hoon DS.

Epigenetic biomarkers in skin cancer Cancer Lett. 2012.

20. Kyoko K, Nomeli P. Ethanol Inhibits B16-Bl6 Melanoma Metastasis and Cell Phenotypes Associated with Metastasis.

In vivo 2012; 26:47-58.

Ábra

Table 1. miRNAs in connection with malignant skin tumours  B16 is a transplantable murine melanoma cell

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