TY  - JOUR
AU  - Bitar, Milad S.
AU  - Ayed, Adel K.
AU  - Abdel-Halim, Samy M.
AU  - Isenović, Esma R.
AU  - Al-Mulla, Fahd
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4010
AB  - Aims: Endothelial dysfunction is a key triggering event in the development of cardiovascular diseases and the current study explored this phenomenon in the context of inflammation, apoptosis, reactive oxygen species (ROS) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during chronic diabetes. Main methods: alpha-Lipoic acid (ALA) and wortmannin (WM) were chronically administered to aged Goto Kakizaki (GK) rats, a genetic model of non-obese type II diabetes. Key indices of inflammation, apoptosis and oxidative stress were assessed using western blotting, real-time PCR and immunofluoresence-based techniques. Key findings: A chronic inflammation (e.g., increased mRNA/protein levels of INF-alpha, ICAM, fractalkine, CD-68, myeloperoxidase) in connection with increased caspase-based apoptotic cell death and heightened state of oxidative stress (HSOS)- appear to exist in diabetic cardiovascular tissues. An assessment of NF-kappa B dynamics in aged diabetic vessels revealed not only a marked increase in cytosolic phosphorylated levels of I kappa B-alpha, NIK, IRK but also an enhancement in nuclear localization of p65 concomitantly with augmented NF-kappa B-DNA binding activity. Most of the aforementioned cardiovascular-based diabetic abnormalities including reduced activities of PI3K and Akt kinase were ameliorated following chronic ALA therapy. WM, given to GK rats negated the anti-inflammatory and anti-apoptotic actions of ALA. Significance: Our data highlight a unifying mechanism whereby HSOS through an induction of NF-kappa B activity together with an impairment in PI3K/Akt pathway favors pro-inflammatory/pro-apoptotic diabetic vascular milieu that culminate in the onset of endothelial dysfunction, a phenomenon which appears to be amenable to treatment with antioxidants and/or PI3/Akt mimetics (e.g., ALA). (C) 2010 Elsevier Inc. All rights reserved.
T2  - Life Sciences
T1  - Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism
VL  - 86
IS  - 23-24
SP  - 844
EP  - 853
DO  - 10.1016/j.lfs.2010.03.019
ER  - 

@article{
author = "Bitar, Milad S. and Ayed, Adel K. and Abdel-Halim, Samy M. and Isenović, Esma R. and Al-Mulla, Fahd",
year = "2010",
abstract = "Aims: Endothelial dysfunction is a key triggering event in the development of cardiovascular diseases and the current study explored this phenomenon in the context of inflammation, apoptosis, reactive oxygen species (ROS) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during chronic diabetes. Main methods: alpha-Lipoic acid (ALA) and wortmannin (WM) were chronically administered to aged Goto Kakizaki (GK) rats, a genetic model of non-obese type II diabetes. Key indices of inflammation, apoptosis and oxidative stress were assessed using western blotting, real-time PCR and immunofluoresence-based techniques. Key findings: A chronic inflammation (e.g., increased mRNA/protein levels of INF-alpha, ICAM, fractalkine, CD-68, myeloperoxidase) in connection with increased caspase-based apoptotic cell death and heightened state of oxidative stress (HSOS)- appear to exist in diabetic cardiovascular tissues. An assessment of NF-kappa B dynamics in aged diabetic vessels revealed not only a marked increase in cytosolic phosphorylated levels of I kappa B-alpha, NIK, IRK but also an enhancement in nuclear localization of p65 concomitantly with augmented NF-kappa B-DNA binding activity. Most of the aforementioned cardiovascular-based diabetic abnormalities including reduced activities of PI3K and Akt kinase were ameliorated following chronic ALA therapy. WM, given to GK rats negated the anti-inflammatory and anti-apoptotic actions of ALA. Significance: Our data highlight a unifying mechanism whereby HSOS through an induction of NF-kappa B activity together with an impairment in PI3K/Akt pathway favors pro-inflammatory/pro-apoptotic diabetic vascular milieu that culminate in the onset of endothelial dysfunction, a phenomenon which appears to be amenable to treatment with antioxidants and/or PI3/Akt mimetics (e.g., ALA). (C) 2010 Elsevier Inc. All rights reserved.",
journal = "Life Sciences",
title = "Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism",
volume = "86",
number = "23-24",
pages = "844-853",
doi = "10.1016/j.lfs.2010.03.019"
}

Bitar, M. S., Ayed, A. K., Abdel-Halim, S. M., Isenović, E. R.,& Al-Mulla, F.. (2010). Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism. in Life Sciences, 86(23-24), 844-853.
https://doi.org/10.1016/j.lfs.2010.03.019

Bitar MS, Ayed AK, Abdel-Halim SM, Isenović ER, Al-Mulla F. Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism. in Life Sciences. 2010;86(23-24):844-853.
doi:10.1016/j.lfs.2010.03.019 .

Bitar, Milad S., Ayed, Adel K., Abdel-Halim, Samy M., Isenović, Esma R., Al-Mulla, Fahd, "Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism" in Life Sciences, 86, no. 23-24 (2010):844-853,
https://doi.org/10.1016/j.lfs.2010.03.019 . .

TY  - JOUR
AU  - Andreyev, HJN
AU  - Benamouzig, R
AU  - Beranek, M
AU  - Clarke, P
AU  - Cunningham, D
AU  - Norman, AR
AU  - Giaretti, W
AU  - de Goeij, AFPM
AU  - Iacopetta, BJ
AU  - Jullian, E
AU  - Krtolica-Žikić, Koviljka
AU  - Lee, JQ
AU  - Wang, ST
AU  - Lees, N
AU  - Al-Mulla, F
AU  - Muller, O
AU  - Pauly, M
AU  - Pricolo, V
AU  - Russo, A
AU  - Troungos, C
AU  - Urosevic, N
AU  - Ward, R
PY  - 2003
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2631
T2  - Gut: An International Journal of Gastroenterology and Hepatology
T1  - Mutant K-ras2 in serum
VL  - 52
IS  - 6
SP  - 915
EP  - 916
DO  - 10.1136/gut.52.6.915-a
ER  - 

@article{
author = "Andreyev, HJN and Benamouzig, R and Beranek, M and Clarke, P and Cunningham, D and Norman, AR and Giaretti, W and de Goeij, AFPM and Iacopetta, BJ and Jullian, E and Krtolica-Žikić, Koviljka and Lee, JQ and Wang, ST and Lees, N and Al-Mulla, F and Muller, O and Pauly, M and Pricolo, V and Russo, A and Troungos, C and Urosevic, N and Ward, R",
year = "2003",
journal = "Gut: An International Journal of Gastroenterology and Hepatology",
title = "Mutant K-ras2 in serum",
volume = "52",
number = "6",
pages = "915-916",
doi = "10.1136/gut.52.6.915-a"
}

Andreyev, H., Benamouzig, R., Beranek, M., Clarke, P., Cunningham, D., Norman, A., Giaretti, W., de Goeij, A., Iacopetta, B., Jullian, E., Krtolica-Žikić, K., Lee, J., Wang, S., Lees, N., Al-Mulla, F., Muller, O., Pauly, M., Pricolo, V., Russo, A., Troungos, C., Urosevic, N.,& Ward, R.. (2003). Mutant K-ras2 in serum. in Gut: An International Journal of Gastroenterology and Hepatology, 52(6), 915-916.
https://doi.org/10.1136/gut.52.6.915-a

Andreyev H, Benamouzig R, Beranek M, Clarke P, Cunningham D, Norman A, Giaretti W, de Goeij A, Iacopetta B, Jullian E, Krtolica-Žikić K, Lee J, Wang S, Lees N, Al-Mulla F, Muller O, Pauly M, Pricolo V, Russo A, Troungos C, Urosevic N, Ward R. Mutant K-ras2 in serum. in Gut: An International Journal of Gastroenterology and Hepatology. 2003;52(6):915-916.
doi:10.1136/gut.52.6.915-a .

Andreyev, HJN, Benamouzig, R, Beranek, M, Clarke, P, Cunningham, D, Norman, AR, Giaretti, W, de Goeij, AFPM, Iacopetta, BJ, Jullian, E, Krtolica-Žikić, Koviljka, Lee, JQ, Wang, ST, Lees, N, Al-Mulla, F, Muller, O, Pauly, M, Pricolo, V, Russo, A, Troungos, C, Urosevic, N, Ward, R, "Mutant K-ras2 in serum" in Gut: An International Journal of Gastroenterology and Hepatology, 52, no. 6 (2003):915-916,
https://doi.org/10.1136/gut.52.6.915-a . .

TY  - JOUR
AU  - Andreyev, HJN
AU  - Norman, AR
AU  - Cunningham, D
AU  - Oates, J
AU  - Dix, BR
AU  - Iacopetta, BJ
AU  - Young, J
AU  - Walsh, T
AU  - Ward, R
AU  - Hawkins, N
AU  - Beranek, M
AU  - Jandik, P
AU  - Benamouzig, R
AU  - Jullian, E
AU  - Laurent-Puig, P
AU  - Olschwang, S
AU  - Muller, O
AU  - Hoffmann, I
AU  - Rabes, HM
AU  - Zietz, C
AU  - Troungos, C
AU  - Valavanis, C
AU  - Yuen, ST
AU  - Ho, JWC
AU  - Croke, CT
AU  - O'Donoghue, DP
AU  - Giaretti, W
AU  - Rapallo, A
AU  - Russo, A
AU  - Bazan, V
AU  - Tanaka, M
AU  - Omura, K
AU  - Azuma, T
AU  - Ohkusa, T
AU  - Fujimori, T
AU  - Ono, Y
AU  - Pauly, M
AU  - Faber, C
AU  - Glaesener, R
AU  - de Goeij, AFPM
AU  - Arends, JW
AU  - Andersen, SN
AU  - Lovig, T
AU  - Breivik, J
AU  - Gaudernack, G
AU  - Clausen, OPF
AU  - De Angelis, P
AU  - Meling, GI
AU  - Rognum, TO
AU  - Smith, R
AU  - Goh, HS
AU  - Font, A
AU  - Rosell, R
AU  - Sun, XF
AU  - Zhang, H
AU  - Benhattar, J
AU  - Losi, L
AU  - Lee, JQ
AU  - Wang, ST
AU  - Clarke, PA
AU  - Bell, S
AU  - Quirke, P
AU  - Bubb, VJ
AU  - Piris, J
AU  - Cruickshank, NR
AU  - Morton, D
AU  - Fox, JC
AU  - Al-Mulla, F
AU  - Lees, N
AU  - Hall, CN
AU  - Snary, D
AU  - Wilkinson, K
AU  - Dillon, D
AU  - Costa, J
AU  - Pricolo, VE
AU  - Finkelstein, SD
AU  - Thebo, JS
AU  - Senagore, AJ
AU  - Halter, SA
AU  - Wadler, S
AU  - Malik, S
AU  - Krtolica-Žikić, Koviljka
AU  - Urosevic, N
PY  - 2001
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2458
AB  - Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes C cancers (failure-free survival. P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. (C) 2001 Cancer Research Campaign.
T2  - British Journal of Cancer
T1  - Kirsten ras mutations in patients with colorectal cancer: the RASCAL II study
VL  - 85
IS  - 5
SP  - 692
EP  - 696
DO  - 10.1054/bjoc.2001.1964
ER  - 

@article{
author = "Andreyev, HJN and Norman, AR and Cunningham, D and Oates, J and Dix, BR and Iacopetta, BJ and Young, J and Walsh, T and Ward, R and Hawkins, N and Beranek, M and Jandik, P and Benamouzig, R and Jullian, E and Laurent-Puig, P and Olschwang, S and Muller, O and Hoffmann, I and Rabes, HM and Zietz, C and Troungos, C and Valavanis, C and Yuen, ST and Ho, JWC and Croke, CT and O'Donoghue, DP and Giaretti, W and Rapallo, A and Russo, A and Bazan, V and Tanaka, M and Omura, K and Azuma, T and Ohkusa, T and Fujimori, T and Ono, Y and Pauly, M and Faber, C and Glaesener, R and de Goeij, AFPM and Arends, JW and Andersen, SN and Lovig, T and Breivik, J and Gaudernack, G and Clausen, OPF and De Angelis, P and Meling, GI and Rognum, TO and Smith, R and Goh, HS and Font, A and Rosell, R and Sun, XF and Zhang, H and Benhattar, J and Losi, L and Lee, JQ and Wang, ST and Clarke, PA and Bell, S and Quirke, P and Bubb, VJ and Piris, J and Cruickshank, NR and Morton, D and Fox, JC and Al-Mulla, F and Lees, N and Hall, CN and Snary, D and Wilkinson, K and Dillon, D and Costa, J and Pricolo, VE and Finkelstein, SD and Thebo, JS and Senagore, AJ and Halter, SA and Wadler, S and Malik, S and Krtolica-Žikić, Koviljka and Urosevic, N",
year = "2001",
abstract = "Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes C cancers (failure-free survival. P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. (C) 2001 Cancer Research Campaign.",
journal = "British Journal of Cancer",
title = "Kirsten ras mutations in patients with colorectal cancer: the RASCAL II study",
volume = "85",
number = "5",
pages = "692-696",
doi = "10.1054/bjoc.2001.1964"
}

Andreyev, H., Norman, A., Cunningham, D., Oates, J., Dix, B., Iacopetta, B., Young, J., Walsh, T., Ward, R., Hawkins, N., Beranek, M., Jandik, P., Benamouzig, R., Jullian, E., Laurent-Puig, P., Olschwang, S., Muller, O., Hoffmann, I., Rabes, H., Zietz, C., Troungos, C., Valavanis, C., Yuen, S., Ho, J., Croke, C., O'Donoghue, D., Giaretti, W., Rapallo, A., Russo, A., Bazan, V., Tanaka, M., Omura, K., Azuma, T., Ohkusa, T., Fujimori, T., Ono, Y., Pauly, M., Faber, C., Glaesener, R., de Goeij, A., Arends, J., Andersen, S., Lovig, T., Breivik, J., Gaudernack, G., Clausen, O., De Angelis, P., Meling, G., Rognum, T., Smith, R., Goh, H., Font, A., Rosell, R., Sun, X., Zhang, H., Benhattar, J., Losi, L., Lee, J., Wang, S., Clarke, P., Bell, S., Quirke, P., Bubb, V., Piris, J., Cruickshank, N., Morton, D., Fox, J., Al-Mulla, F., Lees, N., Hall, C., Snary, D., Wilkinson, K., Dillon, D., Costa, J., Pricolo, V., Finkelstein, S., Thebo, J., Senagore, A., Halter, S., Wadler, S., Malik, S., Krtolica-Žikić, K.,& Urosevic, N.. (2001). Kirsten ras mutations in patients with colorectal cancer: the RASCAL II study. in British Journal of Cancer, 85(5), 692-696.
https://doi.org/10.1054/bjoc.2001.1964

Andreyev H, Norman A, Cunningham D, Oates J, Dix B, Iacopetta B, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes H, Zietz C, Troungos C, Valavanis C, Yuen S, Ho J, Croke C, O'Donoghue D, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij A, Arends J, Andersen S, Lovig T, Breivik J, Gaudernack G, Clausen O, De Angelis P, Meling G, Rognum T, Smith R, Goh H, Font A, Rosell R, Sun X, Zhang H, Benhattar J, Losi L, Lee J, Wang S, Clarke P, Bell S, Quirke P, Bubb V, Piris J, Cruickshank N, Morton D, Fox J, Al-Mulla F, Lees N, Hall C, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo V, Finkelstein S, Thebo J, Senagore A, Halter S, Wadler S, Malik S, Krtolica-Žikić K, Urosevic N. Kirsten ras mutations in patients with colorectal cancer: the RASCAL II study. in British Journal of Cancer. 2001;85(5):692-696.
doi:10.1054/bjoc.2001.1964 .

Andreyev, HJN, Norman, AR, Cunningham, D, Oates, J, Dix, BR, Iacopetta, BJ, Young, J, Walsh, T, Ward, R, Hawkins, N, Beranek, M, Jandik, P, Benamouzig, R, Jullian, E, Laurent-Puig, P, Olschwang, S, Muller, O, Hoffmann, I, Rabes, HM, Zietz, C, Troungos, C, Valavanis, C, Yuen, ST, Ho, JWC, Croke, CT, O'Donoghue, DP, Giaretti, W, Rapallo, A, Russo, A, Bazan, V, Tanaka, M, Omura, K, Azuma, T, Ohkusa, T, Fujimori, T, Ono, Y, Pauly, M, Faber, C, Glaesener, R, de Goeij, AFPM, Arends, JW, Andersen, SN, Lovig, T, Breivik, J, Gaudernack, G, Clausen, OPF, De Angelis, P, Meling, GI, Rognum, TO, Smith, R, Goh, HS, Font, A, Rosell, R, Sun, XF, Zhang, H, Benhattar, J, Losi, L, Lee, JQ, Wang, ST, Clarke, PA, Bell, S, Quirke, P, Bubb, VJ, Piris, J, Cruickshank, NR, Morton, D, Fox, JC, Al-Mulla, F, Lees, N, Hall, CN, Snary, D, Wilkinson, K, Dillon, D, Costa, J, Pricolo, VE, Finkelstein, SD, Thebo, JS, Senagore, AJ, Halter, SA, Wadler, S, Malik, S, Krtolica-Žikić, Koviljka, Urosevic, N, "Kirsten ras mutations in patients with colorectal cancer: the RASCAL II study" in British Journal of Cancer, 85, no. 5 (2001):692-696,
https://doi.org/10.1054/bjoc.2001.1964 . .