TY  - CONF
AU  - Manić, Luka
AU  - Đorđević, Vladimir
AU  - Grubor, Nikica
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
AU  - Uysal-Onganer, Pinar
AU  - Mortoglou, Maria
AU  - Wallace, David
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5512
AB  - Istraživanje u oblasti karcinoma pankreasa i zagađivača iz životne sredine sve je intenzivnije. Za neke od ovih zagađivača pretpostavlja se da su povezani sa nastankom ili progresijom karcinoma pankreasa. Nijedna meta-analiza o povezanosti navedenog nije sprovedena, dok bi rezultati iste mogli pomoći u tumačenju dostupnih podataka i usmeravanju budućeg istraživanja. ...
AB  - There is a rise in research on the connection between pancreatic cancer and environmental pollutants. Some of these pollutants are assumed to be associated with the onset or progression of pancreatic cancer. No meta-analyses summarizing the association between these two have been conducted yet, while the results of such an analysis could help interpret current and guide future research.  ...
PB  - Udruženje toksikologa Srbije
C3  - 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
T1  - Odlomak iz meta-analize: Da li je izloženost zagađivačima iz životne sredine povezana sa karcinomom pankreasa?
T1  - A meta-analysis excerpt: Is exposure to environmental pollutants associated with pancreatic cancer?
SP  - 143
EP  - 146
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5512
ER  - 

@conference{
author = "Manić, Luka and Đorđević, Vladimir and Grubor, Nikica and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela and Uysal-Onganer, Pinar and Mortoglou, Maria and Wallace, David and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Istraživanje u oblasti karcinoma pankreasa i zagađivača iz životne sredine sve je intenzivnije. Za neke od ovih zagađivača pretpostavlja se da su povezani sa nastankom ili progresijom karcinoma pankreasa. Nijedna meta-analiza o povezanosti navedenog nije sprovedena, dok bi rezultati iste mogli pomoći u tumačenju dostupnih podataka i usmeravanju budućeg istraživanja. ..., There is a rise in research on the connection between pancreatic cancer and environmental pollutants. Some of these pollutants are assumed to be associated with the onset or progression of pancreatic cancer. No meta-analyses summarizing the association between these two have been conducted yet, while the results of such an analysis could help interpret current and guide future research.  ...",
publisher = "Udruženje toksikologa Srbije",
journal = "13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book",
title = "Odlomak iz meta-analize: Da li je izloženost zagađivačima iz životne sredine povezana sa karcinomom pankreasa?, A meta-analysis excerpt: Is exposure to environmental pollutants associated with pancreatic cancer?",
pages = "143-146",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5512"
}

Manić, L., Đorđević, V., Grubor, N., Bulat, Z., Antonijević, B., Đukić-Ćosić, D., Uysal-Onganer, P., Mortoglou, M., Wallace, D.,& Buha-Đorđević, A.. (2023). Odlomak iz meta-analize: Da li je izloženost zagađivačima iz životne sredine povezana sa karcinomom pankreasa?. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
Udruženje toksikologa Srbije., 143-146.
https://hdl.handle.net/21.15107/rcub_farfar_5512

Manić L, Đorđević V, Grubor N, Bulat Z, Antonijević B, Đukić-Ćosić D, Uysal-Onganer P, Mortoglou M, Wallace D, Buha-Đorđević A. Odlomak iz meta-analize: Da li je izloženost zagađivačima iz životne sredine povezana sa karcinomom pankreasa?. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book. 2023;:143-146.
https://hdl.handle.net/21.15107/rcub_farfar_5512 .

Manić, Luka, Đorđević, Vladimir, Grubor, Nikica, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, Uysal-Onganer, Pinar, Mortoglou, Maria, Wallace, David, Buha-Đorđević, Aleksandra, "Odlomak iz meta-analize: Da li je izloženost zagađivačima iz životne sredine povezana sa karcinomom pankreasa?" in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book (2023):143-146,
https://hdl.handle.net/21.15107/rcub_farfar_5512 .

TY  - CONF
AU  - Uysal-Onganer, Pinar
AU  - Mortoglou, Maria
AU  - Wallace, David
AU  - Buha-Đorđević, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5500
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, with a 5-year overall survival of less than 8%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. ...
PB  - Udruženje toksikologa Srbije
C3  - 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
T1  - Role of cadmium and nickel on selected microrna expression in pancreatic ductal adenocarcinoma
SP  - 10
EP  - 10
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5500
ER  - 

@conference{
author = "Uysal-Onganer, Pinar and Mortoglou, Maria and Wallace, David and Buha-Đorđević, Aleksandra",
year = "2023",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, with a 5-year overall survival of less than 8%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. ...",
publisher = "Udruženje toksikologa Srbije",
journal = "13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book",
title = "Role of cadmium and nickel on selected microrna expression in pancreatic ductal adenocarcinoma",
pages = "10-10",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5500"
}

Uysal-Onganer, P., Mortoglou, M., Wallace, D.,& Buha-Đorđević, A.. (2023). Role of cadmium and nickel on selected microrna expression in pancreatic ductal adenocarcinoma. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
Udruženje toksikologa Srbije., 10-10.
https://hdl.handle.net/21.15107/rcub_farfar_5500

Uysal-Onganer P, Mortoglou M, Wallace D, Buha-Đorđević A. Role of cadmium and nickel on selected microrna expression in pancreatic ductal adenocarcinoma. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book. 2023;:10-10.
https://hdl.handle.net/21.15107/rcub_farfar_5500 .

Uysal-Onganer, Pinar, Mortoglou, Maria, Wallace, David, Buha-Đorđević, Aleksandra, "Role of cadmium and nickel on selected microrna expression in pancreatic ductal adenocarcinoma" in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book (2023):10-10,
https://hdl.handle.net/21.15107/rcub_farfar_5500 .

TY  - JOUR
AU  - Mortoglou, Maria
AU  - Manić, Luka
AU  - Buha-Đorđević, Aleksandra
AU  - Bulat, Zorica
AU  - Đorđević, Vladimir
AU  - Manis, Katherine
AU  - York, Lauren
AU  - Valle, Elizabeth
AU  - Wallace, David
AU  - Uysal-Onganer, Pinar
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4352
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis.
PB  - MDPI
T2  - Toxics
T1  - Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs
VL  - 10
IS  - 3
DO  - 10.3390/toxics10030148
ER  - 

@article{
author = "Mortoglou, Maria and Manić, Luka and Buha-Đorđević, Aleksandra and Bulat, Zorica and Đorđević, Vladimir and Manis, Katherine and York, Lauren and Valle, Elizabeth and Wallace, David and Uysal-Onganer, Pinar",
year = "2022",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis.",
publisher = "MDPI",
journal = "Toxics",
title = "Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs",
volume = "10",
number = "3",
doi = "10.3390/toxics10030148"
}

Mortoglou, M., Manić, L., Buha-Đorđević, A., Bulat, Z., Đorđević, V., Manis, K., York, L., Valle, E., Wallace, D.,& Uysal-Onganer, P.. (2022). Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs. in Toxics
MDPI., 10(3).
https://doi.org/10.3390/toxics10030148

Mortoglou M, Manić L, Buha-Đorđević A, Bulat Z, Đorđević V, Manis K, York L, Valle E, Wallace D, Uysal-Onganer P. Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs. in Toxics. 2022;10(3).
doi:10.3390/toxics10030148 .

Mortoglou, Maria, Manić, Luka, Buha-Đorđević, Aleksandra, Bulat, Zorica, Đorđević, Vladimir, Manis, Katherine, York, Lauren, Valle, Elizabeth, Wallace, David, Uysal-Onganer, Pinar, "Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs" in Toxics, 10, no. 3 (2022),
https://doi.org/10.3390/toxics10030148 . .

TY  - JOUR
AU  - Manić, Luka
AU  - Wallace, David
AU  - Onganer, Pinar Uysal
AU  - Taalab, Yasmeen
AU  - Farooqi, Ammad
AU  - Antonijević, Biljana
AU  - Buha-Đorđević, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4101
AB  - Many metals exhibit genotoxic and/or carcinogenic effects. These toxic metals can be found ubiquitously – in drinking water, food, air, general use products, in everyday and occupational settings. Exposure to such carcinogenic metals can result in serious health disorders, including cancer. Arsenic, cadmium, chromium, nickel, and their compounds have already been recognized as carcinogens by the International Agency for Research on Cancer. This review summarizes a wide range of epigenetic mechanisms contributing to carcinogenesis induced by these metals, primarily including, but not limited to, DNA methylation, miRNA regulation, and histone posttranslational modifications. The mechanisms are described and discussed both from a metal-centric and a mechanism-centric standpoint. The review takes a broad perspective, putting the mechanisms in the context of real-life exposure, and aims to assist in guiding future research, particularly with respect to the assessment and control of exposure to carcinogenic metals and novel therapy development.
PB  - Elsevier Inc.
T2  - Toxicology Reports
T1  - Epigenetic mechanisms in metal carcinogenesis
VL  - 9
SP  - 778
EP  - 787
DO  - 10.1016/j.toxrep.2022.03.037
ER  - 

@article{
author = "Manić, Luka and Wallace, David and Onganer, Pinar Uysal and Taalab, Yasmeen and Farooqi, Ammad and Antonijević, Biljana and Buha-Đorđević, Aleksandra",
year = "2022",
abstract = "Many metals exhibit genotoxic and/or carcinogenic effects. These toxic metals can be found ubiquitously – in drinking water, food, air, general use products, in everyday and occupational settings. Exposure to such carcinogenic metals can result in serious health disorders, including cancer. Arsenic, cadmium, chromium, nickel, and their compounds have already been recognized as carcinogens by the International Agency for Research on Cancer. This review summarizes a wide range of epigenetic mechanisms contributing to carcinogenesis induced by these metals, primarily including, but not limited to, DNA methylation, miRNA regulation, and histone posttranslational modifications. The mechanisms are described and discussed both from a metal-centric and a mechanism-centric standpoint. The review takes a broad perspective, putting the mechanisms in the context of real-life exposure, and aims to assist in guiding future research, particularly with respect to the assessment and control of exposure to carcinogenic metals and novel therapy development.",
publisher = "Elsevier Inc.",
journal = "Toxicology Reports",
title = "Epigenetic mechanisms in metal carcinogenesis",
volume = "9",
pages = "778-787",
doi = "10.1016/j.toxrep.2022.03.037"
}

Manić, L., Wallace, D., Onganer, P. U., Taalab, Y., Farooqi, A., Antonijević, B.,& Buha-Đorđević, A.. (2022). Epigenetic mechanisms in metal carcinogenesis. in Toxicology Reports
Elsevier Inc.., 9, 778-787.
https://doi.org/10.1016/j.toxrep.2022.03.037

Manić L, Wallace D, Onganer PU, Taalab Y, Farooqi A, Antonijević B, Buha-Đorđević A. Epigenetic mechanisms in metal carcinogenesis. in Toxicology Reports. 2022;9:778-787.
doi:10.1016/j.toxrep.2022.03.037 .

Manić, Luka, Wallace, David, Onganer, Pinar Uysal, Taalab, Yasmeen, Farooqi, Ammad, Antonijević, Biljana, Buha-Đorđević, Aleksandra, "Epigenetic mechanisms in metal carcinogenesis" in Toxicology Reports, 9 (2022):778-787,
https://doi.org/10.1016/j.toxrep.2022.03.037 . .

TY  - JOUR
AU  - Buha, Aleksandra
AU  - Đukić-Ćosić, Danijela
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Moulis, Jean-Marc
AU  - Goumenou, Marina
AU  - Wallace, David
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3659
AB  - Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of "hyperglycemic" metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.
PB  - MDPI AG
T2  - Toxics
T1  - Emerging links between cadmium exposure and insulin resistance: Human, animal, and cell study data
VL  - 8
IS  - 3
DO  - 10.3390/TOXICS8030063
ER  - 

@article{
author = "Buha, Aleksandra and Đukić-Ćosić, Danijela and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Moulis, Jean-Marc and Goumenou, Marina and Wallace, David",
year = "2020",
abstract = "Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of "hyperglycemic" metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.",
publisher = "MDPI AG",
journal = "Toxics",
title = "Emerging links between cadmium exposure and insulin resistance: Human, animal, and cell study data",
volume = "8",
number = "3",
doi = "10.3390/TOXICS8030063"
}

Buha, A., Đukić-Ćosić, D., Ćurčić, M., Bulat, Z., Antonijević, B., Moulis, J., Goumenou, M.,& Wallace, D.. (2020). Emerging links between cadmium exposure and insulin resistance: Human, animal, and cell study data. in Toxics
MDPI AG., 8(3).
https://doi.org/10.3390/TOXICS8030063

Buha A, Đukić-Ćosić D, Ćurčić M, Bulat Z, Antonijević B, Moulis J, Goumenou M, Wallace D. Emerging links between cadmium exposure and insulin resistance: Human, animal, and cell study data. in Toxics. 2020;8(3).
doi:10.3390/TOXICS8030063 .

Buha, Aleksandra, Đukić-Ćosić, Danijela, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Moulis, Jean-Marc, Goumenou, Marina, Wallace, David, "Emerging links between cadmium exposure and insulin resistance: Human, animal, and cell study data" in Toxics, 8, no. 3 (2020),
https://doi.org/10.3390/TOXICS8030063 . .

TY  - JOUR
AU  - Panieri, Emiliano
AU  - Buha, Aleksandra
AU  - Telkoparan-Akillilar, Pelin
AU  - Cevik, Dilek
AU  - Kouretas, Demetrios
AU  - Veskoukis, Aristidis
AU  - Skaperda, Zoi
AU  - Tsatsakis, Aristidis
AU  - Wallace, David
AU  - Suzen, Sibel
AU  - Saso, Luciano
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3551
AB  - The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.
PB  - MDPI
T2  - Antioxidants
T1  - Potential applications of NRF2 modulators in cancer therapy
VL  - 9
IS  - 3
DO  - 10.3390/antiox9030193
ER  - 

@article{
author = "Panieri, Emiliano and Buha, Aleksandra and Telkoparan-Akillilar, Pelin and Cevik, Dilek and Kouretas, Demetrios and Veskoukis, Aristidis and Skaperda, Zoi and Tsatsakis, Aristidis and Wallace, David and Suzen, Sibel and Saso, Luciano",
year = "2020",
abstract = "The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Potential applications of NRF2 modulators in cancer therapy",
volume = "9",
number = "3",
doi = "10.3390/antiox9030193"
}

Panieri, E., Buha, A., Telkoparan-Akillilar, P., Cevik, D., Kouretas, D., Veskoukis, A., Skaperda, Z., Tsatsakis, A., Wallace, D., Suzen, S.,& Saso, L.. (2020). Potential applications of NRF2 modulators in cancer therapy. in Antioxidants
MDPI., 9(3).
https://doi.org/10.3390/antiox9030193

Panieri E, Buha A, Telkoparan-Akillilar P, Cevik D, Kouretas D, Veskoukis A, Skaperda Z, Tsatsakis A, Wallace D, Suzen S, Saso L. Potential applications of NRF2 modulators in cancer therapy. in Antioxidants. 2020;9(3).
doi:10.3390/antiox9030193 .

Panieri, Emiliano, Buha, Aleksandra, Telkoparan-Akillilar, Pelin, Cevik, Dilek, Kouretas, Demetrios, Veskoukis, Aristidis, Skaperda, Zoi, Tsatsakis, Aristidis, Wallace, David, Suzen, Sibel, Saso, Luciano, "Potential applications of NRF2 modulators in cancer therapy" in Antioxidants, 9, no. 3 (2020),
https://doi.org/10.3390/antiox9030193 . .

TY  - JOUR
AU  - Anđelković, Milena
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević, Evica
AU  - Antonijević, Biljana
AU  - Stanić, Momcilo
AU  - Kotur-Stevuljević, Jelena
AU  - Spasojević-Kalimanovska, Vesna
AU  - Jovanović, Miloš
AU  - Boricić, Novica
AU  - Wallace, David
AU  - Bulat, Zorica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3301
AB  - Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.
PB  - MDPI, Basel
T2  - International Journal of Environmental Research and Public Health
T1  - Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney
VL  - 16
IS  - 2
DO  - 10.3390/ijerph16020274
ER  - 

@article{
author = "Anđelković, Milena and Buha-Đorđević, Aleksandra and Antonijević, Evica and Antonijević, Biljana and Stanić, Momcilo and Kotur-Stevuljević, Jelena and Spasojević-Kalimanovska, Vesna and Jovanović, Miloš and Boricić, Novica and Wallace, David and Bulat, Zorica",
year = "2019",
abstract = "Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.",
publisher = "MDPI, Basel",
journal = "International Journal of Environmental Research and Public Health",
title = "Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney",
volume = "16",
number = "2",
doi = "10.3390/ijerph16020274"
}

Anđelković, M., Buha-Đorđević, A., Antonijević, E., Antonijević, B., Stanić, M., Kotur-Stevuljević, J., Spasojević-Kalimanovska, V., Jovanović, M., Boricić, N., Wallace, D.,& Bulat, Z.. (2019). Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney. in International Journal of Environmental Research and Public Health
MDPI, Basel., 16(2).
https://doi.org/10.3390/ijerph16020274

Anđelković M, Buha-Đorđević A, Antonijević E, Antonijević B, Stanić M, Kotur-Stevuljević J, Spasojević-Kalimanovska V, Jovanović M, Boricić N, Wallace D, Bulat Z. Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney. in International Journal of Environmental Research and Public Health. 2019;16(2).
doi:10.3390/ijerph16020274 .

Anđelković, Milena, Buha-Đorđević, Aleksandra, Antonijević, Evica, Antonijević, Biljana, Stanić, Momcilo, Kotur-Stevuljević, Jelena, Spasojević-Kalimanovska, Vesna, Jovanović, Miloš, Boricić, Novica, Wallace, David, Bulat, Zorica, "Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney" in International Journal of Environmental Research and Public Health, 16, no. 2 (2019),
https://doi.org/10.3390/ijerph16020274 . .

TY  - JOUR
AU  - Wallace, David
AU  - Spandidos, Demetrios A.
AU  - Tsatsakis, Aristidis
AU  - Schweitzer, Amie
AU  - Đorđević, Vladimir
AU  - Buha-Đorđević, Aleksandra
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3265
AB  - Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl2)-mediated toxicity in hTERT-HPNE and AsPC-1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl2 (0-100 M) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl2. Initial experiments confirmed that exposure to CdCl2 did not reduce the viability of either cell line until a concentration of >10 M was used. Non-linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 M compared to 42 M in the AsPC-1 cells (P lt 0.01). The CdCl2-mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl2, not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC-1 cells exhibited a 58.8% reduction in IC50 values. In addition, the higher concentration of CdCl2 elicited a significant cell-dependent effect on ATP release in both cell lines, suggestive of CdCl2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl2; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development.
PB  - Spandidos Publ Ltd, Athens
T2  - International Journal of Molecular Medicine
T1  - Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer
VL  - 44
IS  - 1
SP  - 145
EP  - 156
DO  - 10.3892/ijmm.2019.4204
ER  - 

@article{
author = "Wallace, David and Spandidos, Demetrios A. and Tsatsakis, Aristidis and Schweitzer, Amie and Đorđević, Vladimir and Buha-Đorđević, Aleksandra",
year = "2019",
abstract = "Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl2)-mediated toxicity in hTERT-HPNE and AsPC-1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl2 (0-100 M) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl2. Initial experiments confirmed that exposure to CdCl2 did not reduce the viability of either cell line until a concentration of >10 M was used. Non-linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 M compared to 42 M in the AsPC-1 cells (P lt 0.01). The CdCl2-mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl2, not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC-1 cells exhibited a 58.8% reduction in IC50 values. In addition, the higher concentration of CdCl2 elicited a significant cell-dependent effect on ATP release in both cell lines, suggestive of CdCl2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl2; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development.",
publisher = "Spandidos Publ Ltd, Athens",
journal = "International Journal of Molecular Medicine",
title = "Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer",
volume = "44",
number = "1",
pages = "145-156",
doi = "10.3892/ijmm.2019.4204"
}

Wallace, D., Spandidos, D. A., Tsatsakis, A., Schweitzer, A., Đorđević, V.,& Buha-Đorđević, A.. (2019). Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. in International Journal of Molecular Medicine
Spandidos Publ Ltd, Athens., 44(1), 145-156.
https://doi.org/10.3892/ijmm.2019.4204

Wallace D, Spandidos DA, Tsatsakis A, Schweitzer A, Đorđević V, Buha-Đorđević A. Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. in International Journal of Molecular Medicine. 2019;44(1):145-156.
doi:10.3892/ijmm.2019.4204 .

Wallace, David, Spandidos, Demetrios A., Tsatsakis, Aristidis, Schweitzer, Amie, Đorđević, Vladimir, Buha-Đorđević, Aleksandra, "Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer" in International Journal of Molecular Medicine, 44, no. 1 (2019):145-156,
https://doi.org/10.3892/ijmm.2019.4204 . .

TY  - JOUR
AU  - Hernandez, Antonio F.
AU  - Buha, Aleksandra
AU  - Constantin, Carolina
AU  - Wallace, David R.
AU  - Sarigiannis, Dimosthenis
AU  - Neagu, Monica
AU  - Antonijević, Biljana
AU  - Hayes, Wallace A.
AU  - Wilks, Martin F.
AU  - Tsatsakis, Aristidis
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3464
AB  - Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.
PB  - Springer Verlag
T2  - Archives of Toxicology
T1  - Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures
VL  - 93
IS  - 10
SP  - 2741
EP  - 2757
DO  - 10.1007/s00204-019-02547-x
ER  - 

@article{
author = "Hernandez, Antonio F. and Buha, Aleksandra and Constantin, Carolina and Wallace, David R. and Sarigiannis, Dimosthenis and Neagu, Monica and Antonijević, Biljana and Hayes, Wallace A. and Wilks, Martin F. and Tsatsakis, Aristidis",
year = "2019",
abstract = "Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.",
publisher = "Springer Verlag",
journal = "Archives of Toxicology",
title = "Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures",
volume = "93",
number = "10",
pages = "2741-2757",
doi = "10.1007/s00204-019-02547-x"
}

Hernandez, A. F., Buha, A., Constantin, C., Wallace, D. R., Sarigiannis, D., Neagu, M., Antonijević, B., Hayes, W. A., Wilks, M. F.,& Tsatsakis, A.. (2019). Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures. in Archives of Toxicology
Springer Verlag., 93(10), 2741-2757.
https://doi.org/10.1007/s00204-019-02547-x

Hernandez AF, Buha A, Constantin C, Wallace DR, Sarigiannis D, Neagu M, Antonijević B, Hayes WA, Wilks MF, Tsatsakis A. Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures. in Archives of Toxicology. 2019;93(10):2741-2757.
doi:10.1007/s00204-019-02547-x .

Hernandez, Antonio F., Buha, Aleksandra, Constantin, Carolina, Wallace, David R., Sarigiannis, Dimosthenis, Neagu, Monica, Antonijević, Biljana, Hayes, Wallace A., Wilks, Martin F., Tsatsakis, Aristidis, "Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures" in Archives of Toxicology, 93, no. 10 (2019):2741-2757,
https://doi.org/10.1007/s00204-019-02547-x . .

TY  - JOUR
AU  - Đorđević, Vladimir
AU  - Wallace, David
AU  - Schweitzer, Amie
AU  - Boricić, Novica
AU  - Knežević, Đorđe
AU  - Matić, Slavko
AU  - Grubor, Nikola
AU  - Kerkez, Mirko
AU  - Radenković, Dejan
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Matović, Vesna
AU  - Buha, Aleksandra
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3346
AB  - Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scarce. Some of established risk factors of PC are connected to an increased cadmium (Cd) body burden. Hence, the aim of this study was to investigate the role of this environmental pollutant in PC development by conducting human observational, experimental and in vitro studies. The case-control study included 31 patients with a histologically based diagnosis of exocrine PC subjected to radical surgical intervention as cases and 29 accidental fatalities or subjects who died of a nonmalignant illness as controls. Animal study included two treated groups of Wistar rats (15 and 30 mg Cd/kg b.w) and untreated control group, sacrificed 24 h after single oral exposure. In in vitro study pancreas hTERT-HPNE and AsPC-1 cells were exposed to different Cd concentrations corresponding to levels measured in human cancerous pancreatic tissue. Cd content in cancer tissue significantly differed from the content in healthy controls. Odds ratio levels for PC development were 2.79 (95% CI 0.91-8.50) and 3.44 (95% CI 1.19-9.95) in the third and fourth quartiles of Cd distribution, respectively. Animal study confirmed Cd deposition in pancreatic tissue. In vitro studies revealed that Cd produces disturbances in intrinsic pathway of apoptotic activity and the elevation in oxidative stress in pancreatic cells. This study presents three different lines of evidence pointing towards Cd as an agent responsible for the development of PC.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Environment International
T1  - Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies
VL  - 128
SP  - 353
EP  - 361
DO  - 10.1016/j.envint.2019.04.048
ER  - 

@article{
author = "Đorđević, Vladimir and Wallace, David and Schweitzer, Amie and Boricić, Novica and Knežević, Đorđe and Matić, Slavko and Grubor, Nikola and Kerkez, Mirko and Radenković, Dejan and Bulat, Zorica and Antonijević, Biljana and Matović, Vesna and Buha, Aleksandra",
year = "2019",
abstract = "Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scarce. Some of established risk factors of PC are connected to an increased cadmium (Cd) body burden. Hence, the aim of this study was to investigate the role of this environmental pollutant in PC development by conducting human observational, experimental and in vitro studies. The case-control study included 31 patients with a histologically based diagnosis of exocrine PC subjected to radical surgical intervention as cases and 29 accidental fatalities or subjects who died of a nonmalignant illness as controls. Animal study included two treated groups of Wistar rats (15 and 30 mg Cd/kg b.w) and untreated control group, sacrificed 24 h after single oral exposure. In in vitro study pancreas hTERT-HPNE and AsPC-1 cells were exposed to different Cd concentrations corresponding to levels measured in human cancerous pancreatic tissue. Cd content in cancer tissue significantly differed from the content in healthy controls. Odds ratio levels for PC development were 2.79 (95% CI 0.91-8.50) and 3.44 (95% CI 1.19-9.95) in the third and fourth quartiles of Cd distribution, respectively. Animal study confirmed Cd deposition in pancreatic tissue. In vitro studies revealed that Cd produces disturbances in intrinsic pathway of apoptotic activity and the elevation in oxidative stress in pancreatic cells. This study presents three different lines of evidence pointing towards Cd as an agent responsible for the development of PC.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Environment International",
title = "Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies",
volume = "128",
pages = "353-361",
doi = "10.1016/j.envint.2019.04.048"
}

Đorđević, V., Wallace, D., Schweitzer, A., Boricić, N., Knežević, Đ., Matić, S., Grubor, N., Kerkez, M., Radenković, D., Bulat, Z., Antonijević, B., Matović, V.,& Buha, A.. (2019). Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies. in Environment International
Pergamon-Elsevier Science Ltd, Oxford., 128, 353-361.
https://doi.org/10.1016/j.envint.2019.04.048

Đorđević V, Wallace D, Schweitzer A, Boricić N, Knežević Đ, Matić S, Grubor N, Kerkez M, Radenković D, Bulat Z, Antonijević B, Matović V, Buha A. Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies. in Environment International. 2019;128:353-361.
doi:10.1016/j.envint.2019.04.048 .

Đorđević, Vladimir, Wallace, David, Schweitzer, Amie, Boricić, Novica, Knežević, Đorđe, Matić, Slavko, Grubor, Nikola, Kerkez, Mirko, Radenković, Dejan, Bulat, Zorica, Antonijević, Biljana, Matović, Vesna, Buha, Aleksandra, "Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies" in Environment International, 128 (2019):353-361,
https://doi.org/10.1016/j.envint.2019.04.048 . .

TY  - JOUR
AU  - Buha, Aleksandra
AU  - Matović, Vesna
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
AU  - Ćurčić, Marijana
AU  - Renieri, Elisavet A.
AU  - Tsatsakis, Aristidis
AU  - Schweitzer, Amie
AU  - Wallace, David
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3035
AB  - Humans are exposed to a significant number of chemicals that are suspected to produce disturbances in hormone homeostasis. Hence, in recent decades, there has been a growing interest in endocrine disruptive chemicals. One of the alleged thyroid disrupting substances is cadmium (Cd), a ubiquitous toxic metal shown to act as a thyroid disruptor and carcinogen in both animals and humans. Multiple PubMed searches with core keywords were performed to identify and evaluate appropriate studies which revealed literature suggesting evidence for the link between exposure to Cd and histological and metabolic changes in the thyroid gland. Furthermore, Cd influence on thyroid homeostasis at the peripheral level has also been hypothesized. Both in vivo and in vitro studies revealed that a Cd exposure at environmentally relevant concentrations results in biphasic Cd dose-thyroid response relationships. Development of thyroid tumors following exposure to Cd has been studied mainly using in vitro methodologies. In the thyroid, Cd has been shown to activate or stimulate the activity of various factors, leading to increased cell proliferation and a reduction in normal apoptotic activity. Evidence establishing the association between Cd and thyroid disruption remains ambiguous, with further studies needed to elucidate the issue and improve our understanding of Cd-mediated effects on the thyroid gland.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Overview of Cadmium Thyroid Disrupting Effects and Mechanisms
VL  - 19
IS  - 5
DO  - 10.3390/ijms19051501
ER  - 

@article{
author = "Buha, Aleksandra and Matović, Vesna and Antonijević, Biljana and Bulat, Zorica and Ćurčić, Marijana and Renieri, Elisavet A. and Tsatsakis, Aristidis and Schweitzer, Amie and Wallace, David",
year = "2018",
abstract = "Humans are exposed to a significant number of chemicals that are suspected to produce disturbances in hormone homeostasis. Hence, in recent decades, there has been a growing interest in endocrine disruptive chemicals. One of the alleged thyroid disrupting substances is cadmium (Cd), a ubiquitous toxic metal shown to act as a thyroid disruptor and carcinogen in both animals and humans. Multiple PubMed searches with core keywords were performed to identify and evaluate appropriate studies which revealed literature suggesting evidence for the link between exposure to Cd and histological and metabolic changes in the thyroid gland. Furthermore, Cd influence on thyroid homeostasis at the peripheral level has also been hypothesized. Both in vivo and in vitro studies revealed that a Cd exposure at environmentally relevant concentrations results in biphasic Cd dose-thyroid response relationships. Development of thyroid tumors following exposure to Cd has been studied mainly using in vitro methodologies. In the thyroid, Cd has been shown to activate or stimulate the activity of various factors, leading to increased cell proliferation and a reduction in normal apoptotic activity. Evidence establishing the association between Cd and thyroid disruption remains ambiguous, with further studies needed to elucidate the issue and improve our understanding of Cd-mediated effects on the thyroid gland.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Overview of Cadmium Thyroid Disrupting Effects and Mechanisms",
volume = "19",
number = "5",
doi = "10.3390/ijms19051501"
}

Buha, A., Matović, V., Antonijević, B., Bulat, Z., Ćurčić, M., Renieri, E. A., Tsatsakis, A., Schweitzer, A.,& Wallace, D.. (2018). Overview of Cadmium Thyroid Disrupting Effects and Mechanisms. in International Journal of Molecular Sciences
MDPI, Basel., 19(5).
https://doi.org/10.3390/ijms19051501

Buha A, Matović V, Antonijević B, Bulat Z, Ćurčić M, Renieri EA, Tsatsakis A, Schweitzer A, Wallace D. Overview of Cadmium Thyroid Disrupting Effects and Mechanisms. in International Journal of Molecular Sciences. 2018;19(5).
doi:10.3390/ijms19051501 .

Buha, Aleksandra, Matović, Vesna, Antonijević, Biljana, Bulat, Zorica, Ćurčić, Marijana, Renieri, Elisavet A., Tsatsakis, Aristidis, Schweitzer, Amie, Wallace, David, "Overview of Cadmium Thyroid Disrupting Effects and Mechanisms" in International Journal of Molecular Sciences, 19, no. 5 (2018),
https://doi.org/10.3390/ijms19051501 . .

TY  - JOUR
AU  - Buha, Aleksandra
AU  - Wallace, David
AU  - Matović, Vesna
AU  - Schweitzer, Amie
AU  - Oluić, Branislav
AU  - Micić, Dušan
AU  - Đorđević, Vladimir
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2836
AB  - Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.
PB  - Hindawi Ltd, London
T2  - Biomed Research International
T1  - Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence
DO  - 10.1155/2017/1981837
ER  - 

@article{
author = "Buha, Aleksandra and Wallace, David and Matović, Vesna and Schweitzer, Amie and Oluić, Branislav and Micić, Dušan and Đorđević, Vladimir",
year = "2017",
abstract = "Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.",
publisher = "Hindawi Ltd, London",
journal = "Biomed Research International",
title = "Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence",
doi = "10.1155/2017/1981837"
}

Buha, A., Wallace, D., Matović, V., Schweitzer, A., Oluić, B., Micić, D.,& Đorđević, V.. (2017). Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence. in Biomed Research International
Hindawi Ltd, London..
https://doi.org/10.1155/2017/1981837

Buha A, Wallace D, Matović V, Schweitzer A, Oluić B, Micić D, Đorđević V. Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence. in Biomed Research International. 2017;.
doi:10.1155/2017/1981837 .

Buha, Aleksandra, Wallace, David, Matović, Vesna, Schweitzer, Amie, Oluić, Branislav, Micić, Dušan, Đorđević, Vladimir, "Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence" in Biomed Research International (2017),
https://doi.org/10.1155/2017/1981837 . .