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  - 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 . .