Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study

Mortada, Wael I.; Awadalla, Amira; Khater, Sherry M.; Ahmed, Asmaa; Hamam, Eman T.; El-Zayat, Mustafa; Shokeir, Ahmed A.

doi:10.1007/s11356-020-08113-8

Cited by 29 publications

(28 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results derived from this study are promising in terms of deepening of our knowledge of oncogenesis and providing assistance in the future treatment of colon cancer. Several studies have identified that low levels of serum Zn are a risk factor for many kinds of cancer (11,(13)(14)(15)20), including colon cancer (16). Our study further identified that the low level of serum Zn is risk factor of the prognosis of colon cancer.…”

Section: Discussionsupporting

confidence: 74%

Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I–III colon cancer

Wu¹,

Wu²,

Liu³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: It has been reported that serum Zinc (Zn) and tissue ZRT, IRT-like protein 4 (ZIP4) are involved in the oncogenesis of several cancers. However, the relationship between them and the prognosis of colon cancer is unclear.Methods: This was a prospective study including 116 patients with stages I-III colon cancer. The level of serum Zn was measured using a flame atomic absorption spectrometer. The expressions of ZIP4 in cancer tissues were measured using western blot and normal colon tissues from healthy volunteers were used as a control. The primary outcome was 2-year survival and secondary outcomes included the incidences of locoregional recurrence and distant metastasis.Results: The average level of serum Zn in participants was 856.0±322.5 μg/L. Kaplan-Meier survival curves showed that patients with Zn <856.0 μg/L had a significantly higher incidence of distant metastasis (P=0.02) and a significantly lower survival rate than those with Zn ≥856.0 μg/L (P=0.005). Multivariate logistic regression analysis also confirmed that having level Zn <856.0 μg/L was risk factor for the two outcomes. The expression of ZIP4 in cancer tissues was greatly increased as compared with the healthy control, with an average fold change of 2.4. The level of serum Zn was found to be positively correlated with the expression of ZIP4 in tissue. Multivariate logistic regression analysis indicated that increased expression of tissue ZIP4 was an important risk factor for locoregional recurrence (P=0.032), distant metastasis (P=0.039), and overall survival (P=0.035).Conclusions: Both lower levels of serum Zn and increased expression of ZIP4 in tissue are associated with a poorer prognosis of patients with stages I-III colon cancer.

show abstract

Section: Discussionsupporting

confidence: 74%

Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I–III colon cancer

Wu¹,

Wu²,

Liu³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…Since copper plays an important role in the cellular function and metabolism, the question arises as to whether there are significant differences in Cu levels in cancer patients in comparison with healthy cohorts, and if yes, whether Cu levels can be used as a reliable biomarker of disease progression and response to treatment [ 15 ]. Cu concentrations were determined from emission spectrograms or by flame atomic absorption spectrometry in whole blood, plasma [ 16 ] or serum [ 15 ], toenail [ 17 ], hair [ 18 ], saliva [ 19 ], and tissues [ 20 ]. Many studies reported a positive correlation between circulating Cu levels and cancer progression, in particular breast cancer.…”

Section: Systemic Changes In Cu Homeostasis Of Cancer Patientsmentioning

confidence: 99%

Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance

2021

View full text Add to dashboard Cite

Copper (Cu) is a vital element required for cellular growth and development; however, even slight changes in its homeostasis might lead to severe toxicity and deleterious medical conditions. Cancer patients are typically associated with higher Cu content in serum and tumor tissues, indicating increased demand of cancer cells for this micronutrient. Cu is known to readily cycle between the +1 and +2 oxidation state in biological systems. The mechanism of action of Cu complexes is typically based on their redox activity and induction of reactive oxygen species (ROS), leading to deadly oxidative stress. However, there are a number of other biomolecular mechanisms beyond ROS generation that contribute to the activity of anticancer Cu drug candidates. In this review, we discuss how interfering with intracellular Cu balance via either diet modification or addition of inorganic Cu supplements or Cu-modulating compounds affects tumor development, progression, and sensitivity to treatment modalities. We aim to provide the rationale for the use of Cu-depleting and Cu-overloading conditions to generate the best possible patient outcome with minimal toxicity. We also discuss the advantages of the use of pre-formed Cu complexes, such as Cu-(bis)thiosemicarbazones or Cu-N-heterocyclic thiosemicarbazones, in comparison with the in situ formed Cu complexes with metal-binding ligands. In this review, we summarize available clinical and mechanistic data on clinically relevant anticancer drug candidates, including Cu supplements, Cu chelators, Cu ionophores, and Cu complexes.

show abstract

“…Based on our results using the isolated retina model and previous works [35,36], an integrative model of Cu 2+depended cellular responses is presented. Therefore, the involvement of VGCCs could reflect a potential target for interventions of diseases as reported by several researchers [4,37,38]. Further investigation will be necessary to establish the relevance of trace metal ions on VGCCs.…”

Section: Discussionmentioning

confidence: 89%

Submicromolar copper (II) ions stimulate transretinal signaling in the isolated retina from wild type but not from Cav2.3-deficient mice

et al. 2020

View full text Add to dashboard Cite

Background: So far, only indirect evidence exists for the pharmacoresistant R-type voltage-gated Ca 2+ channel (VGCC) to be involved in transretinal signaling by triggering GABA-release onto ON-bipolar neurons. This release of inhibitory neurotransmitters was deduced from the sensitivity of the b-wave to stimulation by Ni 2+ , Zn 2+ and Cu 2+. To further confirm the interpretation of these findings, we compared the effects of Cu 2+ application and chelation (using kainic acid, KA) on the neural retina from wildtype and Ca v 2.3-deficient mice. Furthermore, the immediately effect of KA on the ERG b-wave modulation was assessed. Methods: Transretinal signaling was recorded as an ERG from the superfused murine retina isolated from wildtype and Ca v 2.3-deficient mice. Results: In mice, the stimulating effect of 100 nM CuCl 2 is absent in the retinae from Ca v 2.3-deficient mice, but prominent in Ca v 2.3-competent mice. Application of up to 3 mM tricine does not affect the murine b-wave in both genotypes, most likely because of chelating amino acids present in the murine nutrient solution. Application of 27 μM KA significantly increased the b-wave amplitude in wild type and Ca v 2.3 (−|-) mice. This effect can most likely be explained by the stimulation of endogenous KA-receptors described in horizontal, OFF-bipolar, amacrine or ganglion cells, which could not be fully blocked in the present study. Conclusion: Cu 2+-dependent modulation of transretinal signaling only occurs in the murine retina from Ca v 2.3 competent mice, supporting the ideas derived from previous work in the bovine retina that R-type Ca 2+ channels are involved in shaping transretinal responses during light perception.

show abstract

Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study

Cited by 29 publications

References 33 publications

Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I–III colon cancer

Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I–III colon cancer

Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance

Submicromolar copper (II) ions stimulate transretinal signaling in the isolated retina from wild type but not from Cav2.3-deficient mice

Contact Info

Product

Resources

About