6 results found
Sullivan KV, Moore RET, Capper MS, et al., 2021, Zinc stable isotope analysis reveals Zn dyshomeostasis in benign tumours, breast cancer, and adjacent histologically normal tissue, Matallomics, Vol: 13, Pages: 1-12, ISSN: 1756-591X
The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (δ66Zn) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 µg g−1 greater than in NAT(MT) (p = 0.00056) and 5.1 µg g−1 greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 µg g−1 greater than in HT (p = 0.00012) and 13.3 µg g−1 greater than in NAT(MT) (p < 0.0001), whereas δ66Zn is 0.17‰ lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The δ66Zn of BT is 0.15‰ lower than in NAT(BT) (p = 0.045). The similar light δ66Zn of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (64Zn-rich) expression by activated matrix metalloproteinase (66Zn-rich) in MT, and indicates a resultant 66Zn-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.
Schilling K, Moore RET, Sullivan KV, et al., 2021, Zinc stable isotopes in urine as diagnostic for cancer of secretory organs, Metallomics: integrated biometal science, Vol: 13, Pages: 1-10, ISSN: 1756-5901
Breast, prostate, and pancreatic cancers alter the zinc (Zn) metabolism. Combined analyses of urinary Zn concentrations [Zn] and Zn stable isotope compositions (δ66Zn) may provide a non-invasive approach for tracing malignancy-induced Zn dyshomeostasis. In this study, we measured [Zn] and δ66Zn in urine from prostate (n = 22), breast (n = 16), and from women with benign breast disease (n = 14) and compared those with age-matched healthy controls (22–49 years or 50+ years) and published data for pancreatic cancer (n = 17). Our results show that cancer-induced changes are reflected in higher urinary [Zn] and lower urinary δ66Zn for pancreatic and prostate cancer and benign breast disease when compared with healthy controls. For prostate cancer, the progression of low [Zn] and high δ66Zn for patients of low-risk disease toward high [Zn] and low δ66Zn for the higher risk patients demonstrates that [Zn] and δ66Zn in urine could serve as a reliable prognostic tool. Urinary excretion of isotopically light Zn by patients with prostatic and pancreatic cancer is probably the result of increased reactive oxygen species in cancerous cells, which limits the scavenging of hydroxyl radicals and thus facilitates the oxidation of metalloproteins with sulfur-rich ligands. Urine from breast cancer patients shows undistinguishable δ66Zn to healthy controls, implying that the expression of metalloproteins with sulfur-rich ligands is stronger in breast cancer tissues. In conclusion, urinary δ66Zn may provide a non-invasive diagnostic tool for pancreatic cancer and support disease prognosis for prostate cancer. These findings should translate to comprehensive transverse and longitudinal cohort studies in future.
Capper MS, Enriquez Garcia A, Lai B, et al., 2021, The effect of sodium thiosulfate on cytotoxicity of a diimine Re(i) tricarbonyl complex, DALTON TRANSACTIONS, Vol: 50, Pages: 5968-5977, ISSN: 1477-9226
Capper MS, Rehkämper M, Packman H, 2020, Rhenium-based complexes and in vivo testing: A brief history, ChemBioChem, Vol: 21, Pages: 2111-2115, ISSN: 1439-4227
The success of metal‐based anticancer therapeutics in the treatment of cancer is best exemplified by cisplatin. Currently used in 32 / 78 cancer regimens, the use for metal‐based therapeutics has a clear role in cancer therapy. Despite this, metal‐based therapeutics are not without drawbacks, with issues such as toxic side effects and the development of resistance mechanisms. This has led to investigations of other metal‐based therapeutics such as auranofin, a gold‐based drug candidate as well as ruthenium‐based candidates, NAMI‐A, NKP‐1339 and TLD‐1433. All are undergoing current clinical trials. Another class of complexes under study are rhenium‐based; such complexes have undergone extensive in vitro testing but only seven have displayed antitumor in vivo activity which is a necessary step before entering clinical trials. This present review will document, chronologically, the rhenium‐based drug candidates that have undergone in vivo testing and the outlook for such complexes.
Capper MS, Enriquez Garcia A, Macia N, et al., 2020, Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives, JBIC Journal of Biological Inorganic Chemistry, Vol: 25, Pages: 759-776, ISSN: 0949-8257
Banerjee S, Capper MS, Clarkson GJ, et al., 2019, Dual-action platinum(II) Schiff base complexes: Photocytotoxicity and cellular imaging, Polyhedron, Vol: 172, Pages: 157-166, ISSN: 0277-5387
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