Cancer is the second leading cause of mortality worldwide. Skin cancer is the most common cancer in South Africa with nearly 20,000 reported cases every year and 700 deaths. If diagnosed early, the 5‐year survival rate is about 90%, however, when diagnosed late, the 5‐year survival rate decreases to about 20%. Melanoma is a type of skin cancer with an estimated 5‐year survival rate of approximately 90%. Neuroblastoma is a paediatric cancer with a low survival rate. Sixty percent of patients with metastatic disease do not survive 5 years after diagnosis. Despite recent advances in targeted therapies, there is a crucial need to identify reliable prognostic biomarkers which will be able to contribute to the development of more precision‐based chemotherapeutic strategies to prevent tumour migration and metastasis. The compound, CTCE‐9908 inhibits the binding of CXC chemokine ligand 12 (CXCL12) to the CXC chemokine receptor 4 (CXCR4) receptor leading to reduced metastasis. Kynurenine metabolites are derived tryptophan, which is an essential amino acid. Kynurenine metabolites inhibit T‐cell proliferation resulting in cell growth arrest. For this reason, chemokines receptors represent potential targets for the treatment of cancer growth and metastasis. In this review paper, the role of the CXCL12/CXCR4 signalling pathway in the development of cancer is highlighted together with the current available treatments involving the CTCE‐9908 compound in combination with microtubule inhibitors like paclitaxel and docetaxel.

Background Cutaneous melanoma is a relentless form of cancer which continues to rise in incidence. Currently, cutaneous melanoma is the leading cause of skin cancer‐related mortality, which can mainly be attributed to its metastatic potential. The activation of chemokine axes is a major contributor to melanoma metastasis through its involvement in promoting tumour cell migration, proliferation, survival, and adhesion. This review will focus on the role of chemokines in melanoma and possible therapeutic strategies to alter chemokine activation and subsequently inhibit the activation of signalling cascades that may promote metastasis. Methods A literature review was conducted to evaluate chemokines as possible therapeutic targets in metastatic melanoma. Results The crosstalk between signalling pathways and immune responses in the melanoma microenvironment resembles a complex and dynamic system. Therefore, the involvement of governing chemokine axes in the promotion of cutaneous and metastatic melanoma demands a proper understanding of the tumour microenvironment in order to identify possible targets and develop appropriate treatments against melanoma. Conclusion Even though chemokine axes are regarded as promising therapeutic targets, it has become increasingly evident that chemokines can play a critical role in both tumour inhibition and promotion. The inhibition of chemokine axes to inhibit signalling cascades in target cells that regulate metastasis should, therefore, be carefully approached.

Heavy metals are natural elements characterized by their relatively large atomic mass as well as their high density. Heavy metal poisoning has occurred in numerous countries in the past, with the United States having the highest prevalence. Heavy metals can also be introduced into the ecosystem by the mining of heavy metals from deep within the earth's crust thereby exposing them into air and water systems.Another common source of heavy metal exposure is cigarette smoke. Cigarette smoke has been shown to have carcinogenic, toxic and genotoxic properties. Although all the toxic elements in cigarette smoking have not yet been identified, several heavy metals have been found to contribute to the pathophysiological consequences associated with smoking. A study conducted by Yaprak et al., in 2019 indicated that cadmium, lead and chromium are the most abundant metals found in cigarette smoke. The current study therefore focused on cadmium, lead and chromium, alone and as part of metal mixtures to determine the role of these heavy metals on endothelial cells. The EA.hy926 endothelial cell line was exposed to different concentrations of each of these metal and their combinations and analysed at different time points to determine the effect of the heavy metals on endothelial cell function. The cytotoxicity of the metals was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Crystal Violet assays, reactive oxygen species productions was studied using the 2',7'dichlorodihydrofluorescein diacetate (DCFH-DA) assay, and cell viability was determined using flow cytometry. Finally, morphological changes caused by these metals was studied using scanning electron microscopy.Exposure of endothelial cells to cadmium, lead and chromium alone and in combination at three different concentrations (X0.1, X1 and X2) showed no significant cytotoxicity as indicated by the MTT and Crystal Violet assay results. At 24 h exposure, cadmium alone showed an increase in percentage free radical formation whereas lead alone showed the greatest percentage radical formation for the X1 concentration group. At 48 h exposure, chromium alone as well as the triple combination group showed an increase in the percentage radical formation between 0.1 and X2 concentrations. Cadmium caused the highest percentage radical formation in the X1 concentration group and lead at the X2 concentration group. After 72 h, both the cadmium and lead as single metals showed a gradual increase in percentage radical formation between the 0.1 and X2 concentrations, with cadmium showing the highest increase in the X1 concentration. Flow cytometric analyses with the Annexin V and the Propidium Iodide assay, showed an increase in early apoptotic and necrotic cells with higher concentrations of the lead and chromium © © U Un ni iv ve er rs si it ty y o of f P Pr re et to or ri ia a 4 combination as well as in the triple combination group. Increased necrosis was also evident in the cadmium and chromium combination, the lead and chromium as well...