Background: Receptor tyrosine kinases (RTKs) are signaling enzymes responsible for the transfer of Adenosine triphosphate (ATP) γ-phosphate to the tyrosine residues substrates. RTKs demonstrate essential roles in cellular growth, metabolism, differentiation, and motility. Anomalous expression of RTK customarily leads to cell growth dysfunction, which is connected to tumor takeover, angiogenesis, and metastasis. Understanding the structure, mechanisms of adaptive and acquired resistance, optimizing inhibition of RTKs, and eradicating cum minimizing the havocs of quiescence cancer cells is paramount. MainText: Tyrosine kinase inhibitors (TKIs) vie with RTKs ATP-binding site for ATP and hitherto reduce tyrosine kinase phosphorylation, thus hampering the growth of cancer cells. TKIs can either be monoclonal antibodies that compete for the receptor's extracellular domain or small molecules that inhibit the tyrosine kinase domain and prevent conformational changes that activate RTKs. Progression of cancer is related to aberrant activation of RTKs due to due to mutation, excessive expression, or autocrine stimulation. Conclusions:Understanding the modes of inhibition and structures of RTKs is germane to the design of novel and potent TKIs. This review shed light on the structures of tyrosine kinases, receptor tyrosine kinases, tyrosine kinase inhibitors, minimizing imatinib associated toxicities, optimization of tyrosine kinase inhibition in curtailing quiescence in cancer cells and the prospects of receptor tyrosine kinase based treatments.

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Camphor-induced oxidative stress and histopathological changes (in brain, lung, liver, kidney and testes) have been reported. We therefore investigated the effect of various doses of camphor in an acute study, on renal and testicular levels of some pro-inflammatory mediators in male wistar rats. Twenty rats divided into four groups of five rats each were used in this study. Group 1 served as control and was administered 6 mL/kg olive oil, the vehicle for camphor, while groups 2, 3 and 4 were orally administered 1000, 2000, and 4000 mg/kg body weight camphor, for seven days. Compared with control, levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) were significantly increased kidney and testes by 2000 and 4000 mg/kg body weight, while interleukin 10 (IL-10) was only significantly increased by 1000 mg/kg body weight of camphor in both tissues. Also compared with control, all doses of camphor administered resulted in a significant increase in the expressions of renal and testicular nuclear factor kappa B (NFkB), cyclooxygenase 2 (COX-2), regulated upon activation normal T cell expressed and secreted (RANTES), and monocyte chemo-attractant protein 1 (MCP-1). Conclusively, use and consumption of camphor should be with caution as it could trigger renal and testicular inflammation through activation of NF-kB and up-regulation of pro-inflammatory markers.

Breast cancer is the most prevalent cancer in women. X-linked inhibitor of apoptosis protein (XIAP) that is constantly overexpressed in cancer is a promising therapeutic target in cancer treatments. The mechanisms of the anticancer effects of carotenoid isolates of Spondias mombim in DMBA-induced breast cancer in Wistar rats through XIAP antagonism were investigated in the present study. Carotenoids isolated from the leaves of Spondias mombim were subjected to Liquid Chromatography/Mass Spectrometry (LC/MS) and Electrospray Ionization (ESI) for characterization. The characterized carotenoid isolates were docked against XIAP BIR2 domain and XIAP BIR3 domain. The anticancer effects of the carotenoid isolates of Spondias mombim in DMBA-induced breast cancer in Wistar rats were also investigated through the expression of XIAP, COX-2, TNF, BCl-2 mRNAs by qRT-PCR and biochemical parameters of catalase, lipid peroxidation, LDH, ALP, and ALT. These show the carotenoid isolates demonstrate anticancer effects by antagonism of XIAP, proapoptotic, and anti-inflammatory properties. Practical applications The present study showed that carotenoids (astaxanthin, β-carotene-15,15ʹ-epoxide, and 7,7ʹ,8,8ʹ-tetrahydro-β, β-carotene) isolated from the leaves of Spondias mombim are proapoptotic, it further gives credence to the chemopreventive abilities of carotenoids. This study validated XIAP as a druggable target in cancer treatment and hence more phytochemicals should be screened against it, for possible lead compounds of plant origin. Cancer cells often explore XIAP for antiapoptotic and resistance tendencies, hence, β-carotene-15,15ʹ-epoxide and 7,7ʹ,8,8ʹ-tetrahydro-β, β-carotene (XIAP antagonists) are promising drug candidates that can withstand resistant and prone cancer cells to apoptotic cell death. There is a need to synthesize β-carotene-15,15ʹepoxide and 7,7ʹ,8,8ʹ-tetrahydro-β for further investigation in clinical studies. K E Y W O R D S 7,12-dimethylbenz[a]anthracene (DMBA), baculovirus IAP repeat (BIR), breast cancer, liquid chromatography/mass spectrometry, X-linked inhibitor of apoptosis protein (XIAP) How to cite this article: Metibemu DS, Akinloye OA, Akamo AJ, et al. Carotenoid isolates of Spondias mombin demonstrate anticancer effects in DMBA-induced breast cancer in Wistar rats through X-linked inhibitor of apoptosis protein (XIAP) antagonism and anti-inflammation.

Some snails ( Achatina spp) can be used as a biosensor of heavy metal poisoning. This study thus estimated some heavy metal levels, antioxidant markers, and lipid profiles of snails handpicked around cement factory vicinities in Ogun State, Nigeria. Snails and soil samples were collected from Oke, Ewekoro, Papalanto, and Mowodani Imeko-Afon (control site). Lead (Pb), cadmium (Cd), and arsenic (As) levels were estimated in the soil, snail foot, hemolymph, and shell using Atomic Absorption Spectrophotometry. Triacylglycerol (TAG), phospholipids (PHOL), cholesterol (CHOL), malondialdehyde (MDA), and reduced glutathione (GSH) levels, as well as glutathione- S-transferase (GST), lactate dehydrogenase (LDH), and arylesterase (AR) activities in the hemolymph, were estimated spectrophotometrically. The snails collected from the Oke site had the highest foot Pb (274.66 ± 13.50 mg/g tissue), CHOL, TAG, PHOL levels, and GST activity when compared with other sites. Snails collected from Papa had the highest Cd levels (1.79 ± 0.74 mg/kg), As (1206 ± 18.87 mg/g tissue) in the foot, and LDH activity, while Ewekoro snails had highest MDA levels and AR activities but the lowest GSH levels. Additionally, there were negative correlations between the heavy metal levels and the activities of GST and AR as well as GSH levels, while positively correlating with LDH activity and MDA level. Workers and the general public around cement factories are at a greater risk of heavy metal-induced pathologies. More so, consumption of snails around these sites may be deleterious to health.