In this review, we discuss the interaction between cancer and markers of inflammation (such as levels of inflammatory cells and proteins) in the circulation, and the potential benefits of routinely monitoring these markers in peripheral blood measurement assays. Next, we discuss the prognostic value and limitations of using inflammatory markers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and C-reactive protein measurements. Furthermore, the review discusses the benefits of combining multiple types of measurements and longitudinal tracking to improve staging and prognosis prediction of patients with cancer, and the ability of novel in silico frameworks to leverage this high-dimensional data.

Platelets engage cues of pending vascular injury through coordinated adhesion, secretion and aggregation responses. These rapid, progressive changes in platelet form and function are orchestrated downstream of specific receptors on the platelet cell surface, and through intracellular signaling mechanisms that remain systematically undefined. This study brings together cell physiological and phosphoproteomics methods incorporating peptide tandem mass tag (TMT) labeling, sample multiplexing, synchronous precursor selection (SPS) and triple stage tandem mass spectrometry (MS3) to profile signaling mechanisms downstream of the immunotyrosine activation motif (ITAM) platelet collagen receptor GPVI. Altogether, >3,000 significant (FDR<0.05) phosphorylation events on >1,300 proteins were detected in initial and progressing conditions of GPVI-mediated platelet activation. With literature-guided causal inference tools, >300 site-specific signaling relations were mapped from phosphoproteomics data among key and emerging GPVI effectors (i.e., FcRg, Syk, PLCg2, PKCd, DAPP1). Through signaling validation studies and functional screening, other less-characterized targets were also considered within the context of GPVI/ITAM pathways, including Ras/MAPK axis proteins (i.e., KSR1, SOS1, STAT1, Hsp27). Networks highly regulated in GPVI/ITAM signaling out of context of curated knowledge were also illuminated, including a system of >40 Rab GTPases and associated regulatory proteins - where TAK1-mediated Rab7 S72 phosphorylation associated with endolysosomal maturation and GPVI-mediated platelet function. In addition to serving as a model for generating and testing hypotheses from omics datasets, this study puts forth a means to identify hemostatic effectors, biomarkers and therapeutic targets relevant to thrombosis, vascular inflammation and other platelet-associated disease states.

BackgroundAdequate knowledge of malaria prevention and control can help in reducing the growing burden of malaria among vulnerable groups, particularly pregnant women and children aged under 5 years living in malaria endemic settings. Similar studies have been conducted but with less focus on these vulnerable groups. This study assessed knowledge of malaria prevention and control among the pregnant women and non-pregnant mothers of children aged under 5 years in Ibadan, Oyo State, South West Nigeria.MethodsIn this cross sectional study, data on socio-demographic, clinical and knowledge on malaria prevention was collected using interviewer administered questionnaires from consenting study participants attending Adeoyo maternity hospital between May and November 2016. Data was described using percentages and compared across the two maternal groups in the study population. Knowledge scoring from collected data was computed using the variables on causes, symptoms and prevention of malaria and thereafter dichotomised. Multivariate analyses were used to assess the interactive effect of socio demographic and clinical characteristics with malaria knowledge. Level of statistical significance was set at p < 0.05.ResultsOf the 1373 women in the study, 59.6% (818) were pregnant women while 40.4% (555) were mothers of children aged under 5 years. The respondents mean age was 29 years ± 5.2. A considerable proportion of both the pregnant women (n = 494, 60.4%) and the non-pregnant mothers of children aged under 5 years (n = 254, 45.8%) did not have correct knowledge on malaria prevention measures based on our assessment threshold (p < 0.001). Having a tertiary level education was associated with better knowledge on malaria (4.20 ± 1.18, F = 16.80, p < 0.001). Multivariate analyses showed that marital status, educational attainment, gravidity, and HIV status were significantly associated with knowledge of malaria prevention and control.ConclusionThe findings indicate that socio-demographic factors such as marital and educational status greatly influence knowledge on malaria prevention and control measures. Key health stakeholders and authorities need to implement strategies and direct resources to improve the knowledge of mothers on malaria prevention and control. This would stem the tides of malaria related deaths among pregnant women and children aged under 5 years.

Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and thromboxane A2. Platelet-colon cancer cell interactions potentiated the release of platelet-derived extracellular vesicles (EVs) rather than cancer cell-derived EVs. Our data show that single colon cancer cells were capable of recruiting and activating platelets and generating fibrin in plasma under shear flow. Finally, in a retrospective analysis of colon cancer patients, we found that the number of venous thromboembolism events was 4.5 times higher in colon cancer patients than in a control population. In conclusion, our data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients. Our work may provide rationale for targeting platelet-cancer cell interactions with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis, balancing safety with efficacy.