It is well established that chronic inflammation underpins the development of a number of human cancers, with pro-inflammatory signaling within the tumor microenvironment contributing to tumor progression and metastasis. CXCL8 is an ELR+ pro-inflammatory CXC-chemokine which mediates its effects via signaling through two G protein-coupled receptors, CXCR1 and CXCR2. Elevated CXCL8-CXCR1/2 signaling within the tumor microenvironment of numerous cancers is known to enhance tumor progression via activation of signaling pathways promoting proliferation, angiogenesis, migration, invasion and cell survival. This review provides an overview of established roles of CXCL8-CXCR1/2 signaling in cancer and subsequently, discusses the possible strategies of targeting CXCL8-CXCR1/2 signaling in cancer, covering indirect strategies (e.g., anti-inflammatories, NFκB inhibitors) and direct CXCL8 or CXCR1/2 inhibition (e.g., neutralizing antibodies, small molecule receptor antagonists, pepducin inhibitors and siRNA strategies). Reports of pre-clinical cancer studies and clinical trials using CXCL8-CXCR1/2-targeting strategies for the treatment of inflammatory diseases will be discussed. The future translational opportunities for use of such agents in oncology will be discussed, with emphasis on exploitation in stratified populations.

Objective Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. We therefore examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically-derived classes. Methods 806 participants diagnosed via the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on “robust” normal control performance (n=260). Calculated z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Results Statistical fit indices suggested a 3-class model was the optimal LPA solution. The 3-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be APOE e4+ and have worse AD CSF biomarkers than LPA-derived normal subjects. Conclusions Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent “false-positive” diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive.

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BackgroundThe incidence and prevalence of multidrug–resistant tuberculosis (MDR TB) in the province of KwaZulu-Natal, South Africa, are amongst the highest in the world. Previously, interventions have been largely biomedical based; however, there is growing opinion that interventions must include social aspects such as patient education and attitudes.MethodsThis observational study assessed the knowledge and attitudes of 380 patients diagnosed with MDR TB at a centralised MDR TB unit in Durban. Data were collected using a questionnaire that was distributed to every third patient attending the outpatient MDR TB clinic. Data were collected over an 8-week period and analysed descriptively.ResultsJust under half of the respondents had primary MDR TB. Most respondents were young, female unemployed and did not receive a social grant. Knowledge around diagnosis of MDR TB was generally adequate. There were important misconceptions about spread of the disease and duration of treatment. Most respondents received knowledge of MDR TB from healthcare workers. Some respondents received knowledge from friends, family and Sangomas and believed that the disease was caused by bewitchment or as a form of punishment.DiscussionThe need for strengthening the role of primary care physicians in promoting education and providing support is highlighted. Further study is needed to investigate the high rate of primary MDR TB and to identify the unique challenges faced by women who have MDR TB. Future research could include the possibility of involving traditional healers in a contextually sensitive MDR TB education, training and support programme.