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Mohamed, Mona Mostafa; Schneider, Robert J
doi: 10.1093/qjmed/hcae195pmid: 39437012
Inflammatory breast cancer (IBC) is the most aggressive and lethal phenotype form of breast cancer, which afflicts young women at high incidence in North Africa compared to other continents of the world. IBC is characterized by highly metastatic behavior and possesses specific pathobiological properties different from non-IBC. IBC disease displays unusual common properties at typical presentation, including positive metastatic lymph nodes, high infiltration of tumor-associated monocytes/macrophages (TAMs/Ms), rapid progression to distant metastasis and possibly the production of a unique repertoire of growth factors, cytokines and chemokines, as well as a striking association with different polarized macrophages compared to non-IBC. Indeed, TAMs/Ms play a crucial role in breast cancer development. Previously, we showed that cross-talk between IBC cells and patient-derived TAMs occurs via secretion of inflammatory mediators from TAMs that act on specific extracellular domain receptors activating down-stream signaling pathways that promote the epithelial-to-mesenchymal transition, cancer cell invasion, IBC stem cell properties, drug resistance, local and metastatic recurrence of residual tumor cells and other key markers of malignancy, including in vitro colony formation capacity. In this mini-review, we will discuss the role of TAMs in IBC cancer metastatic potential and molecules involved. The review also discusses the recent discoveries in the field of IBC research.
Burn, L A; Wetscherek, M T; Pharoah, P D; Marciniak, S J
doi: 10.1093/qjmed/hcae129pmid: 38976637
IntroductionSpontaneous pneumothorax recurs in 30–54% of patients without surgery. Identifying individuals likely to suffer a recurrence, who might benefit from pre-emptive surgery, is challenging. Previous meta-analysis suggested a relationship between contralateral recurrence and specific CT findings.MethodsWe analysed CT images and recurrence rates of 243 patients seen by our tertiary referral pneumothorax service.ResultsWe validated the meta-analysis observation that contralateral lung cysts are associated with a higher risk of contralateral recurrence in younger individuals. Furthermore, we observed that the size of contralateral cysts to be associated with increased contralateral recurrence in younger patients.ConclusionThe detection of contralateral lung cysts might therefore help identify younger patients more likely to benefit from pre-emptive surgery.
Seet, R C S; Quek, A M L; Teng, O; Krishnan, S; Ng, G J L; Ng, M Y; Mahadevan, A; Chioh, F W J; Yeo, K P; Lim, H Y; Kim, J; Swa, C L F; Pek, N M Q; Arumugam, T V; Angeli, V; Gunaratne, J; Cheung, C
doi: 10.1093/qjmed/hcae136pmid:
Ouyang, X; Qian, Y; Tan, Y; Shen, Q; Zhang, Q; Song, M; Shi, J; Peng, H
doi: 10.1093/qjmed/hcae147pmid: 39078215
BackgroundThe prognosis of idiopathic pulmonary fibrosis (IPF) patients is highly heterogeneous. Abnormalities in lipids and their metabolism play an important role in the development of IPF.AimTo investigate the value of lipid parameters, C-reactive protein (CRP) and high-density lipoprotein cholesterol/C-reactive protein (HDL-C/CRP) ratio levels in the prognosis of IPF patients.DesignAn observational cohort study.MethodsWe collected baseline data of non-IPF controls and IPF patients, and IPF patients were followed up for 4 years. All-cause death or lung transplantation and IPF-related death were the outcome events. Receiver operating characteristic curves and Cox proportional hazards models were used to analyze the predictive effect of lipid parameters, CRP and HDL-C/CRP ratio on the prognosis of IPF patients.ResultsIPF patients had lower HDL-C, HDL-C/CRP ratio and higher CRP compared to non-IPF controls. IPF patients who died or underwent lung transplantation were older and had worse pulmonary function, lower HDL-C, HDL-C/CRP ratio and higher CRP compared with surviving patients. HDL-C/CRP ratio was better than HDL-C and CRP in predicting all-cause death or lung transplantation. IPF patients with low HDL-C/CRP ratio had shorter survival times. The HDL-C/CRP ratio and diffusing capacity for carbon monoxide(DLCO)% of predicted were independent protective factors for all-cause death or lung transplantation and IPF-related death in IPF patients, while age and gender-age-physiology (GAP) Stage ≥ 2 (HR = 4.927) were independent risk factors for all-cause death or lung transplantation. Age > 65 years (HR = 3.533) was an independent risk factor for IPF-related death.ConclusionHDL-C/CRP ratio was a valid predictor of clinical outcomes in IPF patients, including all-cause death or lung transplantation and IPF-related death.
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BackgroundIschemic stroke patients are more prone to developing another cardiovascular event.AimThis study aims to examine potential biological predispositions to cardiovascular recurrence in patients with ischemic stroke.DesignHuman and preclinical studies.MethodsQuantitative proteomic analysis, animal stroke, atherosclerosis models and circulating endothelial cells (CECs) were employed to examine candidate biomarkers derived from an ischemic stroke cohort in Singapore.ResultsProteomic analysis of pooled microvesicles of ‘Event’ (n = 24) and without ‘Event’ (n = 24) samples identified NOTCH3 as a candidate marker; plasma NOTCH3 were shown to be elevated in ‘Event’ patients compared to those without ‘Events’ and age-matched controls. In a validation cohort comprising 431 prospectively recruited ischemic stroke patients (mean age 59.1 years; median follow-up 3.5 years), men with plasma NOTCH3 (>1600 pg/ml) harbored increased risk of cardiovascular recurrence (adjusted hazards ratio 2.29, 95% CI 1.10–4.77); no significant association was observed in women. Chronic renal failure, peripheral artery disease and NT-pro-brain natriuretic peptide were significant predictors of plasma NOTCH3 in men without ischemic stroke (adjusted r2 = 0.43). Following middle cerebral artery occlusion, NOTCH3 expression in mouse sera increased and peaked at 24 h, persisting thereafter for at least 72 h. In Apoe−/− atherosclerotic mice, NOTCH3 stained the endothelium of defective arterial lining and atherosclerotic plaques. Analysis of CECs isolated from stroke patients revealed increased gene expression of NOTCH3, further supporting endothelial damage underpinning NOTCH3-mediated atherosclerosis.ConclusionFindings from this study suggests that NOTCH3 could be important in cardiovascular recurrence following an ischemic stroke.