Purpose To examine relationships following adjuvant chemotherapy between circulating proinflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. Patients and Methods 33 breast cancer patients who had completed initial treatment (surgery, ± radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and one year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. Results At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the group who did not receive chemotherapy. After one year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the one year time frame (IL-1ra: peak voxel p<0.0005; cluster size p<0.0005, p=0.001 after correction (medial prefrontal), p<0.0005; cluster size p=0.001, p=0.029 corr. (anterior temporal), sTNF-RII: p<0.0005; cluster size p=0.001, p=0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p<0.0005; cluster size p<0.0005, p<0.0005 corr.) and anterior temporal (p<0.0005; cluster size p<0.0005, p=0.002 corr.) cortices at baseline and one year later. Conclusion Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients.

A 56-year-old male presented with complaints of cough with expectoration for 3 months duration and fever for 15 days. He had no associated complaints of breathlessness, wheeze, loss of weight and appetite. For the above complaints, he had received two courses of antibiotics before this presentation elsewhere. He is a smoker for 30 years. There is no significant past medical history. There was no evidence of similar illness in the family. On presentation, patient had investigations done outside like chest x-ray that revealed a right upper and mid-zone cavity and CT thorax that revealed a cavity with fluid level with no evidence of lymphadenopathy or bone erosion. On examination, he was tachypnoeic with respiratory rate of 32/min, pulse rate was 90/min and saturation was 95% on room air. He had no clubbing or lymphadenopathy. Respiratory examination revealed expiratory rhonchi and diminished breath sounds in right mammary, infra-axillary and infrascapular areas.

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MicroRNA-29 is an anti-fibrotic miRNA whose expression is downregulated in multiple fibrotic indications including in cutaneous scars and keloids. Its target genes include numerous collagens and other extracellular matrix molecules, suggesting that restoration of miR-29 expression in a skin wound or at the site of an excised scar could have a therapeutic benefit by reducing scarring and/or preventing scar regrowth. An oligonucleotide mimic of miR-29b (MRG-201) was studied in vivo in mouse, rats and rabbits as well as in vitro in human skin fibroblasts to identify a set of conserved pharmacodynamic biomarkers in the skin. MRG-201 was then evaluated in a Phase 1 double-blinded within-patient randomized clinical trial in 53 normal healthy volunteers (NCT02603224). Expression of miR-29b and its pharmacodynamic biomarkers was assessed in untreated skin incisions and following single or multiple administrations of MRG-201 at the site of a sutured skin incision. miR-29b expression was significantly decreased and direct miR-29 target genes were significantly upregulated with incision alone. Intradermal administration of MRG-201 resulted in a high local concentration of miR-29b with low systemic exposure and good safety/tolerability at all doses tested. Pharmacodynamic activity was seen after MRG-201 treatment: single and multiple doses of MRG-201 reduced collagen mRNA expression as compared to a placebo injected incision in the same subject. Additionally, multiple administrations of MRG-201 reduced fibroplasia as assessed by histopathology (p < 0.01). These findings support further investigation of MRG-201 as a novel therapeutic to inhibit scar formation or prevent hypertrophic scar or keloid recurrence following excision.