Background:Treatment with epidermal growth factor receptor (EGFR) inhibitors can result in clinical response in non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) for some unselected patients. EGFR and KRAS mutation status, amplification of EGFR, or gene expression predictors of response can forecast sensitivity to EGFR inhibition.Methods:Using an NSCLC cell line model system, we identified and characterised microRNA (miRNA) gene expression that predicts response to EGFR inhibition.Results:Expression of 13 miRNA genes predicts response to EGFR inhibition in cancer cell lines and tumours, and discriminates primary from metastatic tumours. Signature genes target proteins that are enriched for epithelial-to-mesenchymal transition (EMT) genes. Epithelial-to-mesenchymal transition predicts EGFR inhibitor resistance and metastatic behaviour. The EMT transcription factor, ZEB1, shows altered expression in erlotinib-sensitive NSCLC and PDAC, where many signature miRNA genes are upregulated. Ectopic expression of mir-200c alters expression of EMT proteins, sensitivity to erlotinib, and migration in lung cells. Treatment with TGFβ1 changes expression of signature miRNA and EMT proteins and modulates migration in lung cells.Conclusion:From these data, we hypothesise that the tumour microenvironment elicits TGFβ1 and stimulates a miRNA gene expression program that induces resistance to anti-EGFR therapy and drives lung tumour cells to EMT, invasion, and metastasis.

Advancements in rheumatoid arthritis (RA) treatment protocols and introduction of targeted biological therapies have markedly improved patient outcomes, despite this, up to 50% of patients still fail to achieve a significant clinical response. In veterinary medicine, stem cell therapy in the form of autologous stromal vascular fraction (SVF) is an accepted therapeutic modality for degenerative conditions with 80% improvement and no serious treatment associated adverse events reported. Clinical translation of SVF therapy relies on confirmation of veterinary findings in targeted patient populations. Here we describe the rationale and preclinical data supporting the use of autologous SVF in treatment of RA, as well as provide 1, 3, 6, and 13 month safety outcomes in 13 RA patients treated with this approach.

To determine if knee pain subjects who received cryopreserved umbilical cord tissue (UCT) injected into knee joints experience less knee pain, better function, decreased physical limitations, and reduction of medications (opiates, NSAIDs, and acetaminophen) over a 24 week period, Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and medication usage data were recorded for 30 consenting human knee pain subjects receiving UCT at a single site in the United States. Subject profile information was gathered and analyzed to gain insight into the effects of age, sex, and BMI on improvement over time. Mean resting VAS scores and mean VAS scores with activity improved over 24 weeks (from 1.95 to 0.83 and from 6.28 to 2.87, respectively, p < 0.001). There was no strong evidence of a correlation between sex and VAS scores. There were statistically significant correlations for BMI vs. pre-injection VAS with activity scores and Age vs. pre-injection VAS with activity scores (r = 0.402, p = 0.028 and r = 0.434, p = 0.017, respectively). Mean WOMAC scores improved from 44.7 to 18.5 over 24 weeks (p < 0.001). 77.8% of patients who used medications at the beginning of the study reduced or eliminated medication use. The analysis demonstrates that injections with UCT decrease pain, improve physical function, and allow for less medication use for at least 24 weeks.

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Context: Injection with homologously-used umbilical cord tissue allograft has not been adequately studied in patients suffering from knee pain. Objectives: The goal of this study is to determine if knee pain subjects who received cryopreserved umbilical cord tissue (UCT) injected into knee joints experience less knee pain, better function, decreased physical limitations, and reduction of medications (e.g., opiates, NSAIDs, and acetaminophen) over a 6-month period. Methods: Prior to initiation of this study, Institutional Review Board (IRB) approval was obtained. Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritic Index (WOMAC), and medication usage data were recorded for thirty (30) consenting knee pain subjects receiving UCT at a single site in the United States. Subject profile information was also gathered and utilized to gain further insight into any effects of age, gender, and BMI on pain improvement over time. Results: Mean resting VAS scores improved from 1.95 to 0.83 over 6 months (p<0.001), while mean VAS scores with activity improved from 6.28 to 2.87 (p<0.001) for the same period. There was no strong evidence of correlation found between gender and VAS scores (resting or with activity). However, there were statistically significant correlations found for both BMI vs. Pre-injection VAS with activity scores (r=0.402, p=.028) and Age vs. Pre-injection VAS with activity scores (r=0.434, p=.017). Mean WOMAC daily activity function scores improved from 44.7 to 18.5 over the same 6 months (p<.001). Overall, of the patients who used medications at the beginning of the study (18), 77.8% of them reduced or eliminated medication use. Conclusion: Analysis demonstrates that injection with UCT decreases pain, improves physical function, and allows for less medication use for at least 6 months.