Background Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. Methods In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro and in vivo analyses of TNBC cell lines were co-cultured with six pooled donors of obASCs (BMI > 30) or ASCs isolated from lean women (lnASCs) (BMI < 25). Results We found that obASCs promote a pro-metastatic phenotype by upregulating genes associated with epithelial-to-mesenchymal transition and promoting migration in vitro. We confirmed our findings using a TNBC patient-derived xenograft (PDX) model. PDX tumors grown in the presence of obASCS in SCID/beige mice had increased circulating HLA1 + human cells as well as increased numbers of CD44 + CD24 − cancer stem cells in the peripheral blood. Exposure of the TNBC PDX to obASCs also increased the formation of metastases. The knockdown of leptin expression in obASCs suppressed the pro-metastatic effects of obASCs. Conclusions Leptin signaling is a potential mechanism through which obASCs promote metastasis of TNBC in both in vitro and in vivo analyses. Electronic supplementary material The online version of this article (10.1186/s13058-019-1153-9) contains supplementary material, which is available to authorized users.

Adipose stem cells (ASCs) have gained attention in the fields of stem cells regenerative medicine due to their multifaceted therapeutic capabilities. Promising preclinical evidence of ASCs has supported the substantial interest in the use of these cells as therapy for human disease. ASCs are an adult stem cell resident in adipose tissue with the potential to differentiation along mesenchymal lineages. They also are known to be recruited to sites of inflammation where they exhibit strong immunomodulatory capabilities to promote wound healing and regeneration. ASCs can be isolated from adipose tissue at a relatively high yield compared to their mesenchymal cell counterparts: bone marrow-derived mesenchymal stem cells (BM-MSCs). Like BM-MSCs, ASCs are easily culture expanded and have a reduced immunogenicity or are perhaps immune privileged, making them attractive options for cellular therapy. Additionally, the heterogeneous cellular product obtained after digestion of adipose tissue, called the stromal vascular fraction (SVF), contains ASCs and several populations of stromal and immune cells. Both the SVF and culture expanded ASCs have the potential to be therapeutic in various diseases. This review will focus on the preclinical and clinical evidence of SVF and ASCs, which make them potential candidates for therapy in regenerative medicine and inflammatory disease processes.

The increasing need for tissue substitutes in reconstructive surgery spurs the development of engineering methods suited for clinical applications. Cell culture and tissue production traditionally require the use of fetal bovine serum (FBS) which is associated with various complications especially from a translational perspective. Using the self-assembly approach of tissue engineering, we hypothesized that all important parameters of tissue reconstruction can be maintained in a production system devoid of FBS from cell extraction to tissue reconstruction. We studied two commercially available serum-free medium (SFM) and xenogen-free serum-free medium (XSFM) for their impact on tissue reconstruction using human adipose-derived stem/stromal cells (ASCs) in comparison to serum-containing medium. Both media allowed higher ASC proliferation rates in primary cultures over five passages compared with 10% FBS supplemented medium while maintaining high expression of mesenchymal cell markers. For both media, we evaluated extracellular matrix production and deposition necessary to engineer manipulatable tissues using the self-assembly approach. Tissues produced in SFM exhibited a significantly increased thickness (up to 6.8-fold) compared with XSFM and FBS-containing medium. A detailed characterization of tissues produced under SFM conditions showed a substantial 50% reduction of production time without compromising key tissue features such as thickness, mechanical resistance and pro-angiogenic secretory capacities (plasminogen activator inhibitor 1, hepatocyte growth factor, vascular endothelial growth factor, angiopoietin-1) when compared to tissues produced in the control FBS-containing medium. Furthermore, we compared ASCs to the frequently used human dermal fibroblasts (DFs) in the SFM culture system. ASC-derived tissues displayed a 2.4-fold increased thickness compared to their DFs counterparts. In summary, we developed all-natural human substitutes using a production system compatible with clinical requirements. Under culture conditions devoid of bovine serum, the resulting engineered tissues displayed similar and even superior structural and functional properties over the classic FBS-containing culture conditions with a considerable 50% shortening of production time.

panel of low passage HNSCC cell lines in vitro and in vivo using MTT assays, clonogenic assays, western blotting, RT-PCR and tumor growth delay using a 3 week fractionated schedule of daily doses of 2 Gy. Results: There is a close relationship between EGFR overexpression and sensitivity to Dacomitinib with UT-SCC-14 and UT-SCC-16A being more sensitive than UT-SCC-15 and UT-SCC-24A, which do not overexpress EGFR. Gedatolisib showed a classical dose response in both the UT-SCC-14 and UT-SCC-15 cell lines with an IC 50 of 0.075mM and 0.2mM, respectively. Gedatolisib was effective at reducing phosphorylation of PI3K, mTOR and AKT in both cell lines. In tumor growth delay experiments with the UT-SCC-14 cell line, Gedatolisib caused a 15 day growth delay to double the tumor volume while Dacomitinib delayed tumor doubling time by 32 days; the combination of the two drugs was similar to Dacomitinib alone. Gedatolisib and radiation delays were similar to radiation alone while combinations involving Dacomitinib and radiation caused profound growth delay and complete cure of 60% of tumors in ongoing studies. Conclusion: Dacomitinib is an extremely potent EGFR targeting agent in the UT-SCC-14 tumor model while Gedatolisib was less effective. Further research is ongoing to establish whether the relationship between EGFR expression levels and Dacomitinib activity is observed in vivo. If this relationship can be established, then a Phase I study using EGFR expression to stratify patients to Dacomitinib treatment would be warranted.

This paper presents a concept using field cameras in combination with Fourier transform spectrometers. The device can produce five-dimensional (position-angle-spectra) data cubes. This can lead to accurate measurements in both spectrum and distance and allows a thorough characterization of the interferometer, as well as adds passive ranging information to hyperspectral images. Shear and tilt fringes are simultaneously observed in a fixed optical path difference interferometer, and a passive spectral ranging demonstration is done in both absorption and emission for the 500-900 nm spectral bands.