TGFβ + small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype

Transforming growth factor β (TGFβ) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro-tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis-promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro-angiogenic phenotype characterized by the upregulation of pro-angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4-nitroquinoline-1-oxide (4-NQO)-driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2-like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC

The analysis of chromatin condensation state and transcriptional activity using DNA microarrays

The DNA microarray-based technique has been developed to semi-quantitatively measure the in vivo global chromatin condensation state at the resolution of a gene. Chromatin was fractionated due to the differential solubility of histone H1-containing and histone H1-free nucleosomes. A set of genes non-randomly distributed between histone H1-free (uncondensed or open) and histone H1-containing (condensed or closed) chromatin fractions has been identified. The transcript levels have been measured for the same group of genes. The correlation between transcriptional activity and chromatin fraction distribution of particular genes has been established

CYFRA 21-1 as a Prognostic Marker of Tumor Response to Radiation Alone or Combined With Chemotherapy in Patients With Carcinoma of Larynx or Hypopharynx

Despite of relatively high rate of complete tumor responses after radiotherapy (RT) alone or in combination with chemotherapy (ChRT), locoregional relapse is a major reason of failure for patients with head and neck squamous cell carcinoma (HNC). If treatment failure is diagnosed early, salvage therapy could be possible. Such diagnosis is difficult due to the lack of early prognostic markers for discrimination between residual tumor and treatment-related changes shortly after treatment. The aim of the study was to evaluate clinical value of CYFRA 21-1 as a potential marker of early failure of radiotherapy in patients with laryngeal (LXC) or hypopharyngeal (HPC) cancer. Material and methods: Consecutive 93 patients with LXC (73%) and HPC (27%) were treated between 2009 and 2011 by RT alone (63%), or ChRT (37%). CYFRA 21-1 was estimated before (CYFRA 21-11) and at the end (CYFRA 21-12) of the treatment. Results: CYFRA 21-11 correlated with T and N stages. Median CYFRA 21-12 in patients with partial and with complete remission was 2.33 ng/ml, and 1.65 ng/ml, respectively (p=0.0001). Statistically significant differences in 3-year LRC (82% vs. 42%) and OS (57% vs. 40%) were observed between patients groups with CYFRA 21-12 lt2 ng/ml and ge 2 ng/ml, respectively. In multivariate analysis CYFRA 21-12 remained significant prognostic factor for LRC (p=0,0003) and OS (p=0.01). Conclusions: CYFRA 21-1 assessed at the end of the RT or ChRT seems to be a prognostic marker for tumor response. Probability of persistent tumor is markedly higher innbspLXC and HPC patients with CYFRA 21-1 ge 2 ng/ml instantly after treatment