Resistance towards VEGF-centered anti-angiogenic therapy still represents a substantial clinical challenge. We report here that mast cells alter the proliferative and organizational state of endothelial cells which reduces the efficacy of anti-angiogenic therapy. Consequently, absence of mast cells sensitizes tumor vessels for anti-angiogenic therapy in different tumor models. Mechanistically, anti-angiogenic therapy only initially reduces tumor vessel proliferation, however, this treatment effect was abrogated over time as a result of mast cell-mediated restimulation of angiogenesis. We show that mast cells secrete increased amounts of granzyme b upon therapy, which mobilizes pro-angiogenic laminin- and vitronectin-bound FGF-1 and GM-CSF from the tumor matrix. In addition, mast cells also diminish efficacy of anti-angiogenic therapy by secretion of FGF-2. These pro-angiogenic factors act beside the targeted VEGFA–VEGFR2-axis and reinduce endothelial cell proliferation and angiogenesis despite the presence of anti-angiogenic therapy. Importantly, inhibition of mast cell degranulation with cromolyn is able to improve efficacy of anti-angiogenic therapy. Thus, concomitant mast cell-targeting might lead to improved efficacy of anti-angiogenic therapy.
Background: The Cancer Genome Atlas (TCGA) network (United States National Cancer Institute) identified four molecular endometrial cancer (EC) subtypes using an extensive multi-method approach. The aim of this study was to determine the four TCGA EC molecular subtypes using a single-method whole-exome sequencing (WES)-based approach provided by MH Guide (Molecular Health, Heidelberg, Germany). Methods: WES and clinical data of n = 232 EC patients were obtained from TCGA. The four TCGA EC molecular subtypes designated as (i) Mutated Polymerase ε (POLE), (ii) Microsatellite Instability (MSI), (iii) Copy Number (CN) low and, (iv) CN-high were determined using the MH Guide software. The prognostic value of the subtypes determined by MH Guide were compared with the TCGA classification. Results: Analysis of WES data using the MH Guide software led to the precise identification of the four EC molecular subtypes analogous to the TCGA classification. Both approaches displayed high concordance in terms of prognostic significance. Conclusions: The multi-method-based TCGA EC molecular subtypes can reliably be reproduced by the single-method-based MH Guide approach. The easy-to-implement single-method MH Guide approach represents a promising diagnostic tool.
rate was 90.9%. The present survey revealed that in seeing the patients the regional health care professionals did check each part of the tools described by multidisciplinary staff; MSW (question item #1, #4), physician (#2, #3, #5), pharmacist (#5), therapist (#6), and palliative care team (#7, #8). The tools invented by Higashi-Nagoya home care social gathering should be useful (10/12) (#9) and enhance the quality of palliative care (12/12) (#10). Conclusions Sharing information via the communication tools of cooperation might contribute to realizing the seamless palliative care in the region adjacent to our hospital.
Conclusion:Comprehensive care for medical oncology patients definitely improves quality of oncologic nursing. And it also enhances nurse's satisfaction and pride in work despite some limitations.
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