Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-017-1977-z) contains supplementary material, which is available to authorized users.

The long Swift gamma-ray burst GRB 120326A at redshift z = 1.798 exhibited a multi-band light curve with a striking feature: a latetime, long-lasting achromatic rebrightening, rarely seen in such events. Peaking in optical and X-ray bands ∼ 35 ks (∼ 12.5 ks in the GRB rest frame) after the 70-s GRB prompt burst, the feature brightens nearly two orders of magnitude above the underlying optical power-law decay. Modelling the multiwavelength light curves, we investigate possible causes of the rebrightening in the context of the standard fireball model. We exclude a range of scenarios for the origin of this feature: reverse-shock flash, late-time forward shock peak due to the passage of the maximal synchrotron frequency through the optical band, late central engine optical/X-ray flares, interaction between the expanding blast wave and a density enhancement in the circumburst medium and gravitational microlensing. Instead we conclude that the achromatic rebrightening may be caused by a refreshed forward shock or a geometrical effect. In addition, we identify an additional component after the end of the prompt emission, that shapes the observed X-ray and optical light curves differently, ruling out a single overall emission component to explain the observed early time emission.

MLD may be associated with a spectrum of gallbladder pathology including neoplastic conditions. Pathologists and clinicians should be aware of this association/risk. The patient may be offered regular ultrasound screening of the gallbladder.

IntroductionHead and neck cancer (HNC) is a highly prevalent and heterogeneous malignancy. Although extensive efforts have been made to advance its treatment, the prognosis remained poor with increased mortality. Human papillomaviruses (HPV) have been associated with high risk in HNC. TP53, a tumor suppressor, is the most frequently altered gene in HNC, therefore, investigating its target genes for the identification of novel biomarkers or therapeutic targets in HPV-related HNC progression is highly recommended.MethodsTranscriptomic profiles from three independent gene expression omnibus (GEO) datasets, including 44 HPV+ and 70 HPV- HNC patients, were subjected to integrative statistical and Bioinformatics analyses. For the top-selected marker, further in-silico validation in TCGA and GTEx databases and experimental validation in 65 (51 HPV- and 14 HPV+) subjects with histologically confirmed head and neck squamous cell carcinoma (HNSCC) have been performed.ResultsA total of 498 differentially expressed genes (DEGs) were identified including 291 up-regulated genes and 207 down-regulated genes in HPV+ compared to HPV- HNSCC patients. Functional annotations and gene set enrichment analysis (GSEA) showed that the up-regulated genes were significantly involved in p53-related pathways. The integrative analysis between the Hub-genes identified in the complex protein-protein network and the top frequent genes resulting from GSEA showed an intriguing correlation with five biomarkers which are EZH2, MDM2, PCNA, STAT5A and TYMS. Importantly, the MDM2 gene showed the highest gene expression difference between HPV+ and HPV- HNSCC (Average log2FC = 1.89). Further in-silico validation in a large HNSCC cohort from TCGA and GTEx databases confirmed the over-expression of MDM2 in HPV+ compared to HPV- HNSCC patients (p = 2.39E-05). IHC scoring showed that MDM2 protein expression was significantly higher in HPV+ compared to HPV- HNSCC patients (p = 0.031).DiscussionOur findings showed evidence that over-expression of MDM2, proto-oncogene, may affect the occurrence and proliferation of HPV-associated HNSCC by disturbing the p53-target genes and consequently the p53-related pathways.

This case represents occult follicular variant of papillary thyroid carcinoma (FVPTC) with large metastasis to the sacrum. The patient, a 42-year-old female, presented after hemithyroidectomy for benign follicular adenoma with lower back pain associated with fever and sweating. A lytic lesion of the left sacral bone was found on the CT with biopsy showing metastatic carcinoma with morphology and immunophenotype of thyroid gland primary tumor proven to be FVPTC. The patient had completion thyroidectomy with benign pathology.