Initiation of and adherence to tamoxifen and aromatase inhibitor therapy among elderly women with ductal carcinoma in situ.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project B35 and International Breast Cancer Intervention Studies II Ductal Carcinoma In Situ trials showed similar treatment effects of anastrozole and tamoxifen in reducing cancer recurrence risk among ductal carcinoma in situ (DCIS) patients. Studies have shown low levels of hormone therapy drug initiation for DCIS patients, but the current body of literature lacks information on the 5-year adherence rates for these drugs from population-based studies. METHODS: This study evaluated the initiation and 5-year adherence levels for women aged 66 to 85 years who had been diagnosed with estrogen receptor (ER)-positive DCIS between 2007 and 2011 according to the Surveillance, Epidemiology, and End Results and Texas Cancer Registry databases linked to Medicare claims. Chi-square tests, trend tests, and logistic regression were used to identify factors associated with treatment initiation. RESULTS: There were 2871 women with ER-positive DCIS, and approximately 45% began treatment with tamoxifen or aromatase inhibitors (AIs) within 1 year of their DCIS diagnosis. The median age was 73 years for the users and 75 years for the nonusers. Women aged 66 to 70 years who underwent lumpectomy and radiation therapy were significantly more likely to initiate hormone therapy. The initiation of therapy was also significantly associated with patients' geographic location, education, marital status, diagnosis year, and race/ethnicity. Among users, adherence decreased from 67% in the first year to 30% in the fifth year. CONCLUSIONS: Initiation and adherence levels for tamoxifen or AIs among older women with ER-positive DCIS are low. Future studies should develop methods to ensure that informed discussions take place between health care providers and patients regarding hormonal therapy for cancer prevention. Cancer 2017;123:940-47. © 2016 American Cancer Society.

Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis-Associated Genetic and Environmental Factors.

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments. METHODS: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype-based longitudinal association test on regions that included the loci identified. RESULTS: The single-nucleotide polymorphism rs58905141 in TNFAIP3 was consistently associated with time-course and/or dose-response expression of MMP3 and MMP1 in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta-analysis. Results of the haplotype-based analysis validated the association signals. CONCLUSION: Our findings indicate that a genetic variant of TNFAIP3 is strongly associated with the silica-induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for TNFAIP3. This is the first genome-wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.

Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types.

Prognostic genes are key molecules informative for cancer prognosis and treatment. Previous studies have focused on the properties of individual prognostic genes, but have lacked a global view of their system-level properties. Here we examined their properties in gene co-expression networks for four cancer types using data from 'The Cancer Genome Atlas'. We found that prognostic mRNA genes tend not to be hub genes (genes with an extremely high connectivity), and this pattern is unique to the corresponding cancer-type-specific network. In contrast, the prognostic genes are enriched in modules (a group of highly interconnected genes), especially in module genes conserved across different cancer co-expression networks. The target genes of prognostic miRNA genes show similar patterns. We identified the modules enriched in various prognostic genes, some of which show cross-tumour conservation. Given the cancer types surveyed, our study presents a view of emergent properties of prognostic genes.

An immunohistochemical study of S-100 protein in the intestinal tract of Chinese soft-shelled turtle, Pelodiscus sinensis.

The present work describes the distribution of S-100 protein in the intestinal tract of a Chinese soft-shelled turtle specimen (Pelodiscus sinensis). S-100 protein positive cells were located in the intestinal tract, from the proximal small to distal large intestine. S-100 protein positive dendritic cells had irregular shape and were positive in both cytoplasm and nucleus. Most of them were located both lamina propria and submucosa in the small intestine, while few were found in the large intestine. S-100 protein, C-kit positive ICCs and Silver staining glial cells were predominantly observed in three locations: (1) in the interspace between the submucosa and circular muscle layer; (2) in the circular muscle layer; and (3) between the circular and longitudinal muscle layers of the intestine. Fewer were found in the large intestinal lamina propria and submucosa. Three types of positive cells (S-100 protein positive cells, C-kit positive ICCs and Silver staining glial cells) with 1-2 long or 2-3 short processes were distributed as lace-like or surrounding blood vessels in the different locations mentioned above. In the lamina propria, all the positive cells with irregular processes were connected with each other and formed a network. In the submucosa, all the positive cells were found surrounding the blood vessels.

Fine structural observation on the oogenesis and vitellogenesis of the Chinese soft-shelled turtle ( Pelodiseus sinensis).

Fine structure observations were performed by means of electron microscopy on oogenesis and vitellogenesis and the special functions of follicular cells in the Chinese soft-shelled turtle (Pelodiseus sinensis). Histological examination of the ovary showed a well developed lacunae system containing fine granules, fibres or gelatiniform materials with one or two germinal beds dispersed on the dorsal surface of the ovarian cortex. The process of oogenesis comprised 10 consecutive phases according to the morphology of the yolk platelets, follicular cells and zona pellucida (ZP). Electron microscopy of vitellogenesis revealed some of the mitochondria gradually being transformed into yolk granules. In the advanced stage of vitellogenesis, large amounts of rough endoplasmic reticula, Golgiosomes and other cell organelles that are involved in synthesis and secretion were observed in follicular cells. The ZP was formed by microvilli, thus increasing the absorptive surface of the oocyte and facilitating transport of nutrients from the follicular epithelium to the ooplasm. This study demonstrated that the ovaries of members of the Testudinidae share more features with Archosaurs than with Squamates, indicating that these features were phylogenetically conserved in the Archosauria. The present observations suggest that the accumulation of yolk materials was controlled by the intrinsic and extrinsic pathways as well as by the activity of follicular cells. These results might also support a sibling relationship of the Testudinidae with the Archosauria and not with all extant reptiles.

Architecture of the blood-spleen barrier in the soft-shelled turtle, Pelodiseus sinensis.

We investigated the structure of the soft-shelled turtle, Pelodiseus sinensi, spleen and demonstrated that there were several microanatomical peculiarities by light and transmission electron microscopy. In the spleen, the white pulp of the spleen was composed of two compartments, the periarteriolar lymphatic sheath (PALS) and periellipsoidal lymphatic sheath (PELS). No lymph nodules and marginal zones were found. The spleen-blood barrier stood in the PELS and the ellipsoid. The high endothelial lining of penicilliform capillary contained small channels. These channels allowed circulating substances or lymphocytes to enter the ellipsoid. The distal portion of the penicilliform capillaries directly opened to pulp cords. The ellipsoid-associated cell (EAC) was located at the surface of the ellipsoid. Reticular fibers were mainly distributed in ellipsoid and the outer PELS. Both reticular cells and macrophages were distributed in the outer layers of PELS. S-100 protein positive dendritic cells were mainly distributed in out cells layer of the PELS and all over the PALS. Forty minutes after injection, carbon particles of Indian ink were mainly observed in the ellipsoid. Few carbon particles were observed in the outer PELS and fewer carbon particles in the red pulp. These findings suggested that a blood-spleen barrier indeed existed in the soft-turtle, P. sinensi, and it was a complex composed of an ellipsoid (including supporting cells, EAC, and reticular fibers) and the outer compartments of PELS (including dendritic cells, reticular fibers and cells, macrophages).

Ultrastructure of anterior uterus of the oviduct and the stored sperm in female soft-shelled turtle, Trionyx sinensis.

Ultrastructure of sperm storage in female soft-shelled turtle, Trionyx sinensis was examined under light and electron microscopes. Sperm storage tubules are restricted to the anterior of the uterus. These tubules developed either by folding or fusion of the oviductal mucosal folds and are lined by both ciliated and secretory cells. Ciliated cells are characterized by a few microvilli and prominent cilia in the apical membranes. A prominent feature of the secretory cell is the presence of secretory granules in the supranuclear region. The size, shape, and electron density of these granules vary markedly. The secretory product is released mainly by exocytosis into the oviductal lumen, where it appears as flocculent material. The unique structure in the base of the epithelium, the basal border of the cell -- the basal lamina -- and a blood vessel layer, is presumed to be a important barrier, by which the nourishment exchange and the microenvironment maintenance are ensured. The gland cell is presented with numerous, round, membrane-bound secretory granules of moderate to high electron densities. We divide these granules into three types according to their appearance: (1) membrane bounded granules with high-homogeneous electron density, (2) membrane bounded granules with moderate-homogeneous electron density, (3) membrane bounded, electron dense granules with concentric structures. These granules are presented as different stages of the secretions in the gland cell. The junction complexes are markedly distributed between cells, which are important in keeping stability and the microenvironment maintenance of the sperm storage tubules. Sperm stored in the tubules are heterogeneous in cytology. In addition to the mature sperm in the lumen, sperm with large chromatic granules are found, which are presumed to be immature sperm and are being in the process of nuclear condensation. Several spermatozoa in the tubules are exhibited with definitive indications of degeneration of the nuclei. The nuclear volume increases. The electron density of the central cores in mitochondria declines, combined with the deterioration of concentric membrane structure. Those changes are possibly due to the long time storage of the sperm in sperm storage tubules, and the leakage of reactive oxygen species is suggested to be a major cause. We conclude that the ultrastructure character of sperm storage in the oviduct of Trionyx sinensis is unique, in addition to having a basal function in secretion and the cilia swing, the tubules also provide an available microenvironment for the sperm to long time stored. The degenerative sperm in the tubules might be related to paternity-specific reproductive adaptations, and the sperm competition might occur during long time storage.