Investigating the effect of cell substrate on cancer cell stiffness by optical tweezers

The mechanical properties of cells are influenced by their microenvironment. Here we report cell stiffness alteration by changing the cell substrate stiffness for isolated cells and cells in contact with other cells. Polydimethylsiloxane (PDMS) is used to prepare soft substrates with three different stiffness values (173, 88 and 17 kPa respectively). Breast cancer cells lines, namely HBL-100, MCF-7 and MDA-MB-231 with different level of aggressiveness are cultured on these substrates and their local elasticity is investigated by vertical indentation of the cell membrane. Our preliminary results show an unforeseen behavior of the MDA-MB-231 cells. When cultured on glass substrate as isolated cells, they are less stiff than the other two types of cells, in agreement with the general statement that more aggressive and metastatic cells are softer. However, when connected to other cells the stiffness of MDA-MB-231 cells becomes similar to the other two cell lines. Moreover, the stiffness of MDA-MB-231 cells cultured on soft PDMS substrates is significantly higher than the stiffness of the other cell types, demonstrating thus the strong influence of the environmental conditions on the mechanical properties of the cells.     

Analysis of DNA adducts by accelerator mass spectrometry in human breast tissue after administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene

Epidemiological evidence has suggested an association between meat consumption and the risk of breast cancer. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, has been implicated in the aetiology of breast cancer and has been shown to induce tumour formation in rodent mammary glands. In addition, polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P) which has also been shown to induce tumour formation at a number of sites in rodents including the breast, are produced during the cooking of meat through the pyrolysis of fats. The aim of this study was to examine the bioavailability of these compounds to human breast tissue and their ability to bind to DNA to form DNA adducts. Patients undergoing breast surgery at York District Hospital were orally administered prior to surgery a capsule containing 20 μg of ¹⁴C PhIP (182 kBq, specific activity 2.05 GBq/mmol) or 5 μg of ¹⁴C B[a]P (36 kBq, specific activity 1.81 GBq/mmol). At surgery, normal and tumour breast tissue was resected and tissue concentrations of carcinogen measured by liquid scintillation counting and DNA adduct levels by accelerator mass spectrometry (AMS) were subsequently determined. It was found that both ¹⁴C PhIP and ¹⁴C B[a]P were able to reach the target organ where they had the ability to form DNA adducts. The level of adducts ranged from 26.22–477.35 and 6.61–208.38 adducts/10¹² nucleotides following administration of ¹⁴C PhIP and ¹⁴C B[a]P, respectively, with no significant difference observed between levels in normal or tumour tissue. In addition, the data obtained in this study were comparable to adduct levels previously found in colon samples following administration of the same compounds to individuals undergoing colorectal surgery. This is the first report that these two carcinogens bind to human breast DNA after administration of a defined low dose.     

Molar enamel thickness in European Miocene and extant hominoidea

Based on a roentgenographic analysis, the molar enamel of certain European Miocene dryopithecines is absolutely thick (r=1.03–1.30 mm in thickness); the molar enamel of certain European pliopithecines is thin (r=0.32–0.82 mm thick). The rank order for enamel thickness in extant hominoids (from thickest to thinnest) is confirmed to beHomo, Pongo, Gorilla, Pan, andHylobates. There is a great deal of enamel thickness variability within the great ape sample. Extant analogues suggest that dryopithecines were probably adapted to a frugivorous/gramnivorous dietary regimen, while pliopithecines were probably better suited to folivory.     

乳腺癌p53蛋白过度表达和雌激素受体免疫组化检测及意义

应用免疫组化方法,对３２例乳腺癌组织中肿瘤抑制基因ｐ５３蛋白的表达和雌激素受体的状态分别进行了检测。结果３２例中ｐ５３蛋白阳性１８例,阳性率５６．３％,１８例伴有同侧腋下淋巴结转移者阳性１３例（７２．２％）３而１４例无转移者阳性５例（３５．７％）二组阳性率差异显著（ＰＭＯ．０５）。３２例中雌激素受体阳性１７例,１８例伴转移者阳性８例（４４．４％）;１４例无转移者阳性９例（６４．３％）。结果表明,ｐ５３蛋白的异常表达与乳腺癌的浸润转移有关,结合雌激素受体的检查,可作为临床预后判断一个有价值的标志。     

Mass transfer limitation of sulfate in methanogenic aggregates

The role of mass transfer limitation of sulfate as a factor governing the competition between sulfate reducing and methane producing bacteria in methanogenic aggregates was theoretically evaluated by the calculation of steady-state sulfate microprofiles using a reference set of parameters obtained from the literature. The shooting method was used as a numerical technique for solving the mathematical model. The effect of the parameters on mass transport limitation was tested by varying each reference value of the parameters with a factor of 3. Sulfate limitation within granules prevailed at moderate (0.1 kg m(-3)) and low sulfate concentrations in the bulk liquid, at high maximum sulfate utilization rates (3.73 x 10(-5) kg SO(4) (2-) kg(-1) VSS S(-1) or biomass concentrations (40 KG VSS m(-3)), and in large aggregates (radius of 7.5 10(-4) m). The effective diffusion coefficient of sulfate and the affinity constant were less determinative for the penetration depth of sulfate within a granule. (c) 1994 John Wiley & Sons, Inc.     

Early response of herbaceous vegetation to Rhododendron ponticum subsp. baeticum invasion in European Atlantic forests

Questions

Rhododendron ponticum subsp. baeticum is an invasive shrub of growing concern in continental Europe, but little is known about its impact on native plant communities. Here we ask: do environmental conditions differ between forest stands invaded by it and uninvaded stands? Do these differences correlate with R. ponticum's cover? Are these differences associated with differences in taxonomic and functional diversity of vascular plant species of the herb layer? Can these vegetation changes be explained by the sorting of certain life-history traits by R. ponticum-induced environmental changes?

Location

Several forests invaded by R. ponticum in the French Atlantic domain.

Methods

We recorded vegetation composition and a number of environmental variables in 400-m² plots that were established in 64 paired forest stands (32 invaded vs 32 uninvaded). We compiled traits from existing databases. We computed several metrics of taxonomic and functional diversity. We compared environmental variables and diversity metrics between invaded and uninvaded stands. We used correlation and regression analyses to relate them with R. ponticum's cover. We ran RLQ and fourth-corner analyses to explore the relationships between R. ponticum invasion, environmental variables, species traits, and vegetation composition.

Results

Independent of its abundance, R. ponticum invasion was associated with lower light arrival at the forest floor and increased litter thickness. Concomitantly, species richness and diversity and trait diversity were reduced. The major driver of species assemblages was soil pH, which strongly interacted with the invasion gradient. R. ponticum did not sort species according to traits associated with shade tolerance and thick-litter tolerance. However, tree and shrub saplings were more abundant in invaded than uninvaded stands, at the expense of graminoid and fern species.

Conclusions

As R. ponticum becomes the dominant shrub, it exerts new selection forces on life-history traits of extant species, mostly via reduced light availability, increased litter thickness, and physical competition, thereby reducing taxonomic and functional diversity of the herb layer, without impeding tree and shrub self-regeneration, at least in the short term.     

ING1 inhibits Twist1 expression to block EMT and is antagonized by the HDAC inhibitor vorinostat

ING1 is a chromatin targeting subunit of the Sin3a histone deacetylase (HDAC) complex that alters chromatin structure to subsequently regulate gene expression. We find that ING1 knockdown increases expression of Twist1, Zeb 1&2, Snai1, Bmi1 and TSHZ1 drivers of EMT, promoting EMT and cell motility. ING1 expression had the opposite effect, promoting epithelial cell morphology and inhibiting basal and TGF-β-induced motility in 3D organoid cultures. ING1 binds the Twist1 promoter and Twist1 was largely responsible for the ability of ING1 to reduce cell migration. Consistent with ING1 inhibiting Twist1 expression in vivo, an inverse relationship between ING1 and Twist1 levels was seen in breast cancer samples from The Cancer Genome Atlas (TCGA). The HDAC inhibitor vorinostat is approved for treatment of multiple myeloma and cutaneous T cell lymphoma and is in clinical trials for solid tumours as adjuvant therapy. One molecular target of vorinostat is INhibitor of Growth 2 (ING2), that together with ING1 serve as targeting subunits of the Sin3a HDAC complex. Treatment with sublethal (LD25-LD50) levels of vorinostat promoted breast cancer cell migration several-fold, which increased further upon ING1 knockout. These observations indicate that correct targeting of the Sin3a HDAC complex, and HDAC activity in general decreases luminal and basal breast cancer cell motility, suggesting that use of HDAC inhibitors as adjuvant therapies in breast cancers that are prone to metastasize may not be optimal and requires further investigation.     

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study

BackgroundBreast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality.MethodsWe performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses.ResultsWe identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44–0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant.ConclusionOur results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.     

人乳腺癌cAMP结合蛋白

建立了测定人乳腺癌胞浆ｃＡＭＰ结合蛋白（ｃＡＭＰｂ．ｐ．）方法。综合研究了其温度、保温时间、配体浓度、稳定性等条件。ｃＡＭＰｂ．ｐ．的Ｋ_Ｄ值为２．９０×１０~（－８）ｍｏｌ／Ｌ．并测定了６０例雌激素受体（ＥＲ）Ｆｕ性乳腺癌标本的ｃＡＭＰｂ．ｐ．含量。此组病人术后均接受系统的内分泌治疗,ＥＲ／ｃＡＭＰｂｐ,比值范围为７．７～３６２×１０~（－３）,ＥＲ／ｃＡＭＰｂ．ｐ．比值≥４０×１０~（－３）的五年生存率明显高于比值＜４０×１０~（－３）组,（ｐ＜０．００５）．表明测定ＥＲ／ｃＡＭＰｂ．ｐ．比值对预测患者内分泌治疗疗效,优于单独测定ＥＲ．