Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model

One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential

Prognostic significance of MIB1-determined proliferative activities in intraductal components and invasive foci associated with invasive ductal breast carcinoma

The prognostic significance of the proliferative activities in intraductal components and invasive foci was investigated using 157 cases of invasive ductal breast carcinoma in which intraductal components predominated. Proliferative activity was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in the most active areas of intraductal components (MLI-DCIS) or invasive foci (MLI-INV). MLI-DCIS correlated closely with MLI-INV (r = 0.710, 95% confidence interval, 0.623–0.780; P< 0.0001). Both MLI-DCIS and MLI-INV were related to oestrogen receptor (ER) (P = 0.0006, P = 0.0028 respectively), grade of invasive tumour (P< 0.0001, P< 0.0001 respectively) and classification of intraductal components (P< 0.0001, P< 0.0001 respectively). In theunivariate disease-free survival analysis, both MLI-DCIS and MLI-INV were found to be significant (P< 0.0001, P = 0.0003 respectively). However, in node-negative cases, only MLI-DCIS was significant (P = 0.0416). Multivariate analysis revealed that MLI-DCIS was significant not only in all cases, but also in node-negative cases (P = 0.0223,P = 0.0426 respectively), whereas MLI-INV was not. These findings indicate that MIB1-determined proliferative activity of intraductal components is a significant prognostic determinant of invasive ductal breast carcinoma in which intraductal components predominate. © 1999 Cancer Research Campaig

Social entrepreneurs in challenging places: A Delphi study of experiences and perspectives

Social Enterprises have grown in number and scope in response to reductions in state-provided welfare and increasing ambition to improve social conditions. While a range of issues have been identified in the literature as affecting the ability of Social Enterprises to successfully conduct their activities, there is currently a dearth of research into the relative influence of these factors. This study explores and ranks the challenges faced by social entrepreneurs in South Wales. Based on a Delphi study with 21 social entrepreneurs, government policy-developers and scholars, it presents a hierarchy of 14 factors, useful instruments for informing social entrepreneurs and policy-makers about the way social enterprises are managed, and how national and local policy should be developed. As part of this, the study also identifies four novel factors that affect the sustainability of social enterprises: ‘Professionalisation of Marketing’, ‘Perception of Validity’, ‘Leadership’ and ‘Situatedness’

Measuring proliferation in breast cancer: practicalities and applications

Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy

Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer

Relativistic Binaries in Globular Clusters

Galactic globular clusters are old, dense star systems typically containing 10\super{4}--10\super{7} stars. As an old population of stars, globular clusters contain many collapsed and degenerate objects. As a dense population of stars, globular clusters are the scene of many interesting close dynamical interactions between stars. These dynamical interactions can alter the evolution of individual stars and can produce tight binary systems containing one or two compact objects. In this review, we discuss theoretical models of globular cluster evolution and binary evolution, techniques for simulating this evolution that leads to relativistic binaries, and current and possible future observational evidence for this population. Our discussion of globular cluster evolution will focus on the processes that boost the production of hard binary systems and the subsequent interaction of these binaries that can alter the properties of both bodies and can lead to exotic objects. Direct {\it N}-body integrations and Fokker--Planck simulations of the evolution of globular clusters that incorporate tidal interactions and lead to predictions of relativistic binary populations are also discussed. We discuss the current observational evidence for cataclysmic variables, millisecond pulsars, and low-mass X-ray binaries as well as possible future detection of relativistic binaries with gravitational radiation.Comment: 88 pages, 13 figures. Submitted update of Living Reviews articl

Measurement of the cross section for e+e−→Ξ−Ξˉ+e^{+}e^{-}\rightarrow\Xi^{-}\bar\Xi^{+} and observation of an excited Ξ\Xi baryon

Using a total of 11.0 fb$^{-1}$ of $e^{+}e^{-}$ collision data with center-of-mass energies between 4.009 GeV and 4.6 GeV and collected with the BESIII detector at BEPCII, we measure fifteen exclusive cross sections and effective form factors for the process $e^{+}e^{-}\rightarrow\Xi^{-}\bar\Xi^{+}$ by means of a single baryon-tag method. After performing a fit to the dressed cross section of $e^{+}e^{-}\rightarrow\Xi^{-}\bar\Xi^{+}$, no significant $\psi(4230)$ or $\psi(4260)$ resonance is observed in the $\Xi^{-}\bar\Xi^{+}$ final states, and upper limits at the 90\% confidence level on $\Gamma_{ee}\mathcal{B}$ for the processes $\psi(4230)$/$\psi(4260)\rightarrow\Xi^{-}\bar\Xi^{+}$ are determined. In addition, an excited $\Xi$ baryon at 1820 MeV/$c^{2}$ is observed with a statistical significance of 6.2 $\sim$ 6.5$\sigma$ by including the systematic uncertainty, and the mass and width are measured to be $M = (1825.5 \pm 4.7 \pm 4.7)$~MeV/$c^{2}$ and $\Gamma = (17.0 \pm 15.0 \pm 7.9)$~MeV, which confirms the existence of the $J^{P}=\frac{3}{2}^{-}$ state $\Xi(1820)$.Comment: 8 pages, 4 figures, 1 Supplemental Material with 2 pages, consistent with paper published in Phys. Rev. Lett. 124, 032002 (2020