Locality hypothesis and the speed of light

The locality hypothesis is generally considered necessary for the study of the kinematics of non-inertial systems in special relativity. In this paper we discuss this hypothesis, showing the necessity of an improvement, in order to get a more clear understanding of the various concepts involved, like coordinate velocity and standard velocity of light. Concrete examples are shown, where these concepts are discussed.Comment: 23 page

The relativistic Sagnac Effect: two derivations

The phase shift due to the Sagnac Effect, for relativistic matter and electromagnetic beams, counter-propagating in a rotating interferometer, is deduced using two different approaches. From one hand, we show that the relativistic law of velocity addition leads to the well known Sagnac time difference, which is the same independently of the physical nature of the interfering beams, evidencing in this way the universality of the effect. Another derivation is based on a formal analogy with the phase shift induced by the magnetic potential for charged particles travelling in a region where a constant vector potential is present: this is the so called Aharonov-Bohm effect. Both derivations are carried out in a fully relativistic context, using a suitable 1+3 splitting that allows us to recognize and define the space where electromagnetic and matter waves propagate: this is an extended 3-space, which we call "relative space". It is recognized as the only space having an actual physical meaning from an operational point of view, and it is identified as the 'physical space of the rotating platform': the geometry of this space turns out to be non Euclidean, according to Einstein's early intuition.Comment: 49 pages, LaTeX, 3 EPS figures. Revised (final) version, minor corrections; to appear in "Relativity in Rotating Frames", ed. G. Rizzi and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht, (2003). See also http://digilander.libero.it/solciclo

An early peak of relapse after surgery for breast cancer

There is great interest among oncologists concerning what we might learn by examining the pattern of relapse after breast cancer surgery. What you see depends upon how hard you look. Up to now, investigators have examined the hazard ratio for relapse every 6–12 months. In a research paper, published in this issue of Breast Cancer Research, the Milan group have looked at the hazard ratio every three months and have found, for the first time, a distinct, very early peak of relapse in a group of premenopausal, node-positive patients not given chemotherapy or hormone therapy. What is now needed is for other groups to repeat this observation and, if found, to examine the characteristics of the tumours producing this phenomenon in order to develop hypotheses about its cause and possible treatments

Environmental Impact on Vascular Development Predicted by High-Throughput Screening

Background: Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease

A Novel Monoclonal Antibody to Secreted Frizzled-Related Protein 2 Inhibits Tumor Growth

Secreted frizzled related protein 2 (SFRP2) is overexpressed in human angiosarcoma and breast cancer, and stimulates angiogenesis via activation of the calcineurin/ NFATc3 pathway. There are conflicting reports in the literature as to whether SFRP2 is an antagonist or agonist of ß-catenin. The aims of these studies were to assess the effects of SFRP2 antagonism on tumor growth and Wnt-signaling, and to evaluate whether SFRP2 is a viable therapeutic target. The anti-angiogenic and anti-tumor properties of SFRP2 monoclonal antibody (mAb) were assessed using in vitro proliferation, migration, and tube formation assays; and in vivo angiosarcoma and triple negative breast cancer models. Wnt-signaling was assessed in endothelial and tumor cells treated with SFRP2 mAb using Western blotting. Pharmacokinetic (PK) and biodistribution data were generated in tumor-bearing and non-tumor bearing mice. SFRP2 mAb was shown to induce anti-tumor and anti-angiogenic effects in vitro, and inhibit activation of ß-catenin and NFATc3 in endothelial and tumor cells. Treatment of SVR angiosarcoma allografts in nude mice with the SFRP2 mAb decreased tumor volume by 58% compared to control (p=0.004). Treatment of MDA-MB-231 breast carcinoma xenografts with SFRP2 mAb decreased tumor volume by 52% (p=0.03) compared to control, while bevacizumab did not significantly reduce tumor volume. Pharmacokinetic studies show the antibody is long circulating in the blood and preferentially accumulates in SFRP2-positive tumors. In conclusion, antagonizing SFRP2 inhibits activation of ß-catenin and NFATc3 in endothelial and tumor cells, and is a novel therapeutic approach to inhibiting angiosarcoma and triple negative breast cancer

Internal mammary lymph node recurrence: rare but characteristic metastasis site in breast cancer

<p>Abstract</p> <p>Background</p> <p>To assess the frequency of IMLN recurrence, its associated risk factors with disease-free interval (DFI) and its predicting factors on overall survival time.</p> <p>Methods</p> <p>133 cases of breast cancer IMLN recurrence were identified via the computerized CT reporting system between February 2003 and June 2008, during which chest CT for patients with breast cancer (n = 8867) were performed consecutively at Cancer Hospital, Fudan University, Shanghai, China. Patients' charts were retrieved and patients' characteristics, disease characteristics, and treatments after recurrence were collected for analysis. The frequency was 1.5% (133/8867).</p> <p>Results</p> <p>IMLN recurrence was presented as the first metastatic site in 121 (91%) patients while 88 (66.2%) had other concurrent metastases. Typical chest CT images included swelling of the IMLN at the ipsilateral side with local lump and sternal erosion located mostly between the second and third intercostal space. The median disease-free interval (DFI) of IMLN recurrence was 38 months. The independent factors that could delay the IMLN recurrence were small tumor size (HR 0.5 95%CI: 0.4 - 0.8; <it>p </it>= 0.002), and positive ER/PR disease (HR 0.6, 95% CI: 0.4 - 0.9; <it>p </it>= 0.006). The median survival time after IMLN recurrence was 42 months, with a 5-year survival rate of 30%. Univariate analysis showed four variables significantly influenced the survival time: DFI of IMLN recurrence (p = 0.001), no concurrent distant metastasis (p = 0.024), endocrine therapy for patients with positive ER/PR (p = 0.000), radiotherapy (p = 0.040). The independent factors that reduced the death risk were no concurrent distant metastases (HR: 0.7, 95% CI: 0.4 - 0.9; <it>p </it>= 0.031), endocrine therapy for patients with positive ER/PR status (HR: 0.2, 95% CI: 0.1 - 0.5; <it>p </it>= 0.001) and palliative radiotherapy (HR: 0.3, 95% CI: 0.1- 0.9; <it>p </it>= 0.026).</p> <p>Conclusions</p> <p>The risk of IMLN recurrence is low and there are certain characteristics features on CT images. ER/PR status is both a risk factor for DFI of IMLN recurrence and a prognostic factor for overall survival after IMLN recurrence. Patients with only IMLN recurrence and/or local lesion have a good prognosis.</p

The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers

Therapies for hormone-independent prostate and breast cancer are limited, with the effectiveness of the taxanes compromised by toxicity, lack of oral bioavailability and drug resistance. This study aims to identify and characterise new microtubule disruptors, which may have improved efficacy relative to the taxanes in hormone-independent cancer. 2-Methoxy-3-O-sulphamoyl-17β-cyanomethyl-oestra-1,3,5(10)-triene (STX641), 2-methoxy-3-hydroxy-17β-cyanomethyl-oestra-1,3,5(10)-triene (STX640) and 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140) were all potent inhibitors of cell proliferation in a panel of prostate and breast cancer cell lines. STX641 and STX640 significantly inhibited tumour growth in the MDA-MB-231 xenograft model. STX641 inhibited both in vitro and in vivo angiogenesis. Despite good in vivo activity, STX641 was not as potent in vivo as STX140. Therefore, STX140 was evaluated in the prostate hormone-independent PC-3 xenograft model. STX140 had superior efficacy to docetaxel, 2-MeOE2 and bevacizumab. In contrast to vinorelbine, no significant toxicity was observed. Furthermore, STX140 could be dosed daily over a 60-day period leading to tumour regression and complete responses, which were maintained after the cessation of dosing. This study demonstrates that STX641 and STX140 have considerable potential for the treatment of hormone-independent breast and prostate cancer. In contrast to the taxanes, STX140 can be dosed orally, with no toxicity being observed even after prolonged daily dosing

Quantification of tumour vasculature and hypoxia by immunohistochemical staining and HbO2 saturation measurements

Despite the possibility that tumour hypoxia may limit radiotherapeutic response, the underlying mechanisms remain poorly understood. A new methodology has been developed in which information from several sophisticated techniques is combined and analysed at a microregional level. First, tumour oxygen availability is spatially defined by measuring intravascular blood oxygen saturations (HbO2) cryospectrophotometrically in frozen tumour blocks. Second, hypoxic development is quantified in adjacent sections using immunohistochemical detection of a fluorescently conjugated monoclonal antibody (ELK3-51) to a nitroheterocyclic hypoxia marker (EF5), thereby providing information relating to both the oxygen consumption rates and the effective oxygen diffusion distances. Third, a combination of fluorescent (Hoechst 33342 or DiOC7(3)) and immunohistological (PECAM-1/CD31) stains is used to define the anatomical vascular densities and the fraction of blood vessels containing flow. Using a computer-interfaced microscope stage, image analysis software and a 3-CCD colour video camera, multiple images are digitized, combined to form a photo-montage and revisited after each of the three staining protocols. By applying image registration techniques, the spatial distribution of HbO2 saturations is matched to corresponding hypoxic marker intensities in adjacent sections. This permits vascular configuration to be related to oxygen availability and allows the hypoxic marker intensities to be quantitated in situ. © 1999 Cancer Research Campaig