Intradural Metastasis from Cutaneous Squamous Cell Carcinoma Causing Cauda Equina Syndrome

BACKGROUND: Spinal leptomeningeal carcinomatosis from a cutaneous squamous cell carcinoma (SCC) origin is exceedingly rare. Herein, we describe the first report of cauda equina syndrome secondary to drop metastases from a skin SCC. CASE DESCRIPTION: A 69-year-old male with a history of recurrent SCC of the face with known cranial nerve involvement presented with acute onset sphincter and lower extremity symptoms. Neuroimaging revealed a compressive intradural mass at the lumbosacral junction. The patient underwent urgent surgical decompression followed by adjuvant fractionated radiotherapy. Substantial improvement in function and quality of life was reported on postoperative follow-up. CONCLUSION: Cauda equina syndrome manifestations in a patient with a history of cutaneous SCC with perineural spread should raise suspicion for drop metastases. In this case, a relatively straight forward surgical procedure resulted in significant improvement in the quality of life. Therefore, operative intervention should be considered to prevent permanent neurological deficits depending on the patient’s goals of care and overall clinical status

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg−1 total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (>35 ng hK6 mg−1 total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg−1 total protein) was higher in late stage disease, serous histotype, residual tumour >1 cm and suboptimal debulking (>1 cm) (P<0.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis

Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status

Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue kallikrein family of serine proteases, for which a prognostic and diagnostic value in breast cancer has been suggested. To further characterise the value of KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR (n=39), and on the protein level (n=127) using a KLK14-specific antibody for immunohistochemistry. We correlated KLK14 protein expression data with available clinico-pathological parameters (mean follow-up time was 55 months) including patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P=0.027), an issue that had not been clarified recently. Concordantly with the RNA data, cytoplasmic KLK14 protein expression was significantly higher in invasive breast carcinomas compared to normal breast tissues (P=0.003). Furthermore, KLK14 protein expression was associated with higher tumour grade (P=0.041) and positive nodal status (P=0.045) but was not significantly associated with shortened disease-free or overall patient survival time in univariate analyses. We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable

Expression of a prostate-associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions

The recent demonstration of human glandular kallikrein (hK2) expression in a breast carcinoma cell line has suggested that this putatively prostate-restricted, steroid hormone-regulated protease may also be expressed in breast epithelium in vivo and secreted into the mammary duct system. Given that the only substrate yet identified for hK2 activity is the precursor of prostate-specific antigen (PSA), the expression of which in breast carcinomas may be associated with favourable prognosis, our purpose was to examine the expression pattern of both hK2 and PSA in breast tumour tissues. Cytosolic extracts of 336 primary breast carcinomas prepared for routine oestrogen receptor (ER) and progesterone receptor (PR) analysis, as well as 31 nipple aspirates from six women with non-diseased mammary glands, were assayed for hK2 and PSA using immunofluorometric assays developed by the authors. In the tumour extracts, measurable hK2 and PSA concentrations were detected in 53% and 73% of cases respectively, and were positively correlated to each other (r = 0.59, P = 0.0001). Higher concentrations of PSA and hK2 were found in tumours expressing steroid hormone receptors (P = 0.0001 for PSA and P = 0.0001 for hK2, by Wilcoxon tests for both ER and PR), and both PSA (r = 0.25, P = 0.0001) and hK2 (r = 0.22, P = 0.0001) correlated directly with PR levels. A negative correlation between patient age and PSA (r = –0.12, P = 0.03) was also found. Both proteins were present in nipple aspirate fluid at relatively high concentrations which were positively correlated (r = 0.53, P = 0.002). The molecular weights of the immunoreactive species quantified by the hK2 and PSA assays were established by high-performance liquid chromatography (HPLC) and were consistent with the known molecular weights of hK2 and PSA. Together these data provide the first evidence, to our knowledge, that both malignant breast tissue and normal breast secretion contain measurable quantities of hK2, and that the degree of hK2 expression or secretion is directly proportional to the expression of PSA and steroid hormone receptors. hK2 expression may therefore be a marker of steroid hormone action in breast tissue. © 2000 Cancer Research Campaig

Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination

p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan–Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(–)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(–) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. © 1999 Cancer Research Campaig

On CPT Symmetry: Cosmological, Quantum-Gravitational and other possible violations and their phenomenology

I discuss various ways in which CPT symmetry may be violated, and their phenomenology in current or immediate future experimental facilities, both terrestrial and astrophysical. Specifically, I discuss first violations of CPT symmetry due to the impossibility of defining a scattering matrix as a consequence of the existence of microscopic or macroscopic space-time boundaries, such as Planck-scale Black-Hole (event) horizons, or cosmological horizons due to the presence of a (positive) cosmological constant in the Universe. Second, I discuss CPT violation due to breaking of Lorentz symmetry, which may characterize certain approaches to quantum gravity, and third, I describe models of CPT non invariance due to violations of locality of interactions. In each of the above categories I discuss experimental sensitivities. I argue that the majority of Lorentz-violating cases of CPT breaking, with minimal (linear) suppression by the Planck-mass scale, are already excluded by current experimental tests. There are however some (stringy) models which can evade these constraints.Comment: 27 pages latex, Conference talk Beyond the Desert 200

Cosmological Dynamics of Phantom Field

We study the general features of the dynamics of the phantom field in the cosmological context. In the case of inverse coshyperbolic potential, we demonstrate that the phantom field can successfully drive the observed current accelerated expansion of the universe with the equation of state parameter $w_{\phi} < -1$. The de-Sitter universe turns out to be the late time attractor of the model. The main features of the dynamics are independent of the initial conditions and the parameters of the model. The model fits the supernova data very well, allowing for $-2.4 < w_{\phi} < -1$ at 95 % confidence level.Comment: Typos corrected. Some clarifications and references added. To appear in Physical Review

Lanthanide-based time-resolved luminescence immunoassays

The sensitive and specific detection of analytes such as proteins in biological samples is critical for a variety of applications, for example disease diagnosis. In immunoassays a signal in response to the concentration of analyte present is generated by use of antibodies labeled with radioisotopes, luminophores, or enzymes. All immunoassays suffer to some extent from the problem of the background signal observed in the absence of analyte, which limits the sensitivity and dynamic range that can be achieved. This is especially the case for homogeneous immunoassays and surface measurements on tissue sections and membranes, which typically have a high background because of sample autofluorescence. One way of minimizing background in immunoassays involves the use of lanthanide chelate labels. Luminescent lanthanide complexes have exceedingly long-lived luminescence in comparison with conventional fluorophores, enabling the short-lived background interferences to be removed via time-gated acquisition and delivering greater assay sensitivity and a broader dynamic range. This review highlights the potential of using lanthanide luminescence to design sensitive and specific immunoassays. Techniques for labeling biomolecules with lanthanide chelate tags are discussed, with aspects of chelate design. Microtitre plate-based heterogeneous and homogeneous assays are reviewed and compared in terms of sensitivity, dynamic range, and convenience. The great potential of surface-based time-resolved imaging techniques for biomolecules on gels, membranes, and tissue sections using lanthanide tracers in proteomics applications is also emphasized

Phase Structure of lattice SU(2)xU_S(1) three-dimensional Gauge Theory

We discuss a phase diagram for a relativistic SU(2) x U_{S}(1) lattice gauge theory, with emphasis on the formation of a parity-invariant chiral condensate, in the case when the $U_{S}(1)$ field is infinitely coupled, and the SU(2) field is moved away from infinite coupling by means of a strong-coupling expansion. We provide analytical arguments on the existence of (and partially derive) a critical line in coupling space, separating the phase of broken SU(2) symmetry from that where the symmetry is unbroken. We review uncoventional (Kosterlitz-Thouless type) superconducting properties of the model, upon coupling it to external electromagnetic potentials. We discuss the r\^ole of instantons of the unbroken subgroup U(1) of SU(2), in eventually destroying superconductivity under certain circumstances. The model may have applications to the theory of high-temperature superconductivity. In particular, we argue that in the regime of the couplings leading to the broken SU(2) phase, the model may provide an explanation on the appearance of a pseudo-gap phase, lying between the antiferromagnetic and the superconducting phases. In such a phase, a fermion mass gap appears in the theory, but there is no phase coherence, due to the Kosterlitz-Thouless mode of symmetry breaking. The absence of superconductivity in this phase is attributed to non-perturbative effects (instantons) of the subgroup U(1) of SU(2).Comment: 51 pages latex, 10 figures incorporate