Lise Christensen

The urokinase‐type plasminogen activator system in cancer metastasis: A review

The urokinase‐type plasminogen activator (u‐PA) system consists of the serine proteinases plasmin and u‐PA; the serpin inhibitors α2‐anti‐plasmin, PAI‐1 and PAI‐2; and the u‐PA receptor (u‐PAR). Two lines of evidence have strongly suggested an important and apparently causal role for the u‐PA system in cancer metastasis: results from experimental model systems with animal tumor metastasis and the finding that high levels of u‐PA, PAI‐1 and u‐PAR in many tumor types predict poor patient prognosis. We discuss here recent observations related to the molecular and cellular mechanisms underlying this role of the u‐PA system. Many findings suggest that the system does not support tumor metastasis by the unrestricted enzyme activity of u‐PA and plasmin. Rather, pericellular molecular and functional interactions between u‐PA, u‐PAR, PAI‐1, extracellular matrix proteins, integrins, endocytosis receptors and growth factors appear to allow temporal and spatial re‐organizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. Differential expression of components of the system by cancer and non‐cancer cells, regulated by paracrine mechanisms, appear to determine the involvement of the system in cancer cell–directed tissue remodeling. A detailed knowledge of these processes is necessary for utilization of the therapeutic potential of interfering with the action of the system in cancers. Int. J. Cancer 72:1–22, 1997.

Adverse Reactions to Injectable Soft Tissue Permanent Fillers

BackgroundSynthetic injectable facial fillers with a permanent effect are widely atoxic and nonimmunogenic, but they differ with respect to composition and in chemical and biologic characteristics. Yet, they all act as foreign bodies in the tissues eliciting a host response that try to remove the gel. Inflammatory nodules may develop at the sites of injection-for some fillers, many years later, for others, not. Why is that?MethodsBiopsies were contributed by various plastic surgeons from Europe and Australia after requests were made at international congresses and workshops. The study was based on (a) 5 biopsies from unreactive tissue obtained at different times after injection of polyacrylamide hydrogel (Aquamid); (b) 28 biopsies from intermediate or late inflammatory nodules after injection of polyacrylamide hydrogel (Aquamid) (20 cases), a hyaluronic acid-polyhydroxyethylmethacrylate/ethylmethacrylate gel (Dermalive) (2 cases), and a gel consisting of polylactic acid in mannitol/carbomethoxycellulose (New-Fill) (6 cases); and (c) a review of the literature on adverse reactions after injection with permanent fillers.ResultsClinically unreactive tissues after injection with Aquamid showed modest or no host reaction. Inflammatory nodules showed an increased foreign body reaction and a bacterial infection after injection with Aquamid, and a combination of moderate foreign body reaction, fibrosis, and in some cases also bacterial infection after injection with Dermalive and New-Fill. According to the literature, inflammatory nodules occur no later than 1 year after injection with polyacrylamide hydrogel, but up to 6 years after injection of combination gels (Artecol), and up to 28 years after injection of silicone gel.ConclusionsInflammatory nodules are likely to be caused by a low-grade infection maintained within a biogfilm surrounding the hydrophobic silicone gel and the combination gels. Aquamid gel may prevent formation of a biofilm through its high water-binding capacity, explaining why late inflammatory nodules are not seen after injection of this polyacrylamide hydrogel product.

Long-term effects of polyacrylamide hydrogel on human breast tissue.

&NA; Polyacrylamide hydrogel is an atoxic, stable, nonresorbable sterile watery gel consisting of approximately 2.5% cross‐linked polyacrylamide and nonpyrogenic water. Polyacrylamide hydrogel is widely used in ophthalmic operations, drug treatment, food packaging products, and water purification. In the former Soviet Union, polyacrylamide hydrogel has been used in plastic and aesthetic surgery for more than 10 years, and Kiev City Hospital treats approximately 300 women a year for breast augmentation using the polyacrylamide hydrogel Interfall (Contura SA, Montreux, Switzerland). Capsule shrinkage following these injections has never been observed. The authors examined breast tissue samples from a total of 27 women who had polyacrylamide hydrogel injected at Kiev City Hospital up to 8 years and 10 months earlier. Age at operation, duration of polyacrylamide hydrogel implantation, history of possible side effects to the gel injection, other intercurrent diseases, the reason for present open breast operation, and breast palpation findings before operation were in each case compared with the histological findings on samples taken from breast tissue bordering the gel. The gel presented itself as a dark violet, homogenous mass with a rounded or ragged outline in large or medium‐size deposits and as elongated strands, which mimicked the extracellular matrix, in small deposits. Histological findings of the breast tissue bordering the gel showed three different patterns: large collections of gel gave rise to a thick, soft‐looking cellular membrane of macrophages and foreign‐body giant cells; medium‐size deposits were surrounded by just a thin layer of macrophages; and small deposits were not associated with any reaction in the surrounding tissue. Projections of the cellular soft membrane, known as granulomas, were seen in six patients. The granulomas were composed of macrophages, foreign‐body giant cells, lymphocytes, and blood cells. A thin layer of fibrous connective tissue was occasionally present around the foreign‐body membrane, but the thick fibrous capsule, which has been described in connection with silicone implants, was completely absent. The gel changes could be correlated to neither time since gel injection nor a history of recent injury or inflammation. It is concluded that the polyacrylamide hydrogel Interfall, which has been used in the former Soviet Union, is stable over time, nondegradable, confined to the breast, and diffusion and migration resistant. When the hydrogel is injected in medium‐size or large quantities a cellular foreign‐body reaction occurs, but in small amounts it is capable of splitting up individual connective tissue fibers and fat cells, substituting for the extracellular connective tissue matrix without eliciting any foreign‐body reaction. As far as these data are concerned, polyacrylamide hydrogel is well tolerated by the breast and does not give rise to severe fibrosis, pain, or capsule shrinkage. However, to determine safety with more certainty, a larger sample size would be necessary. (Plast. Reconstr. Surg. 111: 1883, 2003.)

Spectroscopy of superluminous supernova host galaxies: A preference of hydrogen-poor events for extreme emission line galaxies

Superluminous supernovae (SLSNe) were only discovered recently due to their preference for occurring in faint dwarf galaxies. Understanding why stellar evolution yields dierent types of stellar explosions in these environments is fundamental in order to both uncover the elusive progenitors of SLSNe and to study star formation in dwarf galaxies. In this paper, we present the rst results of our project to study SUperluminous Supernova Host galaxIES (SUSHIES), focusing on the sample for which we have obtained spectroscopy. We show that SLSNe-I and SLSNe-R (hydrogen-poor) often ( 50% in our sample) occur in a class of galaxies that is known as Extreme Emission Line Galaxies (EELGs). The probability of this happening by chance is negligible and we therefore conclude that the extreme environmental conditions and the SLSN phenomenon are related. In contrast, SLSNe-II (hydrogen-rich) occur in more massive, more metal-rich galaxies with softer radiation elds. Therefore, if SLSNe-II constitute a uniform class, their progenitor systems must be dierent from those of H-poor SLSNe. Gamma-ray bursts (GRBs) are, on average, not found in as extreme environments as H-poor SLSNe. We propose that H-poor SLSNe result from the very rst stars exploding in a starburst, even earlier than GRBs. This might indicate a bottom-light initial mass function in these systems. SLSNe present a novel method of selecting candidate EELGs independent of their luminosity.

Histologic changes and silicone concentrations in human breast tissue surrounding silicone breast prostheses.

Using a previously developed method for quantitative measurements of silicone concentrations in breast tissue, material from 86 biopsies from 67 breasts in 55 patients who had silicone implants was examined. In the 49 breasts with unruptured prostheses, there was a positive relation between the concentrations and inflammatory reactions, the only exception being the amount of plasma cells, which showed a negative relation. It is concluded that silicone prostheses provoke an inflammatory response not only because they act as foreign bodies, but also because of silicone seepage through intact membranes.

Different Risk Factor Profiles for Mucinous and Nonmucinous Ovarian Cancer: Results from the Danish MALOVA Study

Objectives: The aim of the study was to examine the overall risk factors for epithelial ovarian cancer and according to histologic subtypes. Materials and Methods: Ovarian cancer cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. A total of 554 cases and 1,564 randomly selected controls were included. The analyses were done using multiple logistic regression models. Results: The overall risk of ovarian cancer decreased with ever being pregnant [odds ratios (OR), 0.40; 95% confidence intervals (CI), 0.30-0.55], with increasing pregnancies (OR, 0.63; 95% CI, 0.45-0.87 and OR, 0.51; 95% CI, 0.37-0.69 for two and three pregnancies as compared with one), and with older age at first and last pregnancy, respectively. Increasing years of ovulation was a very strong risk factor with a 7% to 8% increase in risk for each year of ovulation. Use of oral contraceptives (OR, 0.67, 95% CI, 0.53-0.85) and longer duration of use were associated with a decreased risk of ovarian cancer. Ever use of hormone replacement therapy increased the overall risk (OR, 1.30; 95% CI, 1.05-1.61). For all those variables, the effect was present for serous tumors, endometrioid tumors, and tumors of other histologies, but not for mucinous tumors. In contrast, current smoking was a risk factor only for mucinous tumors (OR, 1.78; 95% CI, 1.01-3.15) and increasing body mass index tended to increase the risk especially for mucinous and endometrioid tumors. Conclusions: We confirmed already known risk factors for ovarian cancer, and we observed significant differences in the risk profiles between mucinous and nonmucinous tumors indicating different etiologies. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1160–6)

High plasma YKL-40 level in patients with ovarian cancer stage III is related to shorter survival

YKL-40 (human cartilage glycoprotein-39) is a member of family 18 glycosyl hydrolases. YKL-40 is a growth factor and is secreted by cancer cells. High serum levels of YKL-40 in patients with colorectal cancer and recurrent metastatic breast cancer have been associated with a poor prognosis. We evaluated the prognostic value of plasma YKL-40 in patients with primary ovarian cancer (OC). YKL-40 was determined by ELISA in plasma obtained preoperatively from 47 women with stage III OC and in plasma from 79 healthy females. The results showed that plasma YKL-40 was elevated compared to healthy females in 57% of the OC patients and was highest in the patients who died during the follow-up compared to the patients still alive (186 vs. 78 micro g/l, p=0.002). Patients with high plasma YKL-40 (>130 micro g/l) had significantly (p=0.0003) shorter survival than patients with normal plasma YKL-40. Multivariate Cox regression analysis showed that plasma YKL-40 (RH=3.95; 95% CI, 1.52-10.27; p=0.005) and radicality after primary surgery (RH=4.03; 95% CI, 1.81-8.97; p=0.001) were independent prognostic factors of survival, whereas age, histological type of tumour and serum CA125 had no independent prognostic value. In conclusion, plasma levels of YKL-40 proved of prognostic value in stage III OC patients.

The low-mass end of the fundamental relation for gravitationally lensed star-forming galaxies at 1 < z < 6

We present Very Large Telescope/X-shooter spectra of 13 galaxies in the redshift range 1 ? z ? 6, which are strongly lensed by massive galaxy clusters. Spectroscopic redshifts are measured for nine galaxies, while three sources have redshifts determined from continuum breaks in their spectra. The stellar masses of the galaxies span four orders of magnitude between 107 and 1011?M? and have luminosities at 1500 angstrom rest frame between 0.004 and 9L* after correcting for the magnification. This allows us to probe a variety of galaxy types from young, low-mass starburst galaxies to massive evolved galaxies. The lensed galaxies with stellar masses less than 1010?M? have a large scatter compared to the fundamental relation between stellar mass, star formation rates and oxygen abundances. We provide a modified fit to the fundamental relation for low-mass, low-metallicity galaxies with a weaker dependence of the metallicity on either the star formation rate or stellar mass compared to low-redshift, high-mass and high-metallicity Sloan Digital Sky Survey galaxies.

Molecular hydrogen in the damped Lyman α system towards GRB 120815A at z = 2.36

We present the discovery of molecular hydrogen (H2), including the presence of vibrationally-excited H2* in the optical spectrum of the afterglow of GRB 120815A at z = 2.36 obtained with X-shooter at the VLT. Simultaneous photometric broad-band data from GROND and X-ray observations by Swift/XRT place further constraints on the amount and nature of dust along the sightline. The galactic environment of GRB 120815A is characterized by a strong DLA with log(N(H i)/cm-2) = 21.95 ± 0.10, prominent H2 absorption in the Lyman-Werner bands (log (N(H2)/cm-2) = 20.54 ± 0.13) and thus a molecular gas fraction log f(H2) = -1.14 ± 0.15. The distance d between the absorbing neutral gas and GRB 120815A is constrained via photo-excitation modeling of fine-structure and meta-stable transitions of Fe ii and Ni ii to d = 0.5 ± 0.1 kpc. The DLA metallicity ([Zn/H] = -1.15 ± 0.12), visual extinction (AV ≲ 0.15 mag) and dust depletion ([Zn/Fe] = 1.01 ± 0.10) are intermediate between the values of well-studied, H2-deficient GRB-DLAs observed at high spectral resolution, and the approximately solar metallicity, highly-obscured and H2-rich GRB 080607 sightline. With respect to N(H i), metallicity, as well as dust-extinction and depletion, GRB 120815A is fairly representative of the average properties of GRB-DLAs. This demonstrates that molecular hydrogen is present in at least a fraction of the more typical GRB-DLAs, and H2 and H2* are probably more wide-spread among GRB-selected systems than the few examples of previous detections would suggest. Because H2* transitions are located redwards of the Lyman α absorption, H2* opens a second route for positive searches for molecular absorption also in GRB afterglows at lower redshifts and observed at lower spectral resolution. Further detections of molecular gas in GRB-DLAs would allow statistical studies, and, coupled with host follow-up and sub-mm spectroscopy, provide unprecedented insights into the process and conditions of star-formation at high redshift.

The prognostic value of tetranectin immunoreactivity and plasma tetranectin in patients with ovarian cancer.

Background. Tetranectin (TN), a tetrameric, plasminogen‐binding protein, was reduced in the plasma of patients with cancer and appears extracellularly in “stimulated” connective tissues, such as the proliferative, connective tissue response to carcinomas known as desmoplasia.