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Wow, id like to have 2 cocks like she had... im so wet right now...
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Kiteboarding News
- 09 July 2009 | Kiteboarding
The first annual Luciano Gonzalez Kitesurfing Pro Open kicks off today, but on a much smaller scale than originally hoped for.
But Gonzales, professional kitesurfer and founder of the charity organization, The Wishspring Foundation, remains optimistic, "Our goal is to be bigger next year, with more international bands and a tour of kitesurfing professionals from around the world. The global economy is just too bad this year."
Which is too bad, indeed. Though the competition still goes on, with a small pot of prize money as well as donated prizes from local stores and restaurants for the surfers, it will not be the grand event that Gonzales himself is used to participating in.
Gonzales, a Cabarete local, has traveled the world as a professional kitesurfer for the last eight years, so he knows how expensive it can get to put this type of event on, "Professional kitesurfers charge around 50,000 Euros to travel to an event." He hopes to bring in several of these pros next year.
Most of the monetary proceeds of this year's competition will go to the Centro de Enseñanza Coral, a struggling school in Cabarete.
The goal of the Wishspring Foundation is to raise money for different schools from the area each year. The parent company of Wishspring and Gonzales's baby, LG Cabarete, aims to fundraise year-round to assist local schools in having more modern and higher quality levels of education.
Registration for this year's kitesurfing event begins today, July 8th, at the hotel/resort Paradiso del Sol and continues through Thursday morning, the 9th. The cost of registration is 500 pesos and opens to all.
- 07 July 2009 | Kiteboarding
South Australia – Kiteboard for Cancer is a great initiative kicked off by SA kiter Ben Howlett. Bens request for WAKSA support was received just as we were planning to begin an ongoing charity sponsorship program of our own.
Coincidentally the cancer charities had already been considered the most appropriate given the support offered to WAKSA by Healthways.
NB: If you havent already heard Healthways contributed an extremely healthy $5000 to Kitestock 08 which we put to very good, very appropriate and very much appreciated use by purchasing the two instant shades which were set up, centre stage at the Kitesock event. These shades will continue to provide protection and spread the Healthways/SunSmart message at future WAKSA events.
Whilst Ben has elected to support the Cancer Council SA with his event the WAKSA committee has resolved to begin seeking out an appropriate charity before committing to what we envisage will be an ongoing sponsorship program of our own.
REDKITE is one such charity which has approached us in the past. It was also the charity independently selected by Graham Baker as the recipient of funds raised at last years Course Racing event at South Beach Fremantle.
Given this background; the obvious common link of the name 'Redkite' and that Redkite is involved with projects related to kids with cancer (pretty apro for us youthful kiters!) it seems obvious our investigation should start there.
- 07 July 2009 | Kiteboarding
Welcome to the last day of competition and the end to another step on the KPWT 2009 tour. All riders, sponsor and organizers had an out of this world celebration last night at Café Del Mar to commemorate this successful event in Tarifa.
KPWT Movistar Kite Pro Tarifa started the day with a skippers meeting at 11h00.
Course Racing kicked things off, followed by the double elimination rounds for men and women. The wind had picked up nicely by 13h30 and the riders were gladly using it to their advantage.
Prize giving was held at 19h00 on the stage in front of Tangana, bringing the event to a close. Trophies were handed to the top 3 placed riders within each discipline.
The KPWT team would like to thank the local organizers, Last Lap. They were always smiling and enthusiastic to help with whatever task. And proved their competence in hosting a super event at such a perfect location, Tarifa! We look forward to working with you in the future.
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The DDJ-SR delivers all the superior performance features of the top-flight four-channel DDJ-SX2, including an inbuilt Serato sound card and pre-mapped controls for the included Serato DJ software.
The DDJ-SR incorporates features from our pro-range include large, low-latency jog wheels and Slip Mode – which silently continues track playback during loops, scratches and reverses, bringing the music back in the right place when the DJ is done.
Sixteen rubber Performance Pads are assigned to four modes – Hot Cue, Roll, Sampler and Slicer – to add a physical element to mashing up tracks.
This compact controller comes with large jog wheels, providing a dynamic performance with great scratch response and accuracy.
With Serato DJ you get access to various FX and advanced features, such as Beat Jump, Slip mode and Quantize. It also allows you to set and trigger cues, loops and samples and map them directly onto your hardware. Just connect your computer to the controller and start DJing.
Keep tracks playing muted during live edits such as loop, scratch or reverse. Release the jog wheel and the track comes back at exactly the right place.
The DDJ is constructed from premium materials and audio circuitry. The robust build ensures durability, while the distinctive styling and aluminium jog wheel deliver a professional feel.
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Didn't find what you're looking for? Maybe use fewer words or a more general search term.
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Abraham Lincoln Elementary School
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|Harbor Day School 0.3 miles
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Brenner's reach has extended well beyond his own research to inspire new generations of young scientists and to promote the development of science and biotechnology around the world. In the 1970s, he entered the passionate debates over the use of recombinant DNA technology, and, in the early 1990s, he encouraged Britain's involvement in the Human Genome Project. He was Director of the renowned Laboratory of Molecular Biology in Cambridge during the 1980s. Later, he advised HHMI's Janelia Farm Research Campus, and helped to develop research and biotechnology in Singapore and restructure molecular biology in Japan.
This book tells the lively story, not only of Brenner himself, but of what came to be known as the "golden age" of biology. It will be of interest to scientists, students, and professionals in the life sciences, as well as science historians and the general public interested in science.
|Contact: Ingrid Benirschke
Cold Spring Harbor Laboratory


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All materials on Kansas Memory are made available for noncommercial educational and research purposes only. It is the patron's responsibility to request and obtain permission from both the image and copyright owner(s) to use materials.
To obtain permission or to purchase a reproduction, please contact the KSHS Reference Desk at 785-272-8681, ext. 117 or email@example.com. See the Copyright and Permission FAQ for more information.
This letter from Joseph Little Bristow, 1861-1944, United States Senator, to Dwight David Eisenhower, 1890-1969, informs him of his nomination to West Point Military Academy. The complete set of correspondence related to Eisenhower's appointment to a military academy is available in Kansas Memory item 208267.
Creator: Bristow, Joseph L. (Joseph Little), 1861-1944
Date: October 24, 1910
This letter shows how Eisenhower's military career began. It can be used as a jumping off point to discuss Eisenhower's many accomplishments.
Item Number: 208270
Call Number: Joseph Little Bristow Coll. #6 Box 32 Folder 5
KSHS Identifier: DaRT ID: 208270
Business and Industry - Occupations/Professions - Military
Business and Industry - Occupations/Professions - Politicians
Collections - Manuscript - Bristow, Joseph Little #6
Curriculum - 4th Grade Standards - Kansas History Standards - Individuals and developments (Benchmark 1) - Notable Kansans (Indicator 1)
Date - 1910s - 1910
Education - Higher education - Students
Government and Politics - Federal Government - Congress - Senate - Bristow, Joseph Little, 1861-1944
Government and Politics - Federal Government - Presidents - Eisenhower, Dwight D.
Military - Service - Army
Military - Wars - World War II
Objects and Artifacts - Communication Artifacts - Documentary Artifact - Letter
People - Notable Kansans - Bristow, Joseph Little, 1861-1944
People - Notable Kansans - Eisenhower, Dwight David, 1890-1969
Places - Cities and towns - Salina
Places - Counties - Saline
Type of Material - Unpublished documents - Letters


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NEW YORK, June 10 /PRNewswire/ -- Vendome Group, publisher of HEALTHCARE DESIGN and Healthcare Building Ideas magazines and producers of the HEALTHCARE DESIGN.09 Conference announces the 2009 HEALTHCARE DESIGN Scholarship Program. The program is designed to provide those who are unable to afford the cost of the conference an opportunity to apply for a scholarship covering the full-conference registration fee.
"We believe, as a company and a magazine publisher, that giving back to the industry is important. The Center for Health Design, along with our association partners -- the AIA Academy of Architecture for Health, and The American Society of Interior Designers (ASID) -- provide cutting-edge content. These scholarships will enable more healthcare and design industry professionals to attend, which will create an even larger, more diverse audience that will help to further the conversation of what will affect the design of healthcare facilities," said Eric Woods VP and Managing Director of Vendome Group.
Vendome Group has committed over $20,000 in scholarship funds. "In providing roughly $20,000 in scholarship money, we hope to enable young and seasoned professionals alike to attend, and to further their knowledge and impact on the healthcare industry. With money and budgets being so tight, we truly feel that this is the right thing to do," says Woods.
In 2008, the HEALTHCARE DESIGN Conference attracted more than 300 exhibiting companies and more than 3,600 attendees. This year, the conference will be held at the Gaylord Palms Resort and Convention Center, in Orlando, Florida on October 31 - November 3.
For more information on HEALTHCARE DESIGN.09 visit www.HCD.09.com. To apply for a scholarship, please visit www.HCD09.com/scho
|SOURCE Vendome Group
Copyright©2009 PR Newswire.
All rights reserved


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Carbonic anhydrase IX is a hypoxia-induced enzyme that has many biologically important functions, including its role in cell adhesion and invasion.
This study was set out to investigate the role of CA IX in a series of 86 oligodendroglial brain tumors (71 primary and 15 recurrent; 48 pure oligodendrogliomas and 40 mixed oligoastrocytomas).
80% of the tumors showed CA IX expression by immunohistochemistry. Tumors with moderate or strong CA IX expression had decreased level of cell proliferation compared to weak or no CA IX expression (median 2.9 vs. 5.8, p = 0.015). CA IX correlated with two antioxidative enzymes, manganese superoxide dismutase (MnSOD) and regulatory gammaglutamylcysteine synthetase (GLCL-R): CA IX expression was significantly higher in MnSOD-positive tumors (p = 0.008) and decreased in GLCL-R-positive tumors (p = 0.044). In Cox multivariate analysis CA IX expression, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma) showed independent prognostic values (p = 0.009, p = 0.003 and p = 0.022, respectively), CA IX positivity predicting poorer outcome.
CA IX was proved to be an independent prognostic indicator in oligodendroglial brain tumors, and it also correlates reversely with cell proliferation. It may have a role in the biology of oligodendrogliomas, and most interestingly, as it is mainly expressed in tumor tissue, CA IX could serve as a target molecule for anticancer treatments.
Oligodendrogliomas account for approximately 5–18% of all intracranial gliomas and they occur primarily in the frontal or temporal lobes of the cerebrum [1,2]. It has been suggested that oligodendrogliomas were previously underdiagnosed, and there are several novel studies where their incidence is considerably higher, up to 33% of gliomas [3]. Accurate diagnosis is important in the case of oligodendrogliomas because the pathophysiology, treatment options and prognosis vary from that of diffusely infiltrating astrocytomas[1].
There are at least two different genetic pathways for the tumorigenesis of oligodendrogliomas. Loss of chromosomal regions on 1p and 19q is characteristic of oligodendrogliomas, but there is also evidence for another subset of oligodendrogliomas that have amplification of EGFR oncogene, loss of heterozygosity on chromosome 10 and homozygous deletion of the CDKN2A tumor suppressor gene. This seems to exclude the more common genetic changes in 1p and 19q [4,5].
Antioxidant enzymes and related proteins (AOEs) are part of the cellular protection mechanisms against functional and structural damage caused by reactive oxygen species [6]. Increased oxidant stress and/or diminished levels of AOEs lead to multiple injurious consequences in living cells, including susceptibility to genetic alterations and carcinogenesis. AOEs such as manganese superoxide dismutase (MnSOD), glutathione associated enzymes (GLCL-C and GLCL-R) and thioredoxin-thioredoxin reductase (Trx, TrxR) have been shown to correlate with tumor grade, metastasis and poor prognosis in invasive carcinomas such as lung and gastrointestinal malignancies and we have earlier studied them in oligodendroglial brain tumors [7-10].
Carbonic anhydrase IX (CA IX) is a tumor-associated metalloenzyme that belongs to the physiologically important family of at least 13 different mammalian carbonic anhydrases, CAs [11-13]. It is localized in the plasma membrane and like other enzymatically active CA isoenzymes (CA I-IV, VA, VB, VI, VII, XII-XV), it contains four important histidine residues: three residues for the coordination of a zinc ion in the active site and one for a proton shuttle. CAs catalyze the reversible interconversion between CO2 and HCO3 -, one of the most fundamental chemical reactions in cells. This reaction is essential for organisms as it influences respiration, pH regulation and homeostasis, exchange of electrolytes and several metabolic biosynthetic pathways [12-15]. Aberrant changes in this fine machinery are implicated in many diseases, including cancer.
CA IX has a special role among human CA isoenzymes because it can only be found in few normal tissues, but it is abundant in several tumors, such as colorectal, bladder, cervical, lung and breast carcinomas [16-18]. Even though the expression of CA IX in these carcinomas is evident, the tissues from which the carcinomas are originally derived are known to be CA IX-negative or they show only low enzyme expression. Furthermore, the few normal tissues or cell types that express CA IX, such as gastrointestinal and gallbladder epithelial cells, have been reported to lose the expression of CA IX during carcinogenesis [19-22]. This quite exceptional phenomenon makes CA IX an interesting tumor-associated protein.
CA IX expression is strongly induced by hypoxia. This transcriptional activation is accomplished via the HIF-1 transcription factor, which accumulates in tissue under the hypoxic condition that is often present in growing tumors. That, in turn, is an outcome of poorly organized and insufficient vasculature in uncontrollably growing malignant tissue. The HIF-1 transcription factor is a trigger for several hypoxia-regulated genes linked to cell survival, proliferation, apoptosis, angiogenesis and metabolism in tumor cells. The activation of these genes helps the cell to adapt to the stress caused by low oxygen level in a particular tissue. Earlier studies have shown that CA IX expression is induced as early as two hours after HIF activation and persists for several days, even if HIF-1 expression has ceased. This means that CA IX reflects both previous and present hypoxia in cells [23-25]. In addition to the important correlation between hypoxia and CA IX expression, it has been found that CA IX expression correlates with poor prognosis in various tumors [26-29]. It has also been suggested that CA IX has a direct role in tumor progression and the regulation of pH balance during tumorigenesis. CA IX has effects on cell adhesion, too, and it has been suggested to play a role in tumor invasion through weakening of cell-cell adhesion as E-cadherin is competing for β-catenin [30]. However, the effect of CA IX on tumor cell invasion is still under debate as some recent results have suggested that there is no evidence of such a correlation [31]. Even though we do not know the exact mechanisms of CA IX in cancer development, it is undoubtedly a promising target for anticancer treatments. It is also known that CA IX is strongly inhibited by aromatic and heterocyclic sulfonamides, and several other potent inhibitors for CAs have already been designed [32,33]. These facts prompted us to investigate the expression of CA IX in a series of histopathologically and genetically verified oligodendroglial brain tumors.
We analyzed oligodendroglial tumor samples from 86 patients who underwent surgery during 1980–2004 at Tampere University Hospital, Turku University Hospital and Kuopio University Hospital, Finland. 71 patients had a primary tumor and 15 a recurrent tumor. Of these tumors 55 were grade II and 31 were grade III. Forty-eight tumors were pure oligodendrogliomas and 38 were oligodendrogliomas with an additional astrocytic component (mixed oligoastrocytomas). All the patients underwent neurosurgical operation with the intention of gross radical tumor resection. The median age of the patients at the time of operation was 40.0 years (mean 41.5, SD +14.2). The median follow-up time was 3.5 years (mean 4.9, SD 4.5). During the follow-up, 43 patients died.
Tumor samples
The tumor samples were fixed in 4% phosphate-buffered formaldehyde and embedded in paraffin. Paraffin sections were stained with hematoxylin and eosin. Histopathological typing and grading were carried out according to WHO criteria (1) independently by two experienced neuropathologists. Histologically representative and most proliferative oligodendroglial tumor regions were selected by a neuropathologist (HH) and the samples from these areas were placed in tissue microarray blocks using a custom-built instrument (Beecher Instruments, Silver Spring, MD, USA). The diameter of the tissue cores in the microarray block was 600 μm. The tumors in the microarray analysis comprised both pure oligodendrogliomas and mixed oligoastrocytomas (for details, see Table 1.).
Table 1. The expression of carbonic anhydrase IX in oligodendrogliomas.
Immunohistochemical procedures
The monoclonal antibody M75, which recognizes the N-terminal proteoglycan domain of human CA IX, has been described previously [34].
Automated immunostaining, which was performed using Power Vision+™ Poly-HRP IHC Kit (ImmunoVision Technologies, Co.) reagents, included the following steps: (a) rinsing in wash buffer; (b) treatment in 3% H2O2 in ddH2O for 5 min and rinsing in wash buffer; (c) blocking with Universal IHC Blocking/Diluent for 30 min and rinsing in wash buffer; (d) incubation with the primary antibody (M75 for CA IX) or normal rabbit serum (NRS) diluted 1:200 (M75) or 1:2000 (NRS) in Universal IHC Blocking/Diluent for 30 min; (e) rinsing in wash buffer for 3 × 5 min; (f) incubation in poly-HRP-conjugated anti-rabbit or anti-mouse IgG for 30 min and rinsing in wash buffer for 3 × 5 min; (g) incubation in DAB (3,3'-diaminobenzidine tetrahydrochloride) solution (one drop of DAB solution A and one drop of DAB solution B in 1 ml) ddH2O for 6 min; (h) rinsing with ddH2O; (i) CuSO4 treatment for 5 min to enhance the signal; and (j) rinsing with ddH2O. All procedures were carried out at room temperature. The sections were mounted in Entellan Neu (Merck; Darmstadt, Germany) and finally examined and photographed with a Zeiss Axioskop 40 microscope (Carl Zeiss; Göttingen, Germany).
Antioxidative enzymes
The antibodies for the AOEs were as follows: a polyclonal rabbit anti-human antibody to MnSOD (a gift from Professor J.D. Crapo, National Jewish Medical Center, Denver, CO, dilution 1:1000); rabbit polyclonal anti-human antibodies to GLCL-C and GLCL-R (a gift from Dr Kavanagh, University of Washington, Seattle, WA, dilution 1:1000 for both); a goat polyclonal human antibody to Trx (American Diagnostica, Greenwich, CT, dilution 1:200); and a polyclonal rabbit anti-rat antibody to TrxR (a gift from Dr Arne Holmgren, Karolinska Institutet, Stockholm, Sweden, dilution 1:1000).
The tissue antigens for MnSOD, GLCL-C, GLCL-R, Trx and TrxR were revealed using the Histostain-Plus Kit (Zymed Laboratories Inc, South San Francisco, CA) as described previously [35].
The immunostaining results were evaluated during one session on a multiheaded microscope by three observers (HH, SJ, SP or YS) semiquantitatively by dividing the CA IX and AOE staining reaction into four categories based on the reactivity of the staining taking equally into account both the intensity and extent of the staining: 0 = no immunostaining present; 1 = weak immunostaining, <10% of the tumor tissue immunostained; 2 = moderate immunostaining, 10–50% of the tumor tissue immunostained; 3 = strong immunostaining present, >50% of the tumor tissue immunostained. For the analysis, the four categories were divided into two groups: the CA IX(-) and AOE(-) group contained negatively and weakly stained tumors. The CA IX(+) and AOE(+) group contained tumors showing moderate or strong immunostaining [10].
The immunostaining of AOEs has been described in more detail in our previous study [10]. Briefly, all the AOEs (MnSOD, GLCL-C, GLCL-R, Trx, TrxR) were expressed diffusely in the sections. MnSOD had granular and TrxR perinuclear cytoplasmic immunoreactivity and rest of the AOEs were stained diffusely in the cytoplasm.
The signal for CA IX is both membrane-associated and intracellular in oligodendroglial tumors. CA IX expression mainly showed focal accentuation and was found to be most intense in perinecrotic areas. When necrotic or microvascular proliferation was present, perinecrotic or microvessel staining was commonly seen.
The CA IX and AOE stainings represent adjacent sections in the same area of the tumor.
Cell proliferation
For the analysis of cell proliferation, a mouse monoclonal antibody MIB-1 recognizing the Ki-67 antigen was used (Immunotech, S.A. Marseille, France) (dilution 1:40). After immunostaining, the tissue sections were counterstained with methyl green. Proliferative activity was reported as a percentage of immunopositive nuclei. Analysis of MIB-1 positive tumor cells was done with a carefully standardized image analysis system (CAS-200™ Software, Becton Dickinson & Co., USA) as described previously [36,37]. Briefly, the analysis was done on areas that were expressing quantitatively the highest number of immunopositive nuclei. Twenty microscopic fields (×400 magnification) were counted along a vertical and horizontal axis perpendicular to each other. Endothelial cells, necrotic and haemorrhagic areas as well as section borders were omitted.
Apoptotic rate
Apoptosis activity was determined by TUNEL-labeling. The deparaffinized tumor microarray tissue sections were first digested with proteinase K (20 μg/ml) for 15 min. Apoptotic cells were demonstrated using ApopTag In Situ Apoptosis Detection Kit (Oncor, Inc., Gaithersburg, MD, USA) according to the manufacturer's instructions. In the terminal deoxynucleotidyl transferase nick end labeling method, the recommended concentration was reduced eightfold. Direct immunoperoxidase detection of digoxigenin labeled dUTP was followed by counterstaining in methyl green [38]. Staining was analyzed by counting all the tumor cells in the core tissue with an image analysis system (CAS-200™). The obtained scores were reported as a percentage of immunopositive nuclei.
Analysis of 1p19q
FISH analysis was performed on tumor cell nuclei isolated from paraffin embedded sections. The sections were first deparaffinized with xylene, followed by an ethanol row with decreasing concentrations (100%, 95%, 70%, and 50% for 10 minutes, respectively). After transfer into distilled water, the deparaffinized sections were incubated with 0.1% protease in 0.1 M Tris, 0.07 M NaCl at 37°C for 30 minutes and occasionally agitated. To check cell density, 5 μl of cell suspension was put on a slide and examined under the microscope. After preparing the slides using 10 μl of cell suspension, the slides were air-dried overnight at room temperature and fixed with 4% buffered formaldehyde for 10 minutes. The slides were used immediately or stored in sealed boxes at -70°C. FISH analysis for 1p and 19q were performed with LSI 1p36/LSI 1q25 and LSI19q13/LSI 19p13 probes (Vysis). Hybridization was done according to the protocols of Vysis included in the probe package insert.
Analysis of 1p and 19q loss was done by FISH for 30 most recent tumor samples. In 24 samples there were both 1p and 19q deletions, 1 had only 1p deletion, 1 only 19q deletion, and 4 had no deletions.
Statistical analysis
The analyses were done by comparing CA IX groups based on the immunostaining reactivity. When stated, CA IX negative group was compared to CA IX positive group.
In survival analysis overall survival was defined from the day of surgery until the death of the patient. The death of patient was considered as an event in the analysis.
Univariate survival analysis was carried out by comparing all the four CA IX categories. In multivariate survival analysis the tumors that had no CA IX immunostaining were compared to those which had weak, moderate or strong staining. This was done to reach the best prognostic cut-off possible.
The tests used for statistical analysis were all part of SPSS 11.0 (SPSS Inc., Chicago, Illinois) for Windows software. Chi-square tests, t-tests, Mann-Whitney tests and Wilcoxon tests were used, as well as multivariate analysis of variance (ANOVA). The log-rank test and Cox multivariate analysis were used for the analysis of prognostic factors. The significance level was set at p < 0.05.
The study design was approved by the Ethics committee of Tampere University Hospital and the National Authority for Medicolegal Affairs.
Expression of CA IX
CA IX expression was analyzed in 71 primary and 15 recurrent oligodendroglial tumors. The distribution of immunopositivity for CA IX is shown in Table 1 and examples of immunostained samples in the four categories (negative, weak, moderate, strong) are shown in Figure 1A–D.
Figure 1. CA IX expression in the four categories (negative (A), weak (B), moderate (C) and strong (D)) in oligodendroglial brain tumor samples. Magnification 400×.
The intensity of CA IX immunostaining in different tumor grades is shown in Table 1. There was no significant difference in CA IX expression between grade II and grade III tumors or between primary and recurrent tumors or between pure oligodendroglial tumors and mixed oligoastrocytomas. The age of the patients at the time of the operation did not differ significantly between the CA IX(-) and CA IX(+) groups.
CA IX expression was significantly higher in MnSOD(+) tumors (p = 0.008, chi-square test). On the other hand, CA IX expression was decreased in GLCL-R(+) tumors (p = 0.044, chi-square test). The other AOEs did not reach any statistical association with CA IX. In addition, there was no correlation between CA IX and 1p19q status in our material.
Analyses for cell proliferation and apoptosis were performed and the results were correlated to CA IX expression (CA IX(-) vs. CA IX(+) tumors). Cell proliferation index (MIB-1) was decreased among CA IX(+) tumors. In Ca IX (+) tumors median was 2.9, mean 3.3, SD ± 4.8 vs. median 5.8, mean11.9 and SD ± 13.9 in CA IX(-) tumors (p = 0.015, Mann-Whitney test). No significant difference was seen in apoptotic activity in CA IX(-) vs. CA IX(+) tumors.
Survival analysis was confined to the primary cases. When the patients with tumors that had no immunostaining for CA IX were compared in univariate survival analysis with those who had positive immunostaining for CA IX, the negative tumors tended to associate with a better survival rate than their positive counterparts (Figure 2.). However, this difference did not reach statistical significance.
Figure 2. Survival by CA IX in primary oligodendroglial brain tumors.
In Cox multivariate analysis the expression of CA IX, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma) showed independent prognostic significance (p = 0.009, Exp(B) = 7.370; p = 0.003, Exp(B) = 3.422 and p = 0.022, Exp(B) = 0.351). CA IX positivity, older age and astrocytic component predicted poorer outcome. Other clinicopathological features, including proliferation status and 1p 19q status, did not reach statistical significance in association to the prognosis.
We investigated the expression of CA IX in a series of oligodendroglial brain tumors. We found that CA IX is expressed in most of these tumors and that it has an independent prognostic value, predicting a poor outcome. In addition, CA IX(+) tumors had decreased cell proliferation compared to CA IX(-) tumors.
Chromosomal loss of 1p and 19q is a common genotypic change in oligodendrogliomas. It is commonly used as a tool to make more precise decisions concerning the treatment. Recently, it has become clear, however, that defects in single chromosomes, genes, or even the sequential acquisition of mutations, are not the entire story in tumorigenesis, given that many cancer susceptibility genes show a high degree of tissue specificity in their association with neoplastic transformation. Also in oligodendrogliomas and other malignant brain tumors, the acquisition of a complete neoplastic phenotype is caused by the activation of several oncogenes and the inactivation of several growth-suppressor genes, and therefore, a number of target molecules are required to be involved in an optimal treatment strategy. There are several characteristics which are important for such a protein target: The molecule (a) is expressed only in tumor cells, and in the majority of tumor cells; (b) is well accessible on the surface of the cell; (c) is not encoded from a mutated gene, but is derived from a stable chromosomal area; (d) can be targeted with a safe drug or inhibitory antibody; (e) is easy to determine in normal laboratory samples and (f) the costs of diagnostic and therapeutic uses are reasonable.
CA IX is an extremely attractive molecule in cancer research because it has several important properties that make it completely unique. First of all, it is mainly expressed in cancerous tissue. Second, it is expressed in various solid tumor types, including some very common ones (for example breast, lung and cervical carcinomas), which can be quite resistant to chemotherapy and radiotherapy. Third, the CA IX antigen is exposed to the surface of the malignant cell, thus making it accessible for antibodies or cancer drugs. Fourth, the structure of the CA IX molecule is amenable to targeting by drugs and it also has good selectivity. Fifth, CA IX expression can be easily verified from tissues with common laboratory protocols. Sixth, CA inhibitors are already being used in both clinical applications and new trials [33,39] and more effective and safer inhibitors are being developed [40]. Therefore, one could conclude that CA IX indeed exhibits several features that are necessary for a good target molecule in anticancer therapy, and at least for now it is clear that in most cases good cancer treatment includes the best combination of different treatments supporting one another. CA IX and its inhibitors could definitely be considered as part of that kind of treatment strategy in the near future.
CA IX has proved to be a surrogate marker for hypoxia and it has also been found to correlate with prognosis in several cancers (including our present tumor material) [17,26,27,29,41]. CA IX expression could thus be useful in the prognostic assessment of certain tumors. For example, the previous study by Haapasalo et al showed that it has a strong association with tumor grade and poor prognosis in astrocytic brain tumors [28]. CA IX immunopositivity was observed in 78% of astrocytic brain tumors (compared to 80% of oligodendrogliomas in our study). In addition, both in astrocytic brain tumors and in oligodendrogliomas perinecrotic accentuation is quite commonly seen. A study by Preusser et al shows that CA IX has a positive correlation with the presence of necrosis [42]. When necrosis or microvascular proliferation was present, perinecrotic or microvessel staining was commonly seen in our present study, too. This could reflect the severe changes disturbing the tissue (hypoxia, insufficient microvasculature etc.) leading finally to necrosis but also enhancing the expression of CA IX. Although the expression of CA IX is common in both astrocytomas and oligodendrogliomas, it was more clearly associated to tumor malignancy grade in astrocytic brain tumors. However, the unique features of CA IX molecule could be useful when designing improvement of therapeutic interventions for both of these tumor groups.
A recent study by Birner et al in 60 oligodendroglial tumors with 1p aberrations showed that CA IX expression is often accompanied with the expression of hypoxia-inducible factor 1α (HIF-1α) [43]. They concluded that when expressed together, they represent a true tissue hypoxia and not just oncogenic activation, which might otherwise be the case, at least for HIF-1α. It is already known that HIF-1α is one of the key factors regulating cellular O2 homeostasis and its activation represent a key step in angiogenesis and adaptation to hypoxia and thus the vitality of the tumor. Overexpression of HIF-1α is shown to be an independent prognostic factor in oligodendroglial tumors and interestingly, it also correlates with the microvessel density in these tumors [44]. They suggested that as tissue hypoxia is known to diminish the efficacy of radiotherapy and thus influence the adjuvant therapy given to the patients, the evaluation of tissue hypoxia using this combination of hypoxia-markers would be helpful for recruitment of patients for individualized therapy strategies, e.g. identification of hypoxic tumors for hyperbaric oxygenation preceding radiotherapy.
In the present study we found that CA IX was expressed more often in MnSOD-positive tumors. In our previous study on AOEs in partly the same subgroup of oligodendroglial brain tumors, MnSOD was associated with the histopathological component (pure oligodendrogliomas vs. mixed astrocytomas), but failed to show a significant correlation with patient survival [10]. The association reported here with CA IX is interesting because CA IX is known to be induced by hypoxia, and MnSOD in turn is induced among other factors by hyperoxia. It seems that CA IX expression and hypoxia are quite consistently associated, while factors that induce MnSOD are quite complex and numerous [7,45]. Another possible explanation for this peculiar association might be that MnSOD and CA IX expression are associated with different phases of tumorigenesis in oligodendrogliomas. MnSOD has been suggested to be a tumor suppressor gene [46,47]. The increased expression of MnSOD may reflect the imbalance during tumorigenesis where cells attempt to control the tumor environment. As the process advances, the environment becomes increasingly hostile for normal cells. Rapidly growing, poorly organized and improperly proliferated cancer cells lead to insufficient microvasculature and low pH, suppressing the growth of normal cells even further, while selectively stimulating the growth of malignant ones. This leads to the activation of hypoxia response elements and consequently induces a number of genes, including the CA9 gene, involved in the adaptation to the stress caused by low oxygen. The association between MnSOD and CA IX may thus represent partly overlapping periods of tumorigenesis during which both proteins are present in neoplastic tissue. Furthermore, the basic reaction of MnSOD where reactive oxygen species superoxide O2- is converted to H2O2 by MnSOD is known to affect to HIF-1α, by letting it accumulate into the cytosol. Thus, MnSOD, HIF-1α and CA IX expressions are representing an exciting and complicated continuum.
We also found an association between CA IX and proliferation index (MIB-1). In our material, CA IX(+) tumors had significantly lower proliferation index than their CA IX(-) counterparts. This could reflect the severe hypoxia that is present in the tumor tissue, thus affecting to cells capability to proliferate. A study by Proescholdt et al shows that the relationship between CA IX and proliferation index is quite complicated [48]. They examined the expression of CA IX and CA XII in different kind of brain tumors and also in the normal brain. They found an association between CA IX positivity and increasing proliferation index. However, their material was quite heterogeneous, and oligodendrogliomas were not included at all. Despite of that, it can be said that the correlation between CA IX and proliferation is interesting and should be studied more thoroughly.
In conclusion, CA IX is expressed in the majority of oligodendroglial tumors and its expression correlates independently with patient survival. It is known to be induced by hypoxia in the tissue, partly by the same elements that induce angiogenesis, and it affects the survival of cancer cells. CA IX seems to play a major role in the pathophysiology of several malignancies, including our material of oligodendroglial tumors, and it may contribute to the abnormal cellular environment of malignant brain tumors by shifting the pH gradient towards higher acidity. Because of its many unique properties, CA IX can be considered a good candidate for a target molecule when designing new anticancer therapies.
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
SJ participated in the design of the study, light microscopy, 1p19q analyses, analyzed the data and drafted the first version of the manuscript. SP participated in the design of the study, tissue processing, immunohistochemical staining and light microscopy. HB participated to the tissue micro-array blocks from the oligodendroglial tumor samples. MK participated to the 1p19q analyses. AKP participated in the study design and tissue processing. YS participated to the analyses of the AOEs in this study and produced the antibodies for the AOEs. SPas and JP participated in the design of the study and produced and characterized the monoclonal S100P antibody. HH participated in the design of the study, immunohistochemical staining, light microscopy. All authors helped to draft the manuscript. All authors read and approved the final manuscript.
Research Support: This study was financially supported by the Finnish Cultural Foundation, the Medical Research Fund of Tampere University Hospital, the Academy of Finland and the Finnish Cancer Foundation.
We wish to thank Ms. Seija Kalmanlehto for her skillfull help in 1p19q analysis.
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Research Triangle Park, NC (PRWEB) June 19, 2013
North Carolina-based life sciences company Entegrion, Inc., announced organizational changes to advance development of its technologies.
Entegrion's Executive Chairman John B. Mowell said, "To support the advanced development of our product candidates Entegrion's Board of Directors has made changes to the Company's management structure and engaged industry leaders as key advisors."
The Company announced that Michael Galiger will serve as Vice President of Operations with primary responsibility for development of Entegrion's plasma product Resusix, as well as supporting the continued advancement of the Company's other technologies. "Mike's technical background, intensive work with the development of Entegrion's products, and his success in attracting a solid product development team, including Stacy Hammonds as Director of Clinical Operations, and Taegen Sullivan, Product Development Engineer, have made a substantial contribution to Entegrion's success," Mowell continued.
Entegrion also announced the formation of a clinical advisory Board initially comprised of Paul Ness, MD, Director of Transfusion Medicine at Johns Hopkins; Professor Peter Rhee, MD, Chief of Trauma, Critical Care, Burns and Emergency Surgery, University of Arizona; Edward Scott, MD, President of Key Biologics; and Philip C. Spinella, MD, Director, Pediatric Critical Care Translational Research Program, Washington University, St. Louis.
"We are immensely proud to be associated with these world-class leaders in transfusion and trauma medicine. Drs. Rhee and Spinella both came out of the Armed Forces and served in Iraq. They will bring a unique 'user perspective' to our technologies. Dr. Scott has decades of experience with the supply of blood and blood derivatives, and Dr. Ness is an expert
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A clinical decision support tool helped physicians identify patients at high risk of bleeding complications prior to undergoing a coronary intervention procedure and helped guide the use of bleeding avoidance strategies, leading to less complications and a shorter hospital stay, according to a study being presented March 10 at the American College of Cardiology Scientific Sessions.
More than 1.3 million percutaneous coronary interventions (PCIs) are performed each year in the United States. Bleeding during and after these procedures is a common risk (3 6%).
"Bleeding complications after PCI can lead to worse outcomes for the patient, including death, as well as an increase in the length of stay in the hospital, which leads to an increase in hospital costs," says the study's lead author Craig E. Strauss, MD, MPH, a research cardiologist at the Minneapolis Heart Institute Foundation and physician at the Minneapolis Heart Institute at Abbott Northwestern Hospital in Minneapolis.
Therefore, the cardiologists across the Allina Health System used a validated pre-PCI bleeding risk score to accurately identify high-risk patients, allowing them to employ strategies to avoid bleeding and improve patient outcomes. Among those strategies, bivalirudin (Angiomax, The Medicines Company) is a direct thrombin inhibitor that has been shown to reduce bleeding complications in PCI.
"This risk-stratification tool can be used real-time in the cath lab to identify and mitigate a patient's risk for bleeding around the time of the procedure," says Strauss. "The cath lab team uses a web-based calculator, which takes less than 1-2 minutes, and determines the risk category of each patient." Due to the ease of use, the tool achieved a high adoption rate of 92 percent at three high-volume PCI centers in Minnesota.
Among the 2,608 PCI cases performed at the three PCI centers, 24.4 percent of the patients were identified as high risk for bleed
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The British Commonwealth Games came about when the meeting of the British
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Reflecting the transition from the old British Empire to the new British Commonwealth, the Tudor (or "Imperial") Crown in the Games Seal was replaced by the St. Edward's Crown, which Queen Elizabeth II had adopted after she assumed the throne. The St. Edwards Crown reflected the fact that the British Monarch no longer ruled over a vast Empire.
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UL joins the Field Museum for World Water Day March 22
CHICAGO, March 19 /PRNewswire/ -- Underwriters Laboratories (UL), a world leader in product safety testing services, will launch its water quality and conservation educational campaign in the East Wing of the Field Museum, 1400 S. Lake Shore Drive in Chicago, from 10:00 a.m. to 2:00 p.m. on Sunday, March 22, 2009. As part of the organization's century-long commitment to public health and safety, UL aims to raise awareness of water sanitation and conservation issues through its educational campaign that includes water quality testing information and conservation tips.
"Nearly a billion people--that's one out of every eight worldwide--lack access to clean drinking water(1)," said Jeff Smith, General Manager, UL Global Water Business. "Children are more vulnerable than any other age group to the health effects of unclean water, so it is imperative that we launch our educational effort with a focus on teaching children the value of this natural resource and how we can protect it."
UL will launch its educational campaign during the World Water Day festivities at The Field Museum, which include family workshops and science demonstrations. At the event, UL will host several hands-on experiments through the use of learning labs, demonstrating how water contaminants such as E. coli and pesticides are analyzed in drinking water. Additionally, UL will host special viewings of the newly released Wild About Safety(R) Timon and Pumbaa Safety Smart(R) Goes Green!, a classroom edition DVD developed through a partnership between UL and various units of The Walt Disney Company. Safety Smart Goes Green! teaches us what we can do to help our environment - our air, our water and our world. Children that participate in UL activities will be rewarded with the Wild About Safety certificate and encouraged to make 'safety smart' decisions during W
|SOURCE Underwriters Laboratories
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