Combined therapy with disintegrin and melphalan as a new strategy in inhibition of endometrial cancer cell line (Ishikawa) growth.

Endometrial cancer is one of the most frequently diagnosed cancer in females with prevalence of 22 in 100,000 women. The etiology of the cancer remains unclear. Despite significant progress towards understanding the patho-mechanism of the disease, effective treatment is still lacking. The results of the study suggest that combined treatment of Ishikawa cells for 24 h with disintegrin and then for 24 h with melphalan severely inhibits important biological functions of the cells. We showed that such strategy have a potent cytotoxic effect. The mechanism of process undergoes probably through inhibition of integrin - dependent signaling. In this study we shown down regulation of Shc and FAK proteins in cells treated with echistatin and melphalan. It suggests that signaling pathways that involve Shc and FAK participation may represent target for antineoplastic strategy. The functional significance of the combined treatment of Ishikwa cells with echistatin and melphalan was found at the level of collagen biosynthesis. Decreased biosynthesis of collagen in extracellular matrix may suppress cell growth and induce apoptosis. The treatment with echistatin and melphalan also showed decreased expression of IGF receptor in comparison to the cells treated with both compounds separately. The data presented suggest that combined therapy with disintegrin - echistatin and alkyalting drug - mephalan may represent a new approach to more effective and safe cancer therapy

Assessment of some of the factors involved in collagen metabolism in the abdominal aortic aneurysm wall

Wstęp. Przebudowa macierzy pozakomórkowej ściany aorty odgrywa istotną rolę w patogenezie tętniaka aorty brzusznej (AAA). Wraz z postępem choroby w jego ścianie zmniejsza się zawartość elastyny i zwiększa się zawartość prekursorowych form kolagenu, podczas gdy całkowita zawartość tego białka nie ulega istotnym zmianom. Celem pracy była ocena następujących czynników regulujących metabolizm kolagenu: insulinopodobnego czynnika wzrostu typu I (IGF-I) i jego białek wiążących (IGFBP-1 i IGFBP-3) oraz metaloproteinaz (MMP-1, MMP-2, MMP-9) w ścianie TAB w porównaniu ze ścianą aorty prawidłowej. Materiał i metody. Materiał do badań stanowiły ściany AAA o średnicy 80 ± 20 mm pobrane od 30 chorych w wieku 65 ± 10 lat podczas planowych zabiegów operacyjnych. Materiałem kontrolnym były prawidłowe aorty brzuszne 10 dawców narządów w wieku 34 ± 5 lat. Metodami radioimmunologicznymi oznaczono stężenie IGF-I, IGFBP-1 i IGFBP-3. Oceniono również ekspresję MMP-1, MMP-2 oraz MMP-9. Wyniki. Wykazano, że zawartość IGF-I zmniejsza się, natomiast zawartość IGFBP-1 oraz IGFBP-3 zwiększa się w ścianie AAA w porównaniu ze ścianą aorty kontrolnej. Ponadto stwierdzono większą intensywność ekspresji MMP-1, MMP-2 oraz MMP-9 w ścianie AAA w porównaniu ze ścianą aorty kontrolnej. Wnioski. W ścianie AAA zmniejsza się zawartość oraz biodostępność IGF-I w porównaniu ze ścianą aorty prawidłowej u osób młodych. Proces ten może utrudniać odtwarzanie kolagenu degradowanego przez metaloproteinazy (kolagenazę, żelatynazy), których zwiększona ekspresja występuje w ścianie AAA.Background. Extracellular matrix remodelling of the aortic wall plays an important role in abdominal aortic aneurysm (AAA) pathogenesis. With progress of the disease, elastin content decreases and the contents of collagen precursor forms increase in the AAA wall; however, total collagen content does not show any significant changes. The aim of the study was to evaluate the following factors involved in collagen metabolism: insulin-like growth factor I (IGF-I) and its binding proteins (IGFBP-1 and IGFBP-3), as well as metalloproteinases (MMP-1, MMP-2 and MMP-9) in the AAA wall when compared to the wall of normal aorta. Material and methods. The studied material consisted of AAA walls that were collected during elective surgical treatment of 30 patients in the age range 65 ± 10 years. The AAA diameter was 80 ± 20 mm. Normal abdominal aortas from 10 organ donors in the age range 34 ± 5 years were the control material. Contents of IGF-I, IGFBP-1 and IGFBP-3 were evaluated according to radioimmunometric methods. Expression of MMP-1, MMP-2 and MMP-9 was also assessed. Results. It was demonstrated that IGF-I content was decreased, whereas content of IGFBP-1 and IGFBP-3 were increased in the AAA wall when compared to the wall of normal aorta. Furthermore, increased intensity of MMP-1, MMP-2 and MMP-9 expression was found in the AAA wall in comparison with the wall of normal aorta. Conclusions. Insulin-like growth factor 1 content and its bioavailability are decreased in the AAA wall when compared to the wall of normal aorta in young subjects. This may impede regeneration of collagen degraded by metalloproteinases (collagenase, gelatinases), increased expression of which is present in the AAA wall

Estrogen receptor beta participate in the regulation of metabolizm of extracellular matrix in estrogen alpha negative breast cancer.

The biology of breast cancer is closely releted to sex steroid hormones. Estrogen receptor beta is overexpressed in around 70% breast cancer cases, referrd to as "ER positive". Estrogens bind to estrogen receptor and stimulate the transcription of genes involved in control of cell proliferation. Moreover, estrogens may induce growth factors and components of extracellular matrix and interact with them in a complex manner. Extracellular matrix and integrins play an important role in cell functions and their aberrant expressions are implicated in breast cancer development, invasion and metastasis. ER beta is certainly associated with more differentiated tumors, while evidence of role of ER beta is controversial. The highly invasive breast cancer ER beta negative cell line MDA-MB 231 can be the model of exam the role of ER beta in breast cancer. The aim of this study was to examine the role of activation of ER beta on the metabolism of the extracellular matrix and the expression of beta-1 integrin in the breast cancer cell line MDA-MB 231. The cells were exposed on the estradiol, tamoxifen, raloxifen and genisteina in dose dependent concentrations. To determine the relative rate of collagen syntesis we measured the time-dependent reduction of collagen-bound radioactivity after pulse-chase labeling with [3 H] prolina by Peterkofsky methods. The expression of beta-1 integrin was determine by Western blot analysis. The activity of MMP2 and 9 were measured using gelatin zymography with an image analysis system. Our data suggest on the role of estrogen receptor beta on the metabolism of extracellular matrix in the breast cancer line MDA - MB 231. Estradiol and SERMs regulate the expression of ECM proteins: collagen, integrins and enhance activity of metaloproteinases 2 and 9

3D PET image reconstruction based on Maximum Likelihood Estimation Method (MLEM) algorithm

Positron emission tomographs (PET) do not measure an image directly. Instead, they measure at the boundary of the field-of-view (FOV) of PET tomograph a sinogram that consists of measurements of the sums of all the counts along the lines connecting two detectors. As there is a multitude of detectors build-in typical PET tomograph structure, there are many possible detector pairs that pertain to the measurement. The problem is how to turn this measurement into an image (this is called imaging). Decisive improvement in PET image quality was reached with the introduction of iterative reconstruction techniques. This stage was reached already twenty years ago (with the advent of new powerful computing processors). However, three dimensional (3D) imaging remains still a challenge. The purpose of the image reconstruction algorithm is to process this imperfect count data for a large number (many millions) of lines-of-responce (LOR) and millions of detected photons to produce an image showing the distribution of the labeled molecules in space.Comment: 10 pages, 7 figure

TOF-PET detector concept based on organic scintillators

In this contribution we present a new concept of the large acceptance detector systems based on organic scintillators which may allow for simultaneous diagnostic of large fraction of the human body. Novelty of the concept lies in employing large blocks of polymer scintillators instead of crystals as detectors of annihilation quanta, and in using predominantly the timing of signals instead of their amplitudes

Plastic scintillators for positron emission tomography obtained by the bulk polymerization method

This paper describes three methods regarding the production of plastic scintillators. One method appears to be suitable for the manufacturing of plastic scintillator, revealing properties which fulfill the requirements of novel positron emission tomography scanners based on plastic scintillators. The key parameters of the manufacturing process are determined and discussed.Comment: 7 pages, 4 figure

Application of the compress sensing theory for improvement of the TOF resolution in a novel J-PET instrument

Nowadays, in positron emission tomography (PET) systems, a time of fl ight (TOF) information is used to improve the image reconstruction process. In TOF-PET, fast detectors are able to measure the difference in the arrival time of the two gamma rays, with the precision enabling to shorten signifi cantly a range along the line-of-response (LOR) where the annihilation occurred. In the new concept, called J-PET scanner, gamma rays are detected in plastic scintillators. In a single strip of J-PET system, time values are obtained by probing signals in the amplitude domain. Owing to compressive sensing (CS) theory, information about the shape and amplitude of the signals is recovered. In this paper, we demonstrate that based on the acquired signals parameters, a better signal normalization may be provided in order to improve the TOF resolution. The procedure was tested using large sample of data registered by a dedicated detection setup enabling sampling of signals with 50-ps intervals. Experimental setup provided irradiation of a chosen position in the plastic scintillator strip with annihilation gamma quanta

Multiple scattering and accidental coincidences in the J-PET detector simulated using GATE package

Novel Positron Emission Tomography system, based on plastic scintillators, is developed by the J-PET collaboration. In order to optimize geometrical configuration of built device, advanced computer simulations are performed. Detailed study is presented of background given by accidental coincidences and multiple scattering of gamma quanta

Strip- PET : a novel detector concept for the TOF-PET scanner

We briefly present a design of a new PET scanner based on strips of polymer scintillators arranged in a barrel constituting a large acceptance detector. The solution proposed is based on the superior timing properties of the polymer scintillators. The position and time of the reaction of the gamma quanta in the detector material will be determined based on the time of arrival of light signals to the edges of the scintillator strips

A novel method based solely on field programmable gate array (FPGA) units enabling measurement of time and charge of analog signals in positron emission tomography (PET)

Abstract: This article presents an application of a novel technique for precise measurements of time and charge based solely on a field programmable gate array (FPGA) device for positron emission tomography (PET). The described approach simplifies electronic circuits, reduces the power consumption, lowers costs, merges front-end electronics with digital electronics, and also makes more compact final design. Furthermore, it allows to measure time when analog signals cross a reference voltage at different threshold levels with a very high precision of ~15 ps (rms) and thus enables sampling of signals in a voltage domain