Browsing by Subject "cell proliferation"
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Item Prevention of posterior capsule opacification by intraoperative single-dose pharmacologic agents(Elsevier Inc., 2001) Inan Ü.Ü.; Öztürk F.; Kaynak S.; Kurt E.; Emiroǧlu L.; Özer E.; Ilker S.S.; Güler C.Purpose: To determine whether an intraoperative single dose of dexamethasone, diclofenac, ethylenediaminetetraacetic acid (EDTA), a combination of EDTA and RGD peptide (arginine-glycin-aspartic acid sequence), or mitomycin-C (MMC) is a pharmacological means of preventing or reducing the development of posterior capsule opacification (PCO). Setting: Department of Ophthalmology, Celal Bayar University, School of Medicine, Manisa, and Department of Pathology, Dokur Eylül University, School of Medicine, izmir, Turkey. Methods: Fifty-four rabbits were randomly divided into 6 groups. Dexamethasone (4 mg/cc), diclofenac (2.5 mg/cc), EDTA (8 mg/cc), a combination of EDTA and RGD peptide (2.5 mg/cc), or MMC (0.04 mg/cc) was given, 0.1 cc by hydrodissection and 0.9 cc into the capsular bag after phacoemulsification. The sixth group served as a control group. After 3 months, the PCO was graded clinically and the proliferation of lens epithelial cells (LECs) was evaluated histologically. Results: The drugs were significantly effective in preventing PCO compared with the control (P < .005). Dexamethasone had a weaker effect than the other drugs. In histological analysis, although monolayer LECs in the dexamethasone and diclofenac groups were observed, there was no proliferative activity on the posterior capsules in the EDTA, EDTA+RGD, and MMC groups in contrast to the multilayer cells in the control. Conclusions: Intraoperative single-dose application of EDTA, EDTA+ RGD peptide combination, and MMC significantly prevented the development of PCO in rabbit eyes. Diclofenac was less effective but also reduced PCO. Although dexamethasone did not prevent the proliferation of LECs, it decreased PCO clinically. © 2001 ASCRS and ESCRS.Item Prevention of posterior capsule opacification by retinoic acid and mitomycin(2001) Inan U.U.; Öztürk F.; Kaynak S.; Ilker S.S.; Özer E.; Güler C.Background: Our aim was to evaluate the effect of an intraoperative single dose of retinoic acid (RA) or mitomycin C (MMC) in preventing posterior capsule opacification (PCO). Methods: Twenty-seven rabbits were divided randomly into three groups. RA (250 μg/ml) and MMC (0.04 mg/ml) were given 0.1 ml by hydrosection and 0.9 ml into the capsular bag after phacoemulsification. The third group served as a control group. Three months after intervention PCO was graded clinically. Furthermore, proliferation of lens epithelial cells was evaluated histologically. Results: Two eyes developed corneal edema in the MMC group. On clinical assessment, RA and MMC were significantly effective in preventing PCO compared with controls (P<0.005). On histological analysis, there was significantly reduced proliferative activity on posterior capsules in the treatment groups, in contrast to multi-layer cells in the control group. Conclusion: Intraoperative single-dose administration of RA and MMC significantly prevented the development of PCO in rabbit eyes. The optimal biocompatible dosage must be carefully determined by further investigation.Item Serum lipids and apolipoproteins in patients with psoriasis(2002) Uyanik B.S.; Ari Z.; Onur E.; Gündüz K.; Tanülkü S.; Durkan K.Psoriasis is characterized by defects in the normal cycle of epidermal development that lead to epidermal hyperproliferation, altered maturation of skin cells, vascular changes and inflammation. Also, psoriasis has been associated with an abnormal plasma lipid metabolism. Changes in plasma lipid and lipoprotein composition in patients with psoriasis may be the reason for the increased risk of atherosclerosis in these patients. We determined serum concentrations of lipids, lipoproteins and apolipoprotein A1 and B (apo A1 and apo B) in 72 patients with psoriasis and 30 age-matched controls. Serum lipoprotein (a) (Lp(a)), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and other biochemical parameters by enzymatic methods. Serum Lp(a) and triglyceride (TG) were significantly higher in patients with psoriasis than in healthy control subjects (p<0.01 for both). Apo B was also found to be higher in the patient group, but the difference was not significant. The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apo A1 did not differ significantly from those of the controls. These observations imply that serum Lp(a) and TG concentrations may play a role as risk factors for atherosclerotic disease in patients with psoriasis.Item The effect of recombinant human growth hormone (rhGH) on trinitrobenzene sulfonic acid-induced colitis in rats: An experimental study(2004) Kara E.; Sungurtekin H.; Sungurtekin U.; Alkanat M.; Ilkgul O.The limited efficacy of standard medical therapies for inflammatory bowel diseases has resulted in a continuing search for alternative treatments. Growth hormone (GH) has shown to have mutagenic and proliferative effects on intestinal cells. This study was designed to identify the effect of growth hormone on trinitrobenzene slfonic acid-induced colitis (TNBSIC) in rats. This study was carried out on 30 rats, divided in 3 groups: group 1: TNBSIC+ GH, group 2: TNBSIC, group 3: saline enema. Colitis was induced in male Sprague-Dawley rats (200 g-250 g) by intracolonic installation of 2, 4, 6-trinitrobenzene sulphonic acid in 50% ethanol. GH treatment has been started and continued throughout the study after inducing colitis. All rats were killed after 5 weeks and colonic segments were examined histopathologically. Microscopic and macroscopic damage scores were caulculated. Intestinal damage scores were found higher in Goups II when compared with treatment group (P < 0.05). There was no damage in group 3 as expected. Both macroscopic and microscopic scores were highest in group 2 (P < 0.05). The myloperoxidase activity was found lower comparing to group 2 (P < 0.05). In conclusion, growth hormone replacement had protective effects against colonic inflammation while reducing intestinal damage on TNB-induced colitis. Copyright © 2004 by Lippincott Williams & Wilkins.Item Cell division and cellular morphology of the chick retinal pigmented epithelial cells in culture. A time-lapse analysis(2005) Tuglu I.; Cezayirli E.; Vural K.; Gungor K.; Varol T.; Bekir N.Objective: To investigate the patterns of cell division, movement and shape during early stages of development of the chick embryo retinal pigmented epithelial (RPE) cells and to evaluate the morphology of dissociated embryonic cells with regard to their proliferation capacity. Methods: We conducted this study at the Department of Histology and Embryology, Celal Bayar University, Manisa, Turkey, between 2002 and 2003. We isolated the cells from chick embryos. We analyzed the images of the embryonic cells originated from neuroepithelia using a computer-based time-lapse acquisition system attached to a differential interference contrast microscope. Results: Retinal pigmented epithelial cells, despite being dissociated, depict a colony-type growth. Cells in the periphery of the colony and those outside the colony showed a tendency to proliferate and migrate and retained contact with the neighboring cells during division. Characteristics of cytokinesis were separation from the neighboring cell while retaining an attachment point, became rounded, moved up and started to shake and ascend to disseminate to the substrate to complete the division. The round-up stage was non-significantly shorter when the cell was closer to the center of the colony. Cells that were in the periphery of, or outside the colony had a round-up time of over one hour while cytokinesis-to-adhesion time was around 5 minutes. However, when we found the cells in the center of the colony, the times were half-an-hour and 1.5 hours for the daughter cells, a 2-fold difference between daughter cells with regard to the duration of attachment. Conclusion: Cell division, migration and proliferation are complex procedures influenced by growth factors, cell adhesion, matrix molecules underneath and the signal mechanisms and can be studied in detail using time-lapse microscopy, immunohistochemistry and confocal microscopy.Item Investigation of histopathological and cytogenetic effects on Lepomis gibbosus (Pisces: Perciformes) in the çine stream (Aydin/Turkey) with determination of water pollution(2005) Koca Y.B.; Koca S.; Yildiz Ş.; Gürcü B.; Osanç E.; Tunçbaş O.; Aksoy G.Water quality and the distribution of some heavy metals in three different organs of Lepomis gibbosus from the Çine Stream were studied. Also, histopathological changes in gill, liver, and muscle tissue were examined at light microscopical level. Micronucleus (MN) formation in fish erytrocytes, as an indicator of chromosomal damage, has been increasingly used to detect the genotoxic potential of environmental contaminants. The frequency of MN was examined from samples of fish from the Çine Stream and a control group. MN frequency was higher in fish samples caught from the Çine Stream than that in the control group. The chemicals ammonia, nitrite, nitrate, orthophosphate, and sulphate were determined as parameters that possibly affect the gill, liver, and muscle morphology. Zn was the most accumulated metal in tissues as well as in water. Maximum metal accumulation occured in both liver and gills. For histopathological examinations, samples of gills, liver, and muscle tissues of L. gibbosus were studied by using light microscopy. In this study, a significant decrease in mean length of primary and secondary lamellae were observed. Moreover, cellular proliferation developed with secondary lamellae fusion, ballooning degenerations or club deformation of secondary lamellae, as well as distribution of necrotic, hyperplastic and clavate secondary lamellae. In the liver, altered staining, swollen and ruptured parenchymal cells, loss of cord structure, reduce of glycogen in hepatocytes, and vacuolar structure filled with cellular debris and many dark particles were seen. In muscle tissue, focal necrosis, cellular dissolution, and a decline or loss of striatation in muscle fibres were found. © 2005 Wiley Periodicals, Inc.Item Early diagnosed but late treated subungual melanoma [8](2006) Sahin M.T.; Ozturkcan S.; Seyhan A.; Demireli P.; Turel-Ermertcan A.[No abstract available]Item Evaluation of histologic changes in the urinary tract of hypercalciuric rats(2006) Akil I.; Kavukçu S.; Inan S.; Yilmaz O.; Atilla P.; Işlekel H.; Neşe N.; Müftüoǧlu S.Idiopathic hypercalciuria (IH) has been speculated to have a predisposing role in the development of urinary tract infection (UTI), due to the uroepithelial cell damage it leads to. In this study, we aimed to investigate the effects of hypercalciuria on the bladder, ureters, and kidneys in rats with experimentally induced hypercalciuria. Normocalcemic hypercalciuria was induced by furosemide (60 mg/100 mL of drinking water) administration to 16-week-old male Wistar Albino rats for 14 days. Calciuria (calcium/creatinine ratio, mg/mg, Ca/Cr) increased from 0.07±0.01 at the beginning of administration to 0.41±0.1 on day 14 (p=0.000). The Ca/Cr ratio was 0.14±0.06 at the beginning of the study and 0.25±0.06 on day 14 in the control group rats (p=0.002 vs. the hypercalciuric group rats on day 14). Bladder, ureter, and kidney specimens of the rats, dissected on the 14th day, were fixed in 10% formalin and 2.5% gluteraldehyde solutions for light and electron microscopic examination, respectively. Histopathological and ultrastructural examination of the hypercalciuric rats revealed proliferation and apical cytoplasmic vacuole formation in transitional epithelial cells, mitotic activity in the intermediate cell line, vasodilatation, edema, and separation of collagen fibers in the bladder and ureter specimens. Light microscopic examination of the kidney specimens revealed a lot of erythrocyte in the glomerular capillary lumen, while electron microscopy revealed vacuolization of proximal and distal tubules, tubular degeneration, interstitial edema, and vasodilatation. In this study, hypercalciuria was observed to have adverse effects on the cell architecture of the uroepithelium and disruption of the epithelial barrier of the bladder and ureters and all kidney structures, especially on the proximal epithelial cells. © IPNA 2006.Item The effect of osteogenic medium on the adhesion of rat bone marrow stromal cell to the hydroxyapatite(2006) Deliloglu-Gurhan I.; Tuglu I.; Vatansever H.S.; Özdal-Kurt F.; Ekren H.; Taylan M.; Sen B.H.Objective: To investigate the adhesive properties of bone marrow stromal cell (BMSC) on the hydroxyapatite (HA) particles and analyze their behavior. Methods: The study took place in the Department of the Histology and Embryology, Celal Bayar University, Manisa and in the Department of Bioengineering, Ege University, Izmir, Turkey between 2004 and 2005. We cultured BMSC from the mature rat tibia and differentiated to the osteoblasts by osteogenic medium. The BMSCs were subcultured and were taken to the HA substrate. We measured their proliferation capacity and viability with MTT assay using the spectrophotometric method. Furthermore, we identified the osteoblast-like cells by inummohistochemical staining of osteonectin and osteocalcin and we analyzed the behavior of the cells on different sized HA particles by SEM at the end of 3 days incubation. Results: Osteogenic medium caused the proliferation capacity of BMSC to speed up and the effects appeared earlier. We confirmed the osteoblastic differentiation by staining of most cells with osteoblastic markers. Subcultured cells were similarly adhesive to the HA particles and the osteogenic medium did not alter this behavior. They spread on the substrate similarly. Most of the cells demonstrated the cytoplasmic protrusion. Morphology of the cells did not change much with or without osteogenic medium. Different sizes of HA particles did not affect the adhesive properties of these cells except HA gel. The spreading and attachment ratios of the cells on HA gel were more than the others. Conclusion: We found that there was heterogeneity in BMSC on differentiation capacity to the osteoblast, which was a sign of a subpopulation. Adhesive cells showed similar morphology and behavior under the effect of osteogenic medium. The only difference was the spreading capacity on the HA gel where cell used this substrate more effectively for adhesion.Item Hormone receptor expressions and proliferation markers in postmenopausal endometrial polyps(2006) Inceboz U.S.; Nese N.; Uyar Y.; Ozcakir H.T.; Kurtul O.; Baytur Y.B.; Kandiloglu A.R.; Caglar H.; Fraser I.S.Background/Aims: Endometrial polyps are quite common in the general population, they have a significant role in postmenopausal bleeding, and the pathogenesis is unclear. The aim of this study was to investigate proliferation markers and expression of estrogen and progesterone receptors in endometrial polyps in postmenopausal women. Methods: Endometrial polyps were removed by hysteroscopy from 36 women who presented with postmenopausal bleeding. None were using hormonal therapy. The control group consisted of 16 inactive-atrophic postmenopausal endometrial specimens removed at hysterectomy. Immunohistochemistry was used to demonstrate expression of estrogen and progesterone receptors and the cell growth and apoptosis markers, Ki67, bcl-2, c-erbB-2. Results: In both the glandular epithelium and stroma of endometrial polyps, estrogen and progesterone receptors, Ki67 and bcl-2 showed significantly more positive staining than the inactive endometrium from the control group. There was no difference in expression of c-erbB-2 between the two groups. Conclusions: Estrogen may have a role in the development of postmenopausal endometrial polyps, either by direct stimulation of localized proliferation or by stimulation of proliferation via other pathways, such as activation of Ki67 or through inhibition of apoptosis via bcl-2. c-erbB-2 is unlikely to play any role in development of these lesions. Copyright © 2006 S. Karger AG.Item Chemotherapy influences inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activity on 3D breast cancer cell line(Tech Science Press, 2006) Öktem G.; Bilir A.; Selvi N.; Yurtseven M.E.; Vatansever S.; Ates U.; Uysal A.; Omay S.B.Multicellular tumor spheroids (MTS) are three-dimensional structural forms of tumors grown in vitro in the laboratory. In this study, the aim was to determine the regulation of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expressions on MTS in response to treatment with the commonly used anti-cancer drugs Doxorubicin and Docetaxel. The spheroids were generated using the "liquid overlay" technique. The distribution of both iNOS and eNOS was detected using indirect immunohistochemistry, while the expression of both iNOS and eNOS was measured using Western blots. Additionally, S-phase analysis using 5-bromo-2′- deoxyuridine (BrdU) was done on the MTS after treatment with doxorubicin, docetaxel, and a combination of the two. The Griess method was used to measure nitric oxide (NO) production in the cells. An increase in iNOS immunoreactivity and a decrease in eNOS immunoreactivity were observed after doxorubicin treatment, when compared with the other groups. Furthermore, upregulation of iNOS and downregulation of eNOS were detected in doxorubicin-treated cells using Western blotting. Insignificant iNOS expression was observed in all of the groups, and it was particularly low in the control and drug combination groups. NO production was also found to be significantly high after docetaxel treatment, and cell proliferation decreased after doxorubicin treatment. In conclusion, chemotherapy influences NOS activity differently with the presence of different drugs. The results with iNOS show that doxorubicin is a more effective drug than docetaxel, and a drug combination may play a helpful role in the suppression of tumorigenicity and cancer metastasis. Interestingly, eNOS expression increased after the addition of both docetaxel and the drug combination, and it was found to negatively correlate with the histological grade of the tumor. Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis. Copyright © 2006 Cognizant Comm. Corp.Item Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in psoriasis(2006) Gündüz K.; Demireli P.; Vatansever S.; Inanir I.Background: Psoriasis is characterised by hyperproliferation and by aberrant differentiation. Blockage of the normal apoptotic process is one of the factors implicated in the pathogenesis. Objective: To determine the apoptotic features by using TUNEL method and also bcl-2 and p53 expressions in psoriatic epidermis. Materials and methods: Biopsies of 35 patients with psoriasis vulgaris and 14 normal skin were evaluated. Apoptotic cells were detected using the dUTP nick-end labelling assay; bc1-2 and p53 expressions were assessed by using immunohistochemical techniques. A semi-quantitative grading system (HSCORE) was used for comparison. Results: Bcl-2 was strongly expressed in basal keratinocytes of normal skin, while no expression was observed in 13 (37.2%) of the psoriatic samples and it was weakly expressed in the spinous cell layer of 22 (62.8%) samples. Moderate p53 expression was observed in the psoriasis group, while it was weak in the control. The percentage of TUNEL positive cells were significantly increased in the psoriasis group (65±2.30) when compared with the control (32.84±7.16). Conclusion: Apoptotic index besides bc1-2 and p53 expressions in psoriasis differ from normal epidermis. Down-regulation of bc1-2 is consistent with the dynamics of psoriasis but increased TUNEL positive cells and p53 expression has not been fully elucidated yet. © Blackwell Munksgaard 2006.Item Characterization of osteoblasts derived from bone marrow stromal cells in a modified cell culture system(Elsevier GmbH, 2006) Deliloglu-Gurhan S.I.; Vatansever H.S.; Ozdal-Kurt F.; Tuglu I.Bone marrow is a complex tissue composed of hematopoietic and stromal stem cells with the potential to differentiate into adipogenic, fibroblastic, reticular, osteogenic and chondrogenic lineages. Identification of differentiation markers during transformation of stromal cells into osteoblasts in a time-dependent manner may be informative for cell-based tissue engineering. Therefore, we investigated the effects of osteogenic medium (OM) on the proliferation and differentiation of rat bone marrow stromal cells (BMSCs). BMSCs from adult male rat tibia and femur were collected and cultured in α-MEM medium with 10% fetal bovine serum, penicillin, streptomycin and gentamycin. After three days of culture, the medium covering the adherent cells in culture was changed to OM containing dexamethasone, Na-β-glycerophosphate and ascorbic acid. As a control, cell culture was also continued in the original medium for the same time period. Differentiated osteoblast cells were collected after 7, 10, 14, 21 and 30 days of culture, fixed with 4% paraformaldehyde and their immunolabelling for osteoblast markers osteonectin (ON) and osteocalcin (OC) was assessed using an indirect immunoperoxidase technique. Immunoabelling of ON and OC was detectable from day 10 of culture, began to increase on day 14, and increased steadily through to day 21. Labelling was highest on day 30 and was more intense in cells cultured with OM compared to the culture without OM. The control cells cultured in the absence of OM produced negligible levels of both markers. In conclusion, our culture system facilitated differentiation of BMSCs into osteoblasts featuring osteoblast markers, and these cells may be useful in autologous bone implant for the treatment of bone wound healing. © 2005 Elsevier GmbH. All rights reserved.Item Muscle-specific PPARβ/δ agonism may provide synergistic benefits with life style modifications(2007) Erol A.Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has emerged as a powerful metabolic regulator in diverse tissues including fat, skeletal muscle, and the heart. It is now established that activation of PPARβ/δ promotes fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. In muscle, PPARβ/δ appears to act as a central regulator of fatty acid catabolism. PPARβ/δ contents are increased in muscle during physiological situations such as physical exercise or long-term fasting, characterized by increased fatty acid oxidation. Targeted expression of an activated form of PPARβ/δ in skeletal muscle induces a switch to form increased numbers of type I muscle fibers resembling the fiber type transition by endurance training. Activation of PPARβ/δ also enhances mitochondrial capacity and fat oxidation in the skeletal muscle that resembles the effect of regular exercise. Therefore, it is hypothesized that muscle-specific PPARβ/δ agonists could be a key strategy to support the poor cardiorespiratory fitness associated with metabolic disorders. Copyright © 2007 Adnan Erol.Item Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress(2007) Erol A.Several protective cellular mechanisms protect against the accumulation of reactive oxygen species (ROS) and the concomitant oxidative stress. Therefore, any reduction in glucose or fatty acid flux into cells leading to a decrease in the production of reducing equivalents would also lead to a decreased ROS production and protect cells against oxidative stress. In the presence of insulin, FOXO proteins are localized from the nucleus to the cytoplasm and degraded. An increase in cellular glucose uptake will lead to increased production of ROS. This in turn activates the stress-responsive Jun-N-terminal kinase (JNK), which promotes nuclear translocation of FOXO proteins, upregulating some important target genes including stress resistance. Consequently, insulin resistance should result in decreased cellular ROS production. For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state. © 2007 Wiley Periodicals, Inc.Item Genotoxic and histopathological effects of water pollution on two fish species, Barbus capito pectoralis and Chondrostoma nasus in the Büyük Menderes River, Turkey(2008) Koca S.; Koca Y.B.; Yildiz Ş.; Gürcü B.The genotoxic and histopathological effects of water pollution were investigated on two fish species caught from the Buyuk Menderes River and from its tributary, the Cine Stream. The Buyuk Menderes basin is an important agricultural area in Turkey. The levels of copper, zinc, cadmium, cobalt, and lead were measured at the surface of the water and in gills, liver, and muscle tissue of Chondrostoma nasus and Barbus capito pectoralis. In some tissues, the concentrations of some of these metals exceeded acceptable levels for human consumption. Zinc was found to be the most abundant metal in water and tissues. Maximal metal accumulation was observed in the liver. To detect the genotoxic potential of contaminants, the formation of micronucleus in erythrocytes was used as indicator of chromosomal damage. The frequency of micronucleus formation did not show significant differences between locations and controls in B. capito pectoralis caught from three locations and C. nasus from two locations. The histological changes included significant decreases of the mean lengths of primary and secondary lamellae. In gills epithelia, we observed cellular proliferation that developed Because of secondary lamellae fusion, ballooning degenerations, or club deformation of secondary lamellae and cystic structures in secondary lamellae. In the liver, the changes included swollen and ruptured parenchymal cells, loss of cord structure, vacuoles filled with cellular debris, focal necrosis, and a significant increase in Kupffer cells. © 2007 Humana Press Inc.Item Profiling of angiogenic cytokines produced by hormone- And drug-refractory prostate cancer cell lines, PC-3 and DU-145 before and after treatment with gossypol(2008) Karaca B.; Kucukzeybek Y.; Gorumlu G.; Erten C.; Gul M.K.; Cengiz E.; Atmaca H.; Uzunoglu S.; Sanli U.A.; Karabulut B.; Uslu R.In this study, we aimed to investigate the angiogenic cytokine profiles of hormone- and drug- refractory prostate carcinoma cell lines, PC-3 and DU-145. We also studied the effect of gossypol, a natural polyphenolic cotton-seed extract, on the angiogenic cytokine profile of these cell lines. XTT cell proliferation assay was used for the assessment of cytotoxicity. For apoptosis, both histone-DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used. Angiogenic cytokine profiles of supernatants from both cell lines, before and after treatment with gossypol, were investigated using the human angiogenesis antibody array I®. It was shown that the two different hormone- and drug-resistant prostate cancer cell lines, PC-3 and DU-145, constitutively express some important angiogenic cytokines, which are known to regulate tumorigenic- ity and angiogenesis in hormone-refractory prostate cancer. However, PC-3 and DU-145 cells have distinct angiogenic cytokine profiles. In addition, these two cells lines respond differently to gossypol treatment in terms of cytotoxicity and angiogenic cytokine secretion. After treatment with 10 μM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7- and 1.8-fold decrease in ENA-78 and GRO-α levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively. We conclude that PC-3 and DU-145 cells secrete significant amounts of different angiogenic cytokines that may explain their aggressive nature and metastatic potential. Gossypol treatment affects angiogenic cyto- kine secretion from these two cell lines in a different manner. By expanding our knowledge of the heterogeneous biological behavior of these two cell lines, novel treatment approaches can be developed for the treatment of prostate cancer.Item Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145(2008) Kucukzeybek Y.; Gul M.K.; Cengiz E.; Erten C.; Karaca B.; Gorumlu G.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.Background. The management of hormone-refractory prostate cancer (HRPC) still remains as an important challenge of daily oncology practice. Docetaxel has proved to be a first line treatment choice. All-trans retinoic acid (ATRA) could potently inhibit the growth of prostate cancer cells in vitro and its combination with various anticancer agents results in increased cytotoxicity. Based on these data, our aim was to examine the synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and ATRA, in hormone- and drug refractory human DU-145 prostate cancer cells. Furthermore, we have searched for the underlying mechanisms of apoptosis by demonstrating apoptosis-related genes. Methods. XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. For detecting the mechanism of apoptosis induced by docetaxel-ATRA combination, OligoGeArray® which consists of 112 apoptosis related genes was used. Results. Our results revealed that docetaxel and ATRA were synergistically cytotoxic and apoptotic in DU-145 cells, in a dose- and time dependent manner. It was also shown by our studies that apoptosis was induced in DU-145 prostate carcinoma cells with significant cytotoxicity, no matter which agent applied first. We have found out that docetaxel-ATRA combination significantly downregulates survivin (BIRC5), myeloid cell leukemia-1 (MCL-1) and lymphotoxin β-receptor (LTβR) genes, which all three have pivotal roles in regulation of apoptosis and cell cycle progression. Conclusion. In conclusion, we strongly suggest that docetaxel and ATRA combination is a good candidate for this challenging era of daily oncologic practice. Also, the combination of docetaxel and ATRA might allow a reduction in docetaxel doses and by this way may diminish docetaxel adverse effects while maintaining the therapeutic effect in patients with HRPC. © 2008 Kucukzeybek et al; licensee BioMed Central Ltd.Item Carcinoma in situ of the urinary bladder: Review of clinicopathologic characteristics with an emphasis on aspects related to molecular diagnostic techniques and prognosis(Jones and Bartlett Publishers, 2009) Nese N.; Gupta R.; Bui M.H.T.; Amin M.B.Carcinoma in situ (CIS) of the urinary bladder is defined as a flat lesion comprising of cytologically malignant cells which may involve either full or partial thickness of the urothelium. De novo CIS constitutes less than 3% of all urothelial neoplasms; however, CIS detected concurrently or secondarily during follow-up of urothelial carcinoma constitutes 45% and 90%, respectively, of bladder cancer. CIS is noted predominantly in male smokers in the sixth or seventh decade. Patients may present with dysuria, nocturia, and urinary frequency and urgency with microscopic hematuria. Cystoscopic findings may range from unremarkable to erythema or edema. Urine cytology is an important diagnostic tool. Cellular anaplasia, loss of polarity discohesion, nuclear enlargement, hyperchromasia, pleomorphism, and atypical mitoses are the histopathologic hallmarks of CIS. Extensive denudation of the urothelium, monomorphic appearance of the neoplastic cells, inflammatory atypia, radiation induced nuclear smudging, multinucleation, and pagetoid spread of CIS may cause diagnostic difficulties. Together with clinical and morphologic correlation, immunostaining with CK 20, p53 (full thickness), and CD44 (absence of staining) may help accurately diagnose CIS. Fluorescent in situ hybridization analysis of voided urine for amplification of chromosomes 3, 7, and 17 and deletion of 9p has high sensitivity and specificity for diagnosing CIS in surveillance cases. Several other molecular markers, such as NMP 22 and BTA, are under evaluation or used variably in clinical pathology. Intravesical bacillus Calmette-Guerin (BCG) instillation is considered the preferred treatment, with radical cystectomy being offered to refractory cases. Chemotherapy, α-interferon, and photodynamic therapy are other modalities that can be considered in BCG-refractory cases. Multifocality, involvement of prostatic urethra, and response to BCG remain the most important prognostic factors, although newer molecular markers are being evaluated for this entity. Patient outcome varies based on whether it is de novo development or diagnosed secondary to prior or concomitant papillary bladder cancer. From a clinical perspective, the principal determinants of outcome are extent of disease, involvement of prostatic urethra, response to therapy, and time to recurrence. © Journal of the National Comprehensive Cancer Network.Item Effects of ocreotide on intestinal mucosa in rats with portal hypertensive enteropathy(2009) Aydede H.; Seda Vatansever H.; Erhan Y.; Ilkgül O.To clarify the effects of long-term ocreotide (a long-acting somatostatin analogue) treatment on mucosal changes in a rat model of portal hypertensive enteropathy, groups of male Swiss albino rats (n=15 each) were randomly assigned to one of three treatment arms. These were: sham laparotomy+twice daily subcutaneous saline 0.5 mL (Group 1); portal hypertension induction+twice daily subcutaneous saline 0.5 mL (Group 2); and portal hypertension induction+subcutaneous ocreotide 100 μg/kg/12 h (Group 3). After 12 weeks of treatment, jejunal and ileal tissue specimens were obtained and evaluated histopathologically (villus/crypt ratio, mean diameter of dilated vessels, mucosal edema, and fibromuscular proliferation in the lamina propria) and immunohistochemically (vascular endothelial growth factor (VEGF), von Willebrand factor (F8), and cluster of differentiation 34 (CD34) labelling). In jejunal specimens, the villus/crypt ratio was markedly lower in Group 2 (2.38±0.46 μm) than in Group 1 (5.07±2.25 μm) or Group 3 (4.97±2.19 μm); mean diameter of dilated vessels was markedly higher in Group 2 (43.30±5.71 μm) than in Group 1 (33.53±4.00 μm) or Group 3 (36.76±3.96 μm); mucosal edema and fibromuscular proliferation were universally absent in Group 1 when compared with the other groups. There were statistically significant differences (p<0.05) between Groups 1 and 2 for villus/crypt ratio, mean diameter of dilated vessels, VEGF immunolabelling intensity, and CD34 immunolabelling intensity; between Groups 1 and 3 for mean diameter of dilated vessels, VEGF immunolabelling intensity, and CD34 immunolabelling intensity; and between Groups 2 and 3 for villus/crypt ratio, mean diameter of dilated vessels, and VEGF immunolabelling intensity. In ileal tissue specimens, the villus/crypt ratio was markedly lower in Group 2 (5.51±0.67 μm) than in either Group 1 (7.19±2.18 μm) or Group 3 (7.62±2.58 μm); mean diameter of dilated vessels was markedly higher in Group 2 (46.36±4.77 μm) than in either Group 1 (36.43±4.57 μm) or Group 3 (41.31±4.70 μm); while mucosal edema was absent in Group 1, it was present in Group 2 and Group 3; and fibromuscular proliferation was universally absent. There were statistically significant differences (p<0.05) between Groups 1 and 2 for villus/crypt ratio and mean diameter of dilated vessels; between Groups 1 and 3 for mean diameter of dilated vessels; and between Groups 2 and 3 for villus/crypt ratio, mean diameter of dilated vessels, and VEGF immunolabelling intensity. Together, these findings indicate that ocreotide treatment ameliorates histomorphological changes in a rat model of portal hypertensive enteropathy. © 2008 Elsevier GmbH. All rights reserved.