ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

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N. A. Gorban

2014-08-01

Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells.

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Goldsmith, Chloe D; Vuong, Quan V; Sadeqzadeh, Elham; Stathopoulos, Costas E; Roach, Paul D; Scarlett, Christopher J

2015-07-17

Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

Daphne striata Tratt. and D. mezereum L.: a study of anti-proliferative activity towards human cancer cells and antioxidant properties.

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Tundis, Rosa; Loizzo, Monica R; Bonesi, Marco; Peruzzi, Lorenzo; Efferth, Thomas

2018-02-12

In this study, we investigated for the first time the anti-proliferative and antioxidant properties of D. mezereum and D. striata. The aerial parts were extracted by maceration with n-hexane, dichloromethane, and methanol. MPLC, GC, and GC-MS were used for the phytochemical study. The anti-proliferative activity was tested against MCF-7, A549, LNCaP, ACHN, and C32 cancer human cells. The antioxidant activity was measured by employing β-carotene bleaching, ABTS, DPPH, and FRAP tests. The Relative Antioxidant Capacity Index (RACI) was applied from the perspective of statistics. D. mezereum dichloromethane extract showed a remarkable anti-proliferative with an IC 50 of 6.08 μg/mL against LNCaP cells. Experimental data indicate that Daphne species have interesting anti-proliferative and antioxidant properties that deserve more investigations to develop novel antineoplastic drugs.

Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

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Vergmann, Anna Stage; Torp, Thomas Lee; Lundberg, Kristian

Title of abstract: Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy Design of study: Three months prospective, interventional clinical study. Purpose: The retinal vascular tree can be measured non-invasively and summarized...... into the central retinal artery and vein equivalent (CRAE and CRVE). The purpose of this study was to evaluate retinal calibers as biomarkers for disease activity 3 months after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). Methods: Fifty one eyes from 40 newly...... with proliferative diabetic retinopathy....

Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

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Bagora Bayala

Full Text Available This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78% and β-caryophyllene (10.54% for Ocimum basilicum; 1, 8-cineol (31.22%, camphor (12.730%, α-pinene (6.87% and trans α-bergamotene (5.32% for Ocimum americanum; β-caryophyllene (21%, α-pinene (20.11%, sabinene (10.26%, β-pinene (9.22% and α-phellandrene (7.03% for Hyptis spicigera; p-cymene (25.27%, β-caryophyllene (12.70%, thymol (11.88, γ-terpinene (9.17% and thymyle acetate (7.64% for Lippia multiflora; precocene (82.10%for Ageratum conyzoides; eucalyptol (59.55%, α-pinene (9.17% and limonene (8.76% for Eucalyptus camaldulensis; arcurcumene (16.67%, camphene (12.70%, zingiberene (8.40%, β-bisabolene (7.83% and β-sesquiphellandrène (5.34% for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides showed the

Two novel prenylated kaempferol derivatives from fresh bud's fur of Platanus acerifolia and their anti-proliferative activities.

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Zuo, Bo; Liao, Zhi-Xin; Xu, Chen; Liu, Chao

2016-01-06

Two novel prenylated kaempferol derivatives (1, 2), together with seven known metabolites were isolated from ethanol extract of fresh Platanus acerifolia bud's fur by multistep chromatographic processing. Structure of compounds 1 and 2 was confirmed by 1D, 2D NMR spectra and HR-ESI-MS. In addition, compound 1 was further analysed by X-ray crystallography. Anti-proliferative activities in vitro against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (Hep-G2) cell lines for compound 1, 2 and 8 were evaluated. Compound 1 exhibited cytotoxic activity towards MCF-7 and Hep-G2 cell lines with the IC 50 values 38.2 and 39.5 μM, respectively. Moreover, compound 2 showed weak cytotoxic activities against the two cell lines.

Benign Proliferative Breast Lesions and Risk of Cancer

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Serap Erel

2010-06-01

Full Text Available Benign breast lesions (BBL includes a wide variety of histologic entities, which have been broadly classified into non-proliferative lesions, proliferative lesions without atypia, and hyperplasia with atypia. With the increased use of mammography, more benign lesions are being detected, and in order to estimate the risk of breast cancer for specific histologic categories is of great importance to guide clinical management. Women with proliferative lesions without atypia are at slightly increased risk of subsequent breast cancer, whereas women with proliferative lesions with atypia have a higher risk. The risk is 1.5- 2-fold in women with proliferative lesions without atypia, 4-5-fold in women with proliferative lesions with atypia, and 8-10 fold in women with ductal carcinoma in situ. Age at diagnosis of BBL, menopausal status, family history of breast cancer in a first-degree relative, and time since BBL diagnosis on risk of breast cancer are important for risk evaluation. [Archives Medical Review Journal 2010; 19(3.000: 155-167

Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice.

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Chinedu, Enegide; Arome, David; Ameh, Solomon F; Ameh, Gift E

2014-09-01

This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h. The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P < 0.001) anti-proliferative effect throughout the experiment. The inhibition of the radicle growth was more after 72 h (87.42%). At a dose of 5% (v/v), the juice showed a slightly significant (P < 0.05) effect affect after 72 h; however, there was no significant effect at 48 h. The juice at doses of 10% and 20% (v/v) showed a highly significant (P < 0.001) anti-proliferative effect throughout the experiment; however, the percentage inhibitions were higher at 72 h. At 72 h, the percentage inhibition for juice at 10% (v/v) was 72.37% and at 20% (v/v) was 91.96%. The concentrations of 40% and 60% (v/v) showed cytostatic effects as no appreciable growth of the radicles of the seeds was observed throughout the experiment. The percentage inhibition for 40% (v/v) was 100% and 99.72% for 48 and 72 h, respectively, while that for the juice concentration of 60% (v/v) was 100% throughout the study. The experiment has shown that C. sinensis fruit juice has a potential for causing both anti-proliferative and cytostatic effects on fast proliferating cells and hence cancerous cells.

Effect of postradiation bleeding on proliferative activity of cells in small intestine crypts of rats

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Petrovic, N V [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia)

1975-12-01

The effect of postradiation bleeding on the dynamics of duodenal crypt's cell proliferation in rats was studied. The animals, females, three months old, weighing 170 or 180 g, were exposed to radiation of 800 R (115 R/min) and immediately after irradiation were bled by cardiac puncture to 50% of total blood volume. Proliferative activity of duodenal epithelium cells was monitored for a period of five days after irradiation. For control purposes normal, irradiated and only bled animals were used. The results demonstrated that although there are no significant differences in proliferative activity of duodenal epithelium cells in irradiated and bled animals and only irradiated animals, the postradiation reparative processes in irradiated and bled animals is considerably more stable. It is considered that bleeding itself by its hypoxic activity reduced the sensitivity of epithelium to the dose of radiation used. On the other hand, bleeding removed the damaging agents which appear after total body irradiation.

Cytosol cathepsin-D content and proliferative activity of human breast cancer. The Comitato Italiano per il Controllo di Qualita del Laboratorio in Oncologia.

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Paradiso, A; Mangia, A; Correale, M; Abbate, I; Ferri, G; Piffanelli, A; Catozzi, L; Amadori, D; Riccobon, A; De Lena, M

1992-01-01

Mitogenic properties have been demonstrated in vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p < 0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = 0.6828; p = 0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.

Lifespan extension by preserving proliferative homeostasis in Drosophila.

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Benoît Biteau

2010-10-01

Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

Proliferative capacity of murine hematopoietic stem cells

International Nuclear Information System (INIS)

Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

1978-01-01

The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

In vitro anti-proliferative activity of clove extract on human gastric carcinoma

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A. Karimi

2017-10-01

Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

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A. G. Rybka

2016-01-01

Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium, and the mean stromal TLI was also increased. The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium or epithelium of nodular hyperplasia. Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium may account for the rarity of seminal vesicular carcinomas

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population.

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Gonzalez-Salinas, Roberto; Garcia-Gutierrez, Maria C; Garcia-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul; Soberon-Ventura, Vidal R; Gonzalez, Victoria; Lechuga, Rodrigo; Garcia-Solis, Pablo; Garcia-Gutierrez, David G; Garcia-Solis, Marco Vinicio; Saenz de Viteri, Manuel; Solis-S, Juan C

2017-01-01

To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P =0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P =0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r 2 =0.1043, P ≤0.0001; rs3025021 vs rs2010963: D'=0.442, r 2 =0.0446, P =0.149; rs3025035 vs rs2010963: D'=0.505, r 2 =0.0214, P =0.142. This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations

uPAR EXPRESSION IN CANINE NORMAL PROSTATE AND WITH PROLIFERATIVE DISORDERS

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Mariana Rodrigues Faleiro

2013-06-01

Full Text Available Prostatic lesions such as prostatic intraepithelial neoplasia (PIN and proliferative inflammatory atrophy (PIA are studied in human and canine species due to their malignance potential. The plasminogen activator (PA system has been suggested to play a central role in cell adhesion, angiogenesis, inflammation, and tumor invasion. The urokinase-type plasminogen activator receptor (uPAR is a component of the PA, with a range of expression in tumor and stromal cells. In this study, uPAR expression in both canine normal prostates and with proliferative disorders (benign prostatic hyperplasia-BPH, proliferative inflammatory atrophy-PIA, prostatic intraepithelial neoplasia-PIN, and carcinoma-PC was evaluated by immunohistochemistry in a tissue microarray (TMA slide to establish the role of this enzyme in extracellular matrix (ECM remodeling and in the processes of tissue invasion. A total of 298 cores and 355 diagnoses were obtained, with 36 (10.1% normal prostates, 46 (13.0% with BPH, 128 (36.1% with PIA, 74 (20.8% with PIN and 71 (20.0% with PC. There is variation in the expression of uPAR in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in tissue with PIA, PIN and PC. The high expression of uPAR in inflammatory and neoplastic microenvironment indicates increased proteolytic activity in canine prostates with PIA, PIN, and PC.

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

DEFF Research Database (Denmark)

Jensen, V; Ladekarl, M; Holm-Nielsen, P

1995-01-01

The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter histological evidence...... analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p breast cancer who might benefit from adjuvant therapy....

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 percent, and that of the normal central (deep) zone was 0.11 percent. Mean normal stromal TLI's were 0.08 percent and 0.06 percent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 percent, which differs significantly from normal epithelium (p less than 0.05), and the mean stromal TLI was also increased (0.16 percent, p less than 0.1). The mean TLI of prostatic adenocarcinomas was 0.90 percent (range 0.14 to 3.90 percent) which was significantly higher than for either normal epithelium (p less than 0.001) or epithelium of nodular hyperplasia (p less than 0.05). Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium (mean TLI 0.02 percent) may account for the rarity of seminal vesicular carcinomas

Evaluation of the effects of ethinylestradiol on sexual differentiation in the olvas-GFP/STII-YI medaka (transgenic Oryzias latipes) strain as estimated by proliferative activity of germ cells

International Nuclear Information System (INIS)

Hano, Takeshi; Oshima, Yuji; Kinoshita, Masato; Tanaka, Minoru; Mishima, Noriko; Wakamatsu, Yuko; Ozato, Kenjiro; Shimasaki, Yohei; Honjo, Tsuneo

2011-01-01

We evaluated the effects of 17(-ethinylestradiol (EE 2 ) on sexual differentiation in transgenic olvas-GFP/STII-YI medaka (Oryzias latipes) in terms of the proliferative activity of germ cells. This strain contains the green fluorescent protein (GFP) gene fused to the regulatory region of the medaka vasa gene, and germ cell-specific expression of GFP can be visualized in living (transparent) individuals. From 0 days post-hatch (0 dph) onwards, juveniles were exposed to graded concentrations of EE 2 (25.2-1710 ng/L) for 35 days. The gonads of live specimens were monitored by measuring their size and calculating their GFP-fluorescence area. GFP-fluorescent area in control females was about 10 times that in control males at 10 days posthatch (dph) whereas the gonadal size of 10 dph males that had been exposed to 158 ng/L of EE 2 significantly increased up to twice the size of control males, indicating that abnormal sexual differentiation towards female might occur in these individuals. Histological examination and identification of the sex-linked marker SL1 indicated that male to female sex reversal occurred at EE 2 exposure ≥45.1 ng/L at 35 dph. These results suggest that observation of proliferative activity of germ cells in the olvas-GFP/STII-YI strain could be applied to facilitated screening fish model to detect adverse effects on sexual differentiation as early as 10 dph juveniles.

Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

International Nuclear Information System (INIS)

Jeng, Yow-Jiun; Watson, Cheryl S

2009-01-01

Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH 3 /B 6 /F 10 , originally subcloned from GH 3 cells based on its ability to express high levels of the membrane estrogen receptor-α. We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities. Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol) were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH 3 /B 6 /F 10 cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for trans-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens. Phytoestrogens can block physiological estrogen-induced tumor cell growth in vitro and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary

Synthesis, characterization, in vitro anti-proliferative and hemolytic activity of hydroxyapatite

Science.gov (United States)

Palanivelu, R.; Ruban Kumar, A.

2014-06-01

Hydroxyapatite (Ca10(PO4)6(OH)2, HAP) nanoparticles are widely used in several biomedical applications due to its compositional similarities to bone mineral, excellent biocompatibility and bioactivity, osteoconductivity. In this present investigation, HAP nanoparticles synthesized by precipitation technique using calcium nitrate and di-ammonium phosphate. The crystalline nature and the functional group analysis are confirmed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Fourier transform Raman spectroscopy (FT-Raman) respectively. The morphological observations are ascertained from field emission electron scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). In vitro anti-proliferative and hemolytic activities are carried out on the synthesized HAP samples and the studies reveals that HAP have mild activity against erythrocytes.

NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy.

Science.gov (United States)

Loukovaara, Sirpa; Piippo, Niina; Kinnunen, Kati; Hytti, Maria; Kaarniranta, Kai; Kauppinen, Anu

2017-12-01

Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro-inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR). Inflammasome components NLRP3 and caspase-1, inflammasome-related pro-inflammatory cytokines IL-1β and IL-18, vascular endothelial growth factor (VEGF), acute-phase cytokines TNF-α and IL-6, as well as adaptive immunity-related cytokine interferon gamma (IFN-γ) were measured from the vitreous samples of 15 non-proliferative diabetic retinopathy (non-PDR) and 23 proliferative diabetic retinopathy (PDR) patients using the enzyme-linked immunosorbent assay (ELISA) method. The adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) was determined using the Western blot technique. Inflammasome components were present in the vitreous of DR patients. Along with VEGF, the levels of caspase-1 and IL-18 were significantly increased, especially in PDR eyes. Interestingly, clearly higher levels of NLRP3 were found in the PDR eyes with tractional retinal detachment (TRD) than from PDR eyes with fully attached retina. There were no significant differences in the amounts of IL-1β, TNF-α, IL-6, and IFN-γ that were detectable in the vitreous of both non-PDR and PDR patients. Our results suggest that NLRP3 inflammasome activation can be associated especially with the pathogenesis of PDR. The lack of differences in TNF-α, IL-6, and IFN-γ also alludes that acute inflammation or T-cell-mediated responses do not dominate in PDR pathogenesis. © 2017 Acta Ophthalmologica Scandinavica Foundation

Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.

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Maria De Salvo

Full Text Available Rhabdomyosarcoma (RMS is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.

PECULIARITIES OF PROLIFERATIVE ACTIVITY OF CERVICAL SQUAMOUS CANCER IN HIV INFECTION.

Science.gov (United States)

Lytvynenko, M; Shkolnikov, V; Bocharova, T; Sychova, L; Gargin, V

2017-09-01

Patients with human immunodeficiency virus (HIV) infection have a statistically significant increased risk of developing cervical cancer. The expression of the human Ki-67 protein is strictly associated with cell proliferation. The purpose of our work was detection of proliferative activity in cervical squamous cancer in women with HIV infection. We investigated 24 cases (12 patients with HIV and 12 patients without HIV infection) of cervical carcinoma, where biopsy had been performed before the treatment. According to histopathological diagnoses, well-differentiated, moderately and poorly differentiated squamous cell carcinoma (7, 13 and 4 cases respectively) was determined. Mean age of women in the group with HIV infection was 32.7 years, and 38.2 years in the group without HIV infection. Detection of protein Ki-67 expression was performed with nuclear staining in the intermediate and superficial cells. The results of this work show that proliferative activity of cervical squamous cancer in women with HIV infection is characterized by a higher level of Ki-67 with averaging level for all histological types of squamous cell carcinoma 62.5±5.6% that is one and half times higher than in group without HIV infection. Depending on a histological type, expression of Ki-67 has increased from 4.7±3.8% in well-differentiated squamous cell carcinoma up to 89.2±5.1% in poorly differentiated squamous cell carcinoma for group with HIV, and from 21.3±2.4% to 79.4±3.7 in group without HIV.

Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

Science.gov (United States)

Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

2015-12-01

Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.

Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

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Andrea del Pilar Sánchez-Camargo

2016-12-01

Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

In vitro anti-proliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb

Czech Academy of Sciences Publication Activity Database

Landa, Přemysl; Skálová, L.; Boušová, I.; Kutil, Zsófia; Langhansová, Lenka; Lou, J.D.; Vaněk, Tomáš

2014-01-01

Roč. 27, č. 1 (2014), s. 103-106 ISSN 1011-601X R&D Projects: GA MŠk ME08070 Institutional support: RVO:61389030 Keywords : anti-proliferative activity * anti-inflammatory activity * breast cancer Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.682, year: 2014 http://www.pjps.pk/wp-content/uploads/pdfs/27/1/Paper-15.pdf

GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

International Nuclear Information System (INIS)

Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

2011-01-01

Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells

International Nuclear Information System (INIS)

Vanova, K.; Boukalova, S.; Gbelcova, H.; Muchova, L.; Neuzil, J.; Gurlich, R.; Ruml, T.; Vitek, L.

2016-01-01

Pancreatic cancer is recognized as one of the most fatal tumors due to its aggressiveness and resistance to therapy. Statins were previously shown to inhibit the proliferation of cancer cells via various signaling pathways. In healthy tissues, statins activate the heme oxygenase pathway, nevertheless the role of heme oxygenase in pancreatic cancer is still controversial. The aim of this study was to evaluate, whether anti-proliferative effects of statins in pancreatic cancer cells are mediated via the heme oxygenase pathway. In vitro effects of various statins and hemin, a heme oxygenase inducer, on cell proliferation were evaluated in PA-TU-8902, MiaPaCa-2 and BxPC-3 human pancreatic cancer cell lines. The effect of statins on heme oxygenase activity was assessed and heme oxygenase-silenced cells were used for pancreatic cancer cell proliferation studies. Cell death rate and reactive oxygen species production were measured in PA-TU-8902 cells, followed by evaluation of the effect of cerivastatin on GFP-K-Ras trafficking and expression of markers of invasiveness, osteopontin (SPP1) and SOX2. While simvastatin and cerivastatin displayed major anti-proliferative properties in all cell lines tested, pravastatin did not affect the cell growth at all. Strong anti-proliferative effect was observed also for hemin. Co-treatment of cerivastatin and hemin increased anti-proliferative potential of these agents, via increased production of reactive oxygen species and cell death compared to individual treatment. Heme oxygenase silencing did not prevent pancreatic cancer cells from the tumor-suppressive effect of cerivastatin or hemin. Cerivastatin, but not pravastatin, protected Ras protein from trafficking to the cell membrane and significantly reduced expressions of SPP1 (p < 0.05) and SOX2 (p < 0.01). Anti-proliferative effects of statins and hemin on human pancreatic cancer cell lines do not seem to be related to the heme oxygenase pathway. While hemin triggers reactive

Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

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Carolyn Gross

2015-09-01

Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

The differential proliferative ability of satellite cells in Lantang and Landrace pigs.

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Xiu-qi Wang

Full Text Available Here, for the first time, we evaluate the hypothesis that the proliferative abilities of satellite cells (SCs isolated from Lantang (indigenous Chinese pigs and Landrace pigs, which differ in muscle characteristics, are different. SCs were isolated from the longissimus dorsi muscle of neonatal Lantang and Landrace pigs. Proliferative ability was estimated by the count and proliferative activity of viable cells using a hemocytometer and MTT assay at different time points after seeding, respectively. Cell cycle information was detected by flow cytometry. Results showed that there was a greater (P<0.05 number of SCs in Lantang pigs compared with Landrace pigs after 72 h of culture. The percentage of cell population in S phase and G(2/M phases in Lantang pigs were higher (P<0.05, while in G(0/G(1 phase was lower (P<0.05 in comparison with the Landrace pigs. The mRNA abundances of MyoD, Myf5, myogenin and Pax7 in SCs from Lantang pigs were higher (P<0.05, while those of myostatin, Smad3 and genes in the mammalian target of rapamycin (mTOR pathway (with the exception of 4EBP1 were lower (P<0.05 than the Landrace pigs. Protein levels of MyoD, myogenin, myostatin, S6K, phosphorylated mTOR and phosphorylated eIF4E were consistent with the corresponding mRNA abundance. Collectively, these findings suggested that SCs in the two breeds present different proliferative abilities, and the proliferative potential of SCs in Lantang pigs is higher than in Landrace pigs.

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth

NARCIS (Netherlands)

Xue, Y.; Sonke, G.; Schoots, C.; Schalken, J.; Verhofstad, A.; de la Rosette, J.; Smedts, F.

2001-01-01

To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. Consecutive

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.

NARCIS (Netherlands)

Xue, Y.; Sonke, G.S.; Schoots, C.; Schalken, J.A.; Verhofstad, A.A.J.; Rosette, J.J.M.H.C. de la; Smedts, F.

2001-01-01

BACKGROUND: To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity.

Antibacterial, antioxidant and cell proliferative properties of Coccinia grandis fruits

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Prashant Sakharkar

2017-06-01

Full Text Available Objective: Little knowledge is available on the antimicrobial and antioxidant properties of Coccina grandis fruits and no study has reported on its cell proliferative property. The aim of this study was to examine the antimicrobial, antioxidant and cell proliferative property of fruits of C. grandis. Material and Methods: Fruits of C. grandis were extracted using water; ethanol and acetone by cold and hot Soxhlet extraction. The antibacterial activities of the extracts were tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa using the modified Kirby-Bauer diffusion method and compared against erythromycin. The antioxidant property was determined using Cayman's antioxidant assay; whereas cell proliferation/cytotoxic properties were evaluated using the Cell Titer 96 Aqueous One Solution Cell MTS assay with MDA-MB 321 breast cancer cells. Data were analyzed for correlation and differences using unpaired student's t-test and one-way ANOVA. A p value of Results: Both cold and hot ethanol and acetone extracts of C. grandis fruits showed some degree of bacterial growth inhibition. Acetone extracts exhibited higher antibacterial activity. Both ethanol extracts showed antioxidant property when compared with standard Trolox. In contrary to cytotoxicity, all four extracts showed cell proliferation compared to controls at different concentrations. However, acetone extracts exhibited greater cell proliferation compared to ethanol extracts and cold extracts performed better than the hot extracts. Conclusion: C. grandis fruits exhibited some degree of antimicrobial, antioxidant and cell proliferative properties. Further investigation is warranted to isolate, confirm and characterize phytochemicals that are responsible for the medicinal properties observed.

[Effect of low-intensity electromagnetic fields of industrial frequency on the ultrastructure and proliferative activity of rat's thymus cells].

Science.gov (United States)

Zhitkevich, T I; Bokut', T B; Netukova, N I

2001-01-01

Effects of two types of low-intensity electromagnetic fields (EMF) of industrial frequency (50 Hz) on the fine structure and proliferative activity of thymic cells in white rats were studied. It was found that a weak EMF with a prevailing electrical component (380-480 V/m, 120-140 nT1) did not affect the DNA synthesis intensity. An EMF with a stronger magnetic induction (10-15 V/m, 800-1500 nT1) diminished the glucose-6-phosphate dehydrogenase activity and proliferative processes in cultured stimulated lymphocytes. Electron microscopic investigation of the thymus after both types of exposure revealed an accumulation of lymphocytes with pyknotic nuclei and electron-dense cytoplasm, as well as hypoplasia of the vascular endothelium. At the same time, EMF with a prevailing magnetic component produced a more marked negative effect on the ultrastructure of thymic cells, which indicated a lowered secretory activity of epitheliocytes.

Nuclear Morphometry in Ductal Breast Carcinoma with Correlation to Cell Proliferative Activity and Prognosis

International Nuclear Information System (INIS)

Radwan, M.M.; Amer, K.A.; Mokhtar, N.M.

2003-01-01

Morphometry is the quantitative description of biologic structures. This study was designed to evaluate the efficiency of morphometric measurements in diagnosis and prognosis of patients with breast carcinoma. Methods: Histological samples from 61 patients of invasive duct carcinoma (IDC) of no special type (NST), 12 cases of ductal carcinoma in situ (DCIS) and 14 control breast samples taken from fibrocystic change disease were retrospectively analyzed by computerized nuclear morphometry. All IDC patients underwent modified radical mastectomy without preoperative chemotherapy. The mean follow up was 28±19 months (range] -71). In each case, 25-50 nuclei were measured and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean maximum nuclear diameter (MMNO) and mean minimal nuclear diameter (Mmnd) were measured. The mean axis ratio (MAR), mean nuclear compactness (MNC), mean nuclear size (MNS) and mean shape factor (MSHF), were calculated mathematically. To measure the nuclear diameters, a new method was employed using the AutoCAD program. Morphometric parameters were compared with different clinico pathologic features, patient's survival and cell proliferative activity as determined by Ki-67 immunostaining which was evaluated quantitatively. Most of the morphometric parameters were significantly higher in DCIS and IDC groups than benign one. In IDC group morphometric features related to nuclear size (MNA, MNP, MMNO, Mmnd and MNS) were significantly correlated to most clinico pathologic features and cell proliferative activity assessed by Ki-67 immunostaining. However, the shape factor failed to achieve this correlation. The univariate analysis using Kaplan Meier curves indicated that short survival time was correlated with high nuclear morphometric values (MNA. MNP, MMND, Mmnd, MNS and MSHF). Moreover, the Spear man correlation analysis showed that Mmnd has the highest converse correlation with survival (r= -0.75, (ρ < 0.0001). In multivariate analysis

Lack of a differential radiation response for proliferative and non-proliferative rat thyroid cells (FRTL-5) in vitro

International Nuclear Information System (INIS)

Brosing, J.W.; Giese, W.L.; Mulcahy, R.T.

1989-01-01

FRTL-5 rat thyroid epithelial cells maintain normal thyroid function and morphology in vitro, exhibit an absolute requirement for thyroid stimulating hormone (TSH) for proliferation and display radiation dose response characteristics indistinguishable from those of rat thyroid epithelial cells in vivo. In TSH-free medium cells remain in a non-proliferative, yet viable, state for prolonged periods of time and respond to TSH re-stimulation by a return to exponential growth. Flow cytometric analysis using two-step acridine orange (AO) staining revealed an accumulation of cells in the G1 phase of the cell cycle accompanied by a pronounced reduction in red fluorescence (indicative of RNA content) in FRTL-5 cells cultured in the absence of TSH. The response of proliferative and non-proliferative FRTL-5 cells to single dose, split dose and fractionated radiation was compared to determine whether proliferative status was an important response determinant. The response of FRTL-5 cells was not influenced by proliferative status at the time of irradiation. Additionally, dose response was not altered by variable (12 hr-8 days) non-proliferative intervals before or after irradiation. As revealed by split dose experiments, the rate and extent of sublethal damage repair was likewise similar for proliferative and non-proliferative cells. Multifraction experiments employing three fractions separated by 6 hr intervals indicate that non-proliferative FRTL-5 cells completely repair sublethal damage between fractions. These results indicate that the radiation response of FRTL-5 cells is not influenced by the proliferative status of the cells prior to or post-irradiation

Inhibition of proliferative activity in tissue culture in vivo of esophagus and stomach tumour cells under preoperative irradiation

International Nuclear Information System (INIS)

Zinchenko, V.A.; Okulov, L.V.; Gol'dshmid, B.Ya.

1988-01-01

Inhibition of proliferative activity of tumor cells as a result of radiation effect. Tumor tissue taken from patiets with preoperative tumor irradiation by 30 Gy cumulative dose (5 Gy per a session) and from patients whose tumors were not subjected to irradiation (control) was used. The tumor tissue was cultivated in the diffusion chamber and then implanted to the abdominal cavity of the non-inbred male rats. On preparations in the growth area pathomorphological changes were evaluated, the share of mitotically dividing and DNA-synthesizing cells was determined. The absence of growth area around the explant, obvious reduction of mitotic activity and DNA-synthesizing function of cells in preparations of irradiated tumors in 88 % of cases testify to the inhibition of the stomach cardial section and esophagus tumor tissue repopulation after radiation effect. The investigation results confirm the advisability of preoperative irradiation of patients with tumors of the given localization

Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down

NARCIS (Netherlands)

J.L. Costa (José); P.P. Eijk (Paul); M.A. van de Wiel (Mark); D. ten Berge (Derk); F. Schmitt (Fernando); C.J. Narvaez (Carmen); J. Welsh; B. Ylstra (Bauke)

2009-01-01

textabstractBackground: The active form of Vitamin D, 1,25-dihydroxyvitamin D3(1,25D), has strong anti-proliferative effects, yet the molecular mechanisms underneath this effect remain unclear. In contrast, the molecular mechanism of 1,25D for the regulation of calcium homeostasis has principally

Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes.

Science.gov (United States)

Chang, William; Lajko, Michelle; Fawzi, Amani A

2018-01-01

To characterize the relationship between endothelin-1 and fibrosis in epiretinal membranes in proliferative diabetic retinopathy and explore the role of endothelial-mesenchymal transition in these membranes. Membranes were obtained from eyes undergoing pars plana vitrectomy for complicated proliferative diabetic retinopathy or idiopathic epiretinal membrane. Through standard immunohistochemical techniques, we labeled membranes to explore the distribution of endothelin-1 and endothelin receptor B, comparing proliferative diabetic retinopathy and idiopathic epiretinal membranes. In addition, membranes were also labeled with markers for fibroblasts, endothelial, and glial cells and studied with confocal laser scanning microscopy. The intensity of endothelin-1 labeling was quantified using standard image analysis software. Fourteen membranes were included in the analysis, nine from eyes with proliferative diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry and quantitative analysis of cross-sectional membranes showed significantly higher endothelin-1 labeling in proliferative diabetic retinopathy membranes compared to idiopathic membranes (pmembranes showed more elements staining positive for S100A4 compared to idiopathic membranes. Epiretinal membrane formation in proliferative diabetic retinopathy involves higher tissue levels of endothelin-1 and fibroblastic activity. Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be correlated, suggestive of endothelial-to-mesenchymal transition in proliferative diabetic retinopathy.

Proliferative activity of stomach cancer and assessment of individual radiosensitivity

International Nuclear Information System (INIS)

Chissov, V.I.; Sergeeva, N.S.; Dar'yalova, S.L.; Petrov, A.N.; Repina, A.G.; Belous, T.A.; Pelevina, I.I.

1991-01-01

An indirect immunofluorescent method with polyclonal antibodies to thymidine was used to assess the proliferative activity (PA-percent of cells in the S-phase of the cell cycle) of 79 stomach tumors from primary cancer patients. Stomach cancer PA was shown to vary from 0.1 to 69.7%. Stomach cancer PA did not depend either on a tumor size or a degree of the involvement of regional lymph nodes. The mean PA of well-differentiated adenocarcinoma was slightly lower (14.9±4.7%) than that of low differentiated ones. Of 79 patients a tumor process was interpreted as a resectable one in 62. They were given preoperative irradiation at a total focal dose of 36 Gy followed by operation. It was shown that tumor radioresistance could be predicted in unchanged PA indices of their increase at the beginning of a course of irradiation with the probability of 95%

The Relationship between Proliferative Scars and Endothelial Function in Surgically Revascularized Patients

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Murat Ziyrek

2015-12-01

Full Text Available Background: Proliferative scars are benign fibrotic proliferations which demonstrate abnormal wound healing in response to skin injuries. As postulated in the “response to injury hypothesis”, atherosclerosis is also triggered by an endothelial injury. Keloid and atherosclerotic processes have many pathophysiological and cytological features in common. Aims: In this study, we investigated the relationship between proliferative scars and endothelial function in surgically revascularized patients. We aimed to test the hypothesis that atherosclerosis is a wound healing abnormality. Study Design: Cross-sectional study. Methods: Consecutive patients who were admitted to the cardiology outpatient clinic with a history of coronary artery bypass grafting operation were evaluated. Thirty-three patients with proliferative scars at the median sternotomy site formed the keloid group, and 36 age- and sex-matched patients with no proliferative scar at the median sternotomy site formed the control group. Endothelial function was evaluated by flow-mediated vasodilatation of the brachial artery via ultrasonograhic examination. Results: There is no signicant difference according to the demographic data, biochemical parameters, clinical parameters and number of grafts between keloid and control groups. Endothelial-dependent vasodilatory response was lower in the keloid group than the control group (9.30±3.5 and 18.68±8.2, respectively; p=0.001. Conclusion: This study showed that endothalial dysfunction, which is strongly correlated with atherosclerosis, was more prominent in patients with proliferative scars. As proliferative scars and atherosclerosis have many features in common, we might conclude that atherosclerosis is a wound healing abnormality.

Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes

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M.C. Boelter

2006-08-01

Full Text Available Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1% (kappa = 0.735; P < 0.001. Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001, insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001 and diabetes duration (OR = 1.04, 95% CI = 1.01-1.07, P = 0.011 were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86-0.96, P < 0.001 was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95% CI = 1.56-6.98, P = 0.002 remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.

Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

Science.gov (United States)

Er, Hui Meng; Cheng, En-Hsiang; Radhakrishnan, Ammu Kutty

2007-09-25

The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (pCactaceae) do not have appreciable anti-proliferative effect on the 4T1 and NIH/3T3 cells as the EC(50) values obtained are greater than 50 microg/mL when tested under optimal culture condition. Moreover, the aqueous extract may form mutagenic compound(s) upon the metabolisation by liver enzymes.

Proliferative retinopathy predicts nephropathy

DEFF Research Database (Denmark)

Karlberg, Charlotte; Falk, Christine; Green, Anders

2012-01-01

We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same...... cohort. All type 1 diabetic patients from Fyn County, Denmark, were identified as of 1 July 1973. One hundred and eighty four patients were examined in 1981-1982 (baseline) and in 2007-2008 (follow-up). The level of retinopathy was graded by ophthalmoscopy at baseline and nine-field digital colour fundus...... and proliferative retinopathy, respectively. In conclusion, proliferative retinopathy is an independent marker of long-term nephropathy in type 1 diabetes. Upcoming studies should examine whether these microvascular complications are also causally linked in type 1 diabetes....

Non-Proliferative Diabetic Retinopathy Vision Simulator

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... Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis Focus On Pediatric Ophthalmology ... Retinopathy Diagnosis Diabetic Retinopathy Treatment Proliferative Diabetic Retinopathy Vision Simulator Non-Proliferative Diabetic ...

A Predictive Model for Estimation Risk of Proliferative Lupus Nephritis

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Dong-Ni Chen

2018-01-01

Conclusion: This study developed and validated a model including demographic and clinical indices to evaluate the probability of presenting proliferative LN to guide therapeutic decisions and outcomes.

Extraction, purification and anti-proliferative activities of polysaccharides from Lentinus edodes.

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Zhao, Yong-Ming; Wang, Jin; Wu, Zhi-Gang; Yang, Jian-Ming; Li, Wei; Shen, Li-Xia

2016-12-01

In this study, the enzyme-assisted extraction of polysaccharides from Lentinus edodes (LEPs) was optimized by response surface methodology, and a preliminary characterization of the extracted LEPs and their anti-proliferative activities were investigated. An orthogonal assay was constructed to determine the optimal amounts of cellulase, papain and pectinase, which were 15, 20 and 15g/kg, respectively. Then effects of extraction conditions were evaluated and optimized using a Box-Behnken design. The results showed that the highest polysaccharides yield of 15.65% was achieved with an extraction temperature of 54°C, pH 5.0, enzymatic treatment time of 93min and a liquid/material ratio of 29:1mL/g, which correlated well with the predicted yield of 15.58%. Subsequently, the crude LEPs were further purified by DEAE-cellulose and Sephadex-100 chromatography to obtain two fractions, which were designated as LEP-1 and LEP-2 and their monosaccharide compositions were characterized by GC. Fourier-transform infrared spectra demonstrated that LEP-1 and LEP-2 were distinct from each other regarding their chemical structures. In addition, the LEPs exhibited inhibition of cell proliferation on HCT-116 and HeLa cells in vitro. In summary, this study provides an efficient enzyme-assisted extraction for LEPs, which can be used as natural antitumor agents in the pharmaceutical and functional food industries. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of analogy in pro-life argumentation

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Simona Mazilu

2012-11-01

Full Text Available The paper is concerned with how analogy is strategically used in pro-life argumentation on abortion. Pragma-dialectics (van Eemeren and Grootendorst 1992 offers a set of critical questions by means of which I will evaluate the use of the argumentation based on a relation of analogy in terms of dialectical soundness. Examining various pro-life texts, I have noticed that the analogies employed remain unexplained. Therefore, despite the apparent similarities between abortion and the German holocaust or slavery, for instance, there are essential differences which are not mentioned. I claim that these analogies mainly have a rhetorical function, to operate what has been called by Micheli (2007: 960 “a transfer of emotional consensus”.

Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

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Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

2016-01-01

To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

Synthesis, characterization and anti-proliferative activity of heterocyclic hypervalent organoantimony compounds.

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Chen, Yi; Yu, Kun; Tan, Nian-Yuan; Qiu, Ren-Hua; Liu, Wei; Luo, Ning-Lin; Tong, Le; Au, Chak-Tong; Luo, Zi-Qiang; Yin, Shuang-Feng

2014-05-22

Three heterocyclic hypervalent organoantimony chlorides RN(CH2C6H4)2SbCl (2a R = t-Bu, 2b R = Cy, 2c R = Ph) and their chalcogenide derivatives [RN(CH2C6H4)2Sb]2O (3a R = t-Bu, 3b R = Cy, 3c R = Ph) were synthesized and characterized by techniques such as (1)H NMR, (13)C NMR, X-ray diffraction, and elemental analysis. It is found that the anti-proliferative activity detected over these compounds can be attributed to the coordination bond between the antimony and nitrogen atoms of these compounds. Moreover, a preliminary study on mechanistic action suggests that the inhibition effect is ascribable to cell cycle arrest and cell apoptosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Shu-Ling; Wu; Dong-Mei; Zhan; Shu-Hong; Xi; Xiang-Lian; He

2014-01-01

AIM:To investigate the role of tissue plasminogen activator(t-PA) and plasminogen activator inhibitor(PAI)in proliferative diabetic retinopathy(PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor(VEGF) expressions.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.

Proliferative activity of elastin-like-peptides depends on charge and phase transition.

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Yuan, Yuan; Koria, Piyush

2016-03-01

Elastin-like-peptides (ELPs) are stimulus-responsive protein-based polymers and are attractive biomaterials due to their biocompatibility and unique properties. This study shows that in addition to their physical properties, ELPs have biological activities that are conducive to tissue regeneration. Specifically, we found that ELPs induce fibroblast proliferation via cell surface heparan sulfate proteoglycans (HSPG). Furthermore, our data suggests that ELP based materials with differential proliferative potential can be designed by controlling the interaction of ELPs with HSPGs by incorporating either hydrophobic or positively charged residues within the ELP sequence. Fibroblast proliferation is important for granulation tissue formation which is important in chronic wounds as well as in healing of other tissues. The customizable biological activity of ELPs coupled with their unique physical properties will enable us to design novel, sustainable and cost effective therapies for different tissue regeneration applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 697-706, 2016. © 2015 Wiley Periodicals, Inc.

TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

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Weisse, N; Jeraj, R [Department of Medical Physics, University of Wisconsin, Madison, WI (United States)

2014-06-15

Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUV_mean, SUV_max, and SUV_CV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUV_mean, SUV_max, and SUV_CV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUV_mean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUV_max correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

Estrogen signaling in the proliferative endometrium: implications in endometriosis

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Rita de Cássia Pereira da Costa e Silva

2016-02-01

Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

International Nuclear Information System (INIS)

Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

1988-01-01

Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

Structural and functional development of rat and mouse gastric mucous cells in relation to their proliferative activity

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Wattel, W.

1978-01-01

An investigation has been carried out to find a relation between the differentiation and the mitotic activity of gastric mucous cells of the rat and the mouse. It is shown that the bulk mucous production is carried out by the older, non-proliferative, surface mucous cells that line the foveolae and the gastric surface. One experiment describes the renewal of mouse gastric mucous cells following fast neutron irradiation. (C.F.)

Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions

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Romana Tomaszewska

1999-01-01

Full Text Available The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia and high‐grade proliferation (atypical papillary hyperplasia and carcinoma in situ. A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives.

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França, Paulo H B; Da Silva-Júnior, Edeildo F; Aquino, Pedro G V; Santana, Antônio E G; Ferro, Jamylle N S; De Oliveira Barreto, Emiliano; Do Ó Pessoa, Cláudia; Meira, Assuero Silva; De Aquino, Thiago M; Alexandre-Moreira, Magna S; Schmitt, Martine; De Araújo-Júnior, João X

2016-03-01

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L(-1) against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

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França Paulo H. B.

2016-03-01

Full Text Available Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma, MDA-MB-435 (melanoma and SF-295 (glioblastoma were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease

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Tadi, Kiranmayi; Chang Yushan; Ashok, Badithe T.; Chen, Yuangen; Moscatello, Augustine; Schaefer, Steven D.; Schantz, Stimsom P.; Policastro, Anthony J.; Geliebter, Jan; Tiwari, Raj K.

2005-01-01

Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3'-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC 50 values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are 'goitrogenic,' DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease

Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

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Park, Jun Won; Lee, Su Hyung; Woo, Gye-Hyung; Kwon, Hyo-Jung; Kim, Dae-Yong

2018-04-06

TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Eco-friendly synthesis, in vitro anti-proliferative evaluation, and 3D-QSAR analysis of a novel series of monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates.

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Racané, Livio; Ptiček, Lucija; Sedić, Mirela; Grbčić, Petra; Kraljević Pavelić, Sandra; Bertoša, Branimir; Sović, Irena; Karminski-Zamola, Grace

2018-04-17

Herein, we describe the synthesis of twenty-one novel water-soluble monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates 3a-3u and present the results of their anti-proliferative assays. Efficient syntheses were achieved by three complementary simple two-step synthetic protocols based on the condensation reaction of aryl/heteroaryl carbaldehydes or carboxylic acid. We developed an eco-friendly synthetic protocol using glycerol as green solvent, particularly appropriate for the condensation of thermally and acid-sensitive heterocycles such as furan, benzofuran, pyrrole, and indole. Screening of anti-proliferative activity was performed on four human tumour cell lines in vitro including pancreatic cancer (CFPAC-1), metastatic colon cancer (SW620), hepatocellular carcinoma (HepG2), and cervical cancer (HeLa), as well as in normal human fibroblast cell lines. All tested compounds showed strong to moderate anti-proliferative activity on tested cell lines depending on the structure containing aryl/heteroaryl moiety coupled to 6-(2-imidazolinyl)benzothiazole moiety. The most potent cytostatic effects on all tested cell lines with [Formula: see text] values ranging from 0.1 to 3.70 [Formula: see text] were observed for benzothiazoles substituted with naphthalene-2-yl 3c, benzofuran-2-yl 3e, indole-3-yl 3j, indole-2-yl 3k, quinoline-2-yl 3s, and quinoline-3-yl 3t and derivatives substituted with phenyl 3a, naphthalene-1-yl 3b, benzothiazole-2-yl 3g, benzothiazole-6-yl 3h, N-methylindole-3-yl 3l, benzimidazole-2-yl 3n, benzimidazole-5(6)-yl 3o, and quinolone-4-yl 3u with [Formula: see text] values ranging from 1.1 to 29.1 [Formula: see text]. Based on obtained anti-proliferative activities, 3D-QSAR models for five cell lines were derived. Molecular volume, molecular surface, the sum of hydrophobic surface areas, molecular mass, and possibility of making dispersion forces were identified by QSAR analyses as molecular properties that are

Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.

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Morales, Fátima; Ramírez, Alberto; Conejo-García, Ana; Morata, Cynthia; Marchal, Juan A; Campos, Joaquín M

2014-04-09

As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

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V V Chernykh

2015-01-01

Full Text Available Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF] in the vitreous of patients with proliferative diabetic retinopathy (PDR and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods : Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1, interleukin-4 (IL-4, IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA were simultaneously measured using enzyme-linked immunoassay. Results : Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05 higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Π < 0.05 positive correlations were observed between vitreous concentrations of VEGF and IL-17ΐ (r = 0.45, VEGF and IL-8 (r = 0.48, VEGF and IL-4 (r = 0.51, PEDF and IL-17ΐ (r = 0.48, PEDF and IL-8 (r = 0.59, MCP-1 and PEDF (r = 0.72, MCP-1 and IL-8 (r0 = 0.45, IL-4 and IL-17ΐ (r = 0.65, IL-4 and IL-8 (r = 0.71, IL-8 and IL-17ΐ (r = 0.59. Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

Immunohistochemical Estimates of Angiogenesis, Proliferative Activity, p53 Expression, and Multiple Drug Resistance Have No Prognostic Impact in Osteosarcoma: A Comparative Clinicopathological Investigation

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Jensen, Kenneth; Vaeth, Michael

2008-01-01

Purpose. To investigate angiogenesis, multiple drug resistance (MDR) and proliferative activity as prognostic variables in patients suffering from osteosarcoma. Methods. Histologic biopsies from 117 patients treated in the period from 1972 through 1999 were immunohistologically investigated...

In vitro anti-proliferative effect of interferon alpha in solid tumors: A potential predicative test

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Fuchsberger, N.; Kubes, M.; Kontsek, P.; Borecky, L.; Hornak, M.; Silvanova; Godal, A.; Svec, J.

1993-01-01

An in vitro test for the anti-proliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to anti-proliferative effect of IFN between individual tumors of the same type were found. The potential of this anti-proliferative test for prediction of treatment response in IFN-therapy is discussed. (author)

Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients

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Grauslund, J; Green, A; Sjølie, A K

2009-01-01

AIMS/HYPOTHESIS: This study aimed to evaluate the prevalence of retinopathy in long-surviving type 1 diabetic patients. It also investigated the 25 year incidence of proliferative retinopathy and associated risk factors in a Danish population-based cohort. METHODS: A population-based cohort of 727...... type 1 diabetic patients from Fyn County, Denmark, was identified in 1973. In 1981-1982, baseline retinopathy was graded and other risk factors were assessed in 573 patients. Twenty-five years later, 308 patients were still alive. Of these, 201 (65.3%) were re-examined at follow-up in 2007......-2008. RESULTS: The median age and duration of diabetes at follow-up were 58.8 and 43 years, respectively. At follow-up, the prevalence of diabetic retinopathy was 97.0%. Non-proliferative retinopathy was found in 45.8%, and 51.2% had proliferative retinopathy. The 25 year incidence of proliferative retinopathy...

Effect of Enterococcus faecium EF 55 on morphometry and proliferative activity of intestinal mucosa in broilers infected with Salmonella Enteritidis

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Ševčíková Zuzana

2016-09-01

Full Text Available Introduction: The present study aimed to investigate the effect of Enterococcus faecium EF55 on chickens, as well as its influence on proliferative activity of epithelial intestinal cells after infection with Salmonella enterica serovar Enteritidis phage type 4 (SE PT4. Moreover, the length and area of duodenal and jejunal villi of the birds were examined.

Comments on 'Standard effective doses for proliferative tumours'

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Dasu, Iuliana Livia; Dasu, Alexandru; Denekamp, Juliana; Fowler, Jack F.

2000-01-01

We should like to make some comments on the paper published by Jones et al (1999). The paper presents some interesting and useful contributions on the theoretical evaluation of different fractionated schedules used now. The use of the linear quadratic equation has been very useful in focusing attention on the differences in fractionation responses of fast and slow proliferating normal tissues and tumours. Unfortunately the BED 10 or BED 3 units for (α/β ratios of 10 Gy and 3 Gy respectively) do not directly relate to anything used in routine clinical practice. The purpose of the paper by Jones et al (1999) is to covert any new schedule into the equivalent total dose as if it was given in the same size fractions as are in common use in that department. They illustrate that, if proliferation is taken into account for the altered schedule, it can be compared in two ways with the standard conventional schedule: (a) the proliferative standard effective dose one (PSED 1 ) in which the proliferation correction is applied in the altered schedule, but not in the standard schedule; (b) the proliferative standard effective dose two (PSED 2 ) in which the proliferation correction is applied to both schedules using the same proliferation parameters. This is expected to provide a better evaluation of the response of a 'real' tumour (i.e. a tumour that also proliferates during the standard treatment). However, there seem to be two errors in the paper. First, the authors quoted a wrong equation for calculating the proliferative standard effective dose two (PSED 2 ) (equations (2) and (A6) in their paper). There are also some special cases with respect to the time available for proliferation and the duration of the treatment that have been neglected in their paper and which require further specification. Therefore, we should like to give the full mathematical derivation of the correct equations for calculating the proliferative standard effective doses. We would also like to make

Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes.

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Li, Yuwei; Ahrens, Molly J; Wu, Amy; Liu, Jennifer; Dudley, Andrew T

2011-01-01

For tissues that develop throughout embryogenesis and into postnatal life, the generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity. Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways. We present an integrated model for the regulation of proliferation potential by CamkII activity that has important implications for studies of growth control and adult progenitor/stem cell populations.

Analysis of the proliferative potential of odontogenic epithelial cells of pericoronal follicles.

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Cimadon, Natalia; Lauxen, Isabel Silva; Carrard, Vinicius Coelho; Sant'Ana Filho, Manoel; Rados, Pantelis Varvaki; Oliveira, Márcia Gaiger

2014-11-01

To evaluate the proliferative potential and the cell proliferation rate of odontogenic epithelial cells. Forty-two cases of pericoronal follicles of impacted third molars were submitted to silver impregnation technique for quantification of argyrophilic nucleolar organizer regions (AgNOR) and immunohistochemical staining for EGFR and Ki-67. For AgNOR quantification, the mean number of active nucleolar organizer regions per nucleus (mAgNOR) and the percentage of cells with 1, 2, 3 and 4 or more AgNORs per nucleus (pAgNOR) were quantified. Ki-67 immunolabeling was quantified, whereas for EGFR, a descriptive analysis of staining patterns (membrane, cytoplasm or membrane + cytoplasm positivity) was performed. We evaluated the reduced epithelium of the enamel organ and/or islands of odontogenic epithelium present in the entire connective tissue. mAgNOR were 1.43 (1.0-2.42) and were significantly different among pericoronary follicles from upper and lower teeth (p = 0.041). Immunostaining of Ki-67 was negative in all cases. EGFR immunolabeling was found mainly in the cytoplasm and was more intense in islands and cords when compared to reduced epithelium of the enamel organ. Odontogenic epithelial cells of some pericoronal follicles have proliferative potential, suggesting their association with the development of odontogenic lesions. The authors suggest that nonerupted, especially of the lower teeth, should be monitored and if necessary removed.

Proliferative lifespan is conserved after nuclear transfer.

Science.gov (United States)

Clark, A John; Ferrier, Patricia; Aslam, Samena; Burl, Sarah; Denning, Chris; Wylie, Diana; Ross, Arlene; de Sousa, Paul; Wilmut, Ian; Cui, Wei

2003-06-01

Cultured primary cells exhibit a finite proliferative lifespan, termed the Hayflick limit. Cloning by nuclear transfer can reverse this cellular ageing process and can be accomplished with cultured cells nearing senescence. Here we describe nuclear transfer experiments in which donor cell lines at different ages and with different proliferative capacities were used to clone foetuses and animals from which new primary cell lines were generated. The rederived lines had the same proliferative capacity and rate of telomere shortening as the donor cell lines, suggesting that these are innate, genetically determined, properties that are conserved by nuclear transfer.

Prolific plant regeneration through organogenesis from scalps of ...

African Journals Online (AJOL)

Four types of potting media comprising of sand, peat, sand + top soil + goat dung (3:2:1 v/v) and top soil + sand (1:1 v/v) were evaluated during acclimatization of the plantlets. Prolific shoot regeneration from scalps was obtained on MS medium containing 2.5 mM BAP, at 9.61 and 40.6 shoots per explant after 4 and 8 weeks ...

Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts.

Science.gov (United States)

Sitte, N; Merker, K; von Zglinicki, T; Grune, T

2000-03-01

One of the highlights of age-related changes of cellular metabolism is the accumulation of oxidized proteins. The aging process on a cellular level can be treated either as the ongoing proliferation until a certain number of cell divisions is reached (the Hayflick limit) or as the aging of nondividing cells, that is, the age-related changes in cells without proliferation. The present investigation was undertaken to reveal the changes in protein turnover, proteasome activity, and protein oxidation status during proliferative senescence. We were able to demonstrate that the activity of the cytosolic proteasomal system declines dramatically during the proliferative senescence of human MRC-5 fibroblasts. Regardless of the loss in activity, it could be demonstrated that there are no changes in the transcription and translation of proteasomal subunits. This decline in proteasome activity was accompanied by an increased concentration of oxidized proteins. Cells at higher proliferation stages were no longer able to respond with increased degradation of endogenous [(35)S]-Met-radiolabeled proteins after hydrogen peroxide- or quinone-induced oxidative stress. It could be demonstrated that oxidized proteins in senescent human MRC-5 fibroblasts are not as quickly removed as they are in young cells. Therefore, our study demonstrates that the accumulation of oxidized proteins and decline in protein turnover and activity of the proteasomal system are not only a process of postmitotic aging but also occur during proliferative senescence and result in an increased half-life of oxidized proteins.

Potent anti-proliferative effects against oral and cervical cancers of Thai medicinal plants selected from the Thai/Lanna medicinal plant recipe database "MANOSROI III".

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Manosroi, Aranya; Akazawa, Hiroyuki; Pattamapun, Kassara; Kitdamrongtham, Worapong; Akihisa, Toshihiro; Manosroi, Worapaka; Manosroi, Jiradej

2015-07-01

Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including oral and cervical cancers. To investigate anti-proliferative activity on human cervical (HeLa) and oral (KB) cancer cell lines of medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III". Twenty-three methanolic plant crude extracts were tested for phytochemicals and anti-proliferative activity on HeLa and KB cell lines for 24 h by the sulforhodamine B (SRB) assay at the doses of 1 × 10(1)-1 × 10(-6 )mg/ml. The nine extracts with the concentrations giving 50% growth inhibition (GI50) lower than 100 µg/ml were further semi-purified by liquid/liquid partition in order to evaluate and enhance the anti-proliferative potency. All extracts contained steroids/triterpenoids, but not xanthones. The methanolic extracts of Gloriosa superba L. (Colchinaceae) root and Albizia chinensis (Osbeck) Merr. (Leguminosae-Mimosoideae) wood gave the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.91 (6.0- and 0.31-fold of cisplatin and doxorubicin) and 0.16 µg/ml (28.78- and 82.29-fold of cisplatin and doxorubicin), respectively. Hexane and methanol-water fractions of G. superba exhibited the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.15 (37- and 1.9-fold of cisplatin and doxorubicin) and 0.058 µg/ml (77.45- and 221.46-fold of cisplatin and doxorubicin), respectively. This study has demonstrated the potential of plants selected from MANOSROI III database especially G. superba and A. chinensis for further development as anti-oral and cervical cancer agents.

Protein metabolism of prolific ewes during late gestation and early lactation

NARCIS (Netherlands)

Sebek, L.B.J.

2001-01-01

Subject headings: protein / metabolism / ewes

Introduction of prolific crossbred ewes and a new protein evaluation system for ruminants, the DVE/OEB system, necessitate a reconsideration of ewe feeding strategies. The objective of this thesis is to investigate the amount

Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

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Lee, Ra H; Jeon, Young-Joo; Cho, Jin H; Jang, Jeong-Yun; Kong, Il-Keun; Kim, Seok-Ho; Kim, MinSeok S; Chung, Hak-Jae; Oh, Keon B; Park, Seon-Min; Shin, Jae-Cheon; Seo, Jae-Min; Ko, Sungho; Shim, Jung-Hyun; Chae, Jung-Il

2017-01-01

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

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Justyna Moskwa

Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

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Djudjaj, Sonja; Lue, Hongqi; Rong, Song; Papasotiriou, Marios; Klinkhammer, Barbara M.; Zok, Stephanie; Klaener, Ole; Braun, Gerald S.; Lindenmeyer, Maja T.; Cohen, Clemens D.; Bucala, Richard; Tittel, Andre P.; Kurts, Christian; Moeller, Marcus J.; Floege, Juergen; Ostendorf, Tammo

2016-01-01

Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN. PMID:26453615

Proliferative Activity of Mammary Carcinoma Cells by AgNOR Count in C3H mice Receiving Ethanol Extract of Sponge Haliclona sp

Science.gov (United States)

Sijabat, Lanceria; Susilaningsih, Neni; Trianto, Agus; Murwani, Retno

2018-02-01

Quantification of argyrophilic nucleolar organizer region (AgNORs) was considered as one of markers of proliferative activity of cancer cells. Sponge Haliclona sp extract contains anticancer bioactive compounds and our previous study showed that the extract was able to improve histological grade of induced mammary adenocarcinoma in mice. The following research was conducted to study the extract administration on the proliferative activity of the carcinoma cells represented by AgNOR count in mice. This experimental study applied post test only control group design. Twenty C3H mice were divided into four groups namely C (control), H1, H2 and H3. Each group was given 0, 0.15, 1.5, and 15 mg Haliclona sp extract respectively. After three weeks of extract administration, mice were inoculated with breast cancer cells from donor mice. The extract administration were continued for another three weeks. AgNOR count was performed on tumor sections and expressed as mean of AgNOR (mAgNOR) and percentage of AgNOR (pAgNOR). Means of mAgNOR in C, H1, H2 and H3 were 4.070, 3.195, 3.450, and 3.190 respectively. Means of pAgNOR in C, H1, H2 and H3 were 34,40, 25,40, 38,40 and 19,80 respectively. The lowest means of mAgNOR and pAgNOR which is an indication of lower proliferative activity of the cancer cells was found in H3. However no significant difference can be found among treatment groups (p>0.05). Using AgNOR count, the ethanol extract of Haliclona sp could not show significant reduction in proliferation of mammary carcinoma cells of C3H mice. This finding support the view that AgNOR alone could not be used to determine pathology of cancer cells.

Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

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Jan Tauchen

Full Text Available ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively, while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively. However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively. Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

Science.gov (United States)

Xiao, Zhitao; Zhang, Xinpeng; Geng, Lei; Zhang, Fang; Wu, Jun; Tong, Jun; Ogunbona, Philip O; Shan, Chunyan

2017-10-26

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Proliferative activity in oral pyogenic granuloma: A comparative immunohistochemical study

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Rezvani Gita

2010-07-01

Full Text Available Context: Pyogenic granuloma (PG is one of the most common reactive vascular lesions in the oral mucosa, which has been divided into the lobular capillary hemangioma (LCH and the non lobular type (non-LCH as two distinct entities, on the basis of some investigations. Aims: This study aims to compare the proliferative and angiogenic activity of two histological types of PG to determine whether they have two distinct types of biological behavior. Settings and Design: In this retrospective cross-sectional study, immunostaining was performed on 10 cases of each type of PG. Materials and Methods: About 4μm sections were cut from formalin-fixed paraffin-embedded blocks and each specimen was stained with both anti-CD31 and anti-Ki-67 antibodies simultaneously. Labeling index (LI was determined for both types by counting Ki-67 and CD31 positive cells separately and simultaneously in 1000 stromal and luminal cells. Micro vessel count (MVC, the mean number of micro vessels in five areas at Χ200 magnification, was also determined for both groups. Statistical Analysis: The results were statistically compared using the Mann-Whitney U-test. Results: Ki-67 LI in LCH (5.4 ± 2.4 was higher than non-LCH (3.9 ± 3.9. The percentage of CD31 positive cells in LCH (28.5 ± 22 was lower than non-LCH (37.1 ± 20.8 and simultaneously immunostaining for both markers in LCH type (2.4 ± 2.1 was higher than non-LCH (1.2 ± 1. The MVC was approximately 77.35 ± 34.6 and 82.6 ± 42.7 in the lobular areas of LCH and central areas of non-LCH PG, respectively. These differences were not statistically significant. Conclusions: These results demonstrate a higher proliferation activity in endothelial cells of LCH PG than in non-LCH.

Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

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Célia Regina Farias de Araújo Lucena

2013-02-01

Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

Science.gov (United States)

Thyroid proliferative lesions are rather common in bony fishes but disagreement exists in the fish pathology community concerning diagnostic criteria for hyperplastic versus neoplastic lesions. To simplify the diagnosis of proliferative thyroid lesions and to reduce confusion reg...

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

DEFF Research Database (Denmark)

Jensen, V; Ladekarl, M; Holm-Nielsen, P

1995-01-01

of invasion of skin or deep fascia (= T1N0M0 and T2N0M0). The median follow-up time was 104 months (range 5-143 months). Immunohistochemical analysis of OA-519 expression was performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was estimated using a Ki-67 equivalent monoclonal...

Proliferative and non-proliferative lesions of the rat and mouse integument.

Science.gov (United States)

Mecklenburg, Lars; Kusewitt, Donna; Kolly, Carine; Treumann, Silke; Adams, E Terence; Diegel, Kelly; Yamate, Jyoji; Kaufmann, Wolfgang; Müller, Susanne; Danilenko, Dimitry; Bradley, Alys

2013-01-01

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the societies of toxicological pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP). Its aim is to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory rodents. A widely accepted international harmonization of nomenclature in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and will provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. The purpose of this publication is to provide a standardized nomenclature for classifying microscopical lesions observed in the integument of laboratory rats and mice. Example colour images are provided for most lesions. The standardized nomenclature presented in this document and additional colour images are also available electronically at http://www.goreni.org. The nomenclature presented herein is based on histopathology databases from government, academia, and industrial laboratories throughout the world, and covers lesions that develop spontaneously as well as those induced by exposure to various test materials. (DOI: 10.1293/tox.26.27S; J Toxicol Pathol 2013; 26: 27S-57S).

Differential expression of follistatin and FLRG in human breast proliferative disorders

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Amaral Vania F

2009-09-01

Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

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Ramaswamy Nagarajan

2008-11-01

Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases

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Andrea Bistrović

2017-11-01

Full Text Available A series of mono-pyrrolo[2,3-d]pyrimidines 4a–4k, unsymmetrical bis-purine isosteres 5a–5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolylphenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1 cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma and p38 MAP (mitogen-activated protein kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer.

VISUAL OUTCOME FOLLOWING PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY

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Nellaye Mani Sindhu

2018-01-01

Full Text Available BACKGROUND Diabetes mellitus can be called as a noninfectious pandemic and the incidence of diabetic retinopathy is also uncontrollable. This vision-threatening complication can be treated by early diagnosis and effective treatment like panretinal photocoagulation. The aim of the study is to evaluate the effect of panretinal photocoagulation on visual acuity, colour vision, contrast sensitivity and severity of visual field changes. MATERIALS AND METHODS Prospective study of visual outcome following panretinal photocoagulation in patients with proliferative diabetic retinopathy conducted in Retina Clinic, RIO, Trivandrum, during the time period one year from April 2008. Inclusion Criteria- Eyes with proliferative diabetic retinopathy, visual acuity better than or equal to 6/60, a follow up of at least 6 months after panretinal photocoagulation. Exclusion Criteria- Eyes with cataractous changes in the lens, eyes, which would be undergoing or have undergone focal photocoagulation eyes, which undergone barrage or sectoral retinal photocoagulation, patients with colour blindness, eyes with vitreous haemorrhage and macular preretinal haemorrhage, glaucomatous patients with peripheral field loss. RESULTS The mean age of the patients was 52 years. Male patients (30 outnumbered the female patients (23. Mean duration of diabetes was 14.42 years. Though, there is a statistically significant reduction in visual acuity in the first followup, which was improved and stabilised by 6 months. There is a statistically significant reduction in the contrast sensitivity, which was stabilised after 3 months. Only, 9.5% patients had peripheral constrictions of visual field and no significant change in the colour vision. CONCLUSION We recommend panretinal photocoagulation for all patients with proliferative diabetic retinopathy.

Proliferative activity (MIB-1 index) is an independent prognostic parameter in patients with high-grade soft tissue sarcomas of subtypes other than malignant fibrous histiocytomas

DEFF Research Database (Denmark)

Jensen, V; Sørensen, Flemming Brandt; Bentzen, S M

1998-01-01

. The proliferative activity was assessed by use of the monoclonal antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. The percentage of proliferating cells (the MIB-1 index) ranged between 1% and 85% (median 12%). A significant increase in mean MIB-1 index was seen with increasing...... histological malignancy grade. Variation in the incidence of p53 accumulation and bcl-2 positivity among different histological subtypes was observed. p53 accumulation was frequent in synovial sarcomas and leiomyo- and rhabdomyosarcomas, whereas bcl-2 preferentially was expressed in synovial sarcomas....... Univariate analysis identified patient age, tumour size, histological grade of malignancy, MIB-1 index and p53 accumulation as significant prognostic parameters. Multivariate Cox analysis, including tests for interaction terms between histological subtypes and MIB-1 index, showed independent prognostic...

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

Energy Technology Data Exchange (ETDEWEB)

Min, Kyung-Won [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Zhang, Xiaobo [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi, 712100 (China); Imchen, Temjenmongla [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Baek, Seung Joon, E-mail: sbaek2@utk.edu [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States)

2012-09-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

International Nuclear Information System (INIS)

Min, Kyung-Won; Zhang, Xiaobo; Imchen, Temjenmongla; Baek, Seung Joon

2012-01-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

A comparative study of proliferative activity and tumor stage of pregnancy-associated melanoma (PAM) and non-PAM in gestational age women.

Science.gov (United States)

Merkel, Emily A; Martini, Mary C; Amin, Sapna M; Yélamos, Oriol; Lee, Christina Y; Sholl, Lauren M; Rademaker, Alfred W; Guitart, Joan; Gerami, Pedram

2016-01-01

The influence of pregnancy on the development, progression, and prognosis of melanoma is controversial. We sought to compare clinical characteristics, histologic features, and proliferative activity in pregnancy-associated melanoma (PAM) and melanoma in nonpregnant women of reproductive age (non-PAM). In this retrospective cohort study, we reviewed medical records and pathology reports from women given a diagnosis of melanoma between 2006 and 2015. We also examined tumor proliferation rates using mitotic count and 2 immunohistochemical markers of proliferation, phosphohistone H3 and Ki-67. In 50 PAM and 122 non-PAM cases, a diagnosis of melanoma in situ was associated with PAM. Among invasive melanomas, there was no difference in proliferative activity between groups. Pregnancy status was also not associated with age at diagnosis, tumor site, Breslow depth, Clark level, ulceration, or overall stage. This was a retrospective study with a small sample size of mostly patients with early-stage melanoma. In our study of primarily early-stage melanoma, pregnancy did not have a significant impact on tumor proliferation. Particularly for patients given a diagnosis of stage I melanoma who are undergoing close surveillance, a history of PAM should not outweigh traditional factors, such as advanced maternal age, in planning future pregnancies. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

2015-11-13

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

International Nuclear Information System (INIS)

Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

2015-01-01

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

Apoptotic and anti-proliferative effects of all-trans retinoic acid

International Nuclear Information System (INIS)

Zamora, Monica; Ortega, Juan Alberto; Alana, Lide; Vinas, Octavi; Mampel, Teresa

2006-01-01

We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy

Atypical proliferative myositis: original MR description with pathologic correlation: Case report

Energy Technology Data Exchange (ETDEWEB)

Jarraya, Mohamed; Guermazi, Ali [Boston University School of Medicine, Department of Radiology, Musculoskeletal Section, Boston, MA (United States); Parva, Pedram [VA Boston Healthcare System, Boston, MA (United States); Stone, Michael [Stamford Hospital, Department of Surgery, Stamford, CT (United States); Klein, Michael J. [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States)

2014-08-15

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

Atypical proliferative myositis: original MR description with pathologic correlation: Case report

International Nuclear Information System (INIS)

Jarraya, Mohamed; Guermazi, Ali; Parva, Pedram; Stone, Michael; Klein, Michael J.

2014-01-01

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

Science.gov (United States)

Kırça, M; Oğuz, N; Çetin, A; Uzuner, F; Yeşilkaya, A

2017-04-01

Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRβ phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRβ phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.

The effect of beta-hydroxy-beta-methylbutyrate (HMB) on the proliferative response of blood lymphocytes and the phagocytic activity of blood monocytes and granulocytes in calves.

Science.gov (United States)

Wójcik, R; Małaczewska, J; Siwicki, A K; Miciński, J; Zwierzchowski, G

2013-01-01

The objective of this study was to evaluate the effect of HMB on selected indicators of immunity in calves. The experiment was performed on 14 calves aged 30 +/- 2 days, divided into two equal groups of control (group I) and experimental (group II) animals. The feed administered to experimental group calves was supplemented with HMB at 40 mg/kg BW, whereas control calves were administered standard farm-made feed without supplementation. Blood was sampled from the jugular vein immediately before the experiment (day 0) and on experimental days 15, 30 and 60 to determine the following parameters of immunity: proliferative response of LPS- and ConA-stimulated lymphocytes (MTT), respiratory burst activity (RBA) and potential killing activity (PKA) of phagocytes. The results revealed a significant increase in RBA and MTT values in calves administered HMB in comparison with the control group throughout the experiment. In the group of animals receiving HMB, an increase in PKA values was noted only on day 30.

Proliferative and morphologic changes in rat colon following bypass surgery.

Science.gov (United States)

Barkla, D H; Tutton, P J

1985-06-01

In this study the proliferative and morphologic changes that occur in the colon of normal and dimethylhydrazine-treated rats following surgical bypass of the middle third of the colon are reported. Proliferative changes were measured by estimating accumulated mitotic indexes following vinblastine treatment and morphologic changes were observed with the use of light microscopy and scanning electron microscopy. Data were collected on Days 0, 7, 14, 30, and 72 after surgery. The results show that surgical bypass produces contrasting effects in the segments proximal to and distal to the suture line. In the proximal segment there was morphologic evidence of hyperplasia, although proliferative activity was unchanged except for an increase at 7 days in normal rats. In the distal segment there was a long-lived increase in the mitotic index, although morphologic changes were not seen. The results for DMH-treated rats were similar to those in normal rats. Groups of isolated dysplastic epithelial cells were often seen in the submucosa adjacent to sutures up to 72 days after surgery. Increased lymphoid infiltration was seen in segments proximal to but not distal to the suture line. It is hypothesized that the different responses of the proximal and distal segments may be related to the different embryologic origins of those segments. It is also hypothesized that the seeding of the submucosa with epithelial cells during suturing may be a factor in tumor recurrence.

Proliferative changes in nonpalpable breast lesions detected by mammography

International Nuclear Information System (INIS)

Vega, A.; Delgado, A.; Ortega, E.; Garijo, F.; Mosquera, J.; Sogo, C.; Alvarez, A.

2000-01-01

To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.

Science.gov (United States)

Huyen, Chu Thi Thanh; Luyen, Bui Thi Thuy; Khan, Ghulam Jilany; Oanh, Ha Van; Hung, Ta Manh; Li, Hui-Jun; Li, Ping

2018-05-04

This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3 , two new lignan glycosides 4 and 7 , one new 9,19-cycloartane triterpenoid glycoside 6 , and thirteen known constituents 1 , 2 , 5 , and 8 ⁻ 17 . The structures of 3 , 4 , 6 , and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects ( p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect ( p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica , including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPARα-tr, autonomously regulates proliferative and pro-inflammatory genes

International Nuclear Information System (INIS)

Thomas, Maria; Bayha, Christine; Klein, Kathrin; Müller, Simon; Weiss, Thomas S.; Schwab, Matthias; Zanger, Ulrich M.

2015-01-01

The peroxisome proliferator-activated receptor alpha (PPARα) controls lipid/energy homeostasis and inflammatory responses. The truncated splice variant PPARα-tr was suggested to exert a dominant negative function despite being unable to bind consensus PPARα DNA response elements. The distribution and variability factor of each PPARα variant were assessed in the well-characterized cohort of human liver samples (N = 150) on the mRNA and protein levels. Specific siRNA-mediated downregulation of each transcript as well as specific overexpression with subsequent qRT-PCR analysis of downstream genes was used for investigation of specific functional roles of PPARα-wt and PPARα-tr forms in primary human hepatocytes. Bioinformatic analyses of genome-wide liver expression profiling data suggested a possible role of PPARα-tr in downregulating proliferative and pro-inflammatory genes. Specific gene silencing of both forms in primary human hepatocytes showed that induction of metabolic PPARα-target genes by agonist WY14,643 was prevented by PPARα-wt knock-down but neither prevented nor augmented by PPARα-tr knock-down. WY14,643 treatment did not induce proliferative genes including MYC, CDK1, and PCNA, and knock-down of PPARα-wt had no effect, while PPARα-tr knock-down caused up to 3-fold induction of these genes. Similarly, induction of pro-inflammatory genes IL1B, PTGS2, and CCL2 by IL-6 was augmented by knock-down of PPARα-tr but not of PPARα-wt. In contrast to human proliferative genes, orthologous mouse genes were readily inducible by WY14,643 in PPARα-tr non-expressing AML12 mouse hepatocytes. Induction was augmented by overexpression of PPARα-wt and attenuated by overexpression of PPARα-tr. Pro-inflammatory genes including IL-1β, CCL2 and TNFα were induced by WY14,643 in mouse and human cells and both PPARα forms attenuated induction. As potential mechanism of PPARα-tr inhibitory action we suggest crosstalk with WNT/β-catenin pathway. Finally

Amniocar as a proliferative medium for mesenchymal cells

Directory of Open Access Journals (Sweden)

V. V. Chestkov

2014-01-01

Full Text Available Objectives. To develop the Amniocar nutrient medium that contains fetal calf serum (FCS and growth factors cocktail for mass cultivation of human fibroblasts. To study proliferative activity of the medium on cultures of HUVEC cells of mesenchymal origin and mesenchymal stromal cells, as well as on cell culture of human amniotic fluid.Materials and methods. Determination of the rate of accumulation of the cellular mass and cell morphology in the course of cultivation of cells of various histogenesis in the Amniocar medium and nutrient medium that contains 10 % of FCS.Results. It has been demonstrated that the Amniocar medium is prevalent as compared to the standard DMEM medium with 10 % of FCS by 2 to 5 times for cultivation of skin fibroblasts, HUVEC, and mesenchymal stem cells. The Amniocar medium increased the quantity of endothelial cells that enter mitosis and maintained the culture of HUVEC cells with prolonged passaging in vitro. Clonal cultivation of human amniotic fluid cells in the Amniocar medium secured development of colonies of both fibroblast and epithelial type.Conclusions. Proliferative Amniocar medium is efficient for mass cultivation of various cells of mesenchymal origin and can be used for diagnostic purposes in medical genetics, oncology, etc.

Facile synthesis of indole-pyrimidine hybrids and evaluation of their anticancer and antimicrobial activity

Directory of Open Access Journals (Sweden)

Nikhila Gokhale

2017-11-01

Full Text Available The paper describes the facile synthesis of new N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives bearing substituted 2-amino pyrimidine moiety at position-3 of the indole ring. All the intermediate and title compounds were characterized adeptly by 1H NMR, 13C NMR, ESI–MS and elemental analyses. These compounds were evaluated for their in vitro anticancer activity against HeLa, HepG2 and MCF-7 cells. Three among 22 molecules, showed more than 70% growth inhibition against all three tested cancer cells. The nature of the substituent group on the pyrimidine ring (R2 affected significantly the anti-proliferative activity of the molecules. The anti-microbial evaluation of the title molecules revealed the significance of fluoro/chloro groups (R2 in enhancing their inhibition activity. Eight molecules which contain fluoro/chloro groups showed potent anti-microbial activity. In addition, the active molecules displayed negligible toxicity to benign Vero cells.

Correlation of proliferative and clonogenic tumor cells in multiple myeloma

International Nuclear Information System (INIS)

Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

1984-01-01

To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

Directory of Open Access Journals (Sweden)

Devesh Kumawat

2018-01-01

Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

International Nuclear Information System (INIS)

Fatema, Chowdhury Nusrat; Yu, Wenwen; Kitagawa, Yoshimasa; Zhao, Songji; Zhao, Yan; Murakami, Masahiro; Nishijima, Ken-ichi; Tamaki, Nagara; Kuge, Yuji

2013-01-01

Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using 18 F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. 3 H-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral 3 H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral 3 H-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral 3 H-FLT level markedly decreased to 45 and 40% of the control, respectively (P 3 H-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral 3 H-FLT levels in both treated groups were 68 and 60% at 24 h (P<0.001), 71 and 77% at 48 h (P<0.001), and 83 and 81% on day 7 (P=NS) compared with the control group. Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time. Sequential evaluation of intratumoral proliferative

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Chu Thi Thanh Huyen

2018-05-01

Full Text Available This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz. Maxim. (Ranunculaceae was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8–17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05, wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05 which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.

Science.gov (United States)

Shannon, Jackilen; King, Irena B; Lampe, Johanna W; Gao, Dao Li; Ray, Roberta M; Lin, Ming-Gang; Stalsberg, Helge; Thomas, David B

2009-01-01

Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

Neoplastic and proliferative disorders of the perinephric space

International Nuclear Information System (INIS)

Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

2012-01-01

The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

Antimicrobial and Anti-Proliferative Effects of Skin Mucus Derived from Dasyatis pastinaca (Linnaeus, 1758

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Virginia Fuochi

2017-11-01

Full Text Available Resistance to chemotherapy occurs in various diseases (i.e., cancer and infection, and for this reason, both are very difficult to treat. Therefore, novel antimicrobial and chemotherapic drugs are needed for effective antibiotic therapy. The aim of the present study was to assess the antimicrobial and anti-proliferative effects of skin mucus derived from Dasyatis pastinaca (Linnaeus, 1758. Our results showed that skin mucus exhibited a significant and specific antibacterial activity against Gram-negative bacteria but not against Gram-positive bacteria. Furthermore, we also observed a significant antifungal activity against some strains of Candida spp. Concerning anti-proliferative activity, we showed that fish mucus was specifically toxic for acute leukemia cells (HL60 with an inhibition of proliferation in a dose dependent manner (about 52% at 1000 μg/mL of fish skin mucous, FSM. Moreover, we did not observe effects in healthy cells, in neuroblastoma cells (SH-SY5Y, and multiple myeloma cell lines (MM1, U266. Finally, it exhibited strong expression and activity of chitinase which may be responsible, at least in part, for the aforementioned results.

Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

International Nuclear Information System (INIS)

Aoki, Shigehisa; Ikeda, Satoshi; Takezawa, Toshiaki; Kishi, Tomoya; Makino, Junichi; Uchihashi, Kazuyoshi; Matsunobu, Aki; Noguchi, Mitsuru; Sugihara, Hajime; Toda, Shuji

2011-01-01

Highlights: ► Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. ► Fluid streaming is a potent factor for peritoneal fibrosis in PD. ► We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. ► A history of fluid streaming exposure promoted mesothelial proliferative activity. ► We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial–mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

Science.gov (United States)

Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells

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Harrell, Permila C.; McCawley, Lisa J.; Fingleton, Barbara; McIntyre, J. Oliver; Matrisian, Lynn M.

2005-01-01

Matrix metalloproteinase-7 (MMP-7) is primarily expressed in glandular epithelium. Therefore, its mechanism of action may be influenced by its regulated vectorial release to either the apical and/or basolateral compartments, where it would act on its various substrates. To gain a better understanding of where MMP-7 is released in polarized epithelium, we have analyzed its pattern of secretion in polarized MDCK cells expressing stably transfected human MMP-7 (MDCK-MMP-7), and HCA-7 and Caco2 human colon cancer cell lines. In all cell lines, latent MMP-7 was secreted to both cellular compartments, but was 1.5- to 3-fold more abundant in the basolateral compartment as compared to the apical. However, studies in the MDCK system demonstrated that MMP-7 activity was 2-fold greater in the apical compartment of MDCK-MMP-7 HIGH -polarized monolayers, which suggests the apical co-release of an MMP-7 activator. In functional assays, MMP-7 over-expression increased cell saturation density as a result of increased cell proliferation with no effect on apoptosis. Apical MMP-7 activity was shown to be responsible for the proliferative effect, which occurred, as demonstrated by media transfer experiments, through cleavage of an apical substrate and not through the generation of a soluble factor. Taken together, our findings demonstrate the importance of MMP-7 secretion in relation to its mechanism of action when expressed in a polarized epithelium

Changes in retinal venular oxygen saturation predict activity of proliferative diabetic retinopathy 3 months after panretinal photocoagulation.

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Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin; Peto, Tunde; Grauslund, Jakob

2018-03-01

Proliferative diabetic retinopathy (PDR) is a severe blinding condition. We investigated whether retinal metabolism, measured by retinal oximetry, may predict PDR activity after panretinal laser photocoagulation (PRP). We performed a prospective, interventional, clinical study of patients with treatment-naive PDR. Wide-field fluorescein angiography (OPTOS, Optomap) and global and focal retinal oximetry (Oxymap T1) were performed at baseline (BL), and 3 months (3M) after PRP. Angiographic findings were used to divide patients according to progression or non-progression of PDR after PRP. We evaluated differences in global and focal retinal oxygen saturation between patients with and without progression of PDR after PRP treatment. We included 45 eyes of 37 patients (median age and duration of diabetes were 51.6 and 20 years). Eyes with progression of PDR developed a higher retinal venous oxygen saturation than eyes with non-progression at 3M (global: +5.9% (95% CI -1.5 to 12.9), focal: +5.4%, (95% CI -4.1 to 14.8)). Likewise, progression of PDR was associated with a lower arteriovenular (AV) oxygen difference between BL and 3M (global: -6.1%, (95% CI -13.4 to -1.4), focal: -4.5% (95% CI -12.1 to 3.2)). In a multiple logistic regression model, increment in global retinal venular oxygen saturation (OR 1.30 per 1%-point increment, p=0.017) and decrement in AV oxygen saturation difference (OR 0.72 per 1%-point increment, p=0.016) at 3M independently predicted progression of PDR. Development of higher retinal venular and lower AV global oxygen saturation independently predicts progression of PDR despite standard PRP and might be a potential non-invasive marker of angiogenic disease activity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Standard effective doses for proliferative tumours

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Jones, L.C.; Hoban, P.

1999-01-01

This study was undertaken to investigate the treatment schedules used clinically for highly proliferative tumours, particularly with reference to the effects of fraction size, fraction number and treatment duration. The linear quadratic model (with time component) is used here to compare non-standard treatment regimens (e.g. accelerated and hyperfractionated schedules), currently the focus of randomized trials, with each other and some common 'standard regimens'. To ensure easy interpretation of results, two parameters known as proliferative standard effective dose one (PSED 1 ) and proliferative standard effective dose two (PSED 2 ) have been calculated for each regimen. Graphs of PSED 1 and PSED 2 versus potential doubling time (T p ) have been generated for a range of fractionation regimens which are currently under trial in various randomized studies. From these graphs it can be seen that the highly accelerated schedules (such as CHART) only show advantages for tumours with very short potential doubling times. Calculations for most of the schedules considered showed at least equivalent tumour control expected for the trial schedule compared with the control arm used and these values agree quite well with clinical results. These calculations are in good agreement with clinical results available at present. The greater the PSED 1 or PSED 2 for the schedule considered the greater the tumour control, which can be expected. However, as has been seen with clinical trials, this higher cell kill also results in higher acute effects which have proved too great for some accelerated schedules to continue. (author)

Synergy among rat T cells in the proliferative response to alloantigen

International Nuclear Information System (INIS)

Wright, P.W.; Loop, S.M.; Bernstein, I.D.

1979-01-01

A synergistic interaction in the proliferative response to alloantigen is described for mixtures of rat thymus and lymph node cells. The optimal conditions for synergy are quantitatively defined. Regression analysis of the slope of the dose-response curve has been utilized to estimate the degree of interaction in thymus--lymph node cell mixtures. The slope of the response of cell mixtures was noted to be significantly greater than the slope for the response of lympth node cells alone. Irradiation was shown to have a differential effect on the response of thymus and lymph node cells in mixtures. Irradiated thymus cells retained the capacity for synergy in mixtures, whereas irradiated lymph node cells did not. Additional studies have demonstrated that both de novo protein synthesis and specific antigen recognition by both responding cell populations in mixtures was required for maximal synergy. These studies demonstrate that synergy cannot be explained as an artifact of altered cell density in vitro. They establish that thymus cells and lymph node cells represent distinct subsets which manifest qualitatively different functions in the proliferative response to alloantigen. Thymus cells can respond directly to alloantigen by proliferation but also have the capacity to amplify the proliferative response of lymph node cells, a capacity which is resistant to X irradiation but requires recognition of alloantigen and de novo protein synthesis. Lymph node cells may similarly respond by proliferation to alloantigen but lack the amplifier activity of thymus cells. Synergy for rat lymphoidcells, like mouse lymphoid cells, has been shown to involve an interaction of thymus-derived lymphocytes

T-cell proliferative responses following sepsis in neonatal rats.

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Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines

Science.gov (United States)

Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

2014-01-01

Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0/G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0/G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer. PMID:24397737

Proliferative glomerulonephritis and primary antiphospholipid syndrome

International Nuclear Information System (INIS)

Abdalla, H. Abdalla; Kfoury, Hala K.; Al-Khader, Abdulla A.; Al-Suleiman, M.

2006-01-01

Little is known regarding the association of primary antiphospholipid syndrome (APLS) and proliferative glomerulonephiritis (GN). We describe a biopsy-documented case with primary APLS and proliferative (GN) with no evidence of thrombotic microangiopathy (TMA), and in the absence of other manifestations of systematic lupus erythematosus (SLE). She presented initially with left popliteal deep venous thrombosis and nephrotic syndrome. Her first pregnancy at the age of 26 years resulted in the intra-uterine fetal death at term. Two subsequent pregnancies ended up with miscarriages at 3 and 4 months of gestation. Urinalysis revealed glomerular red blood cells of 1.0000.000/ml and granular cast; proteinuria of 13.4grams/24 hours, which was non-selective; hemoglobin 12 gm/dl, normal white blood cell and platelets; serum albumin 2.6gm/dl; anti-nuclear antibody (ANA) and anti DNA were negative and complement levels normal. Lupus anticoagulant was positive leading to a diagnosis of primary APLS. The biopsy findings were consistent with membranoproliferative GN. She continued to have steroid-resistant proteinuria, but stable renal function after a 12-year follow up period. She had 2 pregnancies during this period and was delivered at term using caesarian section. She received heparin during the pregnancies. Later she developed hypertension easily controlled by atenolol. This case provides evidence that primary APLS can be associated with proliferative GN due to immune deposits and not only TMA as previously reported, and in the complete absence of SLE. Performing more renal biopsies in this group of patients may disclose a greater prevalence of proleferative GN and may help in devising a rationale for treatment. (author)

The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

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Micheline Sanderson

Full Text Available Glucocorticoid (GC-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs and ADSC-derived pre-osteoblasts (ADSC-OBs. ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

DNA Amplifications and Aneuploidy, High Proliferative Activity and Impaired Cell Cycle Control Characterize Breast Carcinomas with Poor Prognosis

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Harald Blegen

2003-01-01

Full Text Available In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.

PROSPECTIVE STUDY OF HISTOLOGICAL PROLIFERATIVE CHANGES IN ADJACENT AREAS OF BREAST CANCER

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Rema Nair Sarkar

2016-11-01

Full Text Available BACKGROUND Breast cancer remains a global health problem with an increasing incidence. Proliferative breast diseases are recognised as one of the risk factors in the development of carcinoma. This study was undertaken to know the frequency of proliferative lesions and other lesions in association with breast carcinomas in mastectomy specimens. MATERIALS AND METHODS 100 cases of excised carcinoma breast sent to the Department of Pathology for a three-year period at tertiary care centre was thoroughly examined and changes adjacent to the tumour was recorded and tissue was subjected for histopathological examination and results tabulated. RESULTS Infiltrating duct cell carcinoma, Not Otherwise Specified (NOS type was present in 89% of cases. Among the associated lesions, nonproliferative lesions constituted 16%, proliferative breast disease without atypia 29%, proliferative breast disease with atypia 10% and others 45%. Fibrocystic disease constituted 14% of cases, epithelial hyperplasia 15%, sclerosing adenosis 12% and atypical ductal hyperplasia in 10% of cases. Other types of associated lesions were duct carcinoma in situ in 4 cases. CONCLUSION Proliferative lesions adjacent to carcinoma breast were seen in 39% of cases. Fibrocystic disease, epithelial hyperplasia, sclerosing adenosis and atypical ductal hyperplasia being the commonest lesions adjacent to carcinoma breast in the present study.

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

NARCIS (Netherlands)

S. Pastor-Idoate (Salvador); I. Rodriguez-Hernández (Irene); J. Rojas (Jimena); I. Fernandez (Itziar); M.T. García-Gutierrez (María Teresa); J.M. Ruiz-Moreno (Jose María); A. Rocha-Sousa (Amandio); Y. Ramkissoon (Yashin); S. Harsum (Steven); R.E. MacLaren (Robert ); D. Charteris (David); J.C. Vanmeurs (Jan C.); R. González-Sarmiento (Rogelio); J.C. Pastor (Jose Carlos)

2013-01-01

textabstractProliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China123

Science.gov (United States)

Shannon, Jackilen; King, Irena B; Lampe, Johanna W; Gao, Dao Li; Ray, Roberta M; Lin, Ming-Gang; Stalsberg, Helge; Thomas, David B

2009-01-01

Background: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n–3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n–3 fatty acids with risk of benign fibrocystic breast changes. Objectives: The objectives of the study were to evaluate the role of n–3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. Design: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. Results: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. γ-Linolenic acid (18:3n–6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n–7 saturation index) was inversely associated with risk in all comparisons. Conclusion: Our results support a protective effects of n–3 fatty acid intake and the n–7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer. PMID:19056601

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

Energy Technology Data Exchange (ETDEWEB)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxiaoping61@126.com [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); He, Yin-Yan [Department of Obstetrics and Gynecology, Shanghai First People' s Hospital, Shanghai Jiao Tong University, Shanghai (China)

2012-04-06

Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

International Nuclear Information System (INIS)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue; Wan, Xiao-Ping; He, Yin-Yan

2012-01-01

Highlights: ► We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. ► GPR30 mediates the proliferative effects induced by OHT. ► GPR30 mediates the invasive effects induced by OHT. ► GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17β-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

Treatment and prevention of porcine proliferative enteropathy with oral tiamulin.

Science.gov (United States)

McOrist, S; Smith, S H; Shearn, M F; Carr, M M; Miller, D J

The effect of an oral treatment or prevention programme, incorporating the antibiotic tiamulin, on the development of proliferative enteropathy in experimentally challenged pigs was studied. Twenty weaner pigs were challenged orally with a virulent inoculum of Lawsonia intracellularis strain LR189/5/83, a British isolate of the causative agent of porcine proliferative enteropathy, and seven control pigs were dosed with a buffer solution. Seven of the 20 challenged pigs were left untreated; they gained less weight than the controls and three of them developed mild to moderate diarrhoea two weeks after the challenge. All seven developed lesions, six visible grossly, of proliferative enteropathy, and numerous intracellular L intracellularis were detected in sections of the intestines examined three weeks after the challenge. To test a 'prevention' dosing strategy for tiamulin, six of the challenged pigs were dosed orally with 50 ppm tiamulin, incorporated in a 2 per cent stabilised premix, given from two days before the challenge until they were euthanased. To test a 'treatment' strategy, the remaining group of seven challenged pigs were dosed orally with 150 ppm tiamulin given in the premix from seven days after challenge until they were euthanased. All the control pigs and the 13 pigs treated with tiamulin, either before or after challenge, remained clinically normal and had no specific lesions of proliferative enteropathy in sections of the intestines examined post mortem.

Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis of porcine proliferative enteropathy

DEFF Research Database (Denmark)

Boesen, Henriette Toft; Jensen, Tim Kåre; Møller, Kristian

2005-01-01

was a specific and sensitive method for detecting specific antibodies, and may be a good alternative to the existing serological tests for L intracellularis. It may be usable for diagnosis of proliferative enteropathy and for determination of a herd's epidemiologic status....... experimentally infected pigs and 62 serum samples from naturally infected pigs the sensitivity of the ELISA was calculated to 98.0%. The specificity of the test was 99.3%, calculated on the basis of 273 serum samples collected in six herds free of L. intracellularis after medicated eradication. The novel ELISA...

Proliferative myositis: a case report

International Nuclear Information System (INIS)

Kim, Young Sook; Jeon, Ho Jong

2002-01-01

We report a case of proliferative myositis arising in the pectoralis major muscle of a 59-year-old man who presented with palpable mass. The initial clinical impression was a malignant tumor. Ultrasonography revealed the lesion as a spindle-shaped hypoechoic mass, and MR imaging of the left pectoralis major muscle showed hypointensity at T1-weighted imaging, hyperintensity at T2-weighted imaging, and strong enhancement at contrast-enhanced T1-weighted imaging

Proliferative myositis: a case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Sook; Jeon, Ho Jong [Chosun University College of Medicine, Gwangju (Korea, Republic of)

2002-09-01

We report a case of proliferative myositis arising in the pectoralis major muscle of a 59-year-old man who presented with palpable mass. The initial clinical impression was a malignant tumor. Ultrasonography revealed the lesion as a spindle-shaped hypoechoic mass, and MR imaging of the left pectoralis major muscle showed hypointensity at T1-weighted imaging, hyperintensity at T2-weighted imaging, and strong enhancement at contrast-enhanced T1-weighted imaging.

Avaliação da Atividade Proliferativa no Epitélio Mamário Adjacente a Fibroadenoma em Mulheres Tratadas com Tamoxifeno Evaluation of Proliferative Activity in the Mammary Epithelium Adjacent to Fibroadenoma in Women Treated with Tamoxifen

Directory of Open Access Journals (Sweden)

Juarez Antônio de Sousa

2000-08-01

Full Text Available Objetivo: estudar a atividade proliferativa do epitélio mamário normal adjacente a fibroadenoma em mulheres na fase lútea do ciclo menstrual, tratadas com tamoxifeno. Pacientes e Métodos: estudou-se por técnica imuno-histoquímica, com o uso do anticorpo monoclonal MIB-1, a atividade proliferativa no epitélio mamário adjacente a fibroadenoma. O estudo foi randomizado e duplo-cego. As 44 mulheres com fibroadenoma foram divididas em 3 grupos: A (n = 16; placebo, B (n = 15; tamoxifeno, 10 mg e C (n = 13; tamoxifeno, 20 mg. O tamoxifeno foi utilizado por 22 dias, a partir do 2º dia do ciclo menstrual, e a biópsia realizada no 23º dia. Resultados: a porcentagem média de núcleos corados por 1000 células no grupo A foi 9,2, no grupo B, 4,5, e no grupo C, 3,2. O teste de Fisher revelou que o tamoxifeno reduziu de forma significante a imunoexpressão do MIB-1 nas doses de 10 e 20 mg em comparação com o grupo placebo (pPurpose: to study the monoclonal antibody MIB-1 in the normal breast epithelium adjacent to a fibroadenoma in women in the luteal phase of the menstrual cycle treated with tamoxifen. Patients and methods: the proliferative activity of the mammary epithelium adjacent to the fibroadenoma was studied by immunohistochemistry based on immunoexpression of the monoclonal antibody MIB-1. The study was randomized and double blind and was conducted on 44 women with fibroadenomas, divided into 3 groups: A (n = 16; placebo, B (n = 15; tamoxifen, 10 mg, and C (n = 13; tamoxifen, 20 mg. Tamoxifen was administered for 22 days starting on the 2nd day of the menstrual cycle and a biopsy was taken on the 23rd day. Results: the mean percentage of stained nuclei per 1000 cells was 9.2 in group A, 4.5 in group B, and 3.2 in group C. Fisher's test revealed that tamoxifen significantly reduced the immunoexpression of MIB-1 at the doses of 10 and 20 mg compared to the placebo group (p<0.0001, with no significant differences between doses in terms of

Proliferative retinopathy and proteinuria predict mortality rate in type 1 diabetic patients from Fyn County, Denmark

DEFF Research Database (Denmark)

Grauslund, J; Green, A; Sjølie, A K

2008-01-01

AIMS/HYPOTHESIS: We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. METHODS: In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973...... were identified (n=727). In 1981, only 627 patients were still alive and resident in Denmark. Of these, 573 (91%) participated in a clinical baseline examination, in which diabetic retinopathy was graded and other markers of diabetes measured. Mortality rate was examined in a 25 year follow....../INTERPRETATION: Proliferative retinopathy and proteinuria predict mortality rate in a population-based cohort of type 1 diabetic patients. In combination they act even more strongly. Non-proliferative diabetic retinopathy did not affect survival rate....

COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN FIBROCYSTIC MASTOSIS.

Science.gov (United States)

Carauleanu, A; Socolov, R; Rugina, V; Gabia, O; Carauleanu, Daniela Mihaela; Lupascu, Ivona Anghlcelache; Socolov, Demetra

2016-01-01

Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most treatments for fibrocystic mastosis are: hormonl, with beneficial results and non-hormonal, with fluctuating results. A number of 210 cases were studied, which were divided into 7 groups. The study lasted for 9 months and it was carried out on the basis of a personal examination sheet. The following were monitored: age groups, mastodynia, reducing breast nodules, a significant reduction in the volume of the mastosic cysts, reducion of the fibrous tissue, medication tolerance. Mastodynia has declined by 90% in the cases treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the advantages and disadvantages of drugs (contraindications, side effects), age category, breast pain reduction, antiproliferative activity, tolerability, relapse allow us to assess the benefit-risk. Even in those circumstances that remained incompletely clarified for objective reasons, related to the inaccurate/incorrect reporting by the patients, there is a significant difference (p < 0.05) between the frequency of relapses following the treatment with Tamoxifen and the other categories of drugs who were administered. Our study shows that in the groups that were administered Logest, Utrogestan and Bromocriptine, only antalgic effects were achieved (disappearance or only decrease of mastodynia) and no anti-proliferative effects were obtained. Basically, hormone treatment should be made based on a histopathological examination.

Evaluation of Apoptotic and Growth Inhibitory Activity of Phloretin in ...

African Journals Online (AJOL)

Results: The results show that the inhibitory activity of phloretin in BGC823 gastric cancer cells was mediated by induction of apoptosis ... anti-proliferative effects of phloretin was dose-dependent and inhibited the growth of BGC823 gastric cancer cells by 73 % at 30 μM; .... weeks at 37 °C in 5 % CO2 in humidified incubator.

Vitreous vascular endothelial growth factor concentrations in proliferative diabetic retinopathy versus proliferative vitreoretinopathy.

Science.gov (United States)

Citirik, Mehmet; Kabatas, Emrah Utku; Batman, Cosar; Akin, Kadir Okhan; Kabatas, Naciye

2012-01-01

To assess vitreous vascular endothelial growth factor (VEGF) concentrations in proliferative diabetic retinopathy (PDR) in comparison to proliferative vitreoretinopathy (PVR). Vitreous samples were collected from 69 eyes of 69 patients with traumatic lens dislocation (n = 10), grade B PVR with rhegmatogenous retinal detachment (n = 13), grade C PVR with rhegmatogenous retinal detachment (n = 14), PDR with vitreous hemorrhage (n = 18), and PDR with vitreous hemorrhage and tractional retinal detachment (n = 14). Vitreous fluid samples were obtained at vitrectomy, and the levels of VEGF were measured by enzyme-linked immunosorbent assay. The mean vitreous level of VEGF was 15.14 ± 5.22 pg/ml in eyes with grade B PVR, 99.15 ± 38.58 pg/ml in eyes with grade C PVR, 4,534.01 ± 1,193.28 pg/ml in eyes with vitreous hemorrhage secondary to PDR, 5,157.29 ± 969.44 pg/ml in eyes with vitreous hemorrhage and tractional retinal detachment secondary to PDR, and 16.19 ± 5.76 pg/ml in eyes of the control group with traumatic lens dislocation. Vitreous VEGF concentrations were significantly higher in the patients with grade C PVR, PDR with vitreous hemorrhage and PDR with vitreous hemorrhage and tractional retinal detachment in comparison to the control patients (p < 0.05). A significant alteration was not observed in patients with grade B PVR (p = 0.55). Vitreous VEGF concentrations are increased in PDR and grade C PVR. The high VEGF concentrations could suggest a possible effect of VEGF on advanced PVR. Copyright © 2011 S. Karger AG, Basel.

Proliferative response of the murine esophageal epithelium to radiation: Modification by food consumption patterns

International Nuclear Information System (INIS)

Burholt, D.R.

1985-01-01

The single layer of proliferative epithelial cells of the murine esophagus undergoes a sequence of damage and recovery following cytotoxic insult. The modification of both damage and proliferative recovery by the alteration of animal eating patterns was investigated following thoracic field irradiation through the determination of /sup 3/H-TdR incorporation into the esophagus along with selective counting of labeled nuclei and mitotic figures. Initial radiation-induced damage, as determined by /sup 3/H-TdR incorporation suppression and mitotic delay, is under normal conditions dependent on the time of day of treatment. This circadian sensitivity may be altered by changing the eating pattern of the animal. The proliferative recovery following single dose irradiation is also dependent on food consumption patterns: fasting immediately following treatment and then refeeding 2 days later results in a more rapid proliferative recovery than observed under control eating conditions, while reduced food consumption during the period of proliferative hyperplasia reduces the extent of recovery. During multifraction radiation schedules both the damage produced by a subsequent dose and recovery capacity are influenced by the food consumption pattern between fractions

F-18-FDG positron emission tomography findings correlate pathological proliferative activity of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Toyoizumi, Osamu; Oriuchi, Noboru; Miyakubo, Mitsuyuki

2010-01-01

It is still controversial whether fluorodeoxyglucose (FDG) uptake is correlated with cellular proliferation and prognosis of oral squamous cell carcinoma (OSC). In this study, we performed positron emission tomography (PET) study and immunohistochemical analysis to elucidate the relationship between FDG uptake and expression of cellular proliferative markers and pathological prognostic markers in patients with OSC. FDG PET and immunohistochemical staining have been carried out in sixteen patients with OSC. Tumor uptake of FDG was expressed with standardized uptake value (SUV). The expression of Ki-67, Topoisomerase IIα (Topo IIα), p53, and p63 in cancer cells was quantitatively assessed with positivity of the immunohistochemical staining. SUV was compared with the results of immunohistochemical analysis. FDG PET study revealed that SUV ranged from 3.6 to 22.1 with average of 10.4. Average positive rate of Ki-67, Topo IIα, p53, and p63 was 68.9%, 58.9%, 72.0%, and 65.2%, respectively. Pearson product-moment correlation coefficient analysis revealed that SUV was significantly correlated with Ki-67 (r=0.616, p=0.01), Topo IIα (r=0.677, p=0.004), p53 (r=0.613, p=0.01), and p63 (r=0.710, p=0.002), respectively. The present preliminary study indicated that FDG uptake was closely correlated with pathological cellular proliferative and prognostic markers in patients with OSC. (author)

The development of proliferative verrucous leukoplakia in oral lichen planus. A preliminary study

Science.gov (United States)

Llorente-Pendás, Santiago; González-Garcia, Manuel; García-Martín, José-Manuel

2016-01-01

Background Was to describe 14 cases of a proliferative verrucous leukoplakia as a clinical evolution of oral lichen planus. Material and Methods The clinical and histopathological characteristics of 14 cases of OLP that progress towards a plaque-like and verrucous form were indicated, with monitoring over a period of six to 24.3 years. Results The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old. None of the patients smoked during the study. As bilateral reticular was clinically diagnostic criterion, the second most frequent clinical form was the plaque form (n=10; 71.4%), followed by the atrophic (n=6; 42.8%), and erosive forms (n=4; 28.5%). Clinically it spread towards attached gingival mucosa and the hard palate. In the histopathologic study, there were a predominance of hyperkeratosis and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous cell carcinoma, and one patient developed two verrucous carcinoma. Conclusions Further research is needed to demonstrate if proliferative multifocal oral lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin. Key words:Oral lichen planus, proliferative verrucous oral leukoplakia, malignant oral lichen planus, multifocal verrucous oral lichen planus, proliferative verrucous oral lichen planus. PMID:27031060

Atypical hyperplasia, proliferative fibrocystic change, and exogenous hormone use.

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Zera, R T; Danielson, D; Van Camp, J M; Schmidt-Steinbrunn, B; Hong, J; McCoy, M; Anderson, W R; Linzie, B M; Rodriguez, J L

2001-10-01

The association between breast cancer development and exogenous hormone use (EHU) is suggested by indirect clinical evidence. We undertook this study to better define the relationship that EHU has with proliferative fibrocystic change (PFC) and atypical hyperplasia (AH). Women diagnosed with AH without associated carcinoma from January 1990 to December 1999 were compared with control subjects who underwent breast biopsy procedures during the same interval and who were diagnosed with either a proliferative fibrocystic change (PFC) or a nonproliferative fibrocystic change (NPFC). EHU was defined as the use of estrogen or progesterone taken together or separately within 3 months of biopsy. EHU was significantly higher in patients with AH compared with women with NPFC (P =.01). This observation was also significant if all proliferative change (both AH and PFC) was compared with NPFC (P =.03); it was not significant when PFC alone was compared with NPFC. No significant difference in EHU was demonstrated between women with AH and those with PFC. There is strong association between AH and EHU. These results support the theory that a continuum exists between hyperplasia and carcinoma and that EHU may influence the transition from one to the other in an undefined subset of women. We encourage our patients with AH to discontinue EHU.

Different proliferative capacity of lung fibroblasts obtained from control subjects and patients with emphysema

NARCIS (Netherlands)

Noordhoek, JA; Postma, DS; Chong, LL; Vos, JTWM; Kauffman, HF; Timens, W; van Straaten, JFM

2003-01-01

To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients

Cysteine-based 3-substituted 1,5-benzoxathiepin derivatives: Two new classes of anti-proliferative agents

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Nawal Mahfoudh

2018-03-01

Full Text Available Two distinct series of the 3-amino-1,5-benzoxathiepin scaffold, derived from L-cysteine, were synthesized and evaluated for their anti-proliferative activity in the breast cancer MDA-MB-231 and MCF-7 cells, and in the ovarian carcinoma SKOV-3 cell line. (3R-Amino-3,4-dihydro-2H-1,5-benzoxathiepin [(R-10] was diversified into two forms: (a by incorporating different amino acids at its position 3, through an amide bond; and (b by construction of the purine ring to give 6-chloro-9-[2-(3,4-dihydro-2H-1,5-benzoxathiepin-(3R-yl]-9H-purine [(R-28]. Nevertheless, when the introduction of iodine was tried at position 2 of the purine ring of (R-28, 2-{[2-(6-chloro-2-iodo-9H-purin-9-ylprop-2-en-1-yl]thio}phenol (34 was obtained. Compound 34 shows activity against cancer cells. Interestingly, 34 inhibits mammosphere formation at the micromolar range, demonstrating activity against cancer stem cells. Although further studies of its targets and mechanism of action are needed, these findings support the therapeutic potential of this compound in cancer.

Proliferative activity of vervet monkey bone marrow-derived adherent cells

International Nuclear Information System (INIS)

Kramvis, A.; Garnett, H.M.

1987-01-01

Vervet monkey bone marrow-derived adherent cell population cultured in Fischer's medium supplemented with 12.5% fetal calf serum and 12.5% horse serum consists of two cell shapes: fusiform (type I) and polygonal (type II). Limiting-dilution cloning of the cells suggested that the two morphologically distinct cell types belong to the same cellular system even though they differ in their proliferative capabilities. The labeling index of type II cells, as measured by autoradiography, was found to be consistently lower than that of type I cells. It is probable that these two phenotypes represent different stages of differentiation, where progenitor type I gives rise to type II cells. The bone marrow-derived adherent cells were found to be cytokinetically at rest in vivo, using the thymidine suicide test, and relatively radioresistant with a D0 = 2.1 Gy and n = 2.36 at the time of explantation from the bone. Furthermore, in culture these cells are characterized by a relatively long cell cycle of 60 h, where the length of the S phase is 30 h, G2 is 12 h, M is 6 h, and G1 is 12 h. Thus, the vervet monkey bone marrow-derived adherent cells represent a cell population with a low turnover rate both in vivo and in vitro

Proliferative diabetic retinopathy characterization based on fractal features: Evaluation on a publicly available dataset.

Science.gov (United States)

Orlando, José Ignacio; van Keer, Karel; Barbosa Breda, João; Manterola, Hugo Luis; Blaschko, Matthew B; Clausse, Alejandro

2017-12-01

Diabetic retinopathy (DR) is one of the most widespread causes of preventable blindness in the world. The most dangerous stage of this condition is proliferative DR (PDR), in which the risk of vision loss is high and treatments are less effective. Fractal features of the retinal vasculature have been previously explored as potential biomarkers of DR, yet the current literature is inconclusive with respect to their correlation with PDR. In this study, we experimentally assess their discrimination ability to recognize PDR cases. A statistical analysis of the viability of using three reference fractal characterization schemes - namely box, information, and correlation dimensions - to identify patients with PDR is presented. These descriptors are also evaluated as input features for training ℓ1 and ℓ2 regularized logistic regression classifiers, to estimate their performance. Our results on MESSIDOR, a public dataset of 1200 fundus photographs, indicate that patients with PDR are more likely to exhibit a higher fractal dimension than healthy subjects or patients with mild levels of DR (P≤1.3×10-2). Moreover, a supervised classifier trained with both fractal measurements and red lesion-based features reports an area under the ROC curve of 0.93 for PDR screening and 0.96 for detecting patients with optic disc neovascularizations. The fractal dimension of the vasculature increases with the level of DR. Furthermore, PDR screening using multiscale fractal measurements is more feasible than using their derived fractal dimensions. Code and further resources are provided at https://github.com/ignaciorlando/fundus-fractal-analysis. © 2017 American Association of Physicists in Medicine.

Physical activity and its correlation to diabetic retinopathy.

Science.gov (United States)

Praidou, Anna; Harris, Martin; Niakas, Dimitrios; Labiris, Georgios

2017-02-01

The lack of physical activity, along with obesity, smoking, hypertension and hyperglycaemia are considered as risk factors for the occurrence of diseases such as diabetes. Primary objective of the study was to investigate potential correlation between physical activity and diabetic retinopathy. Three hundred and twenty patients were included in the study: 240 patients with diabetes type 2 (80 patients with mild to moderate non-proliferative diabetic retinopathy, 80 patients with severe to very severe non-proliferative diabetic retinopathy and 80 ones with proliferative diabetic retinopathy) were compared with 80 non-diabetic patients (control group). Physical activity of patients was assessed by the international physical activity questionnaire (IPAQ, 2002). HbA1c and BMI were also measured in diabetic patients. Group comparisons were attempted for levels of physical activity and sedentary behavior. Total physical activity was decreased in patients with severe to very severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy as compared to patients with mild to moderate non-proliferative diabetic retinopathy and to the control group (pdiabetic retinopathy and physical activity has been demonstrated (pdiabetic retinopathy, independent of the effects of HbA1c and BMI. Copyright © 2016 Elsevier Inc. All rights reserved.

Dysregulation of T lymphocyte proliferative responses in autoimmunity.

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Sydney K Elizer

Full Text Available T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains-NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains.

Fibrinolysis and proliferative endarteritis: two related processes in chronic infections? The model of the blood-borne pathogen Dirofilaria immitis.

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Javier González-Miguel

Full Text Available The interaction between blood-borne pathogens and fibrinolysis is one of the most important mechanisms that mediate invasion and the establishment of infectious agents in their hosts. However, overproduction of plasmin (final product of the route has been related in other contexts to proliferation and migration of the arterial wall cells and degradation of the extracellular matrix. We have recently identified fibrinolysis-activating antigens from Dirofilaria immitis, a blood-borne parasite whose key pathological event (proliferative endarteritis is produced by similar mechanisms to those indicated above. The objective of this work is to study how two of this antigens [actin (ACT and fructose-bisphosphate aldolase (FBAL] highly conserved in pathogens, activate fibrinolysis and to establish a relationship between this activation and the development of proliferative endarteritis during cardiopulmonary dirofilariasis. We demonstrate that both proteins bind plasminogen, enhance plasmin generation, stimulate the expression of the fibrinolytic activators tPA and uPA in endothelial cell cultures and are located on the surface of the worm in contact with the host's blood. ELISA, western blot and immunofluorescence techniques were employed for this purpose. Additionally, the implication of lysine residues in this interaction was analyzed by bioinformatics. The involvement of plasmin generated by the ACT/FBAL and plasminogen binding in cell proliferation and migration, and degradation of the extracellular matrix were shown in an "in vitro" model of endothelial and smooth muscle cells in culture. The obtained results indicate that ACT and FBAL from D. immitis activate fibrinolysis, which could be used by the parasite like a survival mechanism to avoid the clot formation. However, long-term overproduction of plasmin can trigger pathological events similar to those described in the emergence of proliferative endarteritis. Due to the high degree of

The proliferative human monocyte subpopulation contains osteoclast precursors

Science.gov (United States)

Lari, Roya; Kitchener, Peter D; Hamilton, John A

2009-01-01

Introduction Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors. Methods Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL). Results The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes. Conclusions Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation. PMID:19222861

Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

Science.gov (United States)

Tutton, P J; Barkla, D H

1988-01-01

Glucocorticoid and mineralocorticoid receptors are present in normal epithelial cells of both the small and large intestine and there have also been contentious reports of androgen, oestrogen and progesterone receptors in the epithelium of the normal large intestine. The majority of reports suggest that stimulation of the intestinal glucocorticoid receptors results in increased proliferation of epithelial cells in the small bowel, as does stimulation of androgen receptors and possibly mineralocorticoid receptors. The proliferative response of the normal intestine to oestrogens is difficult to evaluate and that to progestigens appears not to have been reported. Epidemiological studies reveal a higher incidence of bowel cancer in premenopausal women than in men of the same age and yet there is a lower incidence of these tumors in women of higher parity. These findings have been atributted to a variety of non-epithelial gender characteristic such as differences in bile metabolism, colonic bacterial and fecal transit times. In experimental animals, androgens have also been shown to influence carcinogenesis and this could well be attributed to changes in food intake etc. However, many studies have now revealed steroid hormone receptors on colorectal tumor cells and thus a direct effect of the steroid hormones on the epithelium during and after malignant transformation must now be considered.

The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

Science.gov (United States)

Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

2015-04-01

Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19ARF-p53 signaling

NARCIS (Netherlands)

Shvarts, A.; Brummelkamp, T.; Koh, E.; Daley, G.Q.; Bernards, R.A.

2002-01-01

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling

NARCIS (Netherlands)

Shvarts, Avi; Brummelkamp, Thijn R.; Scheeren, Ferenc; Koh, Eugene; Daley, George Q.; Spits, Hergen; Bernards, René

2002-01-01

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

Cetuximab-Associated Crescentic Diffuse Proliferative Glomerulonephritis

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Sukesh Manthri

2017-01-01

Full Text Available Cetuximab-induced nephrotoxicity is very rare, occurring in less than 1% of colorectal cancer patients and not defined in other populations. We report a rare case of crescentic diffuse proliferative glomerulonephritis (GN that developed in close temporal association with cetuximab treatment. A 65-year-old female recently completed chemotherapy with cetuximab treatment for moderately differentiated oral squamous cell carcinoma. She was admitted with acute renal failure and nephrotic-range proteinuria. Laboratory data showed serum creatinine of 6.6 mg/dl and urinalysis showed proteinuria, moderate hemoglobinuria, hyaline casts (41/LPF, WBC (28/HPF, and RBC (81/HPF. Serologic studies were negative for ANA, anti-GBM, ANCA, hepatitis B, and hepatitis C. Serum C3 and C4 level were normal. Renal biopsy showed crescentic diffuse proliferative GN with focal features of thrombotic microangiopathy. Patient was started on cyclophosphamide and steroids. Her renal function did not improve on day 8 and she was started on hemodialysis. Previous reports suggest that EGFR-targeting medications can possibly trigger or exacerbate an IgA-mediated glomerular process leading to renal failure. This case suggests that cetuximab therapy may have triggered or exacerbated a severe glomerular injury with an unfavorable outcome. Treating physicians should maintain a high degree of caution and monitor renal function in patients on EGFR inhibitors.

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

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Helson Lawrence

2007-01-01

Full Text Available Abstract Background With current treatment strategies, nearly half of all medulloblastoma (MB patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. Methods To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected, D341 (c-MYC amplification and D425 (c-MYC amplification human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. Results NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. Conclusion In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit

Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma.

Science.gov (United States)

Mauchle, Ulrike; Selvarajah, Gayathri T; Mol, Jan A; Kirpensteijn, Jolle; Verheije, Monique H

2015-08-01

Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes

International Nuclear Information System (INIS)

Souza, Kátina M.; Braz, Leandro G.; Nogueira, Flávia R.; Souza, Marajane B.; Bincoleto, Lahis F.; Aun, Aline G.; Corrente, José E.; Carvalho, Lídia R.; Braz, José Reinaldo C.; Braz, Mariana G.

2016-01-01

Highlights: • Anesthesiologists exposed to the most commonly used anesthetic gases were evaluated. • No alterations were detected for lymphocyte DNA damage detected by the comet assay. • Decreased frequencies of basal cells were detected in exfoliated buccal cells (BMCyt). • Increased frequencies of micronucleus and cytotoxicity were observed in BMCyt assay. • Anesthesiologists have genomic instability due to occupational exposure. - Abstract: Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide − N 2 O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N 2 O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170 ppm for N 2 O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and pyknosis, and

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes

Energy Technology Data Exchange (ETDEWEB)

Souza, Kátina M.; Braz, Leandro G.; Nogueira, Flávia R.; Souza, Marajane B.; Bincoleto, Lahis F.; Aun, Aline G. [Faculdade de Medicina de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Anestesiologia, Botucatu (Brazil); Corrente, José E.; Carvalho, Lídia R. [Instituto de Biociências de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Bioestatística, Botucatu (Brazil); Braz, José Reinaldo C. [Faculdade de Medicina de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Anestesiologia, Botucatu (Brazil); Braz, Mariana G., E-mail: mgbraz@hotmail.com [Faculdade de Medicina de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Anestesiologia, Botucatu (Brazil)

2016-09-15

Highlights: • Anesthesiologists exposed to the most commonly used anesthetic gases were evaluated. • No alterations were detected for lymphocyte DNA damage detected by the comet assay. • Decreased frequencies of basal cells were detected in exfoliated buccal cells (BMCyt). • Increased frequencies of micronucleus and cytotoxicity were observed in BMCyt assay. • Anesthesiologists have genomic instability due to occupational exposure. - Abstract: Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide − N{sub 2}O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N{sub 2}O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170 ppm for N{sub 2}O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and

Cytomorphology of fibrocystic change, high-risk proliferative breast disease, and premalignant breast lesions.

Science.gov (United States)

Masood, Shahla

2005-12-01

In a prospective study using mammographically guided fine needle aspirates in 100 nonpalpable breast lesions, the author's group assessed the reliability of a cytological grading system to define the cytological features of proliferative and nonproliferative breast disease and to differentiate between benign, premalignant and malignant breast lesions. We developed a cytological grading system evaluating the aspirates for the cellular arrangement, the degrees of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. This grading system, now recognized as the Masood Cytology Index, is commonly used as a surrogate end point biomarker in chemoprevention trials.

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

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Kenichiro Ishii

2018-04-01

Full Text Available Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers.

Antibacterial, antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs.

Science.gov (United States)

Nunes, Ricardo; Pasko, Pawel; Tyszka-Czochara, Malgorzata; Szewczyk, Agnieszka; Szlosarczyk, Marek; Carvalho, Isabel S

2017-12-01

Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal. To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc. Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48 h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24 h) was tested using HEP G2 cells and fibroblasts. Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90 mg AAE/g dw and 783.48 mg TE/g dw, respectively). CM had the highest zinc concentration (37.21 mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91 mg/100 g dw). LS was rich in rosmarinic acid (301.71 mg/100 g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830 μg/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content. The most promising plants for further studies are CM, LS and GP.

Scoring radiologic characteristics to predict proliferative potential in meningiomas

International Nuclear Information System (INIS)

Hashiba, Tetsuo; Hashimoto, Naoya; Maruno, Motohiko; Izumoto, Shuichi; Suzuki, Tsuyoshi; Kagawa, Naoki; Yoshimine, Toshiki

2006-01-01

We investigated the feasibility of using radiologic characteristics to predict the proliferative potential in meningiomas. Our statistical analysis revealed that the presence of peritumoral edema, an ambiguous brain-tumor border, and irregular tumor shape were significantly correlated with a higher MIB-1 staining index (SI) value. We developed the following scoring system for specific features in each tumor: peritumoral edema (tumor with edema=1, tumor without edema=0); brain-tumor border (tumor with any ambiguous border=1, tumor circumscribed by a distinct rim=0); and tumor shape (tumor with irregular shape=1, tumor with smooth shape=0). Using Spearman's correlation coefficient analysis, we found a significant correlation (P<0.005) between total score calculated for each patient and SI value. Our findings suggest that the proliferative potential of meningiomas can be predicted using a less invasive preoperative examination focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and irregular tumor shape. (author)

Anti-proliferative effect of Moringa oleifera Lam (Moringaceae) leaf ...

African Journals Online (AJOL)

Purpose: To investigate the in vitro anti-proliferative effect and mechanism of action of Moringa oleifera Lam. leaf extract on human colon carcinoma HCT116 cell line. Methods: M. oleifera leaves were extracted with methanol. It was fractionated by Sephadex LH-20 column chromatography. Several fractions were identified ...

Body linear traits for identifying prolific goats

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Avijit Haldar

2014-12-01

Full Text Available Aim: The present study was conducted on prolific goat breed to identify body linear type traits that might be associated with prolificacy trait in goats. Materials and Methods: Two-stage stratified random sample survey based data were collected from 1427 non-pregnant goats with the history of single, twin and triplet litter sizes (LZ between January 2008 to February 2011 for 3 years in 68 villages located in East and North East India. Data on sixteen body linear traits were analyzed using logistic regression model to do the step-wise selection for identifying the body linear traits that could determine LZ. An average value for each identified body linear trait was determined for classifying the goats into three categories: Goats having the history of single LZ, goats having the history of twin LZ and goats having the history of triplet LZ. Results: The LZ proportions for single, twin and triplet, were 29.50, 59.14 and 11.36%, respectively, with the prolificacy rate of 181.85% in Indian Black Bengal goats. A total of eight body linear traits that could determine LZ in prolific goats were identified. Heart girth (HG measurement (>60.90 cm, paunch girth (PG (>70.22 cm, wither height (WH (>49.75 cm, neck length (>21.45 cm, ear length (>12.80 cm and distance between trochanter major (DTM bones (>12.28 cm, pelvic triangle area (PTA (>572.25 cm2 and clearance at udder (CU (>23.16 cm showed an increase likelihood of multiple LZ when compared to single LZ. Further, HG measurement (>62.29 cm, WH (>50.54 cm, PG (>71.85 cm and ear length (>13.00 cm, neck length (>22.01 cm, PTA (>589.64 cm2, CU (>23.20 cm and DTM bones (>12.47 cm were associated with increased likelihood of triplet LZ, when compared with that of twin LZ. Conclusion: HG measurement was the best discriminating factor, while PG, neck length, DTM bones, CU, PTA, WH and ear length measurements were other important factors that could be used for identifying prolific goats to achieve economic

Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy

NARCIS (Netherlands)

Woerdeman, J.P.; van Duinkerken, E.; Wattjes, M.P.; Barkhof, F.; Snoek, F.J.; Moll, A.C.; Klein, M.; de Boer, M.P.; IJzerman, R.G.; Serne, E.H.; Diamant, M.

2014-01-01

OBJECTIVE: We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS: Thirty-three patients with proliferative

Too much of a good thing? An observational study of prolific authors.

Science.gov (United States)

Wager, Elizabeth; Singhvi, Sanjay; Kleinert, Sabine

2015-01-01

Introduction. Researchers' productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties. Methods. We analysed Medline publications from 2008-12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation). This enabled us to assess the number and type of publications per author per year. Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days). Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters). Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

Too much of a good thing? An observational study of prolific authors

Directory of Open Access Journals (Sweden)

Elizabeth Wager

2015-08-01

Full Text Available Introduction. Researchers’ productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties.Methods. We analysed Medline publications from 2008–12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation. This enabled us to assess the number and type of publications per author per year.Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days. Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters.Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

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Branka Zorc

2012-01-01

Full Text Available Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1, 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethylphenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1. Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

Proliferative myositis in a patient with AIDS

International Nuclear Information System (INIS)

Wlachovska, B.; Deux, J.F.; Marsault, C.; Le Breton, C.; Abraham, B.; Sibony, M.

2004-01-01

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process. (orig.)

Proliferative myositis in a patient with AIDS

Energy Technology Data Exchange (ETDEWEB)

Wlachovska, B.; Deux, J.F.; Marsault, C.; Le Breton, C. [Department of Radiology, Hopital Tenon, 4 rue de la Chine, 75020, Paris (France); Abraham, B. [Department of Tropical and Infectious Diseases, Hopital Tenon, Paris (France); Sibony, M. [Department of Anatomy, Hopital Tenon, Paris (France)

2004-04-01

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process. (orig.)

Anti-proliferative therapy for HIV cure: a compound interest approach.

Science.gov (United States)

Reeves, Daniel B; Duke, Elizabeth R; Hughes, Sean M; Prlic, Martin; Hladik, Florian; Schiffer, Joshua T

2017-06-21

In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4 + T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation and new infection rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART could result in functional cure within 2-10 years rather than several decades on ART alone.

Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

International Nuclear Information System (INIS)

Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

2012-01-01

In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC 50 ) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC 50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs

Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

NARCIS (Netherlands)

van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

Science.gov (United States)

Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

2017-01-01

P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

VISUALIZATION FROM INTRAOPERATIVE SWEPT-SOURCE MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY IN VITRECTOMY FOR COMPLICATIONS OF PROLIFERATIVE DIABETIC RETINOPATHY.

Science.gov (United States)

Gabr, Hesham; Chen, Xi; Zevallos-Carrasco, Oscar M; Viehland, Christian; Dandrige, Alexandria; Sarin, Neeru; Mahmoud, Tamer H; Vajzovic, Lejla; Izatt, Joseph A; Toth, Cynthia A

2018-01-10

To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated optical coherence tomography in vitrectomy for proliferative diabetic retinopathy complications. In this prospective study, we analyzed a subgroup of patients with proliferative diabetic retinopathy complications who required vitrectomy and who were imaged by the research swept-source microscope-integrated optical coherence tomography system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy-associated pathologies and reviewing the intraoperatively documented surgeon feedback. Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy complications could be imaged. Swept-source microscope-integrated optical coherence tomography provided surgical guidance, e.g., in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%), acceptable images were captured, but they were not useful due to high tractional retinal detachment elevation which was challenging for imaging. Swept-source microscope-integrated optical coherence tomography can provide important guidance during surgery for proliferative diabetic retinopathy complications through intraoperative identification of different complications and facilitation of intraoperative decision making.

Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

Directory of Open Access Journals (Sweden)

Maher Kurdi

2014-01-01

Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

Proliferative and nonproliferative breast disease in atomic-bomb survivors

International Nuclear Information System (INIS)

Tokunaga, Masayoshi; Land, C.E.; Aoki, Yoichiro; Yamamoto, Tsutomu; Asano, Masahide; Sato, Eiichi; Tokuoka, Shoji; Sakamoto, Goi; Page, D.L.

1993-10-01

The risk of female breast cancer in association with radiation exposure is well established, on the basis of follow-up studies of the atomic-bomb survivors and other exposed populations. This association is especially strong for women exposed before age 20 yr and appears to be much weaker among women exposed after age 40 yr. In this study, breast-tissue autopsy samples from high-dose and low-dose individuals in the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative or proliferative breast lesions are associated with radiation exposure. The results suggest that proliferative disease in general and atypical hyperplasia in particular are associated with radiation exposure and that the risk is strongest for subjects who were ages 40-49 yr at the time of the bombings. It is hypothesized that this finding may be related to the age dependence of radiation-induced breast cancer, in the sense that potential cancers reflecting early-stage changes induced at these ages by radiation exposure may receive too little hormonal promotion to progress to frank cancers. (author)

Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria

NARCIS (Netherlands)

Carrard, V.C.; Brouns, E.R.E.A.; van der Waal, I.

2013-01-01

Since its introduction in the literature in 1985, the term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Widespread or multifocal occurrence of oral leukoplakia is not just synonymous to PVL. In the present treatise the

Possible mechanisms for arsenic-induced proliferative diseases

Energy Technology Data Exchange (ETDEWEB)

Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

1996-12-31

Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

Diagnostic value of ductogalactography and cytology in the proliferative changes of the mammary ducts

International Nuclear Information System (INIS)

Sessa, M.; Cerroni, L.; Bertolotti, A.

1991-01-01

Three hundred and thiyrty-six patients with nipple discharge and neither physical signs at breast examination nor pathological findings at mammography, were observed from 1984 to 1988 and studied by means of ductogalactography and cytology of discharge. Of this group, 76 patients (22%) underwent surgery and histology. In 65/76 cases proliferative pathologic conditions were demonstrated: 51 single/ multiple papillomas and 14 carcinomas. Ductogalactography suggested proliferative pathologic conditions in 59 cases and cytology of discharge showed blood in 44 patients, papillary clusters in 23, and atypical cells in 15 (both as single occurrences and in association). In cancer patients discharge appeared to be mostly spontaneous, monoductal and blood-stained. In papillomas, induced discharge was almost as frequent as spontaneous discharge, and milky discharge was also present. Ductogalactography confirmed its value in the diagnosis of proliferative pathologic conditions of the mammary ducts, being especially useful to detect carcinomas without palpable tumors. Cytology of discharge had poorer diagnostic significance

The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases.

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Jerzy Sikora

2008-04-01

Full Text Available RCAS1 expression is related to the regulation of activated immune cells and to connective tissue remodeling within the endometrium. DFF45 seems to play an important role in the apoptotic process, most likely by acting through the regulation of DNA fragmentation. Its expression changes within the endometrium seem to be related to the resistance of endometrial cells to apoptosis. The aim of the present study was to evaluate RCAS1 and DFF45 endometrial expressions during ovulation and the implantation period. RCAS1 and DFF45 expression was assessed by the Western-blot method in endometrial tissue samples obtained from 20 patients. The tissue samples were classified according to the menstrual cycle phases in which they were collected, with a division into three phases: late proliferative, early secretory, and mid-secretory. The lowest level of RCAS1 and the highest level of DFF45 endometrial expression was found during the early secretory cycle phase. Statistically significantly higher RCAS1 and statistically significantly lower DFF45 endometrial expression was identified in the endometrium during the late proliferative as compared to the early secretory cycle phase. Moreover, statistically significantly higher RCAS1 and statistically significantly lower DFF45 expression was found in the endometrium during the mid-secretory as compared to the early secretory cycle phase. The preparation for implantation process in the endometrium is preceded by dynamic changes in endometrial ECM and results from the proper interaction between endometrial and immune cells. The course of this process is conditioned by the immunomodulating activity of endometrial cells and their resistance to immune-mediated apoptosis. These dynamic changes are closely related to RCAS1 and DFF45 expression alterations.

Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas

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Kourt Chatelain

2011-01-01

Full Text Available Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

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Kathleen Jee

Full Text Available The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF, for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR, the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4 is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients. Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient and vitreous (n = 3 patients samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.

Analysis and Enhancements of a Prolific Macroscopic Model of Epilepsy

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Christopher Fietkiewicz

2016-01-01

Full Text Available Macroscopic models of epilepsy can deliver surprisingly realistic EEG simulations. In the present study, a prolific series of models is evaluated with regard to theoretical and computational concerns, and enhancements are developed. Specifically, we analyze three aspects of the models: (1 Using dynamical systems analysis, we demonstrate and explain the presence of direct current potentials in the simulated EEG that were previously undocumented. (2 We explain how the system was not ideally formulated for numerical integration of stochastic differential equations. A reformulated system is developed to support proper methodology. (3 We explain an unreported contradiction in the published model specification regarding the use of a mathematical reduction method. We then use the method to reduce the number of equations and further improve the computational efficiency. The intent of our critique is to enhance the evolution of macroscopic modeling of epilepsy and assist others who wish to explore this exciting class of models further.

A lentiviral vector with expression controlled by E2F-1: A potential tool for the study and treatment of proliferative diseases

International Nuclear Information System (INIS)

Strauss, Bryan E.; Patricio, Juliana Rotelli; Vieira de Carvalho, Anna Carolina; Bajgelman, Marcio C.

2006-01-01

We have constructed a lentiviral vector with expression limited to cells presenting active E2F-1 protein, a potential advantage for gene therapy of proliferative diseases. For the FE2FLW vector, the promoter region of the human E2F-1 gene was utilized to drive expression of luciferase cDNA, included as a reporter of viral expression. Primary, immortalized, and transformed cells were transduced with the FE2FLW vector and cell cycle alterations were induced with serum starvation/replacement, contact inhibition or drug treatment, revealing cell cycle-dependent changes in reporter activity. Forced E2F-1 expression, but not E2F-2 or E2F-3, increased reporter activity, indicating a major role for this factor in controlling expression from the FE2FLW virus. We show the utility of this vector as a reporter of E2F-1 and proliferation-dependent cellular alterations upon cytotoxic/cytostatic treatment, such as the introduction of tumor suppressor genes. We propose that the FE2FLW vector may be a starting point for the development of gene therapy strategies for proliferative diseases, such as cancer or restinosis

Proliferative thyroid lesions in three diplodactylid geckos: Nephrurus amyae, Nephrurus levis, and Oedura marmorata.

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Hadfield, Catherine A; Clayton, Leigh A; Clancy, Meredith M; Beck, Sarah E; Mangus, Lisa M; Montali, Richard J

2012-03-01

Over a 5-mo period, three diplodactylid geckos housed at the National Aquarium were diagnosed with proliferative thyroid lesions: a rough knob-tail gecko (Nephrurus amyae), a smooth knob-tail gecko (Nephrurus levis), and a marbled velvet gecko (Oedura marmorata). Clinical signs included an intraoral mass or ventral throat swelling (or both), oral bleeding, and weight loss. Both of the knob-tail geckos died. The histologic diagnosis for the rough knob-tail gecko was thyroid carcinoma with metastases to the liver and lungs, and thyroid carcinoma with no metastases was reported in the smooth knob-tail gecko. A thyroidectomy was performed on the marbled velvet gecko with a histologic diagnosis of adenomatous hyperplasia. Postoperative weight loss and bradycardia resolved following oral supplementation with levothyroxine. The animal is in normal health 10 mo post-surgery. Five other diplodactylid geckos in the collection remain unaffected, giving a 38% prevalence of proliferative thyroid lesions (3/8). The etiology remains undetermined. This is the first report of a cluster of proliferative thyroid lesions in geckos.

Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

International Nuclear Information System (INIS)

Kolesnichenko, T.S.; Gor'kova, T.G.

1985-01-01

Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

To report a case of unilateral proliferative retinopathy following noncerebral malaria with Plasmodium falciparum in Southern India

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Aditya Verma

2015-01-01

Full Text Available The retinopathy in association with malaria fever described so far includes retinal hemorrhages, vessel changes, retinal discoloration/whitening and papilledema. Malaria retinopathy has been mostly described in severe cases, associated with Plasmodium falciparum, correlating the patho-physiology of retinal and cerebral manifestations. We report an unusual case of proliferative retinopathy as a manifestation of malaria fever, caused by P. falciparum with no cerebral involvement. The patient had features of unilateral retinal vascular occlusion with proliferative changes and vitreous hemorrhage. To the best of our knowledge, such a case has never been reported so far in the literature. This report highlights the possible occurrence of severe proliferative changes associated with malaria fever, which if diagnosed early can prevent possible blindness.

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

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Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

Rehabilitation effect of oral drug on the patients with proliferative diabetic retinopathy after operation

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Wei Zu

2014-08-01

Full Text Available AIM:To observe the rehabilitation effect of oral Calcium Dobesilate Tablets and Epalrestat Tablets on the proliferative diabetic retinopathy(PDRpatients after vitrectomy.METHODS: After vitrectomy patients informed consent, they were randomly divided into intervention group and control group, and their vision and fundus were followed up and compared at 2d; 3, 6, 9, 12mo after operation.RESULTS: The recovery and sustainment of visual acuity, and subsiding of macular edema of patients in drug intervention group were significantly better than that in control group.CONCLUSION: PDR patients after vitrectomy actively orally take medicine to protect retina, which can improve vision and fundus rehabilitation.

Posterior subtenon triamcinolone acetonide in gas-filled eyes as an adjunctive treatment for complicated proliferative diabetic retinopathy.

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Lee, Yongeun; Kang, Seungbum; Park, Young-Hoon

2013-02-01

To evaluate the effect of adjunctive subtenon injection of triamcinolone acetonide (TA) in gas-filled eyes after vitrectomy for complicated proliferative diabetic retinopathy (PDR). This nonrandomized comparative study included 27 patients (27 eyes) who underwent pars plana vitrectomy and gas tamponade for treatment of PDR with tractional or combined tractional-rhegmatogenous retinal detachment and who received subtenon injection of TA (40 mg) at the end of surgery. The study group was compared with the control group (29 eyes), which was matched with the study group for preoperative and intraoperative parameters, but underwent pars plana vitrectomy and gas tamponade without a subtenon injection of TA. Retinal reattachments without reoperation were achieved in 25 eyes (92.6%) and 26 eyes (89.7%) at 6 months (p = 1.000) in the study and control groups, respectively. The study group and the control group did not differ significantly in the frequency of postoperative proliferative vitreoretinopathy, retinal redetachment rate, reoperation rate, macular pucker formation, postoperative vitreous hemorrhage, gain in visual acuity, intraocular pressure, and intraocular inflammation (p > 0.05). The clinical results of pars plana vitrectomy for complicated PDR are not improved significantly by an adjunctive subtenon TA injection in gas-filled eyes.

Is Smoking a Risk Factor for Proliferative Diabetic Retinopathy in Type 1 Diabetes?

DEFF Research Database (Denmark)

Gaedt Thorlund, Mie; Borg Madsen, Mette; Green, Anders

2013-01-01

were asked about their smoking habits. The level of retinopathy was evaluated by ophthalmoscopy at baseline and by nine 45-degree colour field fundus photos at the follow-up. Results: In multivariate analyses there was a trend that current smokers at baseline were more likely to develop PDR......Aim: The aim was to evaluate if smoking was a risk factor for proliferative retinopathy (PDR) in a 25-year follow-up study. Methods: 201 persons from a population-based cohort of Danish type 1 diabetic patients were examined at baseline and again 25 years later. At both examinations the patients...... at the follow-up (odds ratio 1.90, 95% confidence interval 0.88-4.11, p = 0.10). Neither smoking status at the follow-up nor pack-years of smoking were associated with PDR. Conclusions: We found neither a beneficial nor a harmful effect of smoking on long-term incidence. Selective mortality among smokers...

Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes.

LENUS (Irish Health Repository)

Davis, Niall F

2012-01-31

OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4\\

Autologous proliferative therapies in recalcitrant lateral epicondylitis.

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Tetschke, Elisa; Rudolf, Margit; Lohmann, Christoph H; Stärke, Christian

2015-09-01

This study investigates the clinical effects of autologous conditioned plasma (ACP) injections and low-level laser application as therapy options for chronic lateral epicondylitis. A total of 52 patients with chronic lateral epicondylitis were evaluated in this study; 26 of these patients received three ACP injections and the control group, with 26 patients, received 12 laser applications, with standardized physical therapy for all patients afterward. Control examinations took place before treatment, after 2 and 6 mos, and in the 1 yr final follow-up. The control examination included the visual analog scale for pain and Disabilities of the Arm, Shoulder and Hand outcome measure scores. The analysis at final follow-up after 1 yr showed that both treatment options resulted in successful therapy outcome for the patients. In total, 63.5 % were successfully treated. Successful treatment was defined as more than 30% improvement in the visual analog score and more than 10.2 points in the Disabilities of the Arm, Shoulder and Hand score. Both groups showed a significant improvement in time response. This study demonstrates the beneficial effects of autologous proliferative therapies in the treatment of lateral epicondylitis. The data show that laser application and ACP therapy lead to a clinical improvement in epicondylopathia. Especially the new treatment with ACP can be highlighted as an alternative and as an easy-to-apply therapy option for clinical practice.

Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex.

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Heimann, Gábor; Canhos, Luisa L; Frik, Jesica; Jäger, Gabriele; Lepko, Tjasa; Ninkovic, Jovica; Götz, Magdalena; Sirko, Swetlana

2017-08-01

Aging leads to adverse outcomes after traumatic brain injury. The mechanisms underlying these defects, however, are not yet clear. In this study, we found that astrocytes in the aged post-traumatic cerebral cortex develop a significantly reduced proliferative response, resulting in reduced astrocyte numbers in the penumbra. Moreover, experiments of reactive astrocytes in vitro reveal that their diminished proliferation is due to an age-related switch in the division mode with reduced cell-cycle re-entry rather than changes in cell-cycle length. Notably, reactive astrocytes in vivo and in vitro become refractory to stimuli increasing their proliferation during aging, such as Sonic hedgehog signaling. These data demonstrate for the first time that age-dependent, most likely intrinsic changes in the proliferative program of reactive astrocytes result in their severely hampered proliferative response to traumatic injury thereby affecting astrocyte homeostasis. © The Author 2017. Published by Oxford University Press.

Anti-Proliferative and Apoptotic Effects of Beta-Ionone in Human Leukemia Cell Line K562

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Zohreh Faezizadeh

2016-06-01

Full Text Available Background Beta-ionone is an aroma compound found in the Rosaceae family. Some evidence supported that beta-ionone has a great potential for cancer prevention. To date, the anti-proliferative and apoptotic effects of beta-ionone in human leukemia cell line K562 were not studied. Objectives Hence, we investigated whether beta-ionone could inhibit cell growth and induce apoptosis in the K562 cells. Materials and Methods In this experimental study, human leukemia cell line K562 was cultured and anti-proliferation effect of beta-ionone with different doses (25 - 400 µm at different times (24 - 96 hours on treated cells was evaluated by the MTT assay. To determine apoptosis rate, the Hoechst 33342 staining and flow cytometry was performed. Results The MTT assay showed that beta-ionone inhibited proliferation of K562 cells in a dose-dependent manner significantly (P = 0.0008. Moreover, the increased apoptotic rate was found after incubation of K562 cells with 200 µm beta-ionone. The Hoechst staining and flow cytometry analysis indicated that beta-ionone could increase apoptosis of K562 cells in a dose-dependent manner. Conclusions The results demonstrated that beta-ionone has anti-proliferative and apoptotic effects on K562 cells, and in the future may be used in the treatment of some leukemia sub-types.

Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

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Strand, Marie; Micchelli, Craig A

2013-01-01

Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P) axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs) of the acidic copper cell region (CCR), which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

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Marie Strand

Full Text Available Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs of the acidic copper cell region (CCR, which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

Determination of the Antiproliferative Activity of New Theobromine Derivatives and Evaluation of Their In Vitro Hepatotoxic Effects.

Science.gov (United States)

Georgieva, Maya; Kondeva-Burdina, Magdalena; Mitkov, Javor; Tzankova, Virginia; Momekov, Georgi; Zlatkov, Alexander

2016-01-01

A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentrationdependent cytotoxic activity was observed, with 7g outlined as the most active compound within the series. The targed compounds were obtained in yields of 56 to 85% and their structures were elucidated by FTIR, (1)H NMR, (13)C NMR and microanalyses. The compounds purity was proven by elemental analysis and spectral data. In general, the compounds showed low hepatotoxicity on sub-cellular and cellular level. On isolated rat microsomes only 7d showed toxic effect while theobromine, 1-benzyl-theobromine-thioacetic acid (BTTA) and the other new theobromine derivatives were devoid of toxicity. In isolated rat hepatocytes, when compared to theobromine and BTTA, 7f showed lower cytotoxic effects, and 7d exerted higher cytotoxicity. The results indicate 7g as a promising structure for the design of future compounds with low hepatotoxicity and good antiproliferative activity.

Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

Science.gov (United States)

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

Bilateral Proliferative Retinopathy as the Initial Presentation of Chronic Myeloid Leukemia

Science.gov (United States)

Macedo, Mafalda S. F.; Figueiredo, Ana R. M.; Ferreira, Natália N.; Barbosa, Irene M. A.; Furtado, Maria João F. B. S.; Correia, Nuno F. C. B. A.; Gomes, Miguel P.; Lume, Miguel R. B.; Menéres, Maria João S.; Santos, Marinho M. N.; Meireles S., M. Angelina C.

2013-01-01

The authors report a rare case of a 48-year-old male with chronic myeloid leukemia (CML) who initially presented with a bilateral proliferative retinopathy. The patient complained of recent visual loss and floaters in both eyes (BE). Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 20/50 in the right eye and 20/200 in the left eye (LE). Fundoscopy showed the presence of bilateral peripheral capillary dropout with multiple retinal sea fan neovascularisations, which were confirmed on fluorescein angiography. Full blood count revealed hyperleukocytosis, thrombocytosis, anemia, and hyperuricemia. Bone marrow aspiration and biopsy showed the reciprocal chromosomal translocation t (9;22), diagnostic of CML. The patient was started on hydroxyurea, allopurinol and imatinib mesylate. He received bilateral panretinal laser photocoagulation and a vitrectomy was performed in the LE. The patient has been in complete hematologic, cytogenetic, and major molecular remission while on imatinib and his BCVA is 20/25 in BE. PMID:24339689

Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

DEFF Research Database (Denmark)

Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon

2011-01-01

and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....

The Partisan Trajectory of the American Pro-Life Movement: How a Liberal Catholic Campaign Became a Conservative Evangelical Cause

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Daniel K. Williams

2015-04-01

Full Text Available This article employs a historical analysis of the religious composition of the pro-life movement to explain why the partisan identity of the movement shifted from the left to the right between the late 1960s and the 1980s. Many of the Catholics who formed the first anti-abortion organizations in the late 1960s were liberal Democrats who viewed their campaign to save the unborn as a rights-based movement that was fully in keeping with the principles of New Deal and Great Society liberalism, but when evangelical Protestants joined the movement in the late 1970s, they reframed the pro-life cause as a politically conservative campaign linked not to the ideology of human rights but to the politics of moral order and “family values.” This article explains why the Catholic effort to build a pro-life coalition of liberal Democrats failed after Roe v. Wade, why evangelicals became interested in the antiabortion movement, and why the evangelicals succeeded in their effort to rebrand the pro-life campaign as a conservative cause.

Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

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Shao Qing

2014-11-01

Full Text Available Background: Diabetic retinopathy (DR is a retinopathy resulting from diabetes mellitus (DM which was classified into non-proliferative DR (NPDR and proliferative DR (PDR. Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

Wound healing morbidity in STS patients treated with preoperative radiotherapy in relation to in vitro skin fibroblast radiosensitivity, proliferative capacity and TGF-β activity

International Nuclear Information System (INIS)

Akudugu, John M.; Bell, Robert S.; Catton, Charles; Davis, Aileen M.; Griffin, Anthony M.; O'Sullivan, Brian; Waldron, John N.; Ferguson, Peter C.; Wunder, Jay S.; Hill, Richard P.

2006-01-01

Background and purpose: In a recent study, we demonstrated that the ability of dermal fibroblasts, obtained from soft tissue sarcoma (STS) patients, to undergo initial division in vitro following radiation exposure correlated with the development of wound healing morbidity in the patients following their treatment with preoperative radiotherapy. Transforming growth factor beta (TGF-β) is thought to play an important role in fibroblast proliferation and radiosensitivity both of which may impact on wound healing. Thus, in this study we examined the interrelationship between TGF-β activity, radiosensitivity and proliferation of cultured fibroblasts and the wound healing response of STS patients after preoperative radiotherapy to provide a validation cohort for our previous study and to investigate mechanisms. Patients and methods: Skin fibroblasts were established from skin biopsies of 46 STS patients. The treatment group consisted of 28 patients who received preoperative radiotherapy. Eighteen patients constituted a control group who were either irradiated postoperatively or did not receive radiation treatment. Fibroblast cultures were subjected to the colony forming and cytokinesis-blocked binucleation assays (low dose rate: ∼0.02 Gy/min) and TGF-β assays (high dose-rate: ∼1.06 Gy/min) following γ-irradiation. Fibroblast radiosensitivity and initial proliferative ability were represented by the surviving fraction at 2.4 Gy (SF 2.4 ) and binucleation index (BNI), respectively. Active and total TGF-β levels in fibroblast cultures were determined using a biological assay. Wound healing complication (WHC), defined as the requirement for further surgery or prolonged deep wound packing, was the clinical endpoint examined. Results: Of the 28 patients treated with preoperative radiotherapy, 8 (29%) had wound healing difficulties. Fibroblasts from patients who developed WHC showed a trend to retain a significantly higher initial proliferative ability after

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

International Nuclear Information System (INIS)

Weis, Karen E.; Raetzman, Lori T.

2016-01-01

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic based on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

Energy Technology Data Exchange (ETDEWEB)

Weis, Karen E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

2016-12-15

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic based on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.

Influence of constant, alternating and cyclotron low-intensity electromagnetic fields on fibroblast proliferative activity in vitro.

Science.gov (United States)

Afinogenov, Gennadi; Afinogenova, Anna; Kalinin, Andrey

2009-12-16

Available data allow assuming the presence of stimulation of reparative processes under influence of low-intensity electromagnetic field, commensurable with a magnetic field of the Earth. Research of effects of low-intensity electromagnetic fields on fibroblast proliferative activity in human lungs in cell culture was performed.The influence of a constant electromagnetic field, an alternating electromagnetic field by frequency of 50 Hz and cyclotron electromagnetic field with identical intensity for all kinds of fields - 80 mcTl - on value of cellular mass and a correlation of live and dead cells in culture is investigated in three series of experiments. We used the universal electromagnetic radiator generating all three kinds of fields and supplied by a magnetometer which allows measuring the intensity of accurate within 0.1 mcTl including taking into account the Earth's magnetic field intensity.The peak value for stimulation cellular proliferation in the present experiences was two-hour influence by any of the specified kinds of electromagnetic fields. The irradiation by cyclotron electromagnetic field conducts positive dynamics in growth of live cells (up to 206+/-22%) and decreases the number of dead cells (down to 31+/-6%). Application of cyclotron magnetic fields promoted creation of optimum conditions for proliferation. As a result of researches we observed the reliable 30% increase of nitro-tetrazolium index (in nitro-tetrazolium blue test) after irradiation by cyclotron electromagnetic field in experience that testifies to strengthening of the cell breathing of living cells.In our opinion, it is necessary to pay attention not only to a pure gain of cells, but also to reduction of number dead cells that can be criterion of creation of optimum conditions for their specific development and valuable functioning.

Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program.

Science.gov (United States)

Castells, Xavier; Domingo, Laia; Corominas, Josep María; Torá-Rocamora, Isabel; Quintana, María Jesús; Baré, Marisa; Vidal, Carmen; Natal, Carmen; Sánchez, Mar; Saladié, Francina; Ferrer, Joana; Vernet, Mar; Servitja, Sonia; Rodríguez-Arana, Ana; Roman, Marta; Espinàs, Josep Alfons; Sala, María

2015-01-01

Benign breast disease increases the risk of breast cancer. This association has scarcely been evaluated in the context of breast cancer screening programs although it is a prevalent finding in mammography screening. We assessed the association of distinct categories of benign breast disease and subsequent risk of breast cancer, as well as the influence of a family history of breast cancer. A retrospective cohort study was conducted in 545,171 women aged 50-69 years biennially screened for breast cancer in Spain. The median of follow-up was 6.1 years. The age-adjusted rate ratio (RR) of breast cancer for women with benign breast disease, histologically classified into nonproliferative and proliferative disease with and without atypia, compared with women without benign breast disease was estimated by Poisson regression analysis. A stratified analysis by family history of breast cancer was performed in a subsample. All tests were two-sided. The age-adjusted RR of breast cancer after diagnosis of benign breast disease was 2.51 (95 % CI: 2.14-2.93) compared with women without benign breast disease. The risk was higher in women with proliferative disease with atypia (RR = 4.56, 95 % CI: 2.06-10.07) followed by those with proliferative disease without atypia (RR = 3.58; 95 % CI = 2.61-4.91). Women with nonproliferative disease and without a family history of breast cancer remained also at increased risk of cancer (OR = 2.23, 95 % CI: 1.86-2.68). An increased risk of breast cancer was observed among screening participants with proliferative or nonproliferative benign breast disease, regardless of a family history of breast cancer. This information may be useful to explore risk-based screening strategies.

Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

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Grégory Lacraz

Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

Proliferative verrucous leukoplakia: an aggressive form of oral leukoplakia.

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Shopper, Thomas P; Brannon, Robert B; Stalker, William H

2004-01-01

Proliferative verrucous leukoplakia (PVL) is an aggressive form of oral leukoplakia that is persistent, often multifocal, and refractory to treatment with a high risk of recurrence and malignant transformation. This article describes the clinical aspects and histologic features of a case that demonstrated the typical behavior pattern in a long-standing, persistent lesion of PVL of the mandibular gingiva and that ultimately developed into squamous cell carcinoma. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa.

T-dependence of human B lymphocyte proliferative response to mitogens.

Science.gov (United States)

Brochier, J; Samarut, C; Gueho, J P; Revillard, J P

1976-01-01

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.

Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside

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Stavros N. Moysidis

2012-01-01

Full Text Available Proliferative vitreoretinopathy (PVR is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD. Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα, which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU and low-molecular-weight heparin (LMWH, daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside.

Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

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Fero Matthew

2011-10-01

Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

Anatomical and functional outcomes of retinectomies in retinal detachments complicated by proliferative vitreoretinopathy

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Mohammad Idrees Adhi

2017-10-01

Full Text Available Purpose: To study anatomical and functional outcomes of retinectomies in rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy. Methods: This is a retrospective interventional consecutive case series of eyes with rhegmatogenous retinal detachments complicated by advanced proliferative vitreoretinopathy and managed by relaxing retinectomy over a period of seventeen years. Three-port pars plana vitrectomy included core vitrectomy and removal of all epi-retinal membranes. On failure to flatten, retina was cut and excised. Basal vitrectomy and removal of anterior flap of retina then followed. Silicone oil was used as temponade in majority of cases. The dependent variables were anatomical and functional outcomes. The statistical analysis was performed on SPSS 21. Results: Series included 370 eyes of 337 patients. Mean follow up was 39 months. Scleral explant was used in 90(24.39% cases. Two hundred and nine (56.49% eyes were operated with trans conjunctival sutureless vitrectomy technique. Procedure was bilateral in 33 patients (09.79%. Retina attached in 311(84.05% eyes after initial surgery. Final re-attachment after one or more surgeries was achieved in 344(92.97% eyes. Two hundred and eleven (57.02% cases achieved visual acuity of 6/60 or better. Conclusion: Relaxing retinectomies have good and encouraging anatomical and functional outcomes. This surgery can be effectively carried out with trans conjunctival sutureless vitrectomy technique. Keywords: Retinotomy and retinectomy, Proliferative vitreoretinopathy, Trans conjunctival sutureless vitrectomy, Silicone oil

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

Science.gov (United States)

Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

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Angeliki Tiptiri-Kourpeti

Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Science.gov (United States)

Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

International Nuclear Information System (INIS)

Navarrete, Maria Alicia H; Maier, Carolina M; Falzoni, Roberto; Quadros, Luiz Gerk de Azevedo; Lima, Geraldo R; Baracat, Edmund C; Nazário, Afonso CP

2005-01-01

During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. In mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period. Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy. The proliferation index (PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both phases of the menstrual cycle were not statistically significant (P = 0.21). However, the cell renewal index (CRI = PI/AI) was significantly higher in the luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day. We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors

History of Psychology Publish and Perish: Psychology's Most Prolific Authors Are Not Always the Ones We Remember.

Science.gov (United States)

Green, Christopher D

2017-01-01

What is the relationship between being highly prolific in the realm of publication and being remembered as a great psychologist of the past? In this study, the PsycINFO database was used to identify the historical figures who wrote the most journal articles during the half-century from 1890 to 1939. Although a number of the 10 most prolific authors are widely remembered for their influence on the discipline today-E. L. Thorndike, Karl Pearson, E. B. Titchener, Henri Pi6ron-the majority are mostly forgotten. The data were also separated into the 5 distinct decades. Once again, a mixture of eminent and obscure individuals made appearances. Most striking, perhaps, was the great increase in articles published over the course of the half-century-approximately doubling each decade-and the enormous turnover in who was most prolific, decade over decade. In total, 100 distinct individuals appeared across just 5 lists of about 25 names each.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

Science.gov (United States)

Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Medulloblastoma: evaluation of proliferative index by monoclonal antibody Mib-1, its prognostic correlation and therapeutic implications

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Ferrari Antonio Fernandes

2003-01-01

Full Text Available In the past few years, the monoclonal antibody MIB-1 has been used by researchers in order to retrospectively study paraffin imbibed tumor fragments. The medulloblastoma is the most common malignant central nervous system tumor in childhood. The objectives were: determination of the mean Mib-1 LI value from these patients, as well as the prognostic value of the method.This retrospective study represents an analysis of the cellular proliferation index of posterior fossa medulloblastomas collected from 22 patients at A.C. Camargo Hospital, from January 1990 to December 1999. The histopathological diagnosis was confirmed by H&E and proliferative index (LI was achived with Mib-1 which detects proliferating cells during G1, G2, S and M phases.The results demostrated that the mean Mib-1 was 30,1%, and ranged from 5,2% to 62,0%.In conclusion, this method has prognostic value, has to be used as routine for patients harboring medulloblastomas and the ones who have PI greater than the mean value found in this study, should be treated aggressively.

Detection of Lawsonia intracellularis in the tonsils of pigs with proliferative enteropathy

DEFF Research Database (Denmark)

Jensen, Tim Kåre; Møller, Kristian; Lindecrona, R. H.

2000-01-01

to necropsy but not in four pigs with moderate PE lesions. However, L. intracellularis was detected in the tonsils of 4/9 pigs with PE complicated with necroses and in 4/4 pigs with proliferative haemorrhagic enteropathy in which L. intracellularis antigen also was demonstrated in tonsillar macrophages...

Meningiomas: Objective assessment of proliferative indices by immunohistochemistry and automated counting method.

Science.gov (United States)

Chavali, Pooja; Uppin, Megha S; Uppin, Shantveer G; Challa, Sundaram

2017-01-01

The most reliable histological correlate of recurrence risk in meningiomas is increased mitotic activity. Proliferative index with Ki-67 immunostaining is a helpful adjunct to manual counting. However, both show considerable inter-observer variability. A new immunohistochemical method for counting mitotic figures, using antibody against the phosphohistone H3 (PHH3) protein was introduced. Similarly, a computer based automated counting for Ki-67 labelling index (LI) is available. To study the use of these new techniques in the objective assessment of proliferation indices in meningiomas. This was a retrospective study of intracranial meningiomas diagnosed during the year 2013.The hematoxylin and eosin (H and E) sections and immunohistochemistry (IHC) with Ki-67 were reviewed by two pathologists. Photomicrographs of the representative areas were subjected to Ki-67 analysis by Immunoratio (IR) software. Mean Ki-67 LI, both manual and by IR were calculated. IHC with PHH3 was performed. PHH3 positive nuclei were counted and mean values calculated. Data analysis was done using SPSS software. A total of 64 intracranial meningiomas were diagnosed. Evaluation on H and E, PHH3, Ki-67 LI (both manual and IR) were done in 32 cases (22 grade I and 10 grade II meningiomas). Statistically significant correlation was seen between the mitotic count in each grade and PHH3 values and also between the grade of the tumor and values of Ki-67 and PHH3. Both the techniques used in the study had advantage over, as well as, correlated well with the existing techniques and hence, can be applied to routine use.

[Prader-Willi syndrome case with proliferative diabetic retinopathy in both eyes treated by early vitrectomy under local anesthesia].

Science.gov (United States)

Hori, Hideyuki; Sato, Yukihiro; Nakashima, Motohiro; Nakajima, Motohiro

2012-02-01

Although patients with Prader-Willi syndrome have a high rate of diabetes, to date, there have been only 4 reported cases (6 eyes) undergoing vitrectomy for proliferative diabetic retinopathy. Herein, we report a case of Prader-Willi syndrome with proliferative diabetic retinopathy that was treated by early vitrectomy OU under local anesthesia. A 30-year-old man was diagnosed as having Prader-Willi syndrome at the age of 2 years and diabetes at age 17. He was referred to our hospital as diabetic retinopathy had been detected in his first ophthalmological examination at age 29. Visual acuity was 0.6 bilaterally. Proliferative retinopathy, with cataract and macular edema, was identified in both eyes. Panretinal photocoagulation was performed on both eyes. However, proliferative membranes developed bilaterally, and vitreous hemorrhage occurred OS. Visual acuity decreased to 0.3 OU. The patient was hospitalized at our internal medicine department for blood glucose control. Subsequently, with an anesthesiologist on standby, a hypnotic sedative was injected intramuscularly, achieving retro-bulbar anesthesia. Combined cataract and vitreous surgery was performed on the left eye. One week later, a similar operation was performed on the right eye. The patient was discharged four days later. In the two years since these operation, visual acuity has been maintained at 0.8 OU. Patients with Prader-Willi syndrome should be examined for early detection and treatment of diabetic retinopathy.

Chronic proliferative synovitis of the equine metacarpophalangeal joint

International Nuclear Information System (INIS)

Kannegieter, N.J.

1990-01-01

Chronic proliferative synovitis of 27 metacarpophalangeal joints in 16 horses is described. The diagnosis was based on a history of lameness and, or, poor performance, pain on flexion of the metacarpophalangeal joint, the response to intra-articular anaesthesia, and plain and contrast radiography. Radiographic findings included concavity of the distal dorsal metacarpus proximal to the sagittal ridge, and an increase in size of the synovial tissue adjacent to the proximal, dorsal attachment of the joint capsule. Mineralisation of the synovial tissue was present in some joints, and chip fractures from the dorsal aspect of the proximal phalanx were also occasionally seen. Treatment by arthroscopic resection of the tissue gave excellent results

Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.

Science.gov (United States)

Guedes, R M C; França, S A; Machado, G S; Blumer, M A; da Costa Cruz, E C

2009-09-19

The effect of an oral treatment with the tartrate salt of tylvalosin on the development of proliferative enteropathy in 60 experimentally challenged pigs was studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and 30 were fed the unmedicated diet. The treated animals started to receive the medicated feed the day before they were inoculated, and continued to receive it for 14 days. The pigs' bodyweight, feed consumption and clinical signs were evaluated, and they were examined postmortem 20 days after inoculation, and samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia intracellularis. Clinical signs of the disease were more evident in the untreated group than in the treated group. The average daily weight gain, average daily feed consumption and feed conversion efficiency were better in the treated group. The combined length of intestine with lesions was 2847 cm in the untreated group and 183 cm in the treated group. The tylvalosin treatment significantly reduced the level of L intracellularis infection; almost half of the treated pigs were IHC-negative compared with 3.3 per cent of the untreated pigs.

Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

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Hikichi T

2011-05-01

Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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Nesrina eImami

2013-03-01

Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

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Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

2017-06-01

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( Plupus erythematosus patients in comparison to controls ( P lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Resveratrol prevents oxidative stress-induced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes.

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Yasuo Ido

Full Text Available The aging process is perceived as resulting from a combination of intrinsic factors such as changes in intracellular signaling and extrinsic factors, most notably environmental stressors. In skin, the relationship between intrinsic changes and keratinocyte function is not clearly understood. Previously, we found that increasing the activity of AMP-activated protein kinase (AMPK suppressed senescence in hydrogen peroxide (H2O2-treated human primary keratinocytes, a model of oxidative stress-induced cellular aging. Using this model in the present study, we observed that resveratrol, an agent that increases the activities of both AMPK and sirtuins, ameliorated two age-associated phenotypes: cellular senescence and proliferative dysfunction. In addition, we found that treatment of keratinocytes with Ex527, a specific inhibitor of sirtuin 1 (SIRT1, attenuated the ability of resveratrol to suppress senescence. In keeping with the latter observation, we noted that compared to non-senescent keratinocytes, senescent cells lacked SIRT1. In addition to these effects on H2O2-induced senescence, resveratrol also prevented the H2O2-induced decrease in proliferation (as indicated by 3H-thymidine incorporation in the presence of insulin. This effect was abrogated by inhibition of AMPK but not SIRT1. Compared to endothelium, we found that human keratinocytes expressed relatively high levels of Forkhead box O3 (FOXO3, a downstream target of both AMPK and SIRT1. Treatment of keratinocytes with resveratrol transactivated FOXO3 and increased the expression of its target genes including catalase. Resveratrol's effects on both senescence and proliferation disappeared when FOXO3 was knocked down. Finally, we performed an exploratory study which showed that skin from humans over 50 years old had lower AMPK activity than skin from individuals under age 20. Collectively, these findings suggest that the effects of resveratrol on keratinocyte senescence and proliferation

Oral proliferative verrucous leukoplakia: A case report with an update

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Rakhi Issrani

2013-01-01

Full Text Available White lesions both physiologic as well as pathologic are relatively frequent in the oral cavity, the most common pathology being oral leukoplakia (OL. There are many variants of OL, one of which is oral proliferative verrucous leukoplakia (OPVL. OPVL is a rare clinico-pathological entity, which is slow growing, long-term progressive lesion, but remains an enigmatic and difficult to define. The etiology of OPVL remains still unclear. Tobacco use does not seem to have a significant influence on the appearance of OPVL. These lesions may occur both in smokers and non-smokers. It is observed more frequently in women and elderly patients over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. Various published case series have presented OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. This article describes the clinical aspects and histologic features of an OPVL case that demonstrated the typical behavior pattern in a long-standing, persistent lesion and discusses this relatively rare entity in light of current information.

Preliminary observations on the correlation of proliferative phenomena with in vivo /sup 31/P NMR spectroscopy after tumor chemotherapy

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Schiffer, L.M.; Braunschweiger, P.G.; Glickson, J.D.; Evanochko, W.T.; Ng, T.C.

1985-01-01

In order to translate the concepts that have been developed in animal systems to human treatment programs, there is an urgent need for noninvasive techniques to study tumor cell biology. The characteristics of the ideal technique for the noninvasive monitoring of cell proliferation are truly imposing. The method should not require repeated biopsies; it should be amenable to repeated studies at frequent intervals without patient discomfort; it should monitor the proliferative response to the treatment modality; and it should not, in itself, perturb the tumor. Ideally, one would also like to be able to evaluate normal cell proliferation as well. It appears now that a new technique, /sup 31/P nuclear magnetic resonance (/sup 31/PNMR), may fulfill these rather rigid requirements. However, many studies in animal systems are necessary before it can be applied to the study of human tumors. The theory and mechanics of /sup 31/P NMR have been well described. Recently, its use as a noninvasive technique to study in vivo metabolic processes has become important. The authors presented a series of reports on the use of /sup 31/P NMR for the evaluation of tumor metabolism in animal systems under a variety of conditions. Studies of subcutaneously transplanted mouse tumors and human xenografts detected significant changes in nucleotide triphosphate (NTP), phosphocreatine, and inorganic phosphorus (Pi) as a result of tumor growth and perturbation with chemotherapeutic drugs, radiation, and hyperthermia. Their collabortive studies were designed to evaluate the changing effects of a noncurative single dose of cyclophosphamide on the /sup 31/P NMR resonances from the RIF-1 tumor, and to compare them with the proliferative changes that occur with time after drug administration. They were carried out in the hope of finding a noninvasive correlate with tumor cell proliferation

Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.

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Lazova, Rossitza; Yang, Zhe; El Habr, Constantin; Lim, Young; Choate, Keith Adam; Seeley, Erin H; Caprioli, Richard M; Yangqun, Li

2017-09-01

Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.L.) and mass spectrometry imaging analysis rendered a diagnosis of congenital melanocytic nevus with proliferative nodules. In this case, mass spectrometry imaging, a novel method capable of distinguishing benign from malignant melanocytic lesions on a proteomic level, was instrumental in making the diagnosis of a benign nevus. We emphasize the importance of this method as an ancillary tool in the diagnosis of difficult melanocytic lesions.

Proliferative changes in nonpalpable breast lesions detected by mammography; Alteraciones profiferativas de la mama en lesiones no palpables detectadas por mamografia

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Vega, A.; Delgado, A.; Ortega, E.; Garijo, F. [Hospital Universitario Marques de Valdecilla. Santander (Spain); Mosquera, J.; Sogo, C.; Alvarez, A. [Complejo Hospitalario Juan Canalejo. La Coruna (Spain)

2000-07-01

To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs.

Proliferative vitreo-retinal disorders: experimental models in vivo and in vitro.

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Martini, B

1992-01-01

The aim of the present thesis was to develop, refine, and assess experimental models for the study of proliferative vitreo-retinal disorders. An intravitreal injection of a colloidal solution of microparticles was used in the primate eye to produce pathologic changes including intraocular cell invasion, cell proliferation, neovascularization, collagen synthesis, and tractional retinal detachment. In a separate primate model for laser-induced subretinal neovascularization, the origin and the occurrence of macrophages was evaluated. Examinations were performed using ophthalmoscopy, slit-lamp microscopy, light microscopy, and transmission electron microscopy. Cell cultures were employed to study the effects of vitreous humor and macrophages on the proliferation of cultured retinal pigment epithelial (RPE) cells and cultured fibroblasts using a Coulter counter. Morphologic changes were documented by phase micrography. A quantitative estimation of the extracellular matrix deposition of fibrous proteins by macrophage-modulated RPE cells as well as by vitreous-modulated RPE cells was done using enzymatic digestion and radioactive labeling techniques. A qualitative analysis of the types of collagen that was deposited in the extracellular matrices by vitreous modulated cultures was also made using indirect immunofluorescence. Using a newly developed RPE cell specific monoclonal antibody, the avidin-biotin-peroxidase labeling technique was finally employed to test the phenotypic epitope expression of macrophage-modulated and non-modulated RPE cells. A new experimental in vivo model for pathologic changes that characterize proliferative vitreo-retinal disorders was developed in the primate eye. In the model for laser-induced subretinal neovascularization, macrophages were shown to be principally recruited from the systemic circulation. Using cell cultures, it was found that both macrophage-conditioned medium and vitreous humor, separately or combined, exert mitogenic effects

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

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S. W. Olson

2017-01-01

Full Text Available Background. The subclinical pathophysiology of proliferative lupus nephritis (PLN has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA is associated with PLN, but prediagnostic levels have not been reported. Methods. We performed a retrospective case-control Department of Defense Serum Repository (DoDSR study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab. Results. A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p<0.001; 57% versus 5%, p<0.001, resp.. In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p=0.007 and 1–4 years (87% versus 38%, p=0.009 prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p=0.003. Conclusions. Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

Vitrectomy for proliferative diabetic retinopathy

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Chao Peng

2013-10-01

Full Text Available AIM:To observe the clinical effect of vitrectomy for proliferative diabetic retinopathy(PDR.METHODS: The clinical data of 55 cases(65 eyes, underwent vitrectomy, membrane peeling, endolaser photocoagulation and silicone oil or C3F8 injection, were retrospectively studied. During 6 months to 1 year follow-up period, visual acuity, intraocular pressure, retinal conditions and complications were observed.RESULTS: All 65 eyes received vitrectomy, of which silicone oil was tamponaded in 32 eyes, C3F8 was injected in 8 eyes, BBS was filled in 25 eyes. Visual improvement achieved in 42 eyes. Two eyes were manually vision, form count fingers to 0.05 in 18 eyes, >0.05-0.1 in 28 eyes, >0.1-0.3 in 12 eyes and >0.3 in 5 eyes. Retinal hole was occurred in 7 eyes, limitations fibrosis membrane remained in 8 eyes, retinal detachment appeared in 5 eyes, IOP increased in 18 eyes, vitreous hemorrhage relapsed in 12 eyes, 36 eyes received supplemental photocoagulation treatment 1-3 times after operation.CONCLUSION:Vitrectomy combined endophotocoagulation is an effective treatment for PDR. Silicone oil tamponade can limit the hemorrhage.

Structural Changes of the Macula on Optical Coherence Tomography after Vitrectomy for Proliferative Diabetic Retinopathy.

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Im, Jong Chan; Kim, Jong Ho; Park, Dong Ho; Shin, Jae Pil

2017-01-01

This study aimed to evaluate the relationship between macular structural changes and visual prognosis after pars plana vitrectomy (PPV) for proliferative diabetic retinopathy. The study included 60 eyes that had undergone PPV. Macular optical coherence tomography (OCT) findings were classified into 5 groups preoperatively and 10 groups postoperatively. Best-corrected visual acuity (BCVA) were analyzed according to pre- and postoperative OCT. From the preoperative OCT, normal fovea with/without traction, normal fovea with preretinal hemorrhage, and tractional retinal detachment involving fovea showed an increase in BCVA after PPV (all p 20/50). Subfoveal fibrosis, macular hole, loss of foveal depression, and serous foveal detachment showed poor visual prognosis (BCVA <20/100). Macular structural changes were various after PPV, and visual prognosis correlated with these changes. © 2017 S. Karger AG, Basel.

Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

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Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

2017-09-01

Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

Evaluation of chromosomal abnormalities by clg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

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Linardi, C.C.G.; Martinez, G.; Velloso, E.D.R.P.; Leal, A.M.; Kumeda, C.A.; Buccheri, V. [Disciplina de Hematologia e Hemoterapia, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Azevedo, R.S. [Departamento de Patologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Peliçario, L.M.; Dorlhiac-Llacer, P. [Disciplina de Hematologia e Hemoterapia, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2012-08-24

Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

Proliferative capacity of stem/progenitor-like cells in the kidney may associate with the outcome of patients with acute tubular necrosis.

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Ye, Youxin; Wang, Bingyin; Jiang, Xinxin; Hu, Weiming; Feng, Jian; Li, Hua; Jin, Mei; Ying, Yingjuan; Wang, Wenjuan; Mao, Xiaoou; Jin, Kunlin

2011-08-01

Animal studies indicate that adult renal stem/progenitor cells can undergo rapid proliferation in response to renal injury, but whether the same is true in humans is largely unknown. To examine the profile of renal stem/progenitor cells responsible for acute tubular necrosis in human kidney, double and triple immunostaining was performed using proliferative marker and stem/progenitor protein markers on sections from 10 kidneys with acute tubular necrosis and 4 normal adult kidneys. The immunopositive cells were recorded using 2-photon confocal laser scanning microscopy. We found that dividing cells were present in the tubules of the cortex and medulla, as well as the glomerulus in normal human kidney. Proliferative cells in the parietal layer of Bowman capsule expressed CD133, and dividing cells in the tubules expressed immature cell protein markers paired box gene 2, vimentin, and nestin. After acute tubular necrosis, Ki67-positive cells in the cortex tubules significantly increased compared with normal adult kidney. These Ki67-positive cells expressed CD133 and paired box gene 2, but not the cell death marker, activated caspase-3. In addition, the number of dividing cells increased significantly in patients with acute tubular necrosis who subsequently recovered, compared with patients with acute tubular necrosis who consequently developed protracted acute tubular necrosis or died. Our data suggest that renal stem/progenitor cells may reside not only in the parietal layer of Bowman capsule but also in the cortex and medulla in normal human kidney, and the proliferative capacity of renal stem/progenitor cells after acute tubular necrosis may be an important determinant of a patient's outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

Health assessment of environmental pollutants: proliferative and degenerative diseases

International Nuclear Information System (INIS)

Stuart, B.O.

1988-01-01

In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed

The outcomes of pars plana vitrectomy without endotamponade for tractional retinal detachment secondary to proliferative diabetic retinopathy

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Rao Muhammad Rashad Qamar

2013-10-01

Full Text Available AIM: To evaluate the outcomes of pars plana vitrectomy (PPV without the use of an ocular tamponade in patients having tractional retinal detachment (TRD secondary to proliferative diabetic retinopathy (PDR.METHODS: It was an interventional study conducted at the Department of Ophthalmology, B.V. Hospital, Bahawalpur, Pakistan, from July 2011 to July 2012. A total of 75 patients (84 eyes having TRD secondary to PDR were treated by PPV without using an ocular tamponade. All patients included in the study had a tractional retinal detachment secondary to proliferative diabetic retinopathy but didn’t have or develop retinal breaks before or during the study period. The surgical procedure included a PPV combined with the removal of the tractional retinal membranes and the application of endolaser photocoagulation to the retina. The mean follow-up period was 12 months.RESULTS:Successful retinal reattachement was observed in 78 of the operated eyes (92.8%. In these patients, the retina remained attached till the end of the one year follow-up period. Improvement in best corrected visual acuity (BCVA was seen in 63 eyes (75%. The visual acuity remained unchanged in 9 eyes (10.7%. Mean improvement in BCVA was 2.00+1.24 at baseline to 1.24+1.22 (PCONCLUSION: In the absence of the retinal breaks, a TRD secondary to PDR can be successfully treated by pars plana vitrectomy without the use of an ocular tamponade.

Immunochemical expression of proliferative cell nuclear antigen in aging cultured astrocytes

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M. C. Vanzani

2003-08-01

Full Text Available Cell differentiation degree and mitotic activity were sequentially assessed by immunoperoxidase labeling of glial fibrillary acidic protein (GFAP and proliferative cell nuclear antigen (PCNA, respectively, in rat brain cultured astrocytes maintained up to 60 days in vitro (DIV of first subculture, or weekly passaged until their 12th subculture. Cell count was performed through a 0.01 mm2 section reticule and morphometric analysis with a stereological grid. The number of double immunoreactive cells peaked by 2 DIV to achieve its lowest value at 60 DIV. At 24 hs of cell seeding of successive passages, such values peaked by the 6th subculture to gradually decrease thereafter. Increasing cell hypertrophy was found during the long-term first subculture but not after passaging. At the end of the observation period, doubly immunolabeled astrocytes were still recorded, thus evidencing retention of proliferative potential despite aging.El grado de diferenciación celular y la actividad mitótica fueron secuencialmente determinados mediante marcación por inmunoperoxidasa de la proteína gliofibrilar ácida (GFAP y del antígeno nuclear de proliferación celular (PCNA, respectivamente, en cultivos astrocitarios obtenidos de encéfalo de rata y mantenidos hasta 60 días in vitro (DIV de su primer subcultivo, o mediante pasajes semanales hasta el 12do subcultivo. El conteo celular se realizó mediante una retícula de 0.01-mm2 de sección y el análisis morfométrico con una grilla estereológica. El número de células doblemente inmunorreactivas alcanzó valores máximos a los 2 DIV para descender a los menores a los 60 DIV. A las 24 hs de sembrado celular de los sucesivos pasajes, esos valores ascendieron hacia el 6to subcultivo para luego declinar. En cuanto a la hipertrofia celular, se observó en todo el curso del primer subcultivo, pero no durante los posteriores pasajes. Al final del período de observación, todavía se continuaban detectando

Anti-proliferative effect of 20-hydroxyecdysone in a lepidopteran cell line.

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Auzoux-Bordenave, Stéphanie; Hatt, Philippe-Jacques; Porcheron, Patrick

2002-02-01

Ecdysteroids are steroid hormones involved in the epidermal growth of arthropods, controlling cell proliferation and further differentiation of target cells. The epidermal cell line IAL-PID2, established from imaginal discs of the Indian meal moth Plodia interpunctella kept its sensitivity to ecdysteroids in vitro, cells being able to respond to them by cytological and biochemical changes. When added to the culture medium, 20-hydroxyecdysone (20E) stopped cell proliferation and induced formation of epithelial-like aggregates. In order to better understand the cellular sequence of ecdysteroids signalling in epidermal cells we used the IAL-PID2 cell line for in vitro investigations of cytological events induced by the moulting hormone. After a 40 h serum deprivation, formazan assay (XTT) was routinely used to evaluate anti-proliferative effects of 20E during cell cycle. We established a more precise timing of the period of cell sensitivity to the hormone during the cell cycle, by the use of the mitotic index and the BrdU incorporation test. These in vitro assays were performed in parallel with the description of some hormone dependant cytological events, using immunofluorescent labelling with anti-beta tubulin/FITC antibodies and DNA staining.

Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors

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Shuang Cao

2016-07-01

Full Text Available A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin. Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.

Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease

Science.gov (United States)

Shahmanesh, M.; Brunst, M.; Sukthankar, A.; Pearce, J. H.; Gaston, J. S.

1999-01-01

OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could

Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

International Nuclear Information System (INIS)

Lee, Do Kyung; Jang, Seok; Kim, Mi Jin; Kim, Jung Hyun; Chung, Myung Jun; Kim, Kyung Jae; Ha, Nam Joo

2008-01-01

Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line. The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier

Intravitreal methotrexate infusion for proliferative vitreoretinopathy

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Sadaka A

2016-09-01

Full Text Available Ama Sadaka,1 Robert A Sisk,1–3 James M Osher,1,3 Okan Toygar,4 Melinda K Duncan,5 Christopher D Riemann1,3 1Department of Ophthalmology, University of Cincinnati College of Medicine, 2Department of Opthalmology, Cincinnati Children’s Hospital Medical Center, 3Cincinnati Eye Institute, Cincinnati, OH, USA; 4Department of Ophthalmology, Bahcesehir University Medical Faculty, Istanbul, Turkey; 5Department of Biological Sciences, University of Delaware, Newark, DE, USA Purpose: The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI during pars plana vitrectomy (PPV for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR.Methods: Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review.Results: Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22 or a history of severe inflammation associated with high PVR risk (n=7 received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66% and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%. At the last follow-up examination, the retinas of 26 of 29 eyes (90% remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10% developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months.Conclusion: Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. Keywords: tractional retinal detachment, recurrent retinal detachment, pars

Anti-proliferative activity of recombinant melittin expressed in ...

African Journals Online (AJOL)

kesiena

2012-02-09

Feb 9, 2012 ... 44 amino acid residues mediated by dipeptidylpeptidase. IV (Vlasak et al., 1983). It has been reported that the melittin exhibits antimicrobial activity and pro- ... Construction of recombinant expression vector. A pair of complementary oligonucleotides named Mel-1 (5′-GAT. CCG GAA TTG GAG CAG TTC ...

Easy labeling of proliferative phase and sporogonic phase of microsporidia Nosema bombycis in host cells.

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Jie Chen

Full Text Available Microsporidia are eukaryotic, unicellular parasites that have been studied for more than 150 years. These organisms are extraordinary in their ability to invade a wide range of hosts including vertebrates and invertebrates, such as human and commercially important animals. A lack of appropriate labeling methods has limited the research of the cell cycle and protein locations in intracellular stages. In this report, an easy fluorescent labeling method has been developed to mark the proliferative and sporogonic phases of microsporidia Nosema bombycis in host cells. Based on the presence of chitin, Calcofluor White M2R was used to label the sporogonic phase, while β-tubulin antibody coupled with fluorescence secondary antibody were used to label the proliferative phase by immunofluorescence. This method is simple, efficient and can be used on both infected cells and tissue slices, providing a great potential application in microsporidia research.

Activation of double-stranded RNA-dependent protein kinase inhibits proliferation of pancreatic β-cells

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Chen, Shan-Shan [Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing (China); Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing (China); Jiang, Teng [Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing (China); Wang, Yi; Gu, Li-Ze [Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing (China); Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing (China); Wu, Hui-Wen [Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing (China); Tan, Lan [Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing (China); Guo, Jun, E-mail: Guoj@njmu.edu.cn [Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing (China); Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing (China)

2014-01-17

Highlights: •PKR can be activated by glucolipitoxicity and pro-inflammatory cytokines in β-cells. •Activated PKR inhibited β-cell proliferation by arresting cell cycle at G1 phase. •Activated PKR fully abrogated the pro-proliferative effects of IGF-I on β-cells. -- Abstract: Double-stranded RNA-dependent protein kinase (PKR) is revealed to participate in the development of insulin resistance in peripheral tissues in type 2 diabetes (T2DM). Meanwhile, PKR is also characterized as a critical regulator of cell proliferation. To date, no study has focused on the impact of PKR on the proliferation of pancreatic β-cells. Here, we adopted insulinoma cell lines and mice islet β-cells to investigate: (1) the effects of glucolipotoxicity and pro-inflammatory cytokines on PKR activation; (2) the effects of PKR on proliferation of pancreatic β-cells and its underlying mechanisms; (3) the actions of PKR on pro-proliferative effects of IGF-I and its underlying pathway. Our results provided the first evidence that PKR can be activated by glucolipitoxicity and pro-inflammatory cytokines in pancreatic β-cells, and activated PKR significantly inhibited cell proliferation by arresting cell cycle at G1 phase. Reductions in cyclin D1 and D2 as well as increases in p27 and p53 were associated with the anti-proliferative effects of PKR, and proteasome-dependent degradation took part in the reduction of cyclin D1 and D2. Besides, PKR activation abrogated the pro-proliferative effects of IGF-I by activating JNK and disrupting IRS1/PI3K/Akt signaling pathway. These findings indicate that the anti-proliferative actions of PKR on pancreatic β-cells may contribute to the pathogenesis of T2DM.

Activation of double-stranded RNA-dependent protein kinase inhibits proliferation of pancreatic β-cells

International Nuclear Information System (INIS)

Chen, Shan-Shan; Jiang, Teng; Wang, Yi; Gu, Li-Ze; Wu, Hui-Wen; Tan, Lan; Guo, Jun

2014-01-01

Highlights: •PKR can be activated by glucolipitoxicity and pro-inflammatory cytokines in β-cells. •Activated PKR inhibited β-cell proliferation by arresting cell cycle at G1 phase. •Activated PKR fully abrogated the pro-proliferative effects of IGF-I on β-cells. -- Abstract: Double-stranded RNA-dependent protein kinase (PKR) is revealed to participate in the development of insulin resistance in peripheral tissues in type 2 diabetes (T2DM). Meanwhile, PKR is also characterized as a critical regulator of cell proliferation. To date, no study has focused on the impact of PKR on the proliferation of pancreatic β-cells. Here, we adopted insulinoma cell lines and mice islet β-cells to investigate: (1) the effects of glucolipotoxicity and pro-inflammatory cytokines on PKR activation; (2) the effects of PKR on proliferation of pancreatic β-cells and its underlying mechanisms; (3) the actions of PKR on pro-proliferative effects of IGF-I and its underlying pathway. Our results provided the first evidence that PKR can be activated by glucolipitoxicity and pro-inflammatory cytokines in pancreatic β-cells, and activated PKR significantly inhibited cell proliferation by arresting cell cycle at G1 phase. Reductions in cyclin D1 and D2 as well as increases in p27 and p53 were associated with the anti-proliferative effects of PKR, and proteasome-dependent degradation took part in the reduction of cyclin D1 and D2. Besides, PKR activation abrogated the pro-proliferative effects of IGF-I by activating JNK and disrupting IRS1/PI3K/Akt signaling pathway. These findings indicate that the anti-proliferative actions of PKR on pancreatic β-cells may contribute to the pathogenesis of T2DM

CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis

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Ferrari Angelo

2012-03-01

Full Text Available Abstract Background Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. Results A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas, 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did

Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation

International Nuclear Information System (INIS)

Barkley, Laura R.; Hong, Hye Kyung; Kingsbury, Sarah R.; James, Michelle; Stoeber, Kai; Williams, Gareth H.

2007-01-01

The DNA replication (or origin) licensing pathway represents a critical step in cell proliferation control downstream of growth signalling pathways. Repression of origin licensing through down-regulation of the MCM licensing factors (Mcm2-7) is emerging as a ubiquitous route for lowering proliferative capacity as metazoan cells exit the cell division cycle into quiescent, terminally differentiated and senescent 'out-of-cycle' states. Using the HL60 monocyte/macrophage differentiation model system and a cell-free DNA replication assay, we have undertaken direct biochemical investigations of the coupling of origin licensing to the differentiation process. Our data show that down-regulation of the MCM loading factor Cdc6 acts as a molecular switch that triggers loss of proliferative capacity during early engagement of the somatic differentiation programme. Consequently, addition of recombinant Cdc6 protein to in vitro replication reactions restores DNA replication competence in nuclei prepared from differentiating cells. Differentiating HL60 cells over-expressing either wild-type Cdc6 or a CDK phosphorylation-resistant Cdc6 mutant protein (Cdc6A4) exhibit an extended period of cell proliferation compared to mock-infected cells. Notably, differentiating HL60 cells over-expressing the Cdc6A4 mutant fail to down-regulate Cdc6 protein levels, suggesting that CDK phosphorylation of Cdc6 is linked to its down-regulation during differentiation and the concomitant decrease in cell proliferation. In this experimental model, Cdc6 therefore plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme

Anti-Proliferative Activity of Meroditerpenoids Isolated from the Brown Alga Stypopodium flabelliforme against Several Cancer Cell Lines

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Patricia Valentao

2011-05-01

Full Text Available The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2, human neuroblastoma (SH-SY5Y, rat basophilic leukemia (RBL-2H3, murine macrophages (RAW.267 and Chinese hamster fibroblasts (V79. Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents.

XIAP and Ki-67: A Correlation Between Antiapoptotic and Proliferative Marker Expression in Benign and Malignant Tumours of Salivary Gland: An Immunohistochemical Study.

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Bagulkar, Bhupesh Bhayyaji; Gawande, Madhuri; Chaudhary, Minal; Gadbail, Amol Ramchandra; Patil, Swati; Bagulkar, Smita

2015-02-01

Impaired balance between cell proliferation and apoptosis is crucial to the development of malignant neoplasm. The purpose of this study was to evaluate and compare the expression of X-Linked inhibitor of apoptotic protein (XIAP) (antiapoptotic marker) and Ki-67 (proliferative marker) expression in benign and malignant salivary gland (SG) tumours. The study consisted of 40 cases of benign SG tumours and 50 cases of malignant SG tumours. The immunohistochemistry was carried out by using Ki-67 antibody (clone MIB-1) and XIAP antibody in all the groups. XIAP expression was significantly higher in malignant SG tumours than benign SG tumours (p = 0.016). Ki-67 LI was significantly higher in malignant SG tumours than benign SG tumours (p = 0.0002). Statistically significant positive correlation between Ki-67 count and XIAP expression was noted in benign and malignant SG tumours (p = 0.000). As the expression of an antiapoptotic marker (XIAP) increases, the expression of a proliferative marker (Ki-67) also increases from benign to malignant SG tumours. Thus, targeted therapy of XIAP may play a future role in the management of SG malignancy.

Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest

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Tarade, Daniel; Ma, Dennis; Pignanelli, Christopher; Mansour, Fadi; Simard, Daniel; van den Berg, Sean; Gauld, James; McNulty, James; Pandey, Siyaram

2017-01-01

The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents. PMID:28253265

Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest.

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Daniel Tarade

Full Text Available The cis-stilbene, combretastatin A4 (CA4, is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents.

Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

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Zarling, J.M.; Moran, P.A.; Brewer, L.; Ashley, R.; Corey, L.

1988-12-01

Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccinees studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccinees proliferated following stimulation with gD-2, whereas stimulation with Gd-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.

Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

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Arenas-Mena, Cesar; Coffman, James A.

2016-01-01

Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

Proliferative kidney disease (PKD) agent Tetracapsuloides bryosalmonae in brown trout populations in Estonia.

Science.gov (United States)

Dash, Megha; Vasemägi, Anti

2014-05-13

Proliferative kidney disease (PKD) caused by the myxozoan parasite Tetracapsuloides bryosalmonae is a serious parasitic disease threatening both farmed and wild salmonid populations, but very little is currently known about the distribution of the parasite in the Baltic Sea region. In this study we (1) report the development of a novel multiplex PCR method for fast and reliable screening of T. bryosalmonae; (2) use this multiplex PCR method to show that the PKD agent T. bryosalmonae is widespread in natural brown trout Salmo trutta L. populations in Estonia; (3) evaluate monthly and yearly variation of T. bryosalmonae prevalence in juvenile trout; (4) assess T. bryosalmonae prevalence in different age-classes of fish (0+ vs. 1+ and older) and report the presence of the PKD agent in the kidneys of returning sea trout spawners; and (5) suggest the freshwater bryozoan Plumatella fungosa as a putative invertebrate host of T. bryosalmonae in Estonia. Our results demonstrate a highly heterogeneous distribution of T. bryosalmonae at the micro-geographic scale, indicating that PKD could have an important negative effect on recruitment in Estonian brown trout populations.

Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

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Pei-Rong Wang

2015-03-01

Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.

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Giaginis, Constantinos; Georgiadou, Maria; Dimakopoulou, Konstantina; Tsourouflis, Gerasimos; Gatzidou, Elisavet; Kouraklis, Gregorios; Theocharis, Stamatios

2009-02-01

Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.

Transcriptional Regulation of Δ6-Desaturase by Peroxisome Proliferative-Activated Receptor δ Agonist in Human Pancreatic Cancer Cells: Role of MEK/ERK1/2 Pathway

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Maryam Darabi

2013-01-01

Full Text Available The Δ6-desaturase (Δ6D, also known as fatty acid desaturase 2, is a regulatory enzyme in de novo fatty acid synthesis, which has been linked to obesity and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPARδ agonist and MEK/ERK1/2-dependent pathway on the expression of Δ6D in human pancreatic carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPARδ agonist GW0742. Changes in mRNA and protein expression of Δ6D were then determined using real-time RT-PCR and Western blot, respectively. The expression of Δ6D (P40%, P25%, P<0.05 pretreatment. PPARδ and MEK/ERK1/2 signaling pathways affect differentially the expression of Δ6D in pancreatic cancer cells. Furthermore, there may be an inhibitory crosstalk between these two regulatory pathways on the mRNA expression of Δ6D and subsequently on Δ6D protein expression.

The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

International Nuclear Information System (INIS)

Senft, Christian; Polacin, Margareth; Priester, Maike; Seifert, Volker; Kögel, Donat; Weissenberger, Jakob

2010-01-01

New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas

[Effect of internal limiting membrane peeling on morpho-functional state of the retina in patients with proliferative diabetic retinopathy (preliminary report)].

Science.gov (United States)

Bikbov, M M; Fayzrakhmanov, R R; Kalanov, M R

2018-01-01

To compare morpho-functional parameters of retina during vitrectomy with and without internal limiting membrane (ILM) peeling in patients with proliferative diabetic retinopathy. The study included 55 patients (55 eyes) that had underwent vitreoretinal surgery in the setting of antivasoproliferative therapy for proliferative diabetic retinopathy. Patients of the 1 st group (n=27) underwent vitrectomy with silicone tamponade, 2 nd group (n=28) received similar treatment with the addition of ILM peeling. Three months after the treatment, all patients had silicone oil removed. Best Corrected Visual Acuity before treatment was 0.06±0.02 in both groups; after the treatment it improved to 0.1±0.05 (ppeeling during vitrectomy with following silicone oil tamponade eliminates the risk of ERM formation in patients with proliferative diabetic retinopathy in the follow-up period of up to 6-month and results in better morpho-functional parameters in comparison with patients who received similar treatment but without peeling.

APPROACHES TO THE CONSTRUCTION OF THE VITRECTOMY RISK MANAGEMENT SYSTEM IN PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY

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A. M. Ruban

2016-08-01

Full Text Available The article presents the some approaches to create a system support of making decision during vitrectomy in patients with diabetic proliferative retinopathy, promotes objective assessment of individual risk-management for patient and allows optimize ophthalmological care for them.

Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients

DEFF Research Database (Denmark)

Theander, T G; Svenson, M; Bygbjerg, I C

1987-01-01

initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium-derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition...

Temporal changes in retinal vascular parameters associated with successful panretinal photocoagulation in proliferative diabetic retinopathy

DEFF Research Database (Denmark)

Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin

2018-01-01

PURPOSE: We aimed to investigate changes in retinal vascular geometry over time after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). METHODS: Thirty-seven eyes with PDR were included. Wide-field fluorescein angiography (Optomap, Optos PLC., Dunfermline......, Scotland, UK) was used to diagnose PDR at baseline and to assess activity at follow-up month three and six. At each time-point, a trained grader measured retinal vessel geometry on optic disc (OD) centred images using semiautomated software (SIVA, Singapore I Vessel Assessment, National University...... of Singapore, Singapore) according to a standardized protocol. RESULTS: At baseline, the mean age and duration of diabetes were 52.8 and 22.3 years, and 65% were male. Mean HbA1c was 69.9 mmol/mol, and blood pressure was 155/84 mmHg. Of the 37 eyes with PDR, eight (22%) eyes had progression at month three...

HIV-Infected Children Have Elevated Levels of PD-1+ Memory CD4 T Cells With Low Proliferative Capacity and High Inflammatory Cytokine Effector Functions.

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Foldi, Julia; Kozhaya, Lina; McCarty, Bret; Mwamzuka, Mussa; Marshed, Fatma; Ilmet, Tiina; Kilberg, Max; Kravietz, Adam; Ahmed, Aabid; Borkowsky, William; Unutmaz, Derya; Khaitan, Alka

2017-09-15

During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation. Second, in vitro CD4 T-cell proliferative and cytokine responses to HIV-specific and -nonspecific stimuli were assessed with and without PD-1 blockade. HIV-infected children have increased frequencies of PD-1+ memory CD4 T cells that fail to normalize with antiretroviral treatment. These cells are comprised of central and effector memory subsets and correlate with HIV disease progression, measured by viral load, CD4 percentage, CD4:CD8 T-cell ratio, and immune activation. Last, PD-1+ CD4 T cells predict impaired proliferative potential yet preferentially secrete the Th1 and Th17 cytokines interferon-γ and interleukin 17A, and are unresponsive to in vitro PD-1 blockade. This study highlights differences in PD-1+ CD4 T-cell memory phenotype and response to blockade between HIV-infected children and adults, with implications for potential immune checkpoint therapies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Proliferative kinetics of the haematopoietic stem cells of the mouse after several weeks of reconvalescence of an irradiation attack

International Nuclear Information System (INIS)

Huebner, G.

1980-01-01

The 125 IDU(iodo-deoxyuridine) tracer-technique was applied for investigating proliferative kinetics. The intention was to reveal a possible persistent irradiation damage in the haematopoietic stem-cells of the mouse. The three following methodically differing arrangements were made: 1. 35 days after irradiation with 450 rad no difference is found between the measured turnover of incorporated 125 IUD in the bone marrow and not irradiated mice. However, there is a splenic cell population which unambiguously transfers its activity slowlier. A dose-response relationship exists to a limited extent. 2. By four transplantations at different instants the donors were marked first, and then the turnover of the early haematopoietic precursor cells in the bone marrow was detected. It resulted that 35 days after irradiation with 450 rad the turnover takes place slightly slowlier than in not irradiated early precursor cells. Iodised water, which is administered before the tracer technique is applied, seems to have a stimulating effect, particularly on the turnover of irradiated stem cells; the marking with a specific activity of 2000 Ci/mol seems to have a slightly toxic effect. 3. A test was developed, by which the proliferation velocity of stem cells and their descendants is measured when there is a very high proliferation stimulus. Differing amounts of bone marrow cells are transfused to lethally irradiated receivers. Within the logarithmic phase of the 125 IDU incorporation the relative cellular proliferation, originating in the stem cells being in the spleen, is determined for the interval between day 3 and day 5. It results very clearly that the descendants of those stem cells irradiated with 450 rad after a reconvalescence time of 35 days present a lower degree of rapid proliferative ability than the not irradiated cells. (orig./MG) [de

Aging evaluation of active components by using performance evaluation

International Nuclear Information System (INIS)

Jung, S. K.; Jin, T. E.; Kim, J. S.; Jung, I. S.; Kim, T. R.

2003-01-01

Risk analysis and performance evaluation methodology were applied to the aging evaluation of active components in the periodic safety review of Wolsung unit 1. We conclude that evaluation of performance is more effective to discriminate the aging degradation of active component than the evaluation of aging mechanism. It is essential to analyze the common cause failures of low performance components to evaluate the properness of present maintenance system. Past 10 years failure history is used for establishing the performance criteria. Past 2 years failure history is used for the evaluating the recent performance condition. We analyze the failure mode of the components to improve the maintenance system. Performance evaluation methodology is useful for the quantitative evaluation of aging degradation of active components. Analysis on the repeated failures can be useful for the feedback to maintenance plan and interval

Treatment effects of captopril on non-proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

WANG Ning; ZHENG Zhi; JIN Hui-yi; XU Xun

2012-01-01

Background Diabetic retinopathy (DR) is one of the most common complications of diabetes.Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR.The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI,captopril) in the treatment of patients with non-proliferative DR.Methods Three hundred and seventeen type 2 diabetic patients (88.05％ of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n=202) and placebo group (n=115).All subjects received 24-month follow-up.General clinical examinations,including blood pressure and glycated hemoglobin,as well as comprehensive standardized ophthalmic examinations were performed.Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.Results The levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits,suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role.DR classification showed that 169 eyes (83.66％) remained unchanged and the DR grade of 33 eyes (16.34％) increased in captopril group,while 84 eyes (73.04％) remained unchanged and the grade of 31 eyes (26.96％) increased in placebo group (P=0.024).Captopril treatment improved macular edema in 55.45％ eyes,which was significantly higher than the 37.39％ improvement in placebo group (P=0.002).No significant difference was found in the visual acuity between the two groups (P=0.271).Conclusion Captopril can improve or delay the development of DR and macular edema,which can be used in the early treatment of DR patients with type 2 diabetic mellitus.

Proliferative diabetic retinopathy after vitrectomy early factors affect IOP

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Shi-Bo Liu

2013-05-01

Full Text Available AIM:To explore possible causes of early postoperative elevated intraocular pressure caused by proliferative diabetic retinopathy(PDRvitrectomy. METHODS:Totally 72 cases(100 eyeswhich have performed vitrectomy for proliferative diabetic retinopathy were retrospectively analyzed to observe the incidence of postoperative ocular hypertension, and the relevant factors that caused postoperative high intraocular pressure were statistically analyzed. Early postoperative ocular hypertension diagnostic criteria: any time after 2 weeks of non-contact tonometer measured IOP> 25mmHg(1mmHg=0.133kPa. RESULTS:High intraocular pressure after vitrectomy occurred in 27 eyes(27%, the incidence of male and female were 27.27%, 26.79%, the difference was not statistically significant(P>0.05. Eyes filled with balanced liquid filling incidence rate of 30.95%, 6.25%, and the difference was statistically significant(P0.05. Incidences of intraoperative panretinal photocoagulation and additional retinal photocoagulation group were 41%, 20%, and the difference was statistically significant(P<0.05. Preoperative retinopathy of four, five, six groups of incidence were 9.52%, 23.81%, 40.56%, and the groups were statistically significant(P<0.05. Unconsolidated preoperative retinal detachment and retinal detachment incidence rate of 19%, 41%, and the difference was statistically significant(P<0.05. Surgery in the united lens resection with intraoperative unfederated lens the resection group's incidence rate of 34%, 15%, the difference was statistically significant(P<0.05. Logistic regression analysis showed that retinal detachment preoperative and intraoperative intraocular filling were independent risk factors that caused early postoperative ocular hypertension after vitrectomy. CONCLUSION:Post-operative ocular hypertension after PDR vitrectomy is related to preoperative retinal detachment, intraoperative lensectomy, intraoperative intraocular filling, and intraoperative

Effect of exercise on the pulmonary system in proliferative phase of menstrual cycle in a group of perimenopausal women

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Amrith Pakkala

2014-01-01

Full Text Available Background: Hormonal levels influence dynamic lung function parameters. Significant increase in both progesterone (37% and estradiol (13.5%; where as, no change in plasma follicle stimulating hormone (FSH and luteinizing hormone (LH was observed in exercising women in previous studies. Therefore, this study was intended to see the limitations of the pulmonary system in adaptability to exercise in proliferative phase of menstrual cycle in perimenopausal women. Material and Methods: The present study was conducted as a part of cardiopulmonary efficiency studies on two groups of nonathletes (n = 10 and athletes (n = 10 comparable in age and sex. Menstrual history was ascertained to confirm proliferative phase of menstrual cycle. Dynamic lung functions were measured in both groups before exercise and immediately after exercise. Results: It was observed that exercise per se does not cause a statistically significant change in dynamic lung function parameters maximum mid-expiratory flow (MMEF, peak expiratory flow rate (PEFR, and MEF 25-75% in either of the groups. Conclusion: This finding supports the hypothesis that the respiratory system is not normally the most limiting factor in the delivery of oxygen even under the predominant influence of estrogen in proliferative phase, which is further accentuated by exercise.

The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

International Nuclear Information System (INIS)

Wheldon, T.E.; Michalowski, A.S.

1982-01-01

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

Karyopherin alpha2 is essential for rRNA transcription and protein synthesis in proliferative keratinocytes.

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Noriko Umegaki-Arao

Full Text Available Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest KPNA2 expression is induced in tumor cells and is strongly associated with prognosis, although the precise roles and mechanisms of KPNA2 overexpression in proliferative disorders have not been defined. We found that KPNA2 expression is induced in various proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and mycosis fungoides. siRNA-mediated KPNA suppression revealed that KPNA2 is essential for significant suppression of HaCaT proliferation under starvation conditions. Ribosomal RNA transcription and protein synthesis were suppressed by starvation combined with knockdown of KPNA (including KPNA2 expression. KPNA2 localized to the nucleolus and interacted with proteins associated with mRNA processing, ribonucleoprotein complex biogenesis, chromatin modification, and transcription, as demonstrated by tandem affinity purification and mass spectrometry. KPNA2 may be an important promoter of ribosomal RNA and protein synthesis in tumor cells.

Proliferative and antioxidant activity of Symphytum officinale root extract.

Science.gov (United States)

Sowa, Ireneusz; Paduch, Roman; Strzemski, Maciej; Zielińska, Sylwia; Rydzik-Strzemska, Ewelina; Sawicki, Jan; Kocjan, Ryszard; Polkowski, Janusz; Matkowski, Adam; Latalski, Michał; Wójciak-Kosior, Magdalena

2018-03-01

The root of Symphytum officinale L. is commonly used in folk medicine to promote the wound healing, reduce the inflammation and in the treatment of broken bones. The objective of our investigation was to analyse the extract from S. officinale in term of its antioxidant activity and the effect on cell viability and proliferation of human skin fibroblast (HSF). Moreover, the quantification of main phenolics and allantoin was conducted using HPLC-DAD method. Five compounds were found: rosmarinic, p-hydroxybenzoic, caffeic, chlorogenic and p-coumaric acid. DPPH, FRAP and TPC assay showed the high antioxidant activity of the extract. MTT test proved the stimulatory effect on cell metabolism and viability of HSF cells. Moreover, no changes in cytoskeleton structure and cells shape were observed. The obtained results indicate that non-toxic extract from S. officinale root has strong antioxidant potential and a beneficial effect on human skin fibroblasts.

Prevalence status and association with human papilloma virus of anal squamous proliferative lesions in a patient sample in Taiwan.

Science.gov (United States)

Tsai, Tsen-Fang; Kuo, Guan-Tin; Kuo, Lu-Ting; Hsiao, Cheng-Hsiang

2008-08-01

Anal squamous proliferative lesions, including condyloma, anal high-grade squamous intraepithelial lesion (AHSIL) and squamous cell carcinoma (SCC), are associated with human papilloma virus (HPV) infection. The objectives of the study were to investigate the HPV prevalence of anal squamous proliferative lesion in Taiwan. From 1991 to 2005, 41 cases with condyloma, 12 cases with AHSIL, and 13 cases with SCC were collected. DNA was extracted from the tissue sections of these patients, and the HPV genotype was identified using polymerase chain reaction and gene chip. The integration status of HPV16 DNA was also evaluated by quantitative real-time polymerase chain reaction. Anal condyloma mainly occurred in young males, but AHSIL and anal SCC developed in older patients. In the patients with human immunodeficiency virus (HIV) infection, AHSIL developed much earlier than patients without HIV infection (36 vs. 61 years). HPV DNA was detected in all 56 patients whose specimens contained adequate DNA. High-risk HPVs (type 16, 58, etc.) were mainly detected in the AHSIL and SCC. Multiple HPV infection was found in AHSIL (4 of 12) and condyloma (11 of 34) but was rare in invasive cancer (1 of 12). Seven of 8 patients with HPV16 infection had coexistent episomal and integrated forms. HPV58 is a unique high-risk HPV prevalent in Taiwan. The integration status of HPV seems not correlated with the severity of the dysplasia. In our study, emerging HIV-positive AHSIL in recent years indicates that we should devote more efforts to promote sexual safety among the people who engaged in anal intercourse.

Prolifération filamenteuse en boues activées

OpenAIRE

Juzan, L.; Vedrenne, J.

2010-01-01

/ Le développement excessif de bactéries filamenteuses en boues activées peut entrainer des dysfonctionnements biologiques tels qu'un foisonnement et/ou un moussage stable. Quels sont les moyens de prévention, de diagnostic et de traitement actuellement disponibles ?

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer.

Science.gov (United States)

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-04-12

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm². Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted.

Stochastic cellular automata model of neurosphere growth: Roles of proliferative potential, contact inhibition, cell death, and phagocytosis.

Science.gov (United States)

Sipahi, Rifat; Zupanc, Günther K H

2018-05-14

Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres. Simulations based on this model indicated that the proliferative potential of the founder cell and its progenitors has a major influence on neurosphere size. On the other hand, contact inhibition of proliferation limits the final size, and reduces the growth rate, of neurospheres. The effect of this inhibition is particularly dramatic when a stem cell becomes encapsulated by differentiated or other non-proliferating cells, thereby suppressing any further mitotic division - despite the existing proliferative potential of the stem cell. Conversely, clearance of dead cells through phagocytosis is predicted to accelerate growth by reducing contact inhibition. A surprising prediction derived from our model is that cell death, while resulting in a decrease in growth rate and final size of neurospheres, increases the degree of differentiation of neurosphere cells. It is likely that the cellular automata model developed as part of the present investigation is applicable to the study of tissue growth in a wide range of systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

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Gabriele A. Losa

1998-01-01

Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

Nogo-B Promotes Angiogenesis in Proliferative Diabetic Retinopathy via VEGF/PI3K/Akt Pathway in an Autocrine Manner

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Yuelu Zhang

2017-10-01

Full Text Available Background/Aims: Nogo-B, a conservative protein of endoplasmic reticulum, is a member of the reticulon family of proteins. Proliferative diabetic retinopathy (PDR is the major concerning problem of diabetic retinopathy. This study explored the role of Nogo-B in the regulation of angiogenesis in PDR patients and primary human retinal endothelial cells (HRMECs. Methods: Nogo-B was down-regulated through the use of Lentivirus-NogoB-RNAi, the effects of Nogo-B on angiogenesis under high glucose stimulation were evaluated via CCK-8 assay, wound closure assay, transwell assay, and tube formation assay. Expression of Nogo-B, VEGF, PI3K and Akt were determined by western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA. Co-culture systerm was used to explore cell communication. Results: Nogo-B was highly enriched in ocular tissues of PDR patients and in HRMECs exposed to high glucose. Down-regulation of Nogo-B attenuated high glucose induced cell migration and tube formation in HRMECs. Mechanistically, in comparison with the negative control group, Lentivirus-NogoB-RNAi group had exhibited reduced VEGF secretion, weakened PI3K and Akt activation. Besides, high glucose treatment promoted the secretion of Nogo-B and presented as a “long-term memory”. Conclusions: These data collectively indicated that Nogo-B promoted angiogenesis in HRMECs via VEGF/PI3K/Akt pathway in an autocrine manner.

The presence of proliferative breast disease with atypia does not influence outcome in invasive breast cancer treated with conservative surgery and radiation

International Nuclear Information System (INIS)

Fowble, B.; Hanlon, A.L.; Patchefsky, A.; Hoffman, J.P.; Sigurdson, E.R.; Goldstein, L.J.

1997-01-01

Purpose: Atypical hyperplasia (AH) (ductal or lobular) represents a marker for an increased risk for subsequent breast cancer in either breast, especially in premenopausal women and those with a positive family history. However, the impact of the presence of AH in association with an invasive breast cancer on ipsilateral breast recurrence rates or contralateral breast cancer in women treated with conservative surgery and radiation is unknown. For a number of clinicians the presence of marked proliferative changes with atypia at the time of diagnosis of an invasive cancer is an indication for mastectomy. In an attempt to address this issue, we compared the outcome of patients (pts) with proliferative disease with atypia to those in whom this pathologic feature was absent. Materials and Methods: From 1982-1994, 1537 women with stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. 459 of these women had pathologic evaluation of the background adjacent benign breast tissue and represent the study population. The median followup was 6.3 yrs (range .1-14.5). The median age was 55 yrs (range 24 to 88). 23% had positive axillary nodes. 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (16%) tamoxifen. 24% received tamoxifen alone. The study population was divided into 2 groups: 131 pts with atypical hyperplasia (ductal 99 pts, lobular 20 pts, and type not specified 12 pts) and 328 pts with no proliferative changes or proliferative changes without atypia. The comparability of the 2 groups was assessed for the following factors: clinical (race, age, menopausal status, method of detection of primary, primary tumor size, and family history), pathologic (histology, final resection margin, pathologic nodal status, presence or absence of LCIS, histologic subtype DCIS when present and estrogen and progesterone receptor status) and treatment related (re-excision and adjuvant chemotherapy and/or tamoxifen). Outcome was evaluated

GENE EXPRESSION CHANGES AND ANTI-PROLIFERATIVE EFFECT OF NONI (Morinda citrifolia FRUIT EXTRACT ANALYSED BY REAL TIME-PCR

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hermansyah hermansyah

2017-05-01

Full Text Available To elucidate the anti-proliferative effect of noni (Morinda citrifolia fruit extract for a Saccharomyces cerevisiae model organism, analysis of gene expression changes related to cell cycle associated with inhibition effect of noni fruit extract was carried out. Anti-proliferative of noni fruit extract was analyzed using gene expression changes of Saccharomyces cerevisiae (strains FY833 and BY4741.  Transcriptional analysis of genes that play a role in cell cycle was conducted by growing cells on YPDAde broth medium containing 1% (w/v noni fruit extract, and then subjected using quantitative real-time polymerase chain reaction (RT-PCR.  Transcriptional level of genes CDC6 (Cell Division Cycle-6, CDC20 (Cell Division Cycle-20, FAR1 (Factor ARrest-1, FUS3 (FUSsion-3, SIC1 (Substrate/Subunit Inhibitor of Cyclin-dependent protein kinase-1, WHI5 (WHIskey-5, YOX1 (Yeast homeobOX-1 and YHP1 (Yeast Homeo-Protein-1 increased, oppositely genes expression of DBF4 (DumbBell Forming, MCM1 (Mini Chromosome Maintenance-1 and TAH11 (Topo-A Hypersensitive-11 decreased, while the expression level of genes CDC7 (Cell Division Cycle-7, MBP1 (MIul-box Binding Protein-1 and SWI6 (SWItching deficient-6 relatively unchanged. These results indicated that gene expression changes might associate with anti-proliferative effect from noni fruit extract. These gene expressions changes lead to the growth inhibition of S.cerevisiae cell because of cell cycle defect.

Japan turns pro-life: recent change in reproductive health policy and challenges by new technologies

OpenAIRE

Okamoto, Etsuji

2014-01-01

Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA), which prohibits abortions due to “fetal cause”.

Anticardiolipin antibodies in proliferative diabetic retinopathy: An additional risk factor

International Nuclear Information System (INIS)

Shahin, Maha; ElDiasty, Amany M; Mabed, Mohamed

2009-01-01

To report the prevalence of anticardiolipin antibodies in patients with proliferative diabetic retinopathy (PDR) having high-risk criteria (HRC). Diabetic patients having PDR with HRC and diabetics free of retinopathy were compared for the presence of anticardiolipin antibodies. Among the 34 patients, 6 (17.7%) of diabetics having PDR with HRC were positive for anticardiolipin antibodies. There was no significant association of aCL antibodies with sex or type of diabetes. Using Pearson's correlation test, no significant associations of aCL antibodies with duration of diabetes or age of patients were found. All patients who were positive for anticardiolipin antibodies had PDR with HRC. The difference was statistically significant. Presence of anticardiolipin antibodies may represent an additional risk factor for PDR. (author)

Leptin: A proliferative factor for breast cancer?

International Nuclear Information System (INIS)

Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

2005-01-01

Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

Echography of the Cervix and Uterus during the Proliferative and Secretory Phases of the Menstrual Cycle in Bonnet Monkeys (Macaca radiata)

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Chaudhari, Uddhav K; Metkari, Siddnath M; Manjaramkar, Dhyananjay D; Sachdeva, Geetanjali; Katkam, Rajendra; Bandivdekar, Atmaram H; Mahajan, Abhishek; Thakur, Meenakshi H; Kholkute, Sanjiv D

2014-01-01

We undertook the present study to investigate the echographic characteristics of the uterus and cervix of female bonnet monkeys (Macaca radiata) during the proliferative and secretory phases of the menstrual cycle. The cervix was tortuous in shape and measured 2.74 ± 0.30 cm (mean ± SD) in width by 3.10 ± 0.32 cm in length. The cervical lumen contained 2 or 3 colliculi, which projected from the cervical canal. The echogenicity of cervix varied during proliferative and secretory phases. The uterus was pyriform in shape (2.46 ± 0.28 cm × 1.45 ± 0.19 cm) and consisted of serosa, myometrium, and endometrium. The endometrium generated a triple-line pattern; the outer and central lines were hyperechogenic, whereas the inner line was hypoechogenic. The endometrium was significantly thicker during the secretory phase (0.69 ± 0.12 cm) than during the proliferative phase (0.43 ± 0.15 cm). Knowledge of the echogenic changes in the female reproductive organs of bonnet monkeys during a regular menstrual cycle may facilitate understanding of other physiologic and pathophysiologic changes. PMID:24411775

Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

Science.gov (United States)

Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

2011-08-15

Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

Tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy.

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Schwartz, Stephen G; Flynn, Harry W; Lee, Wen-Hsiang; Ssemanda, Elizabeth; Ervin, Ann-Margret

2009-10-07

Retinal detachment (RD) with proliferative vitreoretinopathy (PVR) often requires surgery. During surgery, a tamponade agent is needed to reduce the rate of recurrent retinal detachment. The objective of this review was to evaluate the benefits and adverse outcomes of surgery with various tamponade agents. We searched the Cochrane Controlled Register (CENTRAL), MEDLINE, EMBASE, Latin America and Carribbean Health Sciences (LILACS) and the UK Clinical Trials Gateway (UKCTG). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 9 July 2009. We included randomized clinical trials comparing patients treated with various tamponade agents. Two individuals screened the search results independently. One study with two trials was eligible for inclusion in the review. One study with two trials was included in the review. The first trial randomized 151 eyes to receive either silicone oil or sulfur hexafluoride (SF(6)) gas tamponades; the second trial randomized 271 eyes to receive either silicone oil or perfluropropane (C(3)F(8)) gas tamponades. In patients with RD associated with PVR, pars plana vitrectomy and infusion of either silicone oil or perfluropropane gas appear comparable for a broad variety of cases. Sulfur hexafluoride gas was associated with worse anatomic and visual outcomes than either silicone oil or perfluropropane gas. The use of either C(3)F(8) or silicone oil appears reasonable for most patients with RD associated with PVR. Because there do not appear to be any major differences in outcomes between the two agents, the choice of a tamponade agent should be individualized for each patient.

Japan Turns Pro-Life: Recent Change in Reproductive Health Policy and Controversies over Prenatal Screening

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Etsuji Okamoto

2014-02-01

Full Text Available Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA, which prohibits abortions due to “fetal cause”.

Ccdc85C, a causative protein for hydrocephalus and subcortical heterotopia, is expressed in the systemic epithelia with proliferative activity in rats.

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Tanaka, Natsuki; Izawa, Takeshi; Takenaka, Shigeo; Yamate, Jyoji; Kuwamura, Mitsuru

2015-07-01

Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for spontaneous mutant mouse with non-obstructive hydrocephalus and subcortical heterotopia. Detailed functions of Ccdc85C protein have not been clarified. To reveal roles of Ccdc85C, we examined the distribution and expression pattern of Ccdc85C in the systemic developing organs in rats. Ccdc85C was expressed in various simple epithelia but not stratified epithelia. In the various epithelia, Ccdc85C was localized at cell-cell junctions and its expression was strong at apical junctions. Furthermore, intense expression was seen at developing period and gradually decreased with advancing development. Distribution of Ccdc85C coincides with that of proliferating epithelial cells. These results suggest that Ccdc85C plays an important role in the proliferative property of simple epithelia.

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericum ascyron L.

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Li, Xiu-Mei; Luo, Xue-Gang; He, Jun-Fang; Wang, Nan; Zhou, Hao; Yang, Pei-Long; Zhang, Tong-Cun

2018-03-01

Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V-fluorescein isothiocyanate/propidium iodide, 2',7'-dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase-3 activity analysis were performed. The results demonstrated that the anti-proliferative action of the mixture of kaempferol 3-O-β-(2″-acetyl) galactopyranoside (K) and quercetin (Q) (molar ratio, 1:1) was significantly increased compared with either of these two compounds separately, and the active fraction of the H. ascyron L. extract |(HALE). HALE, indicating that the anti-proliferative function of H. ascyron L. may be a synergic effect of K and Q. Furthermore, the inhibitory effect of KQ on the growth of HeLa cells was mediated by the induction of apoptosis. To the best of our knowledge, the present study is the first to identify that KQ exhibits significant anti-proliferation activity on HeLa cells via the apoptotic pathway, and is also the first to evaluate the anticancer potential of H. ascyron L. The results of the present study may provide a rational base for the use of H. ascyron L. in the clinic, and shed light on the development of novel anticancer drugs.

Studies quantifying modulatory effects of inhaled NO2 and SO2 on tracheal mucus secretion, proliferative activity of airway epithelium and architecture of lung parenchyma

International Nuclear Information System (INIS)

Wagner, U.; Barth, P.J.; Bredenbroeker, D.; Haase, H.; Locher, A.; Janssen, P.; Yu, F.; Wichert, P. von

1995-10-01

The following studies were designed to quantify changes in tracheal mucus secretion and epithelial proliferation of peripheral airways induced by inhaled NO 2 and SO 2 . Groups of male Sprague-Dawley rats were exposed alternatively to 1, 5, 10 and 20 ppm NO 2 and SO 2 the exposure-time being 3 or 25 days (d) respectively. Studies of tracheal mucus secretion radiolabelling mucins with 35 S clearly demonstrated a concentration dependant modulation of mucus secretion. We were able to demonstrate for the first time a significant increase of mucus secretion due to submucosal application of the peptide hormone GLP-1(7-36)amide. We were able to demonstrate amylin to be a potent secretagogue, dose-dependently stimulating mucus secretion. Our morphologic data reveal the effects caused by concentrations between 4-5 ppm NO 2 to be so small, that they are hardly detectable at light microscopic level. The assessment of proliferative activity, however, clearly demonstrates an increased proliferation due to even lower concentrations indicating, that even 1 ppm is able to cause epithelial impairment with consecutive regeneration. Double-labelling techniques of proliferation markers and the 10 kD Clara cell specific antigen reveal the Clara cell to be the only source for epithelial regeneration in peripheral airways under the reported experimental conditions of this study. (orig.) [de

Tc-99m-MIBI Uptake in Active Pulmonary Tuberculosis: A Case Report

International Nuclear Information System (INIS)

Lee, Chang Ho; Park, Chan Hee; Hwang, Hee Sung; Bae, Moon Sun

1996-01-01

Technetium-99m MIBI was developed as a myocardiac perfusion imagine agent and has been used effectively in the detection and post-therapeutic evaluation of various neoplasm such as thyroid, lung, bone and breast tumors. As an infrequent findings, Tc-99m MIBI agent has shown in non-neoplastic pulmonary conditions including fibroding alveolitis, pulmonary actinomycosis, active pulmonary sarcoidosis, pulmonary interstitial fibrosis in progressive systemic sclerosis and active osteomyelitis. In a recent report conducted by Cetin Oncel, Tc-99m MIBI imaging is an effective method in the detection and follow-up of pulmonary tuberculosis. We have also experienced Tc-99m-MIBI uptake in active pulmonary tuberculosis incidentally found in a patient with suspected proliferative villonodular synovitis of the left ankle.

In vitro evaluation of antioxidant and cytotoxic activities of lignin fractions extracted from Acacia nilotica.

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Barapatre, Anand; Meena, Avtar Singh; Mekala, Sowmya; Das, Amitava; Jha, Harit

2016-05-01

Lignin is one of the most important phytomacromolecule with diverse therapeutic properties such as anticancer, antimicrobial, anti-inflammatory and immune-stimulatory. The present study was carried out to evaluate the in vitro antioxidant, free radical scavenging and anti-proliferative/cytotoxic activities of eleven different lignin fractions, extracted from the wood of Acacia nilotica by pressurized solvent extraction (PSE) and successive solvent extraction (SSE) methods. Results indicate that the PSE fractions have high polyphenolic content and reducing power. However, the antioxidant efficiency examined by DPPH and ABTS radical scavenging assay was higher in SSE fractions. All lignin fractions revealed a significant ability to scavenge nitric oxide, hydroxyl and superoxide radicals. The extracted lignin fractions display high ferric ion reducing capacity and also possess excellent antioxidant potential in the hydrophobic (linoleic acid) system. Fractions extracted by polar solvent has the highest iron (Fe(2+)) chelating activity as compared to other factions, indicating their effect on the redox cycling of iron. Four lignin fractions depicted higher cytotoxic potential (IC50: 2-15 μg/mL) towards breast cancer cell line (MCF-7) but were ineffective (IC50: ≥ 100 μg/mL) against normal primary human hepatic stellate cells (HHSteCs). These findings suggest that the lignin extracts of A. nilotica wood has a remarkable potential to prevent disease caused by the overproduction of radicals and also seem to be a promising candidate as natural antioxidant and anti-cancer agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Ki-67 immunoreactivity in meningiomas--determination of the proliferative potential of meningiomas using the monoclonal antibody Ki-67

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1997-01-01

The proliferative potential of 66 human intracranial meningiomas (15 benign, 15 atypical, 15 recurrent, 13 bone-invasive, and 8 brain-invasive) was investigated by means of immunohisto-chemistry using the monoclonal antibody Ki-67. This antibody recognizes a nuclear antigen present in human cells...

Determination of estradiol, estrone and progesterone in serum and human endometrium in correlation to the content of steroid receptors and 17β-hydroxysteroid dehydrogenase activity during menstrual cycle

International Nuclear Information System (INIS)

Schmidt-Gollwitzer, M.; Eiletz, J.; Pachaly, J.

1977-01-01

A study has been carried out to compare the influence of estradiol estrone and progesterone on the estradiol and progesterone receptor levels and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity in human endometrium. The steroid hormone concentrations were measured simultaneously in both serum and endometrial tissue. The estradiol receptor levels were highest during the early proliferative phase and were inversely correlated to the endometrial tissue and serum concentrations of estradiol and progesterone. The highest progesterone binding capacity was found in endometrical cytosol during the late proliferative phase (midcycle) of the menstrual cycle. The midcycle peak of the progesterone receptor level correlated well with the first peak of the serum and tissue concentrations of estradiol. During,the luteal phase, in contrast to the proliferative phase, the progesterone receptor level decreased whereas serum progesterone concentrations were high. Estrone concentrations were higher in secretory than proliferative endometrium and were correlated to the increase of progesterone receptor content and 17β-HSD activity during early secretory phase. The 17β-HSD activity was approximately 10-fold higher during the early secretory than during the proliferative phase. The progesterone receptor level was highly correlated to the specific 17β-HSD activity of the microsomal fraction whereas a significant inverse correlation between the enzyme activity and the estradiol receptor level was observed. (orig.) [de

Adult neurogenesis in the central olfactory pathway of dendrobranchiate and caridean shrimps: New insights into the evolution of the deutocerebral proliferative system in reptant decapods.

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Wittfoth, Christin; Harzsch, Steffen

2018-04-16

Persistent neurogenesis in the central olfactory pathway characterizes many reptant decapods such as lobsters, crayfish and crabs. In these animals, the deutocerebral proliferative system generates new neurons which integrate into the neuronal network of the first order processing neuropil of the olfactory system, the deutocerebral chemosensory lobes (also called olfactory lobes). However, differences concerning the phenotype and the mechanisms that drive adult neurogenesis were reported in crayfish versus spiny lobsters. While numerous studies have focussed on these mechanisms and regulation of adult neurogenesis, investigations about the phylogenetic distribution are missing. To contribute an evolutionary perspective on adult neurogenesis in decapods, we investigated two representatives of basally diverging lineages, the dendrobranchiate Penaeus vannamei and the caridean Crangon crangon using the thymidine analogue Bromodeoxyuridine (BrdU) as marker for the S phase of cycling cells. Compared to reptant decapods, our results suggest a simpler mechanism of neurogenesis in the adult brain of dendrobranchiate and caridean shrimps. Observed differences in the rate of proliferation and spatial dimensions are suggested to correlate with the complexity of the olfactory system. We assume that a more complex and mitotically more active proliferative system in reptant decapods evolved with the emergence of another processing neuropil, the accessory lobes. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

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Hui Guo

2016-07-01

Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

Accounting for treatment delays when treating highly proliferative tumours

International Nuclear Information System (INIS)

Jones, L.; Metcalfe, P.; Hoban, P.

1999-01-01

This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined. (author)

Inheritance of proliferative breast disease in breast cancer kindreds

International Nuclear Information System (INIS)

Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

1990-01-01

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

Wingless promotes proliferative growth in a gradient-independent manner.

Science.gov (United States)

Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

2009-10-06

Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

Impact Of Tissue Sampling On Accuracy Of Ki67 Immunohistochemistry Evaluation In Breast Cancer

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Justinas Besusparis

2016-06-01

The sampling requirements were dependent on the heterogeneity of the biomarker expression. To achieve a coefficient error of 10%, 5-6 cores were needed for homogeneous cases, while 11-12 cores for heterogeneous cases. In mixed tumor population, 8 TMA cores were required. Similarly, to achieve the same accuracy, approximately 4,000 nuclei must be counted when the intra-tumor heterogeneity is mixed/unknown. Tumors at the lower scale of proliferative activity would require larger sampling (10-12 TMA cores, or 5,000 nuclei to achieve the same error measurement results as for highly proliferative tumors. Our data show that optimal tissue sampling for IHC biomarker evaluation is dependent on the heterogeneity of the tissue under study and needs to be determined on a per-use basis. We propose a method that can be applied to determine the TMA sampling strategy for specific biomarkers, tissues and study targets. In addition, our findings highlight the importance of high-capacity computer-based IHC measurement techniques to improve accuracy of the testing.

ABORTION AND VIOLENCE IN JANE MARTIN’S KEELY AND DU: PRO-CHOICE, PRO-LIFE, OR MERELY PROVOCATIVE?

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Eta Farmacelia Nurulhady

2017-04-01

Full Text Available Abortion and violence are global issues, yet different culture might respond to the issues somewhat differently. This study aims to reveal the abortion and violence issues in Jane Martin’s Keely and Du in terms of pro-choice and pro life movements and see how Indonesian students reading the play respond to the issues. In the United States of America, the discussion of abortion issue can be grouped into two major categories: the pro-life and pro-choice. In Indonesia, the majority of people would be against abortion when it is not for medical reasons. The students reading Keely and Du find the play challenging their beliefs as religious people still keeping hold of eastern values. Having discussed the nature of pro-life and pro-choice movements, it is difficult for them to decide whether they are proponent of either one. Keely and Du is successfully provocative in offering insight on how abortion and violence issues cannot be judged in a black and white manner.

Surgical management of retinal diseases: proliferative diabetic retinopathy and traction retinal detachment.

Science.gov (United States)

Cruz-Iñigo, Yousef J; Acabá, Luis A; Berrocal, Maria H

2014-01-01

Current indications for pars plana vitrectomy in patients with proliferative diabetic retinopathy (PDR) include vitreous hemorrhage, tractional retinal detachment (TRD), combined tractional and rhegmatogenous retinal detachment (CTRRD), diabetic macular edema associated with posterior hyaloidal traction, and anterior segment neovascularization with media opacities. This chapter will review the indications, surgical objectives, adjunctive pharmacotherapy, microincision surgical techniques, and outcomes of diabetic vitrectomy for PDR, TRD, and CTRRD. With the availability of new microincision vitrectomy technology, wide-angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from PDR. © 2014 S. Karger AG, Basel

FLT-PET for early response evaluation of colorectal cancer patients with liver metastases

DEFF Research Database (Denmark)

Mogensen, Marie Benzon; Loft, Annika; Aznar, Marianne

2017-01-01

BACKGROUND: Fluoro-L-thymidine (FLT) is a positron emission tomography/computed tomography (PET/CT) tracer which reflects proliferative activity in a cancer lesion. The main objective of this prospective explorative study was to evaluate whether FLT-PET can be used for the early evaluation...... standardised uptake values (SUVmax, SUVmean) were measured. After three cycles of chemotherapy, treatment response was assessed by CT scan based on RECIST 1.1. RESULTS: Thirty-nine consecutive patients were included of which 27 were evaluable. Dropout was mainly due to disease complications. Nineteen patients...... between the response according to RECIST and the early changes in FLT uptake measured as SUVmax(p = 0.24). CONCLUSIONS: No correlation was found between early changes in FLT uptake after the first cycle of treatment and the response evaluated from subsequent CT scans. It seems unlikely that FLT-PET can...

Proliferative sickle cell retinopathy associated with sickle cell trait and gestational diabetes: case report Retinopatia falciforme proliferativa associada a traço falciforme e diabetes gestacional: relato de caso

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Jefferson Augusto Santana Ribeiro

2009-06-01

Full Text Available Proliferative sickle cell retinopathy is an uncommon complication in individuals with sickle cell trait (AS. However, the risk for proliferative retinopathy development is increased in patients with AS hemoglobinopathy associated with systemic conditions or ocular trauma. A case of a patient with AS hemoglobinopathy who developed proliferative sickle cell retinopathy after the occurrence of gestational diabetes and pregnancy-induced hypertension is reported. Hemoglobin electrophoresis revealed presence of A2 5.0%, S 35.0% and A 53.2%. The present case emphasizes the importance of evaluating systemic comorbidities in patients with sickle cell trait during pregnancy since sickle cell retinopathy can progress rapidly, as well as the importance of regular eye fundus examination in these patients.Retinopatia falciforme proliferativa é uma complicação incomum em indivíduos com traço falciforme, havendo, porém, risco aumentado de desenvolver retinopatia proliferativa em pacientes com hemoglobinopatia AS associada a condições sistêmicas ou trauma ocular. Neste artigo será apresentado um caso de paciente com diabetes gestacional, hipertensão arterial sistêmica associada à gravidez e traço falciforme. Eletroforese de hemoglobinas revelou a presença de A2 5,0%, S 35,0% e A 53,2%. Este caso ressalta a importância da avaliação de comorbidades sistêmicas em pacientes com traço falciforme no período gestacional, uma vez que pode ocorrer rápida progressão da retinopatia falciforme, devendo-se realizar também exames regulares do fundo de olho nestes pacientes.

Lymphocyte proliferative responses to mitogens in rats having an ancestry of a perinatal iodine-131 insult

International Nuclear Information System (INIS)

Stevens, R.H.; Cheng, H.F.

1987-01-01

The possible existence of a genealogical memory consisting of altered lymphocyte proliferative responses to a perinatal iodine-131 insult has been investigated in two generations of inbred Fischer F344 rat offspring. The studies which involved exposure to the radioiodine during late pregnancy with concentrations ranging from 1.85 MBq (50 μCi) to 7.4 MBq (200 μCi) revealed that only the peripheral blood T lymphocytes of the first generation male animals were significantly affected. These animals were found to possess T lymphocytes which exhibited increased proliferative responses expressed toward the mitogens concanavalin A and phytohemagglutin; however, no significant changes were noticeable in their B cell population following exposure to lipopolysaccharide. Neither the first generation females nor the male and female offspring of the second generation developed through sibling interbreeding seemed to be affected, this was unlike the cellular, humoral, and natural immunity which had previously been observed to be changed in both the second and third generation animals. These observations suggest that the effects of the radiation insult upon immunocompetency as measured by lymphocyte proliferation do not appear to be inherited

Study of Stevia rebaudiana Bertoni antioxidant activities and cellular properties.

Science.gov (United States)

Bender, Cecilia; Graziano, Sara; Zimmermann, Benno F

2015-01-01

The aim of our study was to determine the antioxidant activities, cytotoxicity and proliferative properties in Stevia rebaudiana leaves and stems. Leaves extracts exhibited a higher antioxidant activity than stems extract, through oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. Stevioside and rebaudioside A, the main sweetening metabolites in stevia leaves, exhibited a low ORAC value in comparison with plant extracts, while did not elicit any CAA. Stevia rebaudiana did not exhibit toxicity against HepG2 (hepatocellular carcinoma) human cells. No proliferative nor catalase modulations were observed in cells treated with such extracts. Our findings support the promising role of stevia that, apart from its sweetness, can act as a source of antioxidants, even at the intracellular level. This activity makes S. rebaudiana crude extract an interesting resource of natural sweetness with antioxidant properties which may find numerous applications in foods and nutritional supplements industries.

Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities.

Science.gov (United States)

Gorgoglione, Bartolomeo; Wang, Tiehui; Secombes, Christopher J; Holland, Jason W

2013-07-16

The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate/inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease.

Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities

Science.gov (United States)

2013-01-01

The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate / inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell / antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease. PMID:23865616

Bioactive Properties of Eremostachys macrophylla Montbr. & Auch. Rhizomes Growing in Iran

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Parina Asgharian, Abbas Delazar, Farzaneh Lotfipour. Solmaz Asnaashari

2017-09-01

Full Text Available Background: The current study was assigned to evaluate the antioxidant, general toxicity, anti-proliferative and antimicrobial activities of different extracts obtained from rhizomes of Eremostachys macrophylla (Lamiaceae. Methods: All activities were evaluated by obtaining extracts of E. macrophylla in n-hexane, DCM (dichloromethane and MeOH (methanol by soxhlet apparatus. The antioxidant activity of the extracts was evaluated in terms of FRST (free radical scavenging activity test by DPPH (2, 2-diphenyl-1-picrylhydrazyl. BSLT (Brine shrimp lethality tests, MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay and disc diffusion method were carried out to determine the general toxicity, anti-proliferative and antibacterial activities of the different extracts, respectively. Results: The findings of the study for antioxidant, anti-proliferative and antibacterial effects showed that DCM extract was the most active fraction, but n-hexane extract indicated the most potent effect against Artemia salina. Conclusion: The results revealed strong bioactive effects of nonpolar fractions of E. macrophylla rhizomes. Thus, it is possible to suggest some new potential antioxidant, cytotoxic and antibacterial agents with no harmful effects on noncancerous cells.

"Antimicrobial and antiproliferative activity of essential oil, aqueous and ethanolic extracts of Ocimum micranthum Willd leaves".

Science.gov (United States)

Caamal-Herrera, Isabel O; Carrillo-Cocom, Leydi M; Escalante-Réndiz, Diana Y; Aráiz-Hernández, Diana; Azamar-Barrios, José A

2018-02-08

Ocimum micranthum Willd is a plant used in traditional medicine practiced in the region of the Yucatan peninsula. In particular, it is used for the treatment of cutaneous infections and wound healing, however there are currently no existing scientific studies that support these applications. The aim of the present study was to evaluate the antimicrobial and the in vitro proliferative activity (on healthy mammalian cell lines) of the essential oil and extracts (aqueous and ethanolic) of this plant. The minimal inhibitory concentration (MIC) of essential oil and aqueous and ethanolic extracts of Ocimum micranthum leaves against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans was determined using the microdilution technique. The in vitro proliferative activity of human fibroblast (hFB) and Chinese hamster ovary (CHO-K1) cells treated with these extracts was evaluated using the MTT test. The hFB cell line was also evaluated using Trypan Blue assay. Candida albicans was more susceptible to the ethanolic extract and the aqueous extract (MIC value of 5 μL/mL and 80 μL/mL respectively). In the case of Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, the MIC of the aqueous and ethanolic extract was 125 μL/mL. The aqueous extract showed a significant (p essential oil and extracts of Ocimum micranthum leaves are sufficient to cause an antiproliferative effect on the hFB cell line but do not produce an antimicrobial effect against the microorganisms evaluated. More studies are necessary to improve understanding of the mechanism of action of the compounds implicated in the bioactivities shown by the crude extracts.

Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer Streptomyces collinus Tü 365

DEFF Research Database (Denmark)

Iftime, Dumitrita; Kulik, Andreas; Härtner, Thomas

2016-01-01

Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynth......Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein...

Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy

NARCIS (Netherlands)

van Duinkerken, Eelco; Ijzerman, Richard G.; Klein, Martin; Moll, Annette C.; Snoek, Frank J.; Scheltens, Philip; Pouwels, Petra J. W.; Barkhof, Frederik; Diamant, Michaela; Tijms, Betty M.

2016-01-01

Type 1 diabetes mellitus (T1DM) patients, especially with concomitant microvascular disease, such as proliferative retinopathy, have an increased risk of cognitive deficits. Local cortical gray matter volume reductions only partially explain these cognitive dysfunctions, possibly because volume

Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

OpenAIRE

Smits, A.; Funa, K.; Vassbotn, F. S.; Beausang-Linder, M.; af Ekenstam, F.; Heldin, C. H.; Westermark, B.; Nistér, M.

1992-01-01

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protei...

ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells

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Tompkins Kathleen

2010-10-01

Full Text Available Abstract Background Unrepaired DNA double-stranded breaks (DSBs cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. Results Here we investigate roles for the NHEJ factor ARTEMIS in multipotent mesenchymal stem/progenitor cells (MSCs, as putative sarcomagenic cells of origin. We demonstrate a key role for ARTEMIS in sarcoma suppression in a sensitized mouse tumor model. In this context, we found that ARTEMIS deficiency led to chromosomal damage but, paradoxically, enhanced resistance and proliferative potential in primary MSCs subjected to various stresses. Gene expression analysis revealed abnormally regulated stress response, cell proliferation, and signal transduction pathways in ARTEMIS-defective MSCs. Finally, we identified candidate regulatory genes that may, in part, mediate a stress-resistant, hyperproliferative phenotype in preneoplastic ARTEMIS-deficient MSCs. Conclusions Our discoveries suggest that Art prevents genome damage and restrains proliferation in MSCs exposed to various stress stimuli. We propose that deficiency leads to a preneoplastic state in primary MSCs and is associated with aberrant proliferative control and cellular stress

Dashed line relaxing retinotomy in the management of retinal detachment with anterior proliferative vitreoretinopathy

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Tsen CL

2015-04-01

Full Text Available Chui-Lien Tsen,1 Yu-Harn Horng,1 Shwu-Jiuan Sheu1,2 1Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan Background: We describe the anatomical and functional outcomes of eyes that underwent a modified technique of relaxing retinotomy, dashed line relaxing retinotomy, in the management of retinal detachment with anterior proliferative vitreoretinopathy.Methods: We retrospectively reviewed 54 consecutive eyes in 52 patients who received pars plana vitrectomy with relaxing retinotomy during retinal detachment repair. Perfluorocarbon liquid (PFCL was used as a standard procedure to stabilize the retina during retinotomy to prevent slippage or inversion of the posterior flap. If PFCL was not available due to economic reasons, dashed line relaxing retinotomy was performed instead. Best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, lens status, and fundus examination were analyzed. We excluded patients who were followed up <4 months.Results: Regarding anatomical success rates and visual outcomes, we found no significant differences between patients treated with intraoperative PFCL and those treated with dashed line relaxing retinotomy without PFCL.Conclusion: Compared to the simple and efficient PFCL-assisted relaxing retinotomy, dashed relaxing retinotomy is not the first choice when PFCL is available. Based on our results, this modified technique may offer an alternative in patients with anterior proliferative vitreoretinopathy for whom PFCL is not available. Keywords: perfluorocarbon liquid, PFCL 

In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

International Nuclear Information System (INIS)

Rivero, Javier; Luzardo, Octavio P.; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

2015-01-01

Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

Energy Technology Data Exchange (ETDEWEB)

Rivero, Javier; Luzardo, Octavio P., E-mail: octavio.perez@ulpgc.es; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

2015-12-15

Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

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Araceli Gutiérrez-Rodríguez

2017-01-01

Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

Small Interfering RNA Targeted to ASPP2 Promotes Progression of Experimental Proliferative Vitreoretinopathy

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Xiao-Li Chen

2016-01-01

Full Text Available Background. Epithelial-mesenchymal transition (EMT of retinal pigment epithelium (RPE is vital in proliferative vitreoretinopathy (PVR development. Apoptosis-stimulating proteins of p53 (ASPP2 have recently been reported to participate in EMT. However, the role of ASPP2 in PVR pathogenesis has not been identified. Methods. Immunohistochemistry was used to investigate the expression of ASPP2 in epiretinal membranes of PVR patients. ARPE-19 cells were transfected with ASPP2-siRNA, followed with measurement of cell cytotoxicity, proliferation, and migration ability. EMT markers and related inflammatory and fibrosis cytokines were measured by western blot or flow cytometry. Additionally, PVR rat models were induced by intravitreal injection of ARPE-19 cells transfected with ASPP2-siRNA and evaluated accordingly. Results. Immunofluorescence analysis revealed less intense expression of ASPP2 in PVR membranes. ASPP2 knockdown facilitated the proliferation and migration of RPE cells and enhanced the expression of mesenchymal markers such as alpha smooth muscle actin, fibronectin, and ZEB1. Meanwhile, ASPP2-siRNA increased EMT-related and inflammatory cytokines, including TGF-β, CTGF, VEGF, TNF-α, and interleukins. PVR severities were more pronounced in the rat models with ASPP2-siRNA treatment. Conclusions. ASPP2 knockdown promoted EMT of ARPE-19 cells in vitro and exacerbated the progression of experimental PVR in vivo, possibly via inflammatory and fibrosis cytokines.

Potent anti-cervical cancer activity: synergistic effects of Thai medicinal plants in recipe N040 selected from the MANOSROI III database.

Science.gov (United States)

Kitdamrongtham, Worapong; Manosroi, Aranya; Akazawa, Hiroyuki; Gidado, Abubakar; Stienrut, Pramote; Manosroi, Worapaka; Lohcharoenkal, Warangkana; Akihisa, Toshihiro; Manosroi, Jiradej

2013-08-26

One of the prestigious Thai/Lanna folklore wisdoms is the medicinal plant recipes. Thai/Lanna medicinal plant recipe database MANOSROI III has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes covering all diseases including cancer. To investigate the in vitro and in vivo anti-cervical cancer activity and the active constituents of the Thai medicinal plant recipe N040 selected from the MANOSROI III database. The extracts of recipe N040 and single medicinal plants in the recipe were prepared by hot water and methanol extraction, respectively. The n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and water fractions of Caesalpinia sappan, the plant which showed the highest anti-proliferative activity were prepared by liquid-liquid partition extraction. The fraction which showed the highest anti-proliferative activity was further isolated for active constituents. Anti-proliferative activity of recipe N040, methanolic extracts, fractions of Caesalpinia sappan and brazilin, an active constituent on HeLa cell were investigated using sulforhodamine B (SRB) assay. Anti-oxidative activities including free radical scavenging and metal ion-chelating activities, as well as the phenolic and flavonoid contents of these fractions were also determined. The in vivo anti-cancer activity of recipe N040 on HeLa cell xenograft and the subchronic toxicity were performed in nude mice and rats, respectively. N040 showed the potent in vitro anti-proliferative activity on HeLa cell with the IC50 value of 0.11 µg/ml. Phytochemicals detected in the plants were steroids/triterpenoids, tannins, flavonoids, saponins and alkaloids. For the single plant, methanolic extract of Caesalpinia sappan gave the highest anti-proliferative activity with the IC50 of 33.46 µg/ml. EtOAc fraction of Caesalpinia sappan showed the highest anti-proliferative and free radical scavenging activities with the IC50 and SC50 of 17.81 and 21.95 µg/ml which were 1.88 and 0.83 folds of

Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy

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Chang-Xia Dong

2017-12-01

Full Text Available AIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8 in proliferative diabetic retinopathy (PDR. METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR patients (idiopathic macular hole patients were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay (ELISA. Experimental diabetes mice model was induced with streptozotocin. The expression of glycosylated hemoglobin and Angptl 8 in sera was detected. Recombinant Angptl 8 was re-infused into wild type (WT diabetic mice and spatial frequency threshold and contrast sensitivity were measured. In vitro retinal pigment epithelium (RPE were stimulated by recombinant Angptl 8 for 24h. MMT assay were used to detect cell proliferation. At the same time, qRT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells. RESULTS: The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients (F=99.02, P<0.0001 in sera; t=10.42, P<0.0001 in aqueous. After successfully establishing the diabetic mice model, we found that glycosylated hemoglobin and Angptl 8 expression levels were increased. Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity (P<0.01. In vitro, RPE cells stimulated by recombinant Angptl 8 could increase the relative absorbance of MMT assay (1.486±0.042 vs 1.000±0.104, P<0.05 and proliferating cell nuclear antigen (PCNA expression (0.55±0.01 vs 0.29±0.03, P<0.05. The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1 (4.973±0.205 vs 2.720±0.197, P<0.05, cyclin F (5.690±0.219 vs 4.297±0.292, P<0.05 and E2F2 (2.297±0.102 vs 1.750±0.146, P<0.05, and reducing the expression of proliferation-inhibiting factors cdkn1 (2.370±0.074 vs 3.317±0.135, P<0.05 and cdkn2 (4.793±0

Enhanced anti-proliferative efficacy of epothilone B loaded with Escherichia coli Nissle 1917 bacterial ghosts on the HeLa cells by mitochondrial pathway of apoptosis.

Science.gov (United States)

Zhu, Wenxing; Hao, Lujiang; Liu, Xinli; Orlando, Borrás-Hidalgo; Zhang, Yuyu

2018-03-20

Epothilones constitute a new class of microtubule-stabilizing anti-cancer agents with promising preclinical and clinical activity. However, its systemic application still causes some toxic side effects. To reduce these undesired effects, advanced drug delivery systems based on cell targeting carriers are needed currently. In this study, the high quality bacterial ghosts of the probiotic Escherichia coli Nissle 1917 (EcN) were prepared in a large scale and retained fully intact surface structures for specific attachment to mammalian cells. The EcN ghosts could be efficiently loaded with the low hydrophilic drug Epothilone B (Epo B) and the maximal load efficiency was approximately 2.5% (w/w). Cytotoxicity assays revealed that Epo B-ghosts exhibited enhanced anti-proliferative properties on the HeLa cells. The Epo B associated with EcN ghosts was more cytotoxic at least 10 times than the free Epo B at the same concentrations. Apoptosis assays showed that both Epo B-ghosts and free Epo B induced time course-dependent apoptosis and necrosis in HeLa cells, respectively. While the former induced more apoptosis and necrosis than the latter. Furthermore, the cytochrome C release and the activation of caspase-3 were more remarkable after treatment with the Epo B-ghosts compared to the free Epo B, which implied that Epo B-ghosts might more effectively induce the apoptosis mediated by mitochondrial pathway in HeLa cells. Therefore, the higher anti-proliferative effects of the Epo B-ghosts on the HeLa cells were mediated by mitochondrial pathway of apoptosis. The EcN ghosts may provide a useful drug delivery carrier for drug candidates in cancer therapy.

Effects of irradiated diet on longevity and prolificity of successive generations of Zabrotes subfasciatus (Boheman, 1833) (Coleoptera, Bruchidae)

International Nuclear Information System (INIS)

Domarco, R.E.

1981-01-01

The study was done in the laboratory of Entomology of the Centro de Energia Nuclear na Agricultura (CENA), University of Sao Paulo, in Piracicaba, State of Sao Paulo, Brazil. This research was carried out to observe the effect of irradiated beans (Phaseolus vulgaris, (L.), cultivar Rosinha) on the longevity and prolificity of Zabrotes subfasciatus (Boheman, 1833) (Coleoptera, Bruchidae). The first part of the study included the rearing of five generations of Zabrotes subfasciatus which were fed with irradiated beans (0, 10, 20, 100 e 200 krad, with a dose rate of approximately 70 krad/h). The second one consisted of growth of seven generations on irradiated beans (0, 100, 500, 1500 and 3000 krad, with a dose rate of approximately 70 krad/h). The data were obtained through daily countings of insect birth and death rates. It was concluded that irradiation modified the nutritional quality of beans, affecting the development of Zabrotes subfasciatus. This effect was studied through the longevity and prolificity, which were altered as compared with the control, once they were higher for the dosis of 1500 and 3000 krad. (author)

Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

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Michael Poulsen

2011-02-01

Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

Gingival proliferative lesions in children and adolescents in Brazil: A 15-year-period cross-sectional study

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Fabiana Caroline daSilva

2016-01-01

Full Text Available Background: Studies assessing the prevalence of oral lesions in children and adolescents, particularly in gingiva are scarce in the literature. The aim of the study was to describe the distribution of gingival proliferative lesions based on clinical and histopathological diagnoses in children and adolescents. Materials and Methods: A review of clinical charts of children and adolescents aged between 0 and 18 years old, admitted to the Oral Medicine Outpatient Unit, of Universidade Federal do Paraná, for 15 years (1994–2009 was performed. Results: Six hundred and sixty-nine out of 5,129 patients treated during this period were aged between 0 and 18 years old, and 45 of these had gingival lesions. The largest number of lesions was observed between 11 and 16 years old. The majority of the patients were referred by Curitiba's public health system. Pyogenic granuloma was the most frequent lesion (19 = 42.2%, followed by peripheral giant cell lesion (11 = 24.4%, gingival fibromatosis (10 = 22.2%, and peripheral ossifying fibroma (5 = 11.1%. Conclusion: Gingival proliferative lesions can show similar clinical characteristics. Appropriate clinical and histopathological diagnoses are necessary to guide the healthcare professional to establish the adequate treatment and to estimate the risk of recurrence.

Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production

DEFF Research Database (Denmark)

Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

2000-01-01

Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year...

HURTLE CELLS IMMUNOHISTOCHEMICAL ACTIVITIES IN HASHIMOTO THYROIDITIS PARENCHYMA.

Science.gov (United States)

Tsagareli, Z; Kvachadze, T; Melikadze, E; Metreveli, L; Nikobadze, E; Gogiashvili, L

2016-11-01

The present study was designed to evaluate the participation and utility of Hǘrtle cells morphological requirment and transformation under Hashimoto autoimmune thyroiditis versus Riedel´s struma. Several markers have been evaluated to detect induced activities of Hǘrtle cells. Study subject - specimens (tissue fragments) collected from TG surgery (thyroidectomy) for mollecular (receptor) diagnosis of Hǘrtle cells activities using routine histological and immunohistochemical samples. 89 cases were selected in Hashimoto thyroiditis diagnosis with Hǘrtle cells history (adenoma and adenomatous grouth of oncocytes). Markers as: TSH receptors, TTF-1, S-100 protein, also anti-TPO and anti-TG levels in blood plasm were detected. It was shown that solid cell claster-nests like agregation of oncocytes and adenomatous growth foci in parafollicular areas with anti-TPO and anti-TG antibodies levels arising while Riedel´s struma shown only large intra- and extra glandular inflammatory proliferative fibrosing process. Large positive expression of TTF-1 and S-100 protein and the negative reaction of TSH receptor factor suggest that Thyroid parenchyma disorganization and mollecular biological atypia with Hǘrtle cells are proceses due to hypothyreoidismus, as well as neuroectodermal cells prominent activities in 70% of Hashimoto cases.

Automated detection of neovascularization for proliferative diabetic retinopathy screening.

Science.gov (United States)

Roychowdhury, Sohini; Koozekanani, Dara D; Parhi, Keshab K

2016-08-01

Neovascularization is the primary manifestation of proliferative diabetic retinopathy (PDR) that can lead to acquired blindness. This paper presents a novel method that classifies neovascularizations in the 1-optic disc (OD) diameter region (NVD) and elsewhere (NVE) separately to achieve low false positive rates of neovascularization classification. First, the OD region and blood vessels are extracted. Next, the major blood vessel segments in the 1-OD diameter region are classified for NVD, and minor blood vessel segments elsewhere are classified for NVE. For NVD and NVE classifications, optimal region-based feature sets of 10 and 6 features, respectively, are used. The proposed method achieves classification sensitivity, specificity and accuracy for NVD and NVE of 74%, 98.2%, 87.6%, and 61%, 97.5%, 92.1%, respectively. Also, the proposed method achieves 86.4% sensitivity and 76% specificity for screening images with PDR from public and local data sets. Thus, the proposed NVD and NVE detection methods can play a key role in automated screening and prioritization of patients with diabetic retinopathy.

Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture

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Antoniana Batsivari

2017-06-01

Full Text Available During development, hematopoietic stem cells (HSCs emerge in the aorta-gonad-mesonephros (AGM region through a process of multi-step maturation and expansion. While proliferation of adult HSCs is implicated in the balance between self-renewal and differentiation, very little is known about the proliferation status of nascent HSCs in the AGM region. Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, we detect increased proliferation during pre-HSC expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs. We observe time-specific changes in intra-aortic hematopoietic clusters corresponding to HSC maturation stages. The proliferative architecture of the clusters is maintained in an orderly anatomical manner with slowly cycling cells at the base and more actively proliferating cells at the more apical part of the cluster, which correlates with c-KIT expression levels, thus providing an anatomical basis for the role of SCF in HSC maturation.

MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of pulmonary vascular fibroblasts.

Science.gov (United States)

Wang, Daren; Zhang, Hui; Li, Min; Frid, Maria G; Flockton, Amanda R; McKeon, B Alexandre; Yeager, Michael E; Fini, Mehdi A; Morrell, Nicholas W; Pullamsetti, Soni S; Velegala, Sivareddy; Seeger, Werner; McKinsey, Timothy A; Sucharov, Carmen C; Stenmark, Kurt R

2014-01-03

Pulmonary hypertensive remodeling is characterized by excessive proliferation, migration, and proinflammatory activation of adventitial fibroblasts. In culture, fibroblasts maintain a similar activated phenotype. The mechanisms responsible for generation/maintenance of this phenotype remain unknown. We hypothesized that aberrant expression of microRNA-124 (miR-124) regulates this activated fibroblast phenotype and sought to determine the signaling pathways through which miR-124 exerts effects. We detected significant decreases in miR-124 expression in fibroblasts isolated from calves and humans with severe pulmonary hypertension. Overexpression of miR-124 by mimic transfection significantly attenuated proliferation, migration, and monocyte chemotactic protein-1 expression of hypertensive fibroblasts, whereas anti-miR-124 treatment of control fibroblasts resulted in their increased proliferation, migration, and monocyte chemotactic protein-1 expression. Furthermore, the alternative splicing factor, polypyrimidine tract-binding protein 1, was shown to be a direct target of miR-124 and to be upregulated both in vivo and in vitro in bovine and human pulmonary hypertensive fibroblasts. The effects of miR-124 on fibroblast proliferation were mediated via direct binding to the 3' untranslated region of polypyrimidine tract-binding protein 1 and subsequent regulation of Notch1/phosphatase and tensin homolog/FOXO3/p21Cip1 and p27Kip1 signaling. We showed that miR-124 directly regulates monocyte chemotactic protein-1 expression in pulmonary hypertension/idiopathic pulmonary arterial hypertension fibroblasts. Furthermore, we demonstrated that miR-124 expression is suppressed by histone deacetylases and that treatment of hypertensive fibroblasts with histone deacetylase inhibitors increased miR-124 expression and decreased proliferation and monocyte chemotactic protein-1 production. Stable decreases in miR-124 expression contribute to an epigenetically reprogrammed, highly

Upregulation of Mir-21 Levels in the Vitreous Humor Is Associated with Development of Proliferative Vitreoretinal Disease.

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Ayumi Usui-Ouchi

Full Text Available MicroRNAs (miRNAs are small noncoding RNAs that regulate gene expression by post-transcriptional inhibition of mRNA translation. Dysregulation of miRNAs, including circulating miRNAs, has been reported to play an important role in the development of various diseases, including fibrotic diseases. Aberrant expression of miRNAs in the vitreous humor of vitreoretinal diseased eyes has been reported. However, the expression pattern of miRNAs present in the vitreous humor of proliferative vitreoretinal disease (PVD patients, including proliferative diabetic retinopathy (PDR, and proliferative vitreoretinopathy (PVR, remains unknown. To investigate the factors important for the development of PVD, we characterized the miRNAs present in the vitreous humor of PVD patients and analyzed the expression profiles of 377 miRNAs using quantitative polymerase chain reaction-based miRNA arrays. The expression of a specific subset of miRNAs, previously reported to be associated with the development of angiogenesis and fibrosis, was significantly altered in the vitreous of PVD patients. Among these miRNAs, we identified miR-21 as a candidate fibrotic miRNA with an important role in the pathogenesis of PVD. Increased miR-21 levels in the vitreous were associated with retinal fibrosis, including PVR and PDR. Because epithelial-mesenchymal transition (EMT of retinal pigment epithelial cells (RPECs plays a critical role in retinal fibrosis, the expression of miR-21 in human RPECs was determined. Its expression in RPECs was induced by transforming growth factor-β, a key growth factor involved in fibrogenesis, and was enhanced by high glucose culture conditions, suggesting that miR-21 expression positively correlates with disease progression. Gain- and loss-of-function studies revealed that miR-21 promoted cell proliferation and migration of ARPE-19 cells without affecting EMT-related gene expression. Together, our studies have identified miR-21 as a potential disease

The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

Science.gov (United States)

Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

2016-03-01

Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Coordination Skills during Vitrectomy in Treatment of Proliferative Diabetic Retinopathy

Institute of Scientific and Technical Information of China (English)

Xuehong Chen; Shanshan Luo; Yanchan Liu

2014-01-01

Purpose:.To discuss effective nursing and coordination skills for vitrectomy in the treatment of diabetic retinopathy. Methods: Fifty patients (51 eyes) with diabetic retinopathy required vitrectomy were enrolled in this study..Individual nursing service was delivered by strengthening preoperative preparation, providing psychological nursing, and intraopera-tive observation of the severity of diseases by circulating nurses;meticulous nursing was given postoperatively. Results:All 50 patients underwent surgery successfully..Intra-operatively,.patients had stable physical signs..Five patients had postoperative visual acuity0.3..No complicated infection was seen. Conclusion: For patients diagnosed with proliferative diabetic retinopathy requiring vitrectomy,.full preparations should be made and psychological nursing should be delivered preopera-tively, the severity of diseases and clinical reactions should be closely observed intraoperatively,.and proper processing and nursing measures should be taken postoperatively,.which col-lectively enhance surgical success rate,.decrease surgical com-plications,.and attain favorable treatment efficacy.(Eye Science 2014; 29:55-58).

Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

International Nuclear Information System (INIS)

Wada, Hiromichi; Abe, Mitsuru; Ono, Koh; Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide; Satoh, Noriko; Fujita, Masatoshi; Kita, Toru; Shimatsu, Akira; Hasegawa, Koji

2008-01-01

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 μM of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-α-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 μM), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs

Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Wada, Hiromichi [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Abe, Mitsuru; Ono, Koh [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Satoh, Noriko [Division of Metabolic Research, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Fujita, Masatoshi [Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kita, Toru [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Shimatsu, Akira [Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Hasegawa, Koji [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan)

2008-10-03

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 {mu}M of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-{alpha}-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 {mu}M), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs.

Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy

Directory of Open Access Journals (Sweden)

Jose Dalma-Weiszhausz

2012-01-01

Full Text Available Proliferative vitreoretinopathy (PVR is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis.

Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy

Science.gov (United States)

Dalma-Weiszhausz, Jose; Franco-Cardenas, Valentina; Dalma, Alejandro

2012-01-01

Proliferative vitreoretinopathy (PVR) is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL) is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis. PMID:23502847

Development of methods for evaluating active faults

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-08-15

The report for long-term evaluation of active faults was published by the Headquarters for Earthquake Research Promotion on Nov. 2010. After occurrence of the 2011 Tohoku-oki earthquake, the safety review guide with regard to geology and ground of site was revised by the Nuclear Safety Commission on Mar. 2012 with scientific knowledges of the earthquake. The Nuclear Regulation Authority established on Sep. 2012 is newly planning the New Safety Design Standard related to Earthquakes and Tsunamis of Light Water Nuclear Power Reactor Facilities. With respect to those guides and standards, our investigations for developing the methods of evaluating active faults are as follows; (1) For better evaluation on activities of offshore fault, we proposed a work flow to date marine terrace (indicator for offshore fault activity) during the last 400,000 years. We also developed the analysis of fault-related fold for evaluating of blind fault. (2) To clarify the activities of active faults without superstratum, we carried out the color analysis of fault gouge and divided the activities into thousand of years and tens of thousands. (3) To reduce uncertainties of fault activities and frequency of earthquakes, we compiled the survey data and possible errors. (4) For improving seismic hazard analysis, we compiled the fault activities of the Yunotake and Itozawa faults, induced by the 2011 Tohoku-oki earthquake. (author)

ANTIBACTERIAL ACTIVITY OF BENTHIC MARINE ALGAE EXTRACTS FROM THE MEDITERRANEAN COAST OF MOROCCO

Directory of Open Access Journals (Sweden)

Hanaâ Zbakh

2012-08-01

Full Text Available Marine organisms are potentially prolific sources of highly bioactive secondary metabolites that might represent useful leads in the development of new pharmaceutical agents. The Moroccan marine biodiversity including macroalgae remains partially unexplored in term of their potential bioactivities. Antibacterial activity of methanolic extracts from 20 species of macroalgae (9 Chlorophyta, 3 Phaeophyta and 8 Rhodophyta collected from Moroccan Mediterranean coasts was evaluated against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis. The extracts of the studied Rhodophyceae inhibited considerably the growth of the three tested bacterial strains and gave inhibition zones between 20 and 24 mm. The results indicate that these species of seaweed present a significant capacity of antibacterial activities, which makes them interesting for screening for natural products.

Lyn kinase is activated following thrombopoietin stimulation of the megakaryocytic cell line B1647

DEFF Research Database (Denmark)

Santini, Valeria; Scappini, Barbara; Gozzini, Antonella

2002-01-01

BACKGROUND AND OBJECTIVES: B1647 is a cell line derived from bone marrow cells of a patient with acute myeloid leukemia (M2) with a complete erythro-megakaryocytic phenotype and bears both k and p isoforms of c-mpl. Interestingly, spontaneous B1647 cell proliferation is significantly potentiated...... by thrombopoietin (TPO). DESIGN AND METHODS: We aimed to evaluate the proliferative signal transduction events following the activation of c-mpl and we stimulated B1647 cells with TPO 40 ng/mL for 3, 7, 15 and 30 minutes; cells were then lysed and whole lysates were immunoprecipitated with anti...

Myeloid-Related Protein-14/MRP-14/S100A9/Calgranulin B is Associated with Inflammation in Proliferative Diabetic Retinopathy.

Science.gov (United States)

Abu El-Asrar, Ahmed M; Alam, Kaiser; Siddiquei, Mohammad M; Van den Eynde, Kathleen; Mohammad, Ghulam; De Hertogh, Gert; Opdenakker, Ghislain

2018-01-01

To investigate the expression of the leukocyte proteins myeloid-related protein (MRP)-8 and MRP-14 in proliferative diabetic retinopathy (PDR) and the effect of MRP-8/MRP-14 (calprotectin) heterodimer on induction of proinflammatory factors in human retinal microvascular endothelial cells (HRMEC). Epiretinal membranes from 20 patients with PDR and 10 patients with proliferative vitreoretinopathy (PVR), vitreous fluid samples from PDR and non-diabetic subjects and HRMEC were studied by immunohistochemistry and Western blot analysis. MRP-14 expression was localized in endothelial cells, leukocytes and myofibroblasts in all PDR membranes. MRP-8 expression was limited to intravascular leukocytes in 42% of the studied membranes. In PVR membranes, MRP-14 was expressed in leukocytes and myofibroblasts, whereas MRP-8 immunoreactivity was limited to leukocytes. MRP-14 was significantly upregulated in vitreous from PDR patients. MRP-8/MRP-14 (calprotectin) increased expression of intercellular adhesion molecule-1, but attenuated vascular cell adhesion molecule-1 expression in HRMEC. Increased MRP-14 levels are associated with inflammation in PDR.

Compositions and methods involving methyladenosine phosphorylase in the diagnosis and treatment of proliferative disorders

Science.gov (United States)

Olopade, Olufunmilayo I.

2007-03-20

Disclosed are novel nucleic acid and peptide compositions comprising methylthioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and identification of tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML).

Science.gov (United States)

Guan, Y; Hogge, D E

2000-12-01

One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard

High fructose-mediated attenuation of insulin receptor signaling does not affect PDGF-induced proliferative signaling in vascular smooth muscle cells.

Science.gov (United States)

Osman, Islam; Poulose, Ninu; Ganapathy, Vadivel; Segar, Lakshman

2016-11-15

Insulin resistance is associated with accelerated atherosclerosis. Although high fructose is known to induce insulin resistance, it remains unclear as to how fructose regulates insulin receptor signaling and proliferative phenotype in vascular smooth muscle cells (VSMCs), which play a major role in atherosclerosis. Using human aortic VSMCs, we investigated the effects of high fructose treatment on insulin receptor substrate-1 (IRS-1) serine phosphorylation, insulin versus platelet-derived growth factor (PDGF)-induced phosphorylation of Akt, S6 ribosomal protein, and extracellular signal-regulated kinase (ERK), and cell cycle proteins. In comparison with PDGF (a potent mitogen), neither fructose nor insulin enhanced VSMC proliferation and cyclin D1 expression. d-[ 14 C(U)]fructose uptake studies revealed a progressive increase in fructose uptake in a time-dependent manner. Concentration-dependent studies with high fructose (5-25mM) showed marked increases in IRS-1 serine phosphorylation, a key adapter protein in insulin receptor signaling. Accordingly, high fructose treatment led to significant diminutions in insulin-induced phosphorylation of downstream signaling components including Akt and S6. In addition, high fructose significantly diminished insulin-induced ERK phosphorylation. Nevertheless, high fructose did not affect PDGF-induced key proliferative signaling events including phosphorylation of Akt, S6, and ERK and expression of cyclin D1 protein. Together, high fructose dysregulates IRS-1 phosphorylation state and proximal insulin receptor signaling in VSMCs, but does not affect PDGF-induced proliferative signaling. These findings suggest that systemic insulin resistance rather than VSMC-specific dysregulation of insulin receptor signaling by high fructose may play a major role in enhancing atherosclerosis and neointimal hyperplasia. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-mitotic activity towards sea urchin eggs of dichloromethane fraction obtained from Allamanda schottii Pohl (Apocynaceae

Directory of Open Access Journals (Sweden)

Louisa M. A. Sousa

Full Text Available Allamanda (Apocynaceae is a genus of climbing shrubs known for producing compounds with a range of biological activities. Previous works have shown the anti-proliferative effect of the ethanolic extract of Allamanda schottii on leukemic cells. The present work was conducted to evaluate the effects of dichloromethane fraction, obtained from Allamanda schottii, on sea urchin Echinometra lucunter eggs, as a multicellular model for evaluating anti-tumor activity. Our results show an inhibition of sea urchin development in a dose-dependent manner in the presence of dichloromethane fraction. The IC50 values for first and third cleavage and blastulae stage were 103.7 µg/mL, 33.1 µg/mL and 10.2 µg/mL, respectively. These results also demonstrate the cumulative effect of this fraction on sea urchin embryos. In the present work, the expressive anti-mitotic activity of dichloromethane fraction towards sea urchin eggs, a multicellular model, reinforces the anti-tumor potential of the Allamanda schotti.

Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

Science.gov (United States)

Anwar, Adil; Li, Min; Frid, Maria G.; Kumar, Binod; Gerasimovskaya, Evgenia V.; Riddle, Suzette R.; McKeon, B. Alexandre; Thukaram, Roopa; Meyrick, Barbara O.; Fini, Mehdi A.

2012-01-01

Increased cell proliferation and migration, of several cell types are key components of vascular remodeling observed in pulmonary hypertension (PH). Our previous data demonstrate that adventitial fibroblasts isolated from pulmonary arteries of chronically hypoxic hypertensive calves (termed PH-Fibs) exhibit a “constitutively activated” phenotype characterized by high proliferative and migratory potential. Osteopontin (OPN) has been shown to promote several cellular activities including growth and migration in cancer cells. We thus tested the hypothesis that elevated OPN expression confers the “activated” highly proproliferative and promigratory/invasive phenotype of PH-Fibs. Our results demonstrate that, both in vivo and ex vivo, PH-Fibs exhibited increased expression of OPN, as well as its cognate receptors, αVβ3 and CD44, compared with control fibroblasts (CO-Fibs). Augmented OPN expression in PH-Fibs corresponded to their high proliferative, migratory, and invasive properties and constitutive activation of ERK1/2 and AKT signaling. OPN silencing via small interfering RNA or sequestering OPN production by specific antibodies led to decreased proliferation, migration, invasion, and attenuated ERK1/2, AKT phosphorylation in PH-Fibs. Furthermore, increasing OPN levels in CO-Fibs via recombinant OPN resulted in significant increases in their proliferative, migratory, and invasive capabilities to the levels resembling those of PH-Fibs. Thus our data suggest OPN as an essential contributor to the activated (highly proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial fibroblasts in hypoxic PH. PMID:22582113

Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription.

Science.gov (United States)

Wang, Weiguang; Lian, Na; Li, Lingzhen; Moss, Heather E; Wang, Weixi; Perrien, Daniel S; Elefteriou, Florent; Yang, Xiangli

2009-12-01

Activating transcription factor 4 (Atf4) is a leucine-zipper-containing protein of the cAMP response element-binding protein (CREB) family. Ablation of Atf4 (Atf4(-/-)) in mice leads to severe skeletal defects, including delayed ossification and low bone mass, short stature and short limbs. Atf4 is expressed in proliferative and prehypertrophic growth plate chondrocytes, suggesting an autonomous function of Atf4 in chondrocytes during endochondral ossification. In Atf4(-/-) growth plate, the typical columnar structure of proliferative chondrocytes is disturbed. The proliferative zone is shortened, whereas the hypertrophic zone is transiently expanded. The expression of Indian hedgehog (Ihh) is markedly decreased, whereas the expression of other chondrocyte marker genes, such as type II collagen (Col2a1), PTH/PTHrP receptor (Pth1r) and type X collagen (Col10a1), is normal. Furthermore, forced expression of Atf4 in chondrocytes induces endogenous Ihh mRNA, and Atf4 directly binds to the Ihh promoter and activates its transcription. Supporting these findings, reactivation of Hh signaling pharmacologically in mouse limb explants corrects the Atf4(-/-) chondrocyte proliferation and short limb phenotypes. This study thus identifies Atf4 as a novel transcriptional activator of Ihh in chondrocytes that paces longitudinal bone growth by controlling growth plate chondrocyte proliferation and differentiation.

Papillary Tubal Hyperplasia. The Putative Precursor of Ovarian Atypical Proliferative (Borderline) Serous Tumors, Noninvasive Implants and Endosalpingiosis

Science.gov (United States)

Kurman, Robert J.; Vang, Russell; Junge, Jette; Hannibal, Charlotte Gerd; Kjaer, Susanne K.; Shih, Ie-Ming

2011-01-01

In contrast to the controversy regarding the terminology and behavior of ovarian noninvasive low-grade serous tumors (atypical proliferative serous tumor [APST] and serous borderline tumor [SBT]), little attention has been directed to their origin. Similarly, until recently, proliferative lesions in the fallopian tube have not been extensively studied. The recent proposal that ovarian high-grade serous carcinomas are derived from intraepithelial carcinoma in the fallopian tube prompted us to evaluate the possible role of the fallopian tube in the genesis of low-grade serous tumors. We have identified a lesion, designated “papillary tubal hyperplasia (PTH)”, characterized by small rounded clusters of tubal epithelial cells and small papillae, with or without associated psammoma bodies, that are present within the tubal lumen and which are frequently associated with APSTs. Twenty-two cases in this study were selected from a population-based study in Denmark of approximately 1000 patients with low-grade ovarian serous tumors in whom implants were identified on the fallopian tube. Seven additional cases were seen recently in consultation at The Johns Hopkins Hospital (JHH). These 7 cases were not associated with an ovarian tumor. Papillary tubal hyperplasia was found in 20 (91%) of the 22 cases in the Danish study. Based on this association of PTH with APSTs with implants and the close morphologic resemblance of PTH, not only to the primary ovarian APSTs but also to the noninvasive epithelial implants and endosalpingiosis, we speculate that the small papillae and clusters of cells from the fallopian tubes implant on ovarian and peritoneal surfaces to produce these lesions. The 7 JHH cases of PTH that were not associated with an ovarian tumor support the view that PTH is the likely precursor lesion. We propose a model for the development of ovarian and extraovarian low-grade serous proliferations (APST, noninvasive epithelial implants and endosalpingiosis) that

Making Women the Subjects of the Abortion Debate: A Class Exercise that Moves beyond "Pro-Choice" and "Pro-Life"

Science.gov (United States)

Crawley, Sara L.; Willman, Rebecca K.; Clark, Leisa; Walsh, Clare

2009-01-01

In this article, the authors describe a classroom exercise designed to put women (and children and men) back at the center of the abortion debate, avoiding the standard rhetoric and engaging reflection on how everyone might find common political goals among the so-called pro-life and pro-choice sides. The exercise the authors offer in this article…

Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients

DEFF Research Database (Denmark)

Tarnow, L; Cambien, Francois; Rossing, P

1995-01-01

Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of diabetic nephropathy and proliferative retinopathy. We studied the relationship between an insertion(I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene...... (40%) had proliferative retinopathy, and 67 patients (17%) had no diabetic retinopathy. There was no difference in genotype distribution between IDDM patients with diabetic nephropathy and those with normalbuminuria: 63 (32%)/95 (48%)/40 (20%) vs. 67 (35%)/77 (41%)/46 (24%) had DD/ID/II genotypes...... by ACE/ID polymorphism, mean arterial blood pressure, and glomerular filtration rate (r2 = 0.30, P retinopathy and those without diabetic retinopathy: 52 (34%)/74 (48%)/29 (19%) vs. 26 (39%)/25 (37...

Actual Proliferating Index and p53 protein expression as prognostic marker in odontogenic cysts.

Science.gov (United States)

Gadbail, A R; Chaudhary, M; Patil, S; Gawande, M

2009-10-01

The purpose of this study was to evaluate the biological aggressiveness of odontogenic keratocyst/keratocystic odontogenic tumour (KCOT), radicular cyst (RC) and dentigerous cyst (DC) by observing the actual proliferative activity of epithelium, and p53 protein expression. The actual proliferative activity was measured by Ki-67 Labelling Index and argyrophilic nucleolar organizing regions (AgNOR) count per nucleus. The p53 protein expression was also evaluated. Ki-67 positive cells were observed higher in suprabasal cell layers of KCOT with uniform distribution, a few of them were predominantly observed in basal cell layer in RC and DC. The AgNOR count was significantly higher in suprabasal cell layers of KCOT. The actual proliferative activity was noted to be higher in suprabasal cell layers of KCOT. The p53 immunolabelling was dense and scattered in basal and suprabasal cell layers in KCOT. The weakly stained p53 positive cells were observed diffusely distributed in KCOT, whereas they were mainly seen in basal cell layer of RC and DC. The quantitative and qualitative differences of the proliferative activity and the p53 protein expression in sporadic KCOT may be associated with intrinsic growth potential that could play a role in its development and explain locally aggressive biological behaviour. AgNOR count and p53 protein detection in odontogenic lesions can be of great consequence to predict the biological behaviour and prognosis.

Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male athlete

LENUS (Irish Health Repository)

Mc Hugh, N

2017-08-01

We describe the case of a 20-year-old rower presenting with an uncommon condition of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare, benign tumour infrequently developing in the upper back. Its rapid growth and firm consistency may mistake it for sarcoma at presentation. Therefore, careful multidisciplinary work-up is crucial, and should involve appropriate radiological and histopathological investigations. Here, we propose the aetiology of LD PM to be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate of progression ultimately determine the management which includes surveillance and\\/or conservative resection. There have been no documented cases of recurrence or malignant transformation.

Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of NADPH oxidase 1 and the alteration of mitochondrial morphology and dynamics.

Science.gov (United States)

Shen, Kaikai; Lu, Fangfang; Xie, Jianling; Wu, Minfeng; Cai, Bo; Liu, Yurong; Zhang, Hong; Tan, Hongsheng; Pan, Yingyi; Xu, Hongxi

2016-08-02

Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1.

Antiproliferative Activity and Chemical Constituents of Hypericum dyeri. Rehder

International Nuclear Information System (INIS)

Ali, M.; Arfan, M.; Zaman, K.

2013-01-01

The antiproliferative activity of hexane (F1), ethyl acetate (F2), butanol (F3) and water (F4) extracts of Hypericum dyeri were tested in vitro for their anti- proliferative (anticancer) activity on the cell lines: HT-29 human colon adenocarcinoma, NCI-H460 human non-small cell lung carcinoma, MCF-7 human breast cancer, OVCAR-3 human ovarian adenocarcinoma and RXF-393 human renal cell carcinoma with etoposide as positive control. Among the various extracts the F1 showed relatively potent anti-proliferative activity (IC50, 17.20 +- 4.80 micro g/mL) on NCI-H460 human non-small cell lung carcinoma cell growth. Six compounds were also isolated for the first time from this source. These phytochemicals were identified as 1-Octatriacontanol (1), Hexacosyl tetracosanoate (2), Geddic acid (3), Octacosanoic acid (4), Ceric acid (5) and Sitosterol (6) on the basis of spectroscopic studies such as 1H NMR ,13C NMR, 2D NMR and Mass spectroscopy as well as established with help of reported literature. (author)

Study on the evaluation index of active power reserve

Science.gov (United States)

Guo, Xiaorui; Liu, Jiantao; Wang, Ke; Min, Lu

2018-01-01

Based on the role of active reserve at different time scales, divides the evaluation dimension of active reserve. Analysis the calculation principle of traditional reliability index such as probability of system safety, lack of power shortage and electricity shortage expectancy, and studies the applicability of these indicators to evaluate the reserve capacity on different dimensions. Resolves the evaluation index of active reserve capacity from the dimensions of time dimension, spatial dimension, system state, risk degree and economy, then construct evaluation index of active reserve capacity.

Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture.

Science.gov (United States)

Batsivari, Antoniana; Rybtsov, Stanislav; Souilhol, Celine; Binagui-Casas, Anahi; Hills, David; Zhao, Suling; Travers, Paul; Medvinsky, Alexander

2017-06-06

During development, hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region through a process of multi-step maturation and expansion. While proliferation of adult HSCs is implicated in the balance between self-renewal and differentiation, very little is known about the proliferation status of nascent HSCs in the AGM region. Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, we detect increased proliferation during pre-HSC expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs. We observe time-specific changes in intra-aortic hematopoietic clusters corresponding to HSC maturation stages. The proliferative architecture of the clusters is maintained in an orderly anatomical manner with slowly cycling cells at the base and more actively proliferating cells at the more apical part of the cluster, which correlates with c-KIT expression levels, thus providing an anatomical basis for the role of SCF in HSC maturation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human telomerase activity regulation

OpenAIRE

Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

2010-01-01

Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

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Chaojun Qi

Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an

Methylthioadenosine phosphorylase compositions and methods of use in the diagnosis and treatment of proliferative disorders

Science.gov (United States)

Olopade, Olufunmilayo I.

2005-03-22

Disclosed are novel nucleic acid and peptide compositions comprising methythlioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and idenification tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

Active spectral imaging nondestructive evaluation (SINDE) camera

Energy Technology Data Exchange (ETDEWEB)

Simova, E.; Rochefort, P.A., E-mail: eli.simova@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada)

2016-06-15

A proof-of-concept video camera for active spectral imaging nondestructive evaluation has been demonstrated. An active multispectral imaging technique has been implemented in the visible and near infrared by using light emitting diodes with wavelengths spanning from 400 to 970 nm. This shows how the camera can be used in nondestructive evaluation to inspect surfaces and spectrally identify materials and corrosion. (author)

Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

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Bérengère Gobin

Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

Development of methods for evaluating active faults

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-08-15

The HERP report for long-term evaluation of active faults and the NSC safety review guide with regard to geology and ground of site were published on Nov. 2010 and on Dec. 2010, respectively. With respect to those reports, our investigation is as follows; (1) For assessment of seismic hazard, we estimated seismic sources around NPPs based on information of tectonic geomorphology, earthquake distribution and subsurface geology. (2) For evaluation on the activity of blind fault, we calculated the slip rate on the 2008 Iwate-Miyagi Nairiku Earthquake fault, using information on late Quaternary fluvial terraces. (3) To evaluate the magnitude of earthquakes whose sources are difficult to identify, we proposed a new method for calculation of the seismogenic layer thickness. (4) To clarify the activities of active faults without superstratum, we carried out the color analysis of fault gouge and divided the activities into thousand of years and tens of thousands. (5) For improving chronology of sediments, we detected new widespread cryptotephras using mineral chemistry and developed late Quaternary cryptotephrostratigraphy around NPPs. (author)

Proliferative, reparative, and reactive benign bone lesions that may be confused diagnostically with true osseous neoplasms.

LENUS (Irish Health Repository)

Wick, Mark R

2014-01-01

Diagnostic problems attending intraosseous and parosteal pseudoneoplastic lesions can be radiographic, or histological, or both. Proliferations in this category may contain cellular fibro-osseous or chondro-osseous tissues that are difficult to separate microscopically from those seen in various true neoplasms of the bones. This review considers the clinicopathologic features of fibrous dysplasia, benign fibro-osseous lesions of the jawbones, osteofibrous dysplasia, metaphyseal fibrous defect, giant-cell reparative granuloma, "brown tumor" of hyperparathyroidism, synovial chondrometaplasia, aneurysmal bone cyst, tumefactive chronic osteomyelitis, proliferative Paget disease, and polyvinylpyrrolidone storage disease of bone.

Histological and morphological evaluation of condylar cartilage of young rats in response to stimulation of mandibular protrusion

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Milena Peixoto Nogueira de Sá

2017-08-01

Full Text Available The aim of this study was to evaluate the histogical and morphological aspects of the condyle in response to mandibular protrusion induced by composite resin occlusal planes. Thirty five-week-old male Wistar rats were selected and randomly divided in two groups. One group received a composite resin type of oclusal plane that induced mandibular protrusion, and the other was the control group, without treatment. Animals were euthanized after experimental time intervals of 7, 21 and 30 days. For histological analysis, thickness of the proliferative, serial and hypertrophic layers was measured, as well as each layer separately. The highest difference in cartilage thickness was observed at day 21, showing a significant increase of the proliferative layer. There were also other histomorphological changes related to occlusal plane interference. Condylar forward repositioning induced by composite occlusal planes influenced the endochondral ossification, increasing the proliferative layer.

Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators.

Science.gov (United States)

Li, Ridong; Ning, Xianling; Zhou, Shuo; Lin, Zhiqiang; Wu, Xingyu; Chen, Hong; Bai, Xinyu; Wang, Xin; Ge, Zemei; Li, Runtao; Yin, Yuxin

2018-01-01

Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti-proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC 50 values from 0.46 μM to 0.81 μM against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

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Charles C Peyton

Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

Evaluation of nuclear reactor based activation analysis techniques

International Nuclear Information System (INIS)

Obrusnik, I.; Kucera, J.

1977-09-01

A survey is presented of the basic types of activation analysis applied in environmental control. Reactor neutron activation analysis is described (including the reactor as a neutron source, sample activation in the reactor, methodology of neutron activation analysis, sample transport into the reactor and sample packaging after irradiation, instrumental activation analysis with radiochemical separation, data measurement and evaluation, sampling and sample preparation). Sources of environmental contamination with trace elements, sampling and sample analysis by neutron activation are described. The analysis is described of soils, waters and biological materials. Methods are shown of evaluating neutron activation analysis results and of their interpretation for purposes of environmental control. (J.B.)

Genetic control of murine T cell proliferative responses to Mycobacterium leprae. V. Evidence for cross-reactivity between host antigens and Mycobacterium leprae

Energy Technology Data Exchange (ETDEWEB)

Harris, D.P.; Jones, A.G.; Wade, S.; Krahenbuhl, J.L.; Gillis, T.P.; Watson, J.D.

1988-09-01

T cell proliferative responses to Mycobacterium leprae were measured by immunization of mice at the base of the tail with Ag and challenging lymphocytes from draining lymph nodes in culture with M. leprae. C57BL/10J and B10.BR mice were identified as low responder mice and the congenic strains B10.M, B10.Q, and B10.AKM as high responders whereas F1 (high x low) hybrid mice were found to be low responders. The cellular basis of low responsiveness did not appear to result from a defect in Ag-presenting cells or the activation of suppressor T cells by M. leprae. The influence of the environment in which T cells developed on responsiveness to M. leprae was analyzed in chimeric mice prepared by irradiating F1(C57BL/10J x B10.M) mice and reconstituting with bone marrow from C57BL/10J, B10.M, or F1 donors. Six weeks later, chimeric mice were immunized with M. leprae, lymph node cells were subsequently prepared, and H-2 phenotyped and challenged in culture with M. leprae Ag. T cell proliferative responses were found to be low in all cases, similar to those observed using lymph node cells from F1 hybrid mice. These results suggested that high responder B10.M lymphocytes developing in the irradiated F1 mice became tolerized to antigenic determinants found on M. leprae. This implied cross-reactive epitopes existed between some mouse strains and M. leprae. Low responsiveness to M. leprae in low responder and F1 hybrid mice may result from tolerance to H-2-encoded Ag that show cross-reactivity with M. leprae.

Genetic control of murine T cell proliferative responses to Mycobacterium leprae. V. Evidence for cross-reactivity between host antigens and Mycobacterium leprae

International Nuclear Information System (INIS)

Harris, D.P.; Jones, A.G.; Wade, S.; Krahenbuhl, J.L.; Gillis, T.P.; Watson, J.D.

1988-01-01

T cell proliferative responses to Mycobacterium leprae were measured by immunization of mice at the base of the tail with Ag and challenging lymphocytes from draining lymph nodes in culture with M. leprae. C57BL/10J and B10.BR mice were identified as low responder mice and the congenic strains B10.M, B10.Q, and B10.AKM as high responders whereas F1 (high x low) hybrid mice were found to be low responders. The cellular basis of low responsiveness did not appear to result from a defect in Ag-presenting cells or the activation of suppressor T cells by M. leprae. The influence of the environment in which T cells developed on responsiveness to M. leprae was analyzed in chimeric mice prepared by irradiating F1(C57BL/10J x B10.M) mice and reconstituting with bone marrow from C57BL/10J, B10.M, or F1 donors. Six weeks later, chimeric mice were immunized with M. leprae, lymph node cells were subsequently prepared, and H-2 phenotyped and challenged in culture with M. leprae Ag. T cell proliferative responses were found to be low in all cases, similar to those observed using lymph node cells from F1 hybrid mice. These results suggested that high responder B10.M lymphocytes developing in the irradiated F1 mice became tolerized to antigenic determinants found on M. leprae. This implied cross-reactive epitopes existed between some mouse strains and M. leprae. Low responsiveness to M. leprae in low responder and F1 hybrid mice may result from tolerance to H-2-encoded Ag that show cross-reactivity with M. leprae

Retinitis pigmentosa reduces the risk of proliferative diabetic retinopathy: a nationwide population-based cohort study.

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Yuh-Fang Chen

Full Text Available PURPOSE: To study the association between retinitis pigmentosa (RP and the progression of diabetic retinopathy (DR. METHODS: Using the Longitudinal Health Insurance Database 2000 of Taiwan, we identified individuals with an initial diagnosis for RP during the period of 1997-2008. A non-RP comparison group, 10-fold frequency matched by sex, age, index year and the year of diabetes diagnosed, were randomly selected from the same database. The occurrence of DR was observed for all subjects until the end of 2009. The Kaplan-Meier curves were used to illustrate the cumulative probability of developing DR for the RP group and comparison groups. The hazard ratio (HR of DR for the RP group relative to the comparison group was estimated using Cox proportional hazards model after adjusting for potential confounders. RESULTS: The Kaplan-Meier curves were not statistically significant different between the RP group and the comparison group. However, the RP group had a higher cumulative probability of developing DR during the first six to seven years. The cumulative probability kept increasing and became higher in the comparison group but remained unchanged in the RP group. The HR for the RP patients comparing with the comparison group was 0.96 (95% confidence interval (CI = 0.43-2.14. Stratified by severity, RP was associated with a non-statistically significant reduced risk of proliferative DR (PDR (HR = 0.70, 95% CI = 0.16-3.14. The HR for non-proliferative DR (NPDR was 1.08 (95% CI = 0.40-2.86. CONCLUSION: In this study, RP was not statistically significant associated with the incidence of DR.

Serum level of expressed in renal carcinoma (ERC)/ mesothelin in rats with mesothelial proliferative lesions induced by multi-wall carbon nanotube (MWCNT).

Science.gov (United States)

Sakamoto, Yoshimitsu; Dai, Nakae; Hagiwara, Yoshiaki; Satoh, Kanako; Ohashi, Norio; Fukamachi, Katsumi; Tsuda, Hiroyuki; Hirose, Akihiko; Nishimura, Tetsuji; Hino, Okio; Ogata, Akio

2010-04-01

Expressed in renal carcinoma (ERC)/mesothelin is a good biomarker for human mesothelioma and has been investigated for its mechanistic rationale during the mesothelioma development. Studies are thus ongoing in our laboratories to assess expression of ERC/mesothelin in sera and normal/proliferative/neoplastic mesothelial tissues of animals untreated or given potentially mesothelioma-inducible xenobiotics, by an enzyme-linked immunosorbent assay (ELISA) for N- and C-(terminal fragments of) ERC/mesothelin and immunohistochemistry for C-ERC/mesothelin. In the present paper, we intend to communicate our preliminary data, because this is the first report to show how and from what stage the ERC/mesothelin expression changes during the chemical induction of mesothelial proliferative/neoplatic lesions. Serum N-ERC/mesothelin levels were 51.4 +/- 5.6 ng/ml in control male Fischer 344 rats, increased to 83.6 +/- 11.2 ng/ml in rats given a single intrascrotal administration of 1 mg/kg body weight of multi-wall carbon nanotube (MWCNT) and bearing mesothelial hyperplasia 52 weeks thereafter, and further elevated to 180 +/- 77 ng/ml in rats similarly treated and becoming moribund 40 weeks thereafter, or killed as scheduled at the end of week 52, bearing mesothelioma. While C-ERC/mesothelin was expressed in normal and hyperplastic mesothelia, the protein was detected only in epithelioid mesothelioma cells at the most superficial layer. It is thus suggested that ERC/mesothelin can be used as a biomarker of mesothelial proliferative lesions also in animals, and that the increase of levels may start from the early stage and be enhanced by the progression of the mesothelioma development.

CASE REPORT OF SEVERE PROLIFERATIVE RETINOPATHY IN A PATIENT WITH CONGENITAL LIPODYSTROPHY.

Science.gov (United States)

Rosin, Boris; Jaouni, Tareq

2017-08-21

A case report of a patient with severe proliferative retinopathy due to congenital lipodystrophy. We reviewed the medical history, imaging, and surgical procedures of a 25-year-old woman with a history of congenital lipodystrophy, presenting with bilateral combined tractional and exudative retinal detachment, poorly controlled diabetes mellitus, and extreme dislipidemia. The patient underwent retinal detachment repair surgery both eyes. On the last follow-up, both retinae were flat, and visual acuity had improved in the right eye to J3 for near and finger counting 3 m for distance. Surgery combining pars plana vitrectomy and scleral bucking successfully flattened both retinae and significantly improved visual acuity in one eye in this case of bilateral retinal detachment with combined tractional and exudative components in a patient with congenital lipodystrophy. Surgical control of retinal complications is thus possible, provided there is adequate control of the underlying risk factors.

PI3K-independent AKT activation in cancers: a treasure trove for novel therapeutics.

Science.gov (United States)

Mahajan, Kiran; Mahajan, Nupam P

2012-09-01

AKT/PKB serine threonine kinase, a critical signaling molecule promoting cell growth and survival pathways, is frequently dysregulated in many cancers. Although phosphatidylinositol-3-OH kinase (PI3K), a lipid kinase, is well characterized as a major regulator of AKT activation in response to a variety of ligands, recent studies highlight a diverse group of tyrosine (Ack1/TNK2, Src, PTK6) and serine/threonine (TBK1, IKBKE, DNAPKcs) kinases that activate AKT directly to promote its pro-proliferative signaling functions. While some of these alternate AKT activating kinases respond to growth factors, others respond to inflammatory and genotoxic stimuli. A common theme emerging from these studies is that aberrant or hyperactivation of these alternate kinases is often associated with malignancy. Consequently, evaluating the use of small molecular inhibitors against these alternate AKT activating kinases at earlier stages of cancer therapy may overcome the pressing problem of drug resistance surfacing especially in patients treated with PI3K inhibitors. Copyright © 2012 Wiley Periodicals, Inc.

The evolution of the vertebrate cerebellum: absence of a proliferative external granule layer in a basal ray-finned fish

OpenAIRE

Butts, Thomas; Modrell, Melinda S.; Baker, Clare V. H.; Wingate, Richard J. T.

2014-01-01

The cerebellum represents one of the most morphologically variable structures in the vertebrate brain. To shed light on its evolutionary history, we have examined the molecular anatomy and proliferation of the developing cerebellum of the North American paddlefish, Polyodon spathula. Absence of an external proliferative cerebellar layer and the restriction of Atonal1 expression to the rhombic lip and valvular primordium demonstrate that transit amplification in a cerebellar external germinal ...

Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

Directory of Open Access Journals (Sweden)

Hanamura Ichiro

2006-10-01

Full Text Available Abstract Background A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results Thirteen of 40 (33% human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM tumors, but the prevalence is 6 to10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60% MM cell lines, and 30 of 50 (60% MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3% MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated

E1(-)E4(+) adenoviral gene transfer vectors function as a "pro-life" signal to promote survival of primary human endothelial cells.

Science.gov (United States)

Ramalingam, R; Rafii, S; Worgall, S; Brough, D E; Crystal, R G

1999-05-01

Although endothelial cells are quiescent and long-lived in vivo, when they are removed from blood vessels and cultured in vitro they die within days to weeks. In studies of the interaction of E1(-)E4(+) replication-deficient adenovirus (Ad) vectors and human endothelium, the cells remained quiescent and were viable for prolonged periods. Evaluation of these cultures showed that E1(-)E4(+) Ad vectors provide an "antiapoptotic" signal that, in association with an increase in the ratio of Bcl2 to Bax levels, induces the endothelial cells to enter a state of "suspended animation," remaining viable for at least 30 days, even in the absence of serum and growth factors. Although the mechanisms initiating these events are unclear, the antiapoptoic signal requires the presence of E4 genes in the vector genome, suggesting that one or more E4 open reading frames of subgroup C Ad initiate a "pro-life" program that modifies cultured endothelial cells to survive for prolonged periods.

OGSA Globus Toolkits evaluation activity at CERN

CERN Document Server

Chen, D; Foster, D; Kalyaev, V; Kryukov, A; Lamanna, M; Pose, V; Rocha, R; Wang, C

2004-01-01

An Open Grid Service Architecture (OGSA) Globus Toolkit 3 (GT3) evaluation group is active at CERN since GT3 was available in early beta version (Spring 2003). This activity focuses on the evaluation of the technology as promised by the OGSA/OGSI paradigm and on GT3 in particular. The goal is to study this new technology and its implications with the goal to provide useful input for the large grid initiatives active in the LHC Computing Grid (LCG) project. A particular effort has been devoted to investigate performance and deployment issues, having in mind the LCG requirements, in particular scalability and robustness.

Biologic activity of the novel small molecule STAT3 inhibitor LLL12 against canine osteosarcoma cell lines

Directory of Open Access Journals (Sweden)

Couto Jason I

2012-12-01

Full Text Available Abstract Background STAT3 [1] has been shown to be dysregulated in nearly every major cancer, including osteosarcoma (OS. Constitutive activation of STAT3, via aberrant phosphorylation, leads to proliferation, cell survival and resistance to apoptosis. The present study sought to characterize the biologic activity of a novel allosteric STAT3 inhibitor, LLL12, in canine OS cell lines. Results We evaluated the effects of LLL12 treatment on 4 canine OS cell lines and found that LLL12 inhibited proliferation, induced apoptosis, reduced STAT3 phosphorylation, and decreased the expression of several transcriptional targets of STAT3 in these cells. Lastly, LLL12 exhibited synergistic anti-proliferative activity with the chemotherapeutic doxorubicin in the OS lines. Conclusion LLL12 exhibits biologic activity against canine OS cell lines through inhibition of STAT3 related cellular functions supporting its potential use as a novel therapy for OS.

Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

Science.gov (United States)

Tutton, P J; Barkla, D H

1987-01-01

embryonic origin and that cells exhibiting an admixture of endocrine and proliferative properties exist in colonic tumours, but not in the normal intestinal epithelium. Thus, it appears that in the normal intestine a clear structural and functional distinction exists between the regulating cells (i.e. the sympathetic neurones and enteroendocrine cells) and the regulated cells (i.e. the undifferentiated crypt cells): cells that have acquired a regulating role are no longer able to divide and cells which are able to divide do not take up or store amines.(ABSTRACT TRUNCATED AT 400 WORDS)

Proliferative activity of endotheliocytes of growing capillaries of the rabbit cornea

International Nuclear Information System (INIS)

Gurina, O.Yu.; Mamontov, S.G.; Banin, V.V.

1987-01-01

The authors studied the intensity of DNA synthesis by cells of newly formed capillaries, growing in the rabbit cornea, after infliction of a silver nitrate burn and local application of colchicine. The intensity of capillary growth was investigated during stimulation and a combination of the burn with colchicine. Changes in activity of DNA synthesis by the endotheliocytes of newly formed capillaries during exposure throughout growth were also investigated. The intensity of cell proliferation was studied by measuring the incorporation of tritium-labelled thymidine into the endotheoiocyte nuclei

Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

International Nuclear Information System (INIS)

Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

2005-01-01

The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

Mitochondrial localization of the low level p53 protein in proliferative cells

Energy Technology Data Exchange (ETDEWEB)

Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Oliver, Lisa [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Rincheval, Vincent; Renaud, Flore [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vallette, Francois M. [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Mignotte, Bernard [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vayssiere, Jean-Luc, E-mail: jean-luc.vayssiere@uvsq.fr [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France)

2009-10-02

p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

Mitochondrial localization of the low level p53 protein in proliferative cells

International Nuclear Information System (INIS)

Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie; Oliver, Lisa; Rincheval, Vincent; Renaud, Flore; Vallette, Francois M.; Mignotte, Bernard; Vayssiere, Jean-Luc

2009-01-01

p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

The expression of the Slit-Robo signal in the retina of diabetic rats and the vitreous or fibrovascular retinal membranes of patients with proliferative diabetic retinopathy.

Science.gov (United States)

Zhou, Weiyan; Wang, Hongya; Yu, Wenzhen; Xie, Wankun; Zhao, Min; Huang, Lvzhen; Li, Xiaoxin

2017-01-01

The Slit-Robo signal has an important role in vasculogenesis and angiogenesis. Our study examined the expression of Slit2 and its receptor, Robo1, in a rat model of streptozotocin-induced diabetes and in patients with proliferative diabetic retinopathy. Diabetes was induced in male Sprague-Dawley rats via a single, intraperitoneal injection of streptozotocin. The rats were sacrificed 1, 3 or 6 months after the injection. The expression of Slit2 and Robo1 in retinal tissue was measured by real-time reverse transcription polymerase chain reaction (RT-PCR), and protein levels were measured by western blotting and immunohistochemistry. Recombinant N-Slit2 protein was used to study the effects of Slit2 on the expression of VEGF in vivo. The concentration of Slit2 protein in human eyes was measured by enzyme-linked immunosorbent assay in 27 eyes with proliferative diabetic retinopathy and 28 eyes in control group. The expression of Slit2, Robo1 and VEGF in the excised human fibrovascular membranes was examined by fluorescence immunostaining and semi-quantitative RT-PCR. The expression of Slit2 and Robo1 in the retina was altered after STZ injection. Recombinant N-Slit2 protein did not increase the retinal VEGF expression. Vitreous concentrations of Slit2 were significantly higher in the study group than in the control group. In the human fibrovascular membranes of the study group, the co-localization of VEGF with the markers for Slit2 and Robo1was observed. The expression of Slit2 mRNA, Robo1 mRNA, and VEGF mRNA was significantly higher in human fibrovascular proliferative diabetic retinopathy membranes than in the control membranes. The alteration of Slit2 and Robo1 expression in the retinas of diabetic rats and patients with proliferative diabetic retinopathy suggests a role for the Slit-Robo signal in the various stages diabetic retinopathy. Further studies should address the possible involvement of the Slit-Robo signal in the pathophysiological progress of diabetic

The impact of octreotide in experimental proliferative vitreoretinopathy

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Ozge Evren

2013-01-01

Full Text Available Aims: This study aims to investigate the effects of intravitreal octreotide on the growth factors, which have significant roles in the pathogenesis of proliferative vitreoretinopathy (PVR. Settings and Design: An experimental trial. Materials and Methods: 21 guinea pigs were randomly assigned to form 3 groups each including 7 animals. In group 1 (the control group, 0.2 ml saline solution was applied intravitreally in a location of 1.5 mm behind the limbus. In group 2 (the sham group, 0.07 IU dispase in 0.1 ml and 0.1 ml saline solution were applied via the same route. The guinea pigs in group 3 (the treatment group were applied 0.07 IU dispase in 0.1 ml and 1 mg octreotide in 0.1 ml via the same route. Octreotide injection was applied twice during the period of 10 weeks of the experiment. At the end of the 10 weeks, eyes were enucleated and retinal homogenates were prepared. The platelet derivated growth factor (PDGF, insulin-like growth factor (IGF 1 and transforming growth factor (TGF ß levels in homogenized retina tissue were measured by Enzyme Linked-Immuno-Sorbent Assay (ELISA method. Statistical Analysis Used: Kruskal-Wallis variance analysis and Mann-Whitney U test. Results: In the treatment group, a significant decrease was observed in retinal PDGF levels (P 0.05. Conclusions: Intravitreally applied octreotide at a dose of 1 mg has a highly strong effect on PDGF. This study suggests that intravitreal octreotide may suppress PVR development and that octreotide may merit investigation for PVR prophylaxis.

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast].

Science.gov (United States)

Oliveira, Agliberto Barbosa de; De Luca, Laurival Antônio; Carvalho, Grigna Teixeira; Arias, Victor Eduardo Arua; Carvalho, Lídia Raquel de; Assunção, Maria do Carmo

2004-01-01

Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

The prognostic relevance of estimates of proliferative activity in early breast cancer

DEFF Research Database (Denmark)

Offersen, B V; Sørensen, Flemming Brandt; Knoop, A

2003-01-01

clinicopathological parameters at diagnosis in early breast cancer patients.MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system.......RESULTS: The systematic random sampling technique resulted in MIB-1 estimates with very high interobserver and intraobserver reproducibilities (P

Detection of Glutamate and γ-aminobutyric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

Institute of Scientific and Technical Information of China (English)

Juan Deng; De-Zheng Wu; Rulong Gao

2000-01-01

Purpose: To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14patients ( 14 eyes) with idiopathic macular hole. Glutamate and GABA detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GABA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR.

Engineering amount of cell-cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton

International Nuclear Information System (INIS)

Gray, Darren S.; Liu, Wendy F.; Shen, Colette J.; Bhadriraju, Kiran; Nelson, Celeste M.; Chen, Christopher S.

2008-01-01

Endothelial cell-cell contact via VE-cadherin plays an important role in regulating numerous cell functions, including proliferation. However, using different experimental approaches to manipulate cell-cell contact, investigators have observed both inhibition and stimulation of proliferation depending on the adhesive context. In this study, we used micropatterned wells combined with active positioning of cells by dielectrophoresis in order to investigate whether the number of contacting neighbors affected the proliferative response. Varying cell-cell contact resulted in a biphasic effect on proliferation; one contacting neighbor increased proliferation, while two or more neighboring cells partially inhibited this increase. We also observed that cell-cell contact increased the formation of actin stress fibers, and that expression of dominant negative RhoA (RhoN19) blocked the contact-mediated increase in stress fibers and proliferation. Furthermore, examination of heterotypic pairs of untreated cells in contact with RhoN19-expressing cells revealed that intracellular, but not intercellular, tension is required for the contact-mediated stimulation of proliferation. Moreover, engagement of VE-cadherin with cadherin-coated beads was sufficient to stimulate proliferation in the absence of actual cell-cell contact. In all, these results demonstrate that cell-cell contact signals through VE-cadherin, RhoA, and intracellular tension in the actin cytoskeleton to regulate proliferation

The evolution of the vertebrate cerebellum: absence of a proliferative external granule layer in a non-teleost ray-finned fish

OpenAIRE

Butts, Thomas; Modrell, Melinda Sue; Baker, Clare Victoria; Wingate, Richard JT

2014-01-01

The cerebellum represents one of the most morphologically variable structures in the vertebrate brain. To shed light on its evolutionary history, we have examined the molecular anatomy and proliferation of the developing cerebellum of the North American paddlefish, Polyodon spathula. Absence of an external proliferative cerebellar layer and the restriction of Atonal1 expression to the rhombic lip and valvular primordium demonstrate that transit amplification in a cerebellar external germinal ...

An APC:WNT counter-current-like mechanism regulates cell division along the colonic crypt axis: a mechanism that explains how APC mutations induce proliferative abnormalities that drive colon cancer development.

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Bruce M Boman

2013-11-01

Full Text Available APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside. WNT signaling, in contrast, is high at the bottom (where SCs reside and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g. survivin are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric. APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly-proliferating cells during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes.

Design and synthesis of thienopyrimidine urea derivatives with potential cytotoxic and pro-apoptotic activity against breast cancer cell line MCF-7.

Science.gov (United States)

Abdelhaleem, Eman F; Abdelhameid, Mohammed K; Kassab, Asmaa E; Kandeel, Manal M

2018-01-01

A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC 50  = 9.29 μM). Moreover, compound 9c showed excellent VEGFR-2 inhibitory activity, at the sub-micromolar level with IC 50 value 0.2 μM, which is 2.1 folds more potent than sorafenib. Moreover, activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Compound 9c showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the expression of the tumor suppressor gene p53, elevation in Bax/BCL-2 ratio and a significant increase in the level of active caspase-3. Quantitative structure-activity relationship (QSAR) studies delivered equations of five 3D descriptors with R 2  = 0.814. This QSAR model provides an effective technique for understanding the observed antitumor properties and thus could be adopted for developing effective lead structures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Combining users' activity survey and simulators to evaluate human activity recognition systems.

Science.gov (United States)

Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

2015-04-08

Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

Combining Users’ Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

Directory of Open Access Journals (Sweden)

Gorka Azkune

2015-04-01

Full Text Available Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

Combining Users' Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

Science.gov (United States)

Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

2015-01-01

Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant. PMID:25856329

Polysaccharide peptide isolated from grass-cultured Ganoderma lucidum induces anti-proliferative and pro-apoptotic effects in the human U251 glioma cell line.

Science.gov (United States)

Wang, Chunhua; Lin, Dongmei; Chen, Quan; Lin, Shuqian; Shi, Songsheng; Chen, Chunmei

2018-04-01

The Ganoderma lucidum ( G. lucidum ) mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novel G. lucidum polysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured G. lucidum . GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88.70:11.30. The polysaccharides were composed of l-arabinose, d-mannose and d-glucose at a molar ratio of 1.329:0.372:2.953 and a total of 17 amino acids were detected. The results of the current study demonstrated that GL-PP significantly inhibited U251 cellular proliferation. The proportion of G 0 /G 1 phase cells and sub-G 1 phase cells significantly increased as the concentration of GL-PP increased, as did the activity of caspase-3. These results indicate that GL-PP directly inhibited human glioma U251 proliferation by inducing cell cycle arrest and promoting apoptosis.

A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

Science.gov (United States)

Yélamos, Oriol; Arva, Nicoleta C; Obregon, Roxana; Yazdan, Pedram; Wagner, Annette; Guitart, Joan; Gerami, Pedram

2015-03-01

Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

Evaluation of Results from Sales Promotion Activities

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Olimpia Ban

2007-02-01

Full Text Available An essential element of the sales promotion strategy and not only is the evaluation of the results obtained from the activities performed. Due to their nature and applicability, the evaluation of the sales promotion is much easier to be achieved, but it raises some problems. Using a hypothetical example, we have tried to develop a "classic" evaluation model of the specialty literature.

A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy

NARCIS (Netherlands)

van Geest, Rob J.; Lesnik-Oberstein, Sarit Y.; Tan, H. Stevie; Mura, Marco; Goldschmeding, Roel; van Noorden, Cornelis J. F.; Klaassen, Ingeborg; Schlingemann, Reinier O.

2012-01-01

Introduction In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF

Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, nonpeptidyl small-molecule agonist of the human thrombopoietin receptor c-Mpl.

Science.gov (United States)

Yoshida, Hiroshi; Yamada, Hajime; Nogami, Wataru; Dohi, Keiji; Kurino-Yamada, Tomomi; Sugiyama, Koji; Takahashi, Koji; Gahara, Yoshinari; Kitaura, Motoji; Hasegawa, Minoru; Oshima, Itsuki; Kuwabara, Kenji

2018-03-01

Lusutrombopag (S-888711), an oral small-molecule thrombopoietin receptor (TPOR) agonist, has gained first approval as a drug to treat thrombocytopenia of chronic liver disease in patients undergoing elective invasive procedures in Japan. Preclinical studies were performed to evaluate its efficacy against megakaryopoiesis and thrombopoiesis. To investigate the proliferative activity and efficacy of megakaryocytic colony formation via human TPOR, lusutrombopag was applied to cultured human c-Mpl-expressing Ba/F3 (Ba/F3-hMpl) cells and human bone marrow-derived CD34-positive cells, respectively. Lusutrombopag caused a robust increase in Ba/F3-hMpl cells by activating pathways in a manner similar to that of thrombopoietin and induced colony-forming units-megakaryocyte and polyploid megakaryocytes in human CD34-positive cells. Because lusutrombopag has high species specificity for human TPOR, there was no suitable experimental animal model for drug evaluation, except for immunodeficient mouse-based xenograft models. Therefore, a novel genetically modified knock-in mouse, TPOR-Ki/Shi, was developed by replacing mouse Mpl with human-mouse chimera Mpl. In TPOR-Ki/Shi mice, lusutrombopag significantly increased circulating platelets in a dose-dependent manner during 21-day repeated oral administration. Histopathological study of the TPOR-Ki/Shi mice on day 22 also revealed a significant increase in megakaryocytes in the bone marrow. These results indicate that lusutrombopag acts on human TPOR to upregulate differentiation and proliferation of megakaryocytic cells, leading to platelet production. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

Science.gov (United States)

Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

2006-02-01

The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

[Heavy silicone oil (Densiron® 68) in proliferative vitreoretinopathy: 4 years of experience].

Science.gov (United States)

Macías-Murelaga, B; Ruiz, M; Bascarán, L; Gibelalde, A; Aldazabal, M; Irigoyen, C

2013-11-01

Prospective observational study including 10 patients (age range: 27-74 years) with recurrent retinal detachment (RD) and proliferative vitreoretinopathy (PVR) and 2.8 mean unsatisfactory previous surgeries. Densiron® was injected in all patients, with surgical retinectomy being required in 70% of them. Minimum follow-up time was 12 months. The mean length of time before Densiron® withdrawal was 4 months. Three patients (30%) presented with a new RD. The main complication detected was cataract development. No relationship was found between re-detachments and tamponade time, baseline disease or RD evolution time. Densiron® may be a good option in cases of recurrent RD in which previous treatment with scleral buckle, gas and/or 1,000/5,000 silicone oils has proven to be unsatisfactory. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Chronic Proliferative Dermatitis in Mice: NFκB Activation Autoinflammatory Disease

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Yanhua Liang

2011-01-01

Full Text Available Autoinflammatory diseases are a heterogeneous group of congenital diseases characterized by the presence of recurrent inflammation, in the absence of infectious agents, detectable autoantibodies or antigen-specific autoreactive T-cells. SHARPIN deficient mice presents multiorgan chronic inflammation without known autoantibodies or autoreactive T-cells, designated Sharpincpdm. Histological studies demonstrated epidermal hyperproliferation, Th-2 inflammation, and keratinocyte apoptosis in this mutant. The mutant mice have decreased behavioral mobility, slower growth, and loss of body weight. Epidermal thickness and mitotic epidermal cells increase along with disease development. K5/K14 expression is distributed through all layers of epidermis, along with K6 expression in interfollicular epidermis, suggesting epidermal hyperproliferation. K1/K10 is only detectable in outer layers of spinosum epidermis, reflecting accelerated keratinocyte migration. Alpha smooth muscle actin is overexpressed in skin blood vessels, which may release the elevated white blood cells to dermis. CD3+CD45+ cells and granulocytes, especially eosinophils and mast cells, aggregate in the mutant skin. TUNEL assay, together with Annexin-V/propidium iodide FACS analysis, confirmed the increase of apoptotic keratinocytes in skin. These data validate and provide new lines of evidence of the proliferation-inflammation-apoptosis triad in Sharpincpdm mice, an NFκB activation autoinflammatory disease.

Research into the evaluation of PR activities in companies from Serbia

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Milan Nikolic

2016-04-01

Full Text Available This paper presents the results of a research into the volume, type and quality of the evaluation of public relations activities in companies in Serbia. The survey was conducted via a web survey. The responses were collected from 50 PR service managers from 50 companies in Serbia. The results are presented through descriptive statistics and correlation analysis where some of the observed sizes of the connection were analyzed. The main conclusions can be summarized as follows: PR functions are often not assigned sufficient importance in companies in Serbia; the evaluation of PR activity is slightly neglected compared to other PR activities; intensive and continuous evaluation of the performances of PR activities increases the likelihood of the complete PR function of the company being successful; companies that are not so successful use evaluation less than successful companies; the evaluation of PR activities is mostly done through a method for measuring quantity; the main problems in the evaluation of PR activities are lack of time and money. The evaluation of PR activities in companies in Serbia can be improved through a greater understanding on the part of top managers, and also by hiring additional PR practitioners.

Consumers' evaluations of socially responsible activities in retailing

NARCIS (Netherlands)

Herpen, van E.; Pennings, J.M.E.; Meulenberg, M.T.G.

2003-01-01

The authors approached Corporate Social Responsibility (CSR) as a process in which particular CSR activities impact on consumers’ store evaluation and trust. They hypothesized that consumers classify CSR activities along two dimensions: (1) the beneficiary of the activity and (2) the intrinsic

Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.

Science.gov (United States)

Tanaskovic, Sara; Price, Patricia; French, Martyn A; Fernandez, Sonia

2017-02-01

HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4 + T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4 + T cell deficiency on ART. Aviremic HIV patients with nadir CD4 + T cell counts cells/μL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (cells/μL; n = 13) or normal (>500 cells/μL; n = 20) CD4 + T cell counts. Ten healthy controls were also recruited. CD4 + T cell proliferation (Ki67) and upregulation of costimulatory molecules (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry. Results were related to proportions of CD4 + T cells expressing markers of T cell senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression of CD27 and/or CD28 on uncultured CD4 + T cells was similar in patients with normal CD4 + T cell counts and healthy controls, but lower in patients with low CD4 + T cell counts. Proportions of CD4 + T cells expressing CD27 and/or CD28 correlated inversely with CD4 + T cell expression of CD57, HLA-DR, and Fas. After anti-CD3 stimulation, induction of CD27 hi CD28 hi expression was independent of CD4 + T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27 hi CD28 hi expression correlated with induction of Ki67 expression in total, naïve, and CD31 + naïve CD4 + T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4 + T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4 + T cell activation and immunosenescence.

An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

Science.gov (United States)

Boman, Bruce M.; Fields, Jeremy Z.

2013-01-01

APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

Evaluation Of Analgesic And Anti-Inflammatory Activity Of Diospyros ...

African Journals Online (AJOL)

Evaluation Of Analgesic And Anti-Inflammatory Activity Of Diospyros Cordifolia Extract. S Das, PK Haldar, G Pramanik, SP Panda, S Bera. Abstract. In this study we evaluated the analgesic and anti- inflammatory activities of the methanol extract of stem bark of Diospyros cordifolia (MEDC) Roxb. The analgesic effects of the ...

Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans.

Science.gov (United States)

Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

2014-01-01

To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions.

Proliferative responses in the local lymph node assay associated with concomitant exposure to 1,4-phenylenediamine and methyldibromo glutaronitrile: evidence for synergy?

Science.gov (United States)

Jowsey, Ian R; Basketter, David A; Irwin, Anita

2008-08-01

A key consideration when undertaking risk assessments should be the potential for synergy between contact allergens. Previously, this concept has only been investigated during elicitation in contact allergic individuals. To determine whether there exists evidence for synergy between contact allergens during the induction phase of skin sensitization using the mouse local lymph node assay (LLNA) as a model system. Proliferative responses in draining lymph nodes were assessed with increasing concentrations of 1,4-phenylenediamine (PPD), methyldibromo glutaronitrile (MDBGN), and a combination of PPD and MDBGN. Data from each of two independent experiments show that lymph node cell proliferation associated with combined exposure to PPD and MDBGN was, in general, only modestly increased relative to that predicted from a simple summation of their individual responses. Although the increase in response is very modest, it does imply a relationship between this combination of sensitizers that may not be simply additive in terms of their ability to stimulate proliferative responses in draining lymph nodes. The reproducibility of this observation should be confirmed in future studies with additional pairs of contact allergens to ascertain whether or not this represents evidence of synergy.

Gene Expression of IGF1, IGF1R, and IGFBP3 in Epiretinal Membranes of Patients with Proliferative Diabetic Retinopathy: Preliminary Study

Directory of Open Access Journals (Sweden)

Dorota Romaniuk

2013-01-01

Full Text Available The molecular mechanism formation of secondary epiretinal membranes (ERMs after proliferative diabetic retinopathy (PDR or primary idiopathic ERMs is still poorly understood. Therefore, the present study focused on the assessment of IGF1, IGF1R, and IGFBP3 mRNA levels in ERMs and PBMCs from patients with PDR. The examined group comprised 6 patients with secondary ERMs after PDR and the control group consisted of 11 patients with idiopathic ERMs. Quantification of IGF1, IGF1R, and IGFBP3 mRNAs was performed by real-time QRT-PCR technique. In ERMs, IGF1 and IGF1R mRNA levels were significantly higher in patients with diabetes compared to control subjects. In PBMCs, there were no statistically significant differences of IGF1, IGF1R, and IGFBP3 expression between diabetic and nondiabetic patients. In conclusion, our study indicated IGF1 and IGF1R differential expression in ERMs, but not in PBMCs, of diabetic and nondiabetic patients, suggesting that these factors can be involved in the pathogenesis or progression of proliferative vitreoretinal disorders. This trial is registered with NCT00841334.

Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities.

Science.gov (United States)

Zhou, Wu-Xi; Sun, Yuan-Yuan; Yuan, Wei-Hui; Zhao, Yu-Qing

2017-05-01

(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH 3 -PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH 3 -PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH 3 -PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH 3 -PPD and its derivatives was tested and the results showed that the solubility of 25-OCH 3 -PPD sulfamic acid and diacid derivatives were better than that of 25-OCH 3 -PPD in water, which may provide valuable data for the research and development of new anti-tumor agents. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of glutathione in lymphocyte activation and proliferation

International Nuclear Information System (INIS)

Messina, J.P.

1990-01-01

The object of this work was to establish the requirement for GSH and cystine during the activation and proliferation of human peripheral blood mononuclear cells (PBMC). In the author's initial experiments the intracellular GSH content of PBMC was altered by continuous culture or pretreatment with BSO, a specific inhibitor of GSH synthesis. His results demonstrate that, continuous culture of mitogen stimulated PBMC in the presence of BSO inhibited entry into S-phase of the cell cycle and produced a simultaneous decrease in intracellular GSH. The influence of BSO on early activation events were determined by BSO pretreatment. Extensive depletion (>90%) of the intracellular GSH level prior to mitogenic stimulation did not impair the ability of these cells to produce IL-2 and express IL-2R, indicating that GSH may not be involved in the generation and response to early activation signals. Furthermore, the removal of BSO from these cultures rapidly reversed its inhibitory effects on DNA and GSH synthesis. Cystine transport activities and metabolism by PBMC were characterized in order to examine its contributions to intracellular GSH and early activation proteins. In spite of the ability of cystine to sustain the proliferative response of PBMC, differences in the kinetics of cystine and cysteine uptake indicated that separate transport systems may be operational. Treatment with 2ME enhanced cystine uptake, but lowered the proliferative responses of these cells. Metabolic studies with [ 35 S] cystine demonstrated that mitogen stimulation of PBMC enhance cystine uptake

Radiation retinopathy as an experimental model for ischemic proliferative retinopathy and rubeosis iridis

International Nuclear Information System (INIS)

Irvine, A.R.; Wood, I.S.

1987-01-01

We produced radiation retinopathy in capuchin monkeys and studied them with fluorescein angiography and light and electron microscopy. The animals were followed up from ten days to 3 1/2 years after radiation in order to determine whether this could provide an experimental model for other chronic ischemic-proliferative retinopathies, such as diabetes. The first change detected after radiation was the focal loss of capillary endothelial cells and pericytes. As the areas of acellular capillaries became confluent, cotton-wool spots became visible ophthalmoscopically. These increased in number and then faded away, leaving large areas of retinal capillary perfusion. Histologic studies showed occlusion first of the deeper, smaller retinal vessels and then gradually of the larger vessels. Intraretinal neovascularization as well as apparent recanalization then developed, but no new vessels extended through the internal limiting lamina into the vitreous. Rubeosis iridis with neovascular glaucoma developed 2 1/2 to 3 1/2 years postirradiation, and vitreous aspirate demonstrated a high level of angiogenic factor

Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Alves, Tercia Rodrigues [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Carvalho da Fonseca, Anna Carolina [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Nunes, Sara Santana; Oliveira da Silva, Aline [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Dubois, Luiz Gustavo Feijo; Faria, Jane; Kahn, Suzana Assad [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Viana, Nathan Bessa [Universidade Federal do Rio de Janeiro, Laboratorio de Pincas Oticas, Coordenacao de Programas de Estudos Avancados, Instituto de Ciencias Biomedicas, Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro, Instituto de Fisica, Rio de Janeiro (Brazil); Marcondes, Jorge [Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Servico de Neurocirurgia, Rio de Janeiro (Brazil); Legrand, Chantal [Institut Universitaire d' Hematologie, Universite Paris-Diderot, Paris 7, INSERM U553, Paris (France); Moura-Neto, Vivaldo [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); and others

2011-09-10

The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24 h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.

Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

International Nuclear Information System (INIS)

Alves, Tercia Rodrigues; Carvalho da Fonseca, Anna Carolina; Nunes, Sara Santana; Oliveira da Silva, Aline; Dubois, Luiz Gustavo Feijo; Faria, Jane; Kahn, Suzana Assad; Viana, Nathan Bessa; Marcondes, Jorge; Legrand, Chantal; Moura-Neto, Vivaldo

2011-01-01

The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24 h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.

105-DR Large Sodium Fire Facility closure activities evaluation report

International Nuclear Information System (INIS)

Adler, J.G.

1996-01-01

This report evaluates the closure activities at the 105-DR Large Sodium Fire Facility. The closure activities discussed include: the closure activities for the structures, equipment, soil, and gravel scrubber; decontamination methods; materials made available for recycling or reuse; and waste management. The evaluation compares these activities to the regulatory requirements and closure plan requirements. The report concludes that the areas identified in the closure plan can be clean closed

Efficacy and safety of adjuvant intravitreal injection of anti-vascular endothelial growth factors prior to vitrectomy in the treatment of proliferative diabetic retinopathy: A Meta-analysis

Directory of Open Access Journals (Sweden)

Jun Li

2017-08-01

Full Text Available AIM: To investigate the effectiveness and safety of intravitreal injection of anti-vascular endothelial growth factors(VEGFdrugs to the patients with proliferative diabetic retinopathy before vitrectomy treatment.METHODS: A Meta-analysis. A comprehensive retrieval was conducted using the database including EMbase, the Cochrane Library, Pubmed, CBM, WanFang Database, CNKI and so on. The retrieval time was limited from the building time of database to Jan. 2017. The randomized controlled trial was adopted with no requirements on languages. The Jadad scale and Cochrance cooperation were used as the tool of the risk and bias evaluation to analyze the literature quality. Quality estimation of evidence-based medicine on the parameters of each evaluation index was made via GRADEpro Software. The publishing biases of enclosed documents were inspected with funnel plot. At last, the Meta analysis was conducted with Review Manager 5.3.RESULTS: Totally 16 literatures published from 2008-2016 were finally put into randomized controlled trial. A total of 923 cases were included, among which 493 cases were grouped as intravitreal injection of anti-VEGF before the combined operation of PPV group(the experimental group, and 430 cases were involved in simple PPV group(the control group. The results of Meta-analysis show:(1The probability of intraoperative bleeding was remarkably lower than the control group \\〖OR=0.06, 95%CI(0.02, 0.15, PWMD=-29.13, 95% CI(-36.95, -21.30, POR=0.34, 95%CI(0.20, 0.58, PWMD=-0.51(LogMAR, 95%CI(-1.10, 0.08, P=0.09\\〗 with no statistical significance.(5The occurrence of iatrogenic retinal rupture was lower than that of the control group\\〖OR=0.24, 95%CI(0.14, 0.40, PCONCLUSION: It is effective and safe for the patients with proliferative diabetic retinopathy to inject anti-VEGF drugs into vitreous cavity before vitrectomy. And it can reduce the occurrence of complications during and after surgery, improving the general treatment

OM-101 Decreases the Fibrotic Response Associated with Proliferative Vitreoretinopathy

Science.gov (United States)

Dvashi, Zeev; Ben-Yaakov, Keren; Weinberg, Tamir; Greenwald, Yoel

2017-01-01

Purpose This study aimed to investigate the effect of OM-101 on the fibrotic response occurring in proliferative vitreoretinopathy (PVR) in an animal model. Methods Antifibrotic effect of OM-101 was investigated in vivo. As control, eight weeks old c57black mice underwent intravitreal injection with Hepes (group A) or dispase (0.3 units), to induce retinal detachment (RD) and PVR. The dispase-injected mice were randomly divided into two groups B and C (N = 25 mice); in group C, the eyes were treated with intravitreal injection of OM-101 (3 μl), and group B with PBS, as a control. After additional five days, mice were injected with the same initial treatment. Three days later, mice were euthanized, and the eyes were enucleated and processed for histological analysis. Results Intravitreal injection of dispase caused RD in 64% of the mice in group B, and 93% of those mice had PVR. Only 32% of mice treated with OM-101 and dispase (group C) developed RD, and only 25% of those developed PVR. Conclusions OM-101 was found effective in reducing the incidence of RD and PVR maintaining the normal architecture of the retina. This study suggests that OM-101 is a potentially effective and safe drug for the treatment of PVR patients. PMID:29109865

Identification and characterization of proliferative retinopathy-related long noncoding RNAs

Energy Technology Data Exchange (ETDEWEB)

Zhou, Rong-Mei; Wang, Xiao-Qun; Yao, Jin [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Shen, Yi; Chen, Sai-Nan [Eye Hospital, Nanjing Medical University, Nanjing (China); Yang, Hong [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Jiang, Qin, E-mail: jqin710@vip.sina.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Institute of Integrated Medicine, Nanjing Medical University, Nanjing (China); Yan, Biao, E-mail: yanbiao1982@hotmail.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Institute of Integrated Medicine, Nanjing Medical University, Nanjing (China)

2015-09-25

Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery, which can lead to severe vision reduction. Long non-coding RNAs (lncRNAs) play critical roles in many biological processes and disease development. We attempted to determine the role of lncRNAs in the setting of PVR. Microarray analysis revealed that 78 lncRNAs were abnormally expressed in the epiretinal membranes (ERMs) of PVR patients, including 48 up-regulated and 30 down-regulated lncRNA transcripts. We subsequently focus on one lncRNA, MALAT1, and investigated its expression pattern in the biofluid of PVR patients. MALAT1 was significantly up-regulated in the cellular and plasma fraction of peripheral blood in PVR patients. MALAT1 expression was obviously reduced after PVR operation. In vitro experiments revealed the role of MALAT1 in regulating RPE proliferation and migration, which is critical for ERMs formation. This study suggests that lncRNAs are the potential regulators of PVR pathology. MALAT1 is a potential prognostic indicator and a target for the diagnosis and gene therapy for PVR diseases. - Highlights: • 78 lncRNAs are differentially expressed between PVR-ERMs and secondary ERMs. • MALAT1 level is elevated in the ERMs of PVR patients. • Circulating MALAT1 level is up-regulated in PVR patients. • MALAT1 knockdown regulates RPE proliferation and migration.

Neurotrophins and Neurotrophin Receptors in Proliferative Diabetic Retinopathy

Science.gov (United States)

Abu El-Asrar, Ahmed M.; Mohammad, Ghulam; De Hertogh, Gert; Nawaz, Mohd Imtiaz; Van Den Eynde, Kathleen; Siddiquei, Mohammad Mairaj; Struyf, Sofie; Opdenakker, Ghislain; Geboes, Karel

2013-01-01

Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR. PMID:23762379

Evaluation on activation activity of reactor in JRR-2 applied 3 dimensional model to neutron flux calculation

International Nuclear Information System (INIS)

Kishimoto, Katsumi; Arigane, Kenji

2005-03-01

Revaluation to activation activity of reactor evaluated at the notification of dismantling submitted in 1997 was carried out in JRR-2 where decommissioning was advanced now. In the revaluation, estimation accuracy on neutron streaming at various horizontal experimental tubes was improved by applying 3 dimensional model to neutron transport calculation that had been carried out by 2 dimensional model, and calculating with TORT. As the result, excessive overestimations on horizontal experimental tubes and biological shield that had greatly contributed to total activation activity in evaluation at the notification of dismantling was revised, sum of their activation activities in the revaluation decreased to 1/18 (case after 1 year from the permanent shutdown of reactor) of evaluation at the notification of dismantling, and the structural materials that had large activation activity were changed. By the above, it was shown that introducing 3 dimensional model was effective in evaluation on activation activity of the research reactor that had a lot of various experimental tubes. Total activation activity of reactor by the revaluation depended on control rods, thermal shield plates and horizontal experimental tubes, and the value after 1 year from the permanent shutdown of reactor was 1.9x10 14 Bq. (author)

An evaluation of factors predicting breast recurrence and prognosis after recurrence, on distinguishing intramammary and extramammary recurrence, in breast-conserving surgery

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko [Kumamoto City Hospital (Japan)] (and others)

2001-06-01

Recurrence of cancer in the breast is an important problem in breast-conserving therapy. We evaluated risk factors for recurrence from the viewpoint of recurrence type and outcome after recurrence. Of 533 cases of breast cancer treated with breast-conserving surgery from April 1989 through July 2000, disease in 66 recurred (12.4%) and were classified as 23 cases of breast recurrence only, 16 cases of both breast recurrence and distant metastasis, and 27 cases of distant metastasis only. The clinical factors examined included age, lymphatic invasion, nodal status, extensive intraductal component (EIC), proliferative activity, and estrogen receptor (ER) status. Of the 39 cases of breast recurrence, 19 had intramammary tumors and 20 had extramammary tumors of the skin, subcutaneous tissue, or muscle, including 8 cases with inflammatory breast recurrence. Multivariate analysis showed that factors correlated with breast recurrence were age, ER status, proliferative activity, and surgical margin. EIC-comedo was related to intramammary recurrence, whereas lymphatic invasion and nodal status were related to extramammary recurrence. Postoperative irradiation was an effective treatment for tumors in young women and tumors with positive margins or a comedo component. Outcome after breast recurrence depended on nodal status at primary operation, and survival rates were worst in patients with inflammatory breast recurrence. In conclusion, age, EIC-comedo status, the surgical margin, and negative ER status were correlated with breast recurrence. Countermeasures against these factors should be investigated. (author)

An evaluation of factors predicting breast recurrence and prognosis after recurrence, on distinguishing intramammary and extramammary recurrence, in breast-conserving surgery

International Nuclear Information System (INIS)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko

2001-01-01

Recurrence of cancer in the breast is an important problem in breast-conserving therapy. We evaluated risk factors for recurrence from the viewpoint of recurrence type and outcome after recurrence. Of 533 cases of breast cancer treated with breast-conserving surgery from April 1989 through July 2000, disease in 66 recurred (12.4%) and were classified as 23 cases of breast recurrence only, 16 cases of both breast recurrence and distant metastasis, and 27 cases of distant metastasis only. The clinical factors examined included age, lymphatic invasion, nodal status, extensive intraductal component (EIC), proliferative activity, and estrogen receptor (ER) status. Of the 39 cases of breast recurrence, 19 had intramammary tumors and 20 had extramammary tumors of the skin, subcutaneous tissue, or muscle, including 8 cases with inflammatory breast recurrence. Multivariate analysis showed that factors correlated with breast recurrence were age, ER status, proliferative activity, and surgical margin. EIC-comedo was related to intramammary recurrence, whereas lymphatic invasion and nodal status were related to extramammary recurrence. Postoperative irradiation was an effective treatment for tumors in young women and tumors with positive margins or a comedo component. Outcome after breast recurrence depended on nodal status at primary operation, and survival rates were worst in patients with inflammatory breast recurrence. In conclusion, age, EIC-comedo status, the surgical margin, and negative ER status were correlated with breast recurrence. Countermeasures against these factors should be investigated. (author)

Pharmaceutically active secondary metabolites of marine actinobacteria.

Science.gov (United States)

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.

Science.gov (United States)

McKey, Jennifer; Martire, Delphine; de Santa Barbara, Pascal; Faure, Sandrine

2016-04-28

Smooth muscle cell (SMC) plasticity maintains the balance between differentiated SMCs and proliferative mesenchymal progenitors, crucial for muscular tissue homeostasis. Studies on the development of mesenchymal progenitors into SMCs have proven useful in identifying molecular mechanisms involved in digestive musculature plasticity in physiological and pathological conditions. Here, we show that Limb Expression 1 (LIX1) molecularly defines the population of mesenchymal progenitors in the developing stomach. Using in vivo functional approaches in the chick embryo, we demonstrate that LIX1 is a key regulator of stomach SMC development. We show that LIX1 is required for stomach SMC determination to regulate the expression of the pro-proliferative gene YAP1 and mesenchymal cell proliferation. However, as stomach development proceeds, sustained LIX1 expression has a negative impact on further SMC differentiation and this is associated with a decrease in YAP1 activity. We demonstrate that expression of LIX1 must be tightly regulated to allow fine-tuning of the transcript levels and state of activation of the pro-proliferative transcriptional coactivator YAP1 to regulate proliferation rates of stomach mesenchymal progenitors and their differentiation. Our data highlight dual roles for LIX1 and YAP1 and provide new insights into the regulation of cell density-dependent proliferation, which is essential for the development and homeostasis of organs.

Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34+ cells of juvenile myelomonocytic leukemia

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Yozo Nakazawa

2016-03-01

Full Text Available Abstract Background Juvenile myelomonocytic leukemia (JMML is a fatal, myelodysplastic/myeloproliferative neoplasm of early childhood. Patients with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF receptor (GMR, CD116 signaling pathway. Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment option for JMML; however, disease recurrence is a major cause of treatment failure. We investigated adoptive immunotherapy using GMR-targeted chimeric antigen receptor (CAR for JMML. Methods We constructed a novel CAR capable of binding to GMR via its ligand, GM-CSF, and generated piggyBac transposon-based GMR CAR-modified T cells from three healthy donors and two patients with JMML. We further evaluated the anti-proliferative potential of GMR CAR T cells on leukemic CD34+ cells from six patients with JMML (two NRAS mutations, three PTPN11 mutations, and one monosomy 7, and normal CD34+ cells. Results GMR CAR T cells from healthy donors suppressed the cytokine-dependent growth of MO7e cells, but not the growth of K562 and Daudi cells. Co-culture of healthy GMR CAR T cells with CD34+ cells of five patients with JMML at effector to target ratios of 1:1 and 1:4 for 2 days significantly decreased total colony growth, regardless of genetic abnormality. Furthermore, GMR CAR T cells from a non-transplanted patient and a transplanted patient inhibited the proliferation of respective JMML CD34+ cells at onset to a degree comparable to healthy GMR CAR T cells. Seven-day co-culture of GMR CAR T cells resulted in a marked suppression of JMML CD34+ cell proliferation, particularly CD34+CD38− cell proliferation stimulated with stem cell factor and thrombopoietin on AGM-S3 cells. Meanwhile, GMR CAR T cells exerted no effects on normal CD34+ cell colony growth. Conclusions Ligand-based GMR CAR T cells may have anti-proliferative effects on stem and progenitor cells in JMML.

Non-proliferative diabetic retinopathy symptoms detection and classification using neural network.

Science.gov (United States)

Al-Jarrah, Mohammad A; Shatnawi, Hadeel

2017-08-01

Diabetic retinopathy (DR) causes blindness in the working age for people with diabetes in most countries. The increasing number of people with diabetes worldwide suggests that DR will continue to be major contributors to vision loss. Early detection of retinopathy progress in individuals with diabetes is critical for preventing visual loss. Non-proliferative DR (NPDR) is an early stage of DR. Moreover, NPDR can be classified into mild, moderate and severe. This paper proposes a novel morphology-based algorithm for detecting retinal lesions and classifying each case. First, the proposed algorithm detects the three DR lesions, namely haemorrhages, microaneurysms and exudates. Second, we defined and extracted a set of features from detected lesions. The set of selected feature emulates what physicians looked for in classifying NPDR case. Finally, we designed an artificial neural network (ANN) classifier with three layers to classify NPDR to normal, mild, moderate and severe. Bayesian regularisation and resilient backpropagation algorithms are used to train ANN. The accuracy for the proposed classifiers based on Bayesian regularisation and resilient backpropagation algorithms are 96.6 and 89.9, respectively. The obtained results are compared with results of the recent published classifier. Our proposed classifier outperforms the best in terms of sensitivity and specificity.

Preclinical evaluation of novel triphenylphosphonium salts with broad-spectrum activity.

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Melissa Millard

Full Text Available BACKGROUND: Recently, there has been a surge of interest in developing compounds selectively targeting mitochondria for the treatment of neoplasms. The critical role of mitochondria in cellular metabolism and respiration supports this therapeutic rationale. Dysfunction in the processes of energy production and metabolism contributes to attenuation of response to pro-apoptotic stimuli and increased ROS production both of which are implicated in the initiation and progression of most human cancers. METHODOLOGY/PRINCIPAL FINDINGS: A high-throughput MTT-based screen of over 10,000 drug-like small molecules for anti-proliferative activity identified the phosphonium salts TP187, 197 and 421 as having IC₅₀ concentrations in the submicromolar range. TP treatment induced cell cycle arrest independent of p53 status, as determined by analysis of DNA content in propidium iodide stained cells. In a mouse model of human breast cancer, TP-treated mice showed significantly decreased tumor growth compared to vehicle or paclitaxel treated mice. No toxicities or organ damage were observed following TP treatment. Immunohistochemical staining of tissue sections from TP187-treated tumors demonstrated a decrease in cellular proliferation and increased caspase-3 cleavage. The fluorescent properties of analog TP421 were exploited to assess subcellular uptake of TP compounds, demonstrating mitochondrial localization. Following mitochondrial uptake cells exhibited decreased oxygen consumption and concomittant increase in mitochondrial superoxide production. Proteomics analysis of results from a 600 target antibody microarray demonstrated that TP compounds significantly affected signaling pathways relevant to growth and proliferation. CONCLUSIONS/SIGNIFICANCE: Through our continued interest in designing compounds targeting cancer-cell metabolism, the Warburg effect, and mitochondria we recently discovered a series of novel, small-molecule compounds containing a

Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

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Abrahim Noor

2012-11-01

Full Text Available Abstract Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml. Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide

Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase.

Science.gov (United States)

Abrahim, Noor Nazirahanie; Kanthimathi, M S; Abdul-Aziz, Azlina

2012-11-15

Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense

ICG-001 affects DRP1 activity and ER stress correlative with its anti-proliferative effect

OpenAIRE

Zinecker, Heidi; Ouaret, Djamila; Ebner, Daniel; Gaidt, Moritz M.; Taylor, Steve; Aulicino, Anna; Jagielowicz, Marta; Hornung, Veit; Simmons, Alison

2017-01-01

Mitochondria form a highly dynamic network driven by opposing scission and fusion events. DRP1 is an essential modulator of mitochondrial fission and dynamics within mammalian cells. Its fission activity is regulated by posttranslational modifications such as activating phosphorylation at serine 616. DRP1 activity has recently been implicated as being dysregulated in numerous human disorders such as cancer and neurodegenerative diseases. Here we describe the development of a cell-based screen...

Quantitative nucleic features are effective for discrimination of intraductal proliferative lesions of the breast

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Masatoshi Yamada

2016-01-01

Full Text Available Background: Intraductal proliferative lesions (IDPLs of the breast are recognized as a risk factor for subsequent invasive carcinoma development. Although opportunities for IDPL diagnosis have increased, these lesions are difficult to diagnose correctly, especially atypical ductal hyperplasia (ADH and low-grade ductal carcinoma in situ (LG-DCIS. In order to define the difference between these lesions, many molecular pathological approaches have been performed. However, still we do not have a molecular marker and objective histological index about IDPLs of the breast. Methods: We generated full digital pathology archives from 175 female IDPL patients, including usual ductal hyperplasia (UDH, ADH, LG-DCIS, intermediate-grade (IM-DCIS, and high-grade (HG-DCIS. After total 2,035,807 nucleic segmentations were extracted, we evaluated nuclear features using step-wise linear discriminant analysis (LDA and a support vector machine. Results: High diagnostic accuracy (81.8–99.3% was achieved between pathologists' diagnoses and two-group LDA predictions from nucleic features for IDPL discrimination. Grouping of nuclear features as size and shape-related or intranuclear texture-related revealed that the latter group was more important when distinguishing between normal duct, UDH, ADH, and LG-DCIS. However, these two groups were equally important when discriminating between LG-DCIS and HG-DCIS. The Mahalanobis distances between each group showed that the smallest distance values occurred between LG-DCIS and IM-DCIS and between ADH and Normal. On the other hand, the distance value between ADH and LG-DCIS was larger than this distance. Conclusions: In this study, we have presented a practical and useful digital pathological method that incorporates nuclear morphological and textural features for IDPL prediction. We expect that this novel algorithm is used for the automated diagnosis assisting system for breast cancer.

Quantitative nucleic features are effective for discrimination of intraductal proliferative lesions of the breast

Science.gov (United States)

Yamada, Masatoshi; Saito, Akira; Yamamoto, Yoichiro; Cosatto, Eric; Kurata, Atsushi; Nagao, Toshitaka; Tateishi, Ayako; Kuroda, Masahiko

2016-01-01

Background: Intraductal proliferative lesions (IDPLs) of the breast are recognized as a risk factor for subsequent invasive carcinoma development. Although opportunities for IDPL diagnosis have increased, these lesions are difficult to diagnose correctly, especially atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (LG-DCIS). In order to define the difference between these lesions, many molecular pathological approaches have been performed. However, still we do not have a molecular marker and objective histological index about IDPLs of the breast. Methods: We generated full digital pathology archives from 175 female IDPL patients, including usual ductal hyperplasia (UDH), ADH, LG-DCIS, intermediate-grade (IM)-DCIS, and high-grade (HG)-DCIS. After total 2,035,807 nucleic segmentations were extracted, we evaluated nuclear features using step-wise linear discriminant analysis (LDA) and a support vector machine. Results: High diagnostic accuracy (81.8–99.3%) was achieved between pathologists’ diagnoses and two-group LDA predictions from nucleic features for IDPL discrimination. Grouping of nuclear features as size and shape-related or intranuclear texture-related revealed that the latter group was more important when distinguishing between normal duct, UDH, ADH, and LG-DCIS. However, these two groups were equally important when discriminating between LG-DCIS and HG-DCIS. The Mahalanobis distances between each group showed that the smallest distance values occurred between LG-DCIS and IM-DCIS and between ADH and Normal. On the other hand, the distance value between ADH and LG-DCIS was larger than this distance. Conclusions: In this study, we have presented a practical and useful digital pathological method that incorporates nuclear morphological and textural features for IDPL prediction. We expect that this novel algorithm is used for the automated diagnosis assisting system for breast cancer. PMID:26955499

Arsenic interferes with the signaling transduction pathway of T cell receptor activation by increasing basal and induced phosphorylation of Lck and Fyn in spleen cells

International Nuclear Information System (INIS)

Soto-Pena, Gerson A.; Vega, Libia

2008-01-01

Arsenic is known to produce inhibition as well as induction of immune cells proliferative responses depending on the doses as one of its mechanisms of immunotoxicity. Here we evaluate the effect of arsenic exposure on the activation of splenic mononuclear cells (SMC) in male CD57BL6N mice. Intra-gastric exposure to arsenic (as sodium arsenite) for 30 days (1, 0.1, or 0.01 mg/kg/day), reduced the proportion of CD4+ cells and the CD4+/CD8+ ratio in the spleen, increasing the proportion of CD11b+ cells. Arsenic exposure did not modify the proportion of B cells. SMC showed an increased level of phosphorylation of lck and fyn kinases (first kinases associated to TCR complex when activated). Although normal levels of apoptosis were observed on freshly isolated SMC, an increase in apoptotic cells related with the increase in phosphorylation of lck and fyn was observed when SMC were activated with Concanavalin-A (Con-A). Arsenic exposure reduced the proliferative response of SMC to Con-A, and also reduced secretion of IL-2, IL-6, IL-12 and IFNγ. No effect was observed on IL-4, and IL-10 secretion. The same effects were observed when SMC of exposed animals were activated with anti-CD3/CD28 antibodies for 24 h, but these effects were transitory since a recovery, up to control levels or even higher, were observed after 72 h of stimulation. This study demonstrates that repeated and prolonged exposure to arsenic alters cell populations and produces functional changes depending on the specific activation pathway, and could be related with the phosphorylation status of lck and fyn kinases

Performance in physiology evaluation: possible improvement by active learning strategies.

Science.gov (United States)

Montrezor, Luís H

2016-12-01

The evaluation process is complex and extremely important in the teaching/learning process. Evaluations are constantly employed in the classroom to assist students in the learning process and to help teachers improve the teaching process. The use of active methodologies encourages students to participate in the learning process, encourages interaction with their peers, and stimulates thinking about physiological mechanisms. This study examined the performance of medical students on physiology over four semesters with and without active engagement methodologies. Four activities were used: a puzzle, a board game, a debate, and a video. The results show that engaging in activities with active methodologies before a physiology cognitive monitoring test significantly improved student performance compared with not performing the activities. We integrate the use of these methodologies with classic lectures, and this integration appears to improve the teaching/learning process in the discipline of physiology and improves the integration of physiology with cardiology and neurology. In addition, students enjoy the activities and perform better on their evaluations when they use them. Copyright © 2016 The American Physiological Society.

Iron(III-salophene: an organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells.

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Thilo S Lange

2008-05-01

Full Text Available In this pioneer study to the biological activity of organometallic compound Iron(III-salophene (Fe-SP the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated.Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma cell lines at concentrations between 100 nM and 1 microM, while the viability of HeLa cells (epithelial cervix adenocarcinoma or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8 and intrinsic (Caspase-9 pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC(50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model.The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo.

Evaluation the index of ophthalmic arteries in diabetic patients with retinopathy compared to diabetic patients without retinopathy using color Doppler ultrasound

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Mohammad Ghasem Hanafi

2016-12-01

Full Text Available Diabetic retinopathy is the most common eye complication in diabetic patients that early detection of this complication is essential. The aim of this study was to evaluate ophthalmic artery index in diabetic retinopathy by Doppler ultrasound. . In this cross-sectional study, 64 patients were studied in 4 groups (healthy, diabetic without retinopathy, background retinopathy and proliferative retinopathy. Resistance index (RI and Pulsatile Index (PI were assessed by color Doppler ultrasound. The obtained data were analyzed by ANOVA and chi-square test and ROC curve. RI in diabetic patients with proliferative retinopathy has the highest mean (0.83 and the lowest mean was observed in healthy subjects (0.54 (P <0.001 as well as in PI, the highest rate was in diabetic patients with proliferative retinopathy (1.41 and the lowest was in healthy subjects (0.92 (P <0.001. The results of our study showed that the sensitivity, specificity, positive and negative predictive values and overall accuracy of RI and PI in diabetic patients with proliferative retinopathy in the best cut-off points (0.645 and 1.0175 respectively were 100%.Ophthalmic artery index RI and PI was significantly increased in patients with diabetic retinopathy and the sensitivity and specificity for detection retinopathy was 100%. Color Doppler ultrasound method is more efficient for screening diabetic patients with retinopathy.

Systemic factors related to soluble (prorenin receptor in plasma of patients with proliferative diabetic retinopathy.

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Keitaro Hase

Full Text Available (Prorenin receptor [(PRR], a new component of the tissue renin-angiotensin system (RAS, plays a crucial role in inflammation and angiogenesis in the eye, thus contributing to the development of proliferative diabetic retinopathy (PDR. In this study, we investigated systemic factors related to plasma levels of soluble form of (PRR [s(PRR] in patients with PDR. Twenty type II diabetic patients with PDR and 20 age-matched, non-diabetic patients with idiopathic macular diseases were enrolled, and plasma levels of various molecules were measured by enzyme-linked immunosorbent assays. Human retinal microvascular endothelial cells were stimulated with several diabetes-related conditions to evaluate changes in gene expression using real-time quantitative PCR. Of various systemic parameters examined, the PDR patients had significantly higher blood sugar and serum creatinine levels than non-diabetic controls. Protein levels of s(PRR, prorenin, tumor necrosis factor (TNF-α, complement factor D (CFD, and leucine-rich α-2-glycoprotein 1 (LRG1 significantly increased in the plasma of PDR subjects as compared to non-diabetes, with positive correlations detected between s(PRR and these inflammatory molecules but not prorenin. Estimated glomerular filtration rate and serum creatinine were also correlated with plasma s(PRR, but not prorenin, levels. Among the inflammatory molecules correlated with s(PRR in the plasma, TNF-α, but not CFD or LRG1, application to retinal endothelial cells upregulated the mRNA expression of (PRR but not prorenin, while stimulation with high glucose enhanced both (PRR and prorenin expression. These findings suggested close relationships between plasma s(PRR and diabetes-induced factors including chronic inflammation, renal dysfunction, and hyperglycemia in patients with PDR.

Evaluation of the activity of rheumatoid arthritis in clinical practice. Agreement between self-rated clinimetric evaluation and clinical evaluation with activity indexes: DAS28, CDAI and SDAI.

Science.gov (United States)

Horta-Baas, Gabriel; Pérez Bolde-Hernández, Arturo; Hernández-Cabrera, María Fernanda; Vergara-Sánchez, Imelda; Romero-Figueroa, María Del Socorro

2017-10-11

To achieve control of rheumatoid arthritis (RA) it is necessary to be able to evaluate its activity. The American College of Rheumatology (ACR) recommends for this purpose indexes of activity that can be performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective was to analyze the concordance between self-rated clinimetric evaluation and clinimetric evaluation performed by the physician. Analytical cross-sectional study in 126 patients with RA. The agreement was evaluated through the weighted κ coefficient and the Krippendorff's α coefficient. The PAS-II and RAPID-3 significantly correlated with all variables included in the core set of measures recommended by the ACR/EULAR. The agreement between PAS-II and CDAI-SDAI was good (κ: 0.6, α: 0.61-0.62), and moderate with DAS28-ESR (κ: 0.53, α: 0.56). The concordance between RAPID-3 and CDAI-SDAI was moderate (κ: 0.55-0.57, α: 0.50-0.51), and moderate with DAS28-ESR (κ: 0.55, α: 0.53). When categorizing the activity in remission/low activity vs. moderate/severe activity, the agreement was greater with the PAS-II (0.59 vs. 0.34; P=.012). The good concordance between PAS-II and SDAI supports their use in clinical practice, especially if biomarkers of inflammation or the possibility of joint count are not available. However, in order to recommend its routine application in clinical practice, it is necessary to perform longitudinal studies that assess its responsiveness. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Evaluating Maximum Wind Energy Exploitation in Active Distribution Networks

DEFF Research Database (Denmark)

Siano, Pierluigi; Chen, Peiyuan; Chen, Zhe

2010-01-01

The increased spreading of distributed and renewable generation requires moving towards active management of distribution networks. In this paper, in order to evaluate maximum wind energy exploitation in active distribution networks, a method based on a multi-period optimal power flow (OPF......) analysis is proposed. Active network management schemes such as coordinated voltage control, energy curtailment and power factor control are integrated in the method in order to investigate their impacts on the maximization of wind energy exploitation. Some case studies, using real data from a Danish...... distribution system, confirmed the effectiveness of the proposed method in evaluating the optimal applications of active management schemes to increase wind energy harvesting without costly network reinforcement for the connection of wind generation....

Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia.

Science.gov (United States)

Ferrucci, Danilo; Biancardi, Manoel F; Nishan, Umar; Rosa-Ribeiro, Rafaela; Carvalho, Hernandes F

2017-11-01

In this commentary, we propose a relationship between desquamation, initially described as the collective detachment and deletion of epithelial cell in the prostate gland after castration, and proliferative inflammatory atrophy (PIA) and stromal growth in benign prostate hyperplasia (BPH). First, in response to diverse stimuli, including inflammatory mediators, epithelial cells desquamate and leave a large surface of the luminal side of the basement membrane (BM) exposed. Basal cells are activated into intermediate-type cells, which change morphology to cover and remodel the exposed BM (simple atrophy) to a new physiological demand (such as in the hypoandrogen environment, simulated by surgical and/or chemical castration) and/or to support re-epithelialization (under normal androgen levels). In the presence of inflammation (that might be the cause of desquamation), the intermediate-type cells proliferate and characterize PIA. Second, in other circumstances, desquamation is an early step of epithelial-to-mesenchymal transition (EMT), which contributes to stromal growth, as suggested by some experimental models of BPH. The proposed associations correlate unexplored cell behaviors and reveal the remarkable plasticity of the prostate epithelium that might be at the origin of prostate diseases. © 2017 International Federation for Cell Biology.

Evaluation of Emotional Literacy Activities: A Phenomenological Study

Science.gov (United States)

Oksuz, Yucel

2016-01-01

The present study aims to evaluate impact of the emotional literacy activities through participant student's experiences. Emotional literacy activities, including social-emotional skills Goleman's emotional intelligence and Fapuel's emotional literacy model designed and conducted for 2 months on primary school students, who study in 4th grade. The…

Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa

NARCIS (Netherlands)

Gijbels, M. J.; HogenEsch, H.; Bruijnzeel, P. L.; Elliott, G. R.; Zurcher, C.

1995-01-01

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process

Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death

NARCIS (Netherlands)

Dunning, Sandra; Rehman, Atta Ur; Tiebosch, Marjolein H.; Hannivoort, Rebekka A.; Haijer, Floris W.; Woudenberg, Jannes; van den Heuvel, Fiona A. J.; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han

2013-01-01

Background: In chronic liver disease, hepatic stellate cells (HSCs) are activated, highly proliferative and produce excessive amounts of extracellular matrix, leading to liver fibrosis. Elevated levels of toxic reactive oxygen species (ROS) produced during chronic liver injury have been implicated

S-phase cell distribution in the small intestine irradiated at different times of the day. I. Acute irradiation injury

Energy Technology Data Exchange (ETDEWEB)

Becciolini, A; Balzi, M; Cremonini, D; Fabbrica, D [Florence Univ. (Italy). Ist. di Radiologia

1983-01-01

The S-phase cell distribution has been analysed to evaluate the behaviour of proliferative cells in the intestinal epithelium after irradiation at different times of the day. A marked reduction of S cell frequency was observed at early intervals after abdominal irradiation; this reduction was particularly evident in the lower half of the crypts. At subsequent intervals a progressive extension of the proliferative compartment, with labelled cells also at the top of the crypt, was present. The irradiated groups generally showed a homogeneous behaviour even if a more marked reduction in S-phase cells was observed in group C. The invertase activity, a brush border enzyme synthetized during the differentiation process, presented a different behaviour at the early intervals in the irradiated groups. When the extension of the proliferative compartment occurred the invertase activity reached values close to zero. The modifications in brush border enzymes and in S-phase cell distribution, at early killing times, led to the hypothesis of an early differentiation.

In vitro evaluation of antioxidant activity of Cordia dichotoma (Forst f.) bark.

Science.gov (United States)

Nariya, Pankaj B; Bhalodia, Nayan R; Shukla, Vinay J; Acharya, Rabinarayan; Nariya, Mukesh B

2013-01-01

Cordia dichotoma Forst. f. bark, identified as botanical source of Shleshmataka in Ayurvedic pharmacopoeia. Present investigation was undertaken to evaluate possible antioxidant potential of methanolic and butanol extract of C. dichotoma bark. In vitro antioxidant activity of methanolic and butanol extract was determined by 1,1, diphenyl-2, picrylhydrazyl (DPPH) free radical scavenging assay. The extracts were also evaluated for their phenolic contents and antioxidant activity. Phenolic content was measured using Folin-Ciocalteu reagent and was calculated as Gallic acid equivalents. Antiradical activity of methanolic extract was measured by DPPH assay and was compared to ascorbic acid and ferric reducing power of the extract was evaluated by Oyaizu method. In the present study three in vitro models were used to evaluate antioxidant activity. The first two methods were for direct measurement of radical scavenging activity and remaining one method evaluated the reducing power. The present study revealed that the C. dichotoma bark has significant radical scavenging activity.

Preregistered Replication of "Affective Flexibility: Evaluative Processing Goals Shape Amygdala Activity".

Science.gov (United States)

Lumian, Daniel S; McRae, Kateri

2017-09-01

The human amygdala is sensitive to stimulus characteristics, and growing evidence suggests that it is also responsive to cognitive framing in the form of evaluative goals. To examine whether different evaluations of stimulus characteristics shape amygdala activation, we conducted a preregistered replication of Cunningham, Van Bavel, and Johnsen's (2008) study demonstrating flexible mapping of amygdala activation to stimulus characteristics, depending on evaluative goals. Participants underwent functional MRI scanning while viewing famous names under three conditions: They were asked to report their overall attitude toward each name, their positive associations only, or their negative associations only. We observed an interaction between condition and rating type, identified as the effect of interest in Cunningham et al. (2008). Specifically, postscan positivity, but not negativity, ratings predicted left amygdala activation when participants were asked to evaluate positive, but not negative, associations with the names. These results provide convergent evidence that cognitive framing, in the form of evaluative goals, can significantly alter whether amygdala activation indexes positivity or negativity.

THE CONTROL AND EVALUATION OF PROMOTIONAL ACTIVITIES

Directory of Open Access Journals (Sweden)

Felicia Sabou

2012-01-01

Full Text Available The paper focused on importance and benefits of control and evaluation of marketing activities. The control of efficiency review the assessment of the resources for marketing activity, checking also the efficiency of the human resources, advertising, promotion activities and distribution activities. In the analyse of human resources the most important ratio are: the average of costumers visits on a day, the number of custom order received from 100 visits, the number of new customers from a period, the number of lost customers from a period, the marketing human expenditures from all the sales.The strategic control is made to check if the objectives and the company strategy are adapted to the marketing environment.

20 CFR 404.1584 - Evaluation of work activity of blind people.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Evaluation of work activity of blind people... Evaluation of work activity of blind people. (a) General. If you are blind (as explained in § 404.1581), we... gainful activity are the same for blind people as for others. See § 404.1574(b)(2) for the earnings...

MYC activation is a hallmark of cancer initiation and maintenance.

Science.gov (United States)

Gabay, Meital; Li, Yulin; Felsher, Dean W

2014-06-02

The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Active film of poly(vinyl chloride)/silver: synthesis, characterization and evaluation as antimicrobial active packaging

International Nuclear Information System (INIS)

Braga, Lilian R.; Rangel, Ellen T.; Machado, Fabricio

2015-01-01

The antimicrobial films based on poly(vinyl chloride) (PVC) mediated silver (1, 2, 4 and 8 wt%) were evaluated as antimicrobial active packaging using the casting method. The structure of the active films was characterized by SEM, EDX-XRF, XRD, FTIR and TG. FTIR spectra confirmed the PVC-Ag interaction due to the presence of new bands at 1745 cm"-"1 and 1165 cm"-"1 bands, which are absent in the PVC control. The FRX-EDX spectrum confirmed the presence of silver ions in all the films. TG and SEM results showed that the increased concentration of silver provided an improved thermal stability and presence of pores in the active films, respectively. Antimicrobial activity was evaluated by disk diffusion method for Bacillus subtilis, Fusarium solani and Apergillus niger, which proved the efficiency of the films active. (author)

Evaluation of Activity Recognition Algorithms for Employee Performance Monitoring

OpenAIRE

Mehreen Mumtaz; Hafiz Adnan Habib

2012-01-01

Successful Human Resource Management plays a key role in success of any organization. Traditionally, human resource managers rely on various information technology solutions such as Payroll and Work Time Systems incorporating RFID and biometric technologies. This research evaluates activity recognition algorithms for employee performance monitoring. An activity recognition algorithm has been implemented that categorized the activity of employee into following in to classes: job activities and...

Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line.

Science.gov (United States)

Fattahi, Sadegh; Ardekani, Ali Motevalizadeh; Zabihi, Ebrahim; Abedian, Zeinab; Mostafazadeh, Amrollah; Pourbagher, Roghayeh; Akhavan-Niaki, Haleh

2013-01-01

Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r(2)=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.