Antitumor activity of intratracheal inhalation of temozolomide (TMZ) loaded into gold nanoparticles and/or liposomes against urethane-induced lung cancer in BALB/c mice.

PubMed

Hamzawy, Mohamed A; Abo-Youssef, Amira M; Salem, Heba F; Mohammed, Sameh A

2017-11-01

The current study aimed to develop gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) as drug carriers for temozolomide (TMZ) and investigate the possible therapeutic effects of intratracheal inhalation of nanoformulation of TMZ-loaded gold nanoparticles (TGNPs) and liposome-embedded TGNPs (LTGNPs) against urethane-induced lung cancer in BALB/c mice. Physicochemical characters and zeta potential studies for gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) were performed. The current study was conducted by inducing lung cancer chemically via repeated exposure to urethane in BALB/C mice. GNPs and LGNPs were exhibited in uniform spherical shape with adequate dispersion stability. GNPs and LGNPs showed no significant changes in comparison to control group with high safety profile, while TGNPs and LTGNPs succeed to improve all biochemical data and histological patterns. GNPs and LGNPs are promising drug carriers and succeeded in the delivery of small and efficient dose of temozolomide in treatment lung cancer. Antitumor activity was pronounced in animal-treated LTGNPs, these effects may be due to synergistic effects resulted from combination of temozolomide and gold nanoparticles and liposomes that may improve the drug distribution and penetration.

A Novel Modification of the AOM/DSS Model for Inducing Intestinal Adenomas in Mice.

PubMed

Angelou, Anastasios; Andreatos, Nikolaos; Antoniou, Efstathios; Zacharioudaki, Argiro; Theodoropoulos, George; Damaskos, Christos; Garmpis, Nikolaos; Yuan, Chunhui; Xiao, Weidong; Theocharis, Stamatios; Zografos, George; Papalois, Apostolos; Margonis, Georgios Antonios

2018-06-01

Our aim was to develop an animal model of the precancerous stages of colitis-associated carcinogenesis by modifying the established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Six mice were treated with varying cycles of DSS following AOM administration as above (group 1: three mice received three 5-day cycles of 3.0% DSS and group 2: three mice received three 7-day cycles of 2.5% DSS; every cycle was followed by a 2-week rest period) and were sacrificed on day 84 of the experiment. By contrast, three female C57BL6 mice (group 3) were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 5-day cycles of oral 2.5% DSS, with each cycle interrupted by a 2-week rest period. The mice of this group were sacrificed at 60 days. In groups 1 and 2, cancer was noted in five out of the six mice. In group 3, adenomas with dysplastic lesions were noted in all of the mice, but none had developed adenocarcinoma. Our results suggest that the administration of three 5-day cycles of 2.5% DSS following an initial dose of AOM may successfully induce adenoma formation without the concurrent presence of carcinoma in female C57BL6 mice that are sacrificed on experimental day 60. In turn, this modification of the widely used AOM/DSS protocol may constitute a novel approach for investigating colitis-related colonic adenomas. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

PubMed

Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

2016-01-01

The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

AKT1E17K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer

PubMed Central

Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

2016-01-01

The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype. PMID:26859676

Relationship of Metabolism and Cell Proliferation to the Mode of Action of Fluensulfone-Induced Mouse Lung Tumors. II: Additional Mechanistic Studies.

PubMed

Strupp, Christian; Bomann, Werner; Cohen, Samuel M; Weber, Klaus

2016-12-01

Fluensulfone is a nematicide for agricultural use. Chronic dietary exposure led to bronchiolo-alveolar hyperplasia and bronchiolo-alveolar adenomas in CD-1 mice but not in rats. Genotoxicity could be excluded as a mode of action (MOA). An earlier publication (Strupp, C., Banas, D. A., Cohen, S. M., Gordon, E. B., Jaeger, M., and Weber, K. (2012). Relationship of metabolism and cell proliferation to the mode of action of fluensulfone-induced mouse lung tumors: analysis of their human relevance using the IPCS framework. Toxicol. Sci. 128, 284-294.) reported MOA studies identifying the following key events: increased metabolism of fluensulfone by CYP2f2 in mouse lung Club cells, followed by local proliferation, finally leading to adenoma formation. Human lung microsomes were found not to metabolize fluensulfone. The Joint FAO/WHO Meeting on Pesticide Residues has reviewed the previous data and concluded that the MOA is plausible however some areas of uncertainty were identified. This publication provides additional data to address these. New cell proliferation studies in mice showed that the MOA is functionally independent of sex. A threshold of cell proliferation in Club cells correlating with the dose response for adenoma formation was shown. CYP2f2 knockout mice did not react to fluensulfone exposure with cell proliferation like wild-type mice, confirming the key role of this enzyme. The collective data for fluensulfone were evaluated according to the International Programme on Chemical Safety (IPCS) Mode of Action Framework which leads to the conclusion that the mouse-specific lung tumors after fluensulfone are not relevant to humans. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pertussis toxin inhibits somatostatin-induced K/sup +/ conductance in human pituitary tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamashita, N.; Kojima, I.; Shibuya, N.

1987-07-01

The effect of pertussis toxin on somatostatin-induced K/sup +/ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K/sup +/ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K/sup +/, Na/sup +/, and Ca/sup 2 +/ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with (/sup 32/P)NAD, a 41K protein wasmore » ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.« less

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

PubMed Central

Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo

2011-01-01

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

IL-33 activates tumor stroma to promote intestinal polyposis.

PubMed

Maywald, Rebecca L; Doerner, Stephanie K; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M; Dawson, Emily P; Lanza, Denise G; Berger, Nathan A; Markowitz, Sanford D; Lenz, Heinz-Josef; Nadeau, Joseph H; Pizarro, Theresa T; Heaney, Jason D

2015-05-12

Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc(Min/+) mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc(Min/+) polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc(Min/+) polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.

Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

PubMed Central

Liskay, R.Michael

2014-01-01

Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.

PubMed

Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

2016-08-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

PubMed

Xu, Zhiyuan; Lee Vance, Mary; Schlesinger, David; Sheehan, Jason P

2013-04-01

Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS)-induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism. This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately before SRS and in regular follow-ups. Assessment consisted of 24-hour urine free cortisol (patients with Cushing disease), serum adrenocorticotropic hormone, cortisol, follicle-stimulating hormone, luteinizing hormone, insulin-like growth factor-1, growth hormone, testosterone (men), prolactin, thyroid-stimulating hormone, and free T(4). Endocrine remission occurred in 144 of 199 patients with a functioning adenoma. Tumor control rate was 89%. Eighty patients experienced at least 1 axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based on endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years after SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior radiation therapy, and age at SRS. SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were 2 independent predictors of SRS-induced hypopituitarism.

Hypoxia induces hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

PubMed

Xiao, Zhengzheng; Liu, Qin; Zhao, Boxi; Wu, Jun; Lei, Ting

2011-12-01

The hypoxia inducible factor 1 α (HIF-1α) activity has been associated with various hemorrhagic events. The biological role of HIF-1α in the hemorrhagic transformation of pituitary adenomas remains unknown. We hypothesized that fast growing tumor cells tend to predispose themselves to sublethal hypoxia and activate the HIF-1α signaling pathway, leading to hemorrhagic transformation in pituitary adenomas. Here, we used apoplectic and non-apoplectic pituitary adenomas to determine the involvement of HIF-1α signaling in intratumoral hemorrhage. We employed HIF-1α overexpression/knockdown strategies to examine the association between HIF-1α signaling and hemorrhagic presentation in vitro and in vivo. In support of our hypothesis, compared with non-hemorrhagic pituitary adenomas, higher cellular proliferation was observed in hemorrhagic ones and it correlated with increased HIF-1α signaling. HIF-1α overexpression activated its downstream genes, vascular endothelial growth factor and the proapoptotic BNIP3, in MMQ pituitary adenoma cells and this up-regulation was attenuated by HIF-1 siRNA. In vivo studies using MMQ cell xenografts in nude mice showed that HIF-1α overexpression significantly promoted hemorrhagic transformation. Our study indicates that tumor hypoxia, following rapid tumor growth, may promote hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

In vitro studies on the effect of physical cross-linking on the biological performance of aliphatic poly(urethane urea) for blood contact applications.

PubMed

Thomas, V; Kumari, T V; Jayabalan, M

2001-01-01

The effect of physical cross-linking in candidate cycloaliphatic and hydrophobic poly(urethane urea) (4,4'-methylenebis(cyclohexylisocyanate), H(12)MDI/hydroxy-terminated polybutadiene, HTPBD/hexamethylenediamine, HDA) and poly(ether urethane urea)s (H(12)MDI/HTPBD-PTMG/HDA) on the in vitro calcification and blood-material interaction was studied. All the candidate poly(urethane urea)s and poly(ether urethane urea)s elicit acceptable hemolytic activity, cytocompatibility, calcification, and blood compatibility in vitro. The studies on blood-material interaction reveal that the present poly(urethane urea)s are superior to polystyrene microtiter plates which were used for the studies on blood-material interaction. The present investigation reveals the influence of physical cross-link density on biological interaction differently with poly(urethane urea) and poly(ether urethane urea)s. The higher the physical cross-link density in the poly(urethane urea)s, the higher the calcification and consumption of WBC in whole blood. On the other hand, the higher the physical cross-link density in the poly(ether urethane urea)s, the lesser the calcification and consumption of WBC in whole blood. However a reverse of the above trend has been observed with the platelet consumption in the poly(urethane urea)s and poly(ether urethane urea)s.

Case-Control Study of Candidate Gene Methylation and Adenomatous Polyp Formation

PubMed Central

M, Alexander; JB, Burch; SE, Steck; C-F, Chen; TG, Hurley; P, Cavicchia; N, Shivappa; J, Guess; H, Zhang; SD, Youngstedt; KE, Creek; S, Lloyd; K, Jones; JR, Hébert

2016-01-01

Purpose Colorectal cancer (CRC) is one of the most common and preventable forms of cancer, but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70–90% of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation. Methods Patients recruited from a local endoscopy clinic provided informed consent, and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy, or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios and 95% confidence intervals (OR, 95% CI) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders. Results Complete data were available for 107 participants; 36% had adenomas (men: 40%, women: 31%). Hypomethylation of the MINT1 locus (OR: 5.3, 95% CI: 1.0–28.2), and the PER1 (OR: 2.9, 95% CI: 1.1–7.7) and PER3 (OR: 11.6, 95% CI: 1.6–78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71–97%), sensitivity was relatively low (18–45%). Conclusion Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance. PMID:27771773

Effect of cyanidin-3-glucoside and an anthocyanin mixture from bilberry on adenoma development in the ApcMin mouse model of intestinal carcinogenesis--relationship with tissue anthocyanin levels.

PubMed

Cooke, Darren; Schwarz, Michael; Boocock, David; Winterhalter, Peter; Steward, William P; Gescher, Andreas J; Marczylo, Timothy H

2006-11-01

Anthocyanins are dietary flavonoids, which can prevent carcinogen-induced colorectal cancer in rats. Here, the hypotheses were tested that Mirtoselect, an anthocyanin mixture from bilberry, or isolated cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, interfere with intestinal adenoma formation in the Apc(Min) mouse, a genetic model of human familial adenomatous polyposis, and that consumption of C3G or Mirtoselect generates measurable levels of anthocyanins in the murine biophase. Apc(Min) mice ingested C3G or Mirtoselect at 0.03, 0.1 or 0.3% in the diet for 12 weeks, and intestinal adenomas were counted. Plasma, urine and intestinal mucosa were analyzed for presence of anthocyanins by high-pressure liquid chromatography with detection by UV spectrophotometry (520 nm) or tandem mass spectrometry (multiple reaction monitoring). Ingestion of either C3G or Mirtoselect reduced adenoma load dose-dependently. At the highest doses of C3G and Mirtoselect adenoma numbers were decreased by 45% (p < 0.001) or 30% (p < 0.05), respectively, compared to controls. Anthocyanins were found at the analytical detection limit in the plasma and at quantifiable levels in the intestinal mucosa and urine. Anthocyanin glucuronide and methyl metabolites were identified in intestine and urine. Total anthocyanin levels in mice on C3G or Mirtoselect were 43 ng and 8.1 microg/g tissue, respectively, in the intestinal mucosa, and 7.2 and 12.3 microg/ml in the urine. The efficacy of C3G and Mirtoselect in the Apc(Min) mouse renders the further development of anthocyanins as potential human colorectal cancer chemopreventive agents worthwhile.

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

PubMed Central

Radulescu, S; Ridgway, R A; Cordero, J; Athineos, D; Salgueiro, P; Poulsom, R; Neumann, J; Jung, A; Patel, S; Woodgett, J; Barker, N; Pritchard, D M; Oien, K; Sansom, O J

2013-01-01

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach. PMID:22665058

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats

PubMed Central

Chiang, Bing-Juin; Chen, Tien-Wen; Chung, Shiu-Dong; Lee, Way-Zen; Chien, Chiang-Ting

2017-01-01

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction. PMID:29285288

Use Of New Industrial Coatings for the U.S. Navy Waterfront Structures

DTIC Science & Technology

2008-01-01

as a coating for the interior and exterior of piping systems, which either are located in harsh environments or are transporting substances with...SSPC SP 10 Surfaces) (5). SyslCm Coating Sys\\~m A Zinc -rich urethane/MIOa·filled urethane/urethane 314/315/314 B Zinc -rich urethane/MIO-filled...urethanc/MIO-urethane 336/3361336 C Zinc -rich urethancl1vfiO & Alb-fined urethaneiMIO-fiIled 337/3401336 ,1 MicaceQus iron oxide. b Aluminum. urethane

Genomic Landscape of Colorectal Mucosa and Adenomas in Familial Adenomatous Polyposis

PubMed Central

Borras, Ester; San Lucas, F. Anthony; Chang, Kyle; Zhou, Ruoji; Masand, Gita; Fowler, Jerry; Mork, Maureen E.; You, Y. Nancy; Taggart, Melissa W.; McAllister, Florencia; Jones, David A.; Davies, Gareth E.; Edelmann, Winfried; Ehli, Erik A.; Lynch, Patrick M.; Hawk, Ernest T.; Capella, Gabriel; Scheet, Paul; Vilar, Eduardo

2016-01-01

Purpose The molecular basis of the adenoma to carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. Experimental Design We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Results Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer-driver genes (APC, KRAS, FBXW7, TCF7L2) and allelic imbalances in chromosomes 5, 7 and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. Conclusions The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. PMID:27221540

Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas.

PubMed

Barbieri, Federica; Bajetto, Adriana; Stumm, Ralf; Pattarozzi, Alessandra; Porcile, Carola; Zona, Gianluigi; Dorcaratto, Alessandra; Ravetti, Jean-Louis; Minuto, Francesco; Spaziante, Renato; Schettini, Gennaro; Ferone, Diego; Florio, Tullio

2008-08-15

Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division. We evaluated the expression of the chemokine stromal cell-derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation. The expression of SDF1 and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitaries was determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1 was evaluated in eight fibroblast-free human pituitary adenoma cell cultures. CXCR4 mRNA was expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1 showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1 were expressed only in a subset of anterior pituitary cells, with a lower expression of SDF1 compared with its cognate receptor. CXCR4 and SDF1 were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone-secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1 induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin. CXCR4 and SDF1 are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development in humans.

Chemoenzymatic Synthesis and Chemical Recycling of Poly(ester-urethane)s

PubMed Central

Hayashi, Hiroto; Yanagishita, Yoshio; Matsumura, Shuichi

2011-01-01

Novel poly(ester-urethane)s were prepared by a synthetic route using a lipase that avoids the use of hazardous diisocyanate. The urethane linkage was formed by the reaction of phenyl carbonate with amino acids and amino alcohols that produced urethane-containing diacids and hydroxy acids, respectively. The urethane diacid underwent polymerization with polyethylene glycol and α,ω-alkanediols and also the urethane-containing hydroxy acid monomer was polymerized by the lipase to produce high-molecular-weight poly(ester-urethane)s. The periodic introduction of ester linkages into the polyurethane chain by the lipase-catalyzed polymerization afforded chemically recyclable points. They were readily depolymerized in the presence of lipase into cyclic oligomers, which were readily repolymerized in the presence of the same enzyme. Due to the symmetrical structure of the polymers, poly(ester-urethane)s synthesized in this study showed higher Tm, Young’s modulus and tensile strength values. PMID:22016604

Comparison of Polyurethanes with Polyhydroxyurethanes: Effect of the Hydroxyl Group on Structure-Property Relationships

NASA Astrophysics Data System (ADS)

Leitsch, Emily K.; Lombardo, Vince M.; Scheidt, Karl A.; Torkelson, John M.

2014-03-01

Polyurethanes (PUs) are commonly synthesized by rapid step-growth polymerization through the reaction of a multifunctional alcohol with a polyisocyanate. PUs can be prepared at ambient conditions utilizing a variety of starting material molecular weights and backbones, resulting in highly tunable thermal and physical properties. The urethane linkages as well as the nanophase separated morphology attainable in PU materials lead to desirable properties including elastomeric character and adhesion. The isocyanate-based monomers used in the synthesis of traditional PUs have come under increasing regulatory pressure and thus inspired the investigation of alternative routes for the formation of PU materials. We examine an alternative route to synthesize PU- the reaction of five-membered cyclic carbonate with amines. This reaction results in the formation of a urethane linkage with an adjacent alcohol group. The effects of this hydroxyl group on the thermal and mechanical properties of the resulting polymer are investigated and compared with an analogous traditional PU system.

In vivo evaluation of a fluorine-acryl-stylene-urethane-silicone antithrombogenic coating material copolymer for intravascular stents.

PubMed

Matsuhashi, T; Miyachi, H; Ishibashi, T; Sakamoto, K; Yamadera, A

1996-07-01

We evaluated the effectiveness of a fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer as an antithrombogenic coating material for intravascular stents in dogs. FASUS copolymer-coated stents were placed in the right iliac veins, and uncoated 304 stainless steel stents were placed in the left iliac veins. We examined platelet deposition, microthrombus formation, and neointimal hyperplasia 4 weeks after stent placement by measuring the activity of 111In-labeled platelets, by using scanning electron microscopy, and by measuring neointimal thickness. Platelet deposition was significantly decreased on coated than on uncoated stents (p < .05). A less pronounced increase in red blood cell deposition was observed at the sites of the coated than uncoated stents (p < .05). Neointimal thickness 4 weeks after stent placement also was significantly less at the sites of the coated stents (0.27 +/- 0.08 mm versus 0.48 +/- 0.23 mm, p < .05). FASUS copolymer coating over the vascular stent is effective for preventing thrombus formation and neointimal hyperplasia.

Understanding the potential and challenges of adenoma treatment as a prevention opportunity: insights from the BeWEL formative study.

PubMed

Stead, Martine; Caswell, Stephen; Craigie, Angela M; Eadie, Douglas; Anderson, Annie S

2012-01-01

To explore prevention opportunities presented by colorectal adenoma diagnosis and inform engagement strategies for the BeWEL study (body weight and physical activity lifestyle intervention for colorectal cancer screening participants who have undergone adenoma removal). Qualitative study comprising 4 purposively sampled focus groups conducted in urban and rural areas in Tayside, Scotland, with different deprivation levels. Participants were men and women (n=17) aged 50-74 with BMI>25 kg/m(2) with removal of adenoma detected by colorectal cancer screening. Adenoma diagnosis presents both opportunities and challenges for prevention. Some patients perceived adenoma as minor and not sufficiently motivating to act as a 'teachable moment'. Patients had low awareness of the relationship between adenoma and lifestyle factors, and received little information on prevention during screening and treatment. Consequently they interpreted post-treatment 'all clear' messages as validation of existing lifestyles, and did not see the relevance of prevention advice. Receptiveness increased when the association between lifestyle, adenoma recurrence and other illness was explained. The study illustrates the value of exploratory research into patient understanding to improve communications and health services. Without unduly worrying patients, professionals should explain how to reduce risk of adenoma, cancer and other diseases, particularly through diet, physical activity and weight reduction. Copyright © 2011 Elsevier Inc. All rights reserved.

Urethane anesthesia blocks the development and expression of kindled seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cain, D.P.; Raithby, A.; Corcoran, M.E.

1989-01-01

The effect of anesthetic and subanesthetic doses of urethane on the development of amygdala kindled seizures and on the expression of previously kindled seizures was studied in hooded rats. An anesthetic dose of urethane almost completely eliminated evoked after discharge and completely eliminated convulsive behavior in both groups. It also eliminated the seizure response to pentylenetetrazol. Subanesthetic doses of urethane strongly attenuated the expression of previously kindled seizures. These results suggest that urethane may not be an appropriate anesthetic for the study of epileptiform phenomena.

Urethane/Silicone Adhesives for Bonding Flexing Metal Parts

NASA Technical Reports Server (NTRS)

Edwards, Paul D.

2004-01-01

Adhesives that are blends of commercially available urethane and silicone adhesives have been found to be useful for bonding metal parts that flex somewhat during use. These urethane/silicone adhesives are formulated for the specific metal parts to be bonded. The bonds formed by these adhesives have peel and shear strengths greater than those of bonds formed by double-sided tapes and by other adhesives, including epoxies and neat silicones. In addition, unlike the bonds formed by epoxies, the bonds formed by these adhesives retain flexibility. In the initial application for which the urethane/silicone adhesives were devised, there was a need to bond spring rings, which provide longitudinal rigidity for inflatable satellite booms, with the blades that provide the booms axial strength. The problem was to make the bonds withstand the stresses, associated with differences in curvature between the bonded parts, that arose when the booms were deflated and the springs were compressed. In experiments using single adhesives (that is, not the urethane/ silicone blends), the bonds were broken and, in each experiment, it was found that the adhesive bonded well with either the ring or with the blade, but not both. After numerous experiments, the adhesive that bonded best with the rings and the adhesive that bonded best with the blades were identified. These adhesives were then blended and, as expected, the blend bonded well with both the rings and the blades. The two adhesives are Kalex (or equivalent) high-shear-strength urethane and Dow Corning 732 (or equivalent) silicone. The nominal mixture ratio is 5 volume parts of the urethane per 1 volume part of the silicone. Increasing the proportion of silicone makes the bond weaker but more flexible, and decreasing the proportion of silicone makes the bond stronger but more brittle. The urethane/silicone blend must be prepared and used quickly because of the limited working time of the urethane: The precursor of the urethane adhesive is supplied in a two-part form, comprising a resin and a hardener that must be mixed. The resulting urethane adhesive has a working time of 3 to 5 minutes. To prepare the urethane/silicone blend, one must quickly add the silicone to the urethane adhesive and mix it in thoroughly within the working time of the urethane. Once the urethane/silicone blend has been mixed and applied to the bond surfaces, it takes about 2 hours for the adhesive to cure under pressure. However, it takes about 24 hours for the adhesive to reach full strength.

Dietary Heme Induces Gut Dysbiosis, Aggravates Colitis, and Potentiates the Development of Adenomas in Mice

PubMed Central

Constante, Marco; Fragoso, Gabriela; Calvé, Annie; Samba-Mondonga, Macha; Santos, Manuela M.

2017-01-01

Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD), where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria, particularly Enterobacteriaceae. These changes were similar to shifts seen in dextran sodium sulfate (DSS)-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC) mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis. Thus, luminal heme levels may further exacerbate colitis through the modulation of the gut microbiota and its metagenomic functional composition. Our data may have implications in the development of novel targets for therapeutic approaches aimed at lowering gastrointestinal heme levels through heme chelation or degradation using probiotics and nutritional interventions. PMID:28983289

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

PubMed

Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

2016-10-18

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

Fetal Onset of Aberrant Gene Expression Relevant to Pulmonary Carcinogenesis in Lung Adenocarcinoma Development Induced by In Utero Arsenic Exposure

PubMed Central

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A.; Waalkes, Michael P.

2009-01-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-α (ER-α) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-β-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. in utero arsenic exposure also induced overexpression of α-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-α expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-α expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-α activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. PMID:17077188

Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

PubMed

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A; Waalkes, Michael P

2007-02-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

[Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)].

PubMed

Kuznetsov, S V; Sizonov, V A; Dmitrieva, L E

2014-01-01

On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the intersystemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and many-minute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason--are weakly enhanced.

Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells

PubMed Central

Leite de Oliveira, Felipe; Soares, Nathália; de Mattos, Rômulo Medina; Hecht, Fábio; Dezonne, Rômulo Sperduto; Vairo, Leandro; Goldenberg, Regina Coeli dos Santos; Gomes, Flávia Carvalho Alcântara; de Carvalho, Denise Pires; Gadelha, Mônica R.; Nasciutti, Luiz Eurico; Miranda-Alves, Leandro

2013-01-01

Pituitary adenomas comprise approximately 10–15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing’s disease. PMID:23667519

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis

PubMed Central

Niccum, David E.; Billings, Joanne L.; Dunitz, Jordan M.; Khoruts, Alexander

2018-01-01

Background Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. Methods We analyzed prospectively collected results of colonoscopies initiated at age 40 years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30–39 years performed during the same time period at the Center. Results The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. Conclusions Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population. PMID:26851188

Evaluation of urethane for feasibility of use in wind turbine blade design

NASA Technical Reports Server (NTRS)

Lieblein, S.; Ross, R. S.; Fertis, D. G.

1979-01-01

A preliminary evaluation was conducted of the use of cast urethane as a possible material for low-cost blades for wind turbines. Specimen test data are presented for ultimate tensile strength, elastic modulus, flexural strain, creep, and fatigue properties of a number of urethane formulations. Data are also included for a large-scale urethane blade section composed of cast symmetrical half-profiles tested as a cantilever beam. Based on these results, an analysis was conducted of a full-scale blade design of cast urethane that meets the design specifications of the rotor blades for the NASA/DOE experimental 100-kW MOD-0 wind turbine. Because of the low value of elastic modulus for urethane (around 457 000 psi), the design loads would have to be carried by metal reinforcement. Considerations for further evaluation are noted.

Development of urethane coating and potting material with improved hydrolytic and oxidative stability

NASA Technical Reports Server (NTRS)

Morris, D. E.

1981-01-01

A series of saturated hydrocarbon based urethanes was prepared and characterized for hydrolytic and oxidative stability. A series of ether based urethanes was used as a basis for comparison. The alkane base urethanes were found to be hydrolytically and oxidatively stable and had excellent electrical properties. The alkane based materials absorbed little or no water and were reversion resistant. There was little loss in hardness or weight when exposed to high temperature and humidity. Dielectric properties were excellent and suffered little adverse effects from the high temperature/humidity conditions. The alkane based urethanes were not degraded by ozone exposure.

K-ras mutations and HLA-DR expression in large bowel adenomas.

PubMed Central

Norheim Andersen, S.; Breivik, J.; Løvig, T.; Meling, G. I.; Gaudernack, G.; Clausen, O. P.; Schjölberg, A.; Fausa, O.; Langmark, F.; Lund, E.; Rognum, T. O.

1996-01-01

A total of 72 sporadic colorectal adenomas in 56 patients were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene and for HLA-DR antigen expression related to clinicopathological variables. Forty K-ras mutations in 39 adenomas were found (54%): 31 (77%) in codon 12 and nine (23%) in codon 13. There was a strong relationship between the incidence of K-ras mutations and adenoma type, degree of dysplasia and sex. The highest frequency of K-ras mutations was seen in large adenomas of the villous type with high-grade dysplasia. Fourteen out of 15 adenomas obtained from 14 women above 65 years of age carried mutations. HLA-DR positivity was found in 38% of the adenomas, large tumours and those with high-grade dysplasia having the strongest staining. Coexpression of K-ras mutations and HLA-DR was found significantly more frequently in large and highly dysplastic adenomas, although two-way analysis of variance showing size and grade of dysplasia to be the most important variable. None of the adenomas with low-grade dysplasia showed both K-ras mutation and HLA-DR positivity (P = 0.004). K-ras mutation is recognised as an early event in colorectal carcinogenesis. The mutation might give rise to peptides that may be presented on the tumour cell surface by class II molecules, and thereby induce immune responses against neoplastic cells. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:8679466

l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats.

PubMed

Tsai, Wen-Hsin; Wu, Chung-Hsin; Yu, Hong-Jeng; Chien, Chiang-Ting

2017-02-01

Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy-mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. l-Theanine dose-dependently depressed H 2 O 2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP-induced bladder hyperactivity via the inhibition of proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis, and autophagy. Neurourol. Urodynam. 36:297-307, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Continuous N-alkylation reactions of amino alcohols using γ-Al2O3 and supercritical CO2: unexpected formation of cyclic ureas and urethanes by reaction with CO2.

PubMed

Streng, Emilia S; Lee, Darren S; George, Michael W; Poliakoff, Martyn

2017-01-01

The use of γ-Al 2 O 3 as a heterogeneous catalyst in scCO 2 has been successfully applied to the amination of alcohols for the synthesis of N -alkylated heterocycles. The optimal reaction conditions (temperature and substrate flow rate) were determined using an automated self-optimising reactor, resulting in moderate to high yields of the target products. Carrying out the reaction in scCO 2 was shown to be beneficial, as higher yields were obtained in the presence of CO 2 than in its absence. A surprising discovery is that, in addition to cyclic amines, cyclic ureas and urethanes could be synthesised by incorporation of CO 2 from the supercritical solvent into the product.

Method of making thermally removable polyurethanes

DOEpatents

Loy, Douglas A.; Wheeler, David R.; McElhanon, James R.; Saunders, Randall S.; Durbin-Voss, Marvie Lou

2002-01-01

A method of making a thermally-removable polyurethane material by heating a mixture of a maleimide compound and a furan compound, and introducing alcohol and isocyanate functional groups, where the alcohol group and the isocyanate group reacts to form the urethane linkages and the furan compound and the maleimide compound react to form the thermally weak Diels-Alder adducts that are incorporated into the backbone of the urethane linkages during the formation of the polyurethane material at temperatures from above room temperature to less than approximately 90.degree. C. The polyurethane material can be easily removed within approximately an hour by heating to temperatures greater than approximately 90.degree. C. in a polar solvent. The polyurethane material can be used in protecting electronic components that may require subsequent removal of the solid material for component repair, modification or quality control.

40 CFR 721.10524 - Fluorinated alkylsulfonamidol urethane polymer (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... polymer (generic). 721.10524 Section 721.10524 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10524 Fluorinated alkylsulfonamidol urethane polymer (generic). (a... generically as fluorinated alkylsulfonamidol urethane polymer (PMN P-11-384) is subject to reporting under...

40 CFR 721.10524 - Fluorinated alkylsulfonamidol urethane polymer (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... polymer (generic). 721.10524 Section 721.10524 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10524 Fluorinated alkylsulfonamidol urethane polymer (generic). (a... generically as fluorinated alkylsulfonamidol urethane polymer (PMN P-11-384) is subject to reporting under...

Site-selective modification of cellulose nanocrystals with isophorone diisocyanate and formation of polyurethane-CNC composites

Treesearch

Natalie M. Girouard; Shanhong Xu; Gregory T. Schueneman; Meisha L. Shofner; J. Carson Meredith

2016-01-01

The unequal reactivity of the two isocyanate groups in an isophorone diisocyante (IPDI) monomer was exploited to yield modified cellulose nanocrystals (CNCs) with both urethane and isocyanate functionality. The chemical functionality of the modified CNCs was verified with ATR-FTIR analysis and elemental analysis. The selectivity for the secondary isocyanate group using...

Carcinogenesis of urethane: simulation versus experiment.

PubMed

Lajovic, Andrej; Nagy, Leslie D; Guengerich, F Peter; Bren, Urban

2015-04-20

The carcinogenesis of urethane (ethyl carbamate), a byproduct of fermentation that is consistently found in various food products, was investigated with a combination of kinetic experiments and quantum chemical calculations. The main objective of the study was to find ΔG(⧧), the activation free energy for the rate-limiting step of the SN2 reaction among the ultimate carcinogen of urethane, vinyl carbamate epoxide (VCE), and different nucleobases of the DNA. In the experimental part, the second-order reaction rate constants for the formation of the main 7-(2-oxoethyl)guanine adduct in aqueous solutions of deoxyguanosine and in DNA were determined. A series of ab initio, density functional theory (DFT), and semiempirical molecular orbital (MO) calculations was then performed to determine the activation barriers for the reaction between VCE and nucleobases methylguanine, methyladenine, and methylcytosine. Effects of hydration were incorporated with the use of the solvent reaction field method of Tomasi and co-workers and the Langevine dipoles model of Florian and Warshel. The computational results for the main adduct were found to be in good agreement with the experiment, thus presenting strong evidence for the validity of the proposed SN2 mechanism. This allowed us to predict the activation barriers of reactions leading to side products for which kinetic experiments have not yet been performed. Our calculations have shown that the main 7-(2-oxoethyl)deoxyguanosine adduct indeed forms preferentially because the emergence of other adducts either proceeds across a significantly higher activation barrier or the geometry of the reaction requires the Watson-Crick pairs of the DNA to be broken. The computational study also considered the questions of stereoselectivity, the ease of the elimination of the leaving group, and the relative contributions of the two possible reaction paths for the formation of the 1,N(2)-ethenodeoxyguanosine adduct.

Age-related difference in susceptibility of Apc(Min/+) mice towards the chemopreventive efficacy of dietary aspirin and curcumin.

PubMed

Perkins, S; Clarke, A R; Steward, W; Gescher, A

2003-05-06

The nonsteroidal anti-inflammatory drug aspirin and the spice curcumin retard adenoma formation when administered long-term to Apc(Min/+) mice, a model of human familial adenomatous polyposis coli. Both agents interfere with cyclooxygenase activity. When aspirin is administered to Apc(Min/+) mice only postweaning, but not before, it is inefficacious, while curcumin given postweaning is active. Here the hypothesis was tested that dietary aspirin (0.05%) or curcumin (0.2%) prevent or delay adenoma formation in offsprings when administered to Apc(Min/+) mothers and up to the end of weaning, but not afterwards. Whereas curcumin was without effect when administered in this way, aspirin reduced numbers of intestinal adenomas by 21%. When aspirin given up to the end of weaning was combined with curcumin administered from the end of weaning for the rest of the animals' lifetime, intestinal adenoma numbers were reduced by 38%. The combination was not superior to intervention postweaning with curcumin alone. These results show that aspirin exerts chemopreventive activity in the Apc(Min/+) mouse during tumour initiation/early promotion, while curcumin is efficacious when given at a later stage of carcinogenic progression. Thus, the results suggest that in this mouse model aspirin and curcumin act during different 'windows' of neoplastic development.

Genetics, gene expression and bioinformatics of the pituitary gland.

PubMed

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2009-04-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. Copyright 2009 S. Karger AG, Basel.

Genetics, Gene Expression and Bioinformatics of the Pituitary Gland

PubMed Central

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W.; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P.; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2011-01-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown etiology. These studies reveal critical roles for Wnt signalling pathways including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic proteins antagonists, and targets of notch signalling. Current studies are investigating roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. PMID:19407506

Use of New Industrial Coatings for the U.S. Navy Waterfront Structures

DTIC Science & Technology

2008-12-01

utilized as a coating for the interior and exterior of piping systems, which either are located in harsh environments or are transporting substances with...typical application process, a separate set of test Table 7. MCU Coating Systems (SSPC SP 10 Surfaces) (5). SystelD CoatiIli System A Zinc -rich urethane...urethane/MID & AI-filled Urethane/MIO-filled urethane 315/315/314 336/336/336 340/340/336 ~ Micaceous iron oxide. \\) Aluminum. C Zinc . 12 as well as an

Chemoprevention with special reference to inherited colorectal cancer.

PubMed

Lynch, Patrick M

2008-01-01

Familial Adenomatous Polyposis (FAP) is a model for the adenoma-carcinoma sequence in several respects. One important area in which FAP serves as a model is chemoprevention. Early prevention trials mainly utilized micronutrients and were largely unsuccessful in preventing or causing regression of adenomas. A new era was ushered in by the recognition that antiarthritic doses of a nonsteroidal anti-inflammatory agent (NSAID), sulindac, could actually induce regression of colorectal adenomas in patients with FAP. Follow-up studies showed positive but variable long-term efficacy for colorectal adenomas, but sulindac appears to lack significant benefit in regressing duodenal adenomas or preventing initial occurrence of adenomas in APC mutation carriers. Due to the well-known side effects of traditional NSAIDs, selective COX-2 inhibitors have been studied rather extensively. Celecoxib has shown benefit in regressing colorectal adenomas and appears to have some duodenal activity as well. Rofecoxib, in smaller trials, showed efficacy as well. However, the entire field of NSAID research in chemoprevention is undergoing reexamination in light of recent demonstration of cardiovascular toxicity in nonfamilial or sporadic adenoma prevention trials. Whether NSAIDs will have a significant future in FAP chemoprevention will depend on a sober assessment of risks and benefits. These same issues will likely foster a more intensive search for new agents. FAP will undoubtedly continue to have a lead role in the testing of new agents, both in the interest of FAP management as such, and in anticipation of trials in nonfamilial adenomas, a problem with even greater societal impact. The historical development of chemoprevention in FAP will be presented, with an emphasis on issues of trial design.

Poly(glycerol sebacate urethane)-cellulose nanocomposites with water-active shape-memory effects.

PubMed

Wu, Tongfei; Frydrych, Martin; O'Kelly, Kevin; Chen, Biqiong

2014-07-14

Biodegradable and biocompatible materials with shape-memory effects (SMEs) are attractive for use as minimally invasive medical devices. Nanocomposites with SMEs were prepared from biodegradable poly(glycerol sebacate urethane) (PGSU) and renewable cellulose nanocrystals (CNCs). The effects of CNC content on the structure, water absorption, and mechanical properties of the PGSU were studied. The water-responsive mechanically adaptive properties and shape-memory performance of PGSU-CNC nanocomposites were observed, which are dependent on the content of CNCs. The PGSU-CNC nanocomposite containing 23.2 vol % CNCs exhibited the best SMEs among the nanocomposites investigated, with the stable shape fixing and shape recovery ratios being 98 and 99%, respectively, attributable to the formation of a hydrophilic, yet strong, CNC network in the elastomeric matrix. In vitro degradation profiles of the nanocomposites were assessed with and without the presence of an enzyme.

Synthesis of palm-based polyurethane-LiClO{sub 4} via prepolymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sien, Jason Wong Chee; School of Biosciences, Taylor’s University, Subang Jaya; Badri, Khairiah Haji

2015-09-25

Palm-based polyurethane (pPU) with varying lithium salt (LiClO{sub 4}) content was synthesized. Higher loading percentage of LiClO{sub 4} in the pPU led to the inhibition of prepolymerization process from taking place. Hydrogen bonded C=O was detected in the FTIR spectrum indicating the hydrogen bonding between the urethane bonds. Ordered complexed C=O was observed in the FTIR spectrum confirming the complex formation between urethane bond and Li{sup +} ion. DSC thermogram showed the increase in the LiClO{sub 4} content could increase the glass transition temperature. SEM micrographs exhibited that more bubbles were formed when the LiClO{sub 4} increased from 10 tomore » 30wt% indicating the reaction between free isocyanate groups with moisture presence in the salt due to the hygroscopic properties of LiClO{sub 4}.« less

Celecoxib induces proliferation and Amphiregulin production in colon subepithelial myofibroblasts, activating erk1-2 signaling in synergy with EGFR.

PubMed

Benelli, Roberto; Venè, Roberta; Minghelli, Simona; Carlone, Sebastiano; Gatteschi, Beatrice; Ferrari, Nicoletta

2013-01-01

The COX-2 inhibitor Celecoxib, tested in phase III trials for the prevention of sporadic colon adenomas, reduced the appearance of new adenomas, but was unable to affect the incidence of colon cancer. Moreover the 5years follow-up showed that patients discontinuing Celecoxib treatment had an increased incidence of adenomas as compared to the placebo arm. In the APC(min/+) mouse model short term treatment with Celecoxib reduced gut adenomas, but a prolonged administration of the drug induced fibroblast activation and intestinal fibrosis with a final tumor burden. The way Celecoxib could directly activate human colon myofibroblasts (MF) has not yet been investigated. We found that MF are activated by non toxic doses of Celecoxib. Celecoxib induces erk1-2 and Akt phosphorylation within 5'. This short term activation is apparently insufficient to cause phenotypic changes, but the contemporary triggering of EGFR causes an impressive synergic effect inducing MF proliferation and the neo-expression and release of Amphiregulin (AREG), a well known EGFR agonist involved in colon cancer progression. As a confirm to these observations, the erk inhibitor U0126 and the EGFR inhibitors Tyrphostin and Cetuximab were able to contrast AREG induction. Our data provide evidence that Celecoxib directly activates MF empowering EGFR signaling. According to these results the association with EGFR (or erk1-2) inhibitors could abolish the off-target activity of Celecoxib, possibly extending the potential of this drug for colon cancer prevention. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Strong photoluminescence characteristics of sulforhodamine B attached on photonic crystal

NASA Astrophysics Data System (ADS)

Kim, Byoung-Ju; Kang, Kwang-Sun

2014-10-01

The optical properties of sulforhodamine B (SRH) impregnated in photonic crystal by two step synthetic processes including a urethane bond formation between a 3-isocyanatopropyl triethoxysilane (ICPTES, -N=C=O) and a SRH with elevated temperature in pyridine and hydrolysis-condensation reactions between synthesized ICPTES/SRH (ICPSRH) and tetraethoxyorthosilicate (TEOS) in NH4OH. The monodisperse silica spheres impregnated the ICPSRH (ICPSRHS) are fabricated. The reduction of the absorption peak at 2270 cm-1 representing asymmetric stretching vibration of -N=C=O indicates the progress of the reaction and new absorption peak at 1712 cm-1 characterizing -C=O stretching vibration indicates the formation of urethane bond. The UV-visible absorption spectra show the broadened spectral line width by intermolecular interaction. The photoluminescence (PL) peak of the SRH in methanol shows a hypsochromic shift with the increase the excitation wavelength. However, the PL peak for the ICPSRH exhibits a bathochromic shift as the excitation wavelength increases. The PL peak for the ICPSRH shows no hypsochromic or bathochromic shift. The PL peaks for SRH in methanol, ICPSRH and ICPSRHS are at 568, 598 and 572 nm, respectively. The main cause of the PL peak shift is due to the intermolecular interaction.

Novel carboxy functionalized sol-gel precursors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolter, H.; Storch, W.; Gellermann, C.

1996-12-31

A novel family of inorganic-organic copolymers (ORMOCER`s) derived from urethane- and thioether(meth)acrylate alkoxysilanes has been successfully exploited for a variety of diverse applications. In order to widen the range of applications an additional functionality (carboxy group) has been incorporated int his silane type. Conventional sol-gel processing facilitates the formation of an inorganic Si-O-Si-network via hydrolysis and polycondensation reactions of alkoxysilyl moieties and in addition, the (meth)acrylate groups are available for radically induced polymerization to obtain a complementary organic polymer structure. The presence of a carboxy group would appear to have great potential for a range of diverse areas of application,more » such as an internal catalyst for the sol-gel process, complexation of elements such as Zr and Ti, increasing the adhesion to various substrates and modification of solubility. A number of novel silanes and their syntheses will be described in this paper.« less

Suppression of Familial Adenomatous Polyposis by CP-31398, a TP53 modulator, in APCmin/+ Mice1

PubMed Central

Rao, Chinthalapally V.; Swamy, Malisetty V.; Patlolla, Jagan M.R.; Kopelovich, Levy

2008-01-01

p53 mutations occur in a large number of human malignancies. Mutant p53 is unable to affect downstream genes necessary for DNA repair, cell cycle regulation, and apoptosis. The styrylquinazoline CP-31398 can rescue destabilized mutant p53 expression and promote activity of wild-type p53. The present study examines chemopreventive effects of CP-31398 on intestinal adenoma development in an animal model of familial adenomatous polyposis (FAP). Effects were examined at both early and late stages of adenoma formation. Effects of CP-31398 on early-stage adenomas were determined by feeding 7-week-old female C57B/6J-APCmin (heterozygous) and wild-type C57BL/6J mice with American Institute of Nutrition (AIN)-76A diets containing 0, 100, or 200 ppm CP-31398 for 75 days. To examine activity toward late-stage adenomas, CP31398 administration was delayed until 15 weeks of age and continued for 50 days. During early-stage intervention, dietary CP-31398 suppressed development of intestinal tumors by 36% (p < 0.001) and 75% (p < 0.0001), at low and high dose, respectively. During late-stage intervention, CP-31398 also significantly suppressed intestinal polyp formation, albeit to a lesser extent than observed with early intervention. Adenomas in treated mice showed increased apoptotic cell death and decreased proliferation in conjunction with increased expression of p53, p21WAF1/CIP, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP). These observations demonstrate for the first time that the p53-modulating agent CP-31398 possesses significant chemopreventive activity in vivo against intestinal neoplastic lesions in genetically-predisposed APCmin/+ mice. Chemopreventive activity of other agents that restore tumor suppressor functions of mutant p53 in tumor cells is currently under investigation. PMID:18794156

Phenotypical and Pharmacological Characterization of Stem-Like Cells in Human Pituitary Adenomas.

PubMed

Würth, Roberto; Barbieri, Federica; Pattarozzi, Alessandra; Gaudenzi, Germano; Gatto, Federico; Fiaschi, Pietro; Ravetti, Jean-Louis; Zona, Gianluigi; Daga, Antonio; Persani, Luca; Ferone, Diego; Vitale, Giovanni; Florio, Tullio

2017-09-01

The presence and functional role of tumor stem cells in benign tumors, and in human pituitary adenomas in particular, is a debated issue that still lacks a definitive formal demonstration. Fifty-six surgical specimens of human pituitary adenomas were processed to establish tumor stem-like cultures by selection and expansion in stem cell-permissive medium or isolating CD133-expressing cells. Phenotypic and functional characterization of these cells was performed (1) ex vivo, by immunohistochemistry analysis on paraffin-embedded tissues; (2) in vitro, attesting marker expression, proliferation, self-renewal, differentiation, and drug sensitivity; and (3) in vivo, using a zebrafish model. Within pituitary adenomas, we identified rare cell populations expressing stem cell markers but not pituitary hormones; we isolated and expanded in vitro these cells, obtaining fibroblast-free, stem-like cultures from 38 pituitary adenoma samples. These cells grow as spheroids, express stem cell markers (Oct4, Sox2, CD133, and nestin), show sustained in vitro proliferation as compared to primary cultures of differentiated pituitary adenoma cells, and are able to differentiate in hormone-expressing pituitary cells. Besides, pituisphere cells, apparently not tumorigenic in mice, engrafted in zebrafish embryos, inducing pro-angiogenic and invasive responses. Finally, pituitary adenoma stem-like cells express regulatory pituitary receptors (D2R, SSTR2, and SSTR5), whose activation by a dopamine/somatostatin chimeric agonist exerts antiproliferative effects. In conclusion, we provide evidence that human pituitary adenomas contain a subpopulation fulfilling biological and phenotypical signatures of tumor stem cells that may represent novel therapeutic targets for therapy-resistant tumors.

Low doses of urethane effectively inhibit spinal seizures evoked by sudden cooling of toad isolated spinal cord

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pina-crespo, J.C.; Dalo, N.L.

1992-01-01

The effect of low doses of urethane on three phases of spinal seizures evoked by sudden cooling (SSSC) of toad isolated spinal cord was studied. In control toads, SSSC began with a latency of 91[plus minus]3 sec exhibiting brief tremors, followed by clonic muscle contractions and finally reaching a tonic contraction. The latency of onset of seizures was significantly enhanced. The tonic phase was markedly abolished in toads pretreated intralymphaticaly with 0.15 g/kg of urethane. Tremors were the only phase observed in 55% of toads that received doses of 0.2 g/kg, and a total blockage of seizures was seen aftermore » doses of 0.25 g/kg of urethane in 50% of the preparations. A possible depressant effect of urethane on transmission mediated by excitatory amino acids is suggested.« less

Molecular layer deposition of polyurethane-Polymerisation at the very contact to native aluminium and copper

NASA Astrophysics Data System (ADS)

Fug, Frank; Petry, Adrien; Jost, Hendrik; Ahmed, Aisha; Zamanzade, Mohammad; Possart, Wulff

2017-12-01

Thin layers of polyurethane monomers (diol, triol, diisocyanate) are deposited from gas phase onto native aluminium and copper surfaces. According to infrared external reflection absorption spectra both alcohols undergo only weak physical interactions with both metals. The diisocyanate on the other hand reveals resistance against desorption and rich new spectral features indicate strong adhesion. Preparation of urethane layers by sequential deposition of diisocyanate and diol yields urethane linkages. Urethane is formed faster on Cu than on Al. Scanning force microscopy reveals heterogeneous layers with metal dependent morphology. They show poor resistance against tetrahydrofuran rinsing i.e. most part of the formed urethane containing molecules are removed. Nevertheless, a residue of molecules sticks on the metal. It contains strongly adsorbed isocyanates and few isocyanate units which are bonded to diol units via urethane links. Further improvement of the molecular layer deposition is necessary to achieve well-crosslinked polyurethane layers.

Pressor responses to nasal stimulation are unaltered after disrupting the CPA.

PubMed

Panneton, W Michael; Sun, Wei; Gan, Qi

2008-12-15

Stimulation of either the caudal pressor area (CPA) in the most caudal ventrolateral medulla with glutamate, or the nasal mucosa with ammonia vapors, induces an increase in mean arterial blood pressure (MABP). In the present study, we determined if neurons in the CPA serve as a relay for the increase in MABP seen after nasal stimulation. Ammonia vapors stimulated the nasal mucosa of rats anesthetized with either urethane alone or ketamine/xylazine and urethane to induce an increase in MABP, a bradycardia, and an apnea. Bilateral injections (50 nl) of glycine (1 M) or muscimol (2 mM) were placed in the CPA and the nasal mucosa again stimulated. The increases in MABP, the bradycardia and the duration of apnea to nasal stimulation were unchanged after either injection. However, resting MABP and HR were decreased significantly after glycine injections and resting MABP and resting respiratory rate were decreased after muscimol injections. The increase in MABP seen with nasal stimulation also did not change after multiple bilateral injections (3x40 nl) of ibotenate (5 microg/microl) in the CPA, but the bradycardia was eliminated and the duration of apnea was significantly shorter. These results suggest that the increase in MABP induced by nasal stimulation is via routes that do not include neurons in the CPA.

Low-VOC wood floor varnishes from waterborne oil-modified urethanes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ingle, D.M.; Petschke, G.H.

Varnishes protect wood flooring and enhance its beauty. Varnish compositions have varied from drying oils and alkyds to more durable systems (moisture-cured urethanes, oil-modified urethanes, epoxies and UV-curable coatings). Some chemistries are better suited for professional or factory applied situations. Oils, alkyds and oil-modified urethanes (OMU) are suitable for onsite professional application or even refinish application by homeowners (DIY market). These materials traditionally have been high in VOC. Recently, waterborne (WB) systems (such as polyurethane dispersions) with greatly reduced VOC have been used; high costs and relatively poor durability are drawbacks. A new generation of high performance waterborne oil-modified urethanemore » is now available with extended shelf-stability required for contractor and consumer markets. Formulated varnishes are coming onto the market that offer performance similar to conventional OMU, but with significant reductions in VOC. For example, a typical formulation for a conventional solvent-borne oil-modified urethane can be supplied at 1.6 lb/gal (less water). This represents a VOC reduction of 70-75% at equal application coating weight. Furthermore, waterborne oil-modified urethane offers advantages over polyurethane dispersions in performance areas such as durability and mar resistance.« less

Ultrastructure of the C cells forming adenoma-like nodules of the thyroid in experimental hypervitaminosis A.

PubMed

Roszkiewicz, J; Roszkiewicz, A

1977-01-01

The degranulation of the C cells, their hypertrophy and hyperplasia leading to the formation adenoma-like nodules were observed under conditions of prolonged hypervitaminosis A which causes bone damage without associated hypercalcemia. These changes which are probably the morphologic manifestation of the increased requirement of the body for calcitonin, connected with the damage of the bone tissue seem to indicate that calcitonin is an important factor essential for the protection of skeleton from its excessive mineralization.

Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway

PubMed Central

Fu, Wei; Tang, Hao; Chen, Xiao; Zhao, Yao; Zheng, Lili; Pan, Sijian; Wang, Weiqing; Bian, Liuguan; Sun, Qingfang

2016-01-01

Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence. PMID:26824322

The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas Causing Cushing's Disease.

PubMed

Perez-Rivas, Luis G; Theodoropoulou, Marily; Ferraù, Francesco; Nusser, Clara; Kawaguchi, Kohei; Stratakis, Constantine A; Faucz, Fabio Rueda; Wildemberg, Luiz E; Assié, Guillaume; Beschorner, Rudi; Dimopoulou, Christina; Buchfelder, Michael; Popovic, Vera; Berr, Christina M; Tóth, Miklós; Ardisasmita, Arif Ibrahim; Honegger, Jürgen; Bertherat, Jerôme; Gadelha, Monica R; Beuschlein, Felix; Stalla, Günter; Komada, Masayuki; Korbonits, Márta; Reincke, Martin

2015-07-01

We have recently reported somatic mutations in the ubiquitin-specific protease USP8 gene in a small series of adenomas of patients with Cushing's disease. To determine the prevalence of USP8 mutations and the genotype-phenotype correlation in a large series of patients diagnosed with Cushing's disease. We performed a retrospective, multicentric, genetic analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger sequencing. Biochemical and clinical features were collected and examined within the context of the mutational status of USP8, and new mutations were characterized by functional studies. A total of 145 patients who underwent surgery for an ACTH-producing pituitary adenoma. Mutational status of USP8. Biochemical and clinical features included sex, age at diagnosis, tumor size, preoperative and postoperative hormonal levels, and comorbidities. We found somatic mutations in USP8 in 48 (36%) pituitary adenomas from patients with Cushing's disease but in none of 11 silent corticotropinomas. The prevalence was higher in adults than in pediatric cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8-mutated adenomas were diagnosed at an earlier age than those with wild-type lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 ± 7 mm and were inversely associated with the development of postoperative adrenal insufficiency. All the mutations affected the residues Ser718 or Pro720, including five new identified alterations. Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells. USP8 is frequently mutated in adenomas causing Cushing's disease, especially in those from female adult patients diagnosed at a younger age.

Investigating the reactivity of pMDI with wood cell walls using high-resolution solution-state NMR spectroscopy

Treesearch

Daniel J. Yelle; John Ralph; Charles R. Frihart

2009-01-01

The objectives of this study are the following: (1) Use solution-state NMR to assign contours in HSQC spectra of the reaction products between pMDI model compounds and: (a) lignin model compounds, (b) milled-wood lignin, (c) ball-milled wood, (d) microtomed loblolly pine; (2) Determine where and to what degree urethane formation occurs with loblolly pine cell wall...

Hollow multilayer microcapsules for pH-/thermally responsive drug delivery using aliphatic poly(urethane-amine) as smart component.

PubMed

Shi, Jun; Du, Chao; Shi, Jin; Wang, Yaming; Cao, Shaokui

2013-04-01

Hollow multilayer microcapsules made of aliphatic poly(urethane-amine) (PUA) and sodium poly(styrene sulfonate) (PSS), templated on PSS-doped CaCO3 particles, are prepared for pH-/thermally responsive drug delivery. The electrostatic interaction and hydrogen bonding under weak-acid conditions between aliphatic PUA and PSS contribute to the formation of multilayer microcapsules. Scanning electron microscopy (SEM) results demonstrate an obvious variation of the hollow multilayer microcapsules in response to changes in temperature and pH value. Drug-release behaviors using DOX as a model drug demonstrate that the drug release increases on decreasing the pH value because of the interaction weakness between aliphatic PUA and PSS in acidic conditions. Moreover, the drug release is higher at 55 °C than that at 37 °C for the sake of the shrinkage of aliphatic PUA above its lower critical solution temperature (LCST). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stomach Polyps

MedlinePlus

... polyps are: Chronic stomach inflammation. Also known as gastritis, this condition can cause the formation of hyperplastic ... pylori) bacteria are a common cause of the gastritis that contributes to hyperplastic polyps and adenomas. Familial ...

Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?

PubMed

Castinetti, Frederic; Brue, Thierry

2010-08-01

Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

Peptostreptococcus anaerobius Induces Intracellular Cholesterol Biosynthesis in Colon Cells to Induce Proliferation and Causes Dysplasia in Mice.

PubMed

Tsoi, Ho; Chu, Eagle S H; Zhang, Xiang; Sheng, Jianqiu; Nakatsu, Geicho; Ng, Siew C; Chan, Anthony W H; Chan, Francis K L; Sung, Joseph J Y; Yu, Jun

2017-05-01

Stool samples from patients with colorectal cancer (CRC) have a higher abundance of Peptostreptococcus anaerobius than stool from individuals without CRC, based on metagenome sequencing. We investigated whether P anaerobius contributes to colon tumor formation in mice and its possible mechanisms of carcinogenesis. We performed quantitative polymerase chain reaction analyses to measure P anaerobius in 112 stool samples and 255 colon biopsies from patients with CRC or advanced adenoma and from healthy individuals (controls) undergoing colonoscopy examination at hospitals in Hong Kong and Beijing. C57BL/6 mice were given broad-spectrum antibiotics, followed by a single dose of azoxymethane, to induce colon tumor formation. Three days later, mice were given P anaerobius or Esherichia coli MG1655 (control bacteria), via gavage, for 6 weeks. Some mice were also given the nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin. Intestine tissues were collected and analyzed histologically. The colon epithelial cell line NCM460 and colon cancer cell lines HT-29 and Caco-2 were exposed to P anaerobius or control bacteria; cells were analyzed by immunoblot, proliferation, and bacterial attachment analyses and compared in gene expression profiling studies. Gene expression was knocked down in these cell lines with small interfering RNAs. P anaerobius was significantly enriched in stool samples from patients with CRC and in biopsies from patients with colorectal adenoma or CRC compared with controls. Mice depleted of bacteria and exposed to azoxymethane and P anaerobius had a higher incidence of intestinal dysplasia (63%) compared with mice not given the bacteria (8.3%; P < .01). P anaerobius mainly colonized the colon compared with the rest of the intestine. Colon cells exposed to P anaerobius had significantly higher levels of proliferation than control cells. We found genes that regulate cholesterol biosynthesis, Toll-like receptor (TLR) signaling, and AMP-activated protein kinase signaling to be significantly up-regulated in cells exposed to P anaerobius. Total cholesterol levels were significantly increased in colon cell lines exposed to P anaerobius via activation of sterol regulatory element-binding protein 2. P anaerobius interacted with TLR2 and TLR4 to increase intracellular levels of reactive oxidative species, which promoted cholesterol synthesis and cell proliferation. Depletion of reactive oxidative species by knockdown of TLR2 or TLR4, or incubation of cells with an antioxidant, prevented P anaerobius from inducing cholesterol biosynthesis and proliferation. Levels of P anaerobius are increased in human colon tumor tissues and adenomas compared with non-tumor tissues; this bacteria increases colon dysplasia in a mouse model of CRC. P anaerobius interacts with TLR2 and TLR4 on colon cells to increase levels of reactive oxidative species, which promotes cholesterol synthesis and cell proliferation. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

G-Protein-Coupled Estrogen Receptor Antagonist G15 Decreases Estrogen-Induced Development of Non-Small Cell Lung Cancer.

PubMed

Liu, Changyu; Liao, Yongde; Fan, Sheng; Fu, Xiangning; Xiong, Jing; Zhou, Sheng; Zou, Man; Wang, Jianmiao

2017-08-25

G-protein-coupled estrogen receptor (GPER) was found to promote Non-small cell lung cancer (NSCLC) by estrogen, indicating the potential necessity of inhibiting GPER by selective antagonist. This study was performed to elucidate the function of GPER selective inhibitor G15 in NSCLC development. Cytoplasmic GPER (cGPER) and nuclear GPER (nGPER) were detected by immunohistochemical analysis in NSCLC samples. The relation of GPER and estrogen receptor β (ERβ) expression and correlation between GPER, ERβ and clinical factors were analyzed. The effects of activating GPER and function of G15 were analyzed in proliferation of A549, H1793 cell lines and development of urethane-induced adenocarcinoma. Overexpression of cGPER and nGPER was detected in 80.49% (120/150) and 52.00% (78/150) of the NSCLC samples. High expression of GPER related with higher stages, poorer differentiation and high expression of ERβ. Protein level of GPER in A549 and H1793 cell lines increased by treatment of E2, G1 (GPER agonist) or Ful (fulvestrant, ERβ antagonist), and decreased by G15. Administration with G15 reversed the E2- or G1-induced cell growth by inhibiting GPER. In urethane-induced adenocarcinoma mice, number of tumor nodules and tumor index increased in E2 or G1 group and decreased by treatment of G15. These findings deomonstrate that using of G15 to block GPER signaling may be considered as a new therapeutic target in NSCLC.

Developmental Hypothyroidism Reduces the Expression of ...

EPA Pesticide Factsheets

Disruption of thyroid hormone (TH) is a known effect of environmental contaminants. Neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been implicated in brain dysfunction resulting from severe developmental TH insufficiency. Neurotrophins are also implicated in activity-dependent plasticity, a process critical for appropriate use-dependent connectivity in the developing brain and for memory formation in the adult. This study examined activity-induced expression of neurotrophin gene products in the hippocampus using the long-term potentiation (LTP) after developmental hypothyroidism induced by propylthiouracil (PTU). Pregnant rats were exposed to PTU (0 or I0ppm) via the drinking water from early gestation to weaning. Adult male offspring were anesthetized with urethane and implanted with electrodes in the dentate gyrus (00) and perforant path (PP). LTP was induced by PP stimulation and responses from 00 were monitored at 15m intervals until sacrifice of the animals 5 h later. The 00 was dissected from the stimulated and nonstimulated hemispheres for rtPCR analysis of the neurotrophins Bdnf, Ngf, Ntf3 and related genes Egrl, Arc, Klf9. We found no PTU-induced difference in basal levels of expression of any of these genes in the nonstimulated 00. LTP increased expression of Bdnf, Ngf, Arc and Klj9 in the control DG, and reduced expression of Ntf3. LTP in DG from PTU animals failed to increase expression of Bdnf,

Colorectal carcinogenesis: Review of human and experimental animal studies

PubMed Central

Tanaka, Takuji

2009-01-01

This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model) will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma). These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries. PMID:19332896

Identification of cancer initiating cells in K-Ras driven lung adenocarcinoma.

PubMed

Mainardi, Sara; Mijimolle, Nieves; Francoz, Sarah; Vicente-Dueñas, Carolina; Sánchez-García, Isidro; Barbacid, Mariano

2014-01-07

Ubiquitous expression of a resident K-Ras(G12V) oncogene in adult mice revealed that most tissues are resistant to K-Ras oncogenic signals. Indeed, K-Ras(G12V) expression only induced overt tumors in lungs. To identify these transformation-permissive cells, we induced K-Ras(G12V) expression in a very limited number of adult lung cells (0.2%) and monitored their fate by X-Gal staining, a surrogate marker coexpressed with the K-Ras(G12V) oncoprotein. Four weeks later, 30% of these cells had proliferated to form small clusters. However, only SPC(+) alveolar type II (ATII) cells were able to form hyperplastic lesions, some of which progressed to adenomas and adenocarcinomas. In contrast, induction of K-Ras(G12V) expression in lung cells by intratracheal infection with adenoviral-Cre particles generated hyperplasias in all regions except the proximal airways. Bronchiolar and bronchioalveolar duct junction hyperplasias were primarily made of CC10(+) Clara cells. Some of them progressed to form benign adenomas. However, only alveolar hyperplasias, exclusively made up of SPC(+) ATII cells, progressed to yield malignant adenocarcinomas. Adenoviral infection induced inflammatory infiltrates primarily made of T and B cells. This inflammatory response was essential for the development of K-Ras(G12V)-driven bronchiolar hyperplasias and adenomas, but not for the generation of SPC(+) ATII lesions. Finally, activation of K-Ras(G12V) during embryonic development under the control of a Sca1 promoter yielded CC10(+), but not SPC(+), hyperplasias, and adenomas. These results, taken together, illustrate that different types of lung cells can generate benign lesions in response to K-Ras oncogenic signals. However, in adult mice, only SPC(+) ATII cells were able to yield malignant adenocarcinomas.

The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Kang Nyeong; Choi, Ho Soon, E-mail: hschoi96@hanyang.ac.kr; Yang, Sun Young

Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastricmore » adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.« less

Development of low viscosity alkane-based urethane for connector potting applications

NASA Technical Reports Server (NTRS)

Morris, D. E.

1983-01-01

Two series of saturated hydrocarbon-based urethanes were prepared with isophorone diisocyanate and one series with methyl bis (4-cyclohexyl isocyanate). The urethanes with molecular weights as great as 2500 had viscosities low enough and a working life long enough to be used in potting, molding, and coating applications. Specimens were prepared and mechanical properties such as hardness, tensile strength elongation, and tear strength were determined. Thermomechanical properties (glass transition and expansion coefficient) and thermogravimetric properties were determined.

Thio-urethanes improve properties of dual-cured composite cements.

PubMed

Bacchi, A; Dobson, A; Ferracane, J L; Consani, R; Pfeifer, C S

2014-12-01

This study aims at modifying dual-cure composite cements by adding thio-urethane oligomers to improve mechanical properties, especially fracture toughness, and reduce polymerization stress. Thiol-functionalized oligomers were synthesized by combining 1,3-bis(1-isocyanato-1-methylethyl)benzene with trimethylol-tris-3-mercaptopropionate, at 1:2 isocyanate:thiol. Oligomer was added at 0, 10 or 20 wt% to BisGMA-UDMA-TEGDMA (5:3:2, with 25 wt% silanated inorganic fillers) or to one commercial composite cement (Relyx Ultimate, 3M Espe). Near-IR was used to measure methacrylate conversion after photoactivation (700 mW/cm(2) × 60s) and after 72 h. Flexural strength and modulus, toughness, and fracture toughness were evaluated in three-point bending. Polymerization stress was measured with the Bioman. The microtensile bond strength of an indirect composite and a glass ceramic to dentin was also evaluated. Results were analyzed with analysis of variance and Tukey's test (α = 0.05). For BisGMA-UDMA-TEGDMA cements, conversion values were not affected by the addition of thio-urethanes. Flexural strength/modulus increased significantly for both oligomer concentrations, with a 3-fold increase in toughness at 20 wt%. Fracture toughness increased over 2-fold for the thio-urethane modified groups. Contraction stress was reduced by 40% to 50% with the addition of thio-urethanes. The addition of thio-urethane to the commercial cement led to similar flexural strength, toughness, and conversion at 72h compared to the control. Flexural modulus decreased for the 20 wt% group, due to the dilution of the overall filler volume, which also led to decreased stress. However, fracture toughness increased by up to 50%. The microtensile bond strength increased for the experimental composite cement with 20 wt% thio-urethane bonding for both an indirect composite and a glass ceramic. Novel dual-cured composite cements containing thio-urethanes showed increased toughness, fracture toughness and bond strength to dentin while demonstrating reduced contraction stress. All of these benefits are derived without compromising the methacrylate conversion of the resin component. The modification does not require changing the operatory technique. © International & American Associations for Dental Research.

Thio-urethanes Improve Properties of Dual-cured Composite Cements

PubMed Central

Bacchi, A.; Dobson, A.; Ferracane, J.L.; Consani, R.; Pfeifer, C.S.

2014-01-01

This study aims at modifying dual-cure composite cements by adding thio-urethane oligomers to improve mechanical properties, especially fracture toughness, and reduce polymerization stress. Thiol-functionalized oligomers were synthesized by combining 1,3-bis(1-isocyanato-1-methylethyl)benzene with trimethylol-tris-3-mercaptopropionate, at 1:2 isocyanate:thiol. Oligomer was added at 0, 10 or 20 wt% to BisGMA-UDMA-TEGDMA (5:3:2, with 25 wt% silanated inorganic fillers) or to one commercial composite cement (Relyx Ultimate, 3M Espe). Near-IR was used to measure methacrylate conversion after photoactivation (700 mW/cm2 × 60s) and after 72 h. Flexural strength and modulus, toughness, and fracture toughness were evaluated in three-point bending. Polymerization stress was measured with the Bioman. The microtensile bond strength of an indirect composite and a glass ceramic to dentin was also evaluated. Results were analyzed with analysis of variance and Tukey’s test (α = 0.05). For BisGMA-UDMA-TEGDMA cements, conversion values were not affected by the addition of thio-urethanes. Flexural strength/modulus increased significantly for both oligomer concentrations, with a 3-fold increase in toughness at 20 wt%. Fracture toughness increased over 2-fold for the thio-urethane modified groups. Contraction stress was reduced by 40% to 50% with the addition of thio-urethanes. The addition of thio-urethane to the commercial cement led to similar flexural strength, toughness, and conversion at 72h compared to the control. Flexural modulus decreased for the 20 wt% group, due to the dilution of the overall filler volume, which also led to decreased stress. However, fracture toughness increased by up to 50%. The microtensile bond strength increased for the experimental composite cement with 20 wt% thio-urethane bonding for both an indirect composite and a glass ceramic. Novel dual-cured composite cements containing thio-urethanes showed increased toughness, fracture toughness and bond strength to dentin while demonstrating reduced contraction stress. All of these benefits are derived without compromising the methacrylate conversion of the resin component. The modification does not require changing the operatory technique. PMID:25248610

Do Interleukin Polymorphisms Play a Role in the Prevention of Colorectal Adenoma Recurrence by Dietary Flavonols?

PubMed Central

Bobe, Gerd; Murphy, Gwen; Albert, Paul S.; Sansbury, Leah B.; Young, Matthew R.; Lanza, Elaine; Schatzkin, Arthur; Colburn, Nancy H.; Cross, Amanda J.

2010-01-01

Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1β, 6, 8, and 10, alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence.. Overall, SNPs in genes encoding IL-1β, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR = 2.23, 95% CI: 1.07–4.66, P interaction = 0.03) or IL-10 -819 C (OR = 2.18, 95% CI: 1.05–4.51, P interaction = 0.05) had an elevated risk of high risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 -174 GG in combination with above median flavonol intake (OR = 0.14, 95% CI: 0.03–0.66) or with decreased IL 6 concentrations (OR = 0.14, 95% CI: 0.03–0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence. PMID:21160427

Use of a Lysine-Derived Urethane Surgical Adhesive as an Alternative to Progressive Tension Sutures in Abdominoplasty Patients: A Cohort Study.

PubMed

Spring, Michelle A

2018-04-07

Fluid accumulation is a common complication after abdominoplasty procedures, and is typically managed by the placement of post-surgical drains. Progressive tension sutures (PTS) have been shown to be an effective approach to reduce the dead space by point-wise mechanical fixation, allowing for drain-free procedures. Lysine-derived urethane surgical adhesive provides an alternative approach for mechanical fixation and reduction of dead space, and may reduce surgery time compared to PTS. This prospective, controlled, single center clinical study compared progressive tension suture wound closure technique without drains (control) to tissue adhesive wound closure technique without drains (test) during abdominoplasty surgery. The objective was to determine if lysine-derived urethane surgical adhesive is an effective alternative to PTS for drain-free abdominoplasty procedures. Patients undergoing abdominoplasty who met the established inclusion/exclusion criteria were consented and enrolled in the study. Ten PTS (control) cases were performed, followed immediately by ten tissue adhesive (test) cases. Drains were not used in any procedures. Key outcome measures included all major and minor post-surgical complications requiring any intervention, the time to place progressive tension sutures versus time for tissue adhesive application, and number of PTS attachments versus number of adhesive drops applied. Surgeries were completed over an 8-month period. No statistical differences were identified between the two groups with regard to age, BMI, dissection surface area or flap weight. No clinical seroma formation was observed in either group. In the control (PTS) group, two patients developed small areas of dermal closure suture abscess requiring removal of suture material. One control patient developed drainage and fat necrosis thought to be related to PTS above the incision and later required a scar revision. One tissue adhesive patient developed hypertrophic scars of both her breast reduction and abdominoplasty scars requiring additional treatment. The average time to place PTS in the control group was 10.7 minutes (range, 7-18 minutes) and the average number of sutures placed was 16.6 (range, 12-22 sutures). In the test group, the average time to place the tissue adhesive and hold pressure was 5.9 minutes (range 5.5-8.0 minutes). The average number of tissue adhesive drops applied was 69.6 (range: 63-78 drops). In the tissue adhesive group, both the reduction in time for flap adhesion and the increased number of adhesive points were statistically significant when compared to PTS. Lysine-derived urethane surgical adhesive was applied in less time than progressive tension sutures, even after accounting for holding pressure for 5 minutes. The tissue adhesive provided four times the number of attachment points compared to PTS, although the significance of this is not clear. There were no postoperative clinical seromas detected in either group and there were no major complications in either group. Based on these results, the use of lysine-derived urethane surgical adhesive was found to be a safe and effective alternative to progressive tension sutures to reduce seroma formation in drain-free abdominoplasty procedures.

The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas Causing Cushing's Disease

PubMed Central

Perez-Rivas, Luis G.; Theodoropoulou, Marily; Ferraù, Francesco; Nusser, Clara; Kawaguchi, Kohei; Stratakis, Constantine A.; Faucz, Fabio Rueda; Wildemberg, Luiz E.; Assié, Guillaume; Beschorner, Rudi; Dimopoulou, Christina; Buchfelder, Michael; Popovic, Vera; Berr, Christina M.; Tóth, Miklós; Ardisasmita, Arif Ibrahim; Honegger, Jürgen; Bertherat, Jerôme; Gadelha, Monica R.; Beuschlein, Felix; Stalla, Günter; Komada, Masayuki; Korbonits, Márta

2015-01-01

Context: We have recently reported somatic mutations in the ubiquitin-specific protease USP8 gene in a small series of adenomas of patients with Cushing's disease. Objective: To determine the prevalence of USP8 mutations and the genotype-phenotype correlation in a large series of patients diagnosed with Cushing's disease. Design: We performed a retrospective, multicentric, genetic analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger sequencing. Biochemical and clinical features were collected and examined within the context of the mutational status of USP8, and new mutations were characterized by functional studies. Patients: A total of 145 patients who underwent surgery for an ACTH-producing pituitary adenoma. Main Outcomes Measures: Mutational status of USP8. Biochemical and clinical features included sex, age at diagnosis, tumor size, preoperative and postoperative hormonal levels, and comorbidities. Results: We found somatic mutations in USP8 in 48 (36%) pituitary adenomas from patients with Cushing's disease but in none of 11 silent corticotropinomas. The prevalence was higher in adults than in pediatric cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8-mutated adenomas were diagnosed at an earlier age than those with wild-type lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 ± 7 mm and were inversely associated with the development of postoperative adrenal insufficiency. All the mutations affected the residues Ser718 or Pro720, including five new identified alterations. Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells. Conclusions: USP8 is frequently mutated in adenomas causing Cushing's disease, especially in those from female adult patients diagnosed at a younger age. PMID:25942478

Development of a poly (ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation

PubMed Central

Ma, Hongyan; Darmawan, Erica T.; Zhang, Min; Zhange, Lei; Bryers, James D.

2013-01-01

Traditional antibiotic therapy to control medical device-based infections typically fails to clear biofilm infections and may even promote the evolution of antibiotic resistant species. We report here the development of two novel antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating suspended bacterial growth and biofilm formation. These chelated gallium or zinc complexes act as iron siderophore analogs, surplanting the natural iron uptake of most bacteria. Poly (ether urethane) (PEU; Biospan®) polymer films were fabricated for the controlled sustained release of the Ga- or Zn-complexes, using an incorporated pore-forming agent, poly (ethylene glycol) (PEG). An optimum formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained drug release for at least 3 months. All drug-loaded PEU films exhibited in vitro ≥ 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus the negative control PEU films releasing nothing. Cytotoxicity and endotoxin evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing PEU films. Finally, in vivo studies further substantiate the anti-biofilm efficacy of the PEU films releasing Ga- or Zn- complexes. PMID:24140747

Development of a poly(ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation.

PubMed

Ma, Hongyan; Darmawan, Erica T; Zhang, Min; Zhang, Lei; Bryers, James D

2013-12-28

Traditional antibiotic therapy to control medical device-based infections typically fails to clear biofilm infections and may even promote the evolution of antibiotic resistant species. We report here the development of two novel antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating suspended bacterial growth and biofilm formation. These chelated gallium or zinc complexes act as iron siderophore analogs, supplanting the natural iron uptake of most bacteria. Poly (ether urethane) (PEU; Biospan®) polymer films were fabricated for the controlled sustained release of the Ga- or Zn-complexes, using an incorporated pore-forming agent, poly(ethylene glycol) (PEG). An optimum formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained drug release for at least 3months. All drug-loaded PEU films exhibited in vitro ≥ 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus the negative control PEU films releasing nothing. Cytotoxicity and endotoxin evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing PEU films. Finally, in vivo studies further substantiate the anti-biofilm efficacy of the PEU films releasing Ga- or Zn- complexes. © 2013.

Flame resistant elastic elastomeric fibers

NASA Technical Reports Server (NTRS)

Howarth, J. T.; Massucco, A. A.

1972-01-01

Development of materials to improve flame resistance of elastic elastomeric fibers is discussed. Two approaches, synthesis of polyether based urethanes and modification of synthesized urethanes with flame ratardant additives, are described. Specific applications of both techniques are presented.

A radiation-sensitive monomer of 2,4-hexadiyn-1,6-bis(p-toluene sulphonyl urethane) in PVA as a radiochromic film dosimeter

NASA Astrophysics Data System (ADS)

Soliman, Yasser S.; Abdel-Fattah, A. A.; Hamed, A. A.; Bayomi, A. M. M.

2018-03-01

A conjugated monomer 2,4-hexadiyn-1,6-bis(p-toluene sulphonyl urethane) (HDTU) was synthesized. Thereafter, it was incorporated into polyvinyl alcohol (PVA), and coated on self-adhesive sheet, thus to prepare film dosimeters. The monomer and films were analyzed using X-ray diffraction (XRD), FTIR spectroscopy and specular reflectance colorimetry. This monomer polymerizes in the films by radiation and turns progressively blue in proportion to absorbed dose, indicating the formation of π-conjugated colored poly-HDTU. Color development was investigated at 480 nm and 610 nm for dose monitoring ranging from 10 Gy to 15 kGy. HDTU in PVA film is highly ordered and crystalline and, upon irradiation, it forms a semi-crystalline polymer with nearly the same interplanar distances as the monomer, indicating the occurrence of topochemical polymerization. During irradiation, polymerization of the monomer is nearly independent of humidity in the range of 0-53% and temperature in the range of 25-45 °C. The uncertainty of this system is 5.16% at 95% confidence level.

Flexible Vinyl and Urethane Coating and Printing: New Source Performance Standards (NSPS)

EPA Pesticide Factsheets

Learn about the New Source Performance Standards (NSPS) for flexible vinyl and urethane coating and printing by reading the rule summary, the rule history, the code of federal regulations subpart and related rules

Allergic contact dermatitis due to urethane acrylate in ultraviolet cured inks.

PubMed Central

Nethercott, J R; Jakubovic, H R; Pilger, C; Smith, J W

1983-01-01

Seven workers exposed to ultraviolet printing inks developed contact dermatitis. Six cases were allergic and one irritant. A urethane acrylate resin accounted for five cases of sensitisation, one of which was also sensitive to pentaerythritol triacrylate and another also to an epoxy acrylate resin. One instance of allergy to trimethylpropane triacrylate accounted for the sixth case of contact dermatitis in this group of workers. An irritant reaction is presumed to account for the dermatitis in the individual not proved to have cutaneous allergy by patch tests. In this instance trimethylpropane triacrylate was thought to be the most likely irritating agent. Laboratory investigation proved urethane acrylate to be an allergen. The results of investigations of the sensitisation potentials of urethane acrylate, methylmethacrylate, epoxy acrylate resins, toluene-2,4-diisocyanate, and other multifunctional acrylic monomers in the albino guinea pig are presented. The interpretation of such predictive tests is discussed. Images PMID:6223656

Ectopic expression of the gastric inhibitory polypeptide receptor gene is a sufficient genetic event to induce benign adrenocortical tumor in a xenotransplantation model.

PubMed

Mazzuco, Tania L; Chabre, Olivier; Sturm, Nathalie; Feige, Jean-Jacques; Thomas, Michaël

2006-02-01

Aberrant expression of ectopic G protein-coupled receptors (GPCRs) in adrenal cortex tissue has been observed in several cases of ACTH-independent macronodular adrenal hyperplasias and adenomas associated with Cushing's syndrome. Although there is clear clinical evidence for the implication of these ectopic receptors in abnormal regulation of cortisol production, whether this aberrant GPCR expression is the cause or the consequence of the development of an adrenal hyperplasia is still an open question. To answer it, we genetically engineered primary bovine adrenocortical cells to have them express the gastric inhibitory polypeptide receptor. After transplantation of these modified cells under the renal capsule of adrenalectomized immunodeficient mice, tissues formed had their functional and histological characteristics analyzed. We observed the formation of an enlarged and hyperproliferative adenomatous adrenocortical tissue that secreted cortisol in a gastric inhibitory polypeptide-dependent manner and induced a mild Cushing's syndrome with hyperglycemia. Moreover, we show that tumor development was ACTH independent. Thus, a single genetic event, inappropriate expression of a nonmutated GPCR gene, is sufficient to initiate the complete phenotypic alterations that ultimately lead to the formation of a benign adrenocortical tumor.

Immunoglobulin class switching to IgG4 in Warthin tumor and analysis of serum IgG4 levels and IgG4-positive plasma cells in the tumor.

PubMed

Aga, Mitsuharu; Kondo, Satoru; Yamada, Kazunori; Wakisaka, Naohiro; Yagi-Nakanishi, Sayaka; Tsuji, Akira; Endo, Kazuhira; Murono, Shigeyuki; Ito, Makoto; Muramatsu, Masamichi; Kawano, Mitsuhiro; Yoshizaki, Tomokazu

2014-04-01

We previously reported a case of immunoglobulin (Ig)G4-related immune inflammation in Warthin tumor. Increased serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells are characteristics of IgG4-related disease (IgG4-RD), a newly emerging clinicopathological entity. However, the relationship between IgG4-RD and Warthin tumor remains to be elucidated. We aimed to investigate the involvement of systemic and local IgG4 production and class-switch recombination in Warthin tumor. We examined serum IgG4 levels and also analyzed the involvement of IgG4-positive plasma cells in Warthin tumors (18 cases) compared with those of pleomorphic adenomas (19 cases) as controls. Furthermore, in specimens of Warthin tumors (3 cases), pleomorphic adenomas (2 cases), and IgG4-RDs (2 cases), we examined messenger RNA expression of activation-induced cytidine deaminase, IgG4 germline transcripts and productive IgG4 by reverse transcription polymerase chain reaction. Serum IgG4 levels were increased in 5 of 18 Warthin tumors and not in any of the 19 pleomorphic adenomas. Infiltration of IgG4-positive plasma cells was detected in 4 Warthin tumors and none in the pleomorphic adenomas. Moreover, activation-induced cytidine deaminase, IgG4 germline transcripts, and productive IgG4 messenger RNA were found to be expressed in 2 of 3 Warthin tumors as well as IgG4-RDs by reverse transcription polymerase chain reaction, but not in pleomorphic adenomas. In conclusion, immunoglobulin class switching to IgG4 may be involved in the pathogenesis of Warthin tumor, and it is possible that certain inflammatory background with an immune reaction is involved in the pathogenesis of Warthin tumor. © 2013.

Nelfinavir induces radiation sensitization in pituitary adenoma cells

PubMed Central

Zeng, Jing; See, Alfred P.; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P.; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K.; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T.; Lim, Michael

2017-01-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir’s effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 d, 17 d with nelfinavir treatment, 27 d with radiation 6 Gy, and 41 d with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on protein gel blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies. PMID:21811091

Nelfinavir induces radiation sensitization in pituitary adenoma cells.

PubMed

Zeng, Jing; See, Alfred P; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T; Lim, Michael

2011-10-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution, and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.

Production development of organic nonflammable spacecraft potting encapsulating and conformal coating compounds. Volume 2: Tables

NASA Technical Reports Server (NTRS)

Lieberman, S. L.

1974-01-01

Tables are presented which include: material properties; elemental analysis; silicone RTV formulations; polyester systems and processing; epoxy preblends and processing; urethane materials and processing; epoxy-urethanes elemental analysis; flammability test results, and vacuum effects.

Growth hormone is a cellular senescence target in pituitary and nonpituitary cells

PubMed Central

Chesnokova, Vera; Zhou, Cuiqi; Ben-Shlomo, Anat; Zonis, Svetlana; Tani, Yuji; Ren, Song-Guang; Melmed, Shlomo

2013-01-01

Premature proliferative arrest in benign or early-stage tumors induced by oncoproteins, chromosomal instability, or DNA damage is associated with p53/p21 activation, culminating in either senescence or apoptosis, depending on cell context. Growth hormone (GH) elicits direct peripheral metabolic actions as well as growth effects mediated by insulin-like growth factor 1 (IGF1). Locally produced peripheral tissue GH, in contrast to circulating pituitary-derived endocrine GH, has been proposed to be both proapoptotic and prooncogenic. Pituitary adenomas expressing and secreting GH are invariably benign and exhibit DNA damage and a senescent phenotype. We therefore tested effects of nutlin-induced p53-mediated senescence in rat and human pituitary cells. We show that DNA damage senescence induced by nutlin triggers the p53/p21 senescent pathway, with subsequent marked induction of intracellular pituitary GH in vitro. In contrast, GH is not induced in cells devoid of p53. Furthermore we show that p53 binds specific GH promoter motifs and enhances GH transcription and secretion in senescent pituitary adenoma cells and also in nonpituitary (human breast and colon) cells. In vivo, treatment with nutlin results in up-regulation of both p53 and GH in the pituitary gland, as well as increased GH expression in nonpituitary tissues (lung and liver). Intracrine GH acts in pituitary cells as an apoptosis switch for p53-mediated senescence, likely protecting the pituitary adenoma from progression to malignancy. Unlike in the pituitary, in nonpituitary cells GH exerts antiapoptotic properties. Thus, the results show that GH is a direct p53 transcriptional target and fulfills criteria as a p53 target gene. Induced GH is a readily measurable cell marker for p53-mediated cellular senescence. PMID:23940366

Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage.

PubMed

Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T

2008-07-28

Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

Cold recycle pavement using urea urethane dispersion agent and rubber : final report.

DOT National Transportation Integrated Search

1994-12-01

This research study was a joint venture of the Oregon Department of Transportation (ODOT), Evans, Loosely, Inc., and Roseburg Paving Company, to evaluate the use of Urea Urethane Dispersion (UUD) agent, with finely ground tire rubber, high float emul...

Evaluation of urethane and carbide-tipped blades on wheel-supported snow plows.

DOT National Transportation Integrated Search

1997-01-01

The objective of this study was to evaluate the performance of urethane and carbide-tipped snow plow blades on wheel supported plows. Their performance was compared to that of VDOT's standard blade arrangement: carbide-tipped blades on plows without ...

Biocompatibility of Synthetic Poly(ester urethane)/Polyhedral Oligomeric Silsesquioxane Matrices with Embryonic Stem Cell Proliferation and Differentiation

PubMed Central

Guo, Yan-Lin; Wang, Wenshou; Otaigbe, Joshua U.

2010-01-01

Incorporation of polyhedral oligomeric silsesquioxanes (POSS) into poly (ester urethane)s (PEU) as a building block results in a PEU/POSS hybrid polymer with increased mechanical strength and thermostability. An attractive feature of the new polymer is that it forms a porous matrix when cast in the form of a thin film, making it potentially useful in tissue engineering. In this study, we present detailed microscopic analysis of the PEU/POSS matrix and demonstrate its biocompatibility with cell culture. The PEU/POSS polymer forms a continuous porous matrix with open pores and interconnected grooves. From SEM image analysis, it is calculated that there are about 950 pores per mm2 of the matrix area with pore size ranging from 1 to 15 μm in diameter. The area occupied by the pores represents approximately 7.6 % of matrix area. Using mouse embryonic stem cells (ESCs), we demonstrate that the PEU/POSS matrix provides excellent support for cell proliferation and differentiation. Under the cell culture condition optimized to maintain self-renewal, ESCs grown on a PEU/POSS matrix exhibit undifferentiated morphology, express pluripotency markers, and have similar growth rate to cells grown on gelatin. When induced for differentiation, ESCs underwent dramatic morphological change, characterized by the loss of clonogenecity and increased cell size with well-expanded cytoskeleton networks. Differentiated cells are able to form a continuous monolayer that is closely embedded on the matrix. The excellent compatibility between the PEU/POSS matrix and ESC proliferation/differentiation demonstrates the potential of using PEU/POSS polymers in future ESC-based tissue engineering. PMID:20213627

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.

PubMed

Drozdzik, Agnieszka; Kowalczyk, Robert; Lipski, Mariusz; Łapczuk, Joanna; Urasinska, Elzbieta; Kurzawski, Mateusz

2016-01-01

Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma. Copyright © 2015. Published by Elsevier Ltd.

Evaluation of pressor and visceromotor reflex responses to bladder distension in urethane anesthetized rats.

PubMed

Blatt, Lauren K; Lashinger, Erin S R; Laping, Nicholas J; Su, Xin

2009-01-01

We tested cardiovascular and visceromotor reflex (VMR) responses to urinary bladder distension (UBD) in urethane anesthetized rats to see if it can replicate the response pattern and the inhibition of bladder nociceptive transmission by analgesics seen in isoflurane anesthetized animals. Female Sprague-Dawley rats under 3% isoflurane anesthesia were acutely instrumented with jugular venous, carotid arterial, and bladder cannulas for drug administration, blood pressure (BP) measurement, and bladder distension, respectively. Needle electrodes were placed directly into the abdominal musculature to measure myoelectrical activity subsequent to phasic UBD (30 sec in 3 min intervals). A cardiovascular response (pressor) and a VMR response (a contraction of abdominal and hind limb musculature) to UBD were evaluated in urethane (1.2 g/kg, i.v.) or isoflurane (1%) anesthetized rats. Pressor and VMR responses to noxious UBD (60 mmHg) were generated under both anesthesics. The thresholds of stimulus response functions for both pressor and VMR responses were not affected by either anesthesics. However, the magnitude of the maximal pressor response was significantly reduced in urethane anesthesia. The analgesics, morphine, and mexiletine, significantly inhibited the VMR response to noxious UBD under both anesthetics, but the intensities of the inhibition from both analgesics under urethane anesthesia were much lower than under isoflurane anesthesia (ID50: 2.07 mg/kg vs. 0.88 mg/kg for morphine, >10 mg/kg vs. 0.47 mg/kg for mexiletine). The rat urinary bladder distension model in urethane anesthetized rats demonstrates a blunted maximal pressor response and a reduced inhibition of visceral nociceptive transmission by analgesics. Neurourol. Urodynam. 28:442-446, 2009. (c) 2008 Wiley-Liss, Inc.

[Some neurological and psychiatric complications of the disorders of the hypothalamo-hypophyseal system].

PubMed

Aszalós, Zsuzsa

2007-04-22

Connection between the central nervous system and the endocrine system is extremely complex. The hypothalamus serves as a crucial centre for the integration and coordination of autonomic functions by neuronal and hormonal pathways. It plays a central role in the homeostatic regulation of internal physiological conditions. It controls growth and reproduction, stress reactions, and determines rhythmicity, periodicity and timing of physiological processes. Beside its well-known functions, antidiuretic hormone has a role in social behavior as it enhances aggression via vasopressin receptor 1A. Oxitocin is affected in the formation of maternal behavior, and in other social interactions, like the pair bounding, as well as in analgesia and pain modulation. The corticotrop-releasing hormone acts as a neurotransmitter, it has a special role in stress-behavior, anxiety, and depression, and it blocks deep sleeping. Among the neurotransmitters and neuropeptids of the hypothalamus, serotonin, norepinephrine, GABA, cholecystokinin, neuropeptide-Y, Agouti-related protein, alpha-MSH and ghrelin have essential importance in the eating disorders. The levels of leptin and galanin determine whether formation of anabolic or catabolic neurotransmitters should take place. In the thermoregulation the central thermoreceptors play role, and suprachiasmatic nucleus is responsible for circadian rhythm, through "timing genes". The diseases of the hypothalamus cause most frequently bulimia or anorexia, hypersomnia, impotency, and attacks of anxiety. The most common expansive process of the hypothalamus is craniopharyngioma. The lack or diminution of vasopressin causes diabetes insipidus, while inappropriate antidiuretic hormone secretion induces Schwartz-Barter syndrome. Fröhlich-, Kleine-Levin- or Prader-Willi syndromes have characteristic neuropsychiatric features. The main psychiatric symptom of hypopituitarism is a combination of dementia and delirium. The most characteristic neurological sign of pituitary adenoma is the visual field defect. Carpal tunnel syndrome, obstructive sleeping apnoe and headache are typical neurological features in somatotrop adenomas.

Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and β-Catenin

PubMed Central

Heaton, Joanne H.; Wood, Michelle A.; Kim, Alex C.; Lima, Lorena O.; Barlaskar, Ferdous M.; Almeida, Madson Q.; Fragoso, Maria C.B.V.; Kuick, Rork; Lerario, Antonio M.; Simon, Derek P.; Soares, Ibere C.; Starnes, Elisabeth; Thomas, Dafydd G.; Latronico, Ana C.; Giordano, Thomas J.; Hammer, Gary D.

2013-01-01

Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal β-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal β-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized β-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized β-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis. PMID:22800756

Long-term treatment with bromocriptine of a plurihormonal pituitary adenoma secreting thyrotropin, growth hormone and prolactin.

PubMed

Shimatsu, A; Murabe, H; Nakamura, Y; Mizuta, H; Ihara, C; Nakao, K

1999-02-01

A 48-year-old female presented with acromegaly, amenorrhea and hyperthyroidism associated with high serum free T4 levels and measurable TSH concentrations. The administration of GHRH induced significant increases in GH, PRL and TSH. Conversely, intravenous infusion of dopamine or oral administration of bromocriptine effectively inhibited GH, PRL and TSH secretion. Serum alpha-subunit levels were neither affected by GHRH, dopamine nor bromocriptine. Transsphenoidal surgery was performed and immunostaining of the tissue showed that the adenoma cells were positive for GH, PRL or TSH. The patient was treated with bromocriptine at a daily oral dose of 10 mg after surgery. Serum TSH were initially suppressed but returned within reference intervals with persistent normalized free T4 levels. Serum PRL became undetectable and GH levels were stable around 6 ng/ml except the periods of poor drug compliance, when serum TSH, GH and PRL levels rose considerably. The patient was followed-up for 10 years without any change in the residual adenoma tissues as detected by magnetic resonance imaging. These findings suggest that long-term bromocriptine therapy is effective in treating the hypersecretory state of a plurihormonal adenoma secreting TSH, GH and PRL.

Spectroscopic, semiempirical studies and antibacterial activity of new urethane derivatives of natural polyether antibiotic - Monensin A

NASA Astrophysics Data System (ADS)

Huczyński, Adam; Stefańska, Joanna; Piśmienny, Mieszko; Brzezinski, Bogumil

2013-02-01

A series of new Monensin A dimers linked by diurethane moiety were synthesised and their molecular structures were studied using ESI-MS, FT-IR, 1H and 13C NMR and PM5 methods. The results showed that the compounds form a pseudo-cyclic structure stabilized by three intramolecular hydrogen bonds and the sodium cation was coordinated by five oxygen atoms of polyether skeleton of Monensin moiety. The NMR and FT-IR data of complexes of Monensin urethane sodium salts demonstrated that within the pseudo-cyclic structure the carbonyl oxygen atom of the urethane group did not coordinate the sodium cation. Monensin urethanes were tested in vitro for the activity against Gram-positive and Gram-negative bacteria and fungi as well as against a series of clinical isolates of Staphylococcus: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). The most active compound against MRSA and MSSA was 1,4-phenylene diurethane of Monensin with MIC 10.4-41.4 μmol/L).

Long-Term Outcomes of Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas at the BC Cancer Agency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Julian O.; Ma, Roy; Division of Radiation Oncology and Developmental Radiotherapeutics, University of British Columbia, Vancouver

2013-11-01

Purpose: To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. Methods and Materials: To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions,more » with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. Results: With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. Conclusion: In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.« less

Changes in intestinal immunity, gut microbiota, and expression of energy metabolism-related genes explain adenoma growth in bilberry and cloudberry-fed ApcMin mice.

PubMed

Päivärinta, Essi; Niku, Mikael; Maukonen, Johanna; Storvik, Markus; Heiman-Lindh, Anu; Saarela, Maria; Pajari, Anne-Maria; Mutanen, Marja

2016-11-01

We showed previously that ellagitannin-rich cloudberries and anthocyanin-rich bilberries reduce the number of intestinal adenomas in multiple intestinal neoplasia/+ (Apc Min ) mice. We also found that cloudberries decreased the size of adenomas, whereas bilberries increased it. Here we hypothesized that the difference in adenoma growth could be explained by dissimilar effects of the berries on intestinal immune responses and gut microbiota, potentially driven by the distinct polyphenol compositions of the 2 berries. Our objectives were to investigate lymphocyte subtypes and the predominant cecal bacterial diversity in mice fed with bilberries and cloudberries, and to analyze global gene expression profiles in the intestinal mucosa. Immunostainings of CD3 + T lymphocytes, FoxP3 + regulatory T lymphocytes, and CD45R + B lymphocytes revealed a smaller ratio of intraepithelial to all mucosal CD3 + T lymphocytes in the cloudberry-fed mice compared with controls, suggesting an attenuation of inflammation. Bilberry feeding induced no changes in the density of any of the lymphocyte subtypes. The predominant bacterial diversity in cecal contents, analyzed using polymerase chain reaction-denaturating gradient gel electrophoresis, was higher in the bilberry group than in the control or cloudberry groups. The microbial profiles of cloudberry-fed mice clustered together and were associated with small adenoma size. Pathway analyses of gene expression data showed that cloudberry down-regulated and bilberry up-regulated the expression of energy metabolism-related genes in the intestinal mucosa. In conclusion, attenuation of intestinal inflammation, changes in microbial profiles, and down-regulation of mucosal energy metabolism may account for the smaller adenoma size in cloudberry-fed mice in comparison to bilberry-fed mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Resin cements formulated with thio-urethanes can strengthen porcelain and increase bond strength to ceramics.

PubMed

Bacchi, Atais; Spazzin, Aloisio Oro; de Oliveira, Gabriel Rodrigues; Pfeifer, Carmem; Cesar, Paulo Francisco

2018-06-01

The use of thio-urethane oligomers has been shown to significantly improve the mechanical properties of resin cements (RCs). The aim of this study was to use thio-urethane-modified RC to potentially reinforce the porcelain-RC structure and to improve the bond strength to zirconia and lithium disilicate. Six oligomers were synthesized by combining thiols - pentaerythritol tetra-3-mercaptopropionate (PETMP, P) or trimethylol-tris-3-mercaptopropionate (TMP, T) - with di-functional isocyanates - 1,6-Hexanediol-diissocyante (HDDI) (aliphatic, AL) or 1,3-bis(1-isocyanato-1-methylethyl)benzene (BDI) (aromatic, AR) or Dicyclohexylmethane 4,4'-Diisocyanate (HMDI) (cyclic, CC). Thio-urethanes (20 wt%) were added to a BisGMA/UDMA/TEGDMA organic matrix. Filler was introduced at 60 wt%. The microshear bond strength (μSBS), Weibull modulus (m), and failure pattern of RCs bonded to zirconia (ZR) and lithium disilicate (LD) ceramics was evaluated. Biaxial flexural test and fractographic analysis of porcelain discs bonded to RCs were also performed. The biaxial flexural strength (σ bf ) and m were calculated in the tensile surfaces of porcelain and RC structures (Z = 0 and Z = -t 2 , respectively). The μSBS was improved with RCs formulated with oligomers P_AL or T_AL bonded to LD and P_AL, P_AR or T_CC bonded to zirconia in comparison to controls. Mixed failures predominated in all groups. σ bf had superior values at Z = 0 with RCs formulated with oligomers P_AL, P_AR, T_AL, or T_CC in comparison to control; σ bf increased with all RCs composed by thio-urethanes at Z = -t 2 . Fractographic analysis revealed all fracture origins at Z = 0. The use of specific thio-urethane oligomers as components of RCs increased both the biaxial flexural strength of the porcelain-RC structure and the μSBS to LD and ZR. The current investigation suggests that it is possible to reinforce the porcelain-RC pair and obtain higher bond strength to LD and ZR with RCs formulated with selected types of thio-urethane oligomers. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparison of the circadian variation in cell proliferation in normal and neoplastic colonic epithelial cells.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-15

Circadian variations in cell proliferation in normal tissues have been recognised for many years but comparable phenomena in neoplastic tissues appear not to have been reported. Adenomas and carcinomas were induced in mouse colon by injection of dimethylhydrazine (DMH) and cell proliferation in these tumors was measured stathmokinetically. In normal intestine cell proliferation is fastest at night whereas in both adenomas and carcinomas it was found to be slower at night than in the middle of the day. Chemical sympathectomy was found to abolish the circadian variation in tumor cell proliferation.

Laboratory and test-site testing of moisture-cured urethanes on steel in salt-rich environment.

DOT National Transportation Integrated Search

2000-11-01

Three 3-coat moisture-cured (MC) urethane commercial products formulated for protecting new steel (SSPC-SP 10) and power : tool-cleaned steel (SSPC-SP 3) surfaces against corrosion were evaluated; the total coating film thickness was about 75 : micro...

Laboratory and test-site testing of moisture-cured urethanes on steel in salt-rich environment

DOT National Transportation Integrated Search

2000-12-01

Three 3-coat moisture-cured (MC) urethane commercial products formulated for protecting new steel (SSPC-SP 10) and power tool-cleaned steel (SSPC-SP 3) surfaces against corrosion were evaluated; the total coating film thickness was about 75 microns. ...

Evaluation of urethane snow plow blades as an alternative to rubber blades.

DOT National Transportation Integrated Search

1995-01-01

The purpose of this study was to determine if urethane blades are a suitable alternative to rubber blades for use on snow plows. The importance of finding a suitable alternative is due to the anticipated increased need to protect the new, longer last...

Predictive value of diminutive colonic adenoma trial: the PREDICT trial.

PubMed

Schoenfeld, Philip; Shad, Javaid; Ormseth, Eric; Coyle, Walter; Cash, Brooks; Butler, James; Schindler, William; Kikendall, Walter J; Furlong, Christopher; Sobin, Leslie H; Hobbs, Christine M; Cruess, David; Rex, Douglas

2003-05-01

Diminutive adenomas (1-9 mm in diameter) are frequently found during colon cancer screening with flexible sigmoidoscopy (FS). This trial assessed the predictive value of these diminutive adenomas for advanced adenomas in the proximal colon. In a multicenter, prospective cohort trial, we matched 200 patients with normal FS and 200 patients with diminutive adenomas on FS for age and gender. All patients underwent colonoscopy. The presence of advanced adenomas (adenoma >or= 10 mm in diameter, villous adenoma, adenoma with high grade dysplasia, and colon cancer) and adenomas (any size) was recorded. Before colonoscopy, patients completed questionnaires about risk factors for adenomas. The prevalence of advanced adenomas in the proximal colon was similar in patients with diminutive adenomas and patients with normal FS (6% vs. 5.5%, respectively) (relative risk, 1.1; 95% confidence interval [CI], 0.5-2.6). Diminutive adenomas on FS did not accurately predict advanced adenomas in the proximal colon: sensitivity, 52% (95% CI, 32%-72%); specificity, 50% (95% CI, 49%-51%); positive predictive value, 6% (95% CI, 4%-8%); and negative predictive value, 95% (95% CI, 92%-97%). Male gender (odds ratio, 1.63; 95% CI, 1.01-2.61) was associated with an increased risk of proximal colon adenomas. Diminutive adenomas on sigmoidoscopy may not accurately predict advanced adenomas in the proximal colon.

77 FR 50411 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... environmental control system (ECS) wrapped with BMS 8-39 or Aeronautical Materials Specifications (AMS) 3570... were assembled with duct assemblies in the ECS wrapped with BMS 8-39 urethane foam insulation, a... ECS with burned BMS 8-39 urethane foam insulation. We issued these ADs to prevent a potential...

QUANTITATIVE ULTRAVIOLET SPECTROSCOPY IN WEATHERING OF A MODEL POLYESTER-URETHANE COATING. (R828081E01)

EPA Science Inventory

Spectroscopy was used to quantify the effects of ultraviolet light on a model polyester–urethane coating as it degraded in an accelerated exposure chamber. An explorative calculation of the effective dosage absorbed by the coatings was made and, depending on the quantum...

Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form.

PubMed

Obari, Abdulkader; Sano, Toshiaki; Ohyama, Kenichi; Kudo, Eiji; Qian, Zhi Rong; Yoneda, Akiko; Rayhan, Nasim; Mustafizur Rahman, Muhammad; Yamada, Shozo

2008-01-01

Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function.

PubMed

Barbieri, Federica; Bajetto, Adriana; Porcile, Carola; Pattarozzi, Alessandra; Schettini, Gennaro; Florio, Tullio

2007-03-01

Chemokines are key factors involved in the regulation of immune response, through the activation and control of leukocyte traffic, lymphopoiesis and immune surveillance. However, a large number of chemokines and their receptors are expressed in central nervous system (CNS) cells, either constitutively or induced by inflammatory stimuli, playing a role in many neuropathological processes. Stromal cell-derived factor 1 (SDF1) is a chemokine whose extra-immunological localization and functions have been extensively studied. SDF1 and its receptor CXCR4 were identified in both neurons and glia of many brain areas, including the hypothalamus, as well as at the pituitary level. Importantly, SDF1 and CXCR4 expression is increased in brain tumors in which their activity induced tumor cell proliferation and brain parenchyma invasion. Despite their localization, to date very few reports addressed the role of CXCR4 and SDF1 in the modulation of the hypothalamus/pituitary axis and their possible involvement in the development of pituitary adenomas. In this review, we discuss previous literature data on the role of chemokines in normal and adenomatous pituitary cells, focusing on recent data from our group showing that CXCR4 activation controls proliferation and both prolactin and GH release in the pituitary adenoma cell line GH4C1 through a complex network of intracellular signals. Thus, the SDF1/CXCR4 system together with other chemokinergic ligand-receptor pairs, may represent a novel regulatory pathway for pituitary function and, possibly, be involved in pituitary adenoma development. These lines of evidence suggest that the inhibition of chemokine receptors may represent a novel pharmacological target for the treatment of pituitary adenomas.

Epithelial-mesenchymal transition and nuclear β-catenin induced by conditional intestinal disruption of Cdh1 with Apc is E-cadherin EC1 domain dependent

PubMed Central

Carter, Emma J.; Barnes, David; Hoppe, Hans-Jürgen; Hughes, Jennifer; Cobbold, Stephen; Harper, James; Morreau, Hans; Surakhy, Mirvat; Hassan, A. Bassim

2016-01-01

Two important protein-protein interactions establish E-cadherin (Cdh1) in the adhesion complex; homophilic binding via the extra-cellular (EC1) domain and cytoplasmic tail binding to β-catenin. Here, we evaluate whether E-cadherin binding can inhibit β-catenin when there is loss of Adenomatous polyposis coli (APC) from the β-catenin destruction complex. Combined conditional loss of Cdh1 and Apc were generated in the intestine, intestinal adenoma and adenoma organoids. Combined intestinal disruption (Cdh1fl/flApcfl/flVil-CreERT2) resulted in lethality, breakdown of the intestinal barrier, increased Wnt target gene expression and increased nuclear β-catenin localization, suggesting that E-cadherin inhibits β-catenin. Combination with an intestinal stem cell Cre (Lgr5CreERT2) resulted in ApcΔ/Δ recombination and adenoma, but intact Cdh1fl/fl alleles. Cultured ApcΔ/ΔCdh1fl/fl adenoma cells infected with adenovirus-Cre induced Cdh1fl/fl recombination (Cdh1Δ/Δ), disruption of organoid morphology, nuclear β-catenin localization, and cells with an epithelial-mesenchymal phenotype. Complementation with adenovirus expressing wild-type Cdh1 (Cdh1-WT) rescued adhesion and β-catenin membrane localization, yet an EC1 specific double mutant defective in homophilic adhesion (Cdh1-MutW2A, S78W) did not. These data suggest that E-cadherin inhibits β-catenin in the context of disruption of the APC-destruction complex, and that this function is also EC1 domain dependent. Both binding functions of E-cadherin may be required for its tumour suppressor activity. PMID:27566565

Endocrinological outcomes following endoscopic and microscopic transsphenoidal surgery in 113 patients with acromegaly.

PubMed

Sarkar, Sauradeep; Rajaratnam, Simon; Chacko, Geeta; Chacko, Ari George

2014-11-01

To describe outcomes and complications in patients undergoing transsphenoidal surgery for acromegaly using the 2010 consensus criteria for biochemical remission. Retrospective review of 113 treatment naïve patients who underwent transsphenoidal surgery with the endoscopic (n=66) and the endonasal microscopic technique (n=47). Cure was defined if the age and sex-adjusted IGF-1 level was normal and either the basal GH was <1 ng/ml or the nadir GH was <0.4 ng/ml following oral glucose suppression at last follow-up. The mean age at presentation was 38.1 ± 7.1 years and 86% of tumors were macroadenomas. Adenoma sizes averaged 21.1 ± 9.7 mm, but 56% of all tumors were ≥ 2 cm in size and 43.4% were invasive. Remission rates between endoscopic and microscopic transsphenoidal surgery did not differ significantly overall (28.8% versus 36.2%). On univariate analysis, a preoperative GH level <40 ng/ml, adenoma size <20mm and non-invasiveness were predictors of remission at follow-up. Although there were no statistically significant differences in remission rates between the endoscopic and microsurgical groups, surgically induced hypopituitarism was less frequent with the former. We report our surgical experience with predominantly large, invasive GH adenomas using the 2010 criteria for cure. Patients with smaller, non-invasive tumors with lower preoperative GH levels are most likely to achieve remission. Outcomes with either the microscopic or endoscopic approach do not differ significantly, although the rate of surgically induced hypopituitarism may be higher with the former. Transsphenoidal surgery remains the first line of treatment for patients with acromegaly, but invasive adenomas will frequently require adjuvant therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Applicability of cranial models in urethane resin and foam as a substitute for bone: are synthetic materials reliable?

PubMed

Muccino, Enrico; Porta, Davide; Magli, Francesca; Cigada, Alfredo; Sala, Remo; Gibelli, Daniele; Cattaneo, Cristina

2013-09-01

As literature is poor in functional synthetic cranial models, in this study, synthetic handmade models of cranial vaults were produced in two different materials (a urethane resin and a self-hardening foam), from multiple bone specimens (eight original cranial vaults: four human and four swine), in order to test their resemblance to bone structure in behavior, during fracture formation. All the vaults were mechanically tested with a 2-kg impact weight and filmed with a high-speed camera. Fracture patterns were homogeneous in all swine vaults and heterogeneous in human vaults, with resin fractures more similar to bone fractures. Mean fracture latency time extrapolated by videos were of 0.75 msec (bone), 1.5 msec (resin), 5.12 msec (foam) for human vaults and of 0.625 msec (bone), 1.87 msec (resin), 3.75 msec (foam) for swine vaults. These data showed that resin models are more similar to bone than foam reproductions, but that synthetic material may behave quite differently from bone as concerns fracture latency times. © 2013 American Academy of Forensic Sciences.

Multiscale Molecular Dynamics Simulations of Model Hydrophobically Modified Ethylene Oxide Urethane Micelles.

PubMed

Yuan, Fang; Larson, Ronald G

2015-09-24

The flower-like micelles of various aggregation numbers of a model hydrophobically modified ethylene oxide urethane (HEUR) molecule, C16E45C16, and their corresponding starlike micelles, containing the surfactants C16E22 and C16E23, were studied by atomistic and coarse-grained molecular dynamic (MD) simulations. We used free energies from umbrella sampling to calculate the size distribution of micelle sizes and the average time for escape of a hydrophobic group from the micelle. Using the coarse-grained MARTINI force field, the most probable size of the model HEUR molecule was thereby determined to be about 80 hydrophobes per micelle and the average hydrophobe escape time to be about 0.1 s, both of which are consistent with previous experimental studies. Atomistic simulations reveal that hydrogen bond formation and the mean lifetime of hydration waters of the poly(ethylene oxide) (or PEO) groups are location-dependent in the HEUR micelle, with PEO groups immediately adjacent to the C16 groups forming the fewest hydrogen bonds with water and having hydration waters with longer lifetimes than those of the PEO groups located further away from the C16 groups.

Fabrication of a biodegradable calcium polyphosphate/polyvinyl-urethane carbonate composite for high load bearing osteosynthesis applications.

PubMed

Ramsay, Scott D; Pilliar, Robert M; Santerre, J Paul

2010-07-01

The formation of biodegradable implants for use in osteosynthesis has been a major goal of biomaterials research for the past 2-3 decades. Self-reinforced polylactide systems represent the most significant success of this research to date, however, with elastic constants up to 12-15 GPa at best, they fail to provide the initial stiffness required of devices for stabilizing fractures of major load-bearing bones. Our research has investigated the use of calcium polyphosphate (CPP), an inorganic polymer in combination with polyvinyl-urethane carbonate (PVUC) organic polymers for such applications. Initial studies indicated that composite samples formed as interpenetrating phase composites (IPC) exhibited suitable as-made strength and stiffness, however, they displayed a rapid loss of properties when exposed to in vitro aging. An investigation to determine the mechanism of this accelerated in vitro degradation for the IPCs as well as to identify possible design changes to overcome this drawback was undertaken using a model IPC system. It was found that strong interfacial strength and minimal swelling of the PVUC are very important for obtaining and maintaining appropriate mechanical properties in vitro. (c) 2010 Wiley Periodicals, Inc.

Solvent for urethane adhesives and coatings and method of use

DOEpatents

Simandl, Ronald F.; Brown, John D.; Holt, Jerrid S.

2010-08-03

A solvent for urethane adhesives and coatings, the solvent having a carbaldehyde and a cyclic amide as constituents. In some embodiments the solvent consists only of miscible constituents. In some embodiments the carbaldehyde is benzaldehyde and in some embodiments the cyclic amide is N-methylpyrrolidone (M-pyrole). An extender may be added to the solvent. In some embodiments the extender is miscible with the other ingredients, and in some embodiments the extender is non-aqueous. For example, the extender may include isopropanol, ethanol, tetrahydro furfuryl alcohol, benzyl alcohol, Gamma-butyrolactone or a caprolactone. In some embodiments a carbaldehyde and a cyclic amide are heated and used to separate a urethane bonded to a component.

Tertiary Hyperparathyroidism

PubMed Central

Davies, D. R.; Dent, C. E.; Watson, Lyal

1968-01-01

In our first 200 cases of primary hyperparathyroidism confirmed by operation 12 were also shown to have a long history either of a malabsorption syndrome or of chronic renal-glomerular failure. We consider that they first went through a phase of secondary hyperparathyroidism, during which one or more of the glands became autonomous adenamata. This then produced the biochemical changes of “primary” hyperparathyroidism, necessitating excision of the adenoma. This condition is best described as “tertiary” hyperparathyroidism. The transition from secondary to tertiary hyperparathyroidism occurred in four of the 12 patients while under our observation. We think the same process can be traced retrospectively in the other eight cases. The concept of tertiary hyperparathyroidism may help to explain the high incidence of other diseases in association with primary hyperparathyroidism. The behaviour of the parathyroid glands provides a valuable model for the investigation of tumour formation in man. All states occurred in our patients with primary hyperparathyroidism, from normal through hyperplasia to adenoma formation and finally to parathyroid carcinoma. PMID:5691200

ALTERATIONS IN mRNA GENE EXPRESSION ASSOCIATED WITH CHOLESTEROL METABOLISM, CELL CYCLE, AND OXIDATIVE STRESS INDUCED BY TRIAZOLE CONTAINING CONAZOLES IN RAT LIVER

EPA Science Inventory

Conazoles are fungicides used as pharmaceuticals and in agriculture. Triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland. In contrast,propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. It was proposed that tri...

Vascularization and tissue infiltration of a biodegradable polyurethane matrix

PubMed Central

Ganta, Sudhakar R.; Piesco, Nicholas P.; Long, Ping; Gassner, Robert; Motta, Luis F.; Papworth, Glenn D.; Stolz, Donna B.; Watkins, Simon C.; Agarwal, Sudha

2016-01-01

Urethanes are frequently used in biomedical applications because of their excellent biocompatibility. However, their use has been limited to bioresistant polyurethanes. The aim of this study was to develop a nontoxic biodegradable polyurethane and to test its potential for tissue compatibility. A matrix was synthesized with pentane diisocyanate (PDI) as a hard segment and sucrose as a hydroxyl group donor to obtain a microtextured spongy urethane matrix. The matrix was biodegradable in an aqueous solution at 37°C in vitro as well as in vivo. The polymer was mechanically stable at body temperatures and exhibited a glass transition temperature (Tg) of 67°C. The porosity of the polymer network was between 10 and 2000 µm, with the majority of pores between 100 and 300 µm in diameter. This porosity was found to be adequate to support the adherence and proliferation of bone-marrow stromal cells (BMSC) and chondrocytes in vitro. The degradation products of the polymer were nontoxic to cells in vitro. Subdermal implants of the PDI–sucrose matrix did not exhibit toxicity in vivo and did not induce an acute inflammatory response in the host. However, some foreign-body giant cells did accumulate around the polymer and in its pores, suggesting its degradation is facilitated by hydrolysis as well as by giant cells. More important, subdermal implants of the polymer allowed marked infiltration of vascular and connective tissue, suggesting the free flow of fluids and nutrients in the implants. Because of the flexibility of the mechanical strength that can be obtained in urethanes and because of the ease with which a porous microtexture can be achieved, this matrix may be useful in many tissue-engineering applications. PMID:12522810

Colorectal adenoma stem-like cell populations: associations with adenoma characteristics and metachronous colorectal neoplasia.

PubMed

Bartley, Angela N; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J; Buckmeier, Julie A; Corley, Lynda; Phipps, Ron A; Gallick, Gary; Lance, Peter; Thompson, Patricia A; Hamilton, Stanley R

2013-11-01

Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma ("recurrence"), has not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1-labeling indices (ALI) were similar across patient characteristics and in advanced and nonadvanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (P = 0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (P = 0.03). A best-fit algorithm-based cutoff point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem cell target for chemoprevention. ©2013 AACR

Colorectal adenoma stem-like cell populations: Associations with adenoma characteristics and metachronous colorectal neoplasia

PubMed Central

Bartley, Angela N.; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J.; Buckmeier, Julie A.; Corley, Lynda; Phipps, Ron A.; Gallick, Gary; Lance, Peter; Thompson, Patricia A.; Hamilton, Stanley R.

2014-01-01

Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma (“recurrence”), have not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1 labeling indices (ALIs) were similar across patient characteristics and in advanced and non-advanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (p=0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma-free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (p=0.03). A best-fit algorithm-based cut-point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem-cell target for chemoprevention. PMID:24008128

Prognostic and predictive potential molecular biomarkers in colon cancer.

PubMed

Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

2011-01-01

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

Aldosterone Induced Galectin-3 Secretion In Vitro and In Vivo: From Cells to Humans

PubMed Central

Lin, Yen-Hung; Chou, Chia-Hung; Wu, Xue-Ming; Chang, Yi-Yao; Hung, Chi-Sheng; Chen, Ying-Hsien; Tzeng, Yu-Lin; Wu, Vin-Cent; Ho, Yi-Lwun; Hsieh, Fon-Jou; Wu, Kwan-Dun

2014-01-01

Context Patients with primary aldosteronism are associated with increased myocardial fibrosis. Galectin-3 is one of the most important mediators between macrophage activation and myocardial fibrosis. Objective To investigate whether aldosterone induces galectin-3 secretion in vitro and in vivo. Methods and Results We investigated the possible molecular mechanism of aldosterone-induced galectin-3 secretion in macrophage cell lines (THP-1 and RAW 264.7 cells). Aldosterone induced galectin-3 secretion through mineralocorticoid receptors via the PI3K/Akt and NF-κB transcription signaling pathways. In addition, aldosterone-induced galectin-3 expression enhanced fibrosis-related factor expression in fibroblasts. We observed that galectin-3 mRNA from peripheral blood mononuclear cells and serum galectin-3 levels were both significantly increased in mice implanted with aldosterone pellets on days 7 and 14. We then conducted a prospective preliminary clinical study to investigate the association between aldosterone and galectin-3. Patients with aldosterone-producing adenoma had a significantly higher plasma galectin-3 level than patients with essential hypertension. One year after adrenalectomy, the plasma galectin-3 level had decreased significantly in the patients with aldosterone-producing adenoma. Conclusion This study demonstrated that aldosterone could induce galectin-3 secretion in vitro and in vivo. PMID:25180794

Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides.

PubMed

Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Kodama, Yukio; Gamo, Toshie; Ozawa, Shogo; Yoshida, Midori

2015-04-01

We clarified the involvement of constitutive androstane receptor (CAR) in triazole-induced liver hypertrophy and tumorigenesis using CAR-knockout (CARKO) mice. Seven-week-old male CARKO and wild-type (WT) mice were treated with 200 ppm cyproconazole (Cypro), 1500 ppm tebuconazole (Teb), or 200 ppm fluconazole (Flu) in the diet for 27 weeks after initiation by diethylnitrosamine (DEN). At weeks 4 (without DEN) and 13 (with DEN), WT mice in all treatment groups and CARKO mice in Teb group revealed liver hypertrophy with mainly Cyp2b10 and following Cyp3a11 inductions in the liver. Teb also induced Cyp4a10 in both genotypes. Cypro induced slight and duration-dependent liver hypertrophy in CARKO mice. At week 27, Cypro and Teb significantly increased eosinophilic altered foci and/or adenomas in WT mice. These proliferating lesions were clearly reduced in CARKO mice administered both compounds. The eosinophilic adenomas caused by Flu decreased in CARKO mice. The present study indicates that CAR is the main mediator of liver hypertrophy induced by Cypro and Flu, but not Teb. In contrast, CAR played a crucial role in liver tumor development induced by all three triazoles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adhesive retention of experimental fiber-reinforced composite, orthodontic acrylic resin, and aliphatic urethane acrylate to silicone elastomer for maxillofacial prostheses.

PubMed

Kosor, Begüm Yerci; Artunç, Celal; Şahan, Heval

2015-07-01

A key factor of an implant-retained facial prosthesis is the success of the bonding between the substructure and the silicone elastomer. Little has been reported on the bonding of fiber reinforced composite (FRC) to silicone elastomers. Experimental FRC could be a solution for facial prostheses supported by light-activated aliphatic urethane acrylate, orthodontic acrylic resin, or commercially available FRCs. The purpose of this study was to evaluate the bonding of the experimental FRC, orthodontic acrylic resin, and light-activated aliphatic urethane acrylate to a commercially available high-temperature vulcanizing silicone elastomer. Shear and 180-degree peel bond strengths of 3 different substructures (experimental FRC, orthodontic acrylic resin, light-activated aliphatic urethane acrylate) (n=15) to a high-temperature vulcanizing maxillofacial silicone elastomer (M511) with a primer (G611) were assessed after 200 hours of accelerated artificial light-aging. The specimens were tested in a universal testing machine at a cross-head speed of 10 mm/min. Data were collected and statistically analyzed by 1-way ANOVA, followed by the Bonferroni correction and the Dunnett post hoc test (α=.05). Modes of failure were visually determined and categorized as adhesive, cohesive, or mixed and were statistically analyzed with the chi-squared goodness-of-fit test (α=.05). As the mean shear bond strength values were evaluated statistically, no difference was found among the experimental FRC, aliphatic urethane acrylate, and orthodontic acrylic resin subgroups (P>.05). The mean peel bond strengths of experimental fiber reinforced composite and aliphatic urethane acrylate were not found to be statistically different (P>.05). The mean value of the orthodontic acrylic resin subgroup peel bond strength was found to be statistically lower (P<.05). Shear test failure types were found to be statistically different (P<.05), whereas 180-degree peel test failure types were not found to be statistically significant (P>.05). Shear forces predominantly exhibited cohesive failure (64.4%), whereas peel forces predominantly exhibited adhesive failure (93.3%). The mean shear bond strengths of the experimental FRC and aliphatic urethane acrylate groups were not found to be statistically different (P>.05). The mean value of the 180-degree peel strength of the orthodontic acrylic resin group was found to be lower (P<.05). Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Adenomas - Genetic factors in colorectal cancer prevention.

PubMed

Witold, Kycler; Anna, Kubiak; Maciej, Trojanowski; Jakub, Janowski

2018-01-01

Colorectal cancer is the second most common type of cancer both in Europe and Poland. During the last 30 years more than a 3-fold increase has been observed in Poland due to environmental and genetic factors. Almost all colorectal malignancies are related to the formation and malignant transformation of colorectal dysplasia and adenoma. Efforts aiming to decrease the number of colorectal cancer deaths are focused on the disease early detection. Genetic diagnosis for hereditary syndromes predisposing to colorectal cancer has been developed and is a part of the routine treatment. Most cancers are sporadic. They often develop from polyps in the colon. In addition to the genetic events described in the 1990s, showing the adenoma transformation into carcinoma that has been a prime example of malignant transformation for a long time, there are also other possibilities of neoplastic transformation. The recognition of colorectal cancer risk factors make sense as their nature is lifestyle- and diet-related. In this review paper those risk factors are presented and the prevention of colorectal cancer is discussed taking into account genetic factors.

Expression of TRAIL and Fas in Primary Hyperparathyroidism.

PubMed

Segiet, Oliwia Anna; Deska, Mariusz; Mielańczyk, Łukasz; Brzozowa-Zasada, Marlena; Buła, Grzegorz; Gawrychowski, Jacek; Wojnicz, Romuald

2017-08-01

Differentiating between parathyroid lesions is still difficult and ambiguous. In cases of primary hyperparathyroidism, appropriate and prompt diagnosis is of great importance for effective treatment and follow-up. A great amount of mechanisms contribute to the pathogenesis of primary hyperparathyroidism, such as disturbance in balance between pro- and anti-apoptotic factors. Therefore, we examined whether immunohistochemical expression of apoptotic factors, TNF-related apoptosis-inducing ligand (TRAIL) and Fas, could have clinical utility as a marker of proliferative lesions of parathyroid gland. Parathyroid specimens of 58 consecutive patients who had undertaken surgery due to primary hyperparathyroidism were incubated with purified mouse monoclonal antihuman antibodies: anti-TRAIL and anti-Fas. Staining was considered positive when at least 5% of the cells showed immunoreactivity. The percentage of cells which were positively stained for TRAIL in parathyroid hyperplasia was 9.65%, in parathyroid adenoma 8.31%, and in normal controls 2.24%. Immunoreactivity for TRAIL was detected in 91.89% of parathyroid hyperplasias, 85.71% of parathyroid adenomas, and none in healthy glands. The percentage of cells with a positive reaction to Fas in parathyroid hyperplasia was 8.92%, in parathyroid adenoma 8.09%, and in normal tissue 1.9%. The expression of Fas was found in 94.59% of parathyroid hyperplasias, 90.48% of parathyroid adenomas, and none in healthy glands. In our study, hyperplasias demonstrated the highest expression of TRAIL and Fas, whereas in adenomas it was increased compared to normal tissue, but lower than in hyperplasias. These factors could be an additive tool in the differential diagnosis of parathyroid lesions.

15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis.

PubMed

Myung, Seung-Jae; Rerko, Ronald M; Yan, Min; Platzer, Petra; Guda, Kishore; Dotson, Angela; Lawrence, Earl; Dannenberg, Andrew J; Lovgren, Alysia Kern; Luo, Guangbin; Pretlow, Theresa P; Newman, Robert A; Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D

2006-08-08

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ. Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci.

Evaluation Selection of Encapsulating Plastics for Ordnance Electronic Assemblies

DTIC Science & Technology

1981-05-01

ISP-100 Dow Two-component urethane (>70D) 10 B635/1- 4BD Uniroyal Two-component urethane (ɟD) 68 4. CIRCUIT ENCAPSULATION 4.1 Introduction This phase...HARRY DIAs ’ND LABORATORIES 3975 MCMM RD ATTN CO/ TD /TSO/DIVISION DIRFXTORS ATTN JERRY KRAMR ATTN RECORD COPY, 81200 CINCINNATI, ON 45245 ATTN HDL LIBRARY

Double pituitary adenomas: six surgical cases.

PubMed

Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

1999-05-01

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.

PubMed

Diaz-Rodriguez, Esther; Garcia-Rendueles, Angela R; Ibáñez-Costa, Alejandro; Gutierrez-Pascual, Ester; Garcia-Lavandeira, Montserrat; Leal, Alfonso; Japon, Miguel A; Soto, Alfonso; Venegas, Eva; Tinahones, Francisco J; Garcia-Arnes, Juan A; Benito, Pedro; Angeles Galvez, Maria; Jimenez-Reina, Luis; Bernabeu, Ignacio; Dieguez, Carlos; Luque, Raul M; Castaño, Justo P; Alvarez, Clara V

2014-11-01

Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly.

The effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma.

PubMed

Han, Min Seok; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Won Ho; Kim, Tae Il

2017-08-01

Existing studies suggest that metformin lowers the risk and mortality of colorectal cancer. However, the effect of metformin on the suppression and prevention of colorectal adenomas is not clear. The aim of this study was to evaluate the effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma. Among 423 diabetic patients who underwent surveillance colonoscopy after resection of colorectal adenoma between 2005 and 2011, 257 patients were retrospectively reviewed. The patients were divided into two groups: one group comprising 106 patients who took metformin and another group comprising 151 patients who did not take metformin. The clinical characteristics, colorectal adenoma recurrence, and valuable factors for adenoma recurrence were analyzed. At surveillance colonoscopy after colonoscopic polypectomy for adenoma, 38 patients (35.8%) exhibited colorectal adenoma among 106 patients who took metformin, compared with 85 patients (56.3%) with colorectal adenoma among 151 patients who did not take metformin (odds ratio 0.434, 95% confidence interval 0.260-0.723, P = 0.001). Multivariate Cox analysis showed that metformin was associated with decreased recurrence of colorectal adenoma (hazard ratio 0.572, 95% confidence interval 0.385-0.852, P = 0.006) in diabetic patients with previous colorectal adenoma. The cumulative probability of colorectal adenoma recurrence was significantly lower in the metformin group than in the non-metformin group (P = 0.001). Metformin use in diabetic patients with previous colorectal adenoma is associated with a lower risk of colorectal adenoma recurrence.

Unlocking the Potential of Phenacyl Protecting Groups: CO2-Based Formation and Photocatalytic Release of Caged Amines.

PubMed

Speckmeier, Elisabeth; Klimkait, Michael; Zeitler, Kirsten

2018-04-06

Orthogonal protection and deprotection of amines remain important tools in synthetic design as well as in chemical biology and material research applications. A robust, highly efficient, and sustainable method for the formation of phenacyl-based carbamate esters was developed using CO 2 for the in situ preparation of the intermediate carbamates. Our mild and broadly applicable protocol allows for the formation of phenacyl urethanes of anilines, primary amines, including amino acids, and secondary amines in high to excellent yields. Moreover, we demonstrate the utility by a mild and convenient photocatalytic deprotection protocol using visible light. A key feature of the [Ru(bpy) 3 ](PF 6 ) 2 -catalyzed method is the use of ascorbic acid as reductive quencher in a neutral, buffered, two-phase acetonitrile/water mixture, granting fast and highly selective deprotection for all presented examples.

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice.

PubMed

Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Kodama, Yukio; Yoshida, Midori

2016-01-01

To clarify the major pathway of liver tumor development induced by imazalil (IMA), an imidazole fungicide, male constitutive androstane receptor (CAR)-knockout (CARKO) and wild-type (WT) mice were treated with IMA at 500 ppm in the diet up to 27 weeks after initiation by diethylnitrosamine. After 27 weeks of treatment, neither altered foci nor adenomas were significantly increased in CARKO mice, whereas both eosinophilic altered foci and adenomas were increased in WT mice. After 4 or 13 weeks of IMA treatment, liver hypertrophy was observed at the tumor-inducible dose without differences among genotypes or durations. Analysis of hepatic drug metabolite enzymes, performed after administration of multiple doses during a 1-week period, indicated that pregnane X receptor might be involved in liver hypertrophy because IMA markedly elevated Cyp3a11 and Cyp2b10 expression levels in a dose-dependent manner in both genotypes. Our results demonstrated that the CAR pathway was the main mechanism of liver tumor development induced by IMA. The carcinogenic pathway was different from that of liver hypertrophy.

Inflammation has a role in urethane‑induced lung cancer in C57BL/6J mice.

PubMed

Xu, Cai; Zhou, Lingyu; Lu, Lei; Chen, Ting; Wei, Siyu; Lin, Xiaojing; Lian, Xuemei

2016-10-01

Lung cancer is a common and highly frequent cause of cancer‑associated mortality worldwide. Several studies have indicated that chronic inflammation is associated with an increased risk of several types of human cancer. The lung is vulnerable to various chemical and biological insults, and persistent exposure to these factors may result in the release of several inflammatory cytokines from inflammatory cells, thus leading to chronic inflammation and a risk of lung cancer. Due to the extensive application of C57BL/6J mice in lipid metabolism‑related research, it appears important to establish a lung cancer model based on C57BL/6J mice. Therefore, the present study designed an experimental model, in which C57BL/6J mice received several injections of urethane. The study aimed to explore whether inflammation has a role in this model of lung cancer. The results demonstrated that 10 weekly intraperitoneal injections of urethane induced a 100% lung tumor incidence, and urethane‑treated mice possessed higher numbers of immune cells. In addition, the expression levels of cytokines and chemokines in bronchoalveolar lavage fluid were significantly different between the two groups. Activation of the transcription factor nuclear factor‑κB was increased in the lung tissues of urethane‑treated mice, and its expression was upregulated in a time‑dependent manner. These results suggested that the accumulation of lung inflammation may be associated with the occurrence of lung cancer in C57BL/6J mice.

Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats.

PubMed

Aizawa, Naoki; Wakamatsu, Daisuke; Kida, Jun; Otsuki, Takeya; Saito, Yasuho; Matsuya, Hidekazu; Homma, Yukio; Igawa, Yasuhiko

2017-02-01

Kv7 voltage-gated potassium channels have been suggested to modulate mechano-afferent transduction and nociception in the bladder. We investigated the effects of retigabine, a Kv7 channel activator, on rhythmic bladder contractions (RBCs), and single-unit afferent activities (SAAs) of the primary bladder mechanosensitive afferent nerve fibers in urethane-anesthetized rats. In addition, the effects of pretreatment with retigabine on the nociceptive behaviors provoked by an intravesical instillation of resiniferatoxin (RTX) were evaluated in the conscious condition. Female Sprague-Dawley rats were used. Under urethane anesthesia, saline was instilled into the bladder until RBCs were induced reproducibly. Then, the effects of intravenous, cumulative administrations of retigabine (0.1-3 mg/kg) or vehicle (saline) on RBCs were assessed. In separate animals, SAAs of Aδ- and C-fibers were identified by electrical stimulation of the pelvic nerve and by bladder distention with saline. After baseline recording, vehicle or retigabine (0.01-1 mg/kg) was administered intravenously and further recordings were performed. Under pretreatment with vehicle or retigabine (3 mg/kg intraperitoneally), the frequencies of lower abdominal licking and freezing were counted and scored as the bladder nociceptive behaviors induced by intravesical RTX instillation (3 µM, 0.3 ml). Retigabine dose-dependently decreased both the frequency and the amplitude of RBCs and SAAs of both Aδ- and C-fibers. The effect on RBCs was more potent on the frequency than the amplitude. Retigabine inhibited the RTX-induced abdominal licking, but not freezing. Kv7 channels are likely to be implicated in inhibition of bladder mechano- and nociceptive sensory transduction. Neurourol. Urodynam. 36:280-285, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The effect of virtual cross linking on the oxidative stability and lipid uptake of aliphatic poly(urethane urea).

PubMed

Thomas, Vinoy; Jayabalan, Muthu

2002-01-01

In vitro oxidative degradation and lipid sorption of aliphatic, low elastic modulus and virtually cross-linked poly(urethane urea)s based on 4,4' methylene bis(cyclohexyl isocyanate), hydroxy terminated poly butadiene and hexamethylene diamine were evaluated. The aged samples revealed no weight loss in the oxidation medium. The IR spectral analyses revealed the stability of unsaturated double bonds at 964 cm(-1) (characteristic for polybutadiene soft segment) with no change in peak intensity. The poly(tetramethylene glycol) (PTMG)-added poly(ether urethane urea) polymer also revealed no disappearance of IR peaks for ether and unsaturated double bonds in samples aged in vitro oxidation medium. All the polymers have shown increase in weight due to lipid up take in lipid-rich medium (palm oil) but it was rather low in Dulbecco's modified eagle medium (DMEM) cholesterol. The slight change in mechanical properties of the present polymers in oxidation and DMEM is due to the rearrangement of molecular structure with virtual cross links of hydrogen bonding (physical cross linking) without degradation and plasticization effect of lipid. The influence of these media on the rearrangement of virtual cross links has been observed. Higher the virtual cross-link density, lesser is the loss of tensile properties of poly(urethane urea)s in the oxidation medium and vice versa. On the other hand, higher the virtual cross-link density of poly(urethane urea), higher is the loss of ultimate tensile strength and stress at 100% strain and vice versa in DMEM medium.

Gaskets for low-energy houses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harr, D.

1986-05-01

New materials and techniques make it easier to build today's tight, energy-efficient homes. One system that has won many converts recently is the airtight drywall approach (ADA). ADA relies heavily on the use of foam gasketing. In the ADA building system, nearly all joints--sill to foundation, band joist, wall plate to subfloor, and drywall to frame-are gasketed with foam tapes. The combination of gaskets, drywall, and caulk creates an airtight envelope. Foam gasketing tape is well suited from many of these joints because it is clean, economical, and easy to apply. The right gasket will maintain the seal even ifmore » the joint moves, and won't squeeze out of the joint under compression. Caulk, on the other hand, is messy, hard to apply, and squeezes out of the joint under compression. Saturated urethanes are elastic sealants that always recover, even after being completely compressed. Some saturated urethanes recover faster than others, depending on what saturant is used, but all exert a force to recover because they are urethanes. In the construction industry, where gaskets are likely to be buried permanently within the framework, saturated urethane foam gaskets really make sense.« less

In situ SHG monitoring of dipolar orientation and relaxation in Disperse Red type/derivative urethane-urea copolymer

NASA Astrophysics Data System (ADS)

Samoc, A.; Holland, A.; Tsuchimori, M.; Watanabe, O.; Samoc, M.; Luther-Davies, B.; Kolev, V. Z.

2005-09-01

We investigated linear optical and second-order nonlinear optical (NLO) properties of films of urethane-urea copolymer (UU2) functionalised with a high concentration of an azobenzene chromophore. The polymer films on ITO-coated substrate were corona poled to induce a noncentrosymmetric organization of chromophore dipoles and data on the second harmonic generated with the laser beam (the fundamental wavelength 1053 nm, 6 ps/pulse, 20 Hz repetition rate) was acquired as a function of time and temperature. Second harmonic generation (SHG) was used to monitor in situ the polar alignment and relaxation of orientation of the side-chain Disperse Red-like chromophore molecules in the films poled at room temperature and high above the glass transition temperature (Tg 140-150oC). The deff coefficient was determined from the Maker-fringe method and corrected for absorption. A strong second harmonic effect with a fast relaxation was observed in "cold" (room temperature) poling experiments. A large second-order resonantly enhanced optical nonlinearity (d33 of the order of 200 pm/V) was obtained in high temperature poling. A strong and stable nonlinearity has persisted for years after the films were high-temperature poled.

Modification of hormonal secretion in clinically silent pituitary adenomas.

PubMed

Daems, Tania; Verhelst, Johan; Michotte, Alex; Abrams, Pascale; De Ridder, Dirk; Abs, Roger

2009-01-01

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer.

PubMed

Akino, Kimishige; Toyota, Minoru; Suzuki, Hiromu; Mita, Hiroaki; Sasaki, Yasushi; Ohe-Toyota, Mutsumi; Issa, Jean-Pierre J; Hinoda, Yuji; Imai, Kohzoh; Tokino, Takashi

2005-07-01

Activation of Ras signaling is a hallmark of colorectal cancer (CRC), but the roles of negative regulators of Ras are not fully understood. Our aim was to address that question by surveying genetic and epigenetic alterations of Ras-Ras effector genes in CRC cells. The expression and methylation status of 6 RASSF family genes were examined using RT-PCR and bisulfite PCR in CRC cell lines and in primary CRCs and colorectal adenomas. Colony formation assays and flow cytometry were used to assess the tumor suppressor activities of RASSF1 and RASSF2. Immunofluorescence microscopy was used to determine the effect of altered RASSF2 expression on cell morphology. Mutations of K- ras , BRAF, and p53 were identified using single-strand conformation analysis and direct sequencing. Aberrant methylation and histone deacetylation of RASSF2 was associated with the gene's silencing in CRC. The activities of RASSF2, which were distinct from those of RASSF1, included induction of morphologic changes and apoptosis; moreover, its ability to prevent cell transformation suggests that RASSF2 acts as a tumor suppressor in CRC. Primary CRCs that showed K- ras /BRAF mutations also frequently showed RASSF2 methylation, and inactivation of RASSF2 enhanced K- ras -induced oncogenic transformation. RASSF2 methylation was also frequently identified in colorectal adenomas. RASSF2 is a novel tumor suppressor gene that regulates Ras signaling and plays a pivotal role in the early stages of colorectal tumorigenesis.

Vegetarianism as a protective factor for colorectal adenoma and advanced adenoma in Asians.

PubMed

Lee, Chang Geun; Hahn, Suk Jae; Song, Min Keun; Lee, Jun Kyu; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho; Kang, Hyoun Woo

2014-05-01

Although epidemiologic and animal studies suggest a vegetarian diet protects against the development of colorectal cancer, the relationship between vegetarian diet and incidence of colorectal adenoma is not yet conclusive, especially for Asians. The purpose of this study was to examine the protective effect of a vegetarian diet against colorectal adenoma and advanced adenoma. This cross-sectional study compared the prevalence of colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with that among age and sex-matched controls. All the subjects underwent health checkups in a health-promotion center in Korea. Colorectal adenoma and advanced adenoma were both more prevalent in the general population group than in the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the prevalence of metabolic syndrome, high body mass index, and waist circumference were higher in the Buddhist priest group. According to univariate analysis, non-vegetarian diet (general population) significantly increased the prevalence of colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist priests) (OR 1.54, 95 % CI 1.08-2.21, P = 0.018; OR 3.60, 95 % CI 1.53-8.48, P = 0.003). In a conditional regression analysis model, non-vegetarian diet was also a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52, 95 % CI 0.75-2.07, P = 0.043; OR 2.94, CI 0.97-7.18, P = 0.036). Vegetarianism may be effective in preventing both colorectal adenoma and advanced adenoma in Asians.

Colonic diverticulosis is not a risk factor for colonic adenoma.

PubMed

Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

2018-01-01

Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed Central

Kennedy, M. F.; Tutton, P. J.; Barkla, D. H.

1985-01-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour. PMID:4041364

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.

Immunohistochemichal Assessment of the CrkII Proto-oncogene Expression in Common Malignant Salivary Gland Tumors and Pleomorphic Adenoma.

PubMed

Askari, Mitra; Darabi, Masoud; Jahanzad, Esa; Mostakhdemian Hosseini, Zahra; Musavi Chavoshi, Marjan; Darabi, Maryam

2015-01-01

Background and aims. Various morphologies are seen in different salivary gland tumorsor within an individual tumor, and the lesions show divers biological behaviors. Experimental results support the hypothesis that increased CrkII proto-oncogene is associated with cytokine-induced tumor initiation and progression by altering cell motility signaling pathway. The aim of this study was to assess the CrkII expression in common malignant salivary gland tumors and pleomorphic ade-noma. Materials and methods. Immunohistochemical analysis of CrkII expression was performed on paraffin blocks of 64 car-cinomas of salivary glands, 10 pleomorphic adenomas, and 10 normal salivary glands. Biopsies were subjected to immu-nostaining with EnVision detection system using monoclonal anti-CrkII. Evaluation of immunoreactivity of CrkII was based on the immunoreaction intensity and percentage of stained tumor cells which were scored semi-quantitatively on a scale with four grades 0 to 3. Kruskal-wallis test and additional Mann-Whitney statistical test were used for analysis of CrkII expression levels. Results. Increased expression of CrkII was seen (P=0.005) in malignant tumors including: mucoepidermoid carcinoma, adenoid cystic carcinoma, and carcinoma ex pleomorphic adenoma, but CrkII expression in acinic cell carcinoma was weak. CrkII expression in pleomorphic adenoma was weak or negative. A weak staining was sparsely seen in normal acinar serous cell. Conclusion. Increased expression of CrkII and its higher intensity of staining in tumors with more aggressive biologic behavior in carcinomas of salivary gland is consistent with a role for this proto-oncogene in salivary gland tumorigenesis and cancer progression.

Alternative Fuels Compatibility with Army Equipment Testing - Alternative Fuels Material Compatibility Analysis

DTIC Science & Technology

2012-02-21

Testing and Materials °C Celsius DiEGME Diethylene Glycol Monomethyl Ether EPDM Ethylene Propylene Diene Monomer FARE Forward Area Refueling...urethane class AU, polyether urethane class EU, EPDM , Viton®, fluorosilicone class FQ, polytetrafluoroethylene (PTFE), polyolefin and polyester...sleeve Material not provided AAFARS 4720-00-540-1368 Hose, nonmetallic Material not provided AAFARS 4720-01-218-6958 Hose, preformed Rubber

Air Quality Management Using Pollution Prevention: A Joint Service Approach

DTIC Science & Technology

1998-03-01

sites to promote polymerization. High solids coatings may be one or two component systems based on acrylic , alkyd , epoxy, polyester, or urethane...formulation to form high molecular weight polymers. Examples include acrylic , epoxy/polyester hybrid , functional epoxy, thin film epoxy, and urethane...Air Human System Center (HSC/OEBQ) Naval Facilities Engineering Service Center (NFESC) 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 9

Development of l-Tyrosine-Based Enzyme-Responsive Amphiphilic Poly(ester-urethane) Nanocarriers for Multiple Drug Delivery to Cancer Cells.

PubMed

Aluri, Rajendra; Jayakannan, Manickam

2017-01-09

New classes of enzymatic-biodegradable amphiphilic poly(ester-urethane)s were designed and developed from l-tyrosine amino acid resources and their self-assembled nanoparticles were employed as multiple drug delivery vehicles in cancer therapy. The amine and carboxylic acid functional groups in l-tyrosine were converted into dual functional ester-urethane monomers and they were subjected to solvent free melt polycondensation with hydrophilic polyethylene glycols to produce comb-type poly(ester-urethane)s. The phenolic unit in the l-tyrosine was anchored with hydrophobic alkyl side chain to bring appropriate amphiphilicity in the polymer geometry to self-assemble them as stable nanoscaffolds in aqueous medium. The topology of the polymer was found to play a major role on the glass transition, crystallinity, and viscoelastic rheological properties of l-tyrosine poly(ester-urethane)s. The amphiphilic polymers were self-assembled as 200 ± 10 nm nanoparticles and they exhibited excellent encapsulation capabilities for anticancer drugs such as doxorubicin (DOX) and camptothecin (CPT). In vitro drug release studies revealed that the drug-loaded l-tyrosine nanoparticles were stable at extracellular conditions and they underwent enzymatic-biodegradation exclusively at the intracellular level to release the drugs. Cytotoxicity studies in the cervical cancer (HeLa) and normal WT-MEFs cell lines revealed that the nascent l-tyrosine nanoparticles were nontoxic, whereas the CPT and DOX drug-loaded polymer nanoparticles exhibited excellent cell killing in cancer cells. Confocal microscopic imaging confirmed the cellular internalization of drug-loaded nanoparticles. The drugs were taken up by the cells much higher quantity while delivering them from l-tyrosine nanoparticle platform compared to their free state. Flow cytometry analysis showed that the DOX-loaded polymer nanoscaffolds internalized the drugs 8-10× higher compared to free DOX. Both the synthesis of new classes of poly(ester-urethane)s via melt polycondensation approach and the enzyme-responsive drug delivery concept were accomplished for the first time. Thus, the present investigation is expected to open up new opportunities for l-tyrosine polymeric materials in biomaterial and thermoplastic applications.

Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

PubMed

Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

2014-06-01

Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention.

PubMed

Benamouzig, Robert; Uzzan, Bernard; Martin, Antoine; Deyra, Jacques; Little, Julian; Girard, Bernard; Chaussade, Stanislas

2010-05-01

Low-dose aspirin reduces the incidence of colorectal cancer and recurrence of adenomas. Cyclooxygenase-2 (COX-2), one of its main target enzymes, is reportedly over-expressed in colorectal adenomas. To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo. Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy, separately for epithelium, deep stroma and overall. Architecture, grade of dysplasia, K-ras mutation, p53 and cyclin D1 expression were studied. COX-2 expression could be assessed in 219 adenomas from 136 128 adenomas (58%) from 59 patients strongly expressed COX-2. Strong COX-2 expression predominated in adenomas larger than 10 mm (84/129 vs 44/90; p=0.02) and in adenomas showing high-grade dysplasia (22/29 vs 104/188; p=0.04). Deep stromal but not epithelial initial expression of COX-2 predicted adenoma recurrence in the whole population (30/72 patients or 42% strongly expressed deep stromal COX-2 compared with 16/64 or 25% without recurrent adenoma; p=0.04). The protective effect of aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR for recurrence in patients taking aspirin with low COX-2 expression: 0.59; 95% CI 0.39 to 0.90; p=0.02). There was no significant effect of aspirin at the end of the trial. Over-expression of COX-2 was frequent and predominated in large and high-grade dysplasia adenomas. Deep stromal but not epithelial initial expression of COX-2 predicted recurrence of adenomas. Aspirin did not act preferentially on patients whose initial adenomas strongly expressed COX-2.

Up-regulated EMMPRIN/CD147 protein expression might play a role in colorectal carcinogenesis and its subsequent progression without an alteration of its glycosylation and mRNA level.

PubMed

Zheng, Hua-chuan; Wang, Wei; Xu, Xiao-yan; Xia, Pu; Yu, Miao; Sugiyama, Toshiro; Takano, Yasuo

2011-04-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of colorectal carcinomas (CRC). EMMPRIN expression was examined on tissue microarray containing colorectal carcinomas, adenoma and non-neoplastic mucosa (NNM) by immunohistochemistry and in situ hybridization (ISH). Colorectal carcinoma cell lines (DLD-1, HCT-15, SW480 and WiDr) and tissues were studied for EMMPRIN expression by Western blot or RT-PCR, followed by sequencing. All carcinoma cell lines showed EMMPRIN expression at both mRNA and protein levels. Two synonymous mutations were found in carcinoma cell lines at codon109 (GCT → GCC: Ala) or 179 (GAT → GAC: Asp). Frozen CRC tissues displayed higher EMMPRIN expression than paired NNM (P < 0.05). EMMPRIN expression was immunohistochemically stronger in colorectal high-grade adenoma, adenocarcinoma and metastatic carcinoma than non-neoplastic superficial epithelium and low-grade adenoma (P < 0.05). In contrast, its mRNA level was similar from colorectal NNM, adenoma to adenocarcinoma by ISH, in line with the findings of RT-PCR (P > 0.05). Immunohistochemically, EMMPRIN expression was positively correlated with tumor size, depth of invasion, vascular or lymphatic invasion, grade of infiltration (INF), ki-67 and VEGF expression of CRCs (P < 0.05). Among them, depth of invasion was an independent associated factor for EMMPRIN expression in CRCs (P < 0.05). Up-regulated EMMPRIN protein expression might contribute to colorectal carcinogenesis without the alteration of its glycosylation and mRNA level. Aberrant EMMPRIN protein expression might promote growth or invasion of CRCs possibly through increased ki-67 expression and inducible angiogenesis via up-regulating VEGF expression.

Case report of a pituitary thyrotropin-secreting macroadenoma with Hashimoto thyroiditis and infertility.

PubMed

Li, Jiaqi; Li, Jianwei; Jiang, Shu; Yu, Ruichao; Yu, Yerong

2018-01-01

Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility. Examinations revealed pituitary thyrotropin-secreting macroadenoma. We conducted trans-sphenoidal surgery. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were used for reproductive reconstruction after surgery. This patient successfully fathered a child. To date, the multidisciplinary team treatment of TSHoma was rare, TSHomas are often misdiagnosed as macroadenomas, because the clinical features are varied and it often takes a long time to be diagnosed. So the purpose of this case report is to attract attention to the manifestation of increased thyroid stimulating hormone (TSH) concentration and discuss MDT treatment for TSH-secreting adenoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating FOXC1 expression.

PubMed

Wang, D S; Zhang, H Q; Zhang, B; Yuan, Z B; Yu, Z K; Yang, T; Zhang, S Q; Liu, Y; Jia, X X

2016-03-24

Many studies have shown that microRNA (miR)-133 functions as a tumor suppressor in a variety of metastatic cancers, including breast cancer, gastric cancer, and liver fibrosis. However, the influence of miR-133 on pituitary tumor malignancy has not yet been reported. The purpose of this study was to explore the role of miR-133 in pituitary tumor cell migration and invasive ability and the molecular mechanisms involved. Our findings suggest that in pituitary adenoma cell lines, through direct targeting and negative control of forkhead box C1 (FOXC1), miR-133 can inhibit pituitary adenoma cell migration and invasion. In addition, epithelial-to-mesenchymal transition can be induced by miR-133. Additionally, a negative correlation was found between FOXC1 and miR-133 expression when comparing their expression levels between cancerous tissue and adjacent normal tissue. This suggests that miR-133 can inhibit cell migration and invasion by directly targeting FOXC1, implying that miR-133 could be a potential therapeutic target for treatment of invasive pituitary adenoma.

Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women.

PubMed

Woodson, Karen; Flood, Andrew; Green, Lisa; Tangrea, Joseph A; Hanson, Jeffrey; Cash, Brooks; Schatzkin, Arthur; Schoenfeld, Phillip

2004-03-03

Loss of imprinting (LOI) of insulin-like growth factor-II (IGF-II) may be an inherited epigenetic trait that is polymorphic in the population, and its presence may predispose an individual to the development of colorectal cancer. We evaluated the association between LOI of IGF-II in normal colonic mucosal samples and adenomas in women participating in a colonoscopy screening study. Among 40 participants, 11 (27.5%) had LOI of IGF-II in their normal colonic mucosal tissue. After adjusting for body mass index and family history of colorectal cancer, LOI status was associated with a fivefold increased risk of adenoma formation (odds ratio = 5.2, 95% confidence interval = 1.0 to 26.7). On average, IGF-II expression was more than threefold higher among women with LOI of IGF-II than among women with normal imprinting status. Our findings support the hypothesis that LOI of IGF-II is an epigenetic trait polymorphic in the population and suggest that LOI of IGF-II may play a role in colorectal cancer. These findings are intriguing and need to be confirmed in larger studies.

[Expression of CD10 in tumor-associated fibroblast of cancerized or recurrent colorectal adenomas].

PubMed

Zheng, Jiangjiang; Zhu, Yin; Li, Changshui; Li, Yinya; Nie, Qianqian; Zhu, Ziling; Deng, Hong

2016-05-25

Objective: To investigate the expression of CD10 in tumor-associated fibroblasts (TAF) in colorectal adenomas and its relation to cancerization and recurrence of adenoma. Methods: Tissue samples of low-grade adenoma ( n =50), high-grade adenoma ( n =50) and colorectal adenocarcinoma ( n =50) were collected, and tissue samples at the distal margin of corresponding colorectal lesions were taken as controls. The expression of CD10 in the stromal TAFs, and the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells were detected by immunohistochemistry (Envision). The correlation of CD10 expression in stromal TAFs with the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells was analyzed by Spearmen. One hundred samples of low-grade colorectal adenoma were collected, including 57 non-recurrent cases and 43 recurrent cases (16 cases of recurrent adenoma and 27 cases of recurrent adenocarcinoma); the expression of stromal TAF CD10 were determined and compared among groups. Results: There was no TAF in normal colorectal mucosa. The expression rates of TAF CD10 in low-grade adenoma, high-grade adenoma and colorectal adenocarcinoma were 22%, 50% and 78%, respectively (all P <0.05). The expression of Ki-67 and β-catenin in low-grade adenoma, high-grade adenoma, colorectal adenocarcinoma was on a rising trend (all P <0.01). The expression of CyclinD1 in high-grade adenoma was higher than that in colorectal adenocarcinoma and low-grade adenoma (all P >0.05). The expression of p53 in colorectal adenocarcinoma and high-grade adenoma was higher than that in low grade adenoma (all P <0.01). The expression of TAF CD10 was correlated with the expression of p53, Ki-67 and β-catenin-nucleus( r =0.264、0.307、0.320, all P <0.01),but not correlated with CyclinD1 and β-catenin-membrane ( r =0.012、-0.073, all P >0.05). The TAF CD10 level was significantly higher in low-grade adenoma with recurrence than that in those without recurrence ( P <0.05).The expression of CD10 in recurrent colorectal adenocarcinoma was higher than that in recurrent adenoma ( P <0.05). Conclusion: The expression of TAF CD10 is increased gradually in the process of adenoma-cancer, indicating that it may play an important role in the canceration of adenoma. Adenomas with high expression of CD10 TAF are likely to be recurrent and cancerized, and detection of TAF CD10 combined with p53, Ki-67 and β-catenin may be of value in predicting canceration or recurrence of colorectal adenoma.

Preparation and properties of an internal mold release for rigid urethane foam

NASA Astrophysics Data System (ADS)

Paker, B. G.

1980-08-01

Most mold release agents used in the molding of rigid polyurethane foam are applied to the internal surfaces of the mold. These materials form a thin layer between the surface of the mold and the foam, allowing for easy release of the molded parts. This type of mold release must be applied prior to each molding operation; and, after repeated use, cleaning of the mold is required. Small amounts of this mold release are transferred to the molded part, resulting in a part with poor surface bondability characteristics. An internal release agent, which can be mixed in a urethane foam resin was investigated. The internal mold release provided good releasability and resulted in urethane foam that has excellent surface bondability. No compatibility problems are expected from the use of this type of release agent.

Degradation Mechanisms of Poly(ester urethane) Elastomer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edgar, Alexander S.

This report describes literature regarding the degradation mechanisms associated with a poly(ester urethane) block copolymer, Estane® 5703 (Estane), used in conjunction with Nitroplasticizer (NP), and 1,3,5,7-tetranitro-1,3,5,7-tetrazocane, also known as high molecular weight explosive (HMX) to produce polymer bonded explosive PBX 9501. Two principal degradation mechanisms are reported: NO2 oxidative reaction with the urethane linkage resulting in crosslinking and chain scission events, and acid catalyzed hydrolysis of the ester linkage. This report details future work regarding this PBX support system, to be conducted in late 2017 and 2018 at Engineered Materials Group (MST-7), Materials Science and Technology Division, Los Alamos Nationalmore » Laboratory. This is the first of a series of three reports on the degradation processes and trends of the support materials of PBX 9501.« less

COMPARISON OF GENE EXPRESSION PROFILES FROM RATS FED THREE TOXICOLOGICALLY DIFFERENT CONAZOLES

EPA Science Inventory

Conazoles arc a class of fungicides used as pharmaceutical and agricultural products. In chronic bioassays, triadimefon was hepatotoxic and induced transitional cell adenomas in the thyroid gland. Both propiconazole and myclobutanil were hepatotoxic but had no effect on the thyro...

[Classification and etiology of hyperthyroidism].

PubMed

Łacka, Katarzyna; Fraczek, Magdalena Maria

2014-03-01

The prevalence of hyperthyroidism in women is between 0.5-2% and it is 10 times less common in men. The most common causes are Graves' disease, toxic multinodular goiter, and autonomously functioning thyroid adenoma. Rare causes of hyperthyroidisms are as follow: pituitary adenoma, autoimmune thyroiditis (Hashitoxicosis), levothyroxine overdose, inadequate iodine supplementation (including amiodaron induced hyperthyroidism, iodine-based contrast media), hCG excess (pregnancy, gestational trophoblastic disease, germ-cell tumors), drug induced hyperthyroidism, differentiated thyroid carcinomas and/or their metastases, struma ovarii, and familial nonautoimmune hyperthyroidism. This article focuses on the current data of etiopathogenesis of hyperthyroidisms. Genetic factors (like HLA-DR3,CD40, CTLA-4, PTPN22, FOXP3 CD25) and thyroid specific genes (thyroglobulin, TSHR, G(s)alpha) and environmental and endogenous factors (such as age, iodine, selenium, emotional stress, smoking, gender, pregnancy, sex hormones, fetal microchimerism, fetal growth, bacterial infections, viral infections, allergies, drugs (alemtuzumab, interferon alpha, iplimumab/tremelimumab, tyrosine kinase inhibitors, denileukindiftitox, thalidomide/lenalidomide, exposition to fallout and radiotherapy) have been described.

Growth hormone and prolactin responses to corticotrophin-releasing-hormone in patients with Cushing's disease: a paracrine action of the adenomatous corticotrophic cells?

PubMed

Loli, P; Boccardi, E; Branca, V; Bramerio, M; Barberis, M; Losa, M; Terreni, M T; Lodrini, S; Pollo, B; Vignati, F

1998-10-01

In patients with Cushing's disease multihormonal responses to ovine corticotrophin releasing hormone (oCRH) have been detected in blood from inferior petrosal sinuses. This finding has been explained by co-secretion of other hormones, in addition to ACTH, by the pituitary adenoma itself or by paracrine effects exerted by the adenoma on normal periadenomatous pituitary cells. To assess these hypotheses we compared the presence of a CRH induced GH and/or PRL response during inferior petrosal sinus sampling to the immunohistochemical detection of PRL and GH in adenomatous tissue removed from patients with Cushing's disease. Twenty-two patients with Cushing's disease and two patients with ectopic ACTH syndrome due to a bronchial carcinoid were studied; each patient had undergone preoperative inferior petrosal sinus sampling for diagnostic purposes with determination of GH and PRL in addition to ACTH, before and after administration of oCRH. Immunohistochemical studies for ACTH, GH and PRL detection were carried out on adenomatous tissue removed at surgery in the patients with pituitary dependent Cushing's disease and on the carcinoid tumours from the two patients with ectopic ACTH syndrome. All pituitary adenomas immunostained for ACTH, and four adenomas immunostained for GH or PRL in addition to ACTH. A PRL increase in the inferior petrosal sinus after oCRH administration was found in 11 of 22 patients, but none of their tumours immunostained for PRL. Immunostaining for PRL was found in the pituitary tumours from two patients but in neither patient was there a PRL response after oCRH. A GH response was found in 13 of 20 patients in whom it was sought; no patient showed immunostaining in their tumour. GH immunostaining was found in two tumours but in neither patient was there a GH response after oCRH. The oCRH-induced increase of GH and PRL was always recorded in the dominant inferior petrosal sinus. The ACTH response to oCRH was significantly higher in patients who showed oCRH induced increases in GH and/or PRL than in patients who did not, both in terms of area under the response-curve (22,032 +/- 9876 vs. 4371 +/- 2870 ng/l/10 min; P < 0.05) or mean percentage increase above baseline (754 +/- 229% vs. 147.2 +/- 67%, P < 0.02). A significant correlation was observed between ACTH and GH responses to oCRH. The two patients with ectopic Cushing's syndrome did not show ACTH, GH or PRL increases after oCRH administration and did not show immunostaining for GH or PRL in their tumours. The present data do not support the hypothesis of co-secretion of hormones by the pituitary adenoma as the cause of the GH and PRL responses to ovine corticotrophin releasing hormone observed in patients with Cushing's disease; it is suggested that a different mechanism, possibly involving an interaction between the ACTH secreting adenoma and the normal periadenomatous GH and PRL secreting cells, may be responsible.

Furan in heat-treated foods: formation, exposure, toxicity, and aspects of risk assessment.

PubMed

Moro, Sabrina; Chipman, James Kevin; Wegener, Jan-Willem; Hamberger, Carolin; Dekant, Wolfgang; Mally, Angela

2012-08-01

Furan is formed in a variety of heat-treated foods through thermal degradation of natural food constituents. Relatively high levels of furan contamination are found in ground roasted coffee, instant coffee, and processed baby foods. European exposure estimates suggest that mean dietary exposure to furan may be as high as 1.23 and 1.01 μg/kg bw/day for adults and 3- to 12-month-old infants, respectively. Furan is a potent hepatotoxin and hepatocarcinogen in rodents, causing hepatocellular adenomas and carcinomas in rats and mice, and high incidences of cholangiocarcinomas in rats at doses ≥ 2 mg/kg bw. There is therefore a relatively low margin of exposure between estimated human exposure and doses that cause a high tumor incidence in rodents. Since a genotoxic mode of action cannot be excluded for furan-induced tumor formation, the present exposures may indicate a risk to human health and need for mitigation. This review summarizes the current knowledge on mechanisms of furan formation in food, human dietary exposure to furan, and furan toxicity, and highlights the need to establish the risk resulting from the genotoxic and carcinogenic properties of furan at doses lower than 2 mg/kg bw. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surgical Management of Carney Complex-Associated Pituitary Pathology.

PubMed

Lonser, Russell R; Mehta, Gautam U; Kindzelski, Bogdan A; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O; Dickerman, Robert; Oldfield, Edward H

2017-05-01

Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. Copyright © 2017 by the Congress of Neurological Surgeons

Surgical Management of Carney Complex–Associated Pituitary Pathology

PubMed Central

Mehta, Gautam U.; Kindzelski, Bogdan A.; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O.; Dickerman, Robert; Oldfield, Edward H.

2017-01-01

Abstract BACKGROUND: Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. OBJECTIVE: To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. METHODS: Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. RESULTS: Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CONCLUSION: CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. PMID:27509071

Increased formate overflow is a hallmark of oxidative cancer.

PubMed

Meiser, Johannes; Schuster, Anne; Pietzke, Matthias; Vande Voorde, Johan; Athineos, Dimitris; Oizel, Kristell; Burgos-Barragan, Guillermo; Wit, Niek; Dhayade, Sandeep; Morton, Jennifer P; Dornier, Emmanuel; Sumpton, David; Mackay, Gillian M; Blyth, Karen; Patel, Ketan J; Niclou, Simone P; Vazquez, Alexei

2018-04-10

Formate overflow coupled to mitochondrial oxidative metabolism\\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism.

Mineralocorticoid receptor antagonism protects the aorta from vascular smooth muscle cell proliferation and collagen deposition in a rat model of adrenal aldosterone-producing adenoma.

PubMed

Yan, Yongji; Wang, Chao; Lu, Yiqin; Gong, Huijie; Wu, Zhun; Ma, Xin; Li, Hongzhao; Wang, Baojun; Zhang, Xu

2018-02-01

The number of patients with adrenal aldosterone-producing adenomas (APAs) has gradually increased. However, even after adenoma resection, some patients still suffer from high systolic blood pressure (SBP), which is possibly due to great arterial remodeling. Moreover, mineralocorticoid receptors (MRs) were found to be expressed in vascular smooth muscle cells (VSMCs). This study aims to determine whether MR antagonism protects the aorta from aldosterone-induced aortic remolding. Male rats were subcutaneously implanted with an osmotic minipumps and randomly divided into four groups: control; aldosterone (1 μg/h); aldosterone plus a specific MR antagonist, eplerenone (100 mg/kg/day); and aldosterone plus a vasodilator, hydralazine (25 mg/kg/day). After 8 weeks of infusion, aortic smooth muscle cell proliferation and collagen deposition, as well as the MDM2 and TGF-β1 expression levels in the aorta, were examined. Model rats with APAs were successfully constructed. Compared with the control rats, the model rats exhibited (1) marked SBP elevation, (2) no significant alteration in aortic morphology, (3) increased VSMC proliferation and MDM2 expression in the aorta, and (4) enhanced total collagen and collagen III depositions in the aorta, accompanied with up-regulated expression of TGF-β1. These effects were significantly inhibited by co-administration with eplerenone but not with hydralazine. These findings suggested that specific MR antagonism protects the aorta from aldosterone-induced VSMC proliferation and collagen deposition.

Radiation-induced optic neuropathy: A magnetic resonance imaging study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy, J.; Mancuso, A.; Beck, R.

1991-03-01

Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence ofmore » both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.« less

Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

PubMed Central

Aaltonen, Lauri A.; Daly, Adrian F.

2013-01-01

Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses the current clinical and therapeutic characteristics of more than 200 FIPA families and addresses research findings among AIP mutation-bearing patients in different populations with pituitary adenomas. PMID:23371967

Laser autofluorescent spectroscopy in adrenal tumor surgery

NASA Astrophysics Data System (ADS)

Vetshev, Petr S.; Ippolitov, Leonid I.; Loschenov, Victor B.; Kazaryan, Airazat M.; Minnibaev, Marat T.; Vetshev, Sergei P.

1999-12-01

Determination of a histological type of adrenal lesion at the preoperative or intraoperative stage allows to choose the optimal volume of surgery and in the short time effectively correct the postoperative hormonal therapy. 12 patients with different adrenal tumours (3 - lightcellular adenoma, 3 - mixedcellular adenoma, 1 - darkcellular adenoma, 1 - trabecular adenoma, 1 - malignant lymphoma, 3 - aldosteroma, 1 - pheochromocytoma, including the chance of combination of mixedcellular adenoma and aldosteroma of left adrenal) were operated on. The patients' aged varied from 33 to 62 years. For the first time we made intraoperative laser autofluorescent spectroscopy (IOLAS). The laser ve1ength was 632.8 nm. We defined a autofluorescent intensity. Portable equipment was used. The duration of the procedure did not exceed 2mm. The autofluorescent peak of adrenal tissue was 1.33+/-0.05 relativistic unit (RU) at 685 nm. The autofiurescent peaks of adrenal adenomas were 1 .07 RU, 0.9-1 .15 RU, 1.7-1 .9 RU, 3.4 RU accordingly for trabecular adenoma, lightcellular adenoma, mixedcellular adenoma, darkcellular adenoma Besides greater contribution of longwave component to auflurescence is characteristic for mixecellular adenoma and especially for darkcellular adenoma. The autofiurescent peaks of aldosteroma and pheochromocytoma were accordingly 1.2-1.4 RU and 2.2 RU. Spectral distribution of intensity was like mixedcellular adenoma's one. In the case of malignant lymphoma the autofiurescence peak was 2,3 RU and we also noted displacement of maximum of autoflurescence (-15 nm, from 685 nm to 670 nm).The results of IOLAS application as a adjuvant diagnosticmethod point to promise for intraoperative rapid diagnostics of adrenal tumours.

Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management

PubMed Central

Lim, Chul-Hyun; Cho, Young-Seok

2016-01-01

Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631

Gingerol Reverses the Cancer-Promoting Effect of Capsaicin by Increased TRPV1 Level in a Urethane-Induced Lung Carcinogenic Model.

PubMed

Geng, Shengnan; Zheng, Yaqiu; Meng, Mingjing; Guo, Zhenzhen; Cao, Ning; Ma, Xiaofang; Du, Zhenhua; Li, Jiahuan; Duan, Yongjian; Du, Gangjun

2016-08-10

Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.

Poly(hydroxyl urethane) compositions and methods of making and using the same

DOEpatents

Luebke, David; Nulwala, Hunaid; Tang, Chau

2016-01-26

Methods and compositions relating to poly(hydroxyl urethane) compounds are described herein that are useful as, among other things, binders and adhesives. The cross-linked composition is achieved through the reaction of a cyclic carbonate, a compound having two or more thiol groups, and a compound having two or more amine functional groups. In addition, a method of adhesively binding two or more substrates using the cross-linked composition is provided.

Poly(hydroxyl urethane) compositions and methods of making and using the same

DOEpatents

Luebke, David; Nulwala, Hunaid; Tang, Chau

2014-12-16

Methods and compositions relating to poly(hydroxyl urethane) compounds are described herein that are useful as, among other things, binders and adhesives. The cross-linked composition is achieved through the reaction of a cyclic carbonate, a compound having two or more thiol groups, and a compound having two or more amine functional groups. In addition, a method of adhesively binding two or more substrates using the cross-linked composition is provided.

The Reactions of Nitrogen Peroxide with Possible Stabilisers for Propellants

DTIC Science & Technology

1957-03-01

ether Carbamite Phe nyl-be nzyl-ure thane (pure) Cyclohexanyl-urethane Cyclohexano ne Die thyl phthalate Di-isoamyl phthalate Dibutyl oxalate Glycollic...saponification" arises from the presence of phenyl urethane and diphenyl urea; differences in contents of these impurities and of benzyl aniline...nitrogen that is recovered from a product. 4.2.2 Ure are fairly reactive. Triphenylethylurea present with diphenyl - amine in 蠢 compound" leads to a

FOAM-IN-PLACE FORM FITTING HELMET LINERS

DTIC Science & Technology

A urethane foam formulation has been developed to produce foamed-in-place helmet liners for Air Force crash or flying helmets. High density urethane...foam helmet liners has been foamed-in-place directly on the flying crew member’s head, producing a perfectly fitting helmet liner with a minimum of...time, labor and inconvenience. These liners were produced at an extremely modest cost. Design and fabrication of a suitable mold in which the helmet

Hepatocellular carcinoma arising in a pigmented telangiectatic adenoma with nuclear β-catenin and glutamine synthetase positivity: case report and review of the literature.

PubMed

Hechtman, Jaclyn F; Raoufi, Mohammad; Fiel, M Isabel; Taouli, Bachir; Facciuto, Marcelo; Schiano, Thomas D; Blouin, Amanda G; Thung, Swan N

2011-06-01

Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of hepatocellular adenoma that is often underrecognized by pathologists. We report a case of hepatocellular carcinoma arising within a pigmented telangiectatic hepatocellular adenoma in a noncirrhotic man with diffuse glutamine synthetase and nuclear β-catenin positivity. This case highlights malignant transformation of telangiectatic adenomas, and describes a previously unreported association between pigment deposition and telangiectatic adenoma. Radiology, gross pathology, and histopathology are shown. Review of the literature with attention to β-catenin and glutamine synthetase staining, malignant transformation, patient characteristics, the presence of Dubin-Johnson-like pigment, and genetic characteristics of telangiectatic adenomas are discussed.

Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

PubMed

Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

2018-07-01

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

Simultaneous Occurrence of Pancreatic Adenocarcinoma and Brunner's Gland Adenoma in a Siberian Tiger (Panthera tigris altaica).

PubMed

Gombač, M; Dolenšek, T; Jaušovec, D; Kvapil, P; Švara, T; Pogačnik, M

2015-11-01

We describe a case of pancreatic adenocarcinoma and Brunner's gland adenoma in an 18-year-old male Siberian tiger (Panthera tigris altaica) from the Ljubljana Zoo. The tiger was humanely destroyed due to weakness and progressive weight loss. Necropsy examination revealed a large, grey, predominantly necrotic mass replacing the major part of the pancreatic body. Microscopically, the mass was unencapsulated, poorly demarcated, highly cellular and composed of highly pleomorphic, cuboidal to tall columnar cells with basal, round or oval, moderately anisokaryotic nuclei with prominent nucleoli and moderate to large amounts of eosinophilic cytoplasm. The tumour was diagnosed as pancreatic tubular adenocarcinoma with infiltration into the duodenum and mesentery. There were tumour emboli in mesenteric blood vessels and hepatic metastases. The non-affected part of the pancreas exhibited severe chronic pancreatitis. In addition, one firm white neoplastic nodule was observed in the duodenal wall. The nodule was set in the tunica muscularis and was unencapsulated, well demarcated and highly cellular, and consisted of a closely packed layer of normal Brunner's glands and a centrally positioned group of irregularly branched tubules with small amounts of debris in the lumen. The neoplastic nodule was diagnosed as Brunner's gland adenoma. The present case is, to the best of our knowledge, the first report of concurrent pancreatic adenocarcinoma and Brunner's gland adenoma, most probably induced by chronic pancreatitis, either in man or animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy of sellar opening in the pituitary adenoma resection of transsphenoidal surgery influences the degree of tumor resection.

PubMed

Wang, Shousen; Qin, Yong; Xiao, Deyong; Wei, Liangfeng

2017-07-24

Endonasal transsphenoidal microsurgery is often adopted in the resection of pituitary adenoma, and has showed satisfactory treatment and minor injuries. It is important to accurately localize sellar floor and properly incise the bone and dura matter. Fifty-one patients with pituitary adenoma undergoing endonasal transsphenoidal microsurgery were included in the present study. To identify the scope of sellar floor opening, CT scan of the paranasal sinus and MRI scan of the pituitary gland were performed for each subject. Intraoperatively, internal carotid artery injury, leakage of cerebrospinal fluid, and tumor texture were recorded, and postoperative complications and residual tumors were identified. The relative size of sellar floor opening significantly differed among the pituitary micro-, macro- and giant adenoma groups, and between the total and partial tumor resection groups. The ratio of sellar floor opening area to maximal tumor area was significantly different between the total and partial resection groups. Logistic regression analysis revealed that the ratio of sellar floor opening area to the largest tumor area, tumor texture, tumor invasion and age were independent prognostic factors. The vertical distance between the top point of sellar floor opening and planum sphenoidale significantly differed between the patients with and without leakage of cerebrospinal fluid. These results together indicated that relatively insufficient sellar floor opening is a cause of leading to residual tumor, and the higher position of the opening and closer to the planum sphenoidale are likely to induce the occurrence of leakage of cerebrospinal fluid.

The Relation of Smoking, Alcohol Use and Obesity to Risk of Sigmoid Colon and Rectal Adenomas

PubMed Central

Kono, Suminori; Shinchi, Koichi; Wakabayashi, Kazuo; Todoroki, Isao; Sakurai, Yutaka; Imanishi, Koji; Nishikawa, Hiroshi; Ogawa, Shinsaku; Katsurada, Mitsuhiko

1995-01-01

We conducted a case‐control study, using 429 cases with histologically confirmed sigmoid adenoma, 75 cases with rectal adenoma, and 3101 controls showing normal colonoscopy at least up to 60 cm from the anus. The subjects were male Self‐Defense Forces personnel aged 48–56 who received a retirement health examination including a routine sigmoid‐ or colonoscopy. Lifestyle characteristics were ascertained by a self‐administered questionnaire. Smoking in the recent past (ġ 10 years preceding the colonoscopy) and smoking in the remote past (>10 years before the colonoscopy) were both significantly associated with risk of sigmoid adenoma but not with rectal adenoma as a whole. After reciprocal adjustment for smoking in the two periods, only smoking in the recent past was associated with both sigmoid colon and rectal adenomas. Odds ratios (OR) of sigmoid adenoma (and 95% confidence interval) for the categories of 0, 1‐150, 151‐250 and ġ251 cigarette‐years were 1.0 (reference), 1.9 (1.3‐2,8), 2.1 (1.4‐3.0) and 3.0 (1.9‐4.7), respectively (P for trend < 0.01), and those for rectal adenoma were 1.0 (reference), 1.2 (0.4‐3.2), 3.5 (1.4‐8.5) and 2.0 (0.6‐6.7), respectively (P for trend = 0.03). Alcohol use was significantly positively associated with sigmoid adenoma, and insignificantly associated with rectal adenoma. Body mass index was significantly positively associated with sigmoid adenoma, especially large ones. No such association was found for rectal adenoma. These findings suggest that smoking, especially in the recent past, and alcohol use are common risk factors for sigmoid colon and rectal adenomas while obesity may be exclusively related to the growth of sigmoid adenoma. PMID:8567391

Is IGSF1 involved in human pituitary tumor formation?

PubMed

Faucz, Fabio R; Horvath, Anelia D; Azevedo, Monalisa F; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R; Wit, Jan M; Bernard, Daniel J; Stratakis, Constantine A

2015-02-01

IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. © 2015 Society for Endocrinology.

Is IGSF1 involved in human pituitary tumor formation?

PubMed Central

Faucz, Fabio R.; Horvath, Anelia D.; Azevedo, Monalisa F.; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D.; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R.; Wit, Jan M.; Bernard, Daniel J.; Stratakis, Constantine A.

2014-01-01

IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in sections from GH-producing adenomas, familial somatomammotroph hyperplasia and in normal pituitary. In two male patients, and in one female, with somatomammotroph hyperplasia from the same family, we identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function. Of 60 female controls, two carried the same variant, and seven were heterozygous for other variants. Immunohistochemistry showed increase IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared to a GH-producing adenoma from a patient negative for any IGSF1 variants and to normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. PMID:25527509

Glial cell adhesion and protein adsorption on SAM coated semiconductor and glass surfaces of a microfluidic structure

NASA Astrophysics Data System (ADS)

Sasaki, Darryl Y.; Cox, Jimmy D.; Follstaedt, Susan C.; Curry, Mark S.; Skirboll, Steven K.; Gourley, Paul L.

2001-05-01

The development of microsystems that merge biological materials with microfabricated structures is highly dependent on the successful interfacial interactions between these innately incompatible materials. Surface passivation of semiconductor and glass surfaces with thin organic films can attenuate the adhesion of proteins and cells that lead to biofilm formation and biofouling of fluidic structures. We have examined the adhesion of glial cells and serum albumin proteins to microfabricated glass and semiconductor surfaces coated with self-assembled monolayers of octadecyltrimethoxysilane and N-(triethoxysilylpropyl)-O- polyethylene oxide urethane, to evaluate the biocompatibility and surface passivation those coatings provide.

NMDA receptor gating of information flow through the striatum in vivo.

PubMed

Pomata, Pablo E; Belluscio, Mariano A; Riquelme, Luis A; Murer, M Gustavo

2008-12-10

A role of NMDA receptors in corticostriatal synaptic plasticity is widely acknowledged. However, the conditions that allow NMDA receptor activation in the striatum in vivo remain obscure. Here we show that NMDA receptors contribute to sustain the membrane potential of striatal medium spiny projection neurons close to threshold during spontaneous UP states in vivo. Moreover, we found that the blockade of striatal NMDA receptors reduces markedly the spontaneous firing of ensembles of medium spiny neurons during slow waves in urethane-anesthetized rats. We speculate that recurrent activation of NMDA receptors during UP states allows off-line information flow through the striatum and system level consolidation during habit formation.

OCCURRENCE OF COLORECTAL ADENOMAS IN YOUNGER ADULTS: AN EPIDEMIOLOGIC NECROPSY STUDY

PubMed Central

Pendergrass, Cheryl J.; Edelstein, Daniel L.; Hylind, Linda M.; Phillips, Blaine T.; Iacobuzio-Donahue, Christine; Romans, Katharine; Griffin, Constance A.; Cruz-Correa, Marcia; Tersmette, Anne C.; Offerhaus, G. Johan A.; Giardiello, Francis M.

2009-01-01

Background and Aims The colorectal adenoma is the precursor lesion in virtually all colorectal cancers. Occurrence of colorectal adenomas has been studied in older adults but analysis in younger adults is lacking. Methods The prevalence by age, sex, race, and location, and the number of colorectal adenomas detected was investigated using epidemiologic necropsy in 3558 persons aged 20–89 autopsied from 1985 to 2004 at the Johns Hopkins Hospital. Results were standardized to the general population. Younger adults 20–49 years old were compared to older adults 50 to 89 years old. Results The prevalence of colorectal adenomas in younger adults increased from 1.72% to 3.59% from the 3rd to 5th decade of life and then sharply increased after age 50. In younger adults, adenomas were more prevalent in men than women (RR= 1.09, CI 1.07–1.11) and whites than blacks (RR=1.28, CI 1.26–1.31). Overall, both younger and older adults had predominately left-sided adenomas, but blacks in both age groups had more right-sided adenomas. Occurrence of two or more adenomas in younger adults and five or more in older adults was greater than 2 standard deviations from the mean. Conclusions Colorectal adenomas infrequently occur in younger adults and are more prevalent in the left colon. Irrespective of age, blacks have more right-sided adenomas suggesting need for screening the entire colorectum. Two or more adenomas in younger adults and five or more in older adults represents polyp burden outside the normal expectation. PMID:18558514

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention

PubMed Central

Lance, Peter; Alberts, David S.; Thompson, Patricia A.; Fales, Liane; Wang, Fang; Jose, Jerilyn San; Jacobs, Elizabeth T.; Goodman, Phyllis J.; Darke, Amy K.; Yee, Monica; Minasian, Lori; Thompson, Ian M.; Roe, Denise J.

2017-01-01

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as alpha tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90–1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared to placebo (RR = 1.03, 95% CI, 0.96–1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. PMID:27777235

Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model.

PubMed

Bernard, Valérie; Villa, Chiara; Auguste, Aurélie; Lamothe, Sophie; Guillou, Anne; Martin, Agnès; Caburet, Sandrine; Young, Jacques; Veitia, Reiner A; Binart, Nadine

2018-01-19

Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development. Prlr -/- females develop large secreting prolactinomas from 12 months of age, with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, which is a highly secreting subtype. Mean blood PRL measurements reach 14 902 ng/mL at 24 months in Prlr -/- females while PRL levels were below 15 ng/mL in control mice ( p < 0.01). By comparing pituitary microarray data of Prlr -/- mice and an estrogen-induced prolactinoma model in ACI rats, we pinpointed 218 concordantly differentially expressed (DE) genes involved in cell cycle, mitosis, cell adhesion molecules, dopaminergic synapse and estrogen signaling. Pathway/gene-set enrichment analyses suggest that the transcriptomic dysregulation in both models of prolactinoma might be mediated by a limited set of transcription factors (i.e., STAT5, STAT3, AhR, ESR1, BRD4, CEBPD, YAP, FOXO1) and kinases (i.e., JAK2, AKT1, BRAF, BMPR1A, CDK8, HUNK, ALK, FGFR1, ILK). Our experimental results and their bioinformatic analysis provide insights into early genomic changes in murine models of the most frequent human pituitary tumor.

Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications

PubMed Central

Yildirimer, Lara; Buanz, Asma; Gaisford, Simon; Malins, Edward L.; Remzi Becer, C.; Moiemen, Naiem; Reynolds, Gary M.; Seifalian, Alexander M.

2015-01-01

Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials’ viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications. PMID:26463421

Ameliorative effects of gallic acid, quercetin and limonene on urethane-induced genotoxicity and oxidative stress in Drosophila melanogaster.

PubMed

Nagpal, Isha; Abraham, Suresh K

2017-05-01

The main objective of our present work was to ascertain the efficacy of Drosophila melanogaster model for assessing antigenotoxic and antioxidant effects of dietary phytochemicals gallic acid (GA), quercetin (QC) and limonene (Lim) against urethane (URE), a genotoxic environmental carcinogen. Oregon-K (ORK) adult male flies were fed GA, QC and Lim in combination with URE (20 mM) in 10% sucrose for 72 h. Third instar larvae were fed instant medium containing the above phytochemicals and URE for 24 h. Sex-linked recessive lethal (SLRL) test and assays for estimating glutathione content (GSH), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content) were performed. Adult feeding experiments demonstrated that co-treatment of flies with URE and the test phytochemicals has significantly decreased the frequencies of SLRL mutations in all the germ cell stages when compared to that with URE alone. Larval feeding experiments also showed a similar pattern. The above results correlate well with antioxidative potentials of the test agents where we observed the elevated enzymatic levels with a significant reduction in MDA level in Drosophila larvae. The results further suggest that the dietary phytochemicals have an antioxidant and antimutagenic property which can be assessed using D. melanogaster.

Genotoxicity studies of organically grown broccoli (Brassica oleracea var. italica) and its interactions with urethane, methyl methanesulfonate and 4-nitroquinoline-1-oxide genotoxicity in the wing spot test of Drosophila melanogaster.

PubMed

Heres-Pulido, María Eugenia; Dueñas-García, Irma; Castañeda-Partida, Laura; Santos-Cruz, Luis Felipe; Vega-Contreras, Viridiana; Rebollar-Vega, Rosa; Gómez-Luna, Juan Carlos; Durán-Díaz, Angel

2010-01-01

Broccoli (Brassica oleracea var. italica) has been defined as a cancer preventive food. Nevertheless, broccoli contains potentially genotoxic compounds as well. We performed the wing spot test of Drosophila melanogaster in treatments with organically grown broccoli (OGB) and co-treatments with the promutagen urethane (URE), the direct alkylating agent methyl methanesulfonate (MMS) and the carcinogen 4-nitroquinoline-1-oxide (4-NQO) in the standard (ST) and high bioactivation (HB) crosses with inducible and high levels of cytochrome P450s (CYPs), respectively. Larvae of both crosses were chronically fed with OGB or fresh market broccoli (FMB) as a non-organically grown control, added with solvents or mutagens solutions. In both crosses, the OGB added with Tween-ethanol yielded the expected reduction in the genotoxicity spontaneous rate. OGB co-treatments did not affect the URE effect, MMS showed synergy and 4-NQO damage was modulated in both crosses. In contrast, FMB controls produced damage increase; co-treatments modulated URE genotoxicity, diminished MMS damage, and did not change the 4-NQO damage. The high dietary consumption of both types of broccoli and its protective effects in D. melanogaster are discussed. Copyright 2009 Elsevier Ltd. All rights reserved.

Storage, Preservation, and Recovery of Magnetic Recording Tape

NASA Technical Reports Server (NTRS)

Cuddihy, Edward F.

1994-01-01

During the 1970's, a commercial magnetic recording tape fabricated with magnetic oxide particles, and with oxide and backcoat binders made from polyester urethane was being used for spacecraft tape recorders, and which would periodically manifest operational problems such as layer-to-layer adhesion, stick-slip, and shedding of sticky organic materials. These problems were generally associated with periods of high humidity. An experimental study identified that these problems resulted from hydrolysis of the polyester urethane binders.

An Acoustic-Instrumented Mine for Studying Subsequent Burial

DTIC Science & Technology

2007-01-01

seawater . A strong reflection from the transducer face therefore indicates sediment flush with the mine surface (i.e., the mine surface is buried...variations in seawater sound speed and urethane sound speed that create a slight acoustic impedance mismatch at the water-urethane in- terface. The water...following was used: w. = \\//,„/2f/« TTH, U, T;Sinh( kh ) /„• = 0.237 0.52 /„, is the wave friction factor, Uw is the wave orbital velocity

Isolation and characterization of an ether-type polyurethane-degrading micro-organism and analysis of degradation mechanism by Alternaria sp.

PubMed

Matsumiya, Y; Murata, N; Tanabe, E; Kubota, K; Kubo, M

2010-06-01

To degrade ether-type polyurethane (ether-PUR), ether-PUR-degrading micro-organism was isolated. Moreover, ether-PUR-degrading mechanisms were analysed using model compounds of ether-PUR. A fungus designated as strain PURDK2, capable of changing the configuration of ether-PUR, has been isolated. This isolated fungus was identified as Alternaria sp. Using a scanning electron microscope, the grid structure of ether-PUR was shown to be melted and disrupted by the fungus. The degradation of ether-PUR by the fungus was analysed, and the ether-PUR was degraded by the fungus by about 27.5%. To analyse the urethane-bond degradation by the fungus, a degraded product of ethylphenylcarbamate was analysed using GC/MS. Aniline and ethanol were detected by degradation with the supernatant, indicating that the fungus secreted urethane-bond-degrading enzyme(s). PURDK2 also degraded urea bonds when diphenylmethane-4,4'-dibutylurea was used as a substrate. The enzyme(s) from PURDK2 degraded urethane and urea bonds to convert the high molecular weight structure of ether-PUR to small molecules; and then the fungus seems to use the small molecules as an energy source. Ether-PUR-degrading fungus, strain PURDK2, was isolated, and the urethane- and urea-bonds-degrading enzymes from strain PURDK2 could contribute to the material recycling of ether-PUR.

Clinical evaluation of endoscopic trimodal imaging for the detection and differentiation of colonic polyps.

PubMed

van den Broek, Frank J C; Fockens, Paul; Van Eeden, Susanne; Kara, Mohammed A; Hardwick, James C H; Reitsma, Johannes B; Dekker, Evelien

2009-03-01

Endoscopic trimodal imaging (ETMI) incorporates high-resolution endoscopy (HRE) and autofluorescence imaging (AFI) for adenoma detection, and narrow-band imaging (NBI) for differentiation of adenomas from nonneoplastic polyps. The aim of this study was to compare AFI with HRE for adenoma detection and to assess the diagnostic accuracy of NBI for differentiation of polyps. This was a randomized trial of tandem colonoscopies. The study was performed at the Academic Medical Center in Amsterdam. One hundred patients underwent colonoscopy with ETMI. Each colonic segment was examined twice for polyps, once with HRE and once with AFI, in random order per patient. All detected polyps were assessed with NBI for pit pattern and with AFI for color, and subsequently removed. Histopathology served as the gold standard for diagnosis. The main outcome measures of this study were adenoma miss-rates of AFI and HRE, and diagnostic accuracy of NBI and AFI for differentiating adenomas from nonneoplastic polyps. Among 50 patients examined with AFI first, 32 adenomas were detected initially. Subsequent inspection with HRE identified 8 additional adenomas. Among 50 patients examined with HRE first, 35 adenomas were detected initially. Successive AFI yielded 14 additional adenomas. The adenoma miss-rates of AFI and HRE therefore were 20% and 29%, respectively (P = .351). The sensitivity, specificity, and overall accuracy of NBI for differentiation were 90%, 70%, and 79%, respectively; corresponding figures for AFI were 99%, 35%, and 63%, respectively. The overall adenoma miss-rate was 25%; AFI did not significantly reduce the adenoma miss-rate compared with HRE. Both NBI and AFI had a disappointing diagnostic accuracy for polyp differentiation, although AFI had a high sensitivity.

Prevalence of any size adenomas and advanced adenomas in 40- to 49-year-old individuals undergoing screening colonoscopy because of a family history of colorectal carcinoma in a first-degree relative.

PubMed

Gupta, Akshay K; Samadder, Jewel; Elliott, Eric; Sethi, Saurabh; Schoenfeld, Philip

2011-07-01

Per current guidelines, patients with a first-degree relative (FDR) with colorectal cancer (CRC) should get screened at least at age 40. Data about the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking. To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy for family history of CRC. Retrospective chart review. Asymptomatic patients 40 to 49 years of age undergoing their first screening colonoscopy at the University of Michigan during the period 1999 to 2009 because of an FDR with CRC. Prevalence of adenomas (any size), AAs, and risk factors associated with adenomas. Among 640 study patients, the prevalence of adenomas (any size) was 15.4% and 3.3% for AAs. Adenoma prevalence was lower if the FDR with CRC was younger than 60 years of age versus an FDR with CRC older than 60 years of age (12.4% vs 19%, P = .034). Male sex (odds ratio 2.6; 95% CI, 1.06-4.4) and advancing age (odds ratio 1.16; 95% CI, 1.03-1.31) were associated with adenomas. Limited data on risk factor exposure and insufficient sample size to assess risk factors for AAs. Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with CRC, the prevalence of adenomas and AAs is low. Further research should determine whether these individuals have a higher prevalence of adenomas compared with average-risk individuals. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention.

PubMed

Lance, Peter; Alberts, David S; Thompson, Patricia A; Fales, Liane; Wang, Fang; San Jose, Jerilyn; Jacobs, Elizabeth T; Goodman, Phyllis J; Darke, Amy K; Yee, Monica; Minasian, Lori; Thompson, Ian M; Roe, Denise J

2017-01-01

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR. ©2016 American Association for Cancer Research.

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

PubMed

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-04-25

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

PubMed Central

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-01-01

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor

PubMed Central

Paradis, Valerie; Pote, Nicolas; Jakate, Shriram; Ferrell, Linda D

2016-01-01

Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33–75 years) and four women (29–65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma portion represents a relatively higher grade component of the tumor. PMID:24743216

Depletion of serotonin synthesis with p-CPA pretreatment alters EEG in urethane anesthetized rats under whole body hyperthermia.

PubMed

Sinha, Rakesh Kumar; Aggarwal, Yogender

2007-01-01

Serotonin is believed as an important factor in brain function. The role of serotonin in cerebral psycho-patho-physiology has already been well established. However, the function of serotonin antagonist in anesthetized subjects under hyperthermia has not been studied properly. Experiments were performed in three groups of urethane-anesthetized rats, such as: (i) control group, (ii) whole body hyperthermia group and (iii) p-CPA (para-Chlorophenylalanine) pretreated hyperthermia group. Hyperthermia was produced by subjecting the rats to high ambient temperature of 38 +/- 1 degrees C (relative humidity 45-50%). Each group was divided for EEG (electroencephalogram) study and for determination of edematous swelling in the brain. Urethane anesthetized rats under hyperthermia show highly significant reduction in their survival time. The body temperature recorded during the hyperthermia was observed with significant and linear rise with marked increase in brain water content, which was analyzed just after the death of the subjects. The results of the electroencephalographic study in urethane-anesthetized rats recorded before death indicate that brain function varies in systematic manner during hyperthermia as sequential changes in EEG patterns were observed. However, a serotonin antagonist, p-CPA pretreatment increases the survival time with significant reduction in edematous swelling in brain but it does not affect the relationship between the core body temperature and the brain cortical potentials as observed in urethane anesthetized subjects exposed to whole body hyperthermia. The core body temperature in p-CPA pretreated rats show non-linear relationship with respect to the exposure time as it was observed in drug untreated subjects. The findings of the present study indicate that although pretreatment of p-CPA in rats has a marked correlation between the extravasations of the blood-brain barrier under hyperthermia but shows minimum effect on the EEG in a model of hyperthermia under irreversible anesthesia.

Role of supplemental calcium in the recurrence of colorectal adenomas: a metaanalysis of randomized controlled trials.

PubMed

Shaukat, Aasma; Scouras, Nicole; Schünemann, Holger J

2005-02-01

Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue.

PubMed

Salman, Rida; Sebaaly, Mikhael G; Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad; Al-Kutoubi, Aghiad

2017-06-01

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salman, Rida; Sebaaly, Mikhael G.; Wehbe, Mohammad Rachad

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma.

PubMed

Glebauskiene, Brigita; Liutkeviciene, Rasa; Vilkeviciute, Alvita; Gudinaviciene, Inga; Rocyte, Aurelija; Simonaviciute, Dovile; Mazetyte, Ruta; Kriauciuniene, Loresa; Zaliuniene, Dalia

2018-01-01

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL-17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion . IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas.

PubMed

Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

2014-05-01

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance.

CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas

PubMed Central

Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

2014-01-01

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance. PMID:24518818

SEPT9 and SHOX2 DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas.

PubMed

Semaan, Alexander; van Ellen, Anne; Meller, Sebastian; Bergheim, Dominik; Branchi, Vittorio; Lingohr, Philipp; Goltz, Diane; Kalff, Jörg C; Kristiansen, Glen; Matthaei, Hanno; Pantelis, Dimitrios; Dietrich, Dimo

2016-01-01

Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of SEPT9 and SHOX2 has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions. Assessment of promoter methylation of SEPT9 distinguished adenomas and CRC from controls as well as advanced from non-advanced adenomas (all p  < 0.001). Correspondingly, SHOX2 methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues ( p  < 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of the SEPT9 gene locus. SEPT9 / SHOX2 methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine.

Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials.

PubMed

Veettil, Sajesh K; Lim, Kean Ghee; Ching, Siew Mooi; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-11-14

Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established. Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA). In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal. Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

Effects of hyperthyroidism and hypothyroidism on rat growth hormone release induced by thyrotropin-releasing hormone.

PubMed

Chihara, K; Kato, Y; Ohgo, S; Iwasaki, Y; Maeda, K

1976-06-01

The effect of synthetic thyrotropin-releasing hormone (TRH) on the release of growth hormone (GH) and thyroid-stimulating hormone (TSH) was investigated in euthyroid, hypothyroid, and hyperthyroid rats under urethane anesthesia. In euthyroid control rats, intravenous injection of TRH (200 ng/100 g BW) resulted in a significant increase in both plasma GH and TSH. In rats made hypothyroid by treatment with propylthiouracil or by thyroidectomy, basal GH and TSH levels were significantly elevated with exaggerated responses to TRH. In contrast, plasma GH and TSH responses to TRH were both significantly inhibited in rats made hyperthyroid by L-thyroxine (T4) treatment. These results suggest that altered thyroid status influences GH release as well as TSH secretion induced by TRH in rats.

Flexible, Water-Resistant Urethane Coatings for Ferrous Surfaces on U.S. Army Corps of Engineers’ Dams.

DTIC Science & Technology

1982-07-01

of Opaque Specimens by, Broad-Band Filter Reflectometry , ASTM E 97 (1977). could be produced on a specialty basis by interested 3 TEST SPECIMEN...Aeronautics and Space Adminis- tration ( NASA ) study deals with the long-term hy- drolytic stability of urethane elastomers used with CONCLUSIONS AND...necessary for high hydrolytic stability-are not better than the polyether- solids coatings. The NASA study may be correct in based X series. The highest

Research of low cost wind generator rotors

NASA Technical Reports Server (NTRS)

Fertis, D. G.; Ross, R. S.

1978-01-01

A feasibility program determined that it would be possible to significantly reduce the cost of manufacturing wind generator rotors by making them of cast urethane. Several high modulus urethanes which were structurally tested were developed. A section of rotor was also cast and tested showing the excellent aerodynamic surface which results. A design analysis indicated that a cost reduction of almost ten to one can be achieved with a small weight increase to achieve the same structural integrity as expected of current rotor systems.

NAVFAC Ocean Thermal Energy Conversion (OTEC) Project; OTEC Technology Development Report

DTIC Science & Technology

2010-11-01

platform and CWP. It was a goal of this program to find a material that is high in abrasion resistance and low in friction for the guide layers. Figure...preferred material was a high density urethane. Urethane has very high abrasion resistance – it is often used for marine buoys, fenders, and coatings...design thread in the document. The following is a list of the top level sections in the report. EXECUTIVE SUMMARY  1  1.  INTRODUCTION  2  2

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

PubMed

Yuan, Hai-Xia; Cao, Jia-Ying; Kong, Wen-Tao; Xia, Han-Sheng; Wang, Xi; Wang, Wen-Ping

2015-04-01

Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

TRANSCRIPTIONAL RESPONSES IN THYROID TISSUES FROM RATS TREATED WITH A TUMORIGENIC AND A NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDE

EPA Science Inventory

What is the study?
Conazoles are triazole- or imidazole-containing fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay. The goal of this study was to identify pathways and network...

TRANSCRIPTIONAL RESPONSES IN THYROID TISSUES FROM RATS TREATED WITH A TUMORIGENIC AND A NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDE

EPA Science Inventory

Conazoles are fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay and are considered to pose a hazard to humans. Pathways and networks of genes that were associated with thyroid cancer w...

TRANSCRIPTIONAL PROFILES IN LIVER FROM RATS TREATED WITH TUMORIGENIC AND NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

EPA Science Inventory

Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on t...

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells

PubMed Central

Jian, Fang-Fang; Li, Yun-Feng; Chen, Yu-Fan; Jiang, Hong; Chen, Xiao; Zheng, Li-Li; Zhao, Yao; Wang, Wei-Qing; Ning, Guang; Bian, Liu-Guan; Sun, Qing-Fang

2016-01-01

Background: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD). Methods: The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. Results: Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. Conclusions: Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD. PMID:27569239

Succinate Dehydrogenase (SDH) D Subunit (SDHD) Inactivation in a Growth-Hormone-Producing Pituitary Tumor: A New Association for SDH?

PubMed Central

Xekouki, Paraskevi; Pacak, Karel; Almeida, Madson; Wassif, Christopher A.; Rustin, Pierre; Nesterova, Maria; de la Luz Sierra, Maria; Matro, Joey; Ball, Evan; Azevedo, Monalisa; Horvath, Anelia; Lyssikatos, Charalampos; Quezado, Martha; Patronas, Nicholas; Ferrando, Barbara; Pasini, Barbara; Lytras, Aristides; Tolis, George

2012-01-01

Background: Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD). Aim: Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma. Patients and Methods: A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors. Conclusion: We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis. PMID:22170724

Somatic GNAS Mutation Causes Widespread and Diffuse Pituitary Disease in Acromegalic Patients with McCune-Albright Syndrome

PubMed Central

Vortmeyer, Alexander O.; Gläsker, Sven; Mehta, Gautam U.; Abu-Asab, Mones S.; Smith, Jonathan H.; Zhuang, Zhengping; Collins, Michael T.

2012-01-01

Context: McCune-Albright syndrome (MAS) is caused by sporadic mutations of the GNAS. Patients exhibit features of acromegaly. In most patients, GH-secreting pituitary adenomas have been held responsible for this presentation. However, surgical adenomectomy rarely eliminates excess GH production. Objective: The aim of this study was to elucidate pituitary pathology in patients with MAS and to explain the basis of failure of adenomectomy to eliminate GH hypersecretion. Design and Setting: We conducted a case series at the National Institutes of Health. Intervention(s): Interventions included medical therapy and transsphenoidal surgery. Patients and Main Outcome Measures: We studied clinical and imaging features and the histology and molecular features of the pituitary of four acromegalic MAS patients. Results: We identified widespread and diffuse pituitary gland disease. The primary pathological changes were characterized by hyperplastic and neoplastic change, associated with overrepresentation of somatotroph cells in structurally intact tissue areas. Genetic analysis of multiple microdissected samples of any type of histological area consistently revealed identical GNAS mutations in individual patients. The only patient with remission after surgery received complete hypophysectomy in addition to removal of multiple GH-secreting tumors. Conclusions: These findings indicate developmental effects of GNAS mutation on the entire anterior pituitary gland. The pituitary of individual cases contains a spectrum of changes with regions of normal appearing gland, hyperplasia, and areas of fully developed adenoma formation, as well as transitional stages between these entities. The primary change underlying acromegaly in MAS patients is somatotroph hyperplasia involving the entire pituitary gland, with or without development of somatotroph adenoma. Thus, successful clinical management, whether it is medical, surgical, or via irradiation, must target the entire pituitary, not just the adenomas evident on imaging. PMID:22564667

Ovarian hyperstimulation, hyperprolactinaemia and LH gonadotroph adenoma.

PubMed

Castelo-Branco, Camil; del Pino, Marta; Valladares, Esther

2009-08-01

This report considers a highly exceptional case of ovarian hyperstimulation syndrome due to a gonadotroph adenoma secreting LH in a 31-year-old patient who presented with amenorrhoea and galactorrhoea syndrome and a complex bilateral ovarian mass. Magnetic resonance imaging revealed a pituitary adenoma, and laboratory tests corroborated the hyperprolactinaemia without other hormonal pituitary abnormalities. Ovarian hyperstimulation syndrome due to a gonadotroph adenoma with normal gonadotrophins is extremely rare. Most of the described cases are caused by FSH adenomas. Due to the originality of the case, it was considered useful for understanding the management of this entity, and it is proposed that LH adenomas should also be considered in the differential diagnosis of patients with spontaneous ovarian hyperstimulation syndrome.

Simultaneous Improvement of Oxidative and Hydrolytic Resistance of Polycarbonate Urethanes Based on Polydimethylsiloxane/Poly(hexamethylene carbonate) Mixed Macrodiols.

PubMed

Li, Zhen; Yang, Jian; Ye, Heng; Ding, Mingming; Luo, Feng; Li, Jianshu; Li, Jiehua; Tan, Hong; Fu, Qiang

2018-06-11

The degradation behaviors including oxidation and hydrolysis of silicone modified polycarbonate urethanes were thoroughly investigated. These polyurethanes were based on polyhexamethylene carbonate (PHMC)/polydimethylsiloxane (PDMS) mixed macrodiols with molar ratio of PDMS ranging from 5% to 30%. It was proved that PDMS tended to migrate toward surface and even a small amount of PDMS could form a silicone-like surface. Macrophages-mediated oxidation process indicated that the PDMS surface layer was desirable to protect the fragile soft PHMC from the attack of degradative species. Hydrolysis process was probed in detail after immersing in boiling buffered water using combined analytical tools. Hydrolytically stable PDMS could act as protective shields for the bulk to hinder the chain scission of polycarbonate carbonyls whereas the hydrolysis of urethane linkages was less affected. Although the promoted phase separation at higher PDMS fractions lead to possible physical defects and mechanical compromise after degradation, simultaneously enhanced oxidation and hydrolysis resistance could be achieved for the polyurethanes with proper PDMS incorporation.

A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications.

PubMed

Luque, R M; Ibáñez-Costa, A; López-Sánchez, L M; Jiménez-Reina, L; Venegas-Moreno, E; Gálvez, M A; Villa-Osaba, A; Madrazo-Atutxa, A M; Japón, M A; de la Riva, A; Cano, D A; Benito-López, P; Soto-Moreno, A; Gahete, M D; Leal-Cerro, A; Castaño, J P

2013-10-01

Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Tubular Adenoma of the Breast: A Rare Presentation and Review of the Literature

PubMed Central

Salemis, Nikolaos S.; Gemenetzis, Georgios; Karagkiouzis, Gregorios; Seretis, Charalambos; Sapounas, Konstantinos; Tsantilas, Vlasios; Sambaziotis, Dimitrios; Lagoudianakis, Emmanuel

2012-01-01

Tubular adenomas, also known as pure adenomas, are rare epithelial tumors of the breast. Only a few cases have been reported in the literature, especially in young women of reproductive age. Postmenopausal women are very rarely affected. We describe here a very rare case of tubular breast adenoma in a postmenopausal woman who presented with a gradually enlarging breast lump. Clinical examination and imaging studies revealed a non-tender well circumscribed left breast tumor suggestive of a fibroadenoma. Due to the history of progressive enlargement of the breast lump, a surgical excision was performed. Histological findings were suggestive of a tubular breast adenoma. We conclude that although tubular breast adenoma is rare, it should always be considered in the differential diagnosis in postmenopausal patients presenting with a gradually enlarging breast mass. Preoperative diagnosis is difficult because tubular adenoma is indistinguishable from a fibroadenoma on physical examination and breast imaging. Surgical excision is necessary to establish a definitive diagnosis. Clinical presentation and management of our patient are discussed along with a review of the literature. Keywords Tubular adenoma; Breast; Breast mass. PMID:22383931

Tubular adenoma of the breast: a rare presentation and review of the literature.

PubMed

Salemis, Nikolaos S; Gemenetzis, Georgios; Karagkiouzis, Gregorios; Seretis, Charalambos; Sapounas, Konstantinos; Tsantilas, Vlasios; Sambaziotis, Dimitrios; Lagoudianakis, Emmanuel

2012-02-01

Tubular adenomas, also known as pure adenomas, are rare epithelial tumors of the breast. Only a few cases have been reported in the literature, especially in young women of reproductive age. Postmenopausal women are very rarely affected. We describe here a very rare case of tubular breast adenoma in a postmenopausal woman who presented with a gradually enlarging breast lump. Clinical examination and imaging studies revealed a non-tender well circumscribed left breast tumor suggestive of a fibroadenoma. Due to the history of progressive enlargement of the breast lump, a surgical excision was performed. Histological findings were suggestive of a tubular breast adenoma. We conclude that although tubular breast adenoma is rare, it should always be considered in the differential diagnosis in postmenopausal patients presenting with a gradually enlarging breast mass. Preoperative diagnosis is difficult because tubular adenoma is indistinguishable from a fibroadenoma on physical examination and breast imaging. Surgical excision is necessary to establish a definitive diagnosis. Clinical presentation and management of our patient are discussed along with a review of the literature. Tubular adenoma; Breast; Breast mass.

Synthesis of 19-nor-aldosterone, 18-hydroxy-19-nor-corticosterone and 18,19-dihydroxycorticosterone in the human aldosterone-producing adenoma.

PubMed

Takeda, Y; Lewicka, S; Koch, S; Bige, K; Vecsei, P; Abdelhamid, S; Cojocaru, M; Harnik, M

1990-11-30

The recently synthesized 18-C-steroid derivative, 19-nor-aldosterone(19-nor- aldo) and 18-hydroxy-19-nor-corticosterone(18-OH-19-nor-corticosterone) possess mineralocoroticoid and hypertensinogenic activity. They and an additional newly synthesized steriod, 18,19-dihydroxycorticosterone[18,19(OH)2-corticosterone], may play a role in the etiology and pathogenesis of disorders thought to be caused by steroids with mineralocorticoid and hypertensionogenic properties. In this study we provide evidence that 19-nor-aldo, 18-OH-19-nor-corticosterone and 18,19(OH)2-corticosterone are produced in vitro by aldosterone-producing adrenal adenomas and adenomas and adenoma of Cushing's syndrome. "silent" adrenal adenomas and the adjacent adrenal tissue. Measurable amounts of these steroids were found in the incubation fluids of adrenal tissues using specific RIAs performed after a sequence of HPLC systems. The rates of production of the three steroids were high in the aldosterone-producing adrenal adenomas and in adrenal hyperplasia compared with in either Cushing's adenoma or "silent" adenoma.

Identification of Kininogen 1 as a Serum Protein Marker of Colorectal Adenoma in Patients with a Family History of Colorectal Cancer.

PubMed

Yu, Jiekai; Huang, Yanqin; Lin, Chen; Li, Xiaofen; Fang, Xuefeng; Zhong, Chenhan; Yuan, Ying; Zheng, Shu

2018-01-01

The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85.0% accuracy. The model distinguishing CRA-H from healthy individuals was established with 90.0% specificity and 86.7% sensitivity. Additionally, five peaks (2202, 5821, 3260, 2480, and 2218) showing differential expression in advanced colorectal adenoma patients with a family history of colorectal cancer were selected. The protein Kininogen 1 (KNG1) was identified in colorectal adenoma patients and validated using Western Blotting. KNG1 may be a biomarker for colorectal adenoma patients with a family history of colorectal cancer.

Evaluation of Cancer and Non-cancer Effects of Cumene ...

EPA Pesticide Factsheets

Cumene, also known as isopropyl benzene, is a volatile liquid. Cumene, readily absorbed via inhalation is distributed in several tissues, metabolized extensively by cytochrome P-450 isozymes within hepatic and extra-hepatic tissues and excreted through urine. No epidemiological cancer studies for humans are available, however, chronic inhalation exposure studies in rat and mouse have shown increased nasal lesions including atrophy, basal cell hyperplasia, atypical hyperplasia and hyperplasia of the olfactory epithelium glands. In addition, increased incidences of renal tubular adenoma or carcinoma that are related to a2u-globin-induced nephropathy were observed in male rats. Alveolar/bronchiolar adenomas and carcinomas of the lung are observed in male and female mice exposed to cumene. Although no multi-generational reproductive toxicity is available for cumene, cumene-exposed rats appeared to stay in estrus cycle longer than the controls. Short-term acute exposures of animals at high concentrations seem to induce transient reversible neurotoxic effects. Overall, inhalation exposure to cumene induced dose-related increased in the occurances of tumors at various sites. These cancer and non-cancer data in rats and mice as well as genotoxicity data provides consistence evidence for carcinogenic effects of cumene. This poster will be presented at the Society of Toxicology Meeting in San Diego California. The goal of this presentation is systematic evaluation of bot

Relationship of Diet to Small and Large Adenomas of the Sigmoid Colon

PubMed Central

Imanishi, Koji; Shinchi, Koichi; Yanai, Fumio

1993-01-01

The relation of dietary factors to the risk of adenomas of the sigmoid colon was examined in men receiving a retirement health examination at the Self‐Defense Forces Fukuoka Hospital between October 1986 and 1990. A total of 187 adenoma cases and 1557 controls with normal colonoscopy were identified in the series. Cases were further classified into small‐adenoma (<5 mm, n=78) and large‐adenoma (≥5 mm, n=67) groups. The consumptions of selected foods and beverages were ascertained before colonoscopy by means of a self‐administered questionnaire. After adjustment for smoking, alcohol use, rank and body mass index, low rice consumption and high meat intake were independently associated with an increased risk of large adenomas. The risk of small adenomas was not related to either rice consumption or meat intake. Adjusted odds ratios of large adenomas for the low, intermediate and high consumption levels of rice were estimated to be 1.0 (referent), 0.83 and 0.43, respectively (trend P= 0.08), and the corresponding figures for meat consumption were 1.0 (referent), 1.58 and 2.38, respectively (trend P=0.02). The findings suggest that low rice consumption and high meat intake may promote the growth of colon adenomas, thereby increasing the risk of colon cancer. PMID:8449821

Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

PubMed Central

PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

2016-01-01

Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study.

PubMed

Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

2015-12-14

To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ(2) statistics and t-test. The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies.

A challenging case of an ectopic parathyroid adenoma.

PubMed

Panchani, Roopal; Varma, Tarun; Goyal, Ashutosh; Gupta, Nitinranjan; Saini, Ashish; Tripathi, Sudhir

2012-12-01

The occurrence of ectopic parathyroid adenomas is not uncommon (3-4% of all parathyroid adenomas). A 42-year-old female diagnosed as having GH secreting pituitary adenoma presented with an ectopic mediastinal parathyroid adenoma located between left (Lt) pulmonary artery and Lt main bronchus. The aim of presenting this case is not to appreciate the rarity of the condition but to rather discuss some of the vital practical problems faced during its management. Patient presenting in endocrine OPD with nausea, vomiting, drowsiness and chronic constipation was investigated biochemically and with various imaging modalities and accordingly managed. Patient was also investigated from the perspective of MEN 1 syndrome. Baseline routine investigations revealed hypercalcemia (corrected S. Ca- 16.9 mg/dl) due to primary hyperparathyroidism (PHP, PTH-1190 ng/L) with adenoma located between Lt main bronchus and Lt pulmonary artery. Patient was medically managed and after proper preoperative preparation, surgical excision by open thoracotomy was planned but two days before surgery she developed pulmonary embolism and was shifted to ICU where she died after 20 days. An accurate preoperative localization by various imaging procedures plays a decisive role in case of ectopic adenomas in the chest. Ectopic parathyroid adenomas are frequent cause of failed initial surgery. The best surgical approach to these ectopic adenomas is still controversial. Equally effective newer medical treatment modalities are also required in patients who are awaiting or are unfit for surgery. Lastly combination of MEN 1 with ectopic parathyroid adenoma is rare.

Obesity and Adenomatous Polyps of the Sigmoid Colon

PubMed Central

Kono, Suminori; Honjo, Satoshi; Todoroki, Isao; Sakurai, Yutaka; Imanishi, Koji; Nishikawa, Hiroshi; Ogawa, Shinsaku; Katsurada, Mitsuhiko; Hirohata, Tomio

1994-01-01

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self‐defense officials who received a retirement health examination at three hospitals of the Self‐Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist‐hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (<5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut‐off points. There was a significant two‐fold elevation in the overall adenoma risk among men at the highest BMI level (≥26.95) compared with those at the lowest level (<22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR: odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4–5.9) for the highest (≥0.958) versus lowest (<0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95%CI 1.5–7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth. PMID:8014105

Obesity-related parameters and colorectal adenoma development.

PubMed

Kim, Tae Jun; Kim, Jee Eun; Choi, Yoon-Ho; Hong, Sung Noh; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Kim, Min-Ji; Jung, Sin-Ho; Son, Hee Jung

2017-12-01

Obesity increases the risk of colorectal adenoma and colorectal cancer. However, the obesity-related parameters that are best for assessing the risk of colorectal adenoma development remain unclear. We analyzed the parameters that may best describe the association between obesity and colorectal adenoma development. In this retrospective cohort study, 3405 individuals underwent screening colonoscopy during routine health examinations. We measured body mass index; waist circumference; and metabolic parameters such as high-density lipoprotein-cholesterol, glucose, triglyceride, and systolic blood pressure. We analyzed the risk of developing colorectal adenoma, relative to obesity-related parameters, over a mean interval of 5.8 years from baseline colonoscopy. In a multivariate analysis, waist circumference was the only obesity-related marker associated with an increased risk of metachronous colorectal adenoma. Men with waist circumferences ≥85 cm and women with waist circumference ≥82 cm had a 31% increased risk of metachronous colorectal adenoma compared to those with smaller waist circumferences [odds ratio (OR) 1.31; 95% confidence interval (CI, 1.09-1.57)]. Other factors associated with metachronous colorectal adenoma were age (OR, 1.03; 95% CI 1.02-1.04), male sex (OR 1.49; 95% CI 1.17-1.88), alcohol consumption ≥3/week (OR 1.33; 95% CI 1.10-1.62), the number of adenoma at baseline (OR 1.21; 95% CI 1.10-1.33), and the presence of advanced adenoma at baseline (OR 1.60; 95% CI 1.24-2.06). Our findings suggest that central obesity, represented by waist circumference, is a significant predictor of metachronous colorectal adenoma, independent of body mass index and other metabolic variables.

Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver.

PubMed

Rusyn, Ivan; Peters, Jeffrey M; Cunningham, Michael L

2006-05-01

The industrial plasticizer di-(2-ethylhexyl)phthalate (DEHP) is used in manufacturing of a wide variety of polyvinyl chloride (PVC)-containing medical and consumer products. DEHP belongs to a class of chemicals known as peroxisome proliferators (PPs). PPs are a structurally diverse group of compounds that share many (but perhaps not all) biological effects and are characterized as non-genotoxic rodent carcinogens. This review focuses on the effect of DEHP in liver, a primary target organ for the pleiotropic effects of DEHP and other PPs. Specifically, liver parenchymal cells, identified herein as hepatocytes, are a major cell type that are responsive to exposure to PPs, including DEHP; however, other cell types in the liver may also play a role. The PP-induced increase in the number and size of peroxisomes in hepatocytes, so called 'peroxisome proliferation' that results in elevation of fatty acid metabolism, is a hallmark response to these compounds in the liver. A link between peroxisome proliferation and tumor formation has been a predominant, albeit questioned, theory to explain the cause of a hepatocarcinogenic effect of PPs. Other molecular events, such as induction of cell proliferation, decreased apoptosis, oxidative DNA damage, and selective clonal expansion of the initiated cells have been also been proposed to be critically involved in PP-induced carcinogenesis in liver. Considerable differences in the metabolism and molecular changes induced by DEHP in the liver, most predominantly the activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)alpha, have been identified between species. Both sexes of rats and mice develop adenomas and carcinomas after prolonged feeding with DEHP; however, limited DEHP-specific human data are available, even though exposure to DEHP and other phthalates is common in the general population. This likely constitutes the largest gap in our knowledge on the potential for DEHP to cause liver cancer in humans. Overall, it is believed that the sequence of key events that are relevant to DEHP-induced liver carcinogenesis in rodents involves the following events whereby the combination of the molecular signals and multiple pathways, rather than a single hallmark event (such as induction of PPARalpha and peroxisomal genes, or cell proliferation) contribute to the formation of tumors: (i) rapid metabolism of the parental compound to primary and secondary bioactive metabolites that are readily absorbed and distributed throughout the body; (ii) receptor-independent activation of hepatic macrophages and production of oxidants; (iii) activation of PPARalpha in hepatocytes and sustained increase in expression of peroxisomal and non-peroxisomal metabolism-related genes; (iv) enlargement of many hepatocellular organelles (peroxisomes, mitochondria, etc.); (v) rapid but transient increase in cell proliferation, and a decrease in apoptosis; (vi) sustained hepatomegaly; (vii) chronic low-level oxidative stress and accumulation of DNA damage; (viii) selective clonal expansion of the initiated cells; (ix) appearance of the pre-neoplastic nodules; (x) development of adenomas and carcinomas.

Multistimuli-Responsive Amphiphilic Poly(ester-urethane) Nanoassemblies Based on l-Tyrosine for Intracellular Drug Delivery to Cancer Cells.

PubMed

Aluri, Rajendra; Saxena, Sonashree; Joshi, Dheeraj Chandra; Jayakannan, Manickam

2018-06-11

Multistimuli-responsive l-tyrosine-based amphiphilic poly(ester-urethane) nanocarriers were designed and developed for the first time to administer anticancer drugs in cancer tissue environments via thermoresponsiveness and lysosomal enzymatic biodegradation from a single polymer platform. For this purpose, multifunctional l-tyrosine monomer was tailor-made with a PEGylated side chain at the phenolic position along with urethane and carboxylic ester functionalities. Under melt dual ester-urethane polycondensation, the tyrosine monomer reacted with diols to produce high molecular weight amphiphilic poly(ester-urethane)s. The polymers produced 100 ± 10 nm spherical nanoparticles in aqueous medium, and they exhibited thermoresponsiveness followed by phase transition from clear solution into a turbid solution in heating/cooling cycles. Variable temperature transmittance, dynamic light scattering, and 1 H NMR studies revealed that the polymer chains underwent reversible phase transition from coil-to-expanded chain conformation for exhibiting the thermoresponsive behavior. The lower critical solution temperature of the nanocarriers was found to correspond to cancer tissue temperature (at 42-44 °C), which was explored as an extracellular trigger (stimuli-1) for drug delivery through the disassembly process. The ester bond in the poly(ester-urethane) backbones readily underwent enzymatic biodegradation in the lysosomal compartments that served as intracellular stimuli (stimuli-2) to deliver drugs. Doxorubicin (DOX) and camptothecin (CPT) drug-loaded polymer nanocarriers were tested for cellular uptake and cytotoxicity studies in the normal WT-MEF cell line and cervical (HeLa) and breast (MCF7) cancer cell lines. In vitro drug release studies revealed that the polymer nanoparticles were stable under physiological conditions (37 °C, pH 7.4) and they exclusively underwent disassembly at cancer tissue temperature (at 42 °C) and biodegradation by lysosomal-esterase enzyme to deliver 90% of DOX and CPT. Drug-loaded polymer nanoparticles exhibited better cytotoxic effects than their corresponding free drugs. Live cell confocal microscopy imaging experiments with lysosomal tracker confirmed the endocytosis of the polymer nanoparticles and their biodegradation in the lysosomal compartments in cancer cells. The increment in the drug content in the cells incubated at 42 °C compared to 37 °C supported the enhanced drug uptake by the cancer cells under thermoresponsive stimuli. The present work creates a new platform for the l-amino acid multiple-responsive polymer nanocarrier platform for drug delivery, and the proof-of-concept was successfully demonstrated for l-tyrosine polymers in cervical and breast cancer cells.

Piecemeal Versus En Bloc Resection of Large Rectal Adenomas

ClinicalTrials.gov

2018-06-04

Colorectal Adenoma With Mild Dysplasia; Colorectal Adenoma With Severe Dysplasia; Colorectal Adenomatous Polyp; Colorectal Low Grade Intraepithelial Neoplasia; Colorectal High Grade Intraepithelial Neoplasia

Hepatocellular carcinoma arising in a telangiectatic hepatocellular adenoma.

PubMed

González-Lara, María Fernanda; Córdova-Ramón, Juan Carlos; Gamboa-Domínguez, Armando; Cosme-Labarthe, Juan; Carrillo-Pérez, Diego Luis

2013-01-01

Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of benign liver tumor that may very rarely undergo transformation into hepatocellular carcinoma. We report an unusual case of a 75-year-old woman with no history of oral contraceptive use that underwent malignant transformation of a telangiectactic hepatocellular adenoma. No risk factors for adenoma development were identified in this otherwise healthy woman. Radiological characteristics, gross features and histopathology are herein described. In conclusion, telangiectatic hepatocellular adenoma can undergo malignant transformation. Further studies are needed to better clarify the factors associated with malignant progression.

Telangiectatic adenoma - computed tomography and magnetic resonance findings: a case report and review of the literature.

PubMed

Takayassu, Tatiana Chinem; Marchiori, Edson; Eiras, Antonio; Cabral, Rafael Ferracini; Cabral, Fernanda Caseira; Batista, Raquel Ribeiro; Zanetti, Gláucia; Dias, Paula Cristina Pereira

2009-01-07

Telangiectatic adenoma is a new classification of a hepatic lesion. It was previously named telangiectatic focal nodular hyperplasia but it is in fact true adenoma with telangiectatic features. We report here a case of telangiectatic adenoma in a 72-year-old woman. The image features are lack of a central scar, a heterogeneous lesion, hyperintensity in T1-weighted MR images, strong hyperintensity in T2-weighted MR images, and persistent contrast enhancement in delayed-phase contrast-enhanced CT or T1-weighted MR images. It is a monoclonal lesion with potential of malignancy. The treatment of telangiectatic adenoma is surgery, the same way as hepatic adenoma. Focal nodular hyperplasia may be managed by clinical follow-up alone.

SOT 2008- TRANSCRIPTIONAL RESPONSES IN THYROID TISSUES FROM RATS TREATED WITH A TUMORIGENIC AND A NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDE

EPA Science Inventory

Conazoles are triazole- or imidazole-containing fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay. The goal of this study was to identify pathways and networks of genes that were assoc...

Back-to-back comparison of auto-fluorescence imaging (AFI) versus high resolution white light colonoscopy for adenoma detection.

PubMed

Moriichi, Kentaro; Fujiya, Mikihiro; Sato, Ryu; Watari, Jiro; Nomura, Yoshiki; Nata, Toshie; Ueno, Nobuhiro; Maeda, Shigeaki; Kashima, Shin; Itabashi, Kentaro; Ishikawa, Chisato; Inaba, Yuhei; Ito, Takahiro; Okamoto, Kotaro; Tanabe, Hiroki; Mizukami, Yusuke; Saitoh, Yusuke; Kohgo, Yutaka

2012-06-22

Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma. This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner. The detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI. AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.

Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection

PubMed Central

2012-01-01

Background Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma. Methods This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner. Results The detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI. Conclusions AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE. PMID:22726319

The prevalence of colorectal adenomas in asymptomatic Korean men and women.

PubMed

Yang, Moon Hee; Rampal, Sanjay; Sung, Jidong; Choi, Yoon-Ho; Son, Hee Jung; Lee, Jun Haeng; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Rhee, Jong Chul; Guallar, Eliseo; Cho, Juhee

2014-03-01

Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans. Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The prevalence of adenomas increased annually in both men and women. In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries. Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed. ©2014 AACR.

Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

PubMed

Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

1994-11-01

The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma Prevalence and Distribution Among US Latino Subgroups Undergoing Screening Colonoscopy.

PubMed

Chablani, Sumedha V; Jandorf, Lina; DuHamel, Katherine; Lee, Kristen K; Sriphanlop, Pathu; Villagra, Cristina; Itzkowitz, Steven H

2017-06-01

Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.

Comparison of the clinicopathological features of flat and polypoid colorectal adenomas that are smaller than or equal to five millimeters.

PubMed

Yener, Neşe Arzu; Midi, Ahmet; Ataizi Çelikel, Ciğdem

2014-02-01

Colorectal flat adenomas (FAs) may represent a different histogenesis, since their malignant potential is thought to be higher than polypoid adenomas of the same size. In this study, we classified FAs of ≤5 mm into three subgroups-superficially elevated adenomas (SEAs), completely flat adenomas (CFAs), and depressed adenomas (DAs)-based on their low microscopic shapes and compared their clinicopathological features with polypoid tubular adenomas (pTAs) with the same size. One hundred one pTAs and 46 FAs with tubular morphology with the same size (≤5 mm) were studied. The percentages of high-grade dysplasia in FAs and pTAs were 19.56% and 12.87%, respectively. The percentages of the high-grade dysplasia were 28.57%, 13.63%, and 20.00% in the DA, SEA, and CFA subgroups, respectively. FAs had a significantly higher number of normal epithelium at the basal crypts of the lesion than the pTAs (p=0.001). The presence of pericryptal mesenchymal cells was higher in pTAs than the FAs (78.21% vs 10.86%) (p<0.001). Flat adenoma represents a distinct type of colorectal adenoma with special histopathological properties-existence of a normal epithelium at the basal crypts, lack of pericryptal mesenchymal cells, and a high percentage of high-grade dysplasia-especially when it has a depressed shape at low magnification.

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study

PubMed Central

Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

2015-01-01

AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ2 statistics and t-test. RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies. PMID:26673447

Secondary hypertension due to concomitant aldosterone-producing adenoma and parathyroid adenoma.

PubMed

Chau, Katrina; Holmes, Daniel; Melck, Adrienne; Chan-Yan, Clifford

2015-02-01

There is a growing body of evidence supporting a bidirectional relationship between parathyroid hormone (PTH) and aldosterone (Aldo). We report a case of secondary hypertension due to concomitant Aldo-producing adenoma (APA) and parathyroid adenoma (PA) requiring both unilateral adrenalectomy and parathyroidectomy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Glucose Intolerance, Plasma Insulin Levels, and Colon Adenomas in Japanese Men

PubMed Central

Kono, Suminori; Abe, Hiroshi; Eguchi, Hiroyuki; Shimazaki, Kae; Hatano, Ben; Hamada, Hiroaki

2001-01-01

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross‐sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75‐g oral glucose tolerance test, and subjects were classified as normal, unpaired glucose tolerance (IGT) or non‐insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long‐term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer. PMID:11509114

A Novel Technology for Localization of Parathyroid Adenoma: Ultrasound-Guided Fine Needle Aspiration Combined With Rapid Parathyroid Hormone Detection and Nano-Carbon Technology.

PubMed

Yan, Shouyi; Zhao, Wenxin; Wang, Bo; Zhang, Liyong

2018-06-01

The study aims to evaluate the clinic feasibility of rapid parathyroid hormone (PTH) detection and nano-carbon technology in preoperative diagnosis and localization of parathyroid adenoma. With the guidance of ultrasound, the operator performed the parathyroid puncture and tested the PTH value by using a PTH test kit, and then injected nano-carbon into parathyroid adenoma as a marker to observe whether the parathyroid adenoma was stained black during the final operation. Meanwhile, a part of excised specimen was made into homogenate and detected rapidly again by using the PTH test kit. The remaining was confirmed by intraoperative frozen pathological examination. The sensitivity (12/12) of preoperative diagnosis was significantly higher than that of ultrasound (6/12), magnetic resonance imaging (7/12), and MIBI (9/12). During the operation, we found that the inner part of the parathyroid adenoma was stained black, and the PTH value of the specimen homogenate confirmed as parathyroid adenoma was more than 3000 pg/mL. This novel technology, as a very positive method for localization of parathyroid adenoma, plays an important role in guaranteeing the surgical reliability of parathyroid adenoma with help of nano-carbon technology.

Modeling study of a proposed field calibration source using K-40 and high-Z targets for sodium iodide detectors

DOE PAGES

Rogers, Jeremy; Marianno, Craig; Kallenbach, Gene; ...

2016-06-01

Calibration sources based on the primordial isotope potassium-40 ( 40K) have reduced controls on the source’s activity due to its terrestrial ubiquity and very low specific activity. Potassium–40’s beta emissions and 1,460.8 keV gamma ray can be used to induce K-shell fluorescence x rays in high-Z metals between 60 and 80 keV. A gamma ray calibration source that uses potassium chloride salt and a high-Z metal to create a two-point calibration for a sodium iodide field gamma spectroscopy instrument is thus proposed. The calibration source was designed in collaboration with the Sandia National Laboratory using the Monte Carlo N-Particle eXtendedmore » (MCNPX) transport code. Two methods of x-ray production were explored. First, a thin high-Z layer (HZL) was interposed between the detector and the potassium chloride-urethane source matrix. Second, bismuth metal powder was homogeneously mixed with a urethane binding agent to form a potassium chloride-bismuth matrix (KBM). The bismuth-based source was selected as the development model because it is inexpensive, nontoxic, and outperforms the high-Z layer method in simulation. As a result, based on the MCNPX studies, sealing a mixture of bismuth powder and potassium chloride into a thin plastic case could provide a light, inexpensive field calibration source.« less

Development of Photocrosslinkable Urethane-Doped Polyester Elastomers for Soft Tissue Engineering

PubMed Central

Zhang, Yi; Tran, Richard T.; Gyawali, Dipendra; Yang, Jian

2012-01-01

Finding an ideal biomaterial with the proper mechanical properties and biocompatibility has been of intense focus in the field of soft tissue engineering. This paper reports on the synthesis and characterization of a novel crosslinked urethane-doped polyester elastomer (CUPOMC), which was synthesized by reacting a previously developed photocrosslinkable poly (octamethylene maleate citrate) (POMC) prepolymers (pre-POMC) with 1,6-hexamethylene diisocyanate (HDI) followed by thermo- or photo-crosslinking polymerization. The mechanical properties of the CUPOMCs can be tuned by controlling the molar ratios of pre-POMC monomers, and the ratio between the prepolymer and HDI. CUPOMCs can be crosslinked into a 3D network through polycondensation or free radical polymerization reactions. The tensile strength and elongation at break of CUPOMC synthesized under the known conditions range from 0.73±0.12MPa to 10.91±0.64MPa and from 72.91±9.09% to 300.41±21.99% respectively. Preliminary biocompatibility tests demonstrated that CUPOMCs support cell adhesion and proliferation. Unlike the pre-polymers of other crosslinked elastomers, CUPOMC pre-polymers possess great processability demonstrated by scaffold fabrication via a thermally induced phase separation method. The dual crosslinking methods for CUPOMC pre-polymers should enhance the versatile processability of the CUPOMC used in various conditions. Development of CUPOMC should expand the choices of available biodegradable elastomers for various biomedical applications such as soft tissue engineering. PMID:23565318

Telangiectatic adenoma – computed tomography and magnetic resonance findings: a case report and review of the literature

PubMed Central

2009-01-01

Telangiectatic adenoma is a new classification of a hepatic lesion. It was previously named telangiectatic focal nodular hyperplasia but it is in fact true adenoma with telangiectatic features. We report here a case of telangiectatic adenoma in a 72-year-old woman. The image features are lack of a central scar, a heterogeneous lesion, hyperintensity in T1-weighted MR images, strong hyperintensity in T2-weighted MR images, and persistent contrast enhancement in delayed-phase contrast-enhanced CT or T1-weighted MR images. It is a monoclonal lesion with potential of malignancy. The treatment of telangiectatic adenoma is surgery, the same way as hepatic adenoma. Focal nodular hyperplasia may be managed by clinical follow-up alone. PMID:19128493

Pi (Spleen)-deficiency syndrome in tumor microenvironment is the pivotal pathogenesis of colorectal cancer immune escape.

PubMed

Sun, Xue-Gang; Lin, Xiao-Chang; Diao, Jian-Xin; Yu, Zhi-Ling; Li, Kun

2016-10-01

Cancer immunoediting consists of three sequential phases: elimination, equilibrium, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibrium phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi (Spleen)-deficiency. Classic quotations, immune evidence and clinical observations suggest that Spleen (but not other organs) deficiency is the key pathogenesis of colorectal cancer (CRC) microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-derived immunosuppressive factors and surrendered immune cells-regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages (TAMs) constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting.

Endoscopic management of colorectal adenomas.

PubMed

Meier, Benjamin; Caca, Karel; Fischer, Andreas; Schmidt, Arthur

2017-01-01

Colorectal adenomas are well known precursors of invasive adenocarcinoma. Colonoscopy is the gold standard for adenoma detection. Colonoscopy is far more than a diagnostic tool, as it allows effective treatment of colorectal adenomas. Endoscopic resection of colorectal adenomas has been shown to reduce the incidence and mortality of colorectal cancer. Difficult resection techniques are available, such as endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic full-thickness resection. This review aims to provide an overview of the different endoscopic resection techniques and their indications, and summarizes the current recommendations in the recently published guideline of the European Society of Gastrointestinal Endoscopy.

Endoscopic management of colorectal adenomas

PubMed Central

Meier, Benjamin; Caca, Karel; Fischer, Andreas; Schmidt, Arthur

2017-01-01

Colorectal adenomas are well known precursors of invasive adenocarcinoma. Colonoscopy is the gold standard for adenoma detection. Colonoscopy is far more than a diagnostic tool, as it allows effective treatment of colorectal adenomas. Endoscopic resection of colorectal adenomas has been shown to reduce the incidence and mortality of colorectal cancer. Difficult resection techniques are available, such as endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic full-thickness resection. This review aims to provide an overview of the different endoscopic resection techniques and their indications, and summarizes the current recommendations in the recently published guideline of the European Society of Gastrointestinal Endoscopy. PMID:29118553

[Old phenotype and new genotypes. Pituitary adenomas].

PubMed

Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

2015-11-01

Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

High-resolution(18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease.

PubMed

Chittiboina, Prashant; Montgomery, Blake K; Millo, Corina; Herscovitch, Peter; Lonser, Russell R

2015-04-01

OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of(18)F-fluorodeoxyglucose ((18)F-FDG). To determine the sensitivity of this imaging modality, the authors compared(18)F-FDG hrPET and MRI detection of pituitary adenomas in Cushing disease (CD). METHODS Consecutive patients with CD who underwent preoperative(18)F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11-59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.(18)F-FDG hrPET demonstrated increased(18)F-FDG uptake consistent with an adenoma in 4 patients (40%; adenoma size range 3-14 mm). Maximum SUV was significantly higher for(18)F-FDG hrPET-positive tumors (difference = 5.1, 95% CI 2.1-8.1; p = 0.004) than for(18)F-FDG hrPET-negative tumors.(18)F-FDG hrPET positivity was not associated with tumor volume (p = 0.2) or dural invasion (p = 0.5). Midnight and morning ACTH levels were associated with(18)F-FDG hrPET positivity (p = 0.01 and 0.04, respectively) and correlated with the maximum SUV (R = 0.9; p = 0.001) and average SUV (R = 0.8; p = 0.01). All(18)F-FDG hrPET-positive adenomas had a less than a 180% ACTH increase and(18)F-FDG hrPET-negative adenomas had a greater than 180% ACTH increase after CRH stimulation (p = 0.03). Three adenomas were detected on SPGR MRI sequences that were not detected by(18)F-FDG hrPET imaging. Two adenomas not detected on SE (but no adenomas not detected on SPGR) were detected on(18)F-FDG hrPET. CONCLUSIONS While(18)F-FDG hrPET imaging can detect small functioning corticotroph adenomas and is more sensitive than SE MRI, SPGR MRI is more sensitive than(18)F-FDG hrPET and SE MRI in the detection of CD-associated pituitary adenomas. Response to CRH stimulation can predict(18)F-FDG hrPET-positive adenomas in CD.

Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice.

PubMed

May, Randal; Riehl, Terrence E; Hunt, Clayton; Sureban, Sripathi M; Anant, Shrikant; Houchen, Courtney W

2008-03-01

In the gut, tumorigenesis arises from intestinal or colonic crypt stem cells. Currently, no definitive markers exist that reliably identify gut stem cells. Here, we used the putative stem cell marker doublecortin and CaM kinase-like-1 (DCAMKL-1) to examine radiation-induced stem cell apoptosis and adenomatous polyposis coli (APC)/multiple intestinal neoplasia (min) mice to determine the effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining was demonstrated in the intestinal stem cell zone. Furthermore, we observed apoptosis of the cells negative for DCAMKL-1 at 6 hours. We found DNA damage in all the cells in the crypt region, including the DCAMKL-1-positive cells. We also observed stem cell apoptosis and mitotic DCAMKL-1-expressing cells 24 hours after irradiation. Moreover, in APC/min mice, DCAMKL-1-expressing cells were negative for proliferating cell nuclear antigen and nuclear beta-catenin in normal-appearing intestine. However, beta-catenin was nuclear in DCAMKL-1-positive cells in adenomas. Thus, nuclear translocation of beta-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

PubMed

Fujio, Shingo; Ashari; Habu, Mika; Yamahata, Hitoshi; Moinuddin, F M; Bohara, Manoj; Arimura, Hiroshi; Nishijima, Yui; Arita, Kazunori

2014-01-01

Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 μ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

RET is a potential tumor suppressor gene in colorectal cancer

PubMed Central

Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.

2012-01-01

Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis.

PubMed

Ashraf, Imran; Choudhary, Abhishek; Arif, Murtaza; Matteson, Michelle L; Hammad, Hazem T; Puli, Srinivas R; Bechtold, Matthew L

2012-04-01

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC. Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I (2) measure of inconsistency. RevMan 5 was utilized for statistical analysis. Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19-1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18-1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC. Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

Seminoma and parathyroid adenoma in a snow leopard (Panthera unica).

PubMed

Doster, A R; Armstrong, D L; Bargar, T W

1989-05-01

A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline.

Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas.

PubMed

Sheikh, Rafiq A; Min, Byung Hee; Yasmeen, Shagufta; Teplitz, Raymond; Tesluk, Henry; Ruebner, Boris Henry; Tobi, Martin; Hatfield, James; Fligiel, Suzanne; Lawson, Michael J

2003-01-01

Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared theclinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients with severely dysplastic colorectal adenomas. Adnab-9 antibody may identify a field defect in above-average-risk adenoma-bearing patients.

Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement.

PubMed

Hayashi, Yasuhiko; Kita, Daisuke; Iwato, Masayuki; Fukui, Issei; Oishi, Masahiro; Tsutsui, Taishi; Tachibana, Osamu; Nakada, Mitsutoshi

2016-04-01

Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy. We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11-20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients. All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34-59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16-30). In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

PubMed Central

Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

2015-01-01

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.

PubMed

Rastogi, Amit; Early, Dayna S; Gupta, Neil; Bansal, Ajay; Singh, Vikas; Ansstas, Michael; Jonnalagadda, Sreenivasa S; Hovis, Christine E; Gaddam, Srinivas; Wani, Sachin B; Edmundowicz, Steven A; Sharma, Prateek

2011-09-01

Missing adenomas and the inability to accurately differentiate between polyp histology remain the main limitations of standard-definition white-light (SD-WL) colonoscopy. To compare the adenoma detection rates of SD-WL with those of high-definition white-light (HD-WL) and narrow-band imaging (NBI) as well as the accuracy of predicting polyp histology. Multicenter, prospective, randomized, controlled trial. Two academic medical centers in the United States. Subjects undergoing screening or surveillance colonoscopy. Subjects were randomized to undergo colonoscopy with one of the following: SD-WL, HD-WL, or NBI. The proportion of subjects detected with adenomas, adenomas detected per subject, and the accuracy of predicting polyp histology real time. A total of 630 subjects were included. The proportion of subjects with adenomas was 38.6% with SD-WL compared with 45.7% with HD-WL and 46.2% with NBI (P = .17 and P = .14, respectively). Adenomas detected per subject were 0.69 with SD-WL compared with 1.12 with HD-WL and 1.13 with NBI (P = .016 and P = .014, respectively). HD-WL and NBI detected more subjects with flat and right-sided adenomas compared with SD-WL (all P values <.005). NBI had a superior sensitivity (90%) and accuracy (82%) to predict adenomas compared with SD-WL and HD-WL (all P values <.005). Academic medical centers with experienced endoscopists. There was no difference in the proportion of subjects with adenomas detected with SD-WL, HD-WL, and NBI. However, HD-WL and NBI detected significantly more adenomas per subject (>60%) compared with SD-WL. NBI had the highest accuracy in predicting adenomas in real time during colonoscopy. ( NCT 00614770.). Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

PubMed

Lee, T J W; Blanks, R G; Rees, C J; Wright, K C; Nickerson, C; Moss, S M; Chilton, A; Goddard, A F; Patnick, J; McNally, R J Q; Rutter, M D

2013-01-01

Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy. © Georg Thieme Verlag KG Stuttgart · New York.

Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to the ischemic rat heart.

PubMed

Gu, Xinzhu; Matsumura, Yasumoto; Tang, Ying; Roy, Souvik; Hoff, Richard; Wang, Bing; Wagner, William R

2017-07-01

Biodegradable and elastomeric patches have been applied to the surface of infarcted hearts as temporary mechanical supports to effectively alter adverse left ventricular remodeling processes. In this report, recombinant adeno-associated virus (AAV), known for its persistent transgene expression and low pathogenicity, was incorporated into elastomeric polyester urethane urea (PEUU) and polyester ether urethane urea (PEEUU) and processed by electrospinning into two formats (solid fibers and core-sheath fibers) designed to influence the controlled release behavior. The extended release of AAV encoding green fluorescent protein (GFP) was assessed in vitro. Sustained and localized viral particle delivery was achieved over 2 months in vitro. The biodegradable cardiac patches with or without AAV-GFP were implanted over rat left ventricular lesions three days following myocardial infarction to evaluate the transduction effect of released viral vectors. AAV particles were directly injected into the infarcted hearts as a control. Cardiac function and remodeling were significantly improved for 12 weeks after patch implantation compared to AAV injection. More GFP genes was expressed in the AAV patch group than AAV injection group, with both α-SMA positive cells and cardiac troponin T positive cells transduced in the patch group. Overall, the extended release behavior, prolonged transgene expression, and elastomeric mechanical properties make the AAV-loaded scaffold an attractive option for cardiac tissue engineering where both gene delivery and appropriate mechanical support are desired. Copyright © 2017. Published by Elsevier Ltd.

Microinjection of procaine and electrolytic lesion in the ventral tegmental area suppresses hippocampal theta rhythm in urethane-anesthetized rats.

PubMed

Orzeł-Gryglewska, Jolanta; Jurkowlaniec, Edyta; Trojniar, Weronika

2006-01-30

The midbrain ventral tegmental area (VTA), a key structure of the mesocorticolimbic system is anatomically connected with the hippocampal formation. In addition mesocortical dopamine was found to influence hippocampus-related memory and hippocampal synaptic plasticity, both being linked to the theta rhythm. Therefore, the aim of the present study was to evaluate the possible role of the VTA in the regulation of the hippocampal theta activity. The study was performed on urethane-anesthetized male Wistar rats in which theta rhythm was evoked by tail pinch. It was found that unilateral, temporal inactivation of the VTA by means of direct procaine injection resulted in bilateral suppression of the hippocampal theta which manifested as a loss of synchronization of hippocampal EEG and respective reduction of the power and also the frequency of the 3-6 Hz theta band. Depression of the power of the 3-6 Hz component of the EEG signal was also seen in spontaneous hippocampal EEG after procaine. The permanent destruction of the VTA by means of unilateral electrocoagulation evoked a long-lasting, mainly ipsilateral depression of the power of the theta with some influence on its frequency. Simultaneously, there was a substantial increase of the power in higher frequency bands indicating decrease of a synchrony of the hippocampal EEG activity. On the basis of these results indicating impairment of synchronization of the hippocampal activity the VTA may be considered as another part of the brainstem theta synchroning system.

Cancer emerging from the recurrence of sessile serrated adenoma/polyp resected endoscopically 5 years ago.

PubMed

Chino, A; Nagayama, S; Ishikawa, H; Morishige, K; Kishihara, T; Arai, M; Sugiura, Y; Motoi, N; Yamamoto, N; Tamegai, Y; Igarashi, M

2016-01-01

Since the serrated neoplastic pathway has been regarded as an important pathway of colorectal carcinogenesis, few reports have been published on clinical cases of cancer derived from sessile serrated adenoma/polyp, especially on recurrence after resected sessile serrated adenoma/polyp. An elderly woman underwent endoscopic mucosal resection of a flat elevated lesion, 30 mm in diameter, in the ascending colon; the histopathological diagnosis at that time was a hyperplastic polyp, now known as sessile serrated adenoma/polyp. Five years later, cancer due to the malignant transformation of the sessile serrated adenoma/polyp was detected at the same site. The endoscopic diagnosis was a deep invasive carcinoma with a remnant sessile serrated adenoma/polyp component. The carcinoma was surgically removed, and the pathological diagnosis was an adenocarcinoma with sessile serrated adenoma/polyp, which invaded the muscularis propria. The surgically removed lesion did not have a B-RAF mutation in either the sessile serrated adenoma/polyp or the carcinoma; moreover, the initial endoscopically resected lesion also did not have a B-RAF mutation. Immunohistochemistry confirmed negative MLH1 protein expression in only the cancer cells. Lynch syndrome was not detected on genomic examination. The lesion was considered to be a cancer derived from sessile serrated adenoma/polyp recurrence after endoscopic resection, because both the surgically and endoscopically resected lesions were detected at the same location and had similar pathological characteristics, with a serrated structure and low-grade atypia. Furthermore, both lesions had a rare diagnosis of a sessile serrated adenoma/polyp without B-RAF mutation. This report highlights the need for the follow-up colonoscopy after endoscopic resection and rethinking our resection procedures to improve treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Trimodal endoscopic imaging for the detection and differentiation of colorectal adenomas: a prospective single-centre clinical evaluation.

PubMed

Rotondano, Gianluca; Bianco, Maria Antonia; Sansone, Stefano; Prisco, Antonio; Meucci, Costantino; Garofano, Maria Lucia; Cipolletta, Livio

2012-03-01

The purpose of this study is to evaluate an endoscopic trimodal imaging (ETMI) system (high resolution, autofluorescence, and NBI) in the detection and differentiation of colorectal adenomas. A prospective randomised trial of tandem colonoscopies was carried out using the Olympus XCF-FH260AZI system. Each colonic segment was examined twice for lesions, once with HRE and once with AFI, in random order per patient. All detected lesions were assessed with NBI for pit pattern and with AFI for colour. All lesions were removed and sent for histology. Any lesion identified on the second examination was considered as missed by the first examination. Outcome measures are adenoma miss rates of AFI and HRE, and diagnostic accuracy of NBI and AFI for differentiating neoplastic from non-neoplastic lesions. Ninety-four patients underwent colonoscopy with ETMI (47 in each group). Among 47 patients examined with AFI first, 31 adenomas in 15 patients were detected initially [detection rate 0.66 (0.52-0.75)]. Subsequent HRE inspection identified six additional adenomas. Among 47 patients examined with HRE first, 29 adenomas in 14 patients were detected initially [detection rate 0.62 (0.53-0.79)]. Successive AFI yielded seven additional adenomas. Adenoma miss rates of AFI and HRE were 14% and 16.2%, respectively (p = 0.29). Accuracy of AFI alone for differentiation was lower than NBI (63% vs. 80%, p < 0.001). Combined use of AFI and NBI achieved improved accuracy for differentiation (84%), showing a trend for superiority compared with NBI alone (p = 0.064). AFI did not significantly reduce the adenoma miss rate compared with HRE. AFI alone had a disappointing accuracy for adenoma differentiation, which could be improved by combination of AFI and NBI.

Dietary Intakes of Red Meat, Poultry, and Fish During High School and Risk of Colorectal Adenomas in Women

PubMed Central

Nimptsch, Katharina; Bernstein, Adam M.; Giovannucci, Edward; Fuchs, Charles S.; Willett, Walter C.; Wu, Kana

2013-01-01

Adolescent diet may be etiologically relevant for colorectal carcinogenesis. We examined the association between meat and fish intakes during adolescence and the risk of colorectal adenomas later in life among 19,771 women participating in the Nurses' Health Study II. Subjects had completed a validated food frequency questionnaire in 1998 (when aged 34–51 years) about their diets during high school and subsequently underwent at least 1 lower-bowel endoscopy during the study period (1998–2007). During this period, 1,494 subjects were diagnosed with colorectal adenomas. Intake of red meat during adolescence was not associated with colorectal adenoma risk when comparing those in the highest versus lowest category of intake (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.81, 1.35). Similarly, intake of fish during adolescence was not associated with colorectal adenoma risk (OR = 0.96, 95% CI: 0.78, 1.17). Intake of poultry during adolescence was associated with a lower risk of total colorectal (OR = 0.80, 95% CI: 0.64, 0.99), distal (OR = 0.71, 95% CI: 0.51, 0.99), rectal (OR = 0.51, 95% CI: 0.29, 0.90), and advanced (OR = 0.60, 95% CI: 0.38, 0.93) adenomas. Replacement of 1 serving per day of red meat with 1 serving per day of poultry or fish was associated with 41% and 35% decreased risks for rectal adenomas and advanced adenomas, respectively. Our findings do not suggest an association between red meat intake during adolescence and colorectal adenomas later in life, but higher poultry intake during this time was associated with a lower risk of colorectal adenomas. PMID:23785116

Genetic polymorphisms of methylenetetrahydrofolate reductase and aldehyde dehydrogenase 2, alcohol use and risk of colorectal adenomas: Self-Defense Forces Health Study.

PubMed

Hirose, Maho; Kono, Suminori; Tabata, Shinji; Ogawa, Shinsaku; Yamaguchi, Keizo; Mineshita, Masamichi; Hagiwara, Tomoko; Yin, Guang; Lee, Kyong-Yeon; Tsuji, Akiko; Ikeda, Noriaki

2005-08-01

Methylenetetrahydrofolate reductase is a key enzyme in folate metabolism, which affects DNA synthesis and methylation and is possibly linked to colorectal carcinogenesis. Alcohol and acetaldehyde have an adverse effect on folate metabolism. This study investigated the relationship of functional MTHFR C677T and ALDH2 polymorphisms to colorectal adenomas with reference to alcohol consumption in a case-control study of male officials in the Self-Defense Forces (SDF) who received a preretirement health examination at two SDF hospitals. The study subjects were 452 cases of colorectal adenoma and 1050 controls with no polyp who underwent total colonoscopy. Genotypes were determined by the PCR-RFLP method using genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index, cigarette-years and alcohol intake. Neither MTHFR C677T nor ALDH2 showed a measurable association with colorectal adenoma. While high alcohol consumption was associated with a moderately increased risk of colorectal adenoma, neither of the two polymorphisms showed a significant effect on the association between alcohol and colorectal adenoma. Individuals with the variant alleles ALDH2*2 and MTHFR 677T had a decreased risk of colorectal adenomas, showing adjusted odds ratios of 0.70 (95% confidence interval 0.49-1.00) for all adenomas and 0.57 (0.34-0.95) for large adenomas (> or = 5 mm), as compared to individuals with ALDH2*1/1 and MTHFR 677CC genotypes combined. The findings may be interpreted as suggesting that folate inhibits the growth of colorectal adenomas, but further confirmation is needed.

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

Uneven Distribution of Regional Blood Supply Prompts the Cystic Change of Pituitary Adenoma.

PubMed

Zhang, Jianhe; Gu, Jianjun; Ma, Yiming; Huang, Yinxing; Wang, Jiaxing; Wu, Zhifeng; Zhong, Qun; Wang, Shousen

2017-07-01

Previous studies have suggested that the cystic change of pituitary adenoma might be related to the blood supply and metabolism of the tumor; however, the exact pathologic mechanism underlying the cystic change remains unknown. We aimed to assess the features of regional blood supply of pituitary adenoma and examine its relationship with the cystic change of pituitary adenoma. Patients (N = 79) with pituitary adenoma admitted to our hospital were divided into the parenchyma group (n = 40) or the cystic change group (n = 39). Dynamic contrast-enhanced magnetic resonance imaging of the pituitary adenoma was conducted for the parenchyma group and the steepest slopes (SS max , reflecting regional blood supply) at different areas were calculated. The location of cystic change of the pituitary adenoma was recorded and analyzed for the cystic change group. The parenchyma group showed an upper SS max of 2.52 ± 1.18, a lower SS max of 2.89 ± 1.46, a left SS max of 2.71 ± 1.31, and a right SS max of 2.66 ± 1.29. The difference between the upper and lower SS max was statistically significant (P < 0.001), with no difference between the left and right regions (P = 0.668). The location of cystic change of the pituitary adenoma was mainly in the upper region, accounting for 48.7% of cases. Regional blood supply is unevenly distributed in the parenchymal pituitary adenoma, with reduced blood supply in the upper than the lower region. Cystic change mainly occurs in the upper region of pituitary adenoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of advanced adenomas in small and diminutive colon polyps using direct measurement of size.

PubMed

Tsai, Franklin C; Strum, Williamson B

2011-08-01

Most studies reporting polyp size use visual estimates. Determining the prevalence of advanced histology based on direct measurement of polyp size may help guide the management of polyps found at optical colonoscopy (OC) and CT colonography (CTC). We designed a large, prospective study to assess the prevalence of advanced adenomas based on direct measurement of polyp size by a certified pathologists' assistant as reported in the pathology report. Patients between 40 and 89 years of age who presented for screening colonoscopy were included in our study. Advanced adenomas were defined as ≥10 mm or ≥25% villous features, high grade dysplasia or cancer. Polyps were divided by size into three groups: diminutive (≤5 mm), small (6-9 mm) and large (≥10 mm). If more than one adenoma was present, the most advanced was used for analysis. We evaluated 6,905 consecutive patients referred for colonoscopy between January 2005 and December 2006. Of the 4,967 who met the inclusion criteria, the mean age was 58.8 and consisted of 59% women. Overall, 930 (18.7%) had an adenoma; 248 (5%) were advanced adenomas including 8 (0.16%) cancers. Of 89 polyps≥10 mm, 76 (85%) had advanced histology; of 247 polyps 6-9 mm, 67 (27%) were advanced; of 1,025 polyps ≤5 mm, 105 (10%) were advanced. Thus, 172 of 248 (69%) patients with advanced adenomas had small or diminutive adenomas. Our data indicate the majority (69%) of advanced adenomas are <10 mm. Even among polyps≤5 mm, there was an appreciable prevalence of advanced adenomas (10%). These findings may help guide the management of sub-centimeter colon polyps found by OC or CTC.

Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP.

PubMed

Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

2015-02-01

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients.

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

A New Scoring System to Predict the Risk for High-risk Adenoma and Comparison of Existing Risk Calculators.

PubMed

Murchie, Brent; Tandon, Kanwarpreet; Hakim, Seifeldin; Shah, Kinchit; O'Rourke, Colin; Castro, Fernando J

2017-04-01

Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.

The risks of overlooking the diagnosis of secreting pituitary adenomas.

PubMed

Brue, Thierry; Castinetti, Frederic

2016-10-06

Secreting pituitary adenomas that cause acromegaly and Cushing's disease, as well as prolactinomas and thyrotroph adenomas, are uncommon, usually benign, slow-growing tumours. The rarity of these conditions means that their diagnosis is not familiar to most non-specialist physicians. Consequently, pituitary adenomas may be overlooked and remain untreated, and affected individuals may develop serious comorbidities that reduce their quality of life and life expectancy. Because many signs and symptoms of pituitary adenomas overlap with those of other, more common disorders, general practitioners and non-endocrinology specialists need to be aware of the "red flags" suggestive of these conditions. A long duration of active disease in patients with secreting pituitary adenomas is associated with an increased risk of comorbidities and reduced quality of life. Appropriate treatment can lead to disease remission, and, although some symptoms may persist in some patients, treatment usually reduces the incidence and severity of comorbidities and improves quality of life. Therefore, correct, early diagnosis and characterization of a pituitary adenoma is crucial for patients, to trigger timely, appropriate treatment and to optimize outcome. This article provides an overview of the epidemiology of hormonal syndromes associated with pituitary adenomas, discusses the difficulties of and considerations for their diagnosis, and reviews the comorbidities that may develop, but can be prevented, by accurate diagnosis and appropriate treatment. We hope this review will help general practitioners and non-endocrinology specialists to suspect secreting pituitary adenomas and refer patients to an endocrinologist for confirmation of the diagnosis and treatment.

Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly.

PubMed

Metyolkina, L; Peresedov, V

1995-01-01

Since 1960 we have performed stereotactic transsphenoidal cryohypophysectomy in 70 patients with pituitary adenomas, 42 women and 28 men, aged 11-59 years. The dominant clinical syndrome was acromegaly in 50 patients, galactorrhea in 9, amenorrhea in 5, adiposogenital dystrophy in 4 and gigantism with mild endocrine symptomatology in 2 patients. In 67 patients the histological structure of the tumor was established by biopsy (50 patients with eosinophil adenoma, 10 with mixed-type adenoma, 4 with chromophobe adenoma and 3 with basophil adenoma). Somatotropic hormone, human growth hormone, prolactin, ACTH and 17-ketosteroid levels indicated active/inactive adenomas. In 42 cases the adenoma was only intrasellar, which was confirmed by contrast X-ray investigations, CT scanning, angiography and ophthalmological investigation. Transnasal stereotactic cryohypophysectomy was performed in all 70 cases using a stereotactic apparatus especially designed for operations on the pituitary. All patients (except 2) tolerated the operation well. No complications occurred. Vision deteriorated after operation in 1 patient. Thrombosis of the left middle cerebral artery developed in another patient. All the other patients noted improvement directly after operation - rapid diminution of signs of acromegaly and rapid restoration of normal values in hormonal tests. Six patients with continuing growth of the tumor underwent a second operation 1.5-6 years after the first operation. We conclude from our own clinical experience and information from the literature that transnasal stereotactic cryodestruction is highly effective and relatively safe in the management of pituitary adenoma.

Cyclooxygenase-2 expression in human gastric tubular adenomas and carcinomas; correlation with intratumoral microvessel density and apoptotic index.

PubMed

Honjo, Soichiro; Kase, Satoru; Osaki, Mitsuhiko; Ardyanto, Tonang Dwi; Kaibara, Nobuaki; Ito, Hisao

2004-01-01

Cyclooxygenase (COX)-2 plays an important role in carcinogenesis in various human malignancies. This study examined the relationship among COX-2 expression, angiogenesis and apoptosis in human gastric adenoma and carcinoma. We examined the expression of COX-2 in 30 tubular adenomas and 11 carcinomas, comparing it with intratumoral microvessel density (IMVD) and apoptotic index (AI) by immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxygenin nick-end labeling (TUNEL) procedure. Immunohistochemistry demonstrated positive expression of COX-2 in 15 (50.0%) adenomas and in 50 (53.1%) carcinomas, respectively. The frequency of COX-2 expression was significantly higher in intestinal-type carcinomas than in diffuse-type, regardless of the tumor stage. The IMVD was significantly higher in the early and advanced carcinomas than in the adenomas and also higher in the COX-2-positive adenomas and carcinomas than in the negative ones. The AI was significantly higher in the adenomas than in the carcinomas and also in the COX-2-negative adenomas and intestinal-type early carcinomas than in their positive counterparts, respectively (p < 0.05). The IMVD and AI showed significant inverse correlation in both the adenomas (p=0.02, r=-0.64) and carcinomas (p=0.04, r=-0.18). COX-2 expression might be an early event in gastric tumorigenesis and provide a preferential advantage for tumor cell proliferation because of its vascular-rich microenvironment and escape from tumor cell apoptosis, especially in intestinal-type gastric carcinomas.

Division of constricted and urethane-treated sand dollar eggs: a test of the polar stimulation hypothesis.

PubMed

Rappaport, R; Rappaport, B N

1984-07-01

In spherical cells with a central mitotic apparatus, the centers of the asters are closer to the poles than to the equator. This circumstance is basic to several hypothetical explanations of the way in which the mitotic apparatus establishes the division mechanism. This investigation was designed to determine whether that geometrical relationship is necessary for division. Fertilized, mechanically denuded sand dollar eggs were inserted into glass loops, which reduced the diameter in the constriction plane from the normal 142 to 78-80 microns and partly constricted the cell into equal parts. The mitotic apparatus straddled the constriction, and its length was not significantly changed. The manipulation increased the distance from the astral centers to the poles and decreased the distance from the astral centers to the equator to a degree that reversed the normal distance relations. These cells divided normally. Ethyl urethane (0.06 M) reduces the size of the mitotic apparatus and blocks cleavage in spherical cells. When treated cells are confined in 80-microns i.d. capillaries, they divide. Treated cells also divide when they are constricted by an 80-microns i.d. glass loop if the mitotic apparatus straddles the constriction. An equal degree of constriction in the subfurrow and subpolar areas did not reverse the effect of urethane. The results demonstrate that cleavage does not depend on the normal distance relation between the mitotic apparatus and the poles, and that the urethane effect can be remedied only by reducing the distance between the mitotic apparatus and the equatorial surface. Both findings are inconsistent with the polar stimulation hypothesis.

Nipple adenoma in a 2-year-old boy.

PubMed

Fujisawa, Kou; Kato, Motoi; Kono, Tatsuki; Utsunomiya, Hiroki; Watanabe, Azusa; Watanabe, Shoji

2018-05-01

Nipple adenoma is an uncommon proliferative process of the breast and predominantly occurs in women aged 40-50. Its incidence is extremely low in men, and it has not been reported in a boy. Although nipple adenoma is rare and benign, being familiar with it is important because it clinically resembles Paget disease and histologically adenocarcinoma. We report a case of nipple adenoma in a boy. © 2018 Wiley Periodicals, Inc.

Geographic-Related Differences of Pituitary Adenomas Hormone Profile: Analysis of Two Groups Coming from Southeastern and Eastern Europe.

PubMed

Cimpean, Anca Maria; Melnic, Eugen; Bălinişteanu, Bogdan; Corlan, Ana; Coculescu, Mihail; Rusu, Sergiu; Raica, Marius

2015-01-01

We compared the immunoprofile of pituitary adenomas from Romania and Moldova. One hundred and eighty cases coming from Romania (94 cases, group 1) and Moldova (86 cases, group 2) were assessed by immunohistochemistry regarding all six basic hormones expressed in pituitary adenomas. Specific differences and similarities were found and stated for both groups. In group 1, 70% of cases were pituitary adenomas positive for one hormone, 13% were plurihormonal, while 17% were negative. In group 2, 50,3% of the cases expressed only one hormone and 12,5% were negative for all hormones. The highest difference was observed for plurihormonal adenomas, found in about 37,2% of cases for group 2 (2.86 times higher for group 2 compared with group 1). A higher incidence of GH-secreting adenomas characterized group "1," while group "2" had the highest percent of LH-secreting adenomas, 55% of cases being positive. Triple association was noticed in 4.25% of cases of group 1 and in 8,13% out of total cases, from group 2. Four-hormone association was found only in group 2, noticed in 15,56% of the cases. The present paper highlights strong evidences of a particular and different immunoprofile of pituitary adenomas coming from Romania and Moldova.

Sedentary behavior is associated with colorectal adenoma recurrence in men

PubMed Central

Molmenti, Christine L. Sardo; Hibler, Elizabeth A.; Ashbeck, Erin L.; Thomson, Cynthia A.; Garcia, David O.; Roe, Denise; Harris, Robin B.; Lance, Peter; Cisneroz, Martin; Martinez, Maria Elena; Thompson, Patricia A.; Jacobs, Elizabeth T.

2014-01-01

Purpose The association between physical activity and colorectal adenoma is equivocal. This study was designed to assess the relationship between physical activity and colorectal adenoma recurrence. Methods Pooled analyses from two randomized, controlled trials included 1,730 participants who completed the Arizona Activity Frequency Questionnaire at baseline, had a colorectal adenoma removed within 6 months of study registration, and had a follow-up colonoscopy during the trial. Logistic regression modeling was employed to estimate the effect of sedentary behavior, light-intensity physical activity, and moderate-vigorous physical activity on colorectal adenoma recurrence. Results No statistically significant trends were found for any activity type and odds of colorectal adenoma recurrence in the pooled population. However, males with the highest levels of sedentary time experienced 47% higher odds of adenoma recurrence. Compared to the lowest quartile of sedentary time, the ORs (95% CIs) for the second, third, and fourth quartiles among men were 1.23 (0.88, 1.74), 1.41 (0.99, 2.01), and 1.47 (1.03, 2.11) respectively (P trend=0.03). No similar association was observed for women. Conclusions This study suggests that sedentary behavior is associated with a higher risk of colorectal adenoma recurrence among men, providing evidence of detrimental effects of a sedentary lifestyle early in the carcinogenesis pathway. PMID:25060482

The natural history of thyroid autonomy and hot nodules.

PubMed

Corvilain, B

2003-02-01

Solitary hyperfunctioning thyroid adenomas are benign monoclonal tumors characterized by their capacity to grow and produce thyroxine (T4) and triiodothyronine (T3) autonomously, i.e. in the absence of thyrotropin (TSH). Mutations of the TSH receptor (TSH-R) have been found in the majority of solitary hyperfunctioning thyroid adenomas. On radioisotope scanning they generally appear as hot nodules because they concentrate radioiodide or 99mTc pertechnate, whereas the normal surrounding and contralateral tissue concentrate little isotopes. A toxic adenoma probably evolves gradually from a small autonomously hyperfunctioning adenoma that initially is only slightly more active than the extranodular tissue. This has been referred to as a "warm" nodule or a "compensated" adenoma. The diagnostic criterion for this designation is the persistence of detectable serum TSH maintaining some radioiodine uptake by the extranodular tissue. This "compensated" adenoma persists as long as the autonomous hormone output is not sufficient to suppress thyrotropin, i.e. to cause hyperthyroidism. The rate of development of thyrotoxicosis in patients with hyperfunctioning adenomas who are euthyroid initially is about 4% per year and depends on the size of the adenoma, iodine intake and age of the patient. No clear relationship can be establish between the nature of the TSH receptor mutations and the phenotype of the tumor.

A functional thyrotropin- and growth hormone-secreting pituitary adenoma with a ultrastructurally monomorphic feature: a case study.

PubMed

Ozawa, Y; Kameya, T; Kasuga, A; Naritaka, H; Kanda, N; Maruyama, H; Saruta, T

1998-04-01

A 38-yr-old female with a TSH- and GH-secreting pituitary adenoma is described, who had both overt symptoms, hyperthyroidism and acromegaly. Her serum TSH was not suppressed despite high concentrations of free T3 and free T4, and her alpha-subunit/TSH molar ratio was high. Her serum GH was consistently high, and was not suppressed by an oral glucose tolerance test. Preoperative testing revealed that, although the TSH response was impaired, TSH, alpha-subunit and GH were increased by TRH injection, and that these hormones were reduced by bromocriptine or somatostatin analog. Although she did not have hyperprolactinemia, the in vitro culture and immunohistochemical studies revealed that the adenoma cells produced and released PRL, in addition to TSH, alpha-subunit and GH. Immunohistochemical studies showed the presence of GH in the cytoplasm of many adenoma cells. TSH beta-positive adenoma cells were less frequently seen than GH-positive adenoma cells. No cells showed the coexistence of GH and TSH beta, and a few cells were positive for PRL. By electron microscopy, the adenoma was found to be composed of a single cell type resembling thyrotrophs, and did not have any characteristics of somatotrophs. This case was considered to be of interest, because the adenoma was ultrastructurally monomorphous, but immunohistochemically polymorphous.

PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk.

PubMed

Rifkin, Samara B; Shrubsole, Martha J; Cai, Qiuyin; Smalley, Walter E; Ness, Reid M; Swift, Larry L; Zheng, Wei; Murff, Harvey J

2017-06-01

Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis

PubMed Central

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-01-01

Background Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. Objective The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Methods Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. Results A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. Conclusions The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population. PMID:29511562

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis.

PubMed

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-03-01

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

Application of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology for the diagnosis of colorectal adenoma.

PubMed

Zhou, Zhong-Yin; Tao, DI-DI; Cao, Ji-Wang; Luo, He-Sheng

2013-06-01

The aim of the present study was to identify a specific biological marker for the diagnosis of colorectal adenomas through the analysis of variations in serum protein profiling in colorectal adenoma patients. The study was conducted at the Renmin Hospital of Wuhan University (Wuhan, China) between September 2011 and May 2012. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was performed to compare the serum protein profiles of 50 patients with colorectal adenoma and 50 healthy individuals. The obtained protein profiles were analyzed using Biomarker Wizard software. Twenty protein peaks were identified to exhibit differences in average intensity between colorectal adenomas compared with normal controls, including peaks 8,565.84, 8,694.51 and 5,910.50 Da, in which the intensity between the patients and control individuals was significantly different. Two peaks, 8,565.84 and 8,694.51 Da, were observed to be highly expressed in the colorectal adenomas, however, expression was low in the control samples. By contrast, 5,910.50 Da expression was low in the colorectal adenomas and high in the controls. The results of the current study indicate that the three protein peaks may represent specific biomarkers for colorectal adenomas.

Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo.

PubMed

Lv, You; Ye, Tao; Wang, Hui-Peng; Zhao, Jia-Ying; Chen, Wen-Jie; Wang, Xin; Shen, Chen-Xia; Wu, Yi-Bin; Cai, Yuan-Kun

2017-01-28

To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 μg), and a model + high-dose toxin (ADHT; n = 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa. Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group ( P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05). Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.

Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo

PubMed Central

Lv, You; Ye, Tao; Wang, Hui-Peng; Zhao, Jia-Ying; Chen, Wen-Jie; Wang, Xin; Shen, Chen-Xia; Wu, Yi-Bin; Cai, Yuan-Kun

2017-01-01

AIM To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS). METHODS Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 μg), and a model + high-dose toxin (ADHT; n = 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa. RESULTS Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group (P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05). CONCLUSION Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice. PMID:28216966

Nanoscale Structure of Urethane/Urea Elastomeric Films

NASA Astrophysics Data System (ADS)

Reis, Dennys; Trindade, Ana C.; Godinho, Maria Helena; Silva, Laura C.; do Carmo Gonçalves, Maria; Neto, Antônio M. Figueiredo

2017-02-01

The nanostructure of urethane/urea elastomeric membranes was investigated by small-angle X-ray scattering (SAXS) in order to establish relationships between their structure and mechanical properties. The networks were made up of polypropylene oxide (PPO) and polybutadiene (PB) segments. The structural differences were investigated in two types of membranes with the same composition but with different thermal treatment after casting. Type I was cured at 70-80 °C and type II at 20 °C. Both membranes showed similar phase separation by TEM, with nanodomains rich in PB or PPO and 25 nm dimensions. The main difference between type I and type II membranes was found by SAXS. The type I membrane spectra showed, besides a broad band at a 27-nm q value (modulus of the scattering vector), an extra band at 6 nm, which was not observed in the type II membrane. The SAXS spectra were interpreted in terms of PPO, PB soft segments, and urethane/urea links, as well as hard moiety segregation in the reaction medium. This additional segregation ( q = 7 nm), although subtle, results in diverse mechanical behavior of in both membranes.

Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis.

PubMed

Mahmoud, N N; Carothers, A M; Grunberger, D; Bilinski, R T; Churchill, M R; Martucci, C; Newmark, H L; Bertagnolli, M M

2000-05-01

Epidemiological studies consistently indicate that consumption of fruits and vegetables lowers cancer risk in humans and suggest that certain dietary constituents may be effective in preventing colon cancer. Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis in vivo. In this study, we investigated the efficacy of several plant-derived phenolics, including caffeic acid phenethyl ester (CAPE), curcumin, quercetin and rutin, for the prevention of tumors in C57BL/6J-Min/+ (Min/+) mice. These animals bear a germline mutation in the Apc gene and spontaneously develop numerous intestinal adenomas by 15 weeks of age. At a dietary level of 0.15%, CAPE decreased tumor formation in Min/+ mice by 63%. Curcumin induced a similar tumor inhibition. Quercetin and rutin, however, both failed to alter tumor formation at dietary levels of 2%. Examination of intestinal tissue from the treated animals showed that tumor prevention by CAPE and curcumin was associated with increased enterocyte apoptosis and proliferation. CAPE and curcumin also decreased expression of the oncoprotein beta-catenin in the enterocytes of the Min/+ mouse, an observation previously associated with an antitumor effect. These data place the plant phenolics CAPE and curcumin among a growing list of anti-inflammatory agents that suppress Apc-associated intestinal carcinogenesis.

Nipple adenoma arising from axillary accessory breast: a case report

PubMed Central

2012-01-01

Nipple adenoma is a relatively rare benign breast neoplasm, and cases of the disease arising from the axillary accessory breast have very seldom been reported in the English literature. We report a case of nipple adenoma arising from axillary accessory breast including clinical and pathological findings. An 82-year-old woman presented with the complaint of a small painful mass in the right axilla. Physical examination confirmed a well-defined eczematous crusted mass that was 8 mm in size. The diagnosis of nipple adenoma was made from an excisional specimen on the basis of characteristic histological findings. Microscopic structural features included a compact proliferation of small tubules lined by epithelial and myoepithelial cells, and the merging of glandular epithelial cells of the adenoma into squamous epithelial cells in the superficial epidermal layer. Because clinically nipple adenoma may resemble Paget’s disease and pathologically can be misinterpreted as tubular carcinoma, the correct identification of nipple adenoma is an important factor in the differential diagnosis for axillary tumor neoplasms. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1186821489769063 PMID:23186145

Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging.

PubMed

Lee, John Y K; Cho, Steve S; Zeh, Ryan; Pierce, John T; Martinez-Lage, Maria; Adappa, Nithin D; Palmer, James N; Newman, Jason G; Learned, Kim O; White, Caitlin; Kharlip, Julia; Snyder, Peter; Low, Philip S; Singhal, Sunil; Grady, M Sean

2017-08-25

OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%-20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2-4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance. CONCLUSIONS Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

A Pilot Comparison of 18F-fluorocholine PET/CT, Ultrasonography and 123I/99mTc-sestaMIBI Dual-Phase Dual-Isotope Scintigraphy in the Preoperative Localization of Hyperfunctioning Parathyroid Glands in Primary or Secondary Hyperparathyroidism

PubMed Central

Michaud, Laure; Balogova, Sona; Burgess, Alice; Ohnona, Jessica; Huchet, Virginie; Kerrou, Khaldoun; Lefèvre, Marine; Tassart, Marc; Montravers, Françoise; Périé, Sophie; Talbot, Jean-Noël

2015-01-01

Abstract We compared 18F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and 123I/99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted). The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases. In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with 99mTc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia. This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope 123I/99mTc-scintigraphy. Further studies should evaluate whether FCH could replace 99mTc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions. PMID:26469908

Tumor-associated down-regulation of 15-lipoxygenase-1 is reversed by celecoxib in colorectal cancer.

PubMed

Heslin, Martin J; Hawkins, Ashley; Boedefeld, William; Arnoletti, J Pablo; Frolov, Andrey; Soong, Richie; Urist, Marshall M; Bland, Kirby I

2005-06-01

To evaluate the role of celecoxib on 15-lipoxygenase-1 (15-LOX-1) expression, protein levels, and rates of apoptosis in colorectal cancer cell lines. Also, to evaluate the expression of 15-LOX-1 in human normal mucosa, adenoma, and carcinoma with correlation to overall survival. The function of 15-LOX-1 is to maintain normal rates of apoptosis (programmed cell death). Decreased apoptosis is one mechanism of cancer growth and dissemination. It is our hypothesis that expression of 15-LOX-1 is reduced in human colorectal cancer (CRC) and the administration of celecoxib can reverse this process and induce apoptosis. Effect of celecoxib in cell culture: The effect of 40 micromol/L celecoxib was compared with untreated controls in tissue culture utilizing HT-29 and DLD-1 CRC cell lines. Expression of 15-LOX-1 protein was measured by immunoblot. Induction of apoptosis was evaluated by annexin V staining. All data are presented as mean +/- SEM, with significance defined as P < 0.05. 15-LOX-1 in human CRC: From February 1998 to January 2002, 126 patients underwent surgical resection of either colorectal adenomas (n = 24) or carcinomas (n = 102), or both (n = 25). Tissue was macrodissected, snap frozen, and stored at -80 degrees C. After tissue processing, RNA was extracted and gene expression of 15-LOX-1 was quantified utilizing ABI prism real-time quantitative RT-PCR. Significance evaluated by the Wilcoxon signed rank test. Effect of celecoxib in cell culture: After 72 hours of treatment with celecoxib, immunoblot demonstrated a 1.5- to 2-fold increase in 15-LOX-1 protein expression in HT-29 and DLD-1 cells, respectively. Celecoxib produced greater than a 2-fold increase in the rate of apoptosis compared with control cells in both cell lines (P < 0.05). 15-LOX-1 in human CRC: The mean age of the patients was 62 +/- 1 years; 78% were white and 48% were female. The mean size of the polyps and cancers were 3.0 +/- 0.4 and 5.0 +/- 0.1 cm, respectively. Expression of 15-LOX-1 relative to S9 was 30 in normal mucosa and significantly down-regulated to 11 in adenomas and 16 in carcinomas (P < 0.05). 15-LOX-1 gene expression is significantly reduced in both human colorectal adenomas and carcinomas and associated with decreased survival. Administration of celecoxib restores 15-LOX-1 protein expression and induces apoptosis. Down-regulation of 15-LOX-1 is an early event in the adenoma to carcinoma sequence, and reversal with celecoxib may represent one mechanism for chemoprevention of polyps or treatment of carcinomas.

Atypical β-Catenin Activated Child Hepatocellular Tumor

PubMed Central

Unlu, Havva Akmaz; Karakus, Esra; Yazal Erdem, Arzu; Yakut, Zeynep Ilerisoy

2015-01-01

Hepatocellular adenomas are a benign, focal, hepatic neoplasm that have been divided into four subtypes according to the genetic and pathological features. The β-catenin activated subtype accounts for 10-15% of all hepatocellular adenomas and specific magnetic resonance imaging features have been defined for different hepatocellular adenomas subtypes. The current study aimed to report the magnetic resonance imaging features of a well differentiated hepatocellular carcinoma that developed on the basis of β-catenin activated hepatocellular adenomas in a child. In this case, atypical diffuse steatosis was determined in the lesion. In the literature, diffuse steatosis, which is defined as a feature of the hepatocyte nuclear factor-1α-inactivated hepatocellular adenomas subtype, has not been previously reported in any β-catenin activated hepatocellular adenomas case. Interlacing magnetic resonance imaging findings between subtypes show that there are still many mysteries about this topic and larger studies are warranted. PMID:26157702

Cushing's disease due to mixed pituitary adenoma-gangliocytoma of the posterior pituitary gland presenting with Aspergillus sp. sinus infection.

PubMed

Bridenstine, Mark; Kerr, Janice M; Lillehei, Kevin O; Kleinschmidt-DeMasters, Bette K

2013-01-01

Gangliocytic lesions of the pituitary gland producing Cushing's disease are extremely rare entities that may exist with or without a pituitary adenoma. The latter have been designated mixed pituitary adenoma-gangliocytomas, the majority of which produce growth hormone, not adrenocorticotropin (ACTH), and are localized to the anterior gland. We now report an immunocompetent woman with hypercortisolism who presented with an intranasal aspergilloma eroding the bony sellar floor. The fungal ball was contiguous with, and extended into, a large neurohypophyseal-centered mass. Transsphenoidal resection revealed a gangliocytic lesion of the posterior gland with small clusters of intimately admixed ACTH-immunoreactive adenoma cells as the cause of her Cushing's disease. Rare transitional sizes and shapes of cells coupled with immunohistochemical findings supported interpretation as advanced neuronal metaplasia within an ACTH adenoma. This mixed ACTH adenoma-gangliocytoma is the first example to present clinically with an opportunistic infection.

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans.

PubMed

Sanapareddy, Nina; Legge, Ryan M; Jovov, Biljana; McCoy, Amber; Burcal, Lauren; Araujo-Perez, Felix; Randall, Thomas A; Galanko, Joseph; Benson, Andrew; Sandler, Robert S; Rawls, John F; Abdo, Zaid; Fodor, Anthony A; Keku, Temitope O

2012-10-01

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn's disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1-V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria from 87 taxa than controls; only 5 taxa were more abundant in control samples. The magnitude of the differences in the distal gut microbiota between patients with adenomas and controls was more pronounced than that of any other clinical parameters including obesity, diet or family history of CRC. This suggests that sequence analysis of the microbiota could be used to identify patients at risk for developing adenomas.

Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma.

PubMed

Moy, Andrea P; Arora, Kshitij; Deshpande, Vikram

2016-09-01

Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma. We studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity of expression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively. Diagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH. © 2016 John Wiley & Sons Ltd.

[Clinical and endoscopic features of a selected population with serrated colorectal adenomas in a private clinic in Lima - Peru].

PubMed

Castillo, Ofelia; Barreda, Carlos; Recavarren, Sixto; Barriga, José A; Salazar M, Fernando; Yriberry, Simón; Barriga, Eduardo; Salazar C, Fernando

2013-01-01

To describe the clinical and endoscopic caracteristics of a population that has only serrated polyps of colon (mainly sessile serrated adenomas) in a private clinic in Lima, Perú, from 2009-2011. Retrospective study conducted at the endoscopy center of Clinic Ricardo Palma, Lima, Peru. Olympus colonoscope was used with high definition, including NBI (narrow band imaging) and electronic magnification. Patients had pathologic diagnosis of “polyps and / or colorectal serrated adenomas” and excluded those with synchronous tubular or villous adenomas. Images were evaluated by two endoscopists and then by a third gastroenterologist. We found 201 serrated polyps in 108 patients. Women were 60.2% and overweight predominated. Eighty (74.1%) had only one serrated adenoma and 23 (21.3%) with at least one synchronous hyperplastic polyp. The average size of sessile serrated adenomas was 5.12 mm (± 3.87 DS) and the flat type was 91 (58.7%). There were significant differences in the diameter of sessile serrated adenomas between the distal and proximal colon (4.47 mm ± 2.23 vs. 6.90 mm ± 6.25; p<0.000). The common features of sessile serrated adenomas were: White (31/36, 86.1%), smooth (28/36, 77.8%) and regular margins (26/36, 72.2%). There was a relationship between vascular pattern according NBI and serrated polyp histology (p=0.024). The endoscopic features of sessile serrated adenomas can evade detection to white light. NBI is a useful tool to define some features of these lesions.

TERT promoter mutations: a genetic signature of benign and malignant thyroid tumours occurring in the context of tinea capitis irradiation.

PubMed

Boaventura, Paula; Batista, Rui; Pestana, Ana; Reis, Marta; Mendes, Adélia; Eloy, Catarina; Sobrinho-Simões, Manuel; Soares, Paula

2017-01-01

The aim of this study is to evaluate the frequency and molecular characteristics of TERTp mutations in thyroid adenomas and carcinomas occurring in the low-dose radiation exposure tinea capitis setting. Twenty-seven patients with 34 well-differentiated thyroid carcinomas and 28 patients with 29 follicular adenomas diagnosed in a Portuguese tinea capitis cohort were studied. Blood samples were obtained from all the patients. Screening for TERTp mutations was performed by PCR amplification followed by Sanger sequencing. A series of 33 sporadic thyroid adenomas was used as control. TERTp mutations were detected in six of the 28 patients with adenoma (21.4%) and in four of the 27 patients with carcinoma (14.8%). Three tumours (two carcinomas and one adenoma) had the tandem mutation -124/-125 GG>AA (30.0%), whereas the remaining seven had the -124G > A. The 20.7% frequency of TERTp mutations in adenomas contrasts with the absence of mutations in the adenomas from the control group and from most series on record, whereas the one found in carcinomas (11.8%) is similar to those reported in the literature for sporadic carcinomas. TERTp mutations, including the tandem mutation -124/-125 GG>AA not described previously in thyroid tumours, appear to represent a genetic signature for thyroid tumours in patients submitted to low-dose X-ray irradiation. The high frequency of TERTp mutations in the adenomas of our cohort contrasts with their absence in sporadically occurring, as well as in adenomas of the Chernobyl series. © 2017 European Society of Endocrinology.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

PubMed

Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

2006-01-01

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

PubMed

Kim, Tae-Min; An, Chang Hyeok; Rhee, Je-Keun; Jung, Seung-Hyun; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Lee, Sug Hyung; Chung, Yeun-Jun

2015-09-29

Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four-stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a 'parallel' evolution of synchronous adenoma-to-carcinoma, rather than a 'stepwise' evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent.

Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8.

PubMed

Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A

2006-02-01

The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.

A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

PubMed

Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

2016-06-01

A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

Expression of the pituitary transcription factor Ptx-1, but not that of the trans-activating factor prop-1, is reduced in human corticotroph adenomas and is associated with decreased alpha-subunit secretion.

PubMed

Skelly, R H; Korbonits, M; Grossman, A; Besser, G M; Monson, J P; Geddes, J F; Burrin, J M

2000-07-01

We have studied the expression of the pituitary transcription factors Ptx-1 and Prop-1 in a series of 34 pituitary adenomas fully characterized for in vitro hormone secretion and histological staining. In studies involving mammalian cell lines, the pituitary transcription factor Ptx-1 has been shown to be a pituitary hormone panactivator, whereas more recent studies have shown that it plays an important role in alpha-subunit gene expression. Its expression has not been examined previously in human pituitary adenomas characterized by in vitro hormone secretory profiles. Of the 34 pituitary adenomas studied, Ptx-1 expression was reduced by more than 50% compared to that of the housekeeping gene human glyceraldehyde-3-phosphate dehydrogenase in the 6 corticotroph adenomas, which also had significantly reduced alpha-subunit production (all 6 tumors secreting < or =0.5 ng/24 h). Mutations of the pituitary transcription factor Prop-1, which is responsible for the syndrome of Ames dwarfism in mice, are being increasingly recognized as a cause of combined pituitary hormone deficiency in humans, although ACTH deficiency has been described only once. Prop-1 expression was detected in all 34 pituitary adenomas, including 6 corticotroph adenomas and 5 gonadotroph adenomas. The expression of Prop-1 has not been described previously in these cell phenotypes.

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.

PubMed

Sun, Pin; Zhu, Xiangzhu; Shrubsole, Martha J; Ness, Reid M; Hibler, Elizabeth A; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Hou, Lifang; Smalley, Walter E; Edwards, Todd L; Giovannucci, Edward; Zheng, Wei; Dai, Qi

2017-09-01

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)]. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary Choline and Betaine and the Risk of Distal Colorectal Adenoma in Women

PubMed Central

Cho, Eunyoung; Willett, Walter C.; Colditz, Graham A.; Fuchs, Charles S.; Wu, Kana; Chan, Andrew T.; Zeisel, Steven H.; Giovannucci, Edward L.

2008-01-01

Background Choline and betaine are involved in methyl-group metabolism as methyl-group donors; thus, like folate, another methyl-group donor, they may be associated with a reduced risk of colorectal adenomas. No epidemiologic study has examined the association of intake of these nutrients and colorectal adenoma risk. Methods We investigated the relationship between intakes of choline and betaine and risk of colorectal adenoma in US women enrolled in the Nurses' Health Study. Dietary intake was measured by food-frequency questionnaires, and individual intakes of choline and betaine were calculated by multiplying the frequency of consumption of each food item by its choline and betaine content and summing the nutrient contributions of all foods. Logistic regression models were used to calculate adjusted odds ratios (as approximations for relative risks) and 95% confidence intervals (CIs) of colorectal adenoma. All statistical tests were two-sided. Results Among 39 246 women who were initially free of cancer or polyps and who had at least one endoscopy from 1984 through 2002, 2408 adenoma cases were documented. Increasing choline intake was associated with an elevated risk of colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake, relative to the lowest quintile, were 1.03 (0.90 to 1.18), 1.01 (0.88 to 1.16), 1.23 (1.07 to 1.41), and 1.45 (1.27 to 1.67; Ptrend<.001). Betaine intake had a nonlinear inverse association with colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake were 0.94 (0.83 to 1.07), 0.85 (0.75 to 0.97), 0.86 (0.75 to 0.98), and 0.90 (95% CI = 0.78 to 1.04; Ptrend = .09). Among individual sources of choline, choline from phosphatidylcholine and from sphingomyelin were each positively related to adenoma risk. Conclusions Our findings do not support an inverse association between choline intake and risk of colorectal adenoma. The positive association between choline intake and colorectal adenoma that we observed could represent effects of other components in the foods from which choline was derived and should be investigated further. PMID:17686825

APC gene mutations in individuals with possible attenuated familial adenomatous polyposis coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frayling, J.M.; Talbot, J.; Harocopos, C.A.

Spirio et al. have described an attenuated form of familial adenomatous polyposis (FAP) termed AAPC, where affected individuals have been found to have mutations in exons 3 & 4 of the APC gene. AAPC expression within a family appears to be extremely variable and can overlap clinically with FAP, giving rise to between zero and a few hundred adenomas. The phenotypic range associated with AAPC mutations is undefined and the frequency in the population of such alleles of the APC gene is unknown. In addition, it is as yet unclear how many cases of sporadic colorectal adenomas might have AAPC.more » In order to address this we have identified 110 individuals having a phenotype compatible with a diagnosis of AAPC, in three groups: (1) 30 individuals (15m, 15f; median age = 55y, range 8-71y) with some or all of the following: colonic adenomas (28 cases); colorectal cancer (12 cases); extra-colonic features of FAP, either desmoid tumours (4 cases, including 2 without colonic adenomas) or sebaceous cysts (2 cases). Sixteen cases had a family history of adenomas/colorectal cancer/extra-colonic features of FAP. (2) 16 individuals (10m, 6f) from the St. Mark`s Polyposis Registry, diagnosed with FAP (including a family history), who had unusually few adenomas (median = 200) at colectomy (median age = 43y, range 17-62y). (3) 64 individuals (43m, 21f) from the St. Mark`s Hospital Adenoma Follow-up Study who either had >4 adenomas at presentation (median total adenomas = 9), or >4 adenomas detected during follow-up (median total adenomas = 9). Genomic DNA was obtained from these individuals and exons 1-4 of the APC gene were amplified by PCR. Chemical cleavage of mismatch was used to screen for mutations, followed by sequencing if variant bands were found. Germ-line mutations have been identified in exons 3 and 4 in a proportion of these individuals, thus extending the clinical spectrum of phenotypes associated with mutations in this region of the APC gene.« less

Combined changes in Wnt signaling response and contact inhibition induce altered proliferation in radiation-treated intestinal crypts

PubMed Central

Dunn, S.-J.; Osborne, J. M.; Appleton, P. L.; Näthke, I.

2016-01-01

Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis. PMID:27053661

Male reproductive tract lesions at 6, 12, and 18 months of age following in utero exposure to di(n-butyl) phthalate.

PubMed

Barlow, Norman J; McIntyre, Barry S; Foster, Paul M D

2004-01-01

In utero exposure of male rats to the antiandrogen di(n-butyl) phthalate (DBP) leads to decreased anogenital distance (AGD) on postnatal day (PND) 1, increased areolae retention on PND 13, malformations in the male reproductive tract, and histologic testicular lesions including marked seminiferous epithelial degeneration and a low incidence of Leydig cell (LC) adenomas on PND 90. One objective of this study was to determine the incidence and persistence of decreased AGD, increased areolae retention, and LC adenomas in adult rats following in utero DBP exposure. A second objective was to determine whether AGD and areolae retention during the early postnatal period are associated with lesions in the male reproductive tract. Pregnant Crl:CD(SD)BR rats were gavaged with corn oil or DBP at 100 or 500 mg/kg/day, 10 dams per group. Three replicates of rats (n = 30 rats per replicate) were exposed from gestation day 12 to 21 and the male offspring allowed to mature to 6, 12, or 18 months of age. Gross malformations in the male reproductive tract and histologic lesions in the testes were similar to those previously described. However, testicular dysgenesis, a lesion of proliferating LCs and aberrant tubules that has not been previously described in DBP-exposed testes, was diagnosed. The incidence of this lesion was approximately 20% unilateral and 7-18% bilateral in the high-dose group and was similar among all ages examined, implicating a developmental alteration rather than an age-related change. AGD and areolae retention were found to be permanent changes following in utero exposure to 500 mg/kg/day of DBP. Decreased AGD was a sensitive predictor of lesions in the male reproductive tract, relatively small changes in AGD were associated with a significant incidence of male reproductive malformations. In utero DBP exposure induced proliferative developmental lesions, some of which would have been diagnosed as LC adenomas by the morphological criteria set forth by the Society of Toxicologic Pathology. However, these lesions were dissimilar to traditional LC adenomas as the LCs were poorly differentiated and the lesions contained aberrant seminiferous tubules. While the morphology and incidence of this DBP-induced testicular developmental lesion has been fully characterized by this study, the detailed pathogenesis warrants further investigation.

Meat, meat cooking methods and preservation, and risk for colorectal adenoma.

PubMed

Sinha, Rashmi; Peters, Ulrike; Cross, Amanda J; Kulldorff, Martin; Weissfeld, Joel L; Pinsky, Paul F; Rothman, Nathaniel; Hayes, Richard B

2005-09-01

Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo[4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma.

Noncirrhotic hepatocellular carcinoma: derivation from hepatocellular adenoma? Clinicopathologic analysis

PubMed Central

Liu, Ta-Chiang; Vachharajani, Neeta; Chapman, William C.; Brunt, Elizabeth M.

2018-01-01

The majority of hepatocellular carcinomas arise in background chronic liver disease, particularly cirrhosis. The pathogenesis of non-cirrhotic hepatocellular carcinomas remains unclear. While malignant transformation reportedly occurs in <15% of hepatocellular adenoma, the prevalence of noncirrhotic hepatocellular carcinomas arising from a pre-existing adenoma is a challenge to study. Cirrhotic hepatocellular carcinoma and hepatocellular adenoma may be subclassified by molecular pathways, but little is known in noncirrhotic hepatocellular carcinoma. We aim to delineate clinical, morphologic and immunohistochemical features of noncirrhotic hepatocellular carcinoma to evaluate for possible derivation from hepatocellular adenoma. We evaluated the clinicopathologic features of 74 noncirrhotic hepatocellular carcinomas from 72 patients for underlying clinical conditions and immunohistochemical markers known to be associated with hepatocellular adenoma. Men were more commonly affected (59%); however, in the < 50 year old group, women predominated (8:1). The age range was wide: 18year – 83year; median 64year. Underlying liver diseases were identified in only 7%; however 25% had diabetes mellitus, 69% were overweight or obese, and 58% had metabolic syndrome. Only 50% of the noncirrhotic hepatocellular carcinoma were encapsulated. As published in hepatocellular adenoma, multifocality and larger tumor size were more common in liver fatty acid binding protein-negative noncirrhotic hepatocellular carcinoma. Beta-catenin nuclear positivity was uncommon (5%), and was restricted to hepatocellular carcinomas in older men. Serum amyloid A positivity was not restricted to any subtype. In summary, we present the largest series to date examining noncirrhotic hepatocellular carcinoma. We evaluated these with current hepatocellular adenoma subclassification markers for possible associations. Thirty percent of the 74 noncirrhotic hepatocellular carcinoma had some clinical, morphological or immunophenotypical associations currently described in hepatocellular adenoma. Our data also confirm the association of noncirrhotic hepatocellular carcinoma in middle aged to elderly men, an association with metabolic syndrome, and, as with hepatocellular adenoma, that women predominated in the noncirrhotic hepatocellular carcinoma subjects < 50 years of age. PMID:24051694

Meat intake and risk of colorectal polyps: results from a large population-based screening study in Germany.

PubMed

Carr, Prudence R; Holleczek, Bernd; Stegmaier, Christa; Brenner, Hermann; Hoffmeister, Michael

2017-06-01

Background: Red and processed meats have been shown to be associated with colorectal adenomas in many, but not all, studies, and the association according to the type of colorectal adenoma or the location in the colorectum is unclear. Objectives: We investigated the association of meat intake in relation to colorectal polyps and further investigated the association according to histologic subtypes and subsites in a large population-based screening study in Germany. Design: In this cross-sectional study, 15,950 participants aged ≥55 y underwent a screening colonoscopy. We calculated prevalence ratios (PRs) and 95% CIs for associations between meat intake and the most-advanced findings from a colonoscopy with the use of log binomial regression. Results: Overall, 3340 participants (20.4%) had nonadvanced adenomas, 1643 participants (10.0%) had advanced adenomas, and 189 participants (1.2%) had colorectal cancer. We observed no statistically significant association between red or processed meat consumption and the prevalence of any adenomas or advanced adenomas [highest compared with lowest: red meat, PR: 1.07 (95% CI: 0.83, 1.37); processed meat, PR: 1.11 (95% CI: 0.91, 1.36)]. In site-specific analyses, although no dose-response relation was observed, processed meat was positively associated with the prevalence of advanced adenomas in the rectum only (multiple times per day compared with <1 time/wk, PR: 1.87; 95% CI: 1.19, 2.95). Poultry intake was not associated with any outcome. Conclusions: On the basis of this large colonoscopy-based study, there are no significant associations between red or processed meat intake and the prevalence of any adenomas or advanced adenomas. However, processed meat may be positively associated with the prevalence of advanced adenomas in the rectum, but prospective cohort studies are needed to further clarify this association. There is no association between poultry consumption and the prevalence of colorectal polyps in this study. © 2017 American Society for Nutrition.

Differential diagnosis between gallbladder adenomas and cholesterol polyps on contrast-enhanced harmonic endoscopic ultrasonography.

PubMed

Park, Chan Hyuk; Chung, Moon Jae; Oh, Tak Geun; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Kim, Hyunki; Hwang, Ho Kyoung; Lee, Woo Jung; Song, Si Young

2013-04-01

Differential diagnosis between gallbladder (GB) adenomas and cholesterol polyps based on ultrasonography or endoscopic ultrasonography (EUS) is challenging because they have similar echogenicity and morphology. We evaluated the usefulness of contrast-enhanced harmonic EUS (CEH-EUS) for differentiating between GB adenomas and cholesterol polyps. Between June 2010 and December 2011, a total of 87 patients with GB polyps who underwent a CEH-EUS were reviewed retrospectively. Of the 87 patients, 57 had a cholecystectomy. Of these, 34 patients were diagnosed with adenoma, cholesterol polyp, adenocarcinoma, or adenomyomatosis pathology. The remaining 23 patients were not diagnosed with GB polyps because their lesions separated from the GB mucosal layer during pathological sampling. On CEH-EUS, homogeneous and heterogeneous enhancement was shown in 6 and 2 patients with adenoma and in 4 and 8 patients with cholesterol polyps, respectively. Sensitivity and specificity of CEH-EUS for differential diagnosis of GB adenomas from cholesterol polyps based on the enhancement pattern were 75.0 and 66.6 %, respectively. CEH-EUS might be useful for distinguishing GB adenomas and cholesterol polyps based on enhancement patterns. However, an additional technique such as quantitative perfusion analysis is necessary because visual assessment of CEH-EUS images is subjective.

Pleomorphic adenoma of the palate in a child.

PubMed

Bovino, Brian F; Sohn, Andy; Winston, Daniel

2013-01-01

Presented is a pleomorphic adenoma of the palate in a 12-year-old boy. Pleomorphic adenoma is usually found in adults and is rarely found in patients under 20 years of age. We present initial exam, diagnosis, treatment and a review of literature.

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

PubMed

Torlakovic, Emina Emilia; Gomez, Jose D; Driman, David K; Parfitt, Jeremy R; Wang, Chang; Benerjee, Tama; Snover, Dale C

2008-01-01

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, chi test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to "ectopic crypts" and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between SSA and TSA, because these architectural abnormalities may well be a reflection of abnormalities in genetically programmed mucosal development.

Non-shivering thermogenesis during prostaglandin E1 fever in rats: role of the cerebral cortex.

PubMed

Monda, M; Amaro, S; De Luca, B

1994-07-18

We have tested the hypothesis that there is a role for the cerebral cortex in the control of non-shivering thermogenesis during fever induced by prostaglandin E1 (PGE1). While under urethan anesthesia, the firing rate of nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc) and oxygen (O2) consumption were monitored during the fever from PGE1 injection (400 and 800 ng) in a lateral cerebral ventricle in controls and in functionally decorticated Sprague-Dawley rats. Rats were functionally decorticated by applying 3.3 M KCl solution on the frontal cortex which causes cortical spreading depression (CSD). Pyrogen injections caused dose-related increases in firing rate, TIBAT, Tc and O2 consumption and CSD reduced these enhancements. Our findings indicate that the cerebral cortex could be involved in the control of non-shivering thermogenesis during PGE1-induced febrile response.

Hydrogen Bond Induces Hierarchical Self-Assembly in Liquid-Crystalline Block Copolymers.

PubMed

Huang, Shuai; Pang, Linlin; Chen, Yuxuan; Zhou, Liming; Fang, Shaoming; Yu, Haifeng

2018-03-01

Microphase-separated structures of block copolymers (BCs) with a size of sub-10 nm are usually obtained by hydrogen-bond-induced self-assembly of BCs through doping with small molecules as functional additives. Here, fabrication of hierarchically self-assembled sub-10 nm structures upon microphase separation of amphiphilic liquid-crystalline BCs (LCBCs) at the existence of hydrogen bonds but without any dopants is reported. The newly introduced urethane groups in the side chain of the hydrophobic block of LCBCs interact with the ether groups of the hydrophilic poly(ethylene oxide) (PEO) block, leading to imperfect crystallization of the PEO blocks. Both crystalline and amorphous domains coexist in the separated PEO phase, enabling a lamellar structure to appear inside the PEO nanocylinders. This provides an elegant method to fabricate controllable sub-10 nm microstructures in well-defined polymer systems without the introduction of any dopants. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MDI Exposure for Spray-On Truck Bed Lining.

PubMed

Lofgren, Don J; Walley, Terry L; Peters, Phillip M; Weis, Marty L

2003-10-01

Worker exposure to MDI (methylenediphenyl isocyanate) in the sprayed-on truck bed lining industry was assessed by examining Washington State OSHA inspection files and industrial insurance records. The industry uses MDI to form a protective urethane coating on pick-up truck beds. The lining is applied by a worker using a handheld spray gun with application equipment at temperatures and pressures specified by the urethane supplier. Inspections with MDI sampling were initially identified by searching the agency's laboratory database and were further screened for the targeted process. Data for 13 employers was found and extracted from the inspection records. All were small companies with only 1 to 2 workers exposed to MDI; 10 of the 13 employers had started the bed lining service within the last 4 years. The process was found in truck bed lining specialty shops as well as in other truck-related businesses. Six different urethane products were used with reported MDI monomer concentrations of up to 75 percent along with varying concentrations of MDI pre-polymers and other reactants and solvents. Sampling for MDI by inspectors found 7 worksites with worker exposure in excess of the state and OSHA ceiling limit of 0.200 mg/M(3). Deficiencies in respirator programs and engineering controls for MDI were cited. A review of the industrial insurance records found a total of five MDI-related claims at 4 inspected worksites, two for new-onset asthma. It was concluded that workers in the urethane sprayed-on truck bed lining industry are at an increased risk of developing illnesses associated with isocyanate exposure. Interventions are needed to further assess the hazard as well as motivate and assist franchisers, distributors, and retailers to implement effective engineering controls and respiratory protection programs in this nationally emerging small employer industry.

Lamb Wave Dispersion Ultrasound Vibrometry (LDUV) Method for Quantifying Mechanical Properties of Viscoelastic Solids

PubMed Central

Nenadic, Ivan Z.; Urban, Matthew W.; Mitchell, Scott A.; Greenleaf, James F.

2011-01-01

Diastolic dysfunction is the inability of the left ventricle to supply sufficient stroke volumes under normal physiological conditions and is often accompanied by stiffening of the left-ventricular myocardium. A noninvasive technique capable of quantifying viscoelasticity of the myocardium would be beneficial in clinical settings. Our group has been investigating the use of Shearwave Dispersion Ultrasound Vibrometry (SDUV), a noninvasive ultrasound based method for quantifying viscoelasticity of soft tissues. The primary motive of this study is the design and testing of viscoelastic materials suitable for validation of the Lamb wave Dispersion Ultrasound Vibrometry (LDUV), an SDUV-based technique for measuring viscoelasticity of tissues with plate-like geometry. We report the results of quantifying viscoelasticity of urethane rubber and gelatin samples using LDUV and an embedded sphere method. The LDUV method was used to excite antisymmetric Lamb waves and measure the dispersion in urethane rubber and gelatin plates. An antisymmetric Lamb wave model was fitted to the wave speed dispersion data to estimate elasticity and viscosity of the materials. A finite element model of a viscoelastic plate submerged in water was used to study the appropriateness of the Lamb wave dispersion equations. An embedded sphere method was used as an independent measurement of the viscoelasticity of the urethane rubber and gelatin. The FEM dispersion data were in excellent agreement with the theoretical predictions. Viscoelasticity of the urethane rubber and gelatin obtained using the LDUV and embedded sphere methods agreed within one standard deviation. LDUV studies on excised porcine myocardium sample were performed to investigate the feasibility of the approach in preparation for open-chest in vivo studies. The results suggest that the LDUV technique can be used to quantify mechanical properties of soft tissues with a plate-like geometry. PMID:21403186

Lamb wave dispersion ultrasound vibrometry (LDUV) method for quantifying mechanical properties of viscoelastic solids.

PubMed

Nenadic, Ivan Z; Urban, Matthew W; Mitchell, Scott A; Greenleaf, James F

2011-04-07

Diastolic dysfunction is the inability of the left ventricle to supply sufficient stroke volumes under normal physiological conditions and is often accompanied by stiffening of the left-ventricular myocardium. A noninvasive technique capable of quantifying viscoelasticity of the myocardium would be beneficial in clinical settings. Our group has been investigating the use of shear wave dispersion ultrasound vibrometry (SDUV), a noninvasive ultrasound-based method for quantifying viscoelasticity of soft tissues. The primary motive of this study is the design and testing of viscoelastic materials suitable for validation of the Lamb wave dispersion ultrasound vibrometry (LDUV), an SDUV-based technique for measuring viscoelasticity of tissues with plate-like geometry. We report the results of quantifying viscoelasticity of urethane rubber and gelatin samples using LDUV and an embedded sphere method. The LDUV method was used to excite antisymmetric Lamb waves and measure the dispersion in urethane rubber and gelatin plates. An antisymmetric Lamb wave model was fitted to the wave speed dispersion data to estimate elasticity and viscosity of the materials. A finite element model of a viscoelastic plate submerged in water was used to study the appropriateness of the Lamb wave dispersion equations. An embedded sphere method was used as an independent measurement of the viscoelasticity of the urethane rubber and gelatin. The FEM dispersion data were in excellent agreement with the theoretical predictions. Viscoelasticity of the urethane rubber and gelatin obtained using the LDUV and embedded sphere methods agreed within one standard deviation. LDUV studies on excised porcine myocardium sample were performed to investigate the feasibility of the approach in preparation for open-chest in vivo studies. The results suggest that the LDUV technique can be used to quantify the mechanical properties of soft tissues with a plate-like geometry.

Primary aldosteronism: results of adrenalectomy for nonsingle adenoma.

PubMed

Quillo, Amy R; Grant, Clive S; Thompson, Geoffrey B; Farley, David R; Richards, Melanie L; Young, William F

2011-07-01

Historically, treatment of confirmed primary aldosteronism has been adrenalectomy for unilateral adenoma; bilateral hypersecretion is treated medically. Increasingly, we use adrenal venous sampling (AVS) to define unilateral hypersecretion. Histology of glands resected based on AVS often reveals multiple nodules or hyperplasia. The aim of this study was to compare patients with multiple nodules or hyperplasia with those with single adenoma with regard to cure, preoperative imaging, AVS ratio, and biochemical evaluation to determine if a nonsingle adenoma (NSA) process could be predicted to impact extent of adrenalectomy. This was a retrospective study reviewing a single-institutional surgical experience at a tertiary academic center from 1993 to 2008, during which 215 patients with primary aldosteronism underwent unilateral adrenalectomy based on imaging of a single adenoma (normal contralateral gland) or AVS ratios. Histology included single adenoma versus NSA; cure was defined as normal immediate postoperative plasma or urine aldosterone level, normal aldosterone:renin ratio, or normotension without antihypertensive medications. Follow-up (mean 13 months, range 0 to 185 months) was available for 167 patients: 132 (79%) single adenoma and 35 (21%) NSA. All 35 patients with NSA and 128 patients (97%) with single adenoma were cured. Imaging studies correctly predicted NSA in 29% and 57% when combined with AVS. Identifying patients with NSA preoperatively was impossible biochemically: mean serum and urinary aldosterone levels and AVS ratios were not different than those of the single adenoma group. Twenty-one percent of patients had NSA, all cured by unilateral adrenalectomy. No preoperative evaluation reliably predicted NSA. Therefore, total unilateral adrenalectomy was safest given the potential for incomplete resection with partial adrenalectomy. Accurate AVS is highly predictive of cure irrespective of the unilateral adrenal histology. Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential of Polyps.

PubMed

Druliner, Brooke R; Ruan, Xiaoyang; Johnson, Ruth; Grill, Diane; O'Brien, Daniel; Lai, Tsung-Po; Rashtak, Shahrooz; Felmlee-Devine, Donna; Washechek-Aletto, Jill; Malykh, Andrei; Smyrk, Thomas; Oberg, Ann; Liu, Hongfang; Shay, Jerry W; Ahlquist, David A; Boardman, Lisa A

2016-09-01

Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. Tissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients. The mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04-1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01. Adenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management.

Double separate versus contiguous pituitary adenomas: MRI features and endocrinological follow up.

PubMed

Roberts, Sammie; Borges, Manuel Thomas; Lillehei, Kevin O; Kleinschmidt-DeMasters, B K

2016-10-01

Double pituitary adenomas are defined as two adenomas within a gland. These have distinct light microscopic and immunohistochemical features and may be clearly-separate or contiguous. Most reports have focused on the various hormonal combinations in double tumors rather than on any potential increased risk for residual mass or endocrinopathy. Departmental files were searched to identify all double adenomas from 1/1/2000 to 3/1/2016, with review of magnetic resonance imaging (MRI) to determine if the dual nature of the lesions could be discerned retrospectively after histologic diagnosis of double adenoma. All cases were immunostained for standard anterior pituitary hormones. Eight cases were identified: 2 follicle-stimulating hormone (FSH)/alpha subunit (ASU) + prolactinoma (PRL); 1 PRL + corticotroph (ACTH); 1 hormone-negative + PRL; 1 ACTH + ASU/growth hormone (GH)/PRL; 1 GH/PR + PRL; 1 FSH/ASU, + ACTH; 1 GH + luteinizing hormone (LH). One patient had clearly-separate lesions identified preoperatively and required two surgical procedures for gross total resection. A second patient had 2 lesions recognized at surgery and afterwards on retrospective neuroimaging. The remaining 6 patients had double adenomas discovered at the time of histologic examination that were not resolvable at surgery or on retrospective neuroimaging. Four patients, 2 with clearly-separate and 2 with contiguous double adenomas, had persistent MRI abnormalities, and one had continued endocrine abnormalities. Double contiguous pituitary adenomas are difficult to anticipate preoperatively or to resolve intraoperatively. Although double contiguous adenomas are much more common than double separate lesions, both have a risk for subtotal resection and, thus, residual mass and/or endocrinopathy may ensue.

Development of new non-invasive tests for colorectal cancer screening: the relevance of information on adenoma detection.

PubMed

Haug, Ulrike; Knudsen, Amy B; Lansdorp-Vogelaar, Iris; Kuntz, Karen M

2015-06-15

Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50-years-old persons to whom CRC screening is offered from age 50-75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29-44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation. © 2014 UICC.

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

PubMed

Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Temporal and spatial changes of cells positive for stem-like markers in different compartments and stages of human colorectal adenoma-carcinoma sequence

PubMed Central

Cui, Guanglin; Xu, Gang; Zhu, Li; Pang, Zhigang; Zheng, Wei; Li, Zhenfeng; Yuan, Aping

2017-01-01

Considerable evidence supports the idea that stem-like cells may play an essential role during the development of colorectal cancer (CRC). To accomplish this aim, we use immunohistochemistry (IHC) and double IHC with different potential stem-like markers, anti-musashi (Msi), anti-CD133, anti- LGR5 and anti-ALDH1 to examine the presentation of stem-like cells in different compartments including adenoma/CRC epithelium, transitional crypts and tumor stroma in colorectal adenoma and CRC. The results showed that cells positive for stem-like markers were remarkably increased in number and frequently observed in the adenoma/CRC epithelium, transitional crypts and tumor stroma. Notably, the population of cells positive for stem-liker markers was expanded from the base to the middle part of the transitional crypt in both adenoma and CRC tissues, reflecting that stem-like cells are likely involved in the process of colorectal tumorigenesis. Counting results showed that the grading scores of cells positive for LGR5 and ALDH1 in the adenoma/CRC epithelium were significantly increased relative with the control epithelium, and associated with the degree of dysplasia in the adenoma and node involvement in the CRC (all P < 0.05). In addition, the density of cells positive for stem–like markers in the adenomatous/cancerous stroma was also increased and paralleled an increase in the density of proliferative stromal cells labeled by PCNA, which were primarily identified as vimentin positive fibroblasts. Our results have revealed a changed temporal and spatial presentation of stem-like markers in different stages of human colorectal adenoma-carcinoma sequence, which might be a hallmark of the adenoma-carcinoma transition. PMID:28484082

Adult weight gain and colorectal adenomas-a systematic review and meta-analysis.

PubMed

Schlesinger, S; Aleksandrova, K; Abar, L; Vieria, A R; Vingeliene, S; Polemiti, E; Stevens, C A T; Greenwood, D C; Chan, D S M; Aune, D; Norat, T

2017-06-01

Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

PubMed Central

Hosono, Kunihiro; Yamada, Eiji; Endo, Hiroki; Takahashi, Hirokazu; Inamori, Masahiko; Hippo, Yoshitaka; Nakagama, Hitoshi; Nakajima, Atsushi

2012-01-01

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis. PMID:23082052

Polymorphisms in genes related to inflammation and obesity and colorectal adenoma risk.

PubMed

Huang, Brian Z; Tsilidis, Konstantinos K; Smith, Michael W; Hoffman-Bolton, Judith; Visvanathan, Kala; Platz, Elizabeth A; Joshu, Corinne E

2018-05-26

We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4). Conditional logistic regression was used to calculate odds ratios (OR) for adenomas (overall and by size, histology, location, number). Polymorphisms in the inflammatory-related genes CRP, ADIPOQ, IL6, and TLR4 were observed to be associated with adenoma risk. At rs1205 in CRP, T (minor allele) carriers had a higher risk (OR 1.67, 95%CI 1.07-2.60; reference: CC) of adenomas overall and adenomas with aggressive characteristics. At rs1201299 in ADIPOQ, the AC genotype had a higher risk (OR 1.58, 95%CI 1.00-2.49) of adenomas, while the minor AA genotype had a borderline inverse association (OR 0.44, 95%CI 0.18-1.08; reference: CC). At rs1800797 in IL6, the AA genotype had a borderline inverse association (OR 0.53, 95%CI 0.27-1.05; reference: GG). Three TLR4 tagSNPs (rs10116253, rs1927911, rs7873784) were associated with adenomas among obese participants. None of these SNPs were associated with colorectal cancer in our prior study in CLUE II, possibly suggesting a different genetic etiology for early colorectal neoplasia. © 2018 Wiley Periodicals, Inc.

Risk of colorectal adenomas in patients with celiac disease: a systematic review and meta-analysis.

PubMed

Lasa, J; Rausch, A; Zubiaurre, I

Whether celiac disease increases the risk of presenting with colorectal adenoma or not, has not been extensively evaluated. This question becomes relevant when considering early screening methods in patients with the disease. The aim of our article was to determine the risk of colorectal adenomas in celiac disease patients. A computer-assisted search of the MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library, and Google Scholar databases was carried out, encompassing the time frame of 1966 to December 2016. The search strategy consisted of the following MESH terms: 'celiac disease' OR 'celiac sprue' AND 'colorectal' OR 'colorectal neoplasia' OR 'colorectal adenoma'. A fixed-effect model was used for the analyses. The first analysis dealt with the prevalence of all presentations of colorectal adenoma in patients with celiac disease and the second was on the prevalence of advanced adenomas. The outcomes were described as odds ratios (OR) with their 95% confidence intervals. The search identified 480 bibliographic citations, 17 of which were chosen for evaluation. Fourteen of those studies were rejected, leaving a final total of three for the analysis. Those studies included 367 cases of celiac disease and 682 controls. No significant heterogeneity was observed (I 2 =26%). There was no increased prevalence of colorectal adenomas in the celiac disease patients, when compared with the controls (OR: 0.94 [0.65-1.38]), and no significant difference was observed when assessing the prevalence of advanced adenomas (OR: 0.97 [0.48-1.97]). Celiac disease was not associated with an increased risk of colorectal adenomas. However, due to the limited evidence available, more studies are necessary to determine whether there is an actual association. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Immunohistochemical Expression of Matrix Metalloproteinase-7 in Human Colorectal Adenomas Using Specified Automated Cellular Image Analysis System: A Clinicopathological Study

PubMed Central

Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

2013-01-01

Background/Aim: To evaluate the immunohistochemical expression of matrix metalloproteinase-7 (MMP-7) in colorectal adenomas, and to correlate this expression with different clinicopathological parameters. Patients and Methods: The study was retrospectively designed. Thirty three paraffin blocks from patients with colorectal adenoma and 20 samples of non-tumerous colonic tissue taken as control group were included in the study. MMP-7 expression was assessed by immunohistochemistry method. The scoring of immunohistochemical staining was conducted utilizing a specified automated cellular image analysis system (Digimizer). Results: The frequency of positive immunohistochemical expression of MMP-7 was significantly higher in adenoma than control group (45.45% versus 10%) (P value < 0.001). Strong MMP-7 staining was mainly seen in adenoma cases (30.30%) in comparison with control (0%) the difference is significant (P < 0.001). The three digital parameters of MMP-7 immunohistochemical expression (Area (A), Number of objects (N), and intensity (I)) were significantly higher in adenoma than control. Mean (A and I) of MMP-7 showed a significant correlation with large sized adenoma (≥ 1cm) (P < 0.05), also a significant positive correlation of the three digital parameters (A, N, and I) of MMP-7 expression with villous configuration and severe dysplasia in colorectal adenoma had been identified (P < 0.05). Conclusion: MMP-7 plays an important role in the growth and malignant conversion of colorectal adenomas as it is more likely to be expressed in advanced colorectal adenomatous polyps with large size, severe dysplasia and villous histology. The use of automated cellular image analysis system (Digmizer) to quantify immunohistochemical staining yields more consistent assay results, converts semi-quantitative assay to a truly quantitative assay, and improves assay objectivity and reproducibility. PMID:23319034

Nipple adenoma in a female patient presenting with persistent erythema of the right nipple skin: case report, review of the literature, clinical implications, and relevancy to health care providers who evaluate and treat patients with dermatologic conditions of the breast skin.

PubMed

Spohn, Gina P; Trotter, Shannon C; Tozbikian, Gary; Povoski, Stephen P

2016-05-20

Nipple adenoma is a very uncommon, benign proliferative process of lactiferous ducts of the nipple. Clinically, it often presents as a palpable nipple nodule, a visible nipple skin erosive lesion, and/or with discharge from the surface of the nipple skin, and is primarily seen in middle-aged women. Resultantly, nipple adenoma can clinically mimic the presentation of mammary Paget's disease of the nipple. The purpose of our current case report is to present a comprehensive review of the available data on nipple adenoma, as well as provide useful information to health care providers (including dermatologists, breast health specialists, and other health care providers) who evaluate patients with dermatologic conditions of the breast skin for appropriately clinically recognizing, diagnosing, and treating patients with nipple adenoma. Fifty-three year old Caucasian female presented with a one year history of erythema and induration of the skin of the inferior aspect of the right nipple/areolar region. Skin punch biopsies showed subareolar duct papillomatosis. The patient elected to undergo complete surgical excision with right central breast resection. Final histopathologic evaluation confirmed nipple adenoma. The patient is doing well 31 months after her definitive surgical therapy. Since nipple adenoma represents a benign proliferative process of the nipple, complete surgical excision is curative. However, the coexistence of nipple adenoma and ipsilateral or contralateral breast cancer is well reported in the literature. The potential for a direct causal link or association of nipple adenoma and breast cancer cannot be fully excluded.

Associations Between Markers of Colorectal Cancer Stem Cells and Adenomas Among Ethnic Groups

PubMed Central

Leavell, Bonita J.; Van Buren, Eric; Antaki, Fadi; Axelrod, Bradley N.; Rambus, Mary Ann; Majumdar, Adhip P. N.

2013-01-01

Background and Purposes Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes. Methods We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry. Results The proportion of colonocytes that were CD44+CD166– in effluent from patients with adenomas was significantly greater than from patients without adenomas (P = 0.01); the proportion of CD44+CD166+ colonocytes was also greater (P = 0.07). Effluent from AAs with adenomas had 60 % more CD44+166– colonocytes than from CAs with adenomas. Using cutoff values of 8 % for AAs and 3 % for CAs, the proportion of CD44+166– colonocytes that had positive predictive value for detection of adenomas was 100 % for AAs and CAs, determined by receiver operator characteristic curve analysis. Conclusion The proportion of CD44+166– colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44+166– colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population. PMID:22562538

THE QUESTION "RECOVERY SPEED OR RESISTANCE INCREASE" OF THE X-IRRADIATED SKIN OF FROGS (RANA ESCULENTA) IN SMALL FRACTIONATION (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amoroso, C.; Lorenz, W.

1959-01-01

Sixty-one frogs (Rana esculenta) were irradiated in urethan anesthesia. The right upper leg was irradiated with a surface dose of 12,000 r. The left upper legs of the same animals were irradiated subsequently with a surface dose of 2 times 6000 r, respectively 3 times 4000 r at intervals of 1, 3, 6, 24, or 72 hours. The single irradiation of 12,000 r caused changes of the pigentation and formation of ulcers after 3 weeks. After 8 weeks 35 out of 61 animals had formation of ulcers. The first tendency for healing was observed after 10 weeks. By the usemore » of divided doses of 3 times 4000 r or 2 tirees 6000 r, with intervals as short as one hour, the effect of the irradiation caused less damage, probably due to increased resistence, which may have developed during the intervals between irradiations. (auth)« less

Collision tumors of the sella: coexistence of pituitary adenoma and craniopharyngioma in the sellar region

PubMed Central

2013-01-01

Collision tumors of the sellar region are relatively uncommon and consist mainly of more than one type of pituitary adenoma or a cyst or cystic tumor. The association of a pituitary adenoma and a craniopharyngioma is particularly rare. This study describes a rare occurrence in which a pituitary adenoma and a craniopharyngioma coexisted in the sellar region. The case involves a 47-year-old woman who underwent transsphenoidal surgery with subtotal tumor resection and reoperation using an interhemispheric transcallosal approach for total microsurgical resection of the tumor because the visual acuity in her left eye had re-deteriorated. Histopathological and immunohistochemical examinations of the excised tissue revealed a pituitary adenoma in the first operation and a craniopharyngioma in the second operation. Retrospective analysis found the coexistence of a pituitary adenoma and a craniopharyngioma, known as a collision tumor. Instead of the transsphenoidal approach, a craniotomy should be performed, to explore the suprasellar region. PMID:23919255

Giant pituitary adenoma: histological types, clinical features and therapeutic approaches.

PubMed

Iglesias, Pedro; Rodríguez Berrocal, Víctor; Díez, Juan José

2018-06-16

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

Association between markers of glucose metabolism and risk of colorectal adenoma.

PubMed

Rampal, Sanjay; Yang, Moon Hee; Sung, Jidong; Son, Hee Jung; Choi, Yoon-Ho; Lee, Jun Haeng; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Rhee, Jong Chul; Guallar, Eliseo; Cho, Juhee

2014-07-01

Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location. In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma. Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P = .04) for fasting glucose, 1.07 (0.99-1.15; P = .10) for insulin, 1.09 (1.02-1.18, P = .02) for HOMA, 1.09 (1.01-1.17; P = .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P = .08), 1.10 (0.98-1.24; P = .12), 1.15 (1.02-1.29; P = .02), 1.14 (1.01-1.28; P = .03), and 1.20 (1.05-1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P = .11), 1.23 (0.87-1.75; P = .24), 1.30 (0.92-1.85; P = .14), 1.13 (0.79-1.61; P = .50), and 1.67 (1.15-2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P < .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P = .002). Associations were similar for adenomas located in the distal versus proximal colon. Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System.

PubMed

Barbieri, Federica; Thellung, Stefano; Würth, Roberto; Gatto, Federico; Corsaro, Alessandro; Villa, Valentina; Nizzari, Mario; Albertelli, Manuela; Ferone, Diego; Florio, Tullio

2014-01-01

Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.

Correlation of cytoplasmic beta-catenin and cyclin D1 overexpression during thyroid carcinogenesis around Semipalatinsk nuclear test site.

PubMed

Meirmanov, Serik; Nakashima, Masahiro; Kondo, Hisayoshi; Matsufuji, Reiko; Takamura, Noboru; Ishigaki, Katsu; Ito, Masahiro; Prouglo, Yuri; Yamashita, Shunichi; Sekine, Ichiro

2003-06-01

The Semipalatinsk nuclear test site (SNTS), the Republic of Kazakhstan, has been contaminated by radioactive fallout. The alteration of oncogenic molecules in thyroid cancer around the SNTS was considered worthy of analysis because it presented the potential to elucidate the relationship between radiation exposure and thyroid cancer. This study aimed to analyze both beta-catenin and cyclin D1 expressions in thyroid carcinomas around the SNTS. We examined nine cases of chronic thyroiditis, eight cases of follicular adenomas, and 23 cases of papillary carcinomas. Immunohistochemically, all carcinomas displayed a strong cytosolic beta-catenin expression, while both chronic thyroiditis and follicular adenomas showed a significantly lower cytoplasmic beta-catenin (22.2% and 37.5%, respectively). No cyclin D1 immunoreactivity was evident in chronic thyroiditis. In contrast, 62.5% of follicular adenomas and 87.0% of papillary carcinoma showed cyclin D1 overexpression. Additionally, a strong correlation between cytoplasmic beta-catenin and cyclin D1 expression was suggested in thyroid tumors. This study revealed a higher prevalence of both aberrant beta-catenin expression and cyclin D1 overexpression in papillary thyroid cancers around the SNTS than sporadic cases. The analysis of the alteration of the Wnt signaling-related molecules in thyroid cancer around the SNTS may be important to gain an insight into radiation-induced thyroid tumorigenesis.

Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

PubMed Central

Jaszewski, Richard; Misra, Sabeena; Tobi, Martin; Ullah, Nadeem; Naumoff, Jo Ann; Kucuk, Omer; Levi, Edi; Axelrod, Bradley N; Patel, Bhaumik B; Majumdar, Adhip PN

2008-01-01

AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia. PMID:18680228

Transsphenoidal surgery assisted by a new guidance device: results of a series of 747 cases.

PubMed

Tao, Yang; Jian-wen, Gu; Yong-qin, Kuang; Li-bin, Yang; Hai-dong, Huang; Wen-tao, Yang; Xue-min, Xing

2011-10-01

The objective of this study is to report the efficacy and safety of microsurgical transsphenoidal surgery using a frame for sella guidance in a series of patients with untreated pituitary adenoma. In this study, seven hundred and forty-seven patients undergoing transsphenoidal resection of a pituitary adenoma involving use of the frame were included. Follow-up of twelve to one hundred months was performed in all patients. During the procedures using the frame, pituitary adenomas were fully exposed, and no cavernous sinus haemorrhage due to anteroposterior displacement or internal carotid artery lesion due to right-and-left deviation occurred. The duration of the surgical procedure ranged from 28 min to 87 min with a mean of 44 min. The most frequent tumour type was prolactin-secreting adenoma (32.4%), followed by clinically non-functioning adenoma (NFPA) (28.5%), growth hormone-secreting adenoma (25.0%), and adrenocorticotropin-secreting adenoma (13.7%). Normalisation of visual defects occurred in 226 (42.2%) of the 535 patients with visual disturbances. Normalisation of hormone occurred in 458 of 551 patients with endocrine-active tumour in the follow-up period. Two patients died as a consequence of surgery. The endonasal transsphenoidal technique is a safe, quick, and effective approach to pituitary adenomas. Our guidance frame allows the surgeon to open and close the wound rapidly, which avoids trajectory deviation and shortens the duration of the surgical procedure. Copyright © 2011 Elsevier B.V. All rights reserved.

High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial

PubMed Central

Lanza, Elaine; Hartman, Terryl J.; Albert, Paul S.; Shields, Rusty; Slattery, Martha; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Schatzkin, Arthur

2006-01-01

Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence. PMID:16772456

Biodegradable hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol), poly(ethylene glycol), and polycaprolactone as in situ thermogels.

PubMed

Li, Zibiao; Zhang, Zhongxing; Liu, Kerh Li; Ni, Xiping; Li, Jun

2012-12-10

This paper reports the synthesis and characterization of new hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol) (PPG), poly(ethylene glycol) (PEG), and polycaprolactone (PCL) segments as in situ thermogels. The hyperbranched poly(PPG/PEG/PCL urethane)s, termed as HBPEC copolymers, were synthesized from PPG-diol, PEG-diol, and PCL-triol by using 1,6-hexamethylene diisocyanate (HMDI) as a coupling agent. The compositions and structures of HBPEC copolymers were determined by GPC and 1H NMR spectroscopy. We carried out comparative studies of the new hyperbranched copolymers with their linear counterparts, the linear poly(PPG/PEG/PCL urethane) (LPEC) copolymer and Pluronic F127 PEG-PPG-PEG block copolymer, in terms of their self-assembly and aggregation behaviors and thermoresponsive properties. HBPEC copolymers were found to show thermoresponsive micelle formation and aggregation behaviors. Particularly, the lower critical solution temperature (LCST) of the copolymers was significantly affected by the copolymer architecture. HBPEC copolymers showed much lower LCST than LPEC, the linear counterpart. Our studies revealed that the effect of hyperbranch architecture was more prominent in the gelation of the copolymers. The aqueous solutions of HBPEC copolymers exhibited thermogelling behaviors at critical gelation concentrations (CGCs) ranging from 4.3 to 7.4 wt %. These values are much lower than those reported on other PCL-contained linear thermogelling copolymers and Pluronic F127 copolymer. In addition, the CGC of HBPEC copolymers is much lower than the control LPEC copolymer. More interestingly, at high temperatures, while LPEC and other linear thermogelling copolymers formed turbid sol, HBPEC formed a dehydrated gel. Our data suggest that these phenomena are caused by the hyperbranched structure of HBPEC copolymers, which could increase the interaction of copolymer branches and enhance the chain association through synergetic hydrogen bonding effect. The thermogelling behavior of HBPEC block copolymers was further evidenced by the 1H NMR molecular dynamic study and rheological study, which further support the above hypothesis. The hydrolytic degradation study showed that the HBPEC copolymer hydrogels are biodegradable under physiological conditions. Together with the good cell biocompatibility demonstrated by the cytotoxicity study, the new thermogelling copolymers reported in this paper could potentially be used as in situ-forming hydrogels for biomedical applications.

Charged-Iron-Particles Found in Galactic Cosmic Rays are Potent Inducers of Epithelial Ovarian Tumors.

PubMed

Mishra, Birendra; Lawson, Gregory W; Ripperdan, Ryan; Ortiz, Laura; Luderer, Ulrike

2018-05-21

Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer. Therefore, we hypothesized that charged-iron-particle irradiation induces ovarian tumorigenesis in mice. In this study, three-month-old female mice were exposed to 0 cGy (sham) or 50 cGy iron ions and aged to 18 months. The 50 cGy irradiated mice had increased weight gain with age and lack of estrous cycling, consistent with ovarian failure. A total of 47% and 7% of mice irradiated with 50 cGy had unilateral and bilateral ovarian tumors, respectively, whereas 14% of mice in the 0 cGy group had unilateral tumors. The tumors contained multiple tubular structures, which were lined with cells positive for the epithelial marker cytokeratin, and had few proliferating cells. In some tumors, packets of cells between the tubular structures were immunopositive for the granulosa cell marker FOXL2. Based on these findings, tumors were diagnosed as tubular adenomas or mixed tubular adenoma/granulosa cell tumors. In conclusion, charged-iron-particle-radiation induces ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts.

Organ differences in the impact of p27(kip1) deficiency on carcinogenesis induced by N-methyl-N-nitrosourea.

PubMed

Ogawa, Kumiko; Murasaki, Toshiya; Sugiura, Satoshi; Nakanishi, Makoto; Shirai, Tomoyuki

2013-06-01

To evaluate the impact of p27 on carcinogenesis in various organs, N-methyl-N-nitrosourea (MNU), a direct-acting alkylating agent, was given to p27 knock-out mice. Groups of 20-40 male and female mice with null, hetero- or wild-type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27-null males as compared with both wild- and hetero-type animals. Moreover, in both p27(+/+) and p27(+/-) cases, the rates for p27-positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27-positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU-induced carcinogenesis. Copyright © 2011 John Wiley & Sons, Ltd.

Resting-state functional MRI as a tool for evaluating brain hemodynamic responsiveness to external stimuli in rats.

PubMed

Paasonen, Jaakko; Salo, Raimo A; Huttunen, Joanna K; Gröhn, Olli

2017-09-01

Anesthesia is a major confounding factor in functional MRI (fMRI) experiments attributed to its effects on brain function. Recent evidence suggests that parameters obtained with resting-state fMRI (rs-fMRI) are coupled with anesthetic depth. Therefore, we investigated whether parameters obtained with rs-fMRI, such as functional connectivity (FC), are also directly related to blood-oxygen-level-dependent (BOLD) responses. A simple rs-fMRI protocol was implemented in a pharmacological fMRI study to evaluate the coupling between hemodynamic responses and FC under five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane). Temporal change in the FC was evaluated at 1-hour interval. Supplementary forepaw stimulation experiments were also conducted. Under thiobutabarbital anesthesia, FC was clearly coupled with nicotine-induced BOLD responses. Good correlation values were also obtained under isoflurane and medetomidine anesthesia. The observations in the thiobutabarbital group were supported by forepaw stimulation experiments. Additionally, the rs-fMRI protocol revealed significant temporal changes in the FC in the α-chloralose, thiobutabarbital, and urethane groups. Our results suggest that FC can be used to estimate brain hemodynamic responsiveness to stimuli and evaluate the level and temporal changes of anesthesia. Therefore, analysis of the fMRI baseline signal may be highly valuable tool for controlling the outcome of preclinical fMRI experiments. Magn Reson Med 78:1136-1146, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Strength of titanium intramedullary implant versus miniplate fixation of mandibular condyle fractures.

PubMed

Frake, Paul C; Howell, Rebecca J; Joshi, Arjun S

2012-07-01

To test the strength of internal fixation of mandibular condyle fractures repaired with titanium miniplates versus titanium intramedullary implants. Prospective laboratory experimentation in urethane mandible models and human cadaveric mandibles. Materials testing laboratory at an academic medical center. Osteotomies of the mandibular condyle were created in 40 urethane hemimandible models and 24 human cadaveric specimens. Half of the samples in each group were repaired with traditional miniplates, and the other half were repaired with intramedullary titanium implants. Anteroposterior and mediolateral loads were applied to the samples, and the displacement was measured with reference to the applied force. Titanium intramedullary implants demonstrated statistically significant improved strength and stiffness versus miniplates in the urethane model experimental groups. Despite frequent plastic deformation and mechanical failures of the miniplates, a 1.6-mm-diameter titanium intramedullary pin did not mechanically fail in any of the cases. Intramedullary implantation failures were due to secondary fracture of the adjacent cortical bone or experimental design limitations including rotation of the smooth pin implant. Mechanical implant failures that were encountered with miniplate fixation were not seen with titanium intramedullary implants. These intramedullary implants provide stronger and more rigid fixation of mandibular condyle fractures than miniplates in this in vitro model.

Effect of diisocyanate linkers on the degradation characteristics of copolyester urethanes as potential drug carrier matrices.

PubMed

Mathew, Simi; Baudis, Stefan; Neffe, Axel T; Behl, Marc; Wischke, Christian; Lendlein, Andreas

2015-09-01

In this study, the effect of three aliphatic diisocyanate linkers, L-lysine diisocyanate ethyl ester (LDI), hexamethylene diisocyanate (HDI), and racemic 2,2,4-/2,4,4-trimethyl hexamethylene diisocyanate (TMDI), on the degradation of oligo[(rac-lactide)-co-glycolide] (64:36 mol%) based polyester urethanes (PEU) was examined. Samples were characterized for their molecular weight, mass loss, water uptake, sequence structure, and thermal and mechanical properties. Compared to non-segmented PLGA, the PEU showed higher water uptake and generally degraded faster. Interestingly, the rate of degradation was not directly correlating with the hydrophilicity of the diisocyanate moieties; instead, competing intra-/intermolecular hydrogen bonds in between urethane moieties appear to substantially decrease the rate of degradation for LDI-derived PEU. By comparing microparticles (μm) and films (mm) as matrices of different dimensions, it was shown that autocatalysis remains a contributor to degradation of the larger-sized PEU matrices as it is typical for non-segmented lactide/glycolide copolymers. The shown capacity of lactide/glycolide-based multiblock copolymers to degrade faster than PLGA and exhibit improved elastic properties could be of interest for medical implants and drug release systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Syntheses and properties of elastic copoly(ester-urethane)s containing a phospholipid moiety and the fabrication of nanosheets.

PubMed

Sirithep, Wariya; Morita, Kohei; Iwano, Atsushi; Komachi, Takuya; Okamura, Yosuke; Nagase, Yu

2014-01-01

In these years, we have investigated the syntheses of novel diamine and diol monomers containing phosphorylcholine (PC) group to obtain biocompatible polymers, the backbone components of which were thermally stable and mechanically strong. In this study, the preparations of elastic copoly(ester-urethane)s containing PC group and polycarbonate segment were carried out by polycondensation and polyaddition using a diol monomer containing PC group and polycarbonate diol. It was found that the obtained polymers exhibited the high-thermal stability up to 200 °C and the elasticity derived from the soft segment. The introduction of PC group was effective to improve the resistance to the adhesions of proteins and platelets on the polymer films, which was the result of surface properties derived from the PC moiety. In addition, we tried to prepare ultra-thin polymer films composed of copoly(ester-urethane)s, so-called nanosheets. As a result, the desired nanosheets were successfully fabricated and the obtained nanosheets exhibited the high adhesive strength, indicating that the nanosheets could conform closely to the desired surfaces due to their exquisite flexibility and low roughness.

Delayed Complications After Transsphenoidal Surgery for Pituitary Adenomas.

PubMed

Alzhrani, Gmaan; Sivakumar, Walavan; Park, Min S; Taussky, Philipp; Couldwell, William T

2018-01-01

Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively, and reports are sparse about their occurrence, management, and outcome. Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia, hypopituitarism, hydrocephalus, and sinonasal complications. Our findings from this review revealed an incidence of 0.6%-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases of postoperative vasospasm occurring 8 days postoperatively, a 3.6%-19.8% rate of delayed symptomatic hyponatremia at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4%-5.8% rate of hydrocephalus within 2.2 months postoperatively. Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of Molecular Biomarkers for the Early Detection of Lung Cancer in the setting of Indeterminate Pulmonary Nodules (Lung Team Project #2) — EDRN Public Portal

Cancer.gov

To characterize intra or within subject reproducibility and variability To characterize inter or across subject variability by adenoma phenotype (normal vs. adenoma) To evaluate biomarker expression in relation to long term adenoma recurrence

Adenomas of the common bile duct in familial adenomatous polyposis

PubMed Central

Yan, Mao-Lin; Pan, Jun-Yong; Bai, Yan-Nan; Lai, Zhi-De; Chen, Zhong; Wang, Yao-Dong

2015-01-01

Familial adenomatous polyposis (FAP) or Gardner’s syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner’s syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option. PMID:25780319

Moderate Alcohol Consumption is Protective Against Colorectal Adenomas in Smokers

PubMed Central

Galanko, Joseph A.; Martin, Christopher F.; Sandler, Robert S.

2009-01-01

Background Although some studies have shown an association between alcohol consumption and colorectal adenomas, the effect of moderate alcohol consumption is not well-defined, nor is the interaction between alcohol and smoking. Aim To investigate the relationship between different levels of alcohol consumption and colorectal adenomas and to determine whether smoking modifies this relationship. Methods Eligible patients who underwent a complete colonoscopy were included (179 cases and 466 controls). Alcohol consumption was obtained from a lifestyle questionnaire. Patients were divided into three groups: 1) Abstainers: 0 drinks/week; 2) Moderate drinkers: >0-<7 drinks/week; 3) Heavy drinkers: >=7 drinks/week. Odds ratios (OR) were calculated using logistic regression, controlling for gender, age, body mass index, use of non-steroidal anti-inflammatory medications. Results were stratified by the number of years smoked. Results The proportion of patients with adenomas was 29.6% in abstainers, 22.1% in moderate drinkers, and 36.7% in heavy drinkers. There was significant modification of the relationship between alcohol consumption and colorectal adenomas by smoking. For individuals who had never smoked, heavy drinkers were at significantly increased odds of having an adenoma compared to moderate drinkers (OR 3.08; 95% CI: 1.50-6.32), while no difference was seen for abstainers (OR 0.99; 95% CI: 0.52-1.89). Similarly, among individuals who had smoked 1-14 years, heavy drinkers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.61; 95% CI: 1.04-6.51), and no difference was seen for abstainers (OR 1.02; 95% CI: 0.33-3.10). Somewhat unexpectedly, among individuals who had smoked for 15 or more years, abstainers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.04; 95% CI: 0.91-4.59), while heavy drinkers were not at increased odds of having an adenoma (OR 0.73; 95% CI: 0.27-1.97). Conclusions Consumption of less than seven alcohol drinks per week does not increase the risk of having a colorectal adenoma. We found evidence in this study that moderate alcohol consumption among long-term smokers may potentially decrease the risk of an adenoma compared to abstainers. PMID:17510802

Cytogenetic studies of mice chronically fed carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Director, A.E.; Ramsey, M.J.; Tucker, J.D.

1997-10-01

Over the past few years, we have carried out chronic feeding studies in C57BL/6 female mice. These experiments examined the effect of the chronic ingestion of a single chemical carcinogen on chromosomes. The carcinogens studied were PhIP,MeIQx, cyclophosphamide and urethane. These studies used traditional assays, such as SCEs and MN, as well as chromosome painting. In all four cases, the traditional assays showed an increase in the frequency of lesions, demonstrating that the chemicals, and/or their reactive metabolites, reached the target nuclei. This, however, seemed at odds with the data obtained from chromosome painting, which did not show an increasemore » in the frequency of stable chromosome aberrations. This discrepancy between traditional assays and chromosome painting may be due to the nature of the lesions that each assay identifies. The traditional assays tend to identify lesions on the chromatid level, where as chromosome painting identifies lesions on the chromosome level requires two or more DNA double strand breaks occurring proximally in both time and space. In other words, for exposure to a chemical carcinogen to induce an increase in chromosome aberrations as measured by chromosome painting, the chemical, or its metabolites, would have to cause a large number of double strand breaks. By applying this logic to the data obtained from the four chronic feeding studies, one can infer that the chronic ingestion of chemical carcinogens does not result in the frequent formation of double strand breaks and therefore, does not result in the frequent formation of double strand breaks and therefore, does not result in increased frequencies of stable chromosome aberrations. We must, therefore, look elsewhere for the mechanism(s) underlying carcinogenesis due to chronic exposure to chemical carcinogens.« less

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-05-14

To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-01-01

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or “high-risk” adenomas), and rated each trial’s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted. PMID:27182169

Different cytokeratin and neuronal cell adhesion molecule staining patterns in focal nodular hyperplasia and hepatic adenoma and their significance

PubMed Central

Iyer, Anita; Robert, Marie E.; Bifulco, Carlo B.; Salem, Ronald R.; Jain, Dhanpat

2013-01-01

Summary Differentiating focal nodular hyperplasia from hepatic adenoma can be challenging. Cytokeratin 7, neuronal cell adhesion molecule, and cytokeratin 19 are differentially expressed in hepatocytes, biliary epithelium, and possibly hepatic progenitor/stem cells. CD34 is known to have altered expression patterns in the hepatic endothelium in conditions associated with abnormal perfusion and in hepatocellular carcinoma. The purpose of this study was to examine the expression pattern of these markers in focal nodular hyperplasia and hepatic adenoma and assess their diagnostic use. Ten resection specimens each of hepatic adenoma and focal nodular hyperplasia (including a case of telangiectatic focal nodular hyperplasia) were selected for the study. Immunohistochemical analysis was performed using antibodies against cytokeratin 7, cytokeratin 19, neuronal cell adhesion molecule, and CD34 on formalin-fixed, paraffin-embedded sections from each case. The staining patterns and intensity for each marker were analyzed. In hepatic adenoma, the cytokeratin 7 stain revealed strong positivity in hepatocytes in patches, with a gradual decrease in the staining intensity as the cells differentiated towards mature hepatocytes. Although bile ducts were typically absent in hepatic adenoma, occasional ductules could be identified with cytokeratin 7 stain. In focal nodular hyperplasia, cytokeratin 7 showed strong staining of the biliary epithelium within the fibrous septa and staining of the peripheral hepatocytes of most lobules that was focal and weaker than hepatic adenoma. Cytokeratin 19 and neuronal cell adhesion molecule showed patchy and moderate staining in the biliary epithelium of the ductules in focal nodular hyperplasia. While in the hepatic adenoma, cytokeratin 19 showed only rare positivity in occasional cells within ductules, and neuronal cell adhesion molecule marked occasional isolated cells in the lesion. CD34 showed staining of sinusoids in the inflow areas (periportal areas) in both focal nodular hyperplasia and hepatic adenoma. One case of telangiectatic focal nodular hyperplasia revealed both hepatic adenoma–like and focal nodular hyperplasia–like staining patterns. Distinct cytokeratin 7, cytokeratin 19, and neuronal cell adhesion molecule staining patterns are seen in hepatic adenoma and focal nodular hyperplasia possibly suggest activation of different subsets of hepatic progenitor/stem cell and can be diagnostically useful. PMID:18602664

Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas

PubMed Central

2013-01-01

Background Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas. Methods This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa. Results Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6). Conclusions These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of colorectal adenomas. PMID:23442743

Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice

PubMed Central

Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; Micale, Rosanna T; La Maestra, Sebastiano; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

2014-01-01

The anti-diabetic drug metformin is endowed with anti-cancer properties. Epidemiological and experimental studies, however, did not provide univocal results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of both genders in order to detect early molecular alterations and tumors induced by mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the therapeutic dose in humans. Exposure of mice to smoke for 4 months, starting at birth, induced a systemic clastogenic damage, formation of DNA adducts, oxidative DNA damage, and extensive downregulation of microRNAs in lung after 10 weeks. Preneoplastic lesions were detectable after 7.5 months in both lung and urinary tract along with lung tumors, both benign and malignant. Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFκB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis. In smoke-exposed mice, metformin considerably decreased DNA adduct levels and oxidative DNA damage, and normalized the expression of several microRNAs. It did not prevent smoke-induced lung tumors but inhibited preneoplastic lesions in both lung and kidney. In conclusion, metformin was able to protect the mouse lung from smoke-induced DNA and microRNA alterations and to inhibit preneoplastic lesions in lung and kidney but failed to prevent lung adenomas and malignant tumors induced by this complex mixture. PMID:24683044

[Therapeutic use of somatostatin analogues in endocrinology].

PubMed

Faglia, G; Arosio, M

1992-11-01

The recent availability of the long-acting somatostatin analogue, octreotide, has allowed its therapeutical use in a wide variety of human diseases, including some digestive, neoplastic and autoimmune disorders. This review focuses on the treatment of some endocrine disorders with octreotide. Evidence is accumulating that octreotide treatment is effective in improving the cure rate of pituitary surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I levels in the vaste majority of patients. Octreotide is also effective in ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas. Moreover, octreotide has proved useful in the management of endocrine tumours of the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas, insulinomas, and carcinoids) by reducing hormone levels and in some instances the size of the primary and/or metastatic lesions. Besides the above well-established indications there are some other potential indications (non-secreting pituitary tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome) that still await further investigation. Side-effects of octreotide, particularly the formation of gallstones, should be carefully monitored.

[Sonoelastography, B-mode sonography, and color Doppler sonography findings of pleomorphic adenomas and Warthin tumors of parotid gland].

PubMed

Yerli, Hasan; Eşki, Erkan

2015-01-01

This study aims to investigate the sonoelastography (SE), B-mode sonography, and color Doppler sonography findings of the pleomorphic adenomas and Warthin tumors of the parotid gland. A total of 84 parotid masses (23 pleomorphic adenomas, 25 Warthin tumors) in 72 patients (37 males, 35 females; mean age 59 years; range 30 to 79 years) were retrospectively analyzed. For each lesion, B-mode sonography, color Doppler sonography, and SE images were evaluated. Vascularity and elasticity scores of the tumors during color Doppler sonography and SE examinations were calculated by 4-scoring method. Lobulated contour and cystic areas were more common in the pleomorphic adenomas and Warthin tumors during the B-mode sonography examination (p<0.05). Peripheral vascularity was common in more than half of the pleomorphic adenoma patients, whereas central or mixed vascularity was seen in a large group of the Warthin tumor patients (p<0.05). The mean scores on color Doppler sonography examination were 1.13±0.81 for pleomorphic adenomas and 1.96±0.97 for Warthin tumors (p<0.05). The mean scores on SE examination were 2.69±0.70 for pleomorphic adenomas and 1.83±0.63 for Warthin tumors (p<0.05). Score 1 on SE examination was found in three of five Warthin tumor patients with peripheral vascularity on color Doppler sonography. B-mode, color Doppler and elastography examinations by sonography provide some helpful findings in the differentiation of pleomorphic adenomas and Warthin tumors.

The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis.

PubMed

Cohen, Jonah; Grunwald, Douglas; Grossberg, Laurie B; Sawhney, Mandeep S

2017-10-01

Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.

Rotating night shift work, sleep, and colorectal adenoma in women.

PubMed

Devore, Elizabeth E; Massa, Jennifer; Papantoniou, Kyriaki; Schernhammer, Eva S; Wu, Kana; Zhang, Xuehong; Willett, Walter C; Fuchs, Charles S; Chan, Andrew T; Ogino, Shuji; Giovannucci, Edward; Wei, Esther K

2017-07-01

This study aims to investigate the associations of rotating night shift work history and sleep duration with risk of colorectal adenoma. We evaluated 56,275 cancer-free participants of the Nurses' Health Study II, who had their first colonoscopy or sigmoidoscopy between 1991 and 2011; rotating night shift work and sleep duration were reported by mailed questionnaire. Multivariable-adjusted logistic regression was used to estimate relative risks (RR) of colorectal adenoma, with 95% confidence intervals (CI), across categories of rotating night shift work history (none, 1-4, 5-9, and ≥10 years) and sleep duration (≤5, 6, 7, 8, and ≥9 h/day). We found no association between duration of rotating night shift work and occurrence of colorectal adenoma (p-trend across shift work categories = 0.5). Women with the longest durations of rotating night shift work (≥10 years) had a similar risk of adenoma compared to women without a history of rotating night shift work (multivariable-adjusted RR = 0.96, 95% CI = 0.83-1.11). Similarly, there were no associations of shorter or longer sleep durations with adenoma risk (p-trend = 0.2 across sleep durations of ≤5 through 7 h/day and p-trend = 0.5 across sleep durations of 7 through ≥9 h/day). Results were similar when we examined associations according to adenoma location and subtype. Our results do not support an association between rotating night shift work or sleep duration and risk of colorectal adenoma in women.

Plurihormonal pituitary adenoma immunoreactive for thyroid-stimulating hormone, growth hormone, follicle-stimulating hormone, and prolactin.

PubMed

Luk, Cynthia T; Kovacs, Kalman; Rotondo, Fabio; Horvath, Eva; Cusimano, Michael; Booth, Gillian L

2012-01-01

To describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. We report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment. A 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermittently with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved. Thyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma.

Dietary patterns and risk of colorectal adenoma: a systematic review and meta-analysis of observational studies.

PubMed

Godos, J; Bella, F; Torrisi, A; Sciacca, S; Galvano, F; Grosso, G

2016-12-01

Current evidence suggests that dietary patterns may play an important role in colorectal cancer risk. The present study aimed to perform a systematic review and meta-analysis of observational studies exploring the association between dietary patterns and colorectal adenomas (a precancerous condition). Pubmed and EMBASE electronic databases were systematically searched to retrieve eligible studies. Only studies exploring the risk or association with colorectal adenomas for the highest versus lowest category of exposure to a posteriori dietary patterns were included in the quantitative analysis. Random-effects models were applied to calculate relative risks (RRs) of colorectal adenomas for high adherence to healthy or unhealthy dietary patterns. Statistical heterogeneity and publication bias were explored. Twelve studies were reviewed. Three studies explored a priori dietary patterns using scores identifying adherence to the Mediterranean, Paleolithic and Dietary Approaches to Stop Hypertension (DASH) diet and reported an association with decreased colorectal adenoma risk. Two studies tested the association with colorectal adenomas between a posteriori dietary patterns showing lower odds of disease related to plant-based compared to meat-based dietary patterns. Seven studies identified 23 a posteriori dietary patterns and the analysis revealed that higher adherence to healthy and unhealthy dietary patterns was significantly associated risk of colorectal adenomas (RR = 0.81, 95% confidence interval = 0.71, 0.94 and RR = 1.24, 95% confidence interval = 1.13, 1.35, respectively) with no evidence of heterogeneity or publication bias. The results of this systematic review and meta-analysis indicate that dietary patterns may be associated with the risk of colorectal adenomas. © 2016 The British Dietetic Association Ltd.

Serum Interleukin-6, insulin, and HOMA-IR in male individuals with colorectal adenoma.

PubMed

Sasaki, Yu; Takeda, Hiroaki; Sato, Takeshi; Orii, Tomohiko; Nishise, Shoichi; Nagino, Ko; Iwano, Daisuke; Yaoita, Takao; Yoshizawa, Kazuya; Saito, Hideki; Tanaka, Yasuhisa; Kawata, Sumio

2012-01-15

It is widely acknowledged that chronic low-grade inflammation plays a key role in the development of obesity-related insulin resistance and type 2 diabetes. The level of circulating interleukin-6 (IL-6), one of the major proinflammatory adipokines, is correlated with obesity and insulin resistance, which are known to be risk factors for colorectal adenoma. We examined the association between the circulating level of IL-6 and the presence of colorectal adenoma. In a total colonoscopy-based cross-sectional study conducted between January and December 2008, serum levels of IL-6 were measured in samples of venous blood obtained from 336 male participants attending health checkups (118 individuals with colorectal adenoma and 218 age-matched controls) after an overnight fast. In the colorectal adenoma group, the median levels of serum IL-6 (1.24 vs. 1.04 pg/mL; P = 0.01), triglyceride, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were to be significantly higher than those in the control group. When restricted to individuals with adenoma, levels of IL-6 were positively correlated with body mass index, insulin, and HOMA-IR. Multiple logistic analyses adjusted to include insulin or HOMA-IR showed that high levels of IL-6 were associated with the presence of colorectal adenoma. There was no significant interaction of IL-6 with HOMA-IR to modify this association. Our findings suggest that increased serum levels of IL-6 are positively associated with the presence of colorectal adenoma in men, independently of insulin and HOMA-IR. ©2011 AACR.

Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma.

PubMed

Paradis, Valerie; Benzekri, Asmae; Dargère, Delphine; Bièche, Ivan; Laurendeau, Ingrid; Vilgrain, Valerie; Belghiti, Jacques; Vidaud, Michel; Degott, Claude; Bedossa, Pierre

2004-05-01

"Telangiectatic focal nodular hyperplasia" designate atypical lesions considered as variants of focal nodular hyperplasia (FNH). However, because "telangiectatic FNH" share several morphologic patterns with hepatocellular adenomas, classification of such lesions deserve further clarification. Therefore, the aim of the present study was to reconsider the classification of telangiectatic FNH with the help of a molecular approach. Ten telangiectatic FNH, 6 typical FNH, and 6 hepatocellular adenomas were studied. DNA, RNA, and protein from each lesion were extracted. Clonality was assessed by the study of the X chromosome inactivation pattern (HUMARA assay). Angiopoietin (ANGPT-1 and ANGPT-2) mRNA, genes the expression of which is typically modified in FNH, were quantified by a real-time RT-PCR procedure. Protein profiles were analyzed by SELDI-TOF PROTEINCHIP (Cyphergen Biosystem, Inc., Fremont, CA) technology. Although all informative cases of FNH (5 of 6) and hepatocellular adenomas (6 of 6) were polyclonal and monoclonal, respectively, clonal analysis showed a nonrandom pattern of X chromosome inactivation consistent with a monoclonal lesion in 6 of 8 cases of telangiectatic FNH. The mean value of the ANGPT-1/ANGPT-2 mRNA ratio was 21.4 in FNH, 2.6 in adenomas, and 2.1 in telangiectatic FNH (P

Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients

PubMed Central

Yamaguchi, Tatsuro; Ishida, Hideyuki; Ueno, Hideki; Kobayashi, Hirotoshi; Hinoi, Takao; Inoue, Yasuhiro; Ishida, Fumio; Kanemitsu, Yukihide; Konishi, Tsuyoshi; Tomita, Naohiro; Matsubara, Nagahide; Watanabe, Toshiaki; Sugihara, Kenichi

2016-01-01

Objective The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients. Methods This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study. Results In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively. Conclusions Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population. PMID:26819281

ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

EPA Science Inventory

ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

Humans are exposed to a variety of mutagens from diet, smoking, or occupation. To explore if exposure to mutagens was related to the risk of colorectal adenomas i...

Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

PubMed

Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P

2008-12-01

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

[Gigantism: a mystery explained].

PubMed

Beckers, Alb

2002-01-01

Acromegaly was first described by Pierre Marie in 1886. Some years later, it became clear that acromegaly and gigantism share the same etiology: GH hypersecretion due to a pituitary adenoma, induces gigantism if already present during puberty, or an acromegalic if it appears only during the adulthood. During the XXth century, the disease has been well described and is now well controlled with several treatments. Recently, genetic alterations responsible for the disease have been elucidated.

Validation of a preclinical model of diethylnitrosamine-induced hepatic neoplasia in Yucatan miniature pigs

PubMed Central

Mitchell, Jennifer; Tinkey, Peggy T.; Avritscher, Rony; Van Pelt, Carolyn; Eskandari, Ghazaleh; George, Suraj Konnath; Xiao, Lianchun; Cressman, Erik; Morris, Jeffrey S.; Rashid, Asif; Kaseb, Ahmed O.; Amin, Hesham M.; Uthamanthil, Rajesh

2016-01-01

Objective The purpose of this study was to reduce time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n=2) or DEN (n=6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. Animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (~29 months). Results All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs, as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion To our knowledge, we are the first to demonstrate accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model. PMID:27305144

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

[A systematic review of worldwide natural history models of colorectal cancer: classification, transition rate and a recommendation for developing Chinese population-specific model].

PubMed

Li, Z F; Huang, H Y; Shi, J F; Guo, C G; Zou, S M; Liu, C C; Wang, Y; Wang, L; Zhu, S L; Wu, S L; Dai, M

2017-02-10

Objective: To review the worldwide studies on natural history models among colorectal cancer (CRC), and to inform building a Chinese population-specific CRC model and developing a platform for further evaluation of CRC screening and other interventions in population in China. Methods: A structured literature search process was conducted in PubMed and the target publication dates were from January 1995 to December 2014. Information about classification systems on both colorectal cancer and precancer on corresponding transition rate, were extracted and summarized. Indicators were mainly expressed by the medians and ranges of annual progression or regression rate. Results: A total of 24 studies were extracted from 1 022 studies, most were from America ( n =9), but 2 from China including 1 from the mainland area, mainly based on Markov model ( n =22). Classification systems for adenomas included progression risk ( n =9) and the sizes of adenoma ( n =13, divided into two ways) as follows: 1) Based on studies where adenoma was risk-dependent, the median annual transition rates, from ' normal status' to ' non-advanced adenoma', 'non-advanced' to ' advanced' and ' advanced adenoma' to CRC were 0.016 0 (range: 0.002 2-0.020 0), 0.020 (range: 0.002-0.177) and 0.044 (range: 0.005-0.063), respectively. 2) Median annual transition rates, based on studies where adenoma were classified by sizes, into <10 mm and ≥10 mm ( n =7), from ' normal' to adenoma <10 mm, from adenoma <10 mm to adenoma ≥10 mm and adenoma ≥ 10 mm to CRC, were 0.016 7 (range: 0.015 0-0.037 0), 0.020 (range: 0.015-0.035) and 0.040 0 (range: 0.008 5-0.050 0), respectively. 3) Median annual transition rates, based on studies where adenoma, were classified by sizes into diminutive (≤5 mm), small (6-9 mm) and large adenoma (≥10 mm) ( n =6), from ' normal' to diminutive adenoma,'diminutive' to ' small','small' to ' large', and large adenoma to CRC were 0.013 (range: 0.009-0.019), 0.043 (range: 0.020-0.085), 0.044 (range: 0.020-0.125) and 0.033 5 (range: 0.030-0.040), respectively. Staging system of CRC mainly included LRD (localized/regional/distant, n =10), Dukes' ( n =7) and TNM ( n =3). When using the LRD classification, the median annual transition rates from ' localized' to ' regional' and ' regional' to 'distant' were 0.28 (range: 0.20-0.33) and 0.40 (range: 0.24-0.63), respectively. Under the Dukes' classification, the median annual transition rates appeared as 0.583 (range: 0.050-0.910), 0.656 (range: 0.280-0.720) and 0.830 (range: 0.630-0.865) from Dukes' A to B, B to C and C to Dukes' D, respectively. Again, when using the TNM classification, very limited transition rate was reported. Serrated pathway was only described in one study. Conclusions: Studies on the natural history model of colorectal cancer was still limited worldwide. Adenoma seemed the most common status setting for precancer model, and the risk-dependent classification for adenoma was consistent with the most commonly used system in clinical practice as well as major cancer screening programs in China. Since the staging systems of cancers varied, and shortage of transition rates based on TNM classification (commonly used in China), there will be a challenge for building Chinese population-specific natural history model of colorectal cancer, information from other classification systems could be conditionally applied.

Gut microbiome development along the colorectal adenoma-carcinoma sequence.

PubMed

Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

2015-03-11

Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

The Expression and Significance of Feces Cyclooxygensae-2 mRNA in Colorectal Cancer and Colorectal Adenomas

PubMed Central

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842, P = 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525, P = 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer. PMID:28139497

The expression and significance of feces cyclooxygensae-2 mRNA in colorectal cancer and colorectal adenomas.

PubMed

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842,P= 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525,P= 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer.

ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

PubMed

Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

2017-04-01

To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P < 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC was significantly higher in pheochromocytomas than in adrenal adenomas (all P ≤ 0.001), and showed the highest area under the ROC curve among the ADC histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

Differentiation between Cystic Pituitary Adenomas and Rathke Cleft Cysts: A Diagnostic Model Using MRI.

PubMed

Park, M; Lee, S-K; Choi, J; Kim, S-H; Kim, S H; Shin, N-Y; Kim, J; Ahn, S S

2015-10-01

Cystic pituitary adenomas may mimic Rathke cleft cysts when there is no solid enhancing component found on MR imaging, and preoperative differentiation may enable a more appropriate selection of treatment strategies. We investigated the diagnostic potential of MR imaging features to differentiate cystic pituitary adenomas from Rathke cleft cysts and to develop a diagnostic model. This retrospective study included 54 patients with a cystic pituitary adenoma (40 women; mean age, 37.7 years) and 28 with a Rathke cleft cyst (18 women; mean age, 31.5 years) who underwent MR imaging followed by surgery. The following imaging features were assessed: the presence or absence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, an off-midline location, the presence or absence of an intracystic nodule, size change, and signal change. On the basis of the results of logistic regression analysis, a diagnostic tree model was developed to differentiate between cystic pituitary adenomas and Rathke cleft cysts. External validation was performed for an additional 16 patients with a cystic pituitary adenoma and 8 patients with a Rathke cleft cyst. The presence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, and an off-midline location were more common with pituitary adenomas, whereas the presence of an intracystic nodule was more common with Rathke cleft cysts. Multiple logistic regression analysis showed that cystic pituitary adenomas and Rathke cleft cysts can be distinguished on the basis of the presence of a fluid-fluid level, septation, an off-midline location, and the presence of an intracystic nodule (P = .006, .032, .001, and .023, respectively). Among 24 patients in the external validation population, 22 were classified correctly on the basis of the diagnostic tree model used in this study. A systematic approach using this diagnostic tree model can be helpful in distinguishing cystic pituitary adenomas from Rathke cleft cysts. © 2015 by American Journal of Neuroradiology.

Serrated and adenomatous polyp detection increases with longer withdrawal time: results from the New Hampshire Colonoscopy Registry.

PubMed

Butterly, Lynn; Robinson, Christina M; Anderson, Joseph C; Weiss, Julia E; Goodrich, Martha; Onega, Tracy L; Amos, Christopher I; Beach, Michael L

2014-03-01

Detection and removal of adenomas and clinically significant serrated polyps (CSSPs) is critical to the effectiveness of colonoscopy in preventing colorectal cancer. Although longer withdrawal time has been found to increase polyp detection, this association and the use of withdrawal time as a quality indicator remains controversial. Few studies have reported on withdrawal time and serrated polyp detection. Using data from the New Hampshire Colonoscopy Registry, we examined how an endoscopist's withdrawal time in normal colonoscopies affects adenoma and serrated polyp detection. We analyzed 7,996 colonoscopies performed in 7,972 patients between 2009 and 2011 by 42 endoscopists at 14 hospitals, ambulatory surgery centers, and community practices. CSSPs were defined as sessile serrated polyps and hyperplastic polyps proximal to the sigmoid. Adenoma and CSSP detection rates were calculated based on median endoscopist withdrawal time in normal exams. Regression models were used to estimate the association of increased normal withdrawal time and polyp, adenoma, and CSSP detection. Polyp and adenoma detection rates were highest among endoscopists with 9 min median normal withdrawal time, and detection of CSSPs reached its highest levels at 8-9 min. Incident rate ratios for adenoma and CSSP detection increased with each minute of normal withdrawal time above 6 min, with maximum benefit at 9 min for adenomas (1.50, 95% confidence interval (CI) (1.21, 1.85)) and CSSPs (1.77, 95% CI (1.15, 2.72)). When modeling was used to set the minimum withdrawal time at 9 min, we predicted that adenomas and CSSPs would be detected in 302 (3.8%) and 191 (2.4%) more patients. The increase in detection was most striking for the CSSPs, with nearly a 30% relative increase. A withdrawal time of 9 min resulted in a statistically significant increase in adenoma and serrated polyp detection. Colonoscopy quality may improve with a median normal withdrawal time benchmark of 9 min.

Intraoperative Identification of a Normal Pituitary Gland and an Adenoma Using Near-Infrared Fluorescence Imaging and Low-Dose Indocyanine Green.

PubMed

Verstegen, Marco J T; Tummers, Quirijn R J G; Schutte, Pieter J; Pereira, Alberto M; van Furth, Wouter R; van de Velde, Cornelis J H; Malessy, Martijn J A; Vahrmeijer, Alexander L

2016-09-01

The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the distinction between adenoma and gland.

Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

PubMed Central

Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

2012-01-01

Background/Aim: To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters. Materials and Methods: The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer). Results: PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma. Conclusion: PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic factor. PMID:22824771

Snaring large serrated polyps.

PubMed

Liang, Jennifer; Kalady, Matthew F; Church, James

2013-05-01

Serrated polyps of the large bowel are potentially premalignant, difficult to see, but important to remove. Few studies describe the technique or outcomes of serrated polypectomy. We sought to present outcomes of a series of polypectomies of large serrated polyps in comparison to a series of endoscopic resections of large adenomas. This retrospective, comparative, single endoscopist study was performed in an outpatient colonoscopy department of a tertiary referral medical center. Patients had outpatient colonoscopy where a large (≥2 cm) serrated polyp or adenoma was removed. Outcomes were completeness of excision and complications of polypectomy. A database of endoscopic polypectomies was reviewed. Polypectomy of large serrated polyps was compared with polypectomy of large adenomas. There were 132 large serrated polyps in 112 patients and 563 adenomas in 428 patients. More serrated polyps were right sided (120 of 130, 92.3 %, vs. 379 of 563, 67 %) (p < 0.0001). The serrated polyps were smaller than the adenomas (mean 25.5 ± 7.9 mm standard deviation) versus 36.8 ± 16.9 mm standard deviation (p < 0.001). There were four complications of serrated polypectomy in four patients (4 % of polyps, 5 % of patients): three postpolypectomy bleeds and one postpolypectomy syndrome. There were 33 complications of adenoma removal (31 postpolypectomy bleeding and two postpolypectomy syndrome) (6.9 % of polyps, p = 0.376, 8.4 % of patients, p = 0.371). On follow-up, 36 of 51 patients (71 %) with serrated polyps had metachronous lesions compared to 133 of 298 patients (45 %) with adenomas (p < 0.0001). There were fewer residual polyps in the serrated group (4 of 47 vs. 64 of 298, p = 0.001). Removal of large serrated colorectal polyps is no more complicated than polypectomy of similarly sized adenomas. However, large serrated polyps have a higher rate of metachronous polyps than similarly sized adenomas and surveillance should be adapted to reflect these findings.

Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study.

PubMed

Skjelbred, Camilla F; Saebø, Mona; Nexø, Bjørn A; Wallin, Håkan; Hansteen, Inger-Lise; Vogel, Ulla; Kure, Elin H

2006-07-03

The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender. The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06-1.81), which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15-2.39). The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49-1.01) and carcinomas (OR of 0.49, 95% CI 0.21-1.13) among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95-5.04) compared to all non-carriers although the estimate was not statistically significant. We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women.

The role of APC in WNT pathway activation in serrated neoplasia.

PubMed

Borowsky, Jennifer; Dumenil, Troy; Bettington, Mark; Pearson, Sally-Ann; Bond, Catherine; Fennell, Lochlan; Liu, Cheng; McKeone, Diane; Rosty, Christophe; Brown, Ian; Walker, Neal; Leggett, Barbara; Whitehall, Vicki

2018-03-01

Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively. WNT pathway activation was seen to a lesser extent in serrated pathway lesions. It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001). However, unlike the conventional pathway, truncating APC mutations were rare in the serrated pathway lesions especially sessile serrated adenomas even when dysplastic (15%) and in the BRAF mutant cancers with microsatellite instability that arise from them (8%). In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%). We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis. Moderate impact APC mutations and non-APC-related causes of increased WNT signaling may have a more important role in serrated neoplasia than the truncating APC mutations common in conventional adenomas.

Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies

PubMed Central

Kim, Nam Hee; Suh, Jung Yul; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Choi, Kyuyong

2017-01-01

Purpose Limited data are available regarding the associations between parameters of glucose and lipid metabolism and the occurrence of metachronous adenomas. We investigated whether these parameters affect the occurrence of adenomas detected on surveillance colonoscopy. Materials and Methods This longitudinal study was performed on 5289 subjects who underwent follow-up colonoscopy between 2012 and 2013 among 62171 asymptomatic subjects who underwent an initial colonoscopy for a health check-up between 2010 and 2011. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling. Results The mean interval between the initial and follow-up colonoscopy was 2.2±0.6 years. The occurrence of adenomas detected by the follow-up colonoscopy increased linearly with the increasing quartiles of fasting glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides measured at the initial colonoscopy. These associations persisted after adjusting for confounding factors. The adjusted hazard ratios for adenoma occurrence comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, and triglycerides were 1.50 [95% confidence interval (CI), 1.26–1.77; ptrend<0.001], 1.22 (95% CI, 1.04–1.43; ptrend=0.024), 1.22 (95% CI, 1.02–1.46; ptrend=0.046), 1.36 (95% CI, 1.14–1.63; ptrend=0.004), and 1.19 (95% CI, 0.99–1.42; ptrend=0.041), respectively. In addition, increasing quartiles of low-density lipoprotein-cholesterol and apolipoprotein B were associated with an increasing occurrence of adenomas. Conclusion The levels of parameters of glucose and lipid metabolism were significantly associated with the occurrence of adenomas detected on surveillance colonoscopy. Improving the parameters of glucose and lipid metabolism through lifestyle changes or medications may be helpful in preventing metachronous adenomas. PMID:28120565

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

PubMed Central

Sarkar, Dipak K.

2010-01-01

Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Our knowledge of the formation of these tumors is limited. Experimental work in animal has uncovered that estradiol exposure leads to prolactinoma formation via orchestrated events involving dopamine D2 receptors, transforming growth factor-β (TGF-β) isoforms and their receptors, as well as factors secondary to TGF-β action. Additionally, these studies determined that TGF-β and b-FGF interact to facilitate the communication between lactotropes and folliculo-stellate cells that is necessary for the mitogenic action of estradiol. The downstream signaling that governs lactotropic cell proliferation involves activation of the MAP kinase p44/42-dependent pathway. PMID:16809921

Serrated adenoma of the gallbladder: a case report.

PubMed

Rubio, Carlos A

2015-06-01

A case of serrated adenomatous polyp found in a cholecystectomy specimen is reported. The adenoma was built with mucosal crypts exhibiting unlocked serrations lined with up to high-grade dysplastic cells. A desmoplastic sclerotic tissue having multiple stromal hubs with branched thin spokes replaced the subjacent lamina propia, muscularis mucosae, and submucosa. The generous serrated configurations covering a multi-branched sclerotic stroma, gave the adenoma a papillary appearance. Review of the literature indicates that this appears to be the first reported case of serrated adenoma of the gallbladder. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

ESR1 and its antagonist fulvestrant in pituitary adenomas.

PubMed

Gao, Hua; Xue, Yake; Cao, Lei; Liu, Qian; Liu, Chunhui; Shan, Xiaosong; Wang, Hongyun; Gu, Yi; Zhang, Yazhuo

2017-03-05

Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X 2  = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genomic Instability and Radiation Risk in Molecular Pathways to Colon Cancer

PubMed Central

Kaiser, Jan Christian; Meckbach, Reinhard; Jacob, Peter

2014-01-01

Colon cancer is caused by multiple genomic alterations which lead to genomic instability (GI). GI appears in molecular pathways of microsatellite instability (MSI) and chromosomal instability (CIN) with clinically observed case shares of about 15–20% and 80–85%. Radiation enhances the colon cancer risk by inducing GI, but little is known about different outcomes for MSI and CIN. Computer-based modelling can facilitate the understanding of the phenomena named above. Comprehensive biological models, which combine the two main molecular pathways to colon cancer, are fitted to incidence data of Japanese a-bomb survivors. The preferred model is selected according to statistical criteria and biological plausibility. Imprints of cell-based processes in the succession from adenoma to carcinoma are identified by the model from age dependences and secular trends of the incidence data. Model parameters show remarkable compliance with mutation rates and growth rates for adenoma, which has been reported over the last fifteen years. Model results suggest that CIN begins during fission of intestinal crypts. Chromosomal aberrations are generated at a markedly elevated rate which favors the accelerated growth of premalignant adenoma. Possibly driven by a trend of Westernization in the Japanese diet, incidence rates for the CIN pathway increased notably in subsequent birth cohorts, whereas rates pertaining to MSI remained constant. An imbalance between number of CIN and MSI cases began to emerge in the 1980s, whereas in previous decades the number of cases was almost equal. The CIN pathway exhibits a strong radio-sensitivity, probably more intensive in men. Among young birth cohorts of both sexes the excess absolute radiation risk related to CIN is larger by an order of magnitude compared to the MSI-related risk. Observance of pathway-specific risks improves the determination of the probability of causation for radiation-induced colon cancer in individual patients, if their exposure histories are known. PMID:25356998

Induction of lymphomas on implantation of human oral squamous cell carcinomas in nude mice.

PubMed

Teni, T R; Saranath, D; Mahale, A M; Pai, S A; Ahire, S D; Ingle, A D

2001-02-01

Cancer cells from five oral cancer patients and pleomorphic adenoma cells from one individual were inoculated as single cell suspension into subcutis of 30 Swiss nude mice and tail vein of additional 30 mice. Further, tumor tissue pieces from three oral cancer patients were xenografted s.c. in 18 nude mice, and 10 mice were kept as controls. In animals implanted with tumor pieces, 7/18 (39%) mice, developed squamous cell carcinoma at the site of inoculation within 8-15 days, while tumors were not observed in mice inoculated with single cell suspension, up to 60/90 days. In 8/68 (12%) mice, white foci were observed in several tissues, with hepatomegaly and splenomegaly noted in 27/68 (39%) mice. Histopathological examination of various tissues revealed presence of large cell lymphoma in several organs in 14/68 (21%) mice. No regional or distant metastasis of the implanted oral tumor cells was detected. Mice injected with cells from pleomorphic adenoma, also demonstrated large cell lymphoma in 2/10 (20%) mice, whereas none of the 10 control animals showed any gross abnormalities or microscopic abnormalities in several organs. 2/16 (12%) lymphomas exhibited positive reaction with mouse B cell antibodies illustrating the murine origin of the lymphomas, and these were immunophenotyed as B cell lymphomas. The lymphomas were also examined with mouse T cell antibodies and none reacted positively with the mouse T cell antibodies. The lymphomas also failed to react with human T cell, B cell and human Leucocyte common antigen (LCA) antibodies, indicating that the induced lymphomas were not of human origin. The tumor specimens from seven of eight oral cancer patients and the pleomorphic adenoma patient induced lymphomas in nude mice. Thus it appears that xenografting oral tumor cells into nude mice may cause induction of the murine lymphomas, and this needs further investigation.

Helicobacter pylori infection with intestinal metaplasia: An independent risk factor for colorectal adenomas

PubMed Central

Yan, Ye; Chen, Yi-Na; Zhao, Qian; Chen, Chao; Lin, Chun-Jing; Jin, Yin; Pan, Shuang; Wu, Jian-Sheng

2017-01-01

AIM To explore the association between Helicobacter pylori (H. pylori) infection status, intestinal metaplasia (IM), and colorectal adenomas. METHODS We retrospectively reviewed 1641 individuals aged ≥ 40 years who underwent physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy, and an interview to ascertain baseline characteristics and general state of health. Histopathological results were obtained by gastric and colorectal biopsies. RESULTS The prevalence of H. pylori infection and adenomas was 51.5% (845/1641) and 18.1% (297/1641), respectively. H. pylori infection was significantly correlated with an increased risk of colorectal adenomas (crude OR = 1.535, 95%CI: 1.044-1.753, P = 0.022; adjusted OR = 1.359, 95%CI: 1.035-1.785, P = 0.028). Individuals with IM had an elevated risk of colorectal adenomas (crude OR = 1.664, 95%CI: 1.216-2.277, P = 0.001; adjusted OR = 1.381, 95%CI: 0.998-1.929, P = 0.059). Stratification based on H. pylori infection stage and IM revealed that IM accompanied by H. pylori infection was significantly associated with an increased risk of adenomas (crude OR = 2.109, 95%CI: 1.383-3.216, P = 0.001; adjusted OR = 1.765, 95%CI: 1.130-2.757, P = 0.012). CONCLUSION H. pylori-related IM is associated with a high risk of colorectal adenomas in Chinese individuals. PMID:28293091

Updated Histologic Classification of Adenomas and Carcinomas in the Colon of Carcinogen-treated Sprague-Dawley Rats.

PubMed

Rubio, Carlos A

2017-12-01

Recent studies have disclosed novel histological phenotypes of colon tumours in carcinogen-treated rats. The aim of this study was to update the current histological classification of colonic neoplasias in Sprague-Dawley (SD) rats. Archival sections from 398 SD rats having 408 neoplasias in previous experiments were re-evaluated. Of the 408 colonic neoplasias, 11% (44/408) were adenomas without invasive growth and 89% (364/408) invasive carcinomas. Out of the 44 adenomas, 82% were conventional (tubular or villous), 14% traditional serrated (TSA; with unlocked serrations or with closed microtubules) and 5% gut-associated lymphoid tissue (GALT)-associated adenomas. Out of 364 carcinomas, 57% were conventional carcinomas, 26% GALT carcinomas, 8% undifferentiated, 6% signet-ring cell carcinomas, and 4% traditional serrated carcinomas (TSC). Thus, conventional adenomas, conventional carcinomas and GALT-associated carcinomas predominated (p<0.05). The updated classification of colonic tumours in SD rats includes conventional adenomas, TSA, GALT-associated adenomas, conventional carcinomas, TSC, GALT-associated carcinomas, signet-ring cell carcinomas and undifferentiated carcinomas. Several of the histological phenotypes reported here are not included in any of the current classifications of colonic tumours in rodents. This updated classification fulfils the requirements for an animal model of human disease, inasmuch as similar histological phenotypes of colon neoplasias have been documented in humans. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions.

PubMed

Bertram, Stefanie; Padden, Juliet; Kälsch, Julia; Ahrens, Maike; Pott, Leona; Canbay, Ali; Weber, Frank; Fingas, Christian; Hoffmann, Andreas C; Vietor, Antonie; Schlaak, Joerg F; Eisenacher, Martin; Reis, Henning; Sitek, Barbara; Baba, Hideo A

2016-07-01

The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and identified a diagnostic marker panel including known biomarkers. Subjects included samples from 77 patients with ICC, 33 patients with bile duct adenoma and 47 patients with ductular reactions in liver cirrhosis. Our previously identified biomarkers (stress-induced phosphoprotein 1 (STIP1), SerpinH1, 14-3-3Sigma) were tested immunohistochemically following comparison with candidates from the literature (cluster of differentiation 56, heat shock protein (HSP)27, HSP70, B-cell-lymphoma2, p53, ki67). The expression of SerpinH1 and 14-3-3Sigma was significantly higher in ICC than in bile duct adenomas and ductular reactions (p<0.05), whereas STIP1 expression was significantly higher (p<0.05) in ICC than in ductular reactions, but the difference to the bile duct adenoma group was not significant. A panel of the biomarker SerpinH1, 14-3-3Sigma and ki67 (≥2 marker positive) showed a high diagnostic accuracy (sensitivity 87.8%, specificity 95.9%, accuracy 91.8%) in the differential diagnosis of ICC versus non-malignant bile duct lesions. This suggests that 14-3-3Sigma and SerpinH1 may be useful in the differential diagnosis of malignant, benign and reactive bile duct lesions in addition to ki67 where a cut-off of >5% might be used for the distinction of malignant and non-malignant lesions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFα

PubMed Central

Zhong, Nianxin; Ward, Jerrold M.; Perella, Christine M.; Hoffmann, Victoria J.; Rogers, Keith; Combs, Gerald F.; Schweizer, Ulrich; Merlino, Glenn; Gladyshev, Vadim N.; Hatfield, Dolph L.

2013-01-01

Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (TrsptG37) and/or a cancer driver TGFα transgene. The use of TrsptG37 altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. TrsptG37 transgenic and TGFα/TrsptG37 bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGFα transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα–induced liver tumors. PMID:23460847

Tumor promotion and inhibition by phenobarbital in livers of conditional Apc-deficient mice.

PubMed

Braeuning, Albert; Gavrilov, Alina; Geissler, Miriam; Wenz, Christine; Colnot, Sabine; Templin, Markus F; Metzger, Ute; Römer, Michael; Zell, Andreas; Schwarz, Michael

2016-06-01

Activation of Wnt/β-catenin signaling is important for human and rodent hepatocarcinogenesis. In mice, the tumor promoter phenobarbital (PB) selects for hepatocellular tumors with activating β-catenin mutations via constitutive androstane receptor activation. PB-dependent tumor promotion was studied in mice with genetic inactivation of Apc, a negative regulator of β-catenin, to circumvent the problem of randomly induced mutations by chemical initiators and to allow monitoring of PB- and Wnt/β-catenin-dependent tumorigenesis in the absence of unknown genomic alterations. Moreover, the study was designed to investigate PB-induced proliferation of liver cells with activated β-catenin. PB treatment provided Apc-deficient hepatocytes with only a minor proliferative advantage, and additional connexin 32 deficiency did not affect the proliferative response. PB significantly promoted the outgrowth of Apc-deficient hepatocellular adenoma (HCA), but simultaneously inhibited the formation of Apc-deficient hepatocellular carcinoma (HCC). The probability of tumor promotion by PB was calculated to be much lower for hepatocytes with loss of Apc, as compared to mutational β-catenin activation. Comprehensive transcriptomic and phosphoproteomic characterization of HCA and HCC revealed molecular details of the two tumor types. HCC were characterized by a loss of differentiated hepatocellular gene expression, enhanced proliferative signaling, and massive over-activation of Wnt/β-catenin signaling. In conclusion, PB exerts a dual role in liver tumor formation by promoting the growth of HCA but inhibiting the growth of HCC. Data demonstrate that one and the same compound can produce opposite effects on hepatocarcinogenesis, depending on context, highlighting the necessity to develop a more differentiated view on the tumorigenicity of this model compound.

Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes.

PubMed

Wang, Bo; Hikosaka, Keisuke; Sultana, Nishat; Sharkar, Mohammad Tofael Kabir; Noritake, Hidenao; Kimura, Wataru; Wu, Yi-Xin; Kobayashi, Yoshimasa; Uezato, Tadayoshi; Miura, Naoyuki

2012-01-06

The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with ∼50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age. Copyright © 2011 Elsevier Inc. All rights reserved.

Ethnic disparities in the risk of colorectal adenomas associated with lipid levels: a retrospective multiethnic study.

PubMed

Davis-Yadley, Ashley H; Lipka, Seth; Shen, Huafeng; Devanney, Valerie; Swarup, Supreeya; Barnowsky, Alex; Silpe, Jeff; Mosdale, Josh; Pan, Qinshi; Fridlyand, Svetlana; Sreeharshan, Suhas; Abraham, Albin; Viswanathan, Prakash; Krishnamachari, Bhuma

2015-03-01

Although data exists showing that uncontrolled lipid levels in white and black patients is associated with colorectal adenomas, there are currently no studies looking only at the Hispanic population. With the rapid increase in the Hispanic population, we aimed to look at their risk of colorectal adenomas in association with lipid levels. We retrospectively analyzed 1473 patients undergoing colonoscopy from 2009 to 2011 at a community hospital. Statistical analysis was performed using Chi-squared for categorical variables and t test for continuous variables with age-, gender-, and race-adjusted odds ratios. Unconditional logistic regression model was used to estimate 95 % confidence intervals (CI). SAS 9.3 software was used to perform all statistical analysis. In our general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas with odds ratio (OR) 1.60 (1.03, 2.48). There was an association with proximal colon adenomas and cholesterol levels between 200 and 239 with OR 1.57 (1.07, 2.30), and low-density lipoprotein (LDL) levels of greater than 130 with OR 1.54 (1.04, 2.30). There was no association between high-density lipoproteins (HDL) levels and colorectal adenomas. The Hispanic population showed no statistical correlation between elevated triglycerides, cholesterol, or LDL with the presence, size, location, or multiplicity of colorectal adenomas. We found a significant correlation between elevated lipid levels and colorectal adenomas in white and black patients; however, there was no such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.

Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial.

PubMed

Reid, Mary E; Duffield-Lillico, Anna J; Sunga, Annette; Fakih, Marwan; Alberts, David S; Marshall, James R

2006-04-01

Selenium status has been inversely associated with colorectal cancers (CRC) and adenomas. This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow-up. Of the 1,312 randomized to 200 mcg of selenized yeast of matching placebo, 598 participants underwent endoscopic screening (flexible sigmoidoscopy or colonoscopy) for CRC sometime during the follow-up period, which ended in February 1, 1996. There was no colorectal screening performed at baseline. Of those screened, 77% were male (with a mean age of 62.8 years), 42% were former and 25% were current smokers. Adenomas were classified as prevalent (identified at the first endoscopic examination post-randomization during the follow-up period) or incident (identified at the second or subsequent examination). Ninety-nine prevalent and 61 incident adenomas were ascertained. Logistic regression odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender and smoking status. For prevalent adenomas, there was a suggestive but nonsignificant decrease in risk associated with selenium treatment (OR = 0.67, 95% CI = 0.43-1.05). Subjects in the lowest tertile of baseline selenium (OR = 0.27, 95% CI = 0.09-0.77) and current smokers (OR = 0.27, 95% CI = 0.11-0.66) had significant reductions in risk. The OR for incident adenomas was 0.98 (95% CI = 0.57-1.68). In addition to being associated with a reduced risk of incident CRC, selenium supplementation was associated with a significantly reduced risk of prevalent adenomas, but only among subjects with either a low baseline selenium level or among current smokers.

Latest generation, wide-angle, high-definition colonoscopes increase adenoma detection rate.

PubMed

Adler, Andreas; Aminalai, Alireza; Aschenbeck, Jens; Drossel, Rolf; Mayr, Michael; Scheel, Mathias; Schröder, Andreas; Yenerim, Timur; Wiedenmann, Bertram; Gauger, Ulrich; Roll, Stephanie; Rösch, Thomas

2012-02-01

Improvements to endoscopy imaging technologies might improve detection rates of colorectal cancer and patient outcomes. We compared the accuracy of the latest generation of endoscopes with older generation models in detection of colorectal adenomas. We compared data from 2 prospective screening colonoscopy studies (the Berlin Colonoscopy Project 6); each study lasted approximately 6 months and included the same 6 colonoscopists, who worked in private practice. Participants in group 1 (n = 1256) were all examined by using the latest generation of wide-angle, high-definition colonoscopes that were manufactured by the same company. Individuals in group 2 (n = 1400) were examined by endoscopists who used routine equipment (a mixture of endoscopes from different companies; none of those used to examine group 1). The adenoma detection rate was calculated on the basis of the number of all adenomas/number of all patients. There were no differences in patient parameters or withdrawal time between groups (8.0 vs 8.2 minutes). The adenoma detection rate was significantly higher in group 1 (0.33) than in group 2 (0.27; P = .01); a greater number of patients with least 1 adenoma were identified in group 1 (22.1%) than in group 2 (18.2%; P = .01). A higher percentage of high-grade dysplastic adenomas were detected in group 1 (1.19%) than in group 2 (0.57%), but this difference was not statistically significant (P = .06). The latest generation of wide-angle, high-definition colonoscopes improves rates of adenoma detection by 22%, compared with mixed, older technology endoscopes used in routine private practice. These findings might affect definitions of quality control parameters for colonoscopy screening for colorectal cancer. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cyclooxygenase-2 expression and oxidative DNA adducts in murine intestinal adenomas: modification by dietary curcumin and implications for clinical trials.

PubMed

Tunstall, R G; Sharma, R A; Perkins, S; Sale, S; Singh, R; Farmer, P B; Steward, W P; Gescher, A J

2006-02-01

The natural polphenol, curcumin, retards the growth of intestinal adenomas in the Apc(Min+) mouse model of human familial adenomatous polyposis. In other preclinical models, curcumin downregulates the transcription of the enzyme cyclooxygenase-2 (COX-2) and decreases levels of two oxidative DNA adducts, the pyrimidopurinone adduct of deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). We have studied COX-2 protein expression and oxidative DNA adduct levels in intestinal adenoma tissue from Apc(Min+) mice to try and differentiate between curcumin's direct pharmacodynamic effects and indirect effects via its inhibition of adenoma growth. Mice received dietary curcumin (0.2%) for 4 or 14 weeks. COX-2 protein, M1dG and 8-oxo-dG levels were measured by Western blot, immunochemical assay and liquid chromatography-mass spectrometry, respectively. In control Apc(Min+) mice, the levels of all three indices measured in adenoma tissue were significantly higher than levels in normal mucosa. Lifetime administration of curcumin reduced COX-2 expression by 66% (P = 0.01), 8-oxo-dG levels by 24% (P < 0.05) and M1dG levels by 39% (P < 0.005). Short-term feeding did not affect total adenoma number or COX-2 expression, but decreased M1dG levels by 43% (P < 0.01). COX-2 protein levels related to adenoma size. These results demonstrate the utility of measuring these oxidative DNA adduct levels to show direct antioxidant effects of dietary curcumin. The effects of long-term dietary curcumin on COX-2 protein levels appear to reflect retardation of adenoma development.

Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma.

PubMed

Tonacchera, M; Chiovato, L; Pinchera, A; Agretti, P; Fiore, E; Cetani, F; Rocchi, R; Viacava, P; Miccoli, P; Vitti, P

1998-02-01

Toxic multinodular goiter is a cause of nonautoimmune hyperthyroidism and is believed to differ in its nature and pathogenesis from toxic adenoma. Gain-of-function mutations of the TSH receptor gene have been identified as a cause of toxic adenoma. The pathogenesis at the molecular level of hyperfunctioning nodules in toxic multinodular goiter has yet not been reported. Six patients with a single hot nodule within a multinodular goiter and 11 patients with toxic thyroid adenoma were enrolled in our study. At histology five hyperfunctioning nodules in multinodular goiters showed the features of adenomas, and one was identified as a hyperplastic nodule. The entire exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from genomic DNA obtained from surgical specimens. Functional studies of mutated receptors were performed in COS-7 cells. Five out of 6 (83%) hyperfunctioning nodules within toxic multinodular goiters harbored a TSH receptor mutation. A TSH receptor mutation was also evident in the hyperfunctioning nodule that at histology had the features of noncapsulated hyperplastic nodule. Among toxic adenomas, 8 out of 11 (72%) nodules harbored a TSH receptor mutation. All the mutations were heterozygotic and somatic. Nonfunctioning nodules, whether adenomas or hyperplastic nodules present in association with hyperfunctioning nodules in the same multinodular goiters, had no TSH receptor mutation. All the mutations identified had constitutive activity as assessed by cAMP production after expression in COS-7 cells. Hyperfunctioning thyroid nodules in multinodular goiters recognize the same pathogenetic event (TSH receptor mutation) as toxic adenoma. Other mechanisms are implicated in the growth of nonfunctioning thyroid nodules coexistent in the same gland.

Meat consumption and the risk of incident distal colon and rectal adenoma

PubMed Central

Ferrucci, L M; Sinha, R; Huang, W-Y; Berndt, S I; Katki, H A; Schoen, R E; Hayes, R B; Cross, A J

2012-01-01

Background: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis. Methods: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17 072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression. Results: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04–2.36), well or very well-done meat (OR=1.59, 95% CI=1.05–2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17–2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06–2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03–2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56–0.86) and iron from supplements (OR=0.65, 95% CI=0.44–0.97) were inversely associated with any distal colorectal adenoma. Conclusion: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma. PMID:22166801

Altered saturated and monounsaturated plasma phospholipid fatty acid profiles in adult males with colon adenomas

PubMed Central

Pickens, C. Austin; Lane-Elliot, Ami; Comstock, Sarah S.; Fenton, Jenifer I.

2016-01-01

Background Altered lipid metabolism and plasma fatty acid (FA) levels are associated with colorectal cancer (CRC). Obesity and elevated waist circumference (WC) increase the likelihood of developing precancerous colon adenomas. Methods Venous blood was collected from 126 males, ages 48 to 65 years, who received routine colonoscopies. Plasma phospholipid (PPL) FAs were isolated, derivatized, and then analyzed using gas chromatography. Odds ratios (ORs) and 95% confidence intervals were determined using polytomous logistic regression after adjusting for confounding factors (i.e. age, smoking, WC, and BMI). Results PPL palmitic acid (PA) was inversely correlated with the presence of colon adenomas (p = 0.01). For each unit increase in palmitoleic acid (OR: 3.75, p = 0.04) or elaidic acid (OR: 2.92, p = 0.04) an individual was more likely to have adenomas relative to no colon polyps. Higher enzyme activity estimates (EAEs) of stearoyl-CoA desaturase-1 (SCD-1, p = 0.02) and elongation of very long chain-6 (Elovl-6, p = 0.03) were associated with an individual being approximately 1.5 times more likely to have an adenoma compared to no polyps. Conclusions PPL FAs and EAEs, which have previously been associated with CRC, are significantly different in those with adenomas when compared to those without polyps. PPL PA, elaidic acid, and SCD-1 and Elovl-6 EAEs are associated with adenomas independent of BMI and WC. Impact PPL PA, elaidic acid, and SCD-1 and Elovl-6 EAEs are associated with adenomas even after adjusting for obesity-related risk factors and may function as novel biomarkers of early CRC risk. PMID:26721667

The Molecular Registry of Pituitary Adenomas (REMAH): A bet of Spanish Endocrinology for the future of individualized medicine and translational research.

PubMed

Luque, Raúl M; Ibáñez-Costa, Alejandro; Sánchez-Tejada, Laura; Rivero-Cortés, Esther; Robledo, Mercedes; Madrazo-Atutxa, Ainara; Mora, Mireia; Álvarez, Clara V; Lucas-Morante, Tomás; Álvarez-Escolá, Cristina; Fajardo, Carmen; Castaño, Luis; Gaztambide, Sonia; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Gálvez, María Ángeles; Salvador, Javier; Valassi, Elena; Webb, Susan M; Picó, Antonio; Puig-Domingo, Manel; Gilabert, Montserrat; Bernabéu, Ignacio; Marazuela, Mónica; Leal-Cerro, Alfonso; Castaño, Justo P

2016-01-01

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

The association between cecal insertion time and colorectal neoplasm detection

PubMed Central

2013-01-01

Background Information on the impact of cecal insertion time on colorectal neoplasm detection is limited. Our objective was to determine the association between cecal insertion time and colorectal neoplasm detection rate in colonoscopy screening. Methods We performed a cross-sectional study of 12,679 consecutive subjects aged 40–79 years undergoing screening colonoscopy in routine health check-ups at the Center for Health Promotion of the Samsung Medical Center from December 2007 to June 2009. Fixed effects logistic regression conditioning on colonoscopist was used to eliminate confounding due to differences in technical ability and other characteristics across colonoscopists. Results The mean cecal insertion time was 5.9 (SD, 4.4 minutes). We identified 4,249 (33.5%) participants with colorectal neoplasms, of whom 1,956 had small single adenomas (<5 mm), 595 had medium single adenomas (5–9 mm), and 1,699 had multiple adenomas or advanced colorectal neoplasms. The overall rates of colorectal neoplasm detection by quartiles of cecal insertion time were 36.8%, 33.4%, 32.7%, and 31.0%, respectively (p trend <0.001).The odds for small single colorectal adenoma detection was 16% lower (adjusted OR 0.84; 95% CI 0.71 to 0.99) in the fourth compared to the first quartile of insertion time (p trend 0.005). Insertion time was not associated with the detection rate of single adenomas ≥5 mm, multiple adenomas or advanced colorectal neoplasms. Conclusion Shorter insertion times were associated with increased rates of detection of small colorectal adenomas <5 mm. Cecal insertion time may be clinically relevant as missed small colorectal adenomas may progress to more advanced lesions. PMID:23915303

Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.

PubMed

Thompson, Patricia; Roe, Denise J; Fales, Liane; Buckmeier, Julie; Wang, Fang; Hamilton, Stanley R; Bhattacharyya, Achyut; Green, Sylvan; Hsu, Chiu-Hsieh; Chow, H-H Sherry; Ahnen, Dennis J; Boland, C Richard; Heigh, Russell I; Fay, David E; Martinez, Maria Elena; Jacobs, Elizabeth; Ashbeck, Erin L; Alberts, David S; Lance, Peter

2012-12-01

COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported. ©2012 AACR

Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations.

PubMed

Koutourousiou, Maria; Gardner, Paul A; Fernandez-Miranda, Juan C; Paluzzi, Alessandro; Wang, Eric W; Snyderman, Carl H

2013-03-01

Giant pituitary adenomas (> 4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique. The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome. Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (> 90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size, and intraventricular or posterior fossa extension did not influence the surgical outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1-114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up. Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy.

PubMed

Felix, I A; Horvath, E; Kovacs, K; Smyth, H S; Killinger, D W; Vale, J

1986-01-01

A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.

The Characteristics of Incidental Pituitary Microadenomas in 120 Korean Forensic Autopsy Cases

PubMed Central

Kim, Jang-Hee; Seo, Jung-Seok; Lee, Bong-Woo; Lee, Sang-Young; Jeon, Seok-Hoon

2007-01-01

To investigate the characteristics of incidental pituitary microadenomas, we examined 120 pituitary glands from Korean forensic autopsy cases, from which eight tumors were identified (incidence 6.7%). The average age of the affected subjects was 50 yr (range: 33-96 yr) with a female predominance. The maximum diameters of the tumors ranged from 0.4 to 5.4 mm (mean: 2.8 mm). Immunohistochemical analysis of pituitary hormones revealed three growth hormone-secreting adenomas, one prolactin-producing adenoma, one gonadotropin-producing adenoma, one plurihormonal adenoma, and two null cell adenomas. MIB-1 staining for Ki-67 antigen showed no positive expression. The microvessel density (MVD) of the pituitary microadenomas ranged from 2.3 to 11.6% (mean: 5.3%) and was significantly lower than that of nonneoplastic pituitary glands (11.9-20.1%, mean: 14.8%). Our study provides reference data on incidental pituitary microadenomas in the Korean population. PMID:17923757

Distinct Patterns of Somatic Mosaicism in the APC Gene in Neoplasms From Patients With Unexplained Adenomatous Polyposis.

PubMed

Jansen, Anne M L; Crobach, Stijn; Geurts-Giele, Willemina R R; van den Akker, Brendy E W M; Garcia, Marina Ventayol; Ruano, Dina; Nielsen, Maartje; Tops, Carli M J; Wijnen, Juul T; Hes, Frederik J; van Wezel, Tom; Dinjens, Winand N M; Morreau, Hans

2017-02-01

We investigated the presence and patterns of mosaicism in the APC gene in patients with colon neoplasms not associated with any other genetic variants; we performed deep sequence analysis of APC in at least 2 adenomas or carcinomas per patient. We identified mosaic variants in APC in adenomas from 9 of the 18 patients with 21 to approximately 100 adenomas. Mosaic variants of APC were variably detected in leukocyte DNA and/or non-neoplastic intestinal mucosa of these patients. In a comprehensive sequence analysis of 1 patient, we found no evidence for mosaicism in APC in non-neoplastic intestinal mucosa. One patient was found to carry a mosaic c.4666dupA APC variant in only 10 of 16 adenomas, indicating the importance of screening 2 or more adenomas for genetic variants. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cystic Mammary Adenocarcinoma Associated with a Prolactin-secreting Pituitary Adenoma in a New Zealand White Rabbit (Oryctolagus cuniculus)

PubMed Central

Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

2008-01-01

A 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit. PMID:18589874

Immunophenotype of nipple adenoma in a male patient.

PubMed

Fernandez-Flores, Angel; Suarez-Peñaranda, Jose-Manuel

2011-03-01

Adenoma of the nipple is rare in men. It must be distinguished from a breast carcinoma and from Paget disease. In this sense, immunohistochemistry can be of some help. In women, for instance, immunoexpression of c-erbB-2 favors a diagnosis of Paget disease, according to some studies. Nevertheless, we have not found any studies on HER2/neu status, estrogen receptors, or progesterone receptors in nipple adenoma of male patients. We present a case of an adenoma of the nipple in a 21-year-old man in which we carried out a wide immunohistochemical study. The lesion did not express estrogen receptors, progesterone receptors, or androgen receptors. The HercepTest was negative. Smooth muscle Actin and p63 were remarked in the basal layer of the tumoral tubules, supporting the benignancy of the lesion. This case of adenoma of the nipple in a male shows an immunophenotype that is similar to the ones reported in female patients.

Oriental mystery: ginseng

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yun, T.K.; Cho, H.O.; Yun, Y.S.

1985-01-01

As a mysterious cure-all medicine Korea ginseng has been, since four or five thousand years ago, used as a tonic in the orient. Ginseng has been known to have a tonic effect and it is the general opinion of many investigators that ginseng has the effect of normalization of physical conditions, that is; maintaining individual homeostasis. On the other hand, the authors have found that ginseng extract inhibits the incidence and also the proliferation of tumors induced by carcinogens such as urethane, DMBA and aflatoxin B. The anticarcinogenic effect of ginseng was due to its ability to enhance the naturalmore » killer activity of the host. Korea ginseng is highly effective in preventing or curing various disease such as diabetes, cancer, high blood pressure, etc.« less

Chemoprevention of polyp recurrence with curcumin followed by silibinin in a case of multiple colorectal adenomas.

PubMed

Alfonso-Moreno, Vicente; López-Serrano, Antonio; Moreno-Osset, Eduardo

2017-12-01

Chemoprevention is a practical approach to reduce the risk of various cancers including colorectal cancer (CRC). The goal is to reduce the incidence of pre-neoplastic adenomatous polyps and prevent its progression to CRC. Curcumin and silibinin prevent intestinal polyp formation in mice. Curcumin sensitizes silymarin to exert synergistic anticancer activity in colon cancer cells. Patients presenting with multiple colorectal adenomatous polyps (MCRA) have a high lifetime risk for CRC. We present a 57-year-old man with MCRA, without deleterious germline APC or MYH mutations. Our patient had 54 polyps in the first colonoscopy, most of 3 to 8 mm and one of 20 mm with high grade dysplasia / adenocarcinoma. Four subsequent colonoscopies showed continuous development of adenomatous polyps treated by polypectomy for the most part and some with heat. After the treatment with curcumin for 3 months and a half followed by silibinin for 9 months, we find many less polyps than in the previous colonoscopies, going from the finding of 40 adenomas of 3-6 mm in the pre-treatment colonoscopy to 3 polyps after treatment.

EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas

PubMed Central

Fukuoka, Hidenori; Cooper, Odelia; Ben-Shlomo, Anat; Mamelak, Adam; Ren, Song-Guang; Bruyette, Dave; Melmed, Shlomo

2011-01-01

Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease. PMID:22105169

Water-clear cell adenoma of the parathyroid. A case report with immunohistochemistry and electron microscopy.

PubMed

Grenko, R T; Anderson, K M; Kauffman, G; Abt, A B

1995-11-01

We report a water-clear cell adenoma of the parathyroid gland, a lesion which to our knowledge has not been described previously. Like its rare but well-described hyperplastic counterpart, water-clear cell hyperplasia, this adenoma is composed of cells with abundant foamy-to-granular cytoplasm and mild nuclear pleomorphism. The cells form glandular structures and cell nests separated by fine fibrovascular septae. The tumor cells stain positively with anti-parathyroid hormone and show characteristic glassy and flocculate material by electron microscopy. Unlike water-clear cell hyperplasia, water-clear cell adenoma is a solitary lesion that compresses the residual nonneoplastic parathyroid gland.

A Case Report of Rare Carcinoma Ex Pleomorphic Adenoma of Submandibular Gland and its Detailed Description

PubMed Central

Deshmukh, Ajinkya Amritrao; Deshmukh, Atul A.

2017-01-01

A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy. PMID:28658924

An Atypical Acidophil Cell Line Tumor Showing Focal Differentiation Toward Both Growth Hormone and Prolactin Cells.

PubMed

Naritaka, Heiji; Kameya, Toru; Sato, Yuichi; Furuhata, Shigeru; Okui, Junichi; Kamiguchi, Yuji; Otani, Mitsuhiro; Toya, Shigeo

1995-01-01

We report a case of giant pituitary adenoma in a child. Computerized tomography (CT) scan revealed a suprasellar extension tumor mass with hydrocephalus. There was no clinical evidence of acromegaly, gigantism, and other hormonal symptoms. Endocrinologic studies showed within normal value of serum growth hormone (GH: 4.2 ng/mL) and slightly increased levels of prolactin (PRL: 78 ng/mL) and other pituitary hormone values were within normal range. On suppression test by bromocryptin, both GH and PRL levels were reduced. Histopathological findings revealed that the tumor consisted of predominantly chromophobic and partly eosinophilic adenoma cells. Immunohistochemical staining detected GH and PRL in a small number of distinctly different adenoma cells, respectively. Nonradioactive in situ hybridization (ISH) also showed GH and PRL mRNA expression in identical immunopositive cells. Electron microscopy (EM) demonstrated adenoma cells with moderate or small numbers of two types of dense granules and without fibrous body which are characteristic of sparsely granulated GH-cell adenomas. The adenoma does not fit into any classification but may be an atypical acidophil cell line tumor showing focal differentiation toward both GH and PRL cells.

Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor

PubMed Central

Chin, Sang Ouk; Hwang, Jin-Kyung; Rhee, Sang Youl; Chon, Suk; Oh, Seungjoon; Lee, Misu; Pellegata, Natalia S.

2015-01-01

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor. PMID:25559714

A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.

PubMed

Hull, Mark A; Sandell, Anna C; Montgomery, Alan A; Logan, Richard F A; Clifford, Gayle M; Rees, Colin J; Loadman, Paul M; Whitham, Diane

2013-07-29

The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients. Current Controlled Trials ISRCTN05926847.

Development of high strength siloxane poly(urethane-urea) elastomers based on linked macrodiols for heart valve application.

PubMed

Dandeniyage, Loshini S; Gunatillake, Pathiraja A; Adhikari, Raju; Bown, Mark; Shanks, Robert; Adhikari, Benu

2017-08-31

Mixed macrodiol based siloxane poly(urethane-urea)s (SiPUU) having number average molecular weights in the range 87-129 kDa/mol were synthesized to give elastomers with high tensile and tear strengths required to fabricate artificial heart valves. Polar functional groups were introduced into the soft segment to improve the poor segmental compatibility of siloxane polyurethanes. This was achieved by linking α,ω-bis(6-hydroxyethoxypropyl) poly(dimethylsiloxane) (PDMS) or poly(hexamethylene oxide) (PHMO) macrodiols with either 4,4'-methylenediphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI) or isophorone diisocyanate (IPDI) prior to polyurethane synthesis. The hard segment was composed of MDI, and a 1:1 mixture of 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyldisiloxane and 1,2-ethylene diamine. We report the effect of urethane linkers in soft segments on properties of the SiPUU. PHMO linked with either MDI or IPDI produced SiPUU with the highest tensile and tear strengths. Linking PDMS hardly affected the tensile strength; however, the tear strength was improved. The stress-strain curves showed no plastic deformation region typically observed for conventional polyurethanes indicating good creep resistance. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

Physiological Effects of Touching Coated Wood.

PubMed

Ikei, Harumi; Song, Chorong; Miyazaki, Yoshifumi

2017-07-13

This study examined the physiological effects of touching wood with various coating with the palm of the hand on brain activity and autonomic nervous activity. Participants were 18 female university students (mean age, 21.7 ± 1.6 years). As an indicator of brain activity, oxyhemoglobin concentrations were measured in the left and right prefrontal cortices using near-infrared time-resolved spectroscopy. Heart rate variability (HRV) and heart rate were used as indicators of autonomic nervous activity. The high-frequency (HF) component of HRV, which reflects parasympathetic nervous activity, and the low-frequency (LF)/HF ratio, which reflects sympathetic nervous activity, were measured. Plates of uncoated, oil-finished, vitreous-finished, urethane-finished, and mirror-finished white oak wood were used as tactile stimuli. After sitting at rest with their eyes closed for 60 s, participants touched the stimuli with their palm for 90 s each. The results indicated that tactile stimulation with uncoated wood calmed prefrontal cortex activity (vs. urethane finish and mirror finish), increased parasympathetic nervous activity (vs. vitreous finish, urethane finish, and mirror finish), and decreased heart rate (vs. mirror finish), demonstrating a physiological relaxation effect. Further, tactile stimulation with oil- and vitreous-finished wood calmed left prefrontal cortex activity and decreased heart rate relative to mirror-finished wood.

Physiological Effects of Touching Coated Wood

PubMed Central

2017-01-01

This study examined the physiological effects of touching wood with various coating with the palm of the hand on brain activity and autonomic nervous activity. Participants were 18 female university students (mean age, 21.7 ± 1.6 years). As an indicator of brain activity, oxyhemoglobin concentrations were measured in the left and right prefrontal cortices using near-infrared time-resolved spectroscopy. Heart rate variability (HRV) and heart rate were used as indicators of autonomic nervous activity. The high-frequency (HF) component of HRV, which reflects parasympathetic nervous activity, and the low-frequency (LF)/HF ratio, which reflects sympathetic nervous activity, were measured. Plates of uncoated, oil-finished, vitreous-finished, urethane-finished, and mirror-finished white oak wood were used as tactile stimuli. After sitting at rest with their eyes closed for 60 s, participants touched the stimuli with their palm for 90 s each. The results indicated that tactile stimulation with uncoated wood calmed prefrontal cortex activity (vs. urethane finish and mirror finish), increased parasympathetic nervous activity (vs. vitreous finish, urethane finish, and mirror finish), and decreased heart rate (vs. mirror finish), demonstrating a physiological relaxation effect. Further, tactile stimulation with oil- and vitreous-finished wood calmed left prefrontal cortex activity and decreased heart rate relative to mirror-finished wood. PMID:28703777

Measurement of tritium penetration through concrete material covered by various paints coating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edao, Y.; Kawamura, Y.; Kurata, R.

The present study aims at obtaining fundamental data on tritium migration in porous materials, which include soaking effect, interaction between tritium and cement paste coated with paints and transient tritium sorption in porous cement. The amounts of tritium penetrated into or released from cement paste with epoxy and urethane paint coatings were measured. The tritium penetration amounts were increased with the HTO (tritiated water) exposure time. Time to achieve a saturated value of tritium sorption was more than 60 days for cement paste coated with epoxy paint and with urethane paint, while that for cement paste without any paint coatingmore » took 2 days to achieve it. The effect of tritium permeation reduction by the epoxy paint was higher than that of the urethane. Although their paint coatings were effective for reduction of tritium penetration through the cement paste which was exposed to HTO for a short period, it was found that the amount of tritium trapped in the paints became large for a long period. Tritium penetration rates were estimated by an analysis of one-dimensional diffusion in the axial direction of a thickness of a sample. Obtained data were helpful for evaluation of tritium contamination and decontamination. (authors)« less

Nondegradable magnetic poly (carbonate urethane) microspheres with good shape memory as a proposed material for vascular embolization.

PubMed

Liu, Rongrong; Zhang, Qian; Zhou, Qian; Zhang, Ping; Dai, Honglian

2018-06-01

In this study, nondegradable poly (carbonate urethane) (PCU) and poly (carbonate urethane) incorporated variable Fe 3 O 4 content microspheres (PCU/Fe 3 O 4 ) were synthesized using pre-polymerization and suspension polymerization. Synthesis was confirmed through Fourier transform infrared spectroscopy (FTIR). The effect of Fe 3 O 4 incorporation was investigated on crystalline, thermal, shape memory and degradation properties by X-Ray diffraction (XRD), Differential scanning calorimetery (DSC), compression test and degradation in vitro, respectively. Otherwise, the assessment of magnetic characteristics by vibrational sample magnetometry (VSM) disclosed superparamagnetic behavior. The tunable superparamagnetic behavior depends on the amount of magnetic particles incorporated within the networks. The biological study results of as-synthesized polymers from the platelet adhesion test and the cell proliferation inhibition test indicated they were biocompatible in vitro. Fe 3 O 4 incorporation was conductive to reducing platelet adhesion in blood contacting test and promotion of rat vascular smooth muscle cell proliferation and growth. These nondegradable, superparamagnetic, biocompatible polymers, combined with their good shape memory properties may allow for their future exploitation in the biomedical field, such as, in cardiovascular implants, targeted tumor treatment, tissue engineering and artificial organ's engineering. Copyright © 2018. Published by Elsevier Ltd.

Anesthetic state modulates excitability but not spectral tuning or neural discrimination in single auditory midbrain neurons

PubMed Central

Schumacher, Joseph W.; Schneider, David M.

2011-01-01

The majority of sensory physiology experiments have used anesthesia to facilitate the recording of neural activity. Current techniques allow researchers to study sensory function in the context of varying behavioral states. To reconcile results across multiple behavioral and anesthetic states, it is important to consider how and to what extent anesthesia plays a role in shaping neural response properties. The role of anesthesia has been the subject of much debate, but the extent to which sensory coding properties are altered by anesthesia has yet to be fully defined. In this study we asked how urethane, an anesthetic commonly used for avian and mammalian sensory physiology, affects the coding of complex communication vocalizations (songs) and simple artificial stimuli in the songbird auditory midbrain. We measured spontaneous and song-driven spike rates, spectrotemporal receptive fields, and neural discriminability from responses to songs in single auditory midbrain neurons. In the same neurons, we recorded responses to pure tone stimuli ranging in frequency and intensity. Finally, we assessed the effect of urethane on population-level representations of birdsong. Results showed that intrinsic neural excitability is significantly depressed by urethane but that spectral tuning, single neuron discriminability, and population representations of song do not differ significantly between unanesthetized and anesthetized animals. PMID:21543752

The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.

PubMed

Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

2016-01-01

To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p<0.001 and p<0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma. These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted. Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina. Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada. No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma. Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma colorretal, o aumento das expressões da betacatenina, GSK3β, 1 axina, e ubiquitina indicaram que o complexo de destruição de betacatenina estava alterado.

New Approaches for Prostate Cancer Combination Therapy

DTIC Science & Technology

2009-04-01

promoter methylation have been frequently observed in several types of human cancer (60, 61). In conclusion, the ability of NSAIDs to induce apoptosis...drug. Clin Pharmacokinet 1999; 36:115–26. 31. Yin MJ, Yamamoto Y, Gaynor RB. The anti- inflammatory agents aspirin and salicylate inhibit the activity...expression of the growth inhibitory gene GADD45g, in human pituitary adenomas, is asso- ciated with CpG island methylation . Oncogene 2004;23: 936–44. 61

Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma.

PubMed

Sekine, Shigeki; Yamashita, Satoshi; Tanabe, Taro; Hashimoto, Taiki; Yoshida, Hiroshi; Taniguchi, Hirokazu; Kojima, Motohiro; Shinmura, Kazuya; Saito, Yutaka; Hiraoka, Nobuyoshi; Ushijima, Toshikazu; Ochiai, Atsushi

2016-06-01

The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

PubMed

del Pliego, Margarita González; Aguirre-Benítez, Elsa; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Rangel-Morales, Carlos; Rodríguez-Mata, Verónica; Solano-Agama, Carmen; Martín-Tapia, Dolores; de la Vega, María Teresa; Saldoval-Balanzario, Miguel; Camacho, Javier; Mendoza-Garrido, María Eugenia

2013-01-01

Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

The inflammatory microenvironment in colorectal neoplasia.

PubMed

McLean, Mairi H; Murray, Graeme I; Stewart, Keith N; Norrie, Gillian; Mayer, Claus; Hold, Georgina L; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N Ashley G; Drew, Janice E; El-Omar, Emad M

2011-01-07

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified.

Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.

PubMed Central

Lloyd, R. V.; Cano, M.; Chandler, W. F.; Barkan, A. L.; Horvath, E.; Kovacs, K.

1989-01-01

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2466405

Soy-based polyols

DOEpatents

Suppes, Galen; Lozada, Zueica; Lubguban, Arnold

2013-06-25

The invention provides processes for preparing soy-based oligomeric polyols or substituted oligomeric polyols, as well as urethane bioelasteromers comprising the oligomeric polyols or substituted oligomeric polyols.

Choroid plexus adenoma in a child: expanding the clinical and pathological spectrum.

PubMed

Prendergast, Nicole; Goldstein, Jeffrey D; Beier, Alexandra D

2018-04-01

Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis

PubMed Central

Goltz, Diane; Fischer, Hans-Peter

2015-01-01

Molecular dissection of hepatocellular adenomas has brought forward a diversity of well-defined entities. Their distinction is important for routine practice, since prognosis is tightly related to the individual subgroup. Very recent activity has generated new details on the molecular background of hepatocellular adenoma, which this article aims to integrate into the current concepts of taxonomy. PMID:26404250

Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis.

PubMed

Goltz, Diane; Fischer, Hans-Peter

2015-09-02

Molecular dissection of hepatocellular adenomas has brought forward a diversity of well-defined entities. Their distinction is important for routine practice, since prognosis is tightly related to the individual subgroup. Very recent activity has generated new details on the molecular background of hepatocellular adenoma, which this article aims to integrate into the current concepts of taxonomy.

Effects of calcium on the incidence of recurrent colorectal adenomas

PubMed Central

Veettil, Sajesh K.; Ching, Siew Mooi; Lim, Kean Ghee; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-01-01

Abstract Background: Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence. Methods: The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs). Results: Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79–0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67–1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56–0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73–0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to “low.” Conclusion: The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed. PMID:28796047

Outcome of Surgical Treatment of 200 Children With Cushing's Disease

PubMed Central

Lonser, Russell R.; Wind, Joshua J.; Nieman, Lynnette K.; Weil, Robert J.; DeVroom, Hetty L.

2013-01-01

Context: Factors influencing the outcome of surgical treatment of pediatric Cushing's disease (CD) have not been fully established. Objective: The aim of this study was to examine features influencing the outcome of surgery for pediatric CD. Design: In this prospective observational study, the clinical, imaging, endocrinological, and operative outcomes were analyzed in consecutive patients treated at the National Institutes of Health (NIH) from 1982 through 2010. Setting: The study was conducted in a tertiary referral center. Results: Two hundred CD patients (106 females, 94 males) were included. Mean age at symptom development was 10.6 ± 3.6 years (range, 4.0 to 19.0 y). Mean age at NIH operation was 13.7 ± 3.7 years. Twenty-seven patients (13%) had prior surgery at another institution. Magnetic resonance imaging identified adenomas in 97 patients (50%). When positive, magnetic resonance imaging accurately defined a discrete adenoma in 96 of the 97 patients (99%), which was more accurate than the use of ACTH ratios during inferior petrosal sinus sampling to determine adenoma lateralization (accurate in 72% of patients without prior surgery). A total of 195 of the 200 patients (98%) achieved remission after surgery (189 [97%] were hypocortisolemic; 6 [3%] were eucortisolemic postoperatively). Factors associated with initial remission (P < .05) included identification of an adenoma at surgery, immunohistochemical ACTH-producing adenoma, and noninvasive ACTH adenoma. Younger age, smaller adenoma, and absence of cavernous sinus wall or other dural invasion were associated with long-term remission (P < .05). A minimum morning serum cortisol of less than 1 μg/dl after surgery had a positive predictive value for lasting remission of 96%. Conclusions: With rare disorders, such as pediatric CD, enhanced outcomes are obtained by evaluation and treatment at centers with substantial experience. Resection of pituitary adenomas in pediatric CD in that setting can be safe, effective, and durable. Early postoperative endocrine testing predicts lasting remission. Because lasting remission is associated with younger age at surgery, smaller adenomas, and lack of dural invasion, early diagnosis should improve surgical outcome. PMID:23372173

Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.

PubMed

Mete, Ozgur; Gomez-Hernandez, Karen; Kucharczyk, Walter; Ridout, Rowena; Zadeh, Gelareh; Gentili, Fred; Ezzat, Shereen; Asa, Sylvia L

2016-02-01

Originally classified as a variant of silent corticotroph adenoma, silent subtype 3 adenomas are a distinct histologic variant of pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3 adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary adrenal insufficiency. Significant hormonal excess in 29% of cases included hyperthyroidism in 17%, acromegaly in 8% and hyperprolactinemia above 150 μg/l in 4%. Two individuals with hyperprolactinemia who were younger than 30 years had multiple endocrine neoplasia type 1. Immunohistochemically, all 31 tumors were diffusely positive for the pituitary lineage-specific transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more hormones of Pit-1 cell lineage (growth hormone, prolactin, thyroid-stimulating hormone), as well as alpha-subunit and estrogen receptor. Most tumors exhibited perinuclear reactivity for keratins with the CAM5.2 antibody; scattered fibrous bodies were noted in five (16%) tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171) disease progression was documented in 53% of those cases. These data identify silent subtype 3 adenomas as aggressive monomorphous plurihormonal adenomas of Pit-1 lineage that may be associated with hyperthyroidism, acromegaly or galactorrhea and amenorrhea. Our findings argue against the use of the nomenclature 'silent' for these tumors. To better reflect the characteristics of these tumors, we propose that they be classified as 'poorly differentiated Pit-1 lineage adenomas'.

Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center.

PubMed

Gondim, Jackson A; Schops, Michele; de Almeida, João Paulo C; de Albuquerque, Lucas Alverne F; Gomes, Erika; Ferraz, Tânia; Barroso, Francisca Andréa C

2010-01-01

Pituitary tumors are challenging tumors in the sellar region. Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The introduction of the endoscope have revolutionized pituitary surgery. The aim of this study is to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed the data of 228 consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 10-year period. Pre- and post-operative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormone-secreting adenomas. Gross total removal was achieved in 79.3% of the cases after a median follow-up of 61.5 months. The remission results for patients with nonfunctioning adenomas was 83% and for functioning adenomas were 76.3% (70.6% for GH hormone-secreting, 85.3% for prolactin hormone-secreting, 71.4% for ACTH hormone-secreting, 85.7% for FSH-LH hormone-secreting and 100% for TSH hormone-secreting), with no recurrence at the time of the last follow-up. Post-operative complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (two cases) and CSF leaks (eight cases). There was no death related to the procedure in this series. The endoscopic endonasal approach for resection of pituitary adenomas, provides acceptable results representing a safe alternative procedure to the microscopic approach. This less invasive method, associated with a small number of complications, provides excellent tumor removal rates and represents an important tool for the achievement of good results in the pituitary surgery, mainly for the complete removal of large adenomas.

Biological relevance of effects following chronic administration of octamethylcyclotetrasiloxane (D4) in Fischer 344 rats.

PubMed

Dekant, Wolfgang; Scialli, Anthony R; Plotzke, Kathy; Klaunig, James E

2017-10-20

Octamethylcyclotetrasiloxane (D4) is a cyclic siloxane primarily used as a monomer or intermediate in the production of silicone polymers resulting in potential exposure of workers, and potential low level inhalation or dermal exposure for consumers and the general public. Following a two-year inhalation toxicity study with D4 in rats, increases in uterine endometrial cystic hyperplasia and adenomas were observed at the highest concentration of D4 administered (700ppm). No other neoplasms were increased with D4 treatment. In addition, chronic inhalation exposure of rats to D4 induced changes in relative liver and kidney weights, and produced a chronic nephropathy. This manuscript examines the biological relevance and possible modes of action for the effects observed in the F344 rat following chronic inhalation exposure to D4. D4 is not genotoxic and appears to exert its effects through a nongenotoxic mode of action. An alteration in the estrous cycle in the aging F344 rat was the most likely mode of action for the observed uterine effects following chronic inhalation exposure. Data support the conclusion that D4 acts indirectly via a dopamine-like mechanism leading to alteration of the pituitary control of the estrous cycle in aging F344 rats with a decrease in progesterone and an increase in the estrogen/progesterone ratio most likely induced by a decrease in prolactin concentration. D4 also inhibited the pre-ovulatory LH surge causing a delay in ovulation, persistent follicles and thus a prolonged exposure to elevated estrogen in the adult Sprague Dawely rat. A lengthening of the estrous cycle in the F344 rat with an increase in endogenous estrogen was also induced by D4 inhalation. Although the mode of action responsible for induction of uterine adenomas in the female F344 rat has not been clearly confirmed, the subtlety of effects on the effects of D4 on cyclicity may prevent further assessment and definition of the mode of action. The occurrence of uterine endometrial adenoma in the rat is not relevant for human risk characterization because (1) there are differences in ovulatory cycle regulation in rats compared to humans, (2) cystic hyperplasia without atypia in women is not a cancer precursor, and (3) there is no endometrial lesion in women that is directly analogous to endometrial adenoma in the rat. The effects of D4 on liver are due to a phenobarbital-like mechanism that results in induction of cytochrome P450 and other enzymes of xenobiotic biotransformation. The liver effects are adaptive and not adverse. Kidney findings included chonic progressive nephropathy, a rat lesion that has no counterpart in the human and that should not be used in human risk assessment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Methyl tertiary-butyl ether: studies for potential human health hazards.

PubMed

McGregor, Douglas

2006-04-01

When methyl tertiary-butyl ether (MTBE) in gasoline was first introduced to reduce vehicle exhaust emissions and comply with the Clean Air Act, in the United States, a pattern of complaints emerged characterised by seven "key symptoms." Later, carefully controlled volunteer studies did not confirm the existence of the specific key symptoms, although one study of self-reported sensitive (SRS) people did suggest that a threshold at about 11-15% MTBE in gasoline may exist for SRSs in total symptom scores. Neurobehavioral and psychophysiological studies on volunteers, including SRSs, found no adverse responses associated with MTBE at likely exposure levels. MTBE is well and rapidly absorbed following oral and inhalation exposures. Cmax values for MTBE are achieved almost immediately after oral dosing and within 2 h of continuous inhalation. It is rapidly eliminated, either by exhalation as unchanged MTBE or by urinary excretion of its less volatile metabolites. Metabolism is more rapid humans than in rats, for both MTBE and tert-butyl alcohol (TBA), its more persistent primary metabolite. The other primary metabolite, formaldehyde, is detoxified at a rate very much greater than its formation from MTBE. MTBE has no specific effects on reproduction or development, or on genetic material. Neurological effects were observed only at very high concentrations. In carcinogenicity studies of MTBE, TBA, and methanol (included as an endogenous precursor of formaldehyde, without the presence of TBA), some increases in tumor incidence have been observed, but consistency of outcome was lacking and even some degree of replication was observed in only three cases, none of which had human relevance: alpha(2u)-globulin nephropathy-related renal tubule cell adenoma in male rats; Leydig-cell adenoma in male rats, but not in mice, which provide the better model of the human disease; and B-cell-derived lymphoma/leukemia of doubtful pathogenesis that arose mainly in lungs of orally dosed female rats. In addition, hepatocellular adenomas were significantly higher in female CD-1 mice and thyroid follicular-cell adenomas were increased in female B6C3F1 mice treated with TBA, but these results lack any independent confirmation, which would have been possible from a number of other studies.

The effect of pharmacological inactivation of the mammillary body and anterior thalamic nuclei on hippocampal theta rhythm in urethane-anesthetized rats.

PubMed

Żakowski, Witold; Zawistowski, Piotr; Braszka, Łukasz; Jurkowlaniec, Edyta

2017-10-24

The mammillary body (MB) and the anterior thalamic nuclei (ATN) are closely related structures, which take part in learning and memory processes. However, the exact role of these structures has remained unclear. In both structures neurons firing according to hippocampal theta rhythm have been found, mainly in the medial mammillary nucleus (MM) and anteroventral thalamic nucleus (AV). These neurons are driven by descending projections from the hippocampal formation and are thought to convey theta rhythm back to the hippocampus (HP). We argue that the MB-ATN axis not only relays theta signal, but may also modulate it. To examine it, we performed a pharmacological inactivation of the MM and AV by local infusion of procaine, and measured changes in theta activity in selected structures of the extended hippocampal system in urethane-anesthetized rats. The inactivation of the MM resulted in decrease in EEG power in the HP and AV, the most evidently in the lower theta frequency bands, i.e. 3-5Hz in the HP (down to 9.2% in 3- to 4-Hz band and 37.6% in 4- to 5-Hz band, in comparison to the power in the control conditions) and 3-4Hz in the AV (down to 24.9%). After the AV inactivation, hippocampal EEG power decreased in theta frequency bands of 3-8Hz (down to 61.6% in 6- to 7-Hz band and 69.4% in 7- to 8-Hz band). Our results suggest that the role of the MB-ATN axis in regulating theta rhythm signaling may be much more important than has been speculated so far. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Prolactin-secreting pituitary adenoma in a man with gigantism: a case report.

PubMed

Peillon, F; Philippon, J; Brandi, A M; Fohanno, D; Laplane, D; Dubois, M P; Decourt, J

1979-12-01

A prolactin-secreting pituitary adenoma was removed trans-sphenoidally from a 37 years old man with gigantism (218 cm). Serum levels of prolactin (PRL) were elevated pre-operatively and decreased after administration of L-Dopa with no increase after TRH as is usually observed in PRL-secreting adenomas. Growth hormone (GH) and somatomedin serum levels were normal with no modification of GH after insulin hypoglycemia, oral glucose loading or L-Dopa. Morphological examination of the tumour demonstrated the presence of lactotrophs by light and electron microscopy and by immunofluorescense staining. No somatotrophs were found. In this unique case, the relationship between a PRL-secreting adenoma and gigantism is discussed.

Advanced endoscopic imaging to improve adenoma detection

PubMed Central

Neumann, Helmut; Nägel, Andreas; Buda, Andrea

2015-01-01

Advanced endoscopic imaging is revolutionizing our way on how to diagnose and treat colorectal lesions. Within recent years a variety of modern endoscopic imaging techniques was introduced to improve adenoma detection rates. Those include high-definition imaging, dye-less chromoendoscopy techniques and novel, highly flexible endoscopes, some of them equipped with balloons or multiple lenses in order to improve adenoma detection rates. In this review we will focus on the newest developments in the field of colonoscopic imaging to improve adenoma detection rates. Described techniques include high-definition imaging, optical chromoendoscopy techniques, virtual chromoendoscopy techniques, the Third Eye Retroscope and other retroviewing devices, the G-EYE endoscope and the Full Spectrum Endoscopy-system. PMID:25789092

Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis.

PubMed

Murakami, Akira; Furukawa, Ikuyo; Miyamoto, Shingo; Tanaka, Takuji; Ohigashi, Hajime

2013-01-01

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Oral kanglaite injection (KLTI) attenuates the lung cancer-promoting effect of high-fat diet (HFD)-induced obesity.

PubMed

Cao, Ning; Ma, Xiaofang; Guo, Zhenzhen; Zheng, Yaqiu; Geng, Shengnan; Meng, Mingjing; Du, Zhenhua; Lin, Haihong; Duan, Yongjian; Du, Gangjun

2016-09-20

Obesity is a risk factor for cancer and cancer-related mortality, however, its role in lung cancer progression remains controversial. This study aimed to assess whether high-fat diet (HFD)-induced obesity promotes lung cancer progression and whether the promotion can be decreased by Kanglaite injection (KLTI). In vivo, HFD-induced overweight or obesity increases the lung carcinoma incidence and multiplicity in a urethane-induced lung carcinogenic model and cancer-related mortality in a LLC allograft model by increasing oxidative stress and cellular signaling molecules including JAK, STAT3, Akt, mTOR, NF-κB and cyclin D1. These changes resulted in increases in vascular disruption and the lung water content, thereby promoting lung epithelial proliferation and the epithelial-mesenchymal transition (EMT) during carcinogenesis. Chronic KLTI treatment substantially prevented the weight gain resulting from HFD consumption, thereby reversing the metabolic dysfunction-related physiological changes and reducing susceptibility to lung carcinogenesis. In vitro, KLTI significantly suppressed the proliferation and induced apoptosis and differentiation in 3T3-L1 preadipocyte cells and attenuated endothelial cell permeability in HUVECs. Our study indicates that there is a potential relationship between obesity and lung cancer. This is the first study to show that obesity can directly accelerate carcinogen-induced lung cancer progression and that KLTI can decrease the lung cancer-promoting effect of HFD-induced obesity.

Pigmented well-differentiated hepatocellular neoplasm with beta-catenin mutation.

PubMed

Souza, Lara Neves; de Martino, Rodrigo Bronze; Thompson, Richard; Strautnieks, Sandra; Heaton, Nigel D; Quaglia, Alberto

2015-12-01

According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the beta-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcinomas. We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver. The patient was a 48-year-old woman, who was asymptomatic, and had a clinical history of intra-uterine exposure to diethylstilbestrol, previous cancers and past oral contraceptive use. The recently proposed term "well-differentiated hepatocellular neoplasm of uncertain malignant potential" should be applied in such cases to highlight the different pathogenesis and risk of malignancy compared to the typical adenomas, and to suggest a careful and customized clinical management.

Primary hyperparathyroidism may masquerade as rickets-osteomalacia in vitamin D replete children.

PubMed

Ganie, Mohd Ashraf; Raizada, Nishant; Chawla, Himika; Singh, Arun Kumar; Aggarwala, Sandeep; Bal, Chandra Sekhar

2016-10-01

Primary hyperparathyroidism, typically a disease of the middle aged and the old, is less commonly seen in children. In children the disease has a bimodal age distribution with calcium sensing receptor mutation presenting in infancy as hypercalcemic crises and parathyroid adenoma or hyperplasia presenting later in childhood with bone disease. The childhood parathyroid adenomas are often familial with multiglandular disease and manifest with severe bone disease unlike adults. We report a series of four male patients with juvenile primary hyperparathyroidism, three of whom presented with bone disease masquerading as rickets-osteomalacia. One patient had asymptomatic hypercalcemia with short stature. Parathyroid adenoma was detected in all the four cases and all of them underwent resection of parathyroid adenomas confirmed on histopathology. Post-surgery all the cases had initial hypocalcaemia followed by normocalcemia. One case developed pancreatitis after surgery even after achieving normocalcemia. We conclude that parathyroid adenomas, although uncommon in children, are an important cause of skeletal disease that may initially be confused with hypovitaminosis D.

Fetal adenoma of the pigmented ciliary epithelium associated with persistent hyperplastic primary vitreous.

PubMed

Doro, S; Werblin, T P; Haas, B; Iwamoto, T; Jakobiec, F A

1986-10-01

A 1.5-year-old girl presented with a peripheral iris mass. When the girl was 3 years old, the lesion was excised after it had manifested significant growth. A stalk of fibrovascular tissue was noted to extend from the lesion to the optic disc. Histopathologically, the tumor was a well-circumscribed, pigmented ciliary body adenoma. Electron microscopy revealed characteristic neuroepithelial melanosomes, distinct from those of choroidal melanocytes, and occasional annulate lamellae. A fibrovascular membrane extended over the tumor surface and was adherent to lens capsule. The association of this adenoma with a persistent stalk of primary vitreous indicates a congenital origin of this tumor. Both adenoma and adenocarcinoma of the pigmented and nonpigmented ciliary epithelium tend to be disorders of adults. The authors report the youngest presentation of a pigment epithelium adenoma, the only well-documented case associated with persistent hyperplastic primary vitreous, and the only documentation of annulate lamellae in a ciliary body tumor.

Chemical control of the viscoelastic properties of vinylogous urethane vitrimers

PubMed Central

Denissen, Wim; Droesbeke, Martijn; Nicolaÿ, Renaud; Leibler, Ludwik; Winne, Johan M.; Du Prez, Filip E.

2017-01-01

Vinylogous urethane based vitrimers are polymer networks that have the intrinsic property to undergo network rearrangements, stress relaxation and viscoelastic flow, mediated by rapid addition/elimination reactions of free chain end amines. Here we show that the covalent exchange kinetics significantly can be influenced by combination with various simple additives. As anticipated, the exchange reactions on network level can be further accelerated using either Brønsted or Lewis acid additives. Remarkably, however, a strong inhibitory effect is observed when a base is added to the polymer matrix. These effects have been mechanistically rationalized, guided by low-molecular weight kinetic model experiments. Thus, vitrimer elastomer materials can be rationally designed to display a wide range of viscoelastic properties. PMID:28317893

Reconfigurable and Reprocessable Thermoset Shape Memory Polymer with Synergetic Triple Dynamic Covalent Bonds.

PubMed

Wang, Yongwei; Pan, Yi; Zheng, Zhaohui; Ding, Xiaobin

2018-04-20

Degradable shape memory polymers (SMPs), especially for polyurethane-based SMPs, have shown great potential for biomedical applications. How to reasonably fabricate SMPs with the ideal combination of degradability, shape reconfigurability, and reprocessability is a critical issue and remains a challenge for medical disposable materials. Herein, a shape memory poly(urethane-urea) with synergetic triple dynamic covalent bonds is reported via embedding polycaprolactone unit into poly(urethane-urea) with the hindered urea dynamic bond. The single polymer network is biodegradable, thermadapt, and reprocessable, without sacrificing the outstanding shape memory performance. Such a shape memory network with plasticity and reprocessability is expected to have significant and positive impact on the medical device industry. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Binder and Mold parameters on Collapsibility and Surface Finish of Gray Cast Iron No-bake Sand Molds

NASA Astrophysics Data System (ADS)

Srinivasulu Reddy, K.; Venkata Reddy, Vajrala; Mandava, Ravi Kumar

2017-08-01

Chemically bonded no-bake molds and cores have good mechanical properties and produce dimensionally accurate castings compared to green sand molds. Poor collapsibility property of CO2 hardened sodium silicate bonded sand mold and phenolic urethane no-bake (PUN) binder system, made the reclamation of the sands more important. In the present work fine silica sand is mixed with phenolic urethane no-bake binder and the sand sets in a very short time within few minutes. In this paper it is focused on optimizing the process parameters of PUN binder based sand castings for better collapsibility and surface finish of gray cast iron using Taguchi design. The findings were successfully verified through experiments.

Saffron Aqueous Extract Inhibits the Chemically-induced Gastric Cancer Progression in the Wistar Albino Rat

PubMed Central

Bathaie, S. Zahra; Miri, Hamidreza; Mohagheghi, Mohammad-Ali; Mokhtari- Dizaji, Manijeh; Shahbazfar, Amir-Ali; Hasanzadeh, Hadi

2013-01-01

Objective(s): Gastric cancer is the first and second leading cause of cancer related death in Iranian men and women, respectively. Gastric cancer management is based on the surgery, radiotherapy and chemotherapy. In the present study, for the first time, the beneficial effect of saffron (Crocus sativus L.) aqueous extract (SAE) on the 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced gastric cancer in rat was investigated. Materials and Methods: MNNG was used to induce gastric cancer and then, different concentrations of SAE were administered to rats. After sacrificing, the stomach tissue was investigated by both pathologist and flow cytometry, and several biochemical parameters was determined in the plasma (or serum) and stomach of rats. Results: Pathologic data indicated the induction of cancer at different stages from hyperplasia to adenoma in rats; and the inhibition of cancer progression in the gastric tissue by SAE administration; so that, 20% of cancerous rats treated with higher doses of SAE was completely normal at the end of experiment and there was no rat with adenoma in the SAE treated groups. In addition, the results of the flow cytometry/ propidium iodide staining showed that the apoptosis/proliferation ratio was increased due to the SAE treatment of cancerous rats. Moreover, the significantly increased serum LDH and decreased plasma antioxidant activity due to cancer induction fell backwards after treatment of rats with SAE. But changes in the other parameters (Ca2+, tyrosine kinase activity and carcino-embryonic antigen) were not significant. Conclusion: SAE inhibits the progression of gastric cancer in rats, in a dose dependent manner. PMID:23638290

Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice

PubMed Central

Choi, Yoon Jin; Choi, Yoon Jeong; Kim, Nayoung; Nam, Ryoung Hee; Lee, Seonmin; Lee, Hye Seung; Lee, Ha-Na; Surh, Young-Joon; Lee, Dong Ho

2017-01-01

Background/Aims The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer. PMID:27965474

Biennial Report on Long-Term Dose-Response Studies of Inhaled or Injected Radionuclides, 1991 - 1993

DTIC Science & Technology

1994-01-01

found, multiple uterine fibromas, mammary adenomas, a parathyroid adenoma, and bilateral adrenal cortical adenomas. Dog 1106A, a male control, was...fibroma and uterine leiomyoma. Dog 1154S, a female with an ILB of 0.13 kBq 239Pu/kg body weight, was found dead 5016 days after exposure. At necropsy...vi I ITRI LIFE-SPAN STUDIES IN DOGS ............................................... I A. SPECIFIC PROJECT

Monomorphous Plurihormonal Pituitary Adenoma of Pit-1 Lineage in a Giant Adolescent with Central Hyperthyroidism.

PubMed

Pereira, Bernardo Dias; Raimundo, Luísa; Mete, Ozgur; Oliveira, Ana; Portugal, Jorge; Asa, Sylvia L

2016-03-01

Thyrotropin (TSH)-secreting pituitary adenomas are exceedingly rare at the pediatric age and no cases of co-secretion with other pituitary hormones in these tumors have been described in this age range. We present a case of a monomorphous plurihormonal pituitary adenoma that co-secreted TSH and GH in a pediatric patient. A 13-year-old male presented with increasing height velocity (17.75 cm/year, 9.55SD), weight loss, and visual impairment. Initial biochemical evaluations revealed secondary hyperthyroidism. A giant pituitary tumor compressing the surrounding structures was detected by magnetic resonance, and a transsphenoidal surgery was initially performed. Pathological examinations revealed an atypical, monomorphous plurihormonal Pit-1 lineage tumor with mixed features of silent subtype 3 adenoma and acidophil stem cell adenoma. In the postoperative period, secondary hyperthyroidism recurred with high levels of both GH and IGF1. In addition, due to tumor re-growth, a multimodality treatment plan was undertaken including surgery, somatostatin analogs, and radiotherapy. We report the first pediatric case of a plurihormonal TSH- and GH-secreting pituitary adenoma, further expanding the clinical manifestations of pediatric pituitary tumors. Comprehensive pathological evaluation and close follow-up surveillance are crucial to the prompt delivery of the best therapeutic options in the context of this particularly aggressive pituitary tumor.

Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.

PubMed

Kikuchi, Ryogo; Toda, Masahiro; Tomita, Toshiki; Ogawa, Kaoru; Yoshida, Kazunari

2017-01-01

This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists. We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS. Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed. T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

Interobserver agreement in the histologic diagnosis of colorectal polyps. the experience of the multicenter adenoma colorectal study (SMAC).

PubMed

Costantini, Massimo; Sciallero, Stefania; Giannini, Augusto; Gatteschi, Beatrice; Rinaldi, Paolo; Lanzanova, Giuseppe; Bonelli, Luigina; Casetti, Tino; Bertinelli, Elisabetta; Giuliani, Orietta; Castiglione, Guido; Mantellini, Paola; Naldoni, Carlo; Bruzzi, Paolo

2003-03-01

Current clinical practice guidelines for patients with colorectal polyps are mainly based on the histologic characteristics of their lesions. However, interobserver variability in the assessment of specific polyp characteristics was evaluated in very few studies. The purpose of this study was to evaluate the interobserver agreement of four pathologists in the diagnosis of histologic type of colorectal polyps and in the degree of dysplasia and of infiltrating carcinoma in adenomas. A stratified random sample of 100 polyps was obtained from the 4,889 polyps resected within the Multicentre Adenoma Colorectal Study (SMAC), and the slides were blindly reviewed by the four pathologists. Agreement was analyzed using kappa statistics. A median kappa of 0.89 (range 0.79-1.0) was estimated for the interobserver agreement for the diagnosis of hyperplastic polyp vs. adenoma. The agreement in the diagnosis of tubular, tubulovillous, and villous type, was given by median kappa values of 0.50, 0.15, and 0.36, respectively. The median kappa for the diagnosis of infiltrating carcinoma was 0.78 (range 0.73-0.84). Agreement on diagnosis of adenoma histologic subtypes, degrees of dysplasia, or infiltrating carcinoma in adenoma was moderate. A simpler classifications might help to better identify patients at different risk of colorectal cancer.

Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

ClinicalTrials.gov

2014-11-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.

PubMed

Huber, G F; Hüllner, M; Schmid, C; Brunner, A; Sah, B; Vetter, D; Kaufmann, P A; von Schulthess, G K

2018-06-01

To assess the additional diagnostic value of 18 F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18 F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. A total of 26 patients underwent 18 F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. These results demonstrate that 18 F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.

Clinically non-functioning pituitary adenomas: Pathogenic, diagnostic and therapeutic aspects.

PubMed

Mercado, Moises; Melgar, Virgilio; Salame, Latife; Cuenca, Dalia

Clinically non-functioning pituitary adenomas (NFPAs) are among the most common tumors in the sellar region. These lesions do not cause a hormonal hypersecretion syndrome, and are therefore found incidentally (particularly microadenomas) or diagnosed based on compressive symptoms such as headache and visual field defects, as well as clinical signs of pituitary hormone deficiencies. Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or their subunits and are therefore called gonadotropinomas, while 30% of them show no immunostaining for any hormone and are known as null cell adenomas. The diagnostic approach to NFPAs should include visual field examination, an assessment of the integrity of all anterior pituitary hormone systems, and magnetic resonance imaging of the sellar region to define tumor size and extension. The treatment of choice is transsphenoidal resection of the adenoma, which in many instances cannot be completely accomplished. The recurrence rate after surgery may be up to 30%. Persistent or recurrent adenomas are usually treated with radiation therapy. In a small proportion of these cases, drug treatment with dopamine agonists and, to a lesser extent, somatostatin analogs may achieve reduction or at least stabilization of the tumor. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Inactivation of the tumor suppressor gene on 11q13 in brothers with familial acrogigantism without multiple endocrine neoplasia type 1.

PubMed

Yamada, S; Yoshimoto, K; Sano, T; Takada, K; Itakura, M; Usui, M; Teramoto, A

1997-01-01

Two of three brothers (the second and third brothers) and their uncle (their mother's brother) presented acrogigantism without multiple endocrine neoplasia type 1 (MEN 1). An invasive macroadenoma was found in the second brother, and it was histologically confirmed as a sparsely granulated GH cell adenoma. Two distinct microadenomas were found in the third brother, and these were histologically diagnosed as a mixed GH cell and PRL cell adenoma and a sparsely granulated GH cell adenoma, respectively. The loss of heterozygosity (LOH) was analyzed in two adenomas (GH cell adenoma from the second brother and a mixed GH cell and PRL cell adenoma from the third brother) by determining microsatellite polymorphisms of DNAs from tumors and patients' leukocytes. The LOH was found on the chromosome 11q13, whereas LOH was not detected on 1p31-36, 2p, 3p, 4, 5, 6p, 7, 8, 9p21-22, 12p, and 19q13 in both pituitary adenomas examined. The haplotype analysis showed that the same haplotype on 11q13 was found in their mother and the unaffected first brother as well as in the affected uncle and two brothers. The deleted alleles on chromosome 11q13 in the tumors of two affected brothers were, however, restricted to those transmitted from their unaffected father. These data suggest that inactivation of the MEN 1 gene or other tumor suppressor genes on chromosome 11q13 plays an important role for the development of our familial acrogigantism without MEN 1.

Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study.

PubMed

Shimizu, Masahito; Fukutomi, Yasushi; Ninomiya, Mitsuo; Nagura, Kazuo; Kato, Tomohiro; Araki, Hiroshi; Suganuma, Masami; Fujiki, Hirota; Moriwaki, Hisataka

2008-11-01

Experimental studies indicate the chemopreventive properties of green tea extract (GTE) on colorectal cancer. Epidemiologically, green tea consumption of > 10 cups daily reduced colorectal cancer risk in Japanese. Because colorectal adenomas are the precursors to most sporadic colorectal cancers, we conducted a randomized trial to determine the preventive effect of GTE supplements on metachronous colorectal adenomas by raising green tea consumption in the target population from an average of 6 cups (1.5 g GTE) daily to > or = 10 cups equivalent (2.5 g GTE) by supplemental GTE tablets. We recruited 136 patients, removed their colorectal adenomas by endoscopic polypectomy, and 1 year later confirmed the clean colon (i.e., no polyp) at the second colonoscopy. The patients were then randomized into two groups while maintaining their lifestyle on green tea drinking: 71 patients supplemented with 1.5 g GTE per day for 12 months and 65 control patients without supplementation. Follow-up colonoscopy was conducted 12 months later in 125 patients (65 in the control group and 60 in the GTE group). The incidence of metachronous adenomas at the end-point colonoscopy was 31% (20 of 65) in the control group and 15% (9 of 60) in the GTE group (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < 0.05). The size of relapsed adenomas was also smaller in the GTE group than in the control group (P < 0.001). No serious adverse events occurred in the GTE group. GTE is an effective supplement for the chemoprevention of metachronous colorectal adenomas.

Top 100 Most-cited Articles on Pituitary Adenoma: A Bibliometric Analysis.

PubMed

Guo, Xiaopeng; Gao, Lu; Wang, Zihao; Feng, Chenzhe; Xing, Bing

2018-06-02

Many articles have been published on pituitary adenomas. Bibliometric analyses are helpful for determining the most impactful studies within a field. To identify the top 100 most-cited articles on pituitary adenomas using the bibliometric analysis method. We searched the Thomson Reuters Web of Science on March 31, 2018. Articles were listed in descending order by the total citation (TC) number, and the most-cited articles on pituitary adenomas were identified and analyzed. The most-cited articles were published between 1970 and 2014, with 1999 as the most prolific year. Growth hormone-secreting pituitary adenoma was the most commonly studied tumor subtype (43%), and in clinical studies, treatment options and follow-up were the most important research focuses (62%). The average number of TCs was 326, and the average number of annual citations (ACs) was 17. More review articles were published in the last decade, and the average number of ACs was higher for this decade than for previous decades. Twenty-one articles were recognized as "Citation Classics" with a TC number>400. Twenty-five journals published the top 100 works; the Journal of Clinical Endocrinology and Metabolism published the most articles (25%). The most articles (43%) were published in the United States. S. Melmed authored the greatest number of publications (14%). Departments of Medicine (32%) and Endocrinology (32%) contributed to the largest number of articles. This study identified the research focuses and trends regarding pituitary adenoma and provides key references for investigators in guiding future pituitary adenoma research. Copyright © 2018 Elsevier Inc. All rights reserved.

The Inflammatory Microenvironment in Colorectal Neoplasia

PubMed Central

McLean, Mairi H.; Murray, Graeme I.; Stewart, Keith N.; Norrie, Gillian; Mayer, Claus; Hold, Georgina L.; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N. Ashley G.; Drew, Janice E.; El-Omar, Emad M.

2011-01-01

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified. PMID:21249124

Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

PubMed Central

Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Cázares, Hugo Guerrero; Burger, Peter; Salvatori, Roberto; Quiñones-Hinojosa, Alfredo

2014-01-01

Purpose Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. Results GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Conclusion Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis. PMID:24402129

Rare case of Cushing's disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk.

PubMed

Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno

2014-01-01

We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.