tbuckley/cabot-search huggingface dataset:
A new bronchoscopic treatment of tracheomediastinal fistula using autologous adipose-derived stem cells
Authors: P D.-A. Alvarez, M Garcia-Arranz, T Georgiev-Hristov, D Garcia-Olmo
Journal: Thorax (2008)

Tracheal fistulas represent a challenging management problem. The standard treatment in most cases is based on surgical procedures. Various endoscopic treatment modalities have been proposed in patients at high surgical risk but the results are often unsatisfactory. The fistulas frequently recur with additional complications and sometimes death. The case history is reported of a patient with a tracheomediastinal fistula resulting from laser treatment of tracheal cancer. The fistula was treated by bronchoscopic injection of autologous adipose-derived stem cells (ASC) suspended in fibrin glue. The patient's stem cells were isolated from lipoaspirate according to a standard-ised procedure. No complications due to treatment with ASC occurred during the follow-up period and no fistula-related symptoms were detected. Postoperative bronchoscopic examination of the wall and base of the fistula revealed re-epithelialisation and neovascularisation that led to successful closure. To our knowledge, this is the first report of treatment of tracheal fistula by autologous cell therapy. Further studies are needed to confirm whether this new method should become routine practice.
Use of Replication-Conditional Adenovirus as a Helper System to Enhance Delivery of P450 Prodrug-Activation Genes for Cancer Therapy
Authors: Youssef Jounaidi, David J. Waxman
Journal: Cancer Research (2004)

Abstract Cytochrome P450 (CYP) gene transfer sensitizes tumor xenografts to anticancer prodrugs such as cyclophosphamide (CPA) without a detectable increase in host toxicity. Optimal prodrug activation is achieved when a suitable P450 gene (e.g., human CYP2B6) is delivered in combination with NADPH-cytochrome P450 reductase (P450R), which encodes the flavoenzyme P450 reductase. We sought to improve this gene therapy by coordinated delivery and expression of P450 and P450R on a single bicistronic vector using an internal ribosomal entry site (IRES) sequence. Retrovirus encoding a CYP2B6-IRES-P450R expression cassette was shown to induce strong P450-dependent CPA cytotoxicity in a population of infected 9L gliosarcoma cells. Adeno-P450, a replication-defective, E1/E3 region-deleted adenovirus engineered to express CYP2B6-IRES-P450R, induced intracellular CPA 4-hydroxylation, and CPA cytotoxicity, in a broad range of human cancer cell lines. However, limited Adeno-P450 gene transfer and CPA chemosensitization was seen with certain human tumor cells, notably PC-3 prostate and HT-29 colon cancer cells. Remarkable improvements could be obtained by coinfecting the tumor cells with Adeno-P450 in combination with Onyx-017, an E1b-55k gene-deleted adenovirus that selectively replicates in p53 pathway-deficient cells. Substantial increases in gene expression were observed during the early stages of viral infection, reflecting an apparent coamplification of the Adeno-P450 genome, followed by enhanced viral spread at later stages, as demonstrated in cultured tumor cells, and in A549 and PC-3 solid tumor xenografts grown in scid mice. This combination of the replication-defective Adeno-P450 with a replication-conditional and tumor cell-targeted helper adenovirus dramatically improved the low gene transfer observed with some human tumor cell lines and correspondingly increased tumor cell-catalyzed CPA 4-hydroxylation, CPA cytotoxicity, and in vivo antitumor activity in a PC-3 tumor xenograft model. The use of tumor-selective, replicating adenovirus to promote the spread of replication-defective gene therapy vectors, such as Adeno-P450, substantially increases the therapeutic potential of adenoviral delivery systems, and should lead to increased activity and enhanced tumor selectivity of cytochrome P450 and other gene-directed enzyme prodrug therapies.
Is COPD a risk factor for diabetes
Authors: Laura Ciobanu, Vasile Maciuc, Anca Cretu, Gabriela Grigoras
Journal: European Respiratory Journal (2012)

Introduction : Diabetes mellitus is one of the multiple endocrinological disorders induced by COPD through systemic inflammation, oxidative stress, smoking and administration of glucocorticoids.   Aims and objectives : To investigate if COPD is a risk factor for diabetes mellitus DM and what stage is more risky; also, if there are some other contributing factors.   Methods : 2 groups of pts were assessed for age, gender, body mass index (BMI), smoking, alcohol intake, diabetes and dyslipidemia. First group was compound of non-COPD pts (N 272, 62 M/22.8%, 210 F/77.2%, mean age 60.67, SD 13.75) and the second one of COPD pts (N 178, 103 M/57.9%, 75 F/42.1%, mean age 64.79, SD 10.78). COPD pts were staged according to GOLD criteria in stage I 122/27.1 % pts, stage II 28/6.2 % pts, stage III 22/4.9% and stage IV 6/1.3%.   Results : The relative risk RR for DM to appear in COPD pts is 1.380 (95% CI 1.054-1.806). RR is 1.023 (95% CI 0.896-1.146) in COPD stage I, 1.252 (95% CI 0,904-1.735) in stage II and 2.062 (95% CI 0.863-4.930) in unified stages III and IV. There is a correlation coefficient R of 0.154 between COPD and DM, 0.256 for COPD, BMI and DM and respectively 0.293 for COPD, BMI, dyslipidemia and DM.   Conclusions : There is a small risk for DM to appear in the whole group of COPD pts, but RR increases while advancing the severity of disease. Being mild in stages I and II, RR become moderate in the unified group of pts staged III and IV, considered together due to the low number for each separate stage. Correlation between DM and COPD is weak, but it is moderate and relevant when adding BMI and dyslipidemia. The risk to develop DM in COPD increases with the severity of disease, and the presence of two other important factors, BMI and dyslipidemia.
Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD
Authors: Susan C. Schiavi, Wen Tang, Christina Bracken, Stephen P. O’Brien, Wenping Song, Joseph Boulanger, Susan Ryan, Lucy Phillips, Shiguang Liu, Cynthia Arbeeny, Steven Ledbetter, Yves Sabbagh
Journal: Journal of the American Society of Nephrology (2012)

The incidence of cardiovascular events and mortality strongly correlates with serum phosphate in individuals with CKD. The Npt2b transporter contributes to maintaining phosphate homeostasis in the setting of normal renal function, but its role in CKD-associated hyperphosphatemia is not well understood. Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. Treating Npt2b-deficient mice with the phosphate binder sevelamer carbonate further reduced serum phosphate levels. Uremic mice exhibited high turnover renal osteodystrophy; treatment with sevelamer significantly decreased the number of osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but sevelamer did not affect bone formation and rate of mineral apposition in wild-type mice. Taken together, these data suggest that targeting Npt2b in addition to using dietary phosphorus binders may be a therapeutic approach to modulate serum phosphate in CKD.
Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study
Authors: A. Jatoi
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P = .0001) for appetite and 11% versus 3% (P = .02) for ≥ 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate–treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.
Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial
Authors: Eitan Kerem, Samit Hirawat, Shoshana Armoni, Yasmin Yaakov, David Shoseyov, Michael Cohen, Malka Nissim-Rafinia, Hannah Blau, Joseph Rivlin, Micha Aviram, Gary L Elfring, Valerie J Northcutt, Langdon L Miller, Batsheva Kerem, Michael Wilschanski
Journal: The Lancet (2008)
Tumor-Suppressive miR148a Is Silenced by CpG Island Hypermethylation in <i>IDH1</i>-Mutant Gliomas
Authors: Sichen Li, Reshmi Chowdhury, Fei Liu, Arthur P. Chou, Tie Li, Reema R. Mody, Jerry J. Lou, Weidong Chen, Jean Reiss, Horacio Soto, Robert Prins, Linda M. Liau, Paul S. Mischel, Phioanh L. Nghiemphu, William H. Yong, Timothy F. Cloughesy, Albert Lai
Journal: Clinical Cancer Research (2014)

Abstract Purpose: IDH1/2-mutant gliomas harbor a distinct glioma-CpG island methylation phenotype (G-CIMP) that may promote the initiation and progression of secondary pathway gliomas by silencing tumor-suppressive genes. The potential role of tumor-suppressive microRNAs (miRNA; miR) in this process is not understood. Experimental Design: To identify potential tumor-suppressive miRNA hypermethylated in glioma, the methylation profiles of IDH1/2WT gliomas (n = 11) and IDH1MUT glioma (n = 20) were compared by using massively parallel reduced representation bisulfite sequencing (RRBS). The methylation status of selected miRNA was validated by using targeted bisulfite sequencing (BiSEQ) in a large cohort of glioma tissue samples including 219 IDH1WT and 72 IDH1/2MUT samples. The expression of selected miRNAs was determined by using the TaqMan qPCR. Functional analyses of miR148a were conducted and target genes were identified. Results: We identify miR148a as a novel, G-CIMP–associated miRNA whose methylation is tightly correlated with IDH1 mutation and associated with improved survival in patients with malignant glioma. We confirm that downregulation of miR148a can occur via DNA methylation. We demonstrate that IDH1 mutation provides a mechanism of miR148a methylation and downregulation, and that restoration of miR148a reduced tumorigenic properties of glioma cells, possibly by targeting DNMT1. Conclusions: We identify miR148a as a novel G-CIMP–associated miRNA, and provide results suggesting that miR148a restoration may have therapeutic implications. Clin Cancer Res; 20(22); 5808–22. ©2014 AACR.
570 OUTFLOW RECONSTRUCTION USING NATIVE LIVER VEINS IN RIGHT LOBE GRAFTS WITHOUT MHV HARVESTING: 3 YEARS EXPERIENCE
Authors: H. Soliman, H. Shoreem, T. Ibrahiem, M. Osman, O. Hegazy, S. Saleh, E. Soliman, K. Abuelellela, K. Yassen, M. Hussein, M. Khalil, K. Yassein, H. Zagla, M. Eltabakh, M. Salama, I. Waked, I. Marwan
Journal: Journal of Hepatology (2011)
Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer.
Authors: Karin Collett, Geir E Eide, Jarle Arnes, Ingunn M Stefansson, Johan Eide, Audun Braaten, Turid Aas, Ariel P Otte, Lars A Akslen
Journal: Clinical Cancer Research (2006)

Abstract The polycomb group protein enhancer of zeste homologue 2 (EZH2) has been linked to invasive properties of aggressive breast cancer. In this report, tissue microarray analysis of 190 breast carcinomas from a nested case-control study shows that EZH2 is significantly associated with interval breast cancers. Further, a strong relationship was found with tumor cell proliferation (by Ki-67 expression), locally advanced disease, metastasis at presentation, markers of the basal epithelial phenotype (positivity for cytokeratin 5/6 or P-cadherin), and p53 status. EZH2 expression was also significantly associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype. For prediction of aggressive disease (any event of locally advanced disease, lymph node spread, or distant spread), EZH2 was the only variable of significance in multivariate analysis, whereas no additional information was given by Ki-67. Although EZH2 expression was significant in univariate survival analysis, only tumor cell proliferation and lymph node status were significant in the final multivariate model. In conclusion, our findings indicate an important relationship not only between EZH2 and markers of tumor cell proliferation but also with aggressive disease. These findings might be practically important and relevant because the polycomb group proteins have recently been suggested as candidates for targeted therapy.
Alcohol intake and incidence of type 2 diabetes in men.
Authors: M Wei, L W Gibbons, T L Mitchell, J B Kampert, S N Blair
Journal: Diabetes Care (2000)

OBJECTIVE: To evaluate the relation between alcohol intake and incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: This prospective study included 8,663 men with fasting plasma glucose measurements from at least two medical examinations. Alcohol intake was classified into five groups: nondrinkers and four quartiles (Qs) of drinkers according to the amount of alcohol intake. Type 2 diabetes was diagnosed by 1997 American Diabetes Association criteria. RESULTS: There were 149 incident cases of type 2 diabetes during 52,588 person-years of follow-up. There was a U-shaped association between alcohol intake and diabetes, with the lowest incidence of diabetes at Q2 (61.9-122.7 g/week). As compared with Q2, men in Q3 and Q4 had a 2.2- (95% CI 1.2-3.9, P = 0.01) and 2.4-fold (1.4-4.4, P&amp;lt;0.01) risk of developing diabetes, while nondrinkers and men in Q1 had 1.8- (1.0-3.3, P&amp;lt;0.05) and 1.4-fold (0.7-2.6, P = 0.34) higher risk of diabetes, respectively. These associations persisted after adjustment for age, fasting plasma glucose, smoking, BMI, blood pressure, serum triglyceride concentration, cardiorespiratory fitness, HDL cholesterol, waist circumference, and parental diabetes. CONCLUSIONS: We observed an elevated risk of developing type 2 diabetes in nondrinkers and men with high alcohol intakes, when compared with men who reported moderate alcohol intake. Men with a high alcohol intake may be able to reduce their risk of developing type 2 diabetes if they drink less.
Mental health screening in armed forces before the Iraq war and prevention of subsequent psychological morbidity: follow-up study
Authors: Roberto J Rona, Richard Hooper, Margaret Jones, Lisa Hull, Tess Browne, Oded Horn, Dominic Murphy, Matthew Hotopf, Simon Wessely
Journal: BMJ (2006)

<b>Objective</b> To assess whether screening for mental disorder before the start of the 2003 Iraq war would have predicted subsequent mental disorders. <b>Design</b> Longitudinal cohort study of the United Kingdom armed forces. <b>Participants</b> 2820 of 2873 personnel of the three services who completed an initial questionnaire in 2002 were asked to complete a second questionnaire between June 2004 and 2 March 2006. <b>Setting</b> Regiments, air stations, bases, ships, and homes for those who had left the services. <b>Main outcome measures</b> Positive and negative likelihood ratios, and positive and negative predictive value of first assessment compared with assessment two to three years later of post-traumatic stress disorder, general health questionnaire, physical symptoms, self perception of health, and alcohol misuse for the entire group and for those deployed to the Iraq war. <b>Results</b> The response rate to the follow-up questionnaire was 69%, adjusted for return to senders. The positive likelihood ratio of post-traumatic stress disorder was high (13.1, 95% confidence interval 7.2 to 23.8), but the negative likelihood ratio was close to 1 (0.78, 0.67 to 0.91). The positive predictive values were low because of the low prevalence of post-traumatic stress disorder in the period before the Iraq war. The positive likelihood ratios for the other psychological assessments varied between 2.7 and 5.6, and the negative likelihood ratios were slightly lower than for post-traumatic stress disorder, indicating that these were not good candidates for screening. Results were the same for the analyses restricted to those who were deployed. <b>Conclusions</b> Screening for common mental disorders before deployment in this cohort would not have reduced subsequent morbidity or predicted post-traumatic stress disorder, but this may change if there is a considerable increase in the prevalence of the disorder.
Increased Adenosine Monophosphate–Activated Protein Kinase Activity in Rat Hearts With Pressure-Overload Hypertrophy
Authors: Rong Tian, Nicolas Musi, Jessica D’Agostino, Michael F. Hirshman, Laurie J. Goodyear
Journal: Circulation (2001)

Background Recent reports suggest that activation of adenosine monophosphate (AMP)–activated protein kinase (AMPK), in response to acute changes in cellular energy status in cardiac and skeletal muscles, results in altered substrate utilization. We hypothesized that chronic alterations in myocardial energetics in hypertrophied hearts (left ventricular hypertrophy, LVH) will lead to elevated AMPK activity, which in turn regulates substrate utilization. Methods and Results Using 31 P NMR spectroscopy and biochemical assays, we found that in LVH hearts, adenosine triphosphate (ATP) concentration decreased by 10%, phosphocreatine concentration decreased by 30%, and total creatine concentration was unchanged. Thus, the ratio of phosphocreatine/creatine decreased to one third of controls, and the ratio of AMP/ATP increased to 5 times above controls. These changes were associated with increased α 1 and α 2 AMPK activity (3.5- and 4.8-fold above controls, respectively). The increase in AMPK α 1 activity was accompanied by a 2-fold increase in α 1 expression, whereas α 2 expression was decreased by 30% in LVH. The basal rate of 2-deoxyglucose uptake increased by 3-fold in LVH, which was associated with an increased amount of glucose transporters present on the plasma membrane. Conclusions These results demonstrate for the first time that chronic changes in myocardial energetics in hypertrophied hearts are accompanied by significant elevations in AMPK activity and isoform-specific alterations in AMPK expression. It also raises the possibility that AMPK signaling plays an important role in regulating substrate utilization in hypertrophied hearts.
Neutrophil Gelatinase–Associated Lipocalin: A Novel Suppressor of Invasion and Angiogenesis in Pancreatic Cancer
Authors: Zhimin Tong, Ajaikumar B. Kunnumakkara, Huamin Wang, Yoichi Matsuo, Parmeswaran Diagaradjane, Kuzhuvelil B. Harikumar, Vijaya Ramachandran, Bokyung Sung, Arup Chakraborty, Robert S. Bresalier, Craig Logsdon, Bharat B. Aggarwal, Sunil Krishnan, Sushovan Guha
Journal: Cancer Research (2008)

Abstract Neutrophil gelatinase–associated lipocalin (NGAL) is a 25-kDa secreted acute phase protein, which is also up-regulated in multiple cancers, including breast, lung, and pancreas. Recently, NGAL has been proposed as an early biomarker in pancreatic cancer (PaCa). However, its biological role in PaCa is unknown. In this study, we examined in vitro and in vivo the functional role of NGAL in PaCa. Well- to moderately differentiated PaCa cells (AsPC-1, BxPC-3, and Capan-2) expressed high levels of NGAL but moderately to poorly differentiated PaCa cells (PANC-1 and MIAPaCa-2) expressed undetectable NGAL levels. Immunohistochemistry of untreated tissue microarray showed specific NGAL staining in resected PaCa specimens (P = 0.0167). Stable NGAL overexpression (MIAPaCa-2 and PANC-1) significantly blocked PaCa cell adhesion and invasion in vitro and vice versa with stable PaCa clones (BxPC-3 and AsPC-1). Moreover, NGAL overexpression reduced focal adhesion kinase (FAK) tyrosine-397 phosphorylation in PaCa cells. Furthermore, NGAL overexpression potently decreased angiogenesis in vitro partly through reduced vascular endothelial growth factor (VEGF) production and vice versa. Stable NGAL overexpression or underexpression had no effect on PaCa cell survival, viability, and response to chemotherapeutic drugs. Finally, MIAPaCa-2 cells overexpressing NGAL reduced tumor volume (P = 0.012), local and distant metastasis (P = 0.002), and angiogenesis (P = 0.05) with no effect on K-67 proliferation index (P &amp;gt; 0.1) in an orthotopic nude mouse PaCa model. Collectively, our results suggest that NGAL reduces adhesion/invasion partly by suppressing FAK activation and inhibits angiogenesis partly by blocking VEGF production in PaCa cells. Thus, NGAL is a potential suppressor of invasion and angiogenesis in advanced PaCa. [Cancer Res 2008;68(15):6100–8]
STUDIES ON THE ANTIGENIC COMPOSITION OF GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Robert F. Watson, Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1944)

1. In this study a series of experiments showing the antigenic relationship of type 10 and type 12 group A hemolytic streptococci is reported. Agglutinin, precipitin, and passive protection tests with unabsorbed and reciprocally absorbed antisera were employed to show that representative type 10 and 12 strains contain serologically identical M antigens but unrelated type-specific T antigens. 2. Twenty-three other strains of group A hemolytic streptococci previously classified as either type 10 or type 12, collected from various sources, were shown to have an antigenic composition similar to one or the other of the two representative type strains. 3. The relationship of the two specific antigens, M and T, must be considered when any method employing the agglutinin reaction for the typing of group A hemolytic streptococci is used.