tbuckley/cabot-search huggingface dataset:
Abstract 2065: DDX20 deficiency enhances NF-κB by impairing NF-κB suppressive-microRNA function and leads to hepatocarcinogenesis
Authors: Akemi Takata, Motoyuki Otsuka, Yotaro Kudo, Kentaro Kojima, Shin Maeda, Keisuke Tateishi, Tsuneo Ikenoue, Hideaki Ijichi, Yoshihiro Hirata, Haruhiko Yoshida, Masao Omata, Kazuhiko Koike
Journal: Cancer Research (2010)

Abstract Hepatocellular carcinoma is the third leading cause of cancer mortality worldwide, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we show that DDX20, a DEAD-box protein identified as a tumor suppressor in a recent comprehensive in vivo screening of murine liver cancer, might have a role in human hepatocellular oncogenesis through previously undefined mechanisms. DDX20 expression was frequently decreased in hepatocellular carcinoma cells compared with the hepatocytes in the noncancerous liver tissues from the same patient, as determined by immunohistochemistry using tissue arrays. DDX20-knockdown cells showed enhanced NF-κB activity and higher interleukin-6 expression, a cytokine known to be related to hepatocarcinogenesis. Our microRNA library screening revealed that several microRNAs expressed in hepatocytes, such as miR-140, normally suppress NF-κB activities. The deficiency of DDX20, a component of microRNA-containing ribonucleoprotein complexes, impaired microRNA function and this led to the impairment of the NF-κB-suppressive microRNA function, and consequently, enhanced NF-κB activity. These results indicate that DDX20 deficiency enhances NF-κB activity by impairing NF-κB-suppressive microRNA function and may contribute to hepatocarcinogenesis. “Functional impairment of microRNAs” identified here, induced by aberrant expression or functional abnormalities of the molecules involved in the microRNA pathway, may also be one of the mechanisms of oncogenesis even in other organs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2065.
P430 SELECTIVE INTERNAL RADIATION THERAPY FOR HEPATOCELLULAR CARCINOMA: COMBINATION WITH SORAFENIB IS ASSOCIATED WITH IMPROVED SURVIVAL OUTCOMES
Authors: M.X. Ma, L. Adams, G. Garas, G. Macquillan, M. O'dea, S. Samuelson, J. Tibballs, R. Mac Nicholas
Journal: Journal of Hepatology (2014)
The Demise of Vermont's Single-Payer Plan
Authors: John E. McDonough
Journal: New England Journal of Medicine (2015)

Interview with Prof. John McDonough on Vermont’s attempt to implement a single-payer health care system — and why it failed. (14:12)Download Last December, Vermont Governor Peter Shumlin ended a 4-year initiative to create a single-payer health care system. The plan was abandoned because of legitimate political considerations, and any other state considering single payer will face similar obstacles.
Abstract 4768: Design and development of selective sphingosine kinase 2 inhibitors
Authors: Kai Liu, Shijun Zhang
Journal: Cancer Research (2012)

Abstract Sphingosine-1-phosphate (S1P) has been recently implicated to play a vital role in regulating a variety of physiological and pathological processes including proliferation, differentiation, migration, and cell survival. S1P is produced endogenously by sphingosine kinases (SKs) and the balance of the levels of S1P, its precursor sphingosine, and ceramide, referred to as the “sphingosine rheostat,” is important for normal cellular functions. To date, two isoforms of SPKs have been reported, sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2). Many efforts have been invested to study the roles of SK1 and SK1 has been indicated in the regulation of cancer progression and development. However, much is still remain unknown for SK2 and current results of the function of SK2 are complex and controversial. This is also reflected in the development of SK inhibitors. Several potent selective SK1 inhibitors have been reported and tested as potential cancer treatment agents. However, no potent and selective SK2 inhibitors have been developed to date. Therefore, there is an urgent need to develop SK2 selective inhibitors as pharmacological tools to help unravel the roles of SK2. Recently, we discovered that a series of thiazolidine-2,4-dione analogs selectively inhibit SK2 and one lead compound was identified to inhibit SK2 with sub-µM potency but no activity to SK1 with a concentration up to 10 µM. Herein, we will report the structure activity relationship (SAR) studies of this newly identified lead SK2 inhibitor to optimize its potency and selectivity towards SK2. Furthermore, these analogs will be biologically characterized in human leukemia U937 cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4768. doi:1538-7445.AM2012-4768
Abstract 2534: Novel and stable water-soluble N-mustards with potent therapeutic efficacy against human tumor xenografts in nude mice
Authors: Tsann-Long Su, Rajesh Kakadiya, Huajin Dong, Yi-Ren Chen, Pei-Chih Lee, Ting-Chao Chou, Pei-Wen Hsiao, Te-Chang Lee, Bhavin Marvania
Journal: Cancer Research (2011)

Abstract The bioavailability of drugs is one of the important factors to determine whether a drug can be successfully developed for clinical application. Consequently, the physicochemical properties, including solubility, permeability, stability pKa, and lipophilicity/hydrophilicity balance, are key factors that influence the bioavailability of drugs. Compounds with poor solubility usually have a higher risk of difficulties to overcome during the period of new drug discovery and development because these properties may affect antitumor evaluations in animal models as well as pharmacokinetic and pharmacodynamic properties of the compound. In the present studies, we have synthesized a series of novel water-soluble N-mustard-benzene conjugates bearing a urea linker were synthesized. The benzene moiety contains a variety of hydrophilic side chains. These side chains are linked to the meta- or para-position of the urea linker via a carboxamide or an ether linkage. Compounds having a carboxamide hydrophilic side-chain can be converted into water-soluble hydrochloride or mesylate. The preliminary antitumor studies revealed that these conjugates exhibited potent cytotoxicity in vitro and antitumor therapeutic efficacy against human tumor xenografts in vivo. Furthermore, these derivatives have little or no cross-resistance to either Taxol or Vinblastine. Among these conjugates, compound WS-1707, which bearing a N,N-dimethylaminoethylcarboxamide hydrochloride water-soluble side-chain possessed potent therapeutic efficacy in nude mice bearing human breast carcinoma MX-1 (Remarkably, complete tumor remission in nude mice bearing human breast carcinoma MX-1 xenograft (complete tumor remission), prostate adenocarcinoma PC-3 xenograft (&amp;gt;99% suppression), and human colon cancer HCT-116 xenograft (&amp;gt;95% suppression) at the maximal tolerable dose 30 mg/kg, Q2D×5, intravenous injection. We also compared the therapeutic potency of WS-1707 with Carbopltin, and Doxetaxol in nude mice bearing prostate cancer HL2 xenograft (orthotopic implantation). It reveals that WS-1707 is as potent as Doxetaxol (&amp;gt;82% tumor suppression), but significantly more potent than Carboplatin. Study on the mechanism of action that this agent is able to induce DNA cross-linking through alkaline agarose gel shift assay. Early pharmacokinetic study shows that this conjugates has acceptable profile in rats with a half-life of 0.56 h. These results suggest that this agent is a promising candidate for preclinical studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2534. doi:10.1158/1538-7445.AM2011-2534
Prostate-Specific Antigen as a Serum Marker for Adenocarcinoma of the Prostate
Authors: Thomas A. Stamey, Norman Yang, Alan R. Hay, John E. McNeal, Fuad S. Freiha, Elise Redwine
Journal: New England Journal of Medicine (1987)

To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.
Case 9-2013
Authors: Mary Shannon Fracchia, Chadi M. El Saleeby, Mandakolathur R. Murali, Pallavi Sagar, Mari Mino-Kenudson
Journal: New England Journal of Medicine (2013)

A 9-year-old boy was admitted to the hospital because of fever, cough, respiratory distress, and chest pain. Imaging revealed ill-defined nodular opacities throughout all lung lobes, areas of consolidation, and mediastinal and hilar lymphadenopathy.
874 RAPID VIROLOGICAL RESPONSE IN HIV/HCV-COINFECTED PATIENTS WITH GENOTYPE 1 RECEIVING TELAPREVIR OR BOCEPREVIR OUTSIDE CLINICAL TRIALS: RESULTS FROM HEPAVIR-THERAPY COHORT
Authors: J.A. Mira, A. Camacho, L.F. López-Cortés, M. Márquez, C. Cifuentes, A. Rivero-Juárez, R. Ruiz-Valderas, J. Santos, J. Macías, A. Rivero, A. Torres-Cornejo, G. Ojeda, J.A. Pineda
Journal: Journal of Hepatology (2013)
The assessment of depression: a model for quality review of emergency psychiatry
Authors: F Kass, I Salamon, R Plutchik, I Hyman
Journal: American Journal of Psychiatry (1978)

Of 167 patients appearing in the psychiatric emergency room of a metropolitan hospital, 68 were categorized as significantly depressed by the Zung depression scale but only 43 were considered depressed by clinician-interviewers. The use of a patient self-rating scale, which in this setting permitted the identification of deficiencies in the recognition of depression, is applicable to quality review in a variety of clinical settings.
Ga-67 Uptake in Fibrous Dysplasia
Authors: KIRAN KAPADIA, FRANCESCO FLORIO, SYDNEY HEYMAN
Journal: Clinical Nuclear Medicine (1996)

A 17-year-old girl with Hodgkin's lymphoma showed significant uptake of Ga-67 at a site diagnosed as fibrous dysplasia by Tc-99m scintigraphy and radiographs of the lower extremities. Fibrous dysplasia is a skeletal developmental anomaly of bone-forming mesenchyme in which osteoblasts do not undergo normal morphologic differentiation and maturation. It may affect one or several bones and is not hereditary. Its cause is unknown.
P4-07-15: Insulin-Like Growth Factor Receptor I (IGFIR) Expression in Circulating Tumor Cells (CTCs) of Patients with Early and Metastatic Breast Cancer (BC).
Authors: M Spiliotaki, H Markomanolaki, M Kokotsaki, G Kallergi, D Mavroudis, V Georgoulias, S Agelaki
Journal: Cancer Research (2011)

Abstract Background: Components of the insulin-like growth factor system are deregulated and IGFIR overexpression is commonly observed in BC, however the expression of the receptor in CTCs of patients with BC has not been studied. Methods: IGFIR expression was assessed in CTCs from 65 patients with early and 101 with metastatic breast cancer before the start of adjuvant and first-line chemotherapy, respectively. Peripheral blood mononuclear cells’ (PBMCs) cytospins were stained with a monoclonal A45-B/B3 anti-cytokeratin (CK) antibody and IGFIR β-subunit anti-rabbit antibody. IGFIR(+)CK(+) CTCs were detected using immunofluorescent microscopy (Ariol system). Phosphorylated IGFIR was also evaluated after staining with phospho-IGFIR-β (Tyr1131)/Insulin Receptor-β (Tyr1146) antibody. Results: CK(+) CTCs were detected in 23 (35.3%) patients with early and 48.5% with metastatic BC. IGFIR(+) CTCs were identified in all (100%) patients with early and in 38 (78%) out of 49 patients with metastatic BC (p=0.014). Eighteen (78%) out of 23 patients with early disease had exclusively IGFIR(+) CTCs and 5(22%) had both IGFIR(+) and IGFIR(−) CTCs. There were no patients in whom exclusively IGFIR(−) CTCs were identified. The respective values in patients with metastatic disease were 19 (39%), 19 (39%) and 11 (22%) (p=0.004, compared to early disease). The median percentage of the expression of IGFIR(+) and IGFIR(−) CTCs per patient was 100% (range 25–100) and 0% (range 0–75), in early and 68% (range, 0–100) and 32% (range 0–100), in metastatic disease, respectively (p=0.003). A total of 222 and 386 CTCs were detected in patients with early and metastatic disease, respectively. IGFIR expression was observed in 84% and 64% of all detected CTCs in adjuvant and metastatic patients, respectively (p&amp;lt;0.001). Phosphorylated IGFIR has been evaluated in PBMCs’ cytospins from 6 patients with adjuvant and 6 with metastatic disease. Interestingly, among 18 CTCs detected in early BC, all expressed phosphorylated IGFIR, whereas, among 34 CTCs identified in metastatic patients, none expressed the phosphorylated form of the receptor. The evaluation of phosphorylated IGFIR is ongoing and updated results will be presented. Conclusions: IGFIR expression is commonly observed in CTCs of patients with BC. IGFIR expression is detected in a higher proportion of patients and in a higher proportion of the total number of CTCs identified in early compared to metastatic disease. The above observations suggest that metastatic progression is associated with loss or downregulation of IGFIR expression in breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-15.
Abstract 676: Serological levels of folate at birth and risk of childhood acute lymphoblastic leukemia
Authors: Anand P. Chokkalingam, Danielle Chun, Ling-I Hsu, Catherine Metayer, Daniel J. Rabinowitz, Mindy Zhang, Joseph L. Wiemels, Patricia A. Buffler
Journal: Cancer Research (2012)

Abstract A role for folate in the etiology of childhood acute lymphoblastic leukemia (ALL) has long been suspected due to folate's dual role in control of DNA methylation as well as maintenance of DNA synthesis. Case-control studies examining self-reported maternal folate intake and supplementation during pregnancy have been inconclusive. Furthermore, while studies of children's own folate metabolism and transport genes have identified potential disease loci, the results have been mixed on the whole. A child's exposure to folate in utero is modulated by a number of factors, including maternal intake/supplementation, maternal genes, and child's genes. Therefore, we examined the role of folate in childhood ALL risk more directly by utilizing a quantitative microbiologic assay to measure newborn red blood cell folate levels in archived dried bloodspots collected at birth from 319 incident cases and 413 matched population-based controls who enrolled in the Northern California Childhood Leukemia Study between 1995 and 2002. After adjustment for income, race/ethnicity, gender, and age, we found no difference in newborn folate levels between cases and controls overall (971 vs. 968 nmol/L, p=0.94). In addition, no differences between cases and controls were observed after stratification by birth year to account for the start of folate fortification of grain products in the US (1982-1994: 953 vs. 952 nmol/L, p=0.98; 1995-1998: 1018 vs. 975 nmol/L, p=0.34; and 1999-2002: 878 vs. 990 nmol/L, p=0.23). Children whose mothers reported pre-pregnancy supplement use had somewhat higher newborn folate levels overall, but we observed no case-control differences in folate levels after stratification by supplement use. Our results do not support an association between folate levels at birth and risk of childhood ALL. However, our results do not rule out a role for folate exposures after birth. Future epidemiologic studies of childhood ALL should pay particular attention to post-natal folate exposures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 676. doi:1538-7445.AM2012-676
Nonresponse to reinstituted lithium prophylaxis in previously responsive bipolar patients: prevalence and predictors
Authors: M Maj, R Pirozzi, L Magliano
Journal: American Journal of Psychiatry (1995)

The authors explored the prevalence and predictors of nonresponse to reinstituted lithium prophylaxis in bipolar patients who had relapsed after discontinuation of successful lithium treatment.The study was conducted with 54 bipolar patients for whom lithium had been reintroduced after one or more recurrences following discontinuation of successful prophylaxis. They were followed up, through bimonthly personal interviews, for 1 year after recovery from the episode during which lithium treatment had been resumed, or up to the first recurrence with onset after lithium reinstitution.During the follow-up period, 44 patients did not have any affective episodes, whereas 10 had at least one recurrence. The only significant difference between the two patient groups was the longer duration of prediscontinuation lithium treatment for the patients who relapsed.Nonresponse to reinstituted prophylaxis should be considered among the possible risks of the interruption of effective long-term lithium treatment.
Abstract P5-04-01: Expression of epithelial-mesenchymal transition (EMT)-related markers in primary tumors and matched lymph node metastases in breast cancer patients
Authors: AJ Zaczek, T Ahrends, A Markiewicz, B Seroczynska, J Szade, M Welnicka-Jaskiewicz, J Jassem
Journal: Cancer Research (2012)

Abstract Background. Malignant tumors may include multiple cancer cell populations with various metastatic potential. More aggressive subpopulations might easier be captured in lymph nodes metastases (LNM) than in primary tumors (PT). We evaluated mRNA and protein levels of master EMT regulators: TWIST1, SNAIL and SLUG, protein levels of EMT-related markers: E-cadherin, vimentin, and expression of classical breast cancer receptors: HER2, ER and PR in PT and corresponding LNM. The results were correlated with clinicopathological data and patient outcomes. Methods. Formalin-fixed paraffin-embedded (FFPE) samples from PT and matched LNM from 42 stage II-III breast cancer patients were examined. Expression of TWIST1, SNAIL and SLUG was measured by RT-qPCR, with median as cut off for positive result. Protein expression was examined by immunohistochemistry on tissue microarrays. For TWIST1, SNAIL, SLUG, E-cadherin and vimentin &amp;gt;10% of positively stained cells defined positive result. ER and PR were scored according to Allred system, and HER2 - according to HercepTest criteria. Results were considered concordant if PT and LNM were both positive or both negative. Concordance was measured by estimating Cohen's kappa coefficient (κ), with κ value equal 1 indicating perfect agreement. Disease-free survival (DFS) and overall survival (OS) were compared using F-Cox test. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were computed using Cox regression analysis. Results. On average, expression of TWIST1, SNAIL and SLUG was significantly higher in LNM compared to PT (P &amp;lt; 0.00001 for all). Gene and protein levels of TWIST1, SNAIL and SLUG were highly discordant between PT and matched LNM (Tab 1). Receptor conversion, particularly loss of ER and PgR, occurred in 18% and 29% of cases, respectively. Increased expression of TWIST1 and SNAIL in LNM was associated with shorter OS (p = 0.045 and p = 0.022, respectively) and DFS (p = 0.02 and p = 0.01, respectively), whereas their expression in PT had no prognostic impact. Negative-to-positive switch of TWIST, SNAIL and vimentin correlated with shorter OS and DFS. Conversion of ER and PR had no significant impact on survival. Conclusions. LNM are enriched in cells with more aggressive phenotype, marked by elevated levels of EMT regulators. High expression of TWIST1 and SNAIL in LNM, as well as negative-to-positive conversion of both TWIST1 and SNAIL confer worse prognosis, confirming the correlation of EMT with aggressive disease behavior. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-01.