tbuckley/cabot-search huggingface dataset:
Abstract 4367: Tumor suppressor miR-30a inhibits LOX expression and progression in anaplastic thyroid cancer
Authors: Myriem Boufraqech, Naris Nilubol, Lisa Zhang, Samira Sadowski, Sudheer Kumar Gara, Mei He, Sean Davis, Martha Quezado, Electron Kebebew
Journal: Cancer Research (2014)

Abstract one of the most aggressive human malignancies with a median survival time of less than one year. A better understanding of the molecular events involved in ATC initiation and progression that could be targeted for therapy is gravely needed. There is limited data on the role of miRNAs in ATC. Screening of miRNA expression profile in thyroid cancer samples showed significant downregulation of miR-30a in ATC compared to differentiated thyroid cancer and normal tissue. Ectopic expression of miR-30a in vitro decreased invasion and migration of ATC cells with downregulation of epithelial-mesenchymal transition (EMT) markers and Lysyl Oxidase (LOX) expression, a predicted target of miR-30a. Using an in vivo mouse model of ATC metastases, miR-30a significantly decreased lung metastasis with decreased vimentin, CD44 and LOX expression in lung metastases tumor tissue. We also found that LOX and its downstream target TWIST-1 are highly expressed in ATC, and the expression of both were significantly, inversely correlated with miR-30a expression (p= 0.0026). In addition, the analysis of 454 primary thyroid cancer samples from The Cancer Genome Atlas dataset demonstrated upregulation of LOX and downregulation of miR-30a in high-risk thyroid cancer. These findings suggest that LOX and miR-30a are prognostic markers for aggressive thyroid cancer. To determine whether LOX is a direct effector of miR-30a, the 3′UTR region of LOX was cloned into a luciferase reporter plasmid. Transient transfection of 3′UTR-LOX along with miR-30a in ATC cell lines led to a decrease in luciferase activity when compared to the co-transfection of 3′UTR-LOX with negative control miRNA, demonstrating that LOX is a direct target of miR-30a. In vitro treatment of 4 ATC cell lines with β-aminoproprionitrile (BAPN), an irreversible inhibitor of LOX, had no effect on cell proliferation but inhibited cell invasion and migration and significantly decreased EMT markers and CD44 expression. Moreover, BAPN-treated mice with metastatic human ATC tumors had significantly fewer tumors and smaller size of lung metastases. Our data taken together support a critical role of miR-30a in ATC progression, which is mediated by LOX, and suggests that miR-30a and LOX is possible therapeutic target in ATC. Note: This abstract was not presented at the meeting. Citation Format: Myriem Boufraqech, Naris Nilubol, Lisa Zhang, Samira Sadowski, Sudheer Kumar Gara, Mei He, Sean Davis, Martha Quezado, Electron Kebebew. Tumor suppressor miR-30a inhibits LOX expression and progression in anaplastic thyroid cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4367. doi:10.1158/1538-7445.AM2014-4367
Löfgren's Syndrome
Authors: Johan Grunewald, Anders Eklund
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Sarcoidosis may consist of a number of distinct disease entities, one of which could be Löfgren's syndrome. Patients with Löfgren's syndrome have an acute onset of erythema nodosum (EN) and/or periarticular inflammation or arthritis of the ankles, with bilateral hilar lymphadenopathy (and in some cases parenchymal infiltrates) and usually fever. There is a known association between HLA-DRB1*03 and Löfgren's syndrome.Objectives: To investigate whether human leukocyte antigen type influences clinical manifestations, including the disease course in Löfgren's syndrome.Methods: We clinically characterized and HLA-DRB1 typed 301 patients with Löfgren's syndrome. A total of 275 of the patients were followed for more than 2 years and classified as having a nonresolving or a resolving disease.Measurements and Main Results: Almost every DRB1*03-positive patient had a resolving disease within 2 years, and 49% of the DRB1*03-negative patients developed a nonresolving disease. Mucosal granulomas were identified significantly more often in DRB1*03-negative patients. Among DRB1*03-negative patients who were treated with oral steroids at disease onset, 80% developed a nonresolving disease.Conclusions: Patients with Löfgren's syndrome have a different disease course depending on whether they are DRB1*03 positive or not. This observation has clinical implications, and by comparing DRB1*03-positive and DRB1*03-negative patients with Löfgren's syndrome, we can search for additional markers of importance for developing a resolving or a nonresolving disease, respectively.
Statistical Analysis of a Carcinogen Mixture Experiment. I. Liver Carcinogens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R M Elashoff, T R Fears, M A Schneiderman
Journal: JNCI Journal of the National Cancer Institute (1987)

This paper describes factorial experiments designed to determine whether 2 liver carcinogens act synergistically to produce liver cancers in Fischer 344 rats. Four hepatocarcinogens, cycad flour, lasiocarpine (CAS: 303-34-4), aflatoxin B1 (CAS: 1162-65-8), and dipentylnitrosamine (CAS: 13256-06-9), were studied in pairwise combinations. Each of the 6 possible pairs was studied by means of 4 X 4 factorial experiment, each agent being fed at zero and at 3 non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for one-at-a-time studies. Antagonism was not discovered in any chemical mixture. Some chemical mixtures did interact synergistically. Findings for male and female animals were generally, but not always, in agreement.
Folfoxiri with or Without Bevacizumab (Bev) As First-Line Treatment of Metastatic Colorectal Cancer (Mcrc): a Propensity Score-Based Analysis
Authors: C. Cremolini, F. Loupakis, D. Rossini, G. Masi, L. Salvatore, C. Barbara, I.M. Brunetti, C. Antoniotti, C. Granetto, E. Cortesi, S. Chiara, S. Vitello, S. Lonardi, L. Ciuffreda, G. Tomasello, M. Ronzoni, A. Buonadonna, D. Tomcikova, L. Boni, A. Falcone
Journal: Annals of Oncology (2014)
Complications of Chemotherapy
Authors: Steven M. Gruberg, Robert Sofferman, Thomas Roland, Sandra Shubel
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.1.430 Journal of Clinical Oncology - published online before print September 21, 2016 Complications of Chemotherapy Steven M. GrubergxSteven M. GrubergSearch for articles by this author , Robert SoffermanxRobert SoffermanSearch for articles by this author , Thomas RolandxThomas RolandSearch for articles by this author , Sandra ShubelxSandra ShubelSearch for articles by this author Show More Fletcher Allen Health Care, Burlington, VT https://doi.org/10.1200/JCO.1999.17.1.430 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Surgery, Cancer Chemotherapy, Host Defenses, and Tumor Size&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Daniel S. Martin, Ruth A. Fugmann, P. Hayworth
Journal: JNCI Journal of the National Cancer Institute (1962)

Alteration of host defense mechanisms by large amounts of tumor tissue is indicated as responsible for the failure of otherwise curative courses of chemotherapy to effect eradication of well-established cancer. Reduction of tumor size by simple surgery restored the curative efficacy of chemotherapy. With the use of transplantable tumors Sarcoma 180, Adenocarcinoma 755, Adenocarcinoma RC, and Walker carcinosarcoma 256, the interrelationships of tumor size, immunotherapy, and chemotherapy were explored with surgery, Zymosan, cortisone, 6-mercaptopurine, Puromycin, and tris(laziridinyl)phosphine sulfide. The resultant data show that “cure” can never, or only rarely, be effected on large, well-established transplantable tumors by chemotherapy alone, immunotherapy (Zymosan) alone, or surgery alone. However, combining the 3 therapeutic modalities produced striking cure rates in the range of 70 to 80 percent, which could, in turn, be nullified by the simultaneous administration of an anti-immunity agent (cortisone). Spontaneous breast cancers in mice were markedly susceptible to chemotherapeutic effect only if chemotherapy (uracil mustard) was administered as an adjuvant to surgical enucleation. Complement activity was significantly lower in spontaneous tumor-bearing mice than in normal adult animals. Nullification of chemotherapeutic effect on spontaneous tumors was obtained by the concomitant administration of cortisone with an anticancer agent, uracil mustard. The later experiments strongly indicate the existence of host defenses against spontaneous cancer. Correlation of the results obtained with spontaneous and transplantable tumors is evaluated and clinical implications are discussed. The findings suggest a similarity between the therapeutic problem in cancer and that in bacterial infection; i.e., chemotherapeutic cure of cancer appears similarly dependent on the concomitant interplay of host defenses. A combined immunologic and chemotherapeutic approach to the treatment of neoplastic disease appears indicated.
Humoral Antitumor Immune Responses in Patients With Breast Cancer Measured With the Leukocyte Adherence Inhibition Technique&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: H K Kotlar, T Sanner
Journal: JNCI Journal of the National Cancer Institute (1981)

A modification of the hemacytometer leukocyte adherence inhibition (LAI) test was described. In this modification, 0.25% serum from patients with breast cancer was added with the relevant antigen to the assay system with the use of trypsinized leukocytes from control persons as indicator cells. The modified assay measured a humoral immune response. In studies of patients with untreated breast cancer (stages I and II) with the use of a KCl extract from a breast carcinoma or from MCF-7 cells as antigens, the modified LAI test was found to be at least as sensitive as was the ordinary test. In a blind study on sera collected from patients with breast cancer 0.5-2 years before the LAI measurements and stored at -20 degrees C, 15 of 18 (83%) patients had a positive response. Whereas the ordinary LAI test is limited to the use of fresh blood, the present test can be performed with small amounts of serum that can be frozen and stored.
Type 1 Free Perforation of the Gallbladder
Authors: Christopher Harland, John F Mayberry, Peter J Toghill
Journal: Journal of the Royal Society of Medicine (1985)

A series of 4 cases of free perforation of the gallbladder into the peritoneal cavity associated with peritonitis are reported. Two were diagnosed at laparotomy and 2 at post-mortem. The 3 patients who died were men who were either elderly or had serious concomitant diseases, including diabetes, atherosclerosis or alcoholism. The sole survivor was a fit young woman.
Incidence of human immunodeficiency virus-related and nonrelated malignancies in a large cohort of homosexual men.
Authors: D W Lyter, J Bryant, R Thackeray, C R Rinaldo, L A Kingsley
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine if the rates of malignancies other than Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) are increased in human immunodeficiency virus (HIV)-infected homosexual men. SUBJECTS AND METHODS From 1984 through 1993, 1,199 homosexual men were studied in the Pittsburgh component of the Multicenter AIDS Cohort Study (MACS), an examination of the natural history of HIV infection. The cohort consisted of 769 HIV-seronegative (SN) participants and 430 seropositive (SP) members who were either seroprevalent at the time of enrollment or who seroconverted during the study. Cancer incidence data were collected through semiannual visits, phone interviews, medical records, and death certificates. Five thousand seven hundred eight person-years and 2,344 person-years were contributed to the study by the SN and SP men, respectively. RESULTS In addition to 44 cases of KS, 13 NHLs, and 3 CNS lymphomas (CNSLs), 27 other malignancies occurred (three nonmelanoma skin cancers and eight other malignancies in the SP group, eight nonmelanoma skin cancers, and eight other malignancies in the SN group). Age-adjusted rates were calculated for both groups and compared with each other and with rates for the general male population in Pennsylvania. There were no differences between the SN group and the general population. Among the SP group, the combined frequency of all cancers other than KS, NHL, CNSL, and nonmelanoma skin cancers was statistically significantly increased in comparison to both the SN group and the general population. This increase was secondary to an unusually increased frequency of both seminoma and Hodgkin's disease. CONCLUSION These findings support the hypothesis that the incidences of cancers other than KS and lymphoma are moderately increased in the setting of HIV infection and immunosuppression.
Kinetic Response of Cultured Human Lymphoid Cells to Rubidazone2
Authors: Barthel Barlogie, Benjamin Drewinko, Robert S. Benjamin, Ti Li Loo
Journal: JNCI Journal of the National Cancer Institute (1978)

Analysis of rubidazone, the benzoylhydrazone derivative of daunorubicin, for its effects on cell cycle progression of a human lymphoid cell line showed a kinetic response pattern similar to that of adriamycin. Thus rubidazone induced a G2-block, the magnitude and duration of which were dependent on concentration and incubation time. However, in contrast to adriamycin, a marked phase-dependent sensitivity for the induction of G2-accumulation was observed; cells treated in early and mid-S-phase were most sensitive. This age-dependent kinetic response may account for the smaller G2-accumulation in asynchronous cultures and the closer correlation of the magnitude of this kinetic effect with concentration and duration of rubidazone treatment. Prolonged exposure to high concentrations of rubidazone also delayed the traverse through G1 and/or the G1-S transition, whereas the S-phase transit was not impaired. Interference with cell cycle progression through G1 into S-phase caused a stepwise accumulation of cells in G2-phase.
Immunological and Biological Studies of a Cytotoxic Component From Human Sera&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: David W. Beno, Ralph I. Lytle, Earl A. Edwards
Journal: JNCI Journal of the National Cancer Institute (1969)

HeLa, HEp-2, KB, and WI-38 tissue culture cells showed various degrees of cytotoxicity when exposed to heat-inactivated human sera. Most of the cytotoxicity was not in the ammonium sulfate-precipitated serum fractions, but migrated during preparative electrophoresis in the prealbumin area. Examination of the active fraction by curtain and disc electrophoresis and by microimmunodiffusion tests showed the presence of prealbumin.
Intensified concomitant chemoradiotherapy with and without filgrastim for poor-prognosis head and neck cancer.
Authors: E E Vokes, D J Haraf, R Mick, J M McEvilly, R R Weichselbaum
Journal: Journal of Clinical Oncology (1994)

PURPOSE We previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (FHX). In two trials reported here, we added cisplatin with and without granulocyte colony-stimulating factor (G-CSF) to 5-FU, HU, and concomitant radiotherapy. PATIENTS AND METHODS Eligible patients had failed to respond to prior local therapy (group 1); previously untreated patients with unresectable and/or metastatic disease and a projected 2-year survival rate less than 10% were also eligible (group 2). Chemoradiotherapy consisted of 1.8 to 2.0 Gy on days 1 to 5 with simultaneous infusional 5-FU at 800 mg/m2/d and HU administered every 12 hours for 11 doses at escalating doses. Cisplatin was administered at 100 mg/m2 during every other cycle. Cycles were repeated every 14 days until completion of radiotherapy. In study 2, G-CSF was added on days 6 to 13 at 5 micrograms/kg/d. RESULTS Acute and cumulative myelosuppression limited the feasibility of adding cisplatin to FHX without G-CSF. G-CSF allowed for escalation of HU to 1 g orally every 12 hours without dose-limiting acute toxicity during cycles 1 and 2. Dose-limiting cumulative toxicity consisted of severe or life-threatening myelosuppression and mucositis. To decrease total treatment duration and, thus, cumulative toxicity, a hyperfractionated radiation therapy schedule was investigated using the established chemotherapy doses with 1.5 Gy twice daily on days 1 to 5 (75 Gy over five treatment cycles). No increase in acute toxicities was seen; cumulative toxicities remained frequently severe or life-threatening. Thirty-eight of 45 assessable patients responded. The median survival duration was 12 months for both groups. Median time to treatment failure was 8 months for group 1 and has not been reached for group 2. At 1 year, local control rates were 74% and 91% for groups 1 and 2, respectively. CONCLUSION The addition of cisplatin to 5-FU, HU, and concomitant radiotherapy is feasible using G-CSF. The high locoregional control rate and failure-free interval justify further investigation of this regimen in previously untreated patients.
Adrenomedullin optimizes mortality prediction in COPD
Authors: Marjolein Brusse-Keizer, Maaike Zuur-Telgen, Job van der Palen, Paul vanderValk, Huib Kerstjens, Wim Boerrsma, Francesco Blasi, Kostantinos Kostikas, Branislava Milenkovic, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2014)

In current multicomponent scores that predict mortality in COPD, the systemic component of COPD is under reflected. Therefore, we evaluated the accuracy of plasma proadrenomedulin levels (proADM) alone or combined with the ADO (Age, Dyspnea and airflow Obstruction), updated ADO or BOD (Body mass index, airflow Obstruction, Dyspnea) index to predict all-cause mortality in stable COPD patients.  This study is a pooled analysis of 1285 patients from the COMIC and PROMISE-COPD studies. Patients were categorized into low and high risk based on proADM level (  Patients with high proADM levels had a 2.1 fold (p  Levels of proADM measured in stable state showed to be a powerful predictor of all-cause mortality in COPD. It predicted mortality more accurately than the ADO, the updated ADO, and BOD index. Adding proADM increased the predictive probability of all indices.
Evaluation of Soy Phytoestrogens for the Treatment of Hot Flashes in Breast Cancer Survivors: A North Central Cancer Treatment Group Trial
Authors: Susan K. Quella, Charles L. Loprinzi, Debra L. Barton, James A. Knost, Jeff A. Sloan, Beth I. LaVasseur, Debra Swan, Kenneth R. Krupp, Kathy D. Miller, Paul J. Novotny
Journal: Journal of Clinical Oncology (2000)

Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis.This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects.Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed.The soy product did not alleviate hot flashes in breast cancer survivors.
Growth and Metastasis of Human Melanoma Xenografts in the Hamster Host&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R E Richmond, D L Morton
Journal: JNCI Journal of the National Cancer Institute (1979)

Cells from three human melanoma cell culture lines (UCLASO-M-12, UCLASO-M-7, and WEG-1) were transplanted into the cheek pouches of immunosuppressed hamsters. Tumor nodules were found in the cheek pouches of hamsters receiving any one of these lines, and by 90--100 days after transplantation, nearly all hamsters had grossly visible lung metastases. Metastases were noted only in hamsters receiving continuous immunosuppression during the transplant period.
Hepatitis C virus infects rhesus macaque hepatocytes and simianized mice
Authors: Margaret A. Scull, Chao Shi, Ype P. de Jong, Gisa Gerold, Moritz Ries, Markus von Schaewen, Bridget M. Donovan, Rachael N. Labitt, Joshua A. Horwitz, Jenna M. Gaska, Gabriela Hrebikova, Jing W. Xiao, Brenna Flatley, Canny Fung, Luis Chiriboga, Christopher M. Walker, David T. Evans, Charles M. Rice, Alexander Ploss
Journal: Hepatology (2015)

At least 170 million people are chronically infected with hepatitis C virus (HCV). Owing to the narrow host range of HCV and restricted use of chimpanzees, there is currently no suitable animal model for HCV pathogenesis studies or the development of a HCV vaccine. To identify cellular determinants of interspecies transmission and establish a novel immunocompetent model system, we examined the ability of HCV to infect hepatocytes from a small nonhuman primate, the rhesus macaque ( Macaca mulatta ). We show that the rhesus orthologs of critical HCV entry factors support viral glycoprotein‐dependent virion uptake. Primary hepatocytes from rhesus macaques are also permissive for HCV‐RNA replication and particle production, which is enhanced when antiviral signaling is suppressed. We demonstrate that this may be owing to the diminished capacity of HCV to antagonize mitochondrial antiviral‐signaling protein–dependent innate cellular defenses. To test the ability of HCV to establish persistent replication in vivo , we engrafted primary rhesus macaque hepatocytes into immunocompromised xenorecipients. Inoculation of resulting simian liver chimeric mice with either HCV genotype 1a or 2a resulted in HCV serum viremia for up to 10 weeks. Conclusion : Together, these data indicate that rhesus macaques may be a viable model for HCV and implicate host immunity as a potential species‐specific barrier to HCV infection. We conclude that suppression of host immunity or further viral adaptation may allow robust HCV infection in rhesus macaques and creation of a new animal model for studies of HCV pathogenesis, lentivirus coinfection, and vaccine development. (H epatology 2015;62:57‐67)