tbuckley/cabot-search huggingface dataset:
Targeting Urokinase-Type Plasminogen Activator Receptor on Human Glioblastoma Tumors With Diphtheria Toxin Fusion Protein DTAT
Authors: D. A. Vallera
Journal: JNCI Journal of the National Cancer Institute (2002)

The prognosis for patients with brain cancer is poor, and new therapies are urgently needed. Recombinant toxic proteins that specifically target tumor cells appear to be promising. Urokinase-type plasminogen activator (uPA) receptor (uPAR) is expressed on the surface of glioblastoma and some other tumor cells and endothelial cells. We synthesized a recombinant fusion protein, DTAT, which contains the catalytic portion of diphtheria toxin (DT) for cell killing fused to the noninternalizing amino-terminal (AT) fragment of uPA, and investigated its effectiveness in targeting uPAR-positive tumor cells.In vitro cytotoxicity of DTAT was measured by cell proliferation assays. For in vivo studies, athymic nude mice (four to five animals/group) bearing uPAR-expressing human glioblastoma (U118MG) cell-induced tumors were injected with DTAT or control protein. Tumor volume was assessed over time, and differences between treatments were analyzed by Student's t test. Effects of DTAT on body organ systems were evaluated in normal, tumor-free C57BL/6 mice histologically and functionally by serum enzyme tests. All statistical tests were two-sided.In vitro, DTAT was highly potent and selective in killing uPAR-expressing glioblastoma cells (U118MG, U373MG, and U87MG) and human umbilical vein endothelial cells. In vivo, compared with mice treated with control proteins, DTAT caused a statistically significant (P =.05) regression of small U118MG cell-induced tumors in all mice. Control fusion proteins that did not react with glioblastoma cells had no effect on tumor growth. DTAT given to tumor-free C57BL/6 mice had little effect on kidney, liver, heart, lung, and spleen histologies. Serum analysis in the same mice showed no elevation in blood urea nitrogen, indicating lack of effect on kidney function but a statistically significant (P =.046), albeit non-life-threatening, elevation in liver alanine aminotransferase levels.DTAT may have potential for intracranial glioblastoma therapy because of its ability to target tumor cells and tumor vasculature simultaneously and its apparent lack of systemic effects.
Effect of Self‐adhesive Resin Cement and Tribochemical Treatment on Bond Strength to Zirconia
Authors: Jie Lin, Akikazu Shinya, Harunori Gomi, Akiyoshi Shinya
Journal: International Journal of Oral Science (2010)

To evaluate the interactive effects of different self‐adhesive resin cements and tribochemical treatment on bond strength to zirconia. The following self‐adhesive resin cements for bonding two zirconia blocks were evaluated: Maxcem (MA), Smartcem (SM), Rely X Unicem Aplicap (UN), Breeze (BR), Biscem (BI), Set (SE), and Clearfil SA luting (CL). The specimens were grouped according to conditioning as follows: Group 1, polishing with 600 grit polishing paper; Group 2, silica coating with 110 µm Al2O3 particles which modified with silica; and, Group 3, tribochemical treatment ‐ silica coating + silanization. Specimens were stored in distilled water at 37°C for 24 hours before testing shear bond strength. Silica coating and tribochemical treatment significantly increased the bond strength of the MA, UN, BR, BI, SE and CL to zirconia compared to #600 polishing. For both #600 polished and silica coating treatments, MDP‐containing self‐adhesive resin cement CL had the highest bond strengths to zirconia. Applying silica coating and tribochemical treatment improved the bond strength of self‐adhesive resin cement to zirconia, especially for CL.
Flexible Sigmoidoscopy in the Randomized Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial: Added Yield from a Second Screening Examination
Authors: Joel L. Weissfeld, Robert E. Schoen, Paul F. Pinsky, Robert S. Bresalier, V. Paul Doria-Rose, Adeyinka O. Laiyemo, Timothy Church, Lance A. Yokochi, Susan Yurgalevitch, Joshua Rathmell, Gerald L. Andriole, Saundra Buys, E. David Crawford, Mona Fouad, Claudine Isaacs, Lois Lamerato, Douglas Reding, Philip C. Prorok, Christine D. Berg
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundAmong randomized trials evaluating flexible sigmoidoscopy (FSG) for its effect on colorectal cancer mortality, only the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial screened its participants more than one time. We report outcomes from the PLCO screening FSG program and evaluate the increased yield produced by a second FSG.
Randomized Comparison of Power Doppler Ultrasound-Directed Excisional Biopsy With Standard Excisional Biopsy for the Characterization of Lymphadenopathies in Patients With Suspected Lymphoma
Authors: Marco Picardi, Nicola Gennarelli, Rosanna Ciancia, Amalia De Renzo, Giovanna Gargiulo, Giuseppe Ciancia, Lucianna Sparano, Pio Zeppa, Vincenzo Martinelli, Guido Pettinato, Roberto Lobello, Fabrizio Pane, Bruno Rotoli
Journal: Journal of Clinical Oncology (2004)

The sensitivity of lymph node excisional biopsy requires validation. Power Doppler ultrasound (US) helps predict the malignant status of lymphadenopathies. We used power Doppler US to select for biopsy the lymph node most suspected of malignancy.One hundred fifty-two patients having lymphadenopathies with clinical suspicion of lymphoma were divided into two well-matched groups and randomly assigned to undergo either standard or power Doppler US-directed lymph node excisional biopsy.Histology showed a malignancy in 64% of patients in the standard group (lymphoma, 49 patients; carcinoma, two patients) and in 87% of patients in the US-assisted group (lymphoma, 62 patients; carcinoma, one patient). There were significantly fewer biopsy-related complications in the assisted group than in the standard group. During the follow-up of the patients with lymph nodes reported as being reactive, 14 of 29 patients in the standard group were rebiopsied and were found to have lymphoma (13 patients) or carcinoma at the subsequent lymph node histology, whereas none of the patients in the assisted group (nine patients) required a second biopsy. Thus, biopsy provided false-negative results for malignancy in 21% of patients affected by lymphoma in the standard group and never in the assisted group (P <.01).Power Doppler US is an accurate tool for screening lymphadenopathies to be removed by excisional biopsy in patients with suspected lymphoma.
Dysregulated Expression of Stem Cell Factor Bmi1 in Precancerous Lesions of the Gastrointestinal Tract
Authors: Keisuke Tateishi, Miki Ohta, Fumihiko Kanai, Bayasi Guleng, Yasuo Tanaka, Yoshinari Asaoka, Motohisa Tada, Motoko Seto, Amarsanaa Jazag, Lin Lianjie, Makoto Okamoto, Hiroyuki Isayama, Minoru Tada, Haruhiko Yoshida, Takao Kawabe, Masao Omata
Journal: Clinical Cancer Research (2006)

It is important to identify the definitive molecular switches involved in the malignant transformation of premalignant tissues. Cellular senescence is a specific characteristic of precancerous tissues, but not of cancers, which might reflect tumorigenesis-protecting mechanisms in premalignant lesions. Polycomb protein Bmi1, which is a potent negative regulator of the p16INK4 gene, suppresses senescence in primary cells and is overexpressed in various cancers. We hypothesized that Bmi1 expression would also be dysregulated in precancerous lesions in human digestive precancerous tissues.Bmi1 expression was investigated in cancerous and precancerous tissues of the digestive tract. The expression of p16, beta-catenin, and Gli1 and the in vivo methylation status of the p16 gene were also analyzed in serial sections of colonic precancerous lesions.Bmi1 was clearly overexpressed across a broad spectrum of gastrointestinal cancers, and the expression of Bmi1 increased in a manner that reflected the pathologic malignant features of precancerous colonic tissues (low-grade dysplasia, 12.9 +/- 2.0%; high-grade dysplasia, 82.9 +/- 1.6%; cancer, 87.5 +/- 2.4%). p16 was also strongly expressed in high-grade dysplasia, but not in cancers. p16 promoter methylation was detected only in some Bmi1-positive neoplastic cells.Bmi1 overexpression was correlated with the malignant grades of human digestive precancerous tissues, which suggests that advanced Bmi1 dysregulation might predict malignant progression. The abnormal Bmi1 expression might link to malignant transformation via the disturbance of orderly histone modification.
HIV-specific Cytotoxic T Cells from Long-Term Survivors Select a Unique T Cell Receptor
Authors: Tao Dong, Guillaume Stewart-Jones, Nan Chen, Philippa Easterbrook, Xiaoning Xu, Laura Papagno, Victor Appay, Michael Weekes, Chris Conlon, Celsa Spina, Susan Little, Gavin Screaton, Anton van der Merwe, Douglas D. Richman, Andrew J. McMichael, E. Yvonne Jones, Sarah L. Rowland-Jones
Journal: The Journal of Experimental Medicine (2004)

HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vβ13.2 T cell receptors (TCRs) with very similar and unusually long β-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8–restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vβ13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8–specific CTL using other TCRs. Selection of Vβ13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.
ALTERED CUTANEOUS CONDITIONS IN THE SKIN OF TUBERCULOUS GUINEA PIGS AS DEMONSTRATED WITH A VITAL DYE
Authors: A. L. Joyner, F. R. Sabin
Journal: The Journal of Experimental Medicine (1938)

1. In the skin of the tuberculous guinea pig while it is allergic, the spread of a vital dye, pontamine sky blue, and the drainage of the dye into the vascular system take place much more slowly than in the normal animal. 2. In the skin of moribund tuberculous guinea pigs, animals no longer allergic, dye spreads more rapidly than in the normal animal. 3. The spread of dye is somewhat restricted in the skin of guinea pigs infected with a hemolytic Streptococcus. The animals were allergic. 4. The findings suggest that the dye method may disclose altered tissue conditions in the allergic state.
Virus-Related RNA in Human and Mouse Mammary Tumors&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S. Spiegelman, R. Axel, Jeffrey Schlom
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Virus-Related RNA in Human and Mouse Mammary Tumors Get access S. Spiegelman, S. Spiegelman Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Axel, R. Axel Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032 Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeffrey Schlom Jeffrey Schlom Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 4, April 1972, Pages 1205–1211, https://doi.org/10.1093/jnci/48.4.1205 Published: 01 April 1972
Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes
Authors: Chris P. H. Lexis, Iwan C. C. van der Horst, Erik Lipsic, Wouter G. Wieringa, Rudolf A. de Boer, Ad F. M. van den Heuvel, Hindrik W. van der Werf, Remco A. J. Schurer, Gabija Pundziute, Eng S. Tan, Wybe Nieuwland, Hendrik M. Willemsen, Bernard Dorhout, Barbara H. W. Molmans, Anouk N. A. van der Horst-Schrivers, Bruce H. R. Wolffenbuttel, Gert J. ter Horst, Albert C. van Rossum, Jan G. P. Tijssen, Hans L. Hillege, Bart J. G. L. de Smet, Pim van der Harst, Dirk J. van Veldhuisen
Journal: JAMA (2014)

Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.clinicaltrials.gov Identifier: NCT01217307.
Tumor Regression Model of Cervical Cancer – Letter
Authors: Paoletta Mirk
Journal: Cancer Research (2010)

We read with interest the article by Huang and colleagues (“Predicting Outcomes in Cervical Cancer: A Kinetic Model of Tumor Regression during Radiation Therapy”), which appeared in the January 15, 2010 issue of Cancer Research (1). In their experience the tumor regression rate can be accurately evaluated by sequential magnetic resonance imaging (MRI) exams obtained before, during, and after the course of radiation therapy.Effectiveness of therapy is currently assessed by imaging techniques, such as computerized tomography (CT) and MRI, which rely on morphological changes (tumor shrinkage, signal intensity, etc.). In our opinion, however, imaging methods that rely on different parameters, such as metabolic activity or vascularity, that is on function rather than on anatomy, might be more suitable.Given that functional changes are expected to precede morphological changes, the authors' assumption that “currently available methods … do not allow determination of treatment success or failure until many months/years after therapy” should be, in our opinion, revised in light of the newer evaluation methods. In fact, with cervical cancer, recent studies have shown the prognostic value of positron emission tomography (PET) with the glucose analog [18F-FDG] coupled with low dose CT [18F-FDG PET-CT] after completion of radiotherapy or neoadjuvant chemotherapy (2–4), as well as in early response assessment (5). In this regard, a research study on patients with locally advanced cervical carcinoma has recently been undertaken in our institution, by means of 18F-FDG PET-CT scans obtained before, during (at 2 weeks from the beginning), and after preoperative chemo-radiotherapy, in comparison with the histologic findings at subsequent surgery.On the basis of the abovementioned studies and on our preliminary observations, changes of tumor metabolic activity in response to ongoing therapy can be accurately detected, even in the early PET scan done within the second week of treatment, thus allowing earlier outcome prediction and helping in the selection of the most effective treatment regimen for individual patients.See the Response, p. 6104.No potential conflicts of interest were disclosed.
Inherited Susceptibility to Cancer: Clinical, Predictive and Ethical Perspectives
Authors: H T LYNCH
Journal: Gut (1999)

Inherited Susceptibility to Cancer: Clinical, Predictive and Ethical Perspectives . Edited by Foulkes WD, Hodgson SV. (Pp 456; £60.00, US$95.00.) Cambridge University Press, 1998. ISBN 0 521 56340 2.

This book is timely given the veritable explosion in the molecular genetics of cancer that has occurred over the past decade. The scope …
Effect of P-glycoprotein Expression on Sensitivity to Hormones in MCF-7 Human Breast Cancer Cells
Authors: R. Clarke, S. Currier, O. Kaplan, E. Lovelace, V. Boulay, M. M. Gottesman, R. B. Dickson
Journal: JNCI Journal of the National Cancer Institute (1992)

Background: Data obtained from studies of primary human breast cancers and established cell lines indicate that overexpression of the MDR1 gene (also known as PGY1) is associated with decreased expression of steroid hormone receptors and increased expression of epidermal growth factor (EGF) receptors. Other study results indicate that both progestins and triphenylethylene antiestrogens may be substrates for P-glycoprotein, the product of the MDR1 gene. These findings together suggest an association between over-expression of the MDR1 gene and cross-resistance to progestin and anti-estrogen therapies. Purpose: This study was designed to determine ( a ) the ability of MDR1 expression to alter tumor sensitivity to hormone therapy and ( b ) the role of MDR1 expression in expression of functional hormone receptors in human breast cancer. Methods: We transduced MCF-7 cells with MDR1 complementary DNA, using a retroviral vector directing the constitutive expression of the MDR1 gene. Transduced cells (MCF-7 MDR1 ) were examined for ability to produce P-glycoprotein, expression of steroid hormone receptors, and responsivity to anti-estrogens. For comparison, we used MCF-7 ADR human breast cancer cells, which overexpress MDR1 and have also lost the requirement for 17β-estradiol supplementation to form tumors in nude mice. We also investigated the level of EGF-R mRNA expression by using a sensitive RNase protection analysis. Results: MCF-7 MDR1 cells retained both estrogen receptor and progesterone receptor expression as well as sensitivity to 4-hydroxytamoxifen. Expression of the estrogen-inducible pS2 and EGF receptor genes was similar in parental MCF-7 and transduced MCF-7 MDR1 cells. EGF receptor expression was increased, and pS2 expression was lost (undetectable) in MCF-7 ADR cells. Conclusions: The data indicate that overexpression of the MDR1 gene alone confers a multidrug-resistant phenotype, but it does not directly result in either cross-resistance to antiestrogens or a loss of steroid hormone receptor expression. Implications: MCF-7 MDR1 cells provide an important model for study of the interactions of cytotoxic drugs, hormones, and the MDR1 glycoprotein in human hormone-responsive breast cancer cells. [J Natl Cancer Inst 84:1506–1512, 1992]
Utilizing collagen membranes for guided tissue regeneration‐based root coverage
Authors: Hom‐Lay Wang, Marmar Modarressi, Jia‐Hui Fu
Journal: Periodontology 2000 (2012)

Abstract Gingival recession is a common clinical problem that can result in hypersensitivity, pain, root caries and esthetic concerns. Conventional soft tissue procedures for root coverage require an additional surgical site, thereby causing additional trauma and donor site morbidity. In addition, the grafted tissues heal by repair, with formation of long junctional epithelium with some connective tissue attachment. Guided tissue regeneration‐based root coverage was thus developed in an attempt to overcome these limitations while providing comparable clinical results. This paper addresses the biologic foundation of guided tissue regeneration‐based root coverage, and describes the indications and contraindications for this technique, as well as the factors that influence outcomes. The step‐by‐step clinical techniques utilizing collagen membranes are also described. In comparison with conventional soft tissue procedures, the benefits of guided tissue regeneration‐based root coverage procedures include new attachment formation, elimination of donor site morbidity, less chair‐time, and unlimited availability and uniform thickness of the product. Collagen membranes, in particular, benefit from product biocompatibility with the host, while promoting chemotaxis, hemostasis, and exchange of gas and nutrients. Such characteristics lead to better wound healing by promoting primary wound coverage, angiogenesis, space creation and maintenance, and clot stability. In conclusion, collagen membranes are a reliable alternative for use in root coverage procedures.
Lower β<sub>2</sub>*-Nicotinic Acetylcholine Receptor Availability in Smokers With Schizophrenia
Authors: Deepak Cyril D'Souza, Irina Esterlis, Michelle Carbuto, Maegan Krasenics, John Seibyl, Frederic Bois, Brian Pittman, Mohini Ranganathan, Kelly Cosgrove, Julie Staley
Journal: American Journal of Psychiatry (2011)

There is a strong association between cigarette smoking and schizophrenia. Nicotine's actions in the brain are mediated through nicotinic acetylcholine receptors. Those containing α(4) and β(2) subunits are the most abundant ones in the brain, have the highest affinity for nicotine, and are critical in mediating nicotine's reinforcing properties. Healthy tobacco smokers have significantly higher levels of β(2)*-nicotinic acetylcholine receptors than do nonsmokers. However, in postmortem studies, smokers with schizophrenia do not show these higher levels. The purpose of this study was to measure β(2)*-nicotinic acetylcholine receptors in vivo and to relate levels to concurrent behavioral measures of smoking and schizophrenia.By using single-photon emission computed tomography with the β(2)*-nicotinic acetylcholine receptor agonist radiotracer [(123)I]5-IA-85380, the availability of receptors was measured in smokers with schizophrenia (11 men) and matched comparison smokers after 1 week of confirmed smoking abstinence.Smokers with schizophrenia showed significantly lower (21%-26%) β(2)*-nicotinic acetylcholine receptor availability relative to comparison smokers in the frontal cortex, parietal cortex, and thalamus (in descending order). There was a specific and robust negative correlation between regional β(2)*-nicotinic acetylcholine receptor availability and negative symptoms.These are the first in vivo findings of lower β(2)*-nicotinic acetylcholine receptor availability in smokers with schizophrenia. The relationship between β(2)*-nicotinic acetylcholine receptor availability and negative symptoms may explain the high rates of smoking in schizophrenia and the relationship between smoking and negative symptoms. Findings support the development of medications targeting the β(2)*-nicotinic acetylcholine receptor system for the treatment of negative symptoms.