tbuckley/cabot-search huggingface dataset:
The Non-Hodgkin Lymphoma Pathologic Classification Project
Authors: Richard Simon
Journal: Annals of Internal Medicine (1988)

To document the long-term prognosis of patients with non-Hodgkin lymphoma treated between 1971 and 1975 and to determine how the prognosis varies by histologic subtype and stage.Three cancer referral centers in the United States and one center in Italy.A consecutive sample of 1153 previously untreated patients with non-Hodgkin lymphoma. At the time of analysis, 71% of the patients had died and the median follow-up for patients still alive was 11.2 years.The 10-year survival proportions were 45% (CI, 40% to 50%); 26% (CI, 22% to 30%); and 23% (CI, 18% to 30%) for patients with low-, intermediate-, and high-grade lymphomas, respectively. Patients with intermediate- and high-grade lymphomas were curable, but this was not apparent for patients with advanced stage low-grade lymphomas. For the low-grade follicular small cleaved and follicular mixed lymphomas, the Ann Arbor staging system distinguished the prognosis of patients with stage I disease from those with more extensive involvement. For the diffuse large cell and immunoblastic lymphomas, the Ann Arbor staging system distinguished long-term prognosis for patients with stage I disease from patients with stage II disease and those with more disseminated involvement.The probability of long-term survival for unselected patients with non-Hodgkin lymphoma can be substantial. Long-term prognosis depends on the histologic subtype of the tumor and the extent of dissemination. The Working Formulation for non-Hodgkin lymphomas is a simple and useful nomenclature for selecting treatment and reporting results. The Ann Arbor staging system is a useful but imperfect prognostic indicator.
Abstract 1034: A natural inhibitor of c-Jun N-terminal kinase 1
Authors: Ke Yao, Yong-Yeon Cho, Hanyong Chen, NuRy Song, Kang-Dong Liu, Weihong Wen, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2011)

Abstract The c-Jun N-terminal kinases (JNKs) pathway plays a important role in many physiological processes including cell proliferation, survival, death, DNA repair and metabolism induced by a variety of stress signals and pro-inflammatory stimuli. The JNK proteins are encoded by three genes, jnk1, jnk2, jnk3. The protein products of jnk1 and jnk2 are found in all cells and tissues, whereas the JNK3 protein is found primarily in the brain, but is also found in the heart and the testes. The unequal expression of the different isoforms of JNK is possibly determined by some unique characteristics. Each JNK appears to have a distinct function in cancer, asthma, diabetes, and Parkinson's disease. Recent studies demonstrate that JNK1 is a key contributor for the serine phosphorylation of the IRS-1. Several other studies also demonstrated the importance of JNK1, but not JNK2, in lung fibrosis and gastric cancer. We have identified a novel flavonoid isolated from natural sources, herein referred to Compound-A, that suppressed JNK1 activity, with no effect on JNK2 in vitro. At 10 μM, Compound-A specifically inhibited JNK1 by about 50%. We also found that compound-A inhibits UVB-induced c-Jun phosphorylation in a cell culture system. In contrast to SP600125, a non-selective JNKs inhibitor that binds to the ATP active site, compound-A appears to target the protein-protein interaction between JNK1 and its binding proteins, including the JNK-interacting protein-1(JIP1) rather than the ATP binding site. In a computer simulation model, compound-A complexed with JNK1, but not JNK2, and formed strong hydrogen bonding at Glu329. Glu329 is a key residue for the JNK complex with JIP1. This interaction induces a hinge motion between the JNK N- and C-terminal domains and decreases the affinity of the kinase and ATP. These results demonstrate that compound-A is a selective JNK1 inhibitor. In humans, JNK1 play a key role in obesity-induced type 2 diabetes mellitus and the absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and an enhanced insulin receptor signaling capacity in mouse obesity models. Therefore, we suggest that because of JNK1's critical role in diabetes, compound-A might have therapeutic potential against this devastating disease. 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 1034. doi:10.1158/1538-7445.AM2011-1034
Clinical Survey of 3680 Iris Tumors Based on Patient Age at Presentation
Authors: Carol L. Shields, Swarupa Kancherla, Jinali Patel, Priya Vijayvargiya, Mayerling M. Suriano, Emily Kolbus, Ami Badami, Priya Sharma, Emily Jacobs, Matt Voluck, Zina Zhang, Rishav Kansal, Patrick W. Shields, Carlos G. Bianciotto, Jerry A. Shields
Journal: Ophthalmology (2011)
A Prospective Morphologic Evaluation of Hepatic Toxicity of Chenodeoxycholic Acid in Patients with Cholelithiasis: The National Cooperative Gallstone Study
Authors: Rosemarie L. Fisher, Deborah W. Anderson, James L. Boyer, Kamal Ishak, Gerald Klatskin, John M. Lachin, James M. Phillips
Journal: Hepatology (1982)

A sample of 126 patients with cholelithiasis was treated with chenodeoxycholic acid (CDCA) (375 or 750 mg g.d.) for 2 years. Hepatotoxicity was assessed by sequential light (LM) and electron microscopic (EM) analysis of liver biopsies obtained before and after 9 and 24 months of therapy. Patients were without symptoms of biliary colic for 3 months prior to biopsy, less than 70 years old, and had normal tests of liver function. All light microscopy was read blindly by two morphologists, and electron microscopy by one. Only four biopsies (3%) showed severe (3+) abnormalities preventing admission to the study. On evaluation, moderate (2+) LM changes were present in less than 12% of biopsies, while milder changes (1+) were seen more frequently. No severe, dose–related abnormalities were seen in LM over the 2 years of study. However, mild changes (hepatocyte ballooning and lipofuscin, binucleate cells, glycogen nuclei, ductular proliferation, enlarged and fibrotic triads, and sinusoidal congestion) became more prevalent with time (p ≤ 0.01) regardless of CDCA dose, according to 1 of the 2 morphologists. Because patients with “proven” cholelithiasis for greater than 2 years (33% of the study population) did not have a greater incidence of morphologic abnormalities than those with the diagnosis for less than 2 years, it is unlikely that these changes were due to the natural History of gallstone disease. Furthermore, electron microscopic findings demonstrated worsening intrahepatic cholestasis and a lesion in two patients which was identical to that produced in animals administered lithocholic acid, the 7–a–dehydroxylated metabolite of CDCA. The possibility that clinically significant hepatotoxicity could develop with CDCA therapy greater than 24 months thus cannot be excluded by this study.
Tc-99m HMPAO Brain SPECT in Dementia Due to Transitory Obstructive Hydrocephalus
Authors: R A DIERCKX, B APPEL, J SAERENS, P MARIEN, P P DE DEYN, J VANDEVIVERE
Journal: Clinical Nuclear Medicine (1993)

DIERCKX, R. A. M. D.*; APPEL, B. M. D.†; SAERENS, J. PH. D.‡; MARIEN, P. PH. D.‡; DE DEYN, P. P. M. D., PH. D.‡; VANDEVIVERE, J. M. D.* Author Information
Abstract 2288: CYP3A4 monoxygenase regulates IGF-1 signaling in ER-positive breast cancer cells
Authors: Zhijun Guo, Ranjana Mitra, Monica Milani, Mariangellys Rodriguez, Douglas Yee, Deepali Sachdev, David A. Potter
Journal: Cancer Research (2011)

Abstract Cytochrome P450 3A4 (CYP3A4) is an important monooxygenase that metabolizes a wide range of xenobiotics including many drugs and environmental chemicals, as well as endogenous substances such as steroids. Expression of CYP3A4 has been observed in breast tumors and has been associated with nodal metastases and decreased overall survival in breast cancer. To investigate roles of CYP3A4 on breast cancer progression and the mechanisms involved, we performed RNAi knock down studies, demonstrating that CYP3A4 regulates anchorage-dependent proliferation and clonogenicity of the MCF7 line. Unexpectedly, we found that stable CYP3A4 shRNA knock down MCF7 lines exhibited significant higher clonogenicity relative to the non-target control line in soft agar (P&amp;lt;0.05). Further investigation demonstrated that this increased clonogenicity is due to activation of IGF autocrine pathway, which could be abrogated by an antibody to the IGF1R. The PI3-Kinase inhibitor LY294002 abolished the increase of clonogenicty of CYP3A4 silenced lines, indicating the involvement of PI3-Kinase pathway. Phosphorylation of AKT protein is elevated in these lines, consistent with increased IGF-1 signaling. These results indicate that CYP3A4 may play a role in regulating IGF-1 signaling in ER-positive breast cancer cells. These results suggest that inhibition of CYP3A4 in combination with IGF1R function blocking antibody may have enhanced therapeutic efficacy compared to either modality alone. 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 2288. doi:10.1158/1538-7445.AM2011-2288
Everything changes but you?
Authors: Des Spence
Journal: BMJ (2007)

“The two seats are near each other but NOT together,” the email read. I had just bought tickets on eBay to see Take That and realised that I would be sitting on my own at a boy band concert. How my wife laughed. On the day, I was the designated driver with no opportunity to self medicate before the concert. Nervously I walked past the bawdy mini-skirted gangs smoking outside the venue and reeking of vodka and beer. The hall …
Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics
Authors: Stanleyson V. Hato, Andrea Khong, I. Jolanda M. de Vries, W. Joost Lesterhuis
Journal: Clinical Cancer Research (2014)

Abstract The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the most widely used chemotherapeutics in oncology, showing clinical efficacy against many solid tumors. Their main mechanism of action is believed to be the induction of cancer cell apoptosis as a response to their covalent binding to DNA. In recent years, this picture has increased in complexity, based on studies indicating that cellular molecules other than DNA may potentially act as targets, and that part of the antitumor effects of platinum drugs occurs through modulation of the immune system. These immunogenic effects include modulation of STAT signaling; induction of an immunogenic type of cancer cell death through exposure of calreticulin and release of ATP and high-mobility group protein box-1 (HMGB-1); and enhancement of the effector immune response through modulation of programmed death receptor 1-ligand and mannose-6-phosphate receptor expression. Both basic and clinical studies indicate that at least part of the antitumor efficacy of platinum chemotherapeutics may be due to immune potentiating mechanisms. Clinical studies exploiting this novel mechanism of action of these old cancer drugs have been initiated. Here, we review the literature on the immunogenic effects of platinum, summarize the clinical advances using platinum as a cytotoxic compound with immune adjuvant properties, and discuss the limitations to these studies and the gaps in our understanding of the immunologic effects of these drugs. Clin Cancer Res; 20(11); 2831–7. ©2014 AACR.
IL-6 involvement in epithelial cancers
Authors: Zachary T. Schafer, Joan S. Brugge
Journal: Journal of Clinical Investigation (2007)

In this issue of the JCI, two reports provide intriguing new information on the role of the inflammatory cytokine IL-6 in breast and lung cancer. The study by Sansone et al. implicates IL-6 in the instigation of malignant properties in breast cancer stem cells (see the related article beginning on page 3988). The study by Gao et al. identifies mutant variants of EGFR as inducers of IL-6 in lung adenocarcinomas (see the related article beginning on page 3846). These studies add to our understanding of potential roles for IL-6 in cancer and further motivate investigations of IL-6–targeted chemotherapeutics.
Cardiac Arrest: The Science and Practice of Resuscitation Medicine
Authors: Robert F. Wilson
Journal: JAMA (1996)

The extremely large<i>Cardiac Arrest: The Science and Practice of Resuscitation Medicine</i>is truly an encyclopedia on the subject. The book has virtually everything one would ever want to know about the causes of cardiac arrest, the applied physiology, and its treatment. As the editors point out, more than 300000 persons die each year in the United States of sudden cardiac death, and with early recognition and therapy this number could be greatly reduced. The authors also point out that all our skills and limited knowledge must be applied immediately when cardiac arrest occurs if "hearts and brains too good to die are not to be lost forever." Every physician will at some time attempt to resuscitate patients from sudden death, but few have the opportunity to learn from teachers dedicated to this skill, which this book provides. The editors intend it to be "a comprehensive text incorporating critical analysis
Impact of HIV on tuberculosis in Zambia: a cross sectional study.
Authors: A M Elliott, N Luo, G Tembo, B Halwiindi, G Steenbergen, L Machiels, J Pobee, P Nunn, R J Hayes, K P McAdam
Journal: BMJ (1990)

OBJECTIVE--To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis in central Africa. DESIGN--Cross sectional study. SETTING--Outpatient clinic in teaching hospital, Lusaka, Zambia. PATIENTS--346 Adult patients with tuberculosis. RESULTS--Overall, 206 patients (60%; 95% confidence interval 54% to 65%) were positive for HIV--in one or both assays used. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 73/149 (49%; 41% to 57%) were positive for HIV; 67/83 (81%; 70% to 89%) patients with pleural disease and 16/19 (84%; 60% to 97%) patients with pericardial disease were positive. HIV positive patients with positive sputum culture were less likely to have had a positive sputum smear, and their chest x ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. CONCLUSIONS--The high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.
Crystal habit, characterization and pharmacological activity of various crystal forms of arteether
Authors: Renu Chadha, Sushma Gupta, Geeta Shukla
Journal: Acta Pharmaceutica Sinica B (2011)

The aim of this study was to investigate and characterize different crystal forms of arteether, a rapidly acting, highly potent antimalarial drug for the treatment of acute Plasmodium falciparum malaria. Six different crystal forms were prepared utilizing various polar and non-polar solvents. Scanning electron microscopy (SEM) revealed differences in the surface characteristics of the six forms from those of a commercial sample. Differential scanning calorimetry (DSC) revealed the absence of a desolvation endotherm indicating that the forms were neither hydrates nor solvates. Powder X-ray diffraction (PXRD) patterns of the forms showed much weaker major peaks than in the commercial sample indicating them to be less crystalline. Solubility and dissolution studies showed that the most amorphous form was the most soluble and possessed the highest antimalarial activity.
Plaque Characteristics of Thin-Cap Fibroatheroma Evaluated by OCT and IVUS
Authors: Yoshinori Miyamoto, Hiroyuki Okura, Teruyoshi Kume, Takahiro Kawamoto, Yoji Neishi, Akihiro Hayashida, Ryotaro Yamada, Koichiro Imai, Ken Saito, Kiyoshi Yoshida
Journal: JACC. Cardiovascular imaging (2011)
Antidepressants and Hypothalamic-Pituitary-Adrenocortical Regulation
Authors: FLORIAN HOLSBOER, NICHOLAS BARDEN
Journal: Endocrine Reviews (1996)

PAST studies of antidepressants have focused almost exclusively on their effects on the metabolism and receptors of monoamine neurotransmitters in various brain regions. These studies have been extended to the molecular effects of antidepressants and have led to a profoundly expanded understanding of their actions in the central nervous system. For example, long-term administration of antidepressants decreases the expression of tyrosine hydroxylase, down-regulates cAMP-dependent protein kinase, modulates the mRNA expression of central β-adrenoceptors and serotonin (5-HT) receptors, and alters the functional activity of specific G protein subunits and adenylyl cyclase (1). Taken together, these and many other recent observations clearly indicate that antidepressants interfere not only with the production and release of catecholamines and indolamines but also with the signal transduction of those neurotransmitters that have long been implicated in the pathogenesis and treatment of depression. More recently, additional target genes of antidepressant treatment have been identified, the most intriguing being those related to hypothalamic-pituitary-adrenocortical (HPA) activity. Altered regulation of this neuroendocrine system has been the subject of investigative efforts in depression research since Gibbons (2) reported more than 30 yr ago that plasma cortisol concentrations are elevated in depression and are normalized after clinical remission. Numerous clinical observations are consistent with the possibility that there is a causal link between HPA dysregulation and psychopathology (3). Recently, a large number of preclinical studies have provided evidence pointing in the same direction.
A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors
Authors: Iacopo Petrini, Paul S Meltzer, In-Kyu Kim, Marco Lucchi, Kang-Seo Park, Gabriella Fontanini, James Gao, Paolo A Zucali, Fiorella Calabrese, Adolfo Favaretto, Federico Rea, Jaime Rodriguez-Canales, Robert L Walker, Marbin Pineda, Yuelin J Zhu, Christopher Lau, Keith J Killian, Sven Bilke, Donna Voeller, Sivanesan Dakshanamurthy, Yisong Wang, Giuseppe Giaccone
Journal: Nature Genetics (2014)
Free Radical Biology: A Paradox in Cancer Research
Authors: J. Glover
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Free Radical Biology: A Paradox in Cancer Research Get access Janet Glover Janet Glover Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 11, 6 June 1990, Pages 902–903, https://doi.org/10.1093/jnci/82.11.902 Published: 06 June 1990
Myocardial oxygen consumption in isovolumic hearts with varying cardiac outputs
Authors: J. SIMAAN, G. FAWAZ
Journal: Cardiovascular Research (1974)

Myocardial oxygen consumption in isovolumic hearts with varying cardiac outputs was explored in heart-lung preparations from dogs, modified to measure coronary flow. The venous reservoir was raised in steps to increase stroke volume and with it left ventricular volume; myocardial oxygen consumption being determined at each step. The venous reservoir was then lowered to the starting level, thus restoring stroke volume to control and an intraventricular balloon was distended with saline again in steps, to increase left ventricular volume to the same extent as when the venous reservoir was raised, but maintaining stroke volume constant. Myocardial oxygen consumption was measured at each step and compared with that obtained at an identical left ventricular volume but with a higher cardiac output. The results of 10 comparative studies in six preparations indicate that at constant heart rate and mean systemic pressure, myocardial oxygen consumption was the same in preparations with identical left ventricular volumes but drastically different cardiac outputs. It may be concluded from this study that the oxygen cost of an increase in volume work of the heart, at constant mean aortic pressure and heart rate, is determined by the concomitant increase in the volume of the heart in so far as it affects the development of tension in accordance with the Laplace relationship.
Positive Tissue Antibody Tests in Patients with Prolonged Extrahepatic Biliary Obstruction
Authors: Kui Chun Lam, Steven P. Mistilis, Nancy Perrott
Journal: New England Journal of Medicine (1972)

THE high proportion of antimitochondrial antibodies in primary biliary cirrhosis1 2 3 and the low rate in extrahepatic biliary obstruction3 4 5 have been considered crucial in differentiating these disorders. In many centers a positive reaction is accepted as being diagnostic of primary biliary cirrhosis, obviating the need for exploratory laparotomy. Tissue antibodies are in fact of little value in cases of acute extrahepatic biliary obstruction, since the diagnosis can be made from clinical manifestations. On the other hand, clinical features and liver-biopsy findings in chronic extrahepatic biliary obstruction may be indistinguishable from those found in primary biliary cirrhosis.6 Since considerable emphasis has been . . .
670. Combined Strategy of Minimal Myeloablation and Optimal BMT Regimen To Cure Murine β-Thalassemia
Authors: Hady Felfly, Marie Trudel
Journal: Molecular Therapy (2006)

Using a thalassemic mouse model (hemi-βthal mouse) deleted from the two adult genes in the β-globin locus and reproducing the human β-thalassemia intermedia, we have recently established by a competitive repopulating assay that only 19 to 24% normal bone marrow cells transplanted into lethally irradiated hosts was sufficient to significantly correct the disease. Based on this finding, we hypothesized that a minimal level or absence of myeloablation could be used for therapeutic correction of β-thalassemia and thus, investigated this minimal level as well as the optimal cell transfer conditions to achieve such treatment. A series of bone marrow transplantations was performed on 51 partially irradiated (100 or 200 Rads) hemi-βthal mice divided into 8 groups of 5 to 8 chimeric mice each. The hemi-βthal mice received 20, 40, or 60 million nucleated bone marrow cells in either one dose or two equal doses given at 24h difference. Engraftment and chimerism of hemi-βthal recipient mice were analyzed for short and long-term post- transplantation (2 months to >6 months) using the Gpi1a marker. When one cell dose was given to mice conditioned with 100 Rads, no mice (0/6) engrafted with 40 million cell whereas 42.8% of mice (3/7) engrafted with 60 million cells at 23% mean chimerism in the latter group. Of interest, mice conditioned with 200 Rads showed significantly more engraftment from 50% (4/8 mice, 20 million cells) to 85% (6/7 mice, 40 million cells) leading to 36% and 66% mean chimerism, respectively. Most importantly, when mice conditioned with 100 Rads received two half-doses of cells at 24 hour difference, the engraftment increased from 42.8% (3/7 mice, 2 × 20 million cells) to 100% (6/6 mice, 2 × 30 millions cells) with 40 and 48% mean chimerism respectively, while mice conditioned with 200 Rads showed 80% engraftment (4/5 mice) for 20 and 40 million cells transferred, with 63 and 84% mean chimerism respectively. Mice with 23% bone marrow chimerism showed significant improvement of most hematological parameters on complete blood count (CBC) and of all parameters with chimerism greater than 36%, consistent with our recent findings. Altogether, our results established 100 Rad irradiation and two-cell doses as the minimal therapeutic requirements for optimal engraftment and chimerism. Significantly, this is the first study to determine a transplantation strategy in minimally ablated thalassemic mice to attain 100% engraftment efficiency and a therapeutic chimerism in all mice, constituting a basis amenable to clinical applications for human thalassemia.