tbuckley/cabot-search huggingface dataset:
Del(6)(q22) and <i>BCL6</i> Rearrangements in Primary CNS Lymphoma Are Indicators of an Aggressive Clinical Course
Authors: Francois M. Cady, Brian Patrick O'Neill, Mark E. Law, Paul A. Decker, David M. Kurtz, Caterina Giannini, Alyx B. Porter, Paul J. Kurtin, Patrick B. Johnston, Ahmet Dogan, Ellen D. Remstein
Journal: Journal of Clinical Oncology (2008)

Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center.Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment.The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX.Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.
Superior Survival With Capecitabine Plus Docetaxel Combination Therapy in Anthracycline-Pretreated Patients With Advanced Breast Cancer: Phase III Trial Results
Authors: Joyce O’Shaughnessy, David Miles, Svetislava Vukelja, Vladimir Moiseyenko, Jean-Pierre Ayoub, Guadalupe Cervantes, Pierre Fumoleau, Stephen Jones, Wing-Yiu Lui, Louis Mauriac, Chris Twelves, Guy Van Hazel, Shailendra Verma, Robert Leonard
Journal: Journal of Clinical Oncology (2002)

Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine, show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in preclinical studies. This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC.Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100 mg/m(2) on day 1 (n = 256).Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression (TTP) (hazard ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P =.0001; median, 6.1 v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P =.0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v 30%, P =.006) compared with docetaxel. Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy, whereas myalgia, arthralgia, and neutropenic fever/sepsis were more common with single-agent docetaxel. More grade 3 adverse events occurred with combination therapy (71% v 49%, respectively), whereas grade 4 events were slightly more common with docetaxel (31% v 25% with combination).The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2), with the manageable toxicity profile, indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2). Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC.
Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction
Authors: Sejal Saglani, Kristiina Malmström, Anna S. Pelkonen, L. Pekka Malmberg, Harry Lindahl, Merja Kajosaari, Markku Turpeinen, Andrew V. Rogers, Donald N. Payne, Andrew Bush, Tari Haahtela, Mika J. Mäkelä, Peter K. Jeffery
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

We hypothesized that the epithelial reticular basement membrane (RBM) thickening and eosinophilic inflammation characteristic of asthma would be present in symptomatic infants with reversible airflow obstruction.RBM thickness and numbers of inflammatory cells were determined in ultrathin sections of endobronchial biopsies obtained from 53 infants during clinical bronchoscopy for severe wheeze and/or cough. Group A: 16 infants with a median age of 12 months (range 3.4-26 months), with decreased specific airway conductance (sGaw) and bronchodilator reversibility; Group B: 22 infants with a median age of 12.4 months (5.1-25.9 months), with decreased sGaw but without bronchodilator reversibility; and Group C: 15 infants with a median age of 11.5 months (3.4-24.3 months) with normal sGaw. Additional comparisons were made with the following groups. Group D: 17 children, median age 10.3 years (6-16 years), with difficult asthma; Group E: 10 pediatric control subjects without asthma, median age 10 years (6-16 years); and Group F: nine adult normal, healthy control subjects, median age 27 years (21-42 years).There were no significant differences in RBM thickness or inflammatory cell number between the infant groups. RBM thickness was similar in the infants and Groups E and F. However, the RBM in all infant groups (Group A: median 4.3 microm [range 2.8-9.2 microm]; Group B: median 4.15 microm [range 2.7-5.8 microm]; Group C: median 3.8 microm [range 2.7-5.5 microm]) was significantly less thick than that in the older children with asthma (Group D: median 8.3 microm [range 5.3-12.7 microm]; p < 0.001).RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults are not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.
CLASSIFICATION OF EPSTEIN-BARR VIRUS-ASSOCIATED POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASES: Implications for Understanding their Pathogenesis and Developing Rational Treatment Strategies
Authors: Douglas W. Hanto, M.D., Ph.D
Journal: Annual Review of Medicine (1995)

▪ Abstract The Epstein-Barr virus (EBV) is associated with a spectrum of B-cell lymphoproliferative diseases (LPD) that develop following organ transplantation. A classification scheme for these disorders has been developed based on the clinical, histologic, immunologic cell-typing, cytogenetic, immunoglobulin gene-rearrangement, and virologic characteristics of these LPD. Four disease groups have been identified: (a) uncomplicated posttransplant infectious mononucleosis, (b) benign polyclonal polymorphic B-cell hyperplasia, (c) early malignant transformation in polyclonal polymorphic B-cell lymphoma, and (d) monoclonal polymorphic B-cell lymphoma. This classification has furthered our understanding of the pathogenesis of these diverse LPD and has allowed the development of rational treatment protocols.
First-line bevacizumab combined with reduced dose interferon-α2a is active in patients with metastatic renal cell carcinoma
Authors: B Melichar, P Koralewski, A Ravaud, A Pluzanska, S Bracarda, C Szczylik, C Chevreau, M Filipek, R Delva, E Sevin, S Négrier, J McKendrick, A Santoro, P Pisa, B Escudier
Journal: Annals of Oncology (2008)
ANTIGENIC DIFFERENCES BETWEEN HEMOPOIETIC STEM CELLS AND MYELOID PROGENITORS
Authors: Gerrit J. Van den Engh, Edward S. Golub
Journal: The Journal of Experimental Medicine (1974)

Bone marrow contains pluripotent stem cells which give rise to colonies when injected into irradiated syngenic hosts as well as more differentiated progenitor cells of the myeloid cell which are able to form colonies in vitro. Antisera against brain is known to contain antistem cell antibody. The present experiments were designed to determine if the myeloid progenitor cell still expresses the stem cell antigen. Bone marrow cells were treated with antibrain antiserum plus complement and then survival of stem cells was determined by injection into irradiated hosts. Survival of myeloid progenitor cells was determined by culturing the cells in vitro. It was found that stem cells were eliminated by the antiserum but that myeloid progenitors were not. Inefficient in vitro lysis was ruled out as the reason for this difference since in vitro colonies were not reduced when the cells were treated with anti-immunoglobulin or after passage through an irradiated host. In the differentiation from stem cell to myeloid progenitor there is an associated surface antigen change.
Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and γδ T Cells
Authors: Shayna E.A. Street, Yoshihiro Hayakawa, Yifan Zhan, Andrew M. Lew, Duncan MacGregor, Amanda M. Jamieson, Andreas Diefenbach, Hideo Yagita, Dale I. Godfrey, Mark J. Smyth
Journal: The Journal of Experimental Medicine (2004)

Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking β-2 microglobulin (β2m; and thus MHC class I, CD1d, and CD16) and/or perforin, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perforin gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked β2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/β2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perforin, but not IFN-γ, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1+ and γδTCR+ T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and γδTCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.
TIP30 Induces Apoptosis under Oxidative Stress through Stabilization of <i>p53</i> Messenger RNA in Human Hepatocellular Carcinoma
Authors: Jian Zhao, Jingjing Chen, Bin Lu, Li Dong, Huajing Wang, Chongshan Bi, Guobin Wu, Huaizu Guo, Mengchao Wu, Yajun Guo
Journal: Cancer Research (2008)

Abstract Reactive oxygen species (ROS) and cellular oxidant stress have long been associated with cancer. Here, we show that TIP30, also called CC3, regulates p53 mRNA stability and induces apoptosis by sensing of intracellular oxidative stress in human hepatocellular carcinoma (HCC) cells. Introduction of TIP30 induced more cell death in HepG2 cells with a high level of intracellular ROS than that in normal liver cell line, HL7702, which had low level of intracellular ROS. Treatment with an antioxidant agent attenuated TIP30-induced cell death in HepG2 cells, whereas oxidant H2O2 augmented TIP30-induced cell death in HL7702 cells. The conformation of TIP30 was altered with the formation of an intermolecular disulfide bridge under oxidative stress. TIP30 greatly enhanced p53 expression and its transcriptional activity under oxidative stress, which was probably through stabilization of p53 mRNA. TIP30 induced apoptosis and mitochondrial dysfunction were blocked by silencing of p53 expression. The nuclear import of mRNA-binding protein HuR was blocked upon TIP30 introduction, which might be due to the interruption of the association of HuR with importin β2. The elevated cytoplasmic HuR bound to p53 mRNA 3′-untranslated region, resulting in prolonged half-life of p53 mRNA. Our results suggest that TIP30 is involved in cellular oxidative stress surveillance and induces apoptosis through stabilization of p53 mRNA in HCC cells. [Cancer Res 2008;68(11):4133–41]
More than a gut feeling: predicting surgical necrotising enterocolitis
Authors: Jörn-Hendrik Weitkamp
Journal: Gut (2013)

Despite recent advances in neonatal practice, necrotising enterocolitis (NEC) remains the most common and devastating gastrointestinal emergency in premature infants. In fact, as more extremely premature infants survive, the incidence appears to be increasing worldwide.1 Severe NEC is characterised by coagulative necrosis of the distal ileum and proximal colon with clinical presentation ranging from abdominal distension, pneumatosis intestinalis, frank blood in stools, intestinal gangrene, bowel perforation, sepsis and shock. Approximately 9000 infants develop NEC in the USA each year and mortality rates range from 10%–50%.2 ,3 The associated costs—both financial and personal—are significant; the average hospital stay for infants with surgical NEC is an additional 43.1 days at an average additional cost of US$200 000 per child compared with extremely low birthweight infants without NEC.4 Treatment strategies are mainly supportive and include administration of antibiotics and fluids, blood product replacement and withholding of feedings. About 40% of NEC patients require surgery to remove necrotic bowel, which can result in short bowel syndrome, with prolonged medical expenses and chronic gastrointestinal difficulties. In particular, surgical NEC is a significant predictor of lasting neurodevelopmental morbidity independent of other factors.5 ,6 While the outcomes for many prematurity-related illnesses have improved over the past decades, mortality and …
X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation
Authors: W F Safa, G G Lestringant, P M Frossard
Journal: Thorax (2001)

Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterised by lesions of the skin and appendages. Bone marrow failure occurs in 80% of patients. The gene for the X-linked form of DC has been identified on Xq28 and designated as DKC1. Pulmonary manifestations have rarely been reported. It is not known whether there is a respiratory disease peculiar to these patients and, if so, whether it is associated with a specific genetic mutation. A 40 year old Egyptian man with pulmonary disease and his symptom free 35 year old brother both presented with mucocutaneous lesions characteristic of DC. In the older brother chest imaging revealed generalised intralobular interstitial thickening and honeycombing. Pulmonary function tests showed a restrictive pattern. Open lung biopsy specimens of lung tissue showed various degrees of fibrosis consistent with usual interstitial pneumonia of chronic idiopathic pulmonary fibrosis. The younger brother was free of pulmonary lesions. Both had a novel missense mutation 5C→T in exon 1 of the DKC1 gene. It is concluded that pulmonary disease in DC may be underestimated, possibly because most patients die at an early age of bone marrow failure. No relationship between genotype and phenotype could be established in the patients studied. The genetic diagnosis of DC is now available, which may enable it to be diagnosed in patients with restrictive pulmonary disease and minimal cutaneous signs.
RECOMBINATION WITH PERT87 (DXS164) IN FAMILIES WITH X-LINKED MUSCULAR DYSTROPHY
Authors: K.H Fischbeck, A.W Ritter, D.L Tirschwell, L.M Kunkel, C.J Bertelson, A.P Monaco, J.F Hejtmancik, C Boehm, V Ionasescu, R Ionasescu, M Pericak-Vance, R Kandt, A.D Roses
Journal: The Lancet (1986)
THE INFLUENCE OF HYDROCORTISONE ON THE ACTION OF EXCESS VITAMIN A ON LIMB BONE RUDIMENTS IN CULTURE
Authors: Honor B. Fell, Lewis Thomas
Journal: The Journal of Experimental Medicine (1961)

The effect of hydrocortisone has been studied in organ cultures of the cartilaginous long bone rudiments from 7-day chick embryos and of the well ossified limb bones from late fetal mice. In the chick rudiments, which grow rapidly in culture, the growth rate was much reduced by hydrocortisone, less intercellular material was formed, and the hypertrophic cells of the shaft were much smaller than in the controls in normal medium. In the late fetal mouse bones, which grow very little in culture, hydrocortisone had no obvious effect on growth but arrested resorption of the cartilage. These effects resemble those described by others in the skeleton of animals treated with cortisone or hydrocortisone. The influence of hydrocortisone on the response of the chick and mouse explants to excess vitamin A was investigated. In the presence of excess vitamin A, cartilage (chick, mouse) and bone (mouse) rapidly disintegrated, but when hydrocortisone also was added to the medium, this dissolution of the intercellular material was much retarded, though not suppressed. The retardative action of hydrocortisone on the changes produced by excess vitamin A in skeletal tissue in culture, contrasts sharply with the strongly additive effect of the two agents on the skeleton in the intact animal (Selye, 1958). It is suggested that this discrepancy between the results obtained in vitro and in vivo is probably due to systemic factors that operate in the body but are eliminated in organ cultures.
Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance
Authors: Markus Y. Mapara, Megan Sykes
Journal: Journal of Clinical Oncology (2004)

The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed.
Does etanercept monotherapy enhance the risk of Listeria monocytogenes meningitis?
Authors: P Pagliano
Journal: Annals of the Rheumatic Diseases (2004)

Considerable data have identified tumour necrosis factor α (TNFα) as a pivotal mediator in inflammatory processes, suggesting that it has a role also in the pathogenesis of some autoimmune diseases, such as rheumatoid arthritis (RA).1,2 Currently, two drugs that interfere with TNFα, infliximab and etanercept, have been extensively used for the treatment of patients with RA and other immunological disorders; both have been associated with a higher risk of serious infective complications.3–7

Listeria monocytogenes is a Gram positive intracellular organism seen almost always in neonatal sepsis, elderly meningitis, and in patients with chronic diseases and impairment of cellular immunity, which avoids the host immunity by a mechanism of cell to cell spreading.8

Association between anti-TNFα agents and listeriosis has already been reported in patients …
Treatment of latent tuberculosis with rifampicin is associated with higher completion rates
Authors: V Nadig
Journal: Thorax (2007)

▴ Page KR, Sifakis F, Montes de Oca R, et al. Improved adherence and less toxicity with rifampicin vs. isoniazid for treatment of latent tuberculosis. Arch Intern Med2006;166:1863–70.

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



In this retrospective study, medical records of 2255 patients who received treatment for latent tuberculosis infection (LTBI) at a US centre between January 1999 and January 2004 were reviewed. Adherence to LTBI treatment was …

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Serum CA-125 in Relation to Adnexal Dysplasia and Cancer in Women at Hereditary High Risk of Ovarian Cancer
Authors: Brenda B.J. Hermsen, Silvia von Mensdorff-Pouilly, Johannes Berkhof, Paul J. van Diest, Johan J.P. Gille, Fred H. Menko, Marinus A. Blankenstein, Peter Kenemans, René H.M. Verheijen
Journal: Journal of Clinical Oncology (2007)

Purpose Serum CA-125 level is commonly used as indicator for ovarian cancer recurrence. However, its value for the prediction of neoplastic lesions is unknown. The aim of this study was to investigate whether CA-125 concentrations are indicative of adnexal dysplasia and cancer in women at hereditary high risk of ovarian/tubal cancer. Patients and Methods CA-125 was obtained from 424 women at hereditary high risk of ovarian/tubal cancer attending the VU University Medical Center (Amsterdam, the Netherlands) between 1993 and 2005. Serum samples obtained at the second-to-last (n = 64) and last (n = 98) visit before surgery were tested in women who underwent adnexal surgery for diagnostic (n = 9) or prophylactic (n = 89) reasons. Serum samples obtained from 370 age-matched healthy women were used as controls. Results Both the absolute value (P &lt; .0001) and the serial change (P &lt; .0001) of CA-125 were predictive for ovarian cancer (n = 8). For adnexal dysplasia (n = 23), the absolute value of CA-125 (P = .003) was predictive, but the serial change in CA-125 was not (P = .32). The odds ratio for adnexal dysplasia versus nondysplasia in the highest tertile (CA-125 levels ≥ 14 U/mL) compared with the lowest tertile (CA-125 &lt; 10 U/mL) was 6 (95% CI, 1.32 to 36.66). Conclusion In patients at hereditary high risk for adnexal cancer, both the absolute value of serum CA-125 and the change in serial CA-125 are predictors for ovarian cancer. Remarkably, the absolute value of CA-125 is also predictive for adnexal dysplasia. CA-125 values should, therefore, be taken into account in the decision toward prophylactic bilateral salpingo-oophorectomy.