tbuckley/cabot-search huggingface dataset:
Activation of Akt-1 (PKB-α) Can Accelerate ErbB-2-Mediated Mammary Tumorigenesis but Suppresses Tumor Invasion
Authors: John N. Hutchinson, Jing Jin, Robert D. Cardiff, Jim R. Woodgett, William J. Muller
Journal: Cancer Research (2004)

Abstract Elevated expression of Akt-1 (PKBα) has been noted in a significant percentage of primary human breast cancers. Another frequent event in the genesis of human breast cancers is amplification and overexpression of the ErbB-2 receptor tyrosine kinase, an event which is associated with activation of Akt-1. To directly assess the importance of Akt-1 activation in ErbB-2 mammary tumor progression, we interbred separate strains of transgenic mice carrying mouse mammary tumor virus/activated Akt-1 and mouse mammary tumor virus/activated ErbB-2 to derive progeny that coexpress the transgenes in the mammary epithelium. Female transgenic mice coexpressing activated Akt-1 and ErbB-2 develop multifocal mammary tumors with a significantly shorter latency period than mice expressing activated ErbB-2 alone. This dramatic acceleration of mammary tumor progression correlates with enhanced cellular proliferation, elevated Cyclin D1 protein levels, and phosphorylation of retinoblastoma protein. These bitransgenic mammary tumors also exhibit lower levels of invasion into the surrounding tissue and more differentiated phenotypes. Consistent with these observations, female mice coexpressing activated Akt-1 and ErbB-2 developed significantly fewer metastatic lesions than the activated ErbB-2 strain alone. Taken together, these observations suggest that activation of Akt-1 during ErbB-2-induced mammary tumorigenesis may have opposing effects on tumor growth and metastatic progression.
Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna
Authors: Lars-Henrik Heckmann, Richard M Sibly, Richard Connon, Helen L Hooper, Thomas H Hutchinson, Steve J Maund, Christopher J Hill, Anthony Bouetard, Amanda Callaghan
Journal: Genome biology (2008)

Ibuprofen and other nonsteroidal anti-inflammatory drugs have been designed to interrupt eicosanoid metabolism in mammals, but little is known of how they affect nontarget organisms. Here we report a systems biology study that simultaneously describes the transcriptomic and phenotypic stress responses of the model crustacean Daphnia magna after exposure to ibuprofen.Our findings reveal intriguing similarities in the mode of action of ibuprofen between vertebrates and invertebrates, and they suggest that ibuprofen has a targeted impact on reproduction at the molecular, organismal, and population level in daphnids. Microarray expression and temporal real-time quantitative PCR profiles of key genes suggest early ibuprofen interruption of crustacean eicosanoid metabolism, which appears to disrupt signal transduction affecting juvenile hormone metabolism and oogenesis.Combining molecular and organismal stress responses provides a guide to possible chronic consequences of environmental stress for population health. This could improve current environmental risk assessment by providing an early indication of the need for higher tier testing. Our study demonstrates the advantages of a systems approach to stress ecology, in which Daphnia will probably play a major role.
Immunotherapy of Murine Leukemia. VIII. Efficacy of Passive Serum Therapy of Friend Leukemia Virus-Induced Disease in Immunocompromised Mice&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: E V Genovesi, D Livnat, J J Collins
Journal: JNCI Journal of the National Cancer Institute (1983)

Previous studies have demonstrated that the passive therapy of Friend murine leukemia virus (F-MuLV)-induced disease with chimpanzee anti-F-MuLV serum is accompanied by the development of host antiviral humoral and cellular immunity, the latter measurable in adoptive transfer protocols and by the ability of serum-protected mice to resist virus rechallenge. The present study was designed to further examine the contribution of various compartments of the host immune system to serum therapy itself, as well as to the acquired antiviral immunity that develops in serum-protected mice, through the use of naturally immunocompromised animals [e.g., nude athymic mice and natural killer (NK)-deficient beige mutant mice] or mice treated with immunoabrogating agents such as sublethal irradiation, cyclophosphamide [Cytoxan (Cy)], cortisone, and 89Sr. The studies in nude mice indicate that while mature T-cells are not needed for effective serum therapy, they do appear to be necessary for the long-term resistance of serum-protected mice to virus rechallenge and for the generation of the cell population(s) responsible for adoptive transfer of antiviral immunity. Furthermore, this acquired resistance is not due to virus neutralization by serum antibodies since antibody-negative, Cy-treated, serum-protected mice still reject the secondary virus infection. Lastly, while the immunocompromise systems examined did effect various host antiviral immune responses, none of them, including the NK-deficient beige mutation, significantly diminished the efficacy of the passive serum therapy of F-MuLV-induced disease.
Localized prostate cancer treated by external-beam radiotherapy alone: serum prostate-specific antigen--driven outcome analysis.
Authors: W R Lee, G E Hanks, T E Schultheiss, B W Corn, M A Hunt
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the 5-year rate of survival with no evidence of disease (NED) using strict biochemical criteria in men with prostate cancer treated by external-beam radiotherapy alone and to examine possible clinical and treatment factors that predict the likelihood of NED survival. MATERIALS AND METHODS Five hundred men with clinically localized prostate cancer consecutively treated with external-beam radiotherapy alone with no prior, concomitant, or adjuvant endocrine therapy were identified. All patients had serial serum prostate-specific antigen (PSA) values determined after treatment and 451 patients had pretreatment PSA values determined. The median follow-up duration is 20 months (range, 2 to 72; mean, 36). RESULTS The 5-year rate of overall survival in this group of patients was 80%. The 5-year rate of survival without clinical evidence of disease (cNED) was 72%. The 5-year rate of survival without evidence of clinical, radiographic, or biochemical relapse (bNED) was 51%. Multivariate analysis demonstrated that a pretreatment serum PSA level &lt; or = 15 ng/mL was the most important predictor of bNED survival (P &lt; .0001). Patients with early-stage (T1, T2a/b) tumors and a pretreatment serum PSA less than 15 ng/mL had a 3-year rate of bNED survival of 86%. The rate of bNED survival for patients with a pretreatment PSA level greater than 15 ng/mL was 38% at 3 years. CONCLUSION Pretreatment serum PSA level is the most important predictor of treatment outcome in this group of patients treated with definitive radiotherapy alone. External-beam radiation alone can produce acceptable early rates of bNED survival in patients with clinically organ-confined tumors and a pretreatment PSA level &lt; or = 15 ng/mL. To produce acceptable results in those patients with pretreatment PSA levels more than 15 ng/mL, effective adjuvant treatments in addition to aggressive local treatments are necessary.
A Critique of Freud's Theory of Infantile Sexuality
Authors: PAUL CHODOFF
Journal: American Journal of Psychiatry (1966)

Freud's theories of infantile sexuality may not deserve unhesitating acceptance. Long a bulwark of orthodox analysis, they are critically examined here in light of current knowledge and experience. Empirical, experimental, and psychoanalytic evidence are discussed and shown to present the possibility of serious reservations about the original Freudian construct. The author calls for a calm assessment and an objective, unbiased look at infantile sexuality and its psychic concomitants.
Tinea capitis in two black African adults with HIV infection
Authors: None LATEUR, None ANDRÉ, None DE MAUBEUGE, None PONCIN, None SONG
Journal: British Journal of Dermatology (1999)

Tinea capitis is rare in adults, although a few cases have been described in HIV-infected patients. We present two cases in black African adults who were HIV positive. In one, the condition led to the diagnosis of HIV infection. It is possible that the rarity of tinea capitis in HIV-positive adults could be related to increased colonization of their scalp by Pityrosporum (Malassezia) spp. In patients well controlled with an antiviral therapy, the treatment of tinea capitis seems no more difficult than in non-immunosuppressed patients. There is possibly a relation between clinical presentation and degree of immunodeficiency.
Sarcoid sacroiliitis: successful treatment with infliximab: Figure 1
Authors: S Agrawal, S Bhagat, B Dasgupta
Journal: Annals of the Rheumatic Diseases (2009)

In 1996, a 51-year-old woman was diagnosed as having sarcoidosis of the ethmoid sinuses with lacrimal duct involvement (bilateral hilar prominence on chest radiograph). She underwent endoscopic ethmoidectomy (histopathological evaluation of the tissue confirmed sarcoidosis) followed by a short course of systemic corticosteroids and nasal steroids with complete resolution of symptoms.

She presented again in 2005 with shortness of breath on exertion. High-resolution computed tomography of the thorax showed bilateral parenchymal changes with hilar lymphadenopathy. However, she refused to be treated with corticosteroids. Subsequently, she developed severe inflammatory low backache along with bilateral shoulder pains for which she received diclofenac. As there was no improvement in the …
Air-Rinsing After Dialysis
Authors: F. Marc LaForce
Journal: JAMA (1975)

During a recent outbreak of hepatitis B among patients receiving dialysis, georgraphic and temporal distribution of cases in the absence of exposure to blood products suggested patient-to-patient transmission. The patients who contracted hepatitis used Kiil dialyzers with a single-pass dialysate system, while patients who used hollow-fiber dialyzers appeared to be protected. Blood was returned to patients after Kiil dialysis by the air-rinse technique with the use of a nonsterile plastic tube attached to a manometer bulb. Laboratory experiments demonstrated that Staphylococcus aureus and poliovirus became widely distributed throughout the Kiil dialyzer when introduced during the rinse phase by contaminating the air-rinse tubing.
Risk of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Trials of Adjuvant Epirubicin for Early Breast Cancer: Correlation With Doses of Epirubicin and Cyclophosphamide
Authors: Claudio Praga, Jonas Bergh, Judith Bliss, Jacques Bonneterre, Bruno Cesana, R. Charles Coombes, Pierre Fargeot, Annika Folin, Pierre Fumoleau, Rosa Giuliani, Pierre Kerbrat, Michel Hery, Jonas Nilsson, Francesco Onida, Martine Piccart, Lois Shepherd, Patrick Therasse, Jacques Wils, David Rogers
Journal: Journal of Clinical Oncology (2005)

We reviewed follow-up of patients treated in 19 randomized trials of adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).The patients (N = 9,796) were observed from the start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS) were reported, with disease characteristics. Incidence and cumulative risk were compared for possible risk factors, for assigned regimens, and for administered cumulative doses of epirubicin and cyclophosphamide.In 7,110 patients treated with epirubicin-containing regimens (92% of whom also received cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI, 0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned epirubicin dose per cycle, planned epirubicin dose-intensity, and administered cumulative doses of epirubicin and cyclophosphamide. Patients with administered cumulative doses of both epirubicin and cyclophosphamide not exceeding those used in standard regimens (</= 720 mg/m(2) and </= 6,300 mg/m(2), respectively) had an 8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to 0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered higher cumulative doses of both epirubicin and cyclophosphamide.Patients treated with standard cumulative doses of adjuvant epirubicin (</= 720 mg/m(2)) and cyclophosphamide (</= 6,300 mg/m(2)) for early breast cancer have a lower probability of secondary leukemia than patients treated with higher cumulative doses. Increased risk of secondary leukemia must be considered when assessing the potential benefit to risk ratio of higher than standard doses.
Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging
Authors: Atsushi Yonemura, Yukihiko Momiyama, Zahi A. Fayad, Makoto Ayaori, Reiko Ohmori, Kenji Higashi, Teruyoshi Kihara, Shojiro Sawada, Noriyuki Iwamoto, Masatsune Ogura, Hiroaki Taniguchi, Masatoshi Kusuhara, Masayoshi Nagata, Haruo Nakamura, Seiichi Tamai, Fumitaka Ohsuzu
Journal: Journal of the American College of Cardiology (2005)
Cyclosporin A, FK506, rapamycin
Authors: B D Kahan
Journal: Journal of the American Society of Nephrology (1992)

Potent immunosuppressive agents display toxic complications at full therapeutic doses: cyclosporin A (CsA) produces pleiotropic mesenchymal effects with prominent vasculopathy, whereas FK506 displays severe neurotoxicity associated with a similar range of mesenchymal and possibly vasculitic reactions. The concept of drug synergy seeks to exploit combinations of agents that promote each other's immunosuppressive effects. This article presents a quantitative method to assess synergy in vitro and in vivo--the median-effect analysis. Application of this method revealed synergistic interactions of CsA with steroids, an additive effect with azathioprine, and antagonistic effects with FK506 and enisoprost. Clearly, a synergistic therapeutic combination can be clinically useful only if it is not associated with a similar potentiation of toxic complications. Clinical practice has documented the synergistic relation of CsA plus steroids and the antagonistic relation of CsA with FK506 or enisoprost. Clinical trials of rapamycin, which displays extremely potent synergistic effects with CsA both in vitro with human and in vivo with animal immune responses, may afford important new insights for clinical immunosuppression.
High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodenal disease.
Authors: N Banatvala, G R Davies, Y Abdi, L Clements, D S Rampton, J M Hardie, R A Feldman
Journal: Gut (1994)

A high prevalence of metronidazole resistance in Helicobacter pylori is reported in developing countries. This study examined whether migrants referred for diagnostic gastroscopy at a United Kingdom centre (n = 54), had a higher prevalence of metronidazole resistance than subjects born in the United Kingdom attending endoscopy (n = 46). Records of nitroimidazole treatment prescribed in the United Kingdom was obtained in 83 patients to find out if there was an association between H pylori metronidazole resistance and previous ingestion of either metronidazole or tinidazole. The prevalence of metronidazole resistant isolates varied according to country of birth: Bangladesh (90%, 27 of 30), other countries (67%, 16 of 24), and United Kingdom (37%, 17 of 46) (p < 0.001). Among those born in the United Kingdom, women were more likely to harbour resistant H pylori than men (54% v 18% respectively, p = 0.01) and more likely to have a history of previous nitroimidazole ingestion (41% v 11% respectively, p = 0.02). Patients previously exposed to either metronidazole or tinidazole were more likely to harbour resistant strains (84% (27 of 32) v 41% (21 or 51), p < 0.0001). The distribution of gastroduodenal disease, assessed endoscopically, was not affected by metronidazole resistance status.
Gadolinium Cardiovascular Magnetic Resonance Predicts Reversible Myocardial Dysfunction and Remodeling in Patients With Heart Failure Undergoing β-Blocker Therapy
Authors: David Bello, Dipan J. Shah, George M. Farah, Silvia Di Luzio, Michele Parker, Maryl R. Johnson, William G. Cotts, Francis J. Klocke, Robert O. Bonow, Robert M. Judd, Mihai Gheorghiade, Raymond J. Kim
Journal: Circulation (2003)

In some patients with heart failure, beta-blockers can improve left ventricular (LV) function and reduce morbidity and mortality. We hypothesized that gadolinium-enhanced cardiovascular magnetic resonance imaging (CMR) can predict reversible myocardial dysfunction and remodeling in heart failure patients treated with beta-blockers.Forty-five patients with chronic heart failure underwent CMR. Contrast imaging using gadolinium was performed to obtain high-resolution spatial maps of myocardial scarring and viability. Cine imaging was performed to assess LV function and morphology and was repeated in 35 patients after 6 months of beta-blockade. Gadolinium CMR demonstrated scarring in 30 of 45 patients (67%). Scarring was found in 100% of patients with ischemic cardiomyopathy (28 of 28) but in only 12% with nonischemic cardiomyopathy (2 of 17). In the 35 patients who were maintained on beta-blockers and had a second study, there was an inverse relation between the extent of scarring at baseline and the likelihood of contractile improvement 6 months later (P<0.001). For instance, contractility improved in 56% (674 of 1207) of regions with no scarring but in only 3% with >75% scarring (8 of 232). Multivariate analysis showed that the amount of dysfunctional but viable myocardium by CMR was an independent predictor of the change in ejection fraction (P=0.01), mean wall motion score (P=0.0007), LV end-diastolic volume index (P=0.007), and LV end-systolic volume index (P< or =0.0001).For heart failure patients treated with beta-blockers, gadolinium-enhanced CMR predicts the response in LV function and remodeling.
Phase I Pharmacokinetic and Pharmacodynamic Study of SJG-136, a Novel DNA Sequence Selective Minor Groove Cross-linking Agent, in Advanced Solid Tumors
Authors: Igor Puzanov, Wooin Lee, Alice P. Chen, M. Wade Calcutt, David L. Hachey, Wendy L. Vermeulen, Victoria J. Spanswick, Chih-Yi Liao, John A. Hartley, Jordan D. Berlin, Mace L. Rothenberg
Journal: Clinical Cancer Research (2011)

Abstract Purpose: This phase I study assessed the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SJG-136, a sequence-specific DNA cross-linking agent, in patients with advanced cancer. Experimental Design: In schedule A, seven patients received escalating doses of SJG-136 (6, 12, 24, and 48 μg/m2) daily for 5 of 21 days. Blood samples were collected for PK analysis on days 1 and 5 of cycle 1. In schedule B, SJG-136 was given daily for 3 of 21 days (N = 17; doses 20, 25, 30, and 35 μg/m2). Blood samples were collected on days 1 and 3 of cycles 1 and 2 for PK and PD analysis. Patients in schedule B received dexamethasone and early diuretic care. Results: Schedule A—dose-limiting toxicities included grade 3 edema, dyspnea, fatigue, and delayed liver toxicity (grade 3–4). PK analysis revealed dose-dependent increases in AUC and Cmax. Substantial changes in volume of distribution at steady-state occurred after repeated dosing in some patients prior to the onset of edema. Schedule B—the same toxicities were manageable with steroid premedication and diuretic support. No significant myelosuppression occurred on either schedule. DNA interstrand cross-links correlated with systemic exposure of SJG-136 following the second dose in cycle 1 and were still detectable immediately before cycle 2. Conclusions: The MTD of SJG-136 in this study was 30 μg/m2 administered on a daily 3× basis with no myelosuppression effects. Coupled with supportive management, SJG-136 is now advancing to a phase II trial in ovarian cancer. Clin Cancer Res; 17(11); 3794–802. ©2011 AACR.
Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer
Authors: T.H. van Dijk, K. Tamas, J.C. Beukema, G.L. Beets, A.J. Gelderblom, K.P. de Jong, I.D. Nagtegaal, H.J. Rutten, C.J. van de Velde, T. Wiggers, G.A. Hospers, K. Havenga
Journal: Annals of Oncology (2013)
A Site- and Time-Heterogeneous Model of Amino Acid Replacement
Authors: Samuel Blanquart, Nicolas Lartillot
Journal: Molecular Biology and Evolution (2008)

We combined the category (CAT) mixture model (Lartillot N, Philippe H. 2004) and the nonstationary break point (BP) model (Blanquart S, Lartillot N. 2006) into a new model, CAT–BP, accounting for variations of the evolutionary process both along the sequence and across lineages. As in CAT, the model implements a mixture of distinct Markovian processes of substitution distributed among sites, thus accommodating site-specific selective constraints induced by protein structure and function. Furthermore, as in BP, these processes are nonstationary, and their equilibrium frequencies are allowed to change along lineages in a correlated way, through discrete shifts in global amino acid composition distributed along the phylogenetic tree. We implemented the CAT–BP model in a Bayesian Markov Chain Monte Carlo framework and compared its predictions with those of 3 simpler models, BP, CAT, and the site- and time-homogeneous general time–reversible (GTR) model, on a concatenation of 4 mitochondrial proteins of 20 arthropod species. In contrast to GTR, BP, and CAT, which all display a phylogenetic reconstruction artifact positioning the bees Apis mellifera and Melipona bicolor among chelicerates, the CAT–BP model is able to recover the monophyly of insects. Using posterior predictive tests, we further show that the CAT–BP combination yields better anticipations of site- and taxon-specific amino acid frequencies and that it better accounts for the homoplasies that are responsible for the artifact. Altogether, our results show that the joint modeling of heterogeneities across sites and along time results in a synergistic improvement of the phylogenetic inference, indicating that it is essential to disentangle the combined effects of both sources of heterogeneity, in order to overcome systematic errors in protein phylogenetic analyses.
Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00)
Authors: L. Perey, R. Paridaens, H. Hawle, K. Zaman, F. Nolé, H. Wildiers, M. Fiche, D. Dietrich, P. Clément, D. Köberle, A. Goldhirsch, B. Thürlimann
Journal: Annals of Oncology (2006)